Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. Ho...Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.展开更多
1.Introduction On December 18,2023,a M6.2 earthquake struck central China with epicenter at Jishishan,Gansu(35.70°N,102.79°E).In the USGS Latest Earthquake platform,the event was identified as M_(W)5.9,35.74...1.Introduction On December 18,2023,a M6.2 earthquake struck central China with epicenter at Jishishan,Gansu(35.70°N,102.79°E).In the USGS Latest Earthquake platform,the event was identified as M_(W)5.9,35.743°N,102.827°E,labeled 37 km WNW of Linxia Chengguanzhen,China.This study presents an open-access dataset comprising PGA and PGV records of the main-shock from 202accelerometers and 539 Micro-Electro-Mechanical System(MEMS)sensors within two arcdegrees of the epicenter.展开更多
[Objectives]This study was conducted to explore a functional organic material formula suitable for watermelon cultivation with high quality,high yield and high efficiency.[Methods]Four treatments were set in the exper...[Objectives]This study was conducted to explore a functional organic material formula suitable for watermelon cultivation with high quality,high yield and high efficiency.[Methods]Four treatments were set in the experiment,namely four functional organic materials,garlic straw treatment(T_(1)),onion straw treatment(T_(2)),garlic straw+sheep manure treatment(T_(3))and onion straw+chicken manure treatment(T_(4)),to investigate the effects of different functional organic materials on fresh weight,quality,single-melon weight and SPAD value of watermelon.[Results]The effects of different functional organic materials on fresh weight,quality,single-melon weight and SPAD value of watermelon were quite different.The fresh weight,quality,single-melon weight and SPAD value of watermelon were higher in treatment T_(3)applying garlic straw and sheep manure and treatment T_(4)applying onion straw and chicken manure than in treatment T_(1)applying garlic straw and treatment T_(2)applying onion straw.Specifically,the fresh weight of whole plant was the highest in treatment T_(3),followed by treatment T_(4),and the values of the two treatments increased by 12.83%and 5.94%respectively compared with treatment T_(1);the weight of single melon was the highest in treatment T_(3),followed by treatment T_(4),and the values of the two treatments increased by 42.45%and 31.77%respectively compared with treatment T_(2);and the SPAD values of treatments T_(3)and T_(4)were significantly higher than those of treatments T_(1)and T_(2),and the value of treatment T_(3)was the largest.[Conclusions]This study provides theoretical support for the popularization and application of fertilization techniques combining organic fertilizers and reduced chemical fertilizers for watermelon.展开更多
[Objectives]This study was conducted to explore suitable organic compound application models for watermelon growth.[Methods]With watermelon hybrid material"M22×P18"as the test material,the effects of fo...[Objectives]This study was conducted to explore suitable organic compound application models for watermelon growth.[Methods]With watermelon hybrid material"M22×P18"as the test material,the effects of four functional organic materials,namely garlic straw treatment(T_(1)),onion straw treatment(T_(2)),garlic straw+sheep manure treatment(T_(3))and onion straw+chicken manure treatment(T_(4)),on the morphological indexes,yield and quality of watermelon were investigated.[Results]Different functional organic materials had different effects on morphological indexes,yield and quality of watermelon.The morphological indexes,nutritional quality indexes and yield of watermelon treated with garlic straw and sheep manure compound(T_(3))and onion straw and chicken manure compound(T_(4))were significantly higher than those treated simply with garlic straw(T_(1))and onion straw(T_(2)),and T_(3)performed relatively better.Compared with treatment T_(2),T_(3)showed a stem diameter,vine length and leaf number increasing by 43.05%,46.69%and 40.77%respectively,central sugar and side sugar contents increasing by 11.72%and 21.90%respectively,and a yield increasing by 42.91%,with significant differences from T_(2).[Conclusions]This study provides technical support for high-quality and high-yielding cultivation of watermelon.展开更多
A promising method is to use coring of high-inclination well to find ancient flow direction and orient tiny natural fractures in massive sandstone of sandy debris flow. Determination of ancient flow direction can redu...A promising method is to use coring of high-inclination well to find ancient flow direction and orient tiny natural fractures in massive sandstone of sandy debris flow. Determination of ancient flow direction can reduce the number of exploration wells, and orientation of natural fractures is of guiding significance to the deployment of water injection development well pattern. In Block X of Huaqing Oilfield, Ordos Basin, the cores of Chang 6<sub>3</sub> section were obtained from Well Y through 16 coring operations, with a total length of 105 m. Cores is oriented through drilling parameters, the number of cores, the angle between the core edge and horizontal bedding, the coincidence degree of core profile and directional flame structure. Therefore, the micro-fractures on the core are directional. The ancient flow directions of sandy debris flow were restored by load casting, groove casting, groove casting and imbricate structure. Our results show that the ancient flow directions of sandy debris flows were southwest, southeast, northwest, and west from bottom to top. The front of the Wuqi Delta is the main source of blocky sandstone with the best oil-bearing property. Affected by the topography of the lake bottom, the sandy debris flow turned locally in the northeast direction, and the sandy debris flow from this direction was formed. The NEE-SWW-trending fractures formed in the Yanshanian period are most developed in the Huaqing area, which should be considered in deploying the flooding well network. The north-south micro-fractures formed in the Himalayan period can improve the physical properties of tight sandstone, which is of great significance for tight sandstone reservoirs.展开更多
Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of env...Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of environmental friendliness, mechanical properties, and stability. Here, we report a super-strong, biodegradable, and washable cellulose-based conductive macrofibers, which is prepared by wet-stretching and wet-twisting bacterial cellulose hydrogel incorporated with carbon nanotubes and polypyrrole. The cellulose-based conductive macrofibers possess high tensile strength of 449 MPa(able to lift 2 kg weights), good electrical conductivity(~ 5.32 S cm^(-1)), and excellent stability(Tensile strength and conductivity only decrease by 6.7% and 8.1% after immersing in water for 1 day). The degradation experiment demonstrates macrofibers can be degraded within 108 h in the cellulase solution. The designed fabric-based TENG from the cellulose-base conductive macrofibers shows a maximum open-circuit voltage of 170 V, short-circuit current of 0.8 μA, and output power at 352 μW, which is capable of powering the commercial electronics by charging the capacitors. More importantly, the fabric-based TENGs can be attached to the human body and work as self-powered sensors to effectively monitor human motions. This study suggests the potential of biodegradable, super-strong, and washable conductive cellulose-based fiber for designing eco-friendly fabric-based TENG for energy harvesting and biomechanical monitoring.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new...BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.展开更多
AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from II regular plasma donor...AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from II regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS: Among all of the sequential samples, the original 23 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples (75%) were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples (93.2%) were found HCV RNA-positive in HCV core antigen- positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION: This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period (PWP) plasma donations.展开更多
AIM: To investigate the association between nutrient intakes and high incidence rate of gastric cancer among residents in Zhoushan Islands.METHODS: A frequency-matched design of case-control study was used during the ...AIM: To investigate the association between nutrient intakes and high incidence rate of gastric cancer among residents in Zhoushan Islands.METHODS: A frequency-matched design of case-control study was used during the survey on dietary factors and gastric cancer in Zhoushan Islands, China. A total of 103 cases of gastric cancer diagnosed in 2001 were included in the study and 133 controls were randomly selected from the residents in Zhoushan Islands. A food frequency questionnaire was specifically designed for the Chinese dietary pattern to collect information on dietary intake. A computerized database of the dietary and other relative information of each participant was completed. Total calories and 15 nutrients were calculated according to the food composition table and their adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by gender using unconditional logistic regression models.RESULTS: High intakes of protein, saturated fat, and cholesterol were observed with the increased risk of gastric cancer particularly among males (ORQ4 vsQ1 were 10.3, 3.24, 2.76 respectively). While carbohydrate was a significant high-risk nutrient (ORQ4 vsQ1 = 14.8; Pfor linear trend = 0.024) among females. Regardless of their gender, the cases reported significantly higher daily intake of sodium mainly from salts. As to the nutrients of vitamins A and C, an inversed association with the risk of GC was found. Baseline characteristics of participants were briefly described.CONCLUSION: The findings from this study confirm the role of diet-related exposure in the etiology of gastric cancer from the point of view of epidemiology. An increased risk of gastric cancer is associated with high intakes of protein, saturated fat, cholesterol and sodium,while consumption of polyunsaturated fat, vitamin A and ascorbic acid may have a protective effect against gastric cancer.展开更多
The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has sho...The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration.We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA.However,the mechanism responsible for the elevation of H-type vessels in OA is still unclear.Here,we found that PDGFR-βexpression,predominantly in the CD31^(hi)Emcn^(hi) endothelium,was substantially elevated in subchondral bones from OA patients and rodent OA models.A mouse model of OA with deletion of PDGFR-βin endothelial cells(ECs)exhibited fewer H-type vessels,ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration.Endothelial PDGFR-βpromotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex.Notably,endothelium-specific inhibition of PDGFR-βby local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls.Based on the results from this study,targeting PDGFR-βis a novel and promising approach for the prevention or early treatment of OA.展开更多
AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma(VRL) and primary central nervous system lymphoma(PCNSL).METHODS: The clini...AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma(VRL) and primary central nervous system lymphoma(PCNSL).METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin(IL)-10 and IL-6.RESULTS: Twenty-six eyes(19.4%) out of 134 eyes of 67 patients(47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes(10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes(17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant.CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.展开更多
3-nitro-1,2,4-triazol-5-one(NTO)is the main component of insensitive munitions(IM)formulation because of its outstanding insensitive properties.In this paper,a series of NTO/HMX-based compositeexplosives were prepared...3-nitro-1,2,4-triazol-5-one(NTO)is the main component of insensitive munitions(IM)formulation because of its outstanding insensitive properties.In this paper,a series of NTO/HMX-based compositeexplosives were prepared and characterized.The study focuses on the effect of NTO on the perfommance of the formulations,especially the safety performance.The results revealed that the mechanical sensi-tivity of fomulations was associated with NTO content,as well as the thermal conductivity,specific heat capacity and Arrhenius parameters.Then,the high amount of NTO using in formulation was proved to be helpful for NTO/HMX-based formulation to exhibit good thermal safety.Besides,by accelerating rate calorimeter(ARC)and a modified cook-off equipment,the pressure and pressure rise rate were proved as the important indicator for judging the thermal safety performance in confined spaces.Finally,the numerical simulation was used as a credible method for predicting the respond temperature of cook-off experiment.展开更多
BACKGROUND: Sepsis is a common complication ofinfections, burns, traumas, surgeries, poisonings, and post-cardiopulmonary resuscitation. The present study aimed to investigate prognostic value of CD4+CD25+ regulatory ...BACKGROUND: Sepsis is a common complication ofinfections, burns, traumas, surgeries, poisonings, and post-cardiopulmonary resuscitation. The present study aimed to investigate prognostic value of CD4+CD25+ regulatory T cells(Treg) in peripheral blood of patients with sepsis.METHODS: Periphery blood from 28 patients diagnosed with sepsis was collected on day 1 and 7 after hospitalization in the ICU of Shanghai Changzheng Hospital between December 2013 to April 2014. The blood was used for analyses of Treg ratio using flow cytometry and for analyses of blood routine test, C-reactive protein(CRP), bilirubin, procalcitonin(PCT), and coagulation. APACHE II and sequential organ failure assessment(SOFA) scores were also investigated. The results were compared between two outcome groups of survival or death to evaluate prognostic value for sepsis.RESULTS: The patients had an average age of 60.36±15.03 years, APACHE II score 16.68±7.00, and SOFA score 7.18±3.78. Among the 28 patients, 12 had severe trauma(42.9%), 10 had septic shock(35.7%), and 9(32.2%) died. The median ratio of Tregs was 2.10%(0.80%, 3.10%) in the survival group vs. 1.80%(1.15%, 3.65%) in the death group(Z=–0.148, P=0.883) on day 1; however it was signifi cantly changed to 0.90%(0.30%, 2.80%) vs. 5.70%(2.60%, 8.30%)(Z=–2.905, P=0.004).CONCLUSION: With better prospects for clinical application, dynamic monitoring of Tregs ratio in peripheral blood has potential value in predicting prognosis of sepsis.展开更多
Background:The rapid development of the blockchain technology and its various applications has rendered it important to understand the guidelines for adopting it.Methods:The comparative analysis method is used to anal...Background:The rapid development of the blockchain technology and its various applications has rendered it important to understand the guidelines for adopting it.Methods:The comparative analysis method is used to analyze different dimensions of the maturity model,which is mainly based on the commonly used capability maturity model.Results:The blockchain maturity model and its adoption process have been discussed and presented.Conclusions:This study serves as a guide to institutions to make blockchain adoption decisions more systematically.展开更多
In the present study, thermal hazards of TNT and DNAN used as the molten binder in TKX-50-based meltcast explosives were comparatively studied through accelerating rate calorimeter(ARC) and Cook-off experiments. Two k...In the present study, thermal hazards of TNT and DNAN used as the molten binder in TKX-50-based meltcast explosives were comparatively studied through accelerating rate calorimeter(ARC) and Cook-off experiments. Two kinds of ARC operation modes were performed to investigate the thermal safety performance under adiabatic conditions(HWS mode) and constant heating(CHR mode). The obtained results demonstrated that at both heating modes, DNAN/TKX-50 outperformed TNT/TKX-50 from the thermal safety point of view. However, the sensitivity to heat of the samples was reverse because of the different heating modes. In addition, the results of thermal hazard assessment obtained from the cookoff experiment complied with ARC analysis which indicated the molten binder TNT replaced by DNAN would reduce the hazard of the TKX-50 melt cast explosive. Furthermore, the results of cook-off experiments also showed that DNAN/TKX-50 outperformed TNT/TKX-50 from the aspect of thermal stability, which was consistent with the result of CHR mode because of the similar heating process.展开更多
Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We a...Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBs Ag-positive male adults.Methods: HBs Ag-positive males of 35-69 years old(N=6,153) were included from a multi-center populationbased liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using Bultrasonography and α-fetoprotein(AFP). We used logistic regression models to determine potential risk factors,built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT(γ-glutamyl-transpeptidase), counts of platelets, white cells,concentration of DCP(des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.90-0.93), larger than existing models. At 1.5 points of risk score,26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk,with positive prediction value of 22.85% and 12.35%, respectively.Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.展开更多
基金supported by the National Natural Science Foundation of China(Grant No:81903643)the“Young Talent Support Plan”of Xi'an Jiaotong University,the Shaanxi Province Science and Technology Development Plan Project(Grant No.:2022ZDLSF05-05)+1 种基金the Project of Shaanxi Provincial Administration of Traditional Chinese Medicine(Project No.:2021-03-ZZ-002)the Shaanxi Province Science Fund for Distinguished Young Scholars(Grant No:2023-JC-JQ-59).
文摘Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.
基金supported by the National Natural Science Foundation of China(No.42120104002)Science for Earthquake Resilience(No.XH23052C)the Program of China-Pakistan Joint Research Center on Earth Sciences.
文摘1.Introduction On December 18,2023,a M6.2 earthquake struck central China with epicenter at Jishishan,Gansu(35.70°N,102.79°E).In the USGS Latest Earthquake platform,the event was identified as M_(W)5.9,35.743°N,102.827°E,labeled 37 km WNW of Linxia Chengguanzhen,China.This study presents an open-access dataset comprising PGA and PGV records of the main-shock from 202accelerometers and 539 Micro-Electro-Mechanical System(MEMS)sensors within two arcdegrees of the epicenter.
基金Supported by Shangqiu Science and Technology Research Project(202405).
文摘[Objectives]This study was conducted to explore a functional organic material formula suitable for watermelon cultivation with high quality,high yield and high efficiency.[Methods]Four treatments were set in the experiment,namely four functional organic materials,garlic straw treatment(T_(1)),onion straw treatment(T_(2)),garlic straw+sheep manure treatment(T_(3))and onion straw+chicken manure treatment(T_(4)),to investigate the effects of different functional organic materials on fresh weight,quality,single-melon weight and SPAD value of watermelon.[Results]The effects of different functional organic materials on fresh weight,quality,single-melon weight and SPAD value of watermelon were quite different.The fresh weight,quality,single-melon weight and SPAD value of watermelon were higher in treatment T_(3)applying garlic straw and sheep manure and treatment T_(4)applying onion straw and chicken manure than in treatment T_(1)applying garlic straw and treatment T_(2)applying onion straw.Specifically,the fresh weight of whole plant was the highest in treatment T_(3),followed by treatment T_(4),and the values of the two treatments increased by 12.83%and 5.94%respectively compared with treatment T_(1);the weight of single melon was the highest in treatment T_(3),followed by treatment T_(4),and the values of the two treatments increased by 42.45%and 31.77%respectively compared with treatment T_(2);and the SPAD values of treatments T_(3)and T_(4)were significantly higher than those of treatments T_(1)and T_(2),and the value of treatment T_(3)was the largest.[Conclusions]This study provides theoretical support for the popularization and application of fertilization techniques combining organic fertilizers and reduced chemical fertilizers for watermelon.
基金Supported by Shangqiu Science and Technology Research Project(202405).
文摘[Objectives]This study was conducted to explore suitable organic compound application models for watermelon growth.[Methods]With watermelon hybrid material"M22×P18"as the test material,the effects of four functional organic materials,namely garlic straw treatment(T_(1)),onion straw treatment(T_(2)),garlic straw+sheep manure treatment(T_(3))and onion straw+chicken manure treatment(T_(4)),on the morphological indexes,yield and quality of watermelon were investigated.[Results]Different functional organic materials had different effects on morphological indexes,yield and quality of watermelon.The morphological indexes,nutritional quality indexes and yield of watermelon treated with garlic straw and sheep manure compound(T_(3))and onion straw and chicken manure compound(T_(4))were significantly higher than those treated simply with garlic straw(T_(1))and onion straw(T_(2)),and T_(3)performed relatively better.Compared with treatment T_(2),T_(3)showed a stem diameter,vine length and leaf number increasing by 43.05%,46.69%and 40.77%respectively,central sugar and side sugar contents increasing by 11.72%and 21.90%respectively,and a yield increasing by 42.91%,with significant differences from T_(2).[Conclusions]This study provides technical support for high-quality and high-yielding cultivation of watermelon.
文摘A promising method is to use coring of high-inclination well to find ancient flow direction and orient tiny natural fractures in massive sandstone of sandy debris flow. Determination of ancient flow direction can reduce the number of exploration wells, and orientation of natural fractures is of guiding significance to the deployment of water injection development well pattern. In Block X of Huaqing Oilfield, Ordos Basin, the cores of Chang 6<sub>3</sub> section were obtained from Well Y through 16 coring operations, with a total length of 105 m. Cores is oriented through drilling parameters, the number of cores, the angle between the core edge and horizontal bedding, the coincidence degree of core profile and directional flame structure. Therefore, the micro-fractures on the core are directional. The ancient flow directions of sandy debris flow were restored by load casting, groove casting, groove casting and imbricate structure. Our results show that the ancient flow directions of sandy debris flows were southwest, southeast, northwest, and west from bottom to top. The front of the Wuqi Delta is the main source of blocky sandstone with the best oil-bearing property. Affected by the topography of the lake bottom, the sandy debris flow turned locally in the northeast direction, and the sandy debris flow from this direction was formed. The NEE-SWW-trending fractures formed in the Yanshanian period are most developed in the Huaqing area, which should be considered in deploying the flooding well network. The north-south micro-fractures formed in the Himalayan period can improve the physical properties of tight sandstone, which is of great significance for tight sandstone reservoirs.
基金financially supported by BRICS STI Framework Programme 3rd call 2019the National Key Research and Development Program of China(Grant No.2018YFE0123700)+3 种基金the National Natural Science Foundation of China(Grant Nos.51973076 and 52073031)State Key Laboratory of New Textile Materials and Advanced Processing Technologies(Grant No.FZ2021005)the Fundamental Research Funds for the Central Universities(Grant Nos.2020kfyXJJS035,WUT2018IVB006,and Z191100001119047)。
文摘Electronic fibers used to fabricate wearable triboelectric nanogenerator(TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of environmental friendliness, mechanical properties, and stability. Here, we report a super-strong, biodegradable, and washable cellulose-based conductive macrofibers, which is prepared by wet-stretching and wet-twisting bacterial cellulose hydrogel incorporated with carbon nanotubes and polypyrrole. The cellulose-based conductive macrofibers possess high tensile strength of 449 MPa(able to lift 2 kg weights), good electrical conductivity(~ 5.32 S cm^(-1)), and excellent stability(Tensile strength and conductivity only decrease by 6.7% and 8.1% after immersing in water for 1 day). The degradation experiment demonstrates macrofibers can be degraded within 108 h in the cellulase solution. The designed fabric-based TENG from the cellulose-base conductive macrofibers shows a maximum open-circuit voltage of 170 V, short-circuit current of 0.8 μA, and output power at 352 μW, which is capable of powering the commercial electronics by charging the capacitors. More importantly, the fabric-based TENGs can be attached to the human body and work as self-powered sensors to effectively monitor human motions. This study suggests the potential of biodegradable, super-strong, and washable conductive cellulose-based fiber for designing eco-friendly fabric-based TENG for energy harvesting and biomechanical monitoring.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2016-I2M-1-001PUMC Youth Fund,No.2017320010+1 种基金Chinese Academy of Medical Sciences Research Fund,No.ZZ2016B01Beijing HopeRun Special Fund of Cancer Foundation of China,No.LC2016B15
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.
基金Supported by the National Key Technologies R&D Program of China during the 10th Five-Year Plan, No. 2001BA705B06 National High Technology Research and Development Program of China (863 Program), No. 2006AA020907
文摘AIM: To evaluate the efficacy of a new hepatitis C virus (HCV) core antigen assay developed in China. METHODS: After the determination of HCV infection, 49 serial samples were selected from II regular plasma donors in 5 different plasma stations. To compare the performance of HCV core antigen detection and HCV PCR, these samples were genotyped, and each specimen was analyzed by ELISA for the detection of HCV core antigen and by qualitative HCV PCR. RESULTS: Among all of the sequential samples, the original 23 specimens were HCV RNA-negative, and 36 samples were HCV RNA-positive. Twenty-seven samples (75%) were HCV core antigen-positive from these HCV RNA-positive specimens. Conversely, 27 samples (93.2%) were found HCV RNA-positive in HCV core antigen- positive samples. Intervals between HCV RNA and HCV core antigen-positive, as well as between HCV core antigen-positive and HCV antibody-positive were 36.0 and 32.8 d, respectively. CONCLUSION: This HCV core antigen assay, developed in China, is able to detect much of anti-HCV-negative, HCV RNA-positive preseroconversion window period (PWP) plasma donations.
基金Supported by the Foundation of Ministry of Public Health of China, No. WKZ-2001-1-17
文摘AIM: To investigate the association between nutrient intakes and high incidence rate of gastric cancer among residents in Zhoushan Islands.METHODS: A frequency-matched design of case-control study was used during the survey on dietary factors and gastric cancer in Zhoushan Islands, China. A total of 103 cases of gastric cancer diagnosed in 2001 were included in the study and 133 controls were randomly selected from the residents in Zhoushan Islands. A food frequency questionnaire was specifically designed for the Chinese dietary pattern to collect information on dietary intake. A computerized database of the dietary and other relative information of each participant was completed. Total calories and 15 nutrients were calculated according to the food composition table and their adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by gender using unconditional logistic regression models.RESULTS: High intakes of protein, saturated fat, and cholesterol were observed with the increased risk of gastric cancer particularly among males (ORQ4 vsQ1 were 10.3, 3.24, 2.76 respectively). While carbohydrate was a significant high-risk nutrient (ORQ4 vsQ1 = 14.8; Pfor linear trend = 0.024) among females. Regardless of their gender, the cases reported significantly higher daily intake of sodium mainly from salts. As to the nutrients of vitamins A and C, an inversed association with the risk of GC was found. Baseline characteristics of participants were briefly described.CONCLUSION: The findings from this study confirm the role of diet-related exposure in the etiology of gastric cancer from the point of view of epidemiology. An increased risk of gastric cancer is associated with high intakes of protein, saturated fat, cholesterol and sodium,while consumption of polyunsaturated fat, vitamin A and ascorbic acid may have a protective effect against gastric cancer.
基金This study was supported by the Natural Science Foundation of Guangdong Province,China(2019A1515011614 to ZC)the Science and Technology Program of Guangzhou(202002030483 to ZC)+2 种基金the National Natural Science Foundation of China(81601942 to ZC and 81830079 to BY)the Outstanding Youths Development Scheme of Southern Medical University(2021YQPY008 to ZC)the National Key R&D Program of China(2019YFA0111900 to CL).
文摘The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis(OA)remain unknown.No pharmacological intervention can currently prevent the progression of osteoarthritis.Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration.We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA.However,the mechanism responsible for the elevation of H-type vessels in OA is still unclear.Here,we found that PDGFR-βexpression,predominantly in the CD31^(hi)Emcn^(hi) endothelium,was substantially elevated in subchondral bones from OA patients and rodent OA models.A mouse model of OA with deletion of PDGFR-βin endothelial cells(ECs)exhibited fewer H-type vessels,ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration.Endothelial PDGFR-βpromotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex.Notably,endothelium-specific inhibition of PDGFR-βby local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls.Based on the results from this study,targeting PDGFR-βis a novel and promising approach for the prevention or early treatment of OA.
基金Supported by the National Natural Science Foundation of China(No.81700123)the Shanghai Hospital Development Centre(No.16CR2043B)
文摘AIM: To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma(VRL) and primary central nervous system lymphoma(PCNSL).METHODS: The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin(IL)-10 and IL-6.RESULTS: Twenty-six eyes(19.4%) out of 134 eyes of 67 patients(47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes(10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes(17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant.CONCLUSION: A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.
基金The authors are grateful to the National Defense Foundation of China(3090021322001,3090020221912,3090021211903.)for financial support of this work.
文摘3-nitro-1,2,4-triazol-5-one(NTO)is the main component of insensitive munitions(IM)formulation because of its outstanding insensitive properties.In this paper,a series of NTO/HMX-based compositeexplosives were prepared and characterized.The study focuses on the effect of NTO on the perfommance of the formulations,especially the safety performance.The results revealed that the mechanical sensi-tivity of fomulations was associated with NTO content,as well as the thermal conductivity,specific heat capacity and Arrhenius parameters.Then,the high amount of NTO using in formulation was proved to be helpful for NTO/HMX-based formulation to exhibit good thermal safety.Besides,by accelerating rate calorimeter(ARC)and a modified cook-off equipment,the pressure and pressure rise rate were proved as the important indicator for judging the thermal safety performance in confined spaces.Finally,the numerical simulation was used as a credible method for predicting the respond temperature of cook-off experiment.
文摘BACKGROUND: Sepsis is a common complication ofinfections, burns, traumas, surgeries, poisonings, and post-cardiopulmonary resuscitation. The present study aimed to investigate prognostic value of CD4+CD25+ regulatory T cells(Treg) in peripheral blood of patients with sepsis.METHODS: Periphery blood from 28 patients diagnosed with sepsis was collected on day 1 and 7 after hospitalization in the ICU of Shanghai Changzheng Hospital between December 2013 to April 2014. The blood was used for analyses of Treg ratio using flow cytometry and for analyses of blood routine test, C-reactive protein(CRP), bilirubin, procalcitonin(PCT), and coagulation. APACHE II and sequential organ failure assessment(SOFA) scores were also investigated. The results were compared between two outcome groups of survival or death to evaluate prognostic value for sepsis.RESULTS: The patients had an average age of 60.36±15.03 years, APACHE II score 16.68±7.00, and SOFA score 7.18±3.78. Among the 28 patients, 12 had severe trauma(42.9%), 10 had septic shock(35.7%), and 9(32.2%) died. The median ratio of Tregs was 2.10%(0.80%, 3.10%) in the survival group vs. 1.80%(1.15%, 3.65%) in the death group(Z=–0.148, P=0.883) on day 1; however it was signifi cantly changed to 0.90%(0.30%, 2.80%) vs. 5.70%(2.60%, 8.30%)(Z=–2.905, P=0.004).CONCLUSION: With better prospects for clinical application, dynamic monitoring of Tregs ratio in peripheral blood has potential value in predicting prognosis of sepsis.
基金National Natural Science Foundation of China(No.71601090).
文摘Background:The rapid development of the blockchain technology and its various applications has rendered it important to understand the guidelines for adopting it.Methods:The comparative analysis method is used to analyze different dimensions of the maturity model,which is mainly based on the commonly used capability maturity model.Results:The blockchain maturity model and its adoption process have been discussed and presented.Conclusions:This study serves as a guide to institutions to make blockchain adoption decisions more systematically.
基金the National Defense Foundation of China (3090021322001, 3090020221912, 3090021211903.) for financial support of this work。
文摘In the present study, thermal hazards of TNT and DNAN used as the molten binder in TKX-50-based meltcast explosives were comparatively studied through accelerating rate calorimeter(ARC) and Cook-off experiments. Two kinds of ARC operation modes were performed to investigate the thermal safety performance under adiabatic conditions(HWS mode) and constant heating(CHR mode). The obtained results demonstrated that at both heating modes, DNAN/TKX-50 outperformed TNT/TKX-50 from the thermal safety point of view. However, the sensitivity to heat of the samples was reverse because of the different heating modes. In addition, the results of thermal hazard assessment obtained from the cookoff experiment complied with ARC analysis which indicated the molten binder TNT replaced by DNAN would reduce the hazard of the TKX-50 melt cast explosive. Furthermore, the results of cook-off experiments also showed that DNAN/TKX-50 outperformed TNT/TKX-50 from the aspect of thermal stability, which was consistent with the result of CHR mode because of the similar heating process.
基金supported by State Key Projects Specialized on Infectious Diseases (No. 2017ZX10201201-006)Key research projects for precision medicine (No. 2017YFC0908103)+1 种基金Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences (CIFMS, No. 2019-I2M-2-004, 2016-I2M-1-007, 2019-I2M-1-003)National Natural Science Foundation Fund (No. 81972628, No. 81974492)。
文摘Objective: Hepatocellular carcinoma(HCC) development among hepatitis B surface antigen(HBs Ag) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBs Ag-positive male adults.Methods: HBs Ag-positive males of 35-69 years old(N=6,153) were included from a multi-center populationbased liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using Bultrasonography and α-fetoprotein(AFP). We used logistic regression models to determine potential risk factors,built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.Results: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT(γ-glutamyl-transpeptidase), counts of platelets, white cells,concentration of DCP(des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.90-0.93), larger than existing models. At 1.5 points of risk score,26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk,with positive prediction value of 22.85% and 12.35%, respectively.Conclusions: Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.