E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a mo...E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.展开更多
Tamarix spp. (Saltcedar) is a facultative phreatophyte that can tolerate drought when groundwater is not accessed. In addition to deep water uptake, hydraulic redistribution (HR) is another factor contributing to ...Tamarix spp. (Saltcedar) is a facultative phreatophyte that can tolerate drought when groundwater is not accessed. In addition to deep water uptake, hydraulic redistribution (HR) is another factor contributing to the drought tolerance of Tarnarix spp. In this study, data on soil volumetric moisture content (0), lateral root sap flow, and relevant climate variables were used to investigate the patterns, magnitude, and controlling factors of HR of soil water by roots of Tamarix ramosissima Ledeb. in an extremely arid land in Northwest China. Results showed evident diurnal fluctuations in 0 at the depths of 30 and 50 cm, indicating "hydraulic lift" (HL). 0 increased remarkably at 10 and 140 cm but decreased at 30 and 50 cm and slightly changed at 80 cm after rainfall, suggesting a possible "hydraulic descent" (HD). However, no direct evidence was observed in the negative flow of lateral roots, supporting HR (including HL and HD) of T. ramosissima. The HR pathway unlikely occurred via lateral roots; instead, HR possibly occurred through adventitious roots with a diameter of 2-5 mm and a length of 60-100 cm. HR at depths of 20-60 cm ranged from 0.01-1.77 mm/d with an average of 0.43 mm/d, which accounted for an average of 22% of the estimated seasonal total water depletion at 0-160 cm during the growing season. The climate factors, particularly vapor pressure deficit and soil water potential gradient, accounted for at least 33% and 45% of HR variations with depths and years, respectively. In summary, T. ramosissima can be added to the wide list of existing species involved in HR. High levels of HR may represent a considerable fraction of daily soil water depletion and substantially improve plant water status. HR could vary tremendously in terms of years and depths, and this variation could be attributed to climate factors and soil water potential gradient.展开更多
High-resolution observations of cambial phenology and intra-annual growth dynamics are useful approaches for understanding the response of tree growth to climate and environmental change. During the past two decades, ...High-resolution observations of cambial phenology and intra-annual growth dynamics are useful approaches for understanding the response of tree growth to climate and environmental change. During the past two decades, rapid socioeconomic development has increased the demand for water resources in the oases of the middle reaches of the Heihe River in northwestern China, and the lower reaches of the Heihe River have changed from a perennial river to an ephemeral stream with a decreased and degraded riparian zone. Tamarisk(Tamarix ramosissima) is the dominant shrub species of the desert riparian forest. In this study, the daily and seasonal patterns of tamarisk stem diameter growth, including the main period of tree ring formation, were examined. Observations concerning the driving forces of growth changes, along with implications for the ecology of the dendrohydrological area and management of desert riparian forests in similar arid regions, are also presented. The diurnal-seasonal activity of stem diameter and the dynamics of growth ring formation were studied using a point dendrometer and micro-coring methods during the 2012 growing season in shrub tamarisk in a desert riparian forest stand in the lower reaches of the Heihe River in Ejin Banner, Inner Mongolia of northwestern China. Generally, the variation in diurnal diameter of tamarisk was characterized by an unstable multi-peak pattern, with the cumulative stem diameter growth over the growing season following an S-shaped curve. The period from late May to early August was the main period of stem diameter growth and growth-ring formation. Among all of the hydroclimatic factors considered in this study, only groundwater depth was significantly correlated with stem diameter increment during this period. Therefore, for the dendrochronological study, the annual rings of the tamarisk can be used to reconstruct processes that determine the regional water regime, such as river runoff and fluctuations in groundwater depth. For the management of desert riparian forests, suitable groundwater depths must be maintained in the spring and summer to sustain tree health and a suitable stand structure.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Tamarix ramosissima Ledeb. is a typical hardy desert plant growing in arid regions of Northwest China. Sap flow in stems of Z ramosissima plants were measured continuously to determine the diurnal and seasonal variati...Tamarix ramosissima Ledeb. is a typical hardy desert plant growing in arid regions of Northwest China. Sap flow in stems of Z ramosissima plants were measured continuously to determine the diurnal and seasonal variations of sap flow and to understand the water requirements of this species and the response of sap flow to meteorological factors. This article compared the sap flow rate measured by the heat balance method with the transpiration rate measured by rapid weighing, and validated that heat balance sap flow gauges were reliable for monitoring transpiration. The influence of meteorological factors on stem sap flow during the growing season was: solar radiation 〉 vapor pressure deficit 〉 air temperature 〉 rela- tive humidity 〉 wind speed. Bidirectional sap flows occurred at night, and negative sap flow generally corresponded to high atmospheric humidity. The average error in predicted sap flow rate ranged from -0.78% to 14.00% from June to September and for transpiration the average error was 8.19%. Therefore, based on the functional equations between sap flow and meteorological factors as well as sapwood area, transpiration of an individual plant, and even the stand-level transpiration, can be estimated accurately through extrapolation.展开更多
Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative...Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.展开更多
To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study...To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study involved 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two Malaysian tertiary hospitals. Socio-demographic data were assessed using a pre-tested interviewer-administered structured questionnaire. Anthropometric measurements were carried out according to standard protocols. Clinical and laboratory characteristics were examined. Kappa (k) statistics were used for the agreement between the four MetS definitions. The overall prevalence rates of MetS (95% CI) were 95.8% (93.6-98.1), 96.1% (94.0-98.3), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) according to the WHO, NCEP ATP III, IDF and the Harmonized definitions, respectively. The Kappa statistics demonstrated a slight to substantial agreement between the definitions (k = 0.179-0.875, p k = 0.875, p hest specificity (100%) in identifying MetS. In conclusion, the new Harmonized criteria established the highest prevalence of MetS among the four definitions applied. There was a very good concordance between the WHO and NCEP ATP III criteria. The extremely high prevalence of MetS observed in type 2 diabetic patients indicates an impending pandemic of CVD risk in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.展开更多
Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripher...Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.展开更多
目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diab...目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。展开更多
Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor imm...Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.展开更多
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies th...Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.展开更多
BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate t...BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)vary widely in prognosis,and traditional pathological assessments often lack precision in risk stratification.Advanced imaging techniques,especially magnetic resonance ...BACKGROUND Gastrointestinal stromal tumors(GISTs)vary widely in prognosis,and traditional pathological assessments often lack precision in risk stratification.Advanced imaging techniques,especially magnetic resonance imaging(MRI),offer potential improvements.This study investigates how MRI imagomics can enhance risk assessment and support personalized treatment for GIST patients.AIM To assess the effectiveness of MRI imagomics in improving GIST risk stratification,addressing the limitations of traditional pathological assessments.METHODS Analyzed clinical and MRI data from 132 GIST patients,categorizing them by tumor specifics and dividing into risk groups.Employed dimension reduction for optimal imagomics feature selection from diffusion-weighted imaging(DWI),T1-weighted imaging(T1WI),and contrast enhanced T1WI with fat saturation(CET1WI)fat suppress(fs)sequences.RESULTS Age,lesion diameter,and mitotic figures significantly correlated with GIST risk,with DWI sequence features like sphericity and regional entropy showing high predictive accuracy.The combined T1WI and CE-T1WI fs model had the best predictive efficacy.In the test group,the DWI sequence model demonstrated an area under the curve(AUC)value of 0.960 with a sensitivity of 80.0%and a specificity of 100.0%.On the other hand,the combined performance of the T1WI and CE-T1WI fs models in the test group was the most robust,exhibiting an AUC value of 0.834,a sensitivity of 70.4%,and a specificity of 85.2%.CONCLUSION MRI imagomics,particularly DWI and combined T1WI/CE-T1WI fs models,significantly enhance GIST risk stratification,supporting precise preoperative patient assessment and personalized treatment plans.The clinical implications are profound,enabling more accurate surgical strategy formulation and optimized treatment selection,thereby improving patient outcomes.Future research should focus on multicenter studies to validate these findings,integrate advanced imaging technologies like PET/MRI,and incorporate genetic factors to achieve a more comprehensive risk assessment.展开更多
The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central ...The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central Taurus Mountains(Bolkar, Aladaglar, Tahtali and Binboga Mountains) from 1981 to 2021. Linear trends of snow cover season(November to April) over the last 41 years showed decreases in SCE primarily at lower elevations. The downward trend in SCE was found to be more pronounced and statistically significant for only November and March. SCE in the Central Taurus Mountains has declined about-6.3% per decade for 2500-3000 m in November and about-6.0% per decade for 1000-1500 m and 3000+ m in March over the last 41 years. The loss of SCE has become evident since the 2000s, and the lowest negative anomalies in SCE have been observed in 2014, 2001, and 2007 in the last 41 years, which are consistent with an increase in air temperature and decreased precipitation. SCE was correlated with both mean temperature and precipitation, with temperature having a greater relative importance at all elevated gradients. Results showed that there is a strong linear relationship between SCE and the mean air temperature(r =-0.80) and precipitation(r = 0.44) for all elevated gradients during the snow season. The Arctic Oscillation(AO), the North Atlantic Oscillation(NAO), and the Mediterranean Oscillation(MO) winter indices were used to explain the year-to-year variability in SCE over the Central Taurus Mountains. The results showed that the inter-annual variability observed in the winter SCE on the Central Taurus Mountains was positively correlated with the phases of the winter AO, NAO and MO, especially below 2000 m elevation.展开更多
Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
Aim: This paper aims to evaluate disparities of type 2 diabetes structured health education programmes that is utilised within the communities. Design: systematic review, (a type of secondary research design) aiming t...Aim: This paper aims to evaluate disparities of type 2 diabetes structured health education programmes that is utilised within the communities. Design: systematic review, (a type of secondary research design) aiming to summarize the results of prior primary research studies on available evidence Community type 2 diabetes structured education (CT2DSHE). Methods: Research question: Type 2 diabetic structured health education within a community how effective is it? Qualitative Systematic review, defined as a way to get reliable and objective picture of current available evidence on the specific topic—(CT2DSHE), (Denscombe, 2021) through reflexivity synthesis of available data as an example. This is valuable in time constraints such as project assignments that must be met within specific time and also to bring together available evidence together [1]. Results: This review has shown that CT2DSHE is effective with seven out of the eleven authors supporting, three authors against and one was neutral, further showed that knowledge and skills acquired can last longer with patient activation improved among T2DM patients ideal for sustaining their self-management of T2DM. Conclusion: This research provides suggestive answers to the research question: “Type 2 diabetic structured health education within a community how effective is it?”, This has demonstrated CT2DSHE effectiveness in knowledge acquisition and improving T2DM awareness among T2DM patients, whilst evidencing long effects beyond the study times of 3 - 9 months period in relation to patient activation. Also Identified diabetes education self-management on newly diagnosed (DESMOND) patient as CT2DSHE program for recommendation. Patient or Public Contribution: This work aspires to contribute to CT2DSHE in these areas;Influencing policy decision-making for community diabetes care within the UK and world at large., Contributing to already vast knowledge on diabetes self-management and reasons why?, Influencing educators on how CT2DSHEP are designed, delivered by putting the patient at the Centre and bringing different perspectives on CT2DSHEP in one place that is serving users time of having to consult several resources especially busy clinicians [2] [3].展开更多
In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highw...In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highways,railroads,and water supply pipelines,was particularly severe in areas where these structures intersected the seismogenic fault.Critical infrastructure projects that traverse active faults are susceptible to the influence of fault movement,pulse velocity,and ground motions.In this study,we used a unique approach to analyze the acceleration records obtained from the seismic station array(9 strong ground motion stations)located along the East Anatolian Fault(the seismogenic fault of the MW7.8 mainshock of the 2023 Türkiye earthquake doublet).The acceleration records were filtered and integrated to obtain the velocity and displacement time histories.We used the results of an on-site investigation,jointly conducted by China Earthquake Administration and Türkiye’s AFAD,to analyze the distribution of PGA,PGV,and PGD recorded by the strong motion array of the East Anatolian Fault.We found that the maximum horizontal PGA in this earthquake was 3.0 g,and the maximum co-seismic surface displacement caused by the East Anatolian Fault rupture was 6.50 m.As the fault rupture propagated southwest,the velocity pulse caused by the directional effect of the rupture increased gradually,with the maximum PGA reaching 162.3 cm/s.We also discussed the seismic safety of critical infrastructure projects traversing active faults,using two case studies of water supply pipelines in Türkiye that were damaged by earthquakes.We used a three-dimensional finite element model of the PE(polyethylene)water pipeline at the Islahiye State Hospital and fault displacement observations obtained through on-site investigation to analyze pipeline failure mechanisms.We further investigated the effect of the fault-crossing angle on seismic safety of a pipeline,based on our analysis and the failure performance of the large-diameter Thames Water pipeline during the 1999 Kocaeli earthquake.The seismic method of buried pipelines crossing the fault was summarized.展开更多
Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological mechanisms.Methods Differentially expressed genes related to H...Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model(25 and 10 μmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression.Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.展开更多
文摘E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.
基金supported by the Key Project of the Chinese Academy of Sciences (KZZD-EW-04-05)the National Natural Science Foundation of China (91025024)the Western Light Project of the Chinese Academy of Sciences
文摘Tamarix spp. (Saltcedar) is a facultative phreatophyte that can tolerate drought when groundwater is not accessed. In addition to deep water uptake, hydraulic redistribution (HR) is another factor contributing to the drought tolerance of Tarnarix spp. In this study, data on soil volumetric moisture content (0), lateral root sap flow, and relevant climate variables were used to investigate the patterns, magnitude, and controlling factors of HR of soil water by roots of Tamarix ramosissima Ledeb. in an extremely arid land in Northwest China. Results showed evident diurnal fluctuations in 0 at the depths of 30 and 50 cm, indicating "hydraulic lift" (HL). 0 increased remarkably at 10 and 140 cm but decreased at 30 and 50 cm and slightly changed at 80 cm after rainfall, suggesting a possible "hydraulic descent" (HD). However, no direct evidence was observed in the negative flow of lateral roots, supporting HR (including HL and HD) of T. ramosissima. The HR pathway unlikely occurred via lateral roots; instead, HR possibly occurred through adventitious roots with a diameter of 2-5 mm and a length of 60-100 cm. HR at depths of 20-60 cm ranged from 0.01-1.77 mm/d with an average of 0.43 mm/d, which accounted for an average of 22% of the estimated seasonal total water depletion at 0-160 cm during the growing season. The climate factors, particularly vapor pressure deficit and soil water potential gradient, accounted for at least 33% and 45% of HR variations with depths and years, respectively. In summary, T. ramosissima can be added to the wide list of existing species involved in HR. High levels of HR may represent a considerable fraction of daily soil water depletion and substantially improve plant water status. HR could vary tremendously in terms of years and depths, and this variation could be attributed to climate factors and soil water potential gradient.
基金funded by the National Natural Science Foundation of China (40971032, 91125026)
文摘High-resolution observations of cambial phenology and intra-annual growth dynamics are useful approaches for understanding the response of tree growth to climate and environmental change. During the past two decades, rapid socioeconomic development has increased the demand for water resources in the oases of the middle reaches of the Heihe River in northwestern China, and the lower reaches of the Heihe River have changed from a perennial river to an ephemeral stream with a decreased and degraded riparian zone. Tamarisk(Tamarix ramosissima) is the dominant shrub species of the desert riparian forest. In this study, the daily and seasonal patterns of tamarisk stem diameter growth, including the main period of tree ring formation, were examined. Observations concerning the driving forces of growth changes, along with implications for the ecology of the dendrohydrological area and management of desert riparian forests in similar arid regions, are also presented. The diurnal-seasonal activity of stem diameter and the dynamics of growth ring formation were studied using a point dendrometer and micro-coring methods during the 2012 growing season in shrub tamarisk in a desert riparian forest stand in the lower reaches of the Heihe River in Ejin Banner, Inner Mongolia of northwestern China. Generally, the variation in diurnal diameter of tamarisk was characterized by an unstable multi-peak pattern, with the cumulative stem diameter growth over the growing season following an S-shaped curve. The period from late May to early August was the main period of stem diameter growth and growth-ring formation. Among all of the hydroclimatic factors considered in this study, only groundwater depth was significantly correlated with stem diameter increment during this period. Therefore, for the dendrochronological study, the annual rings of the tamarisk can be used to reconstruct processes that determine the regional water regime, such as river runoff and fluctuations in groundwater depth. For the management of desert riparian forests, suitable groundwater depths must be maintained in the spring and summer to sustain tree health and a suitable stand structure.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金financially supported by the National Natural Science Foundation of China (No. 91125025)
文摘Tamarix ramosissima Ledeb. is a typical hardy desert plant growing in arid regions of Northwest China. Sap flow in stems of Z ramosissima plants were measured continuously to determine the diurnal and seasonal variations of sap flow and to understand the water requirements of this species and the response of sap flow to meteorological factors. This article compared the sap flow rate measured by the heat balance method with the transpiration rate measured by rapid weighing, and validated that heat balance sap flow gauges were reliable for monitoring transpiration. The influence of meteorological factors on stem sap flow during the growing season was: solar radiation 〉 vapor pressure deficit 〉 air temperature 〉 rela- tive humidity 〉 wind speed. Bidirectional sap flows occurred at night, and negative sap flow generally corresponded to high atmospheric humidity. The average error in predicted sap flow rate ranged from -0.78% to 14.00% from June to September and for transpiration the average error was 8.19%. Therefore, based on the functional equations between sap flow and meteorological factors as well as sapwood area, transpiration of an individual plant, and even the stand-level transpiration, can be estimated accurately through extrapolation.
文摘Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.
文摘To determine the prevalence of metabolic syndrome (MetS) in Malaysian type 2 diabetic patients using WHO, NCEP ATP III, IDF and the new Harmonized definitions, and the concordance between these definitions. This study involved 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two Malaysian tertiary hospitals. Socio-demographic data were assessed using a pre-tested interviewer-administered structured questionnaire. Anthropometric measurements were carried out according to standard protocols. Clinical and laboratory characteristics were examined. Kappa (k) statistics were used for the agreement between the four MetS definitions. The overall prevalence rates of MetS (95% CI) were 95.8% (93.6-98.1), 96.1% (94.0-98.3), 84.8% (80.8-88.9) and 97.7% (96.1-99.4) according to the WHO, NCEP ATP III, IDF and the Harmonized definitions, respectively. The Kappa statistics demonstrated a slight to substantial agreement between the definitions (k = 0.179-0.875, p k = 0.875, p hest specificity (100%) in identifying MetS. In conclusion, the new Harmonized criteria established the highest prevalence of MetS among the four definitions applied. There was a very good concordance between the WHO and NCEP ATP III criteria. The extremely high prevalence of MetS observed in type 2 diabetic patients indicates an impending pandemic of CVD risk in Malaysia. Aggressive treatment of MetS components is required to reduce cardiovascular risk in T2DM.
基金supported by grants from the Lone Star Paralysis Foundation,NIH R01NS081063Department of Defense award W81XWH-19-2-0054 to GDB+2 种基金supported by University of Wyoming Startup funds,Department of Defense grant W81XWH-17-1-0402the University of Wyoming Sensory Biology COBRE under National Institutes of Health(NIH)award number 5P20GM121310-02the National Institute of General Medical Sciences of the NIH under award number P20GM103432 to JSB。
文摘Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.
文摘目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。
基金supported by the National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
基金Supported by(in part)Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B(No.17fk0310116h0001) from the Japan Agency for Medical Research and Development(AMED)Extramural Collaborative Research Grant of Cancer Research Institute,Kanazawa University
文摘Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.
文摘Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
文摘BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)vary widely in prognosis,and traditional pathological assessments often lack precision in risk stratification.Advanced imaging techniques,especially magnetic resonance imaging(MRI),offer potential improvements.This study investigates how MRI imagomics can enhance risk assessment and support personalized treatment for GIST patients.AIM To assess the effectiveness of MRI imagomics in improving GIST risk stratification,addressing the limitations of traditional pathological assessments.METHODS Analyzed clinical and MRI data from 132 GIST patients,categorizing them by tumor specifics and dividing into risk groups.Employed dimension reduction for optimal imagomics feature selection from diffusion-weighted imaging(DWI),T1-weighted imaging(T1WI),and contrast enhanced T1WI with fat saturation(CET1WI)fat suppress(fs)sequences.RESULTS Age,lesion diameter,and mitotic figures significantly correlated with GIST risk,with DWI sequence features like sphericity and regional entropy showing high predictive accuracy.The combined T1WI and CE-T1WI fs model had the best predictive efficacy.In the test group,the DWI sequence model demonstrated an area under the curve(AUC)value of 0.960 with a sensitivity of 80.0%and a specificity of 100.0%.On the other hand,the combined performance of the T1WI and CE-T1WI fs models in the test group was the most robust,exhibiting an AUC value of 0.834,a sensitivity of 70.4%,and a specificity of 85.2%.CONCLUSION MRI imagomics,particularly DWI and combined T1WI/CE-T1WI fs models,significantly enhance GIST risk stratification,supporting precise preoperative patient assessment and personalized treatment plans.The clinical implications are profound,enabling more accurate surgical strategy formulation and optimized treatment selection,thereby improving patient outcomes.Future research should focus on multicenter studies to validate these findings,integrate advanced imaging technologies like PET/MRI,and incorporate genetic factors to achieve a more comprehensive risk assessment.
文摘The snow cover over the Taurus Mountains affects water supply, agriculture, and hydropower generation in the region. In this study, we analyzed the monthly Snow Cover Extent(SCE) from November to April in the Central Taurus Mountains(Bolkar, Aladaglar, Tahtali and Binboga Mountains) from 1981 to 2021. Linear trends of snow cover season(November to April) over the last 41 years showed decreases in SCE primarily at lower elevations. The downward trend in SCE was found to be more pronounced and statistically significant for only November and March. SCE in the Central Taurus Mountains has declined about-6.3% per decade for 2500-3000 m in November and about-6.0% per decade for 1000-1500 m and 3000+ m in March over the last 41 years. The loss of SCE has become evident since the 2000s, and the lowest negative anomalies in SCE have been observed in 2014, 2001, and 2007 in the last 41 years, which are consistent with an increase in air temperature and decreased precipitation. SCE was correlated with both mean temperature and precipitation, with temperature having a greater relative importance at all elevated gradients. Results showed that there is a strong linear relationship between SCE and the mean air temperature(r =-0.80) and precipitation(r = 0.44) for all elevated gradients during the snow season. The Arctic Oscillation(AO), the North Atlantic Oscillation(NAO), and the Mediterranean Oscillation(MO) winter indices were used to explain the year-to-year variability in SCE over the Central Taurus Mountains. The results showed that the inter-annual variability observed in the winter SCE on the Central Taurus Mountains was positively correlated with the phases of the winter AO, NAO and MO, especially below 2000 m elevation.
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
文摘Aim: This paper aims to evaluate disparities of type 2 diabetes structured health education programmes that is utilised within the communities. Design: systematic review, (a type of secondary research design) aiming to summarize the results of prior primary research studies on available evidence Community type 2 diabetes structured education (CT2DSHE). Methods: Research question: Type 2 diabetic structured health education within a community how effective is it? Qualitative Systematic review, defined as a way to get reliable and objective picture of current available evidence on the specific topic—(CT2DSHE), (Denscombe, 2021) through reflexivity synthesis of available data as an example. This is valuable in time constraints such as project assignments that must be met within specific time and also to bring together available evidence together [1]. Results: This review has shown that CT2DSHE is effective with seven out of the eleven authors supporting, three authors against and one was neutral, further showed that knowledge and skills acquired can last longer with patient activation improved among T2DM patients ideal for sustaining their self-management of T2DM. Conclusion: This research provides suggestive answers to the research question: “Type 2 diabetic structured health education within a community how effective is it?”, This has demonstrated CT2DSHE effectiveness in knowledge acquisition and improving T2DM awareness among T2DM patients, whilst evidencing long effects beyond the study times of 3 - 9 months period in relation to patient activation. Also Identified diabetes education self-management on newly diagnosed (DESMOND) patient as CT2DSHE program for recommendation. Patient or Public Contribution: This work aspires to contribute to CT2DSHE in these areas;Influencing policy decision-making for community diabetes care within the UK and world at large., Contributing to already vast knowledge on diabetes self-management and reasons why?, Influencing educators on how CT2DSHEP are designed, delivered by putting the patient at the Centre and bringing different perspectives on CT2DSHEP in one place that is serving users time of having to consult several resources especially busy clinicians [2] [3].
基金funded by the China National Key Research and Development Program(No.2022YFC3003505)the Fundamental Research Fund for the Central Public-interest Scientific Institutes(No.DQJB23Y01)+1 种基金the National Natural Science Foundation of China(No.52278540)the Fundamental Research Fund for the Central Public-interest Scientific Institutes(No.DQJB22B28).
文摘In 2023,two consecutive earthquakes exceeding a magnitude of 7 occurred in Türkiye,causing severe casualties and economic losses.The damage to critical urban infrastructure and building structures,including highways,railroads,and water supply pipelines,was particularly severe in areas where these structures intersected the seismogenic fault.Critical infrastructure projects that traverse active faults are susceptible to the influence of fault movement,pulse velocity,and ground motions.In this study,we used a unique approach to analyze the acceleration records obtained from the seismic station array(9 strong ground motion stations)located along the East Anatolian Fault(the seismogenic fault of the MW7.8 mainshock of the 2023 Türkiye earthquake doublet).The acceleration records were filtered and integrated to obtain the velocity and displacement time histories.We used the results of an on-site investigation,jointly conducted by China Earthquake Administration and Türkiye’s AFAD,to analyze the distribution of PGA,PGV,and PGD recorded by the strong motion array of the East Anatolian Fault.We found that the maximum horizontal PGA in this earthquake was 3.0 g,and the maximum co-seismic surface displacement caused by the East Anatolian Fault rupture was 6.50 m.As the fault rupture propagated southwest,the velocity pulse caused by the directional effect of the rupture increased gradually,with the maximum PGA reaching 162.3 cm/s.We also discussed the seismic safety of critical infrastructure projects traversing active faults,using two case studies of water supply pipelines in Türkiye that were damaged by earthquakes.We used a three-dimensional finite element model of the PE(polyethylene)water pipeline at the Islahiye State Hospital and fault displacement observations obtained through on-site investigation to analyze pipeline failure mechanisms.We further investigated the effect of the fault-crossing angle on seismic safety of a pipeline,based on our analysis and the failure performance of the large-diameter Thames Water pipeline during the 1999 Kocaeli earthquake.The seismic method of buried pipelines crossing the fault was summarized.
基金supported by the Jiangsu Province’s Outstanding Medical Academic Leader Program [CXTDA2017029]the Jiangsu Provincial Key Medical Discipline [ZDXK202249].
文摘Objective This study investigated the impact of occupational mercury(Hg) exposure on human gene transcription and expression, and its potential biological mechanisms.Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN lowexpression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA.Results Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model(25 and 10 μmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression.Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels.Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.