AIM: To study the inhibitory effects of Fuzheng Yiliuyin (Decoction for Suppressing Tumors by Strengthening the Body Resistance) in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS...AIM: To study the inhibitory effects of Fuzheng Yiliuyin (Decoction for Suppressing Tumors by Strengthening the Body Resistance) in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS: Fuzheng Yiliuyin (ZY) combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains, then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytorneter was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope. RESULTS: Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with tluorouracil, etoposide and cisplatin (EFP) chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803. CONCLUSION: ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.展开更多
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
Statistical characteristics and the classification of the topside ionospheric mid-latitude trough are systemically analyzed,using observations from the Defense Meteorological Satellite Program F18(DMSP-F18)satellite.T...Statistical characteristics and the classification of the topside ionospheric mid-latitude trough are systemically analyzed,using observations from the Defense Meteorological Satellite Program F18(DMSP-F18)satellite.The data was obtained at an altitude of around 860 km in near polar orbit,throughout 2013.Our study identified the auroral boundary based on the in-situ electron density and electron spectrum,allowing us to precisely determine the location of the mid-latitude trough.This differs from most previous works,which only use Total Electron Content(TEC)or in-situ electron density.In our study,the troughs exhibited a higher occurrence rate in local winter than in summer,and extended to lower latitudes with increasing geomagnetic activity.It was found that the ionospheric mid-latitude trough,which is associated with temperature changes or enhanced ion drift,exhibited distinct characteristics.Specifically,the ionospheric mid-latitude troughs related to electron temperature(Te)peak were located more equatorward of auroral oval boundary in winter than in summer.The ionospheric mid-latitude troughs related to Te-maximum were less frequently observed at 60−70°S magnetic latitude and 90−240°E longitude.Furthermore,the troughs related to ion temperature(Ti)maximums were observed at relatively higher latitudes,occurring more frequently in winter.In addition,the troughs related to ion velocity(Vi)maximums could be observed in all seasons.The troughs with the maximum-Ti and maximum-Vi were located closer to the equatorward boundary of the auroral oval at the nightside,and in both hemispheres.This implies that enhanced ion drift velocity contributes to increased collisional frictional heating and enhanced ion temperatures,resulting in a density depletion within the trough region.展开更多
The hot deformation behavior of Pt−10Ir alloy was studied under a wide range of deformation parameters.At a low deformation temperature(950−1150℃),the softening mechanism is primarily dynamic recovery.In addition,dyn...The hot deformation behavior of Pt−10Ir alloy was studied under a wide range of deformation parameters.At a low deformation temperature(950−1150℃),the softening mechanism is primarily dynamic recovery.In addition,dynamic recrystallization by progressive lattice rotation near grain boundaries(DRX by LRGBs)and microshear bands assisted dynamic recrystallization(MSBs assisted DRX)coordinate the deformation.However,it is difficult for the dynamic softening to offset the stain hardening due to a limited amount of DRXed grains.At a high deformation temperature(1250−1350℃),three main DRX mechanisms associated with strain rates occur:DRX by LRGBs,DRX by a homogeneous increase in misorientation(HIM)and geometric DRX(GDRX).With increasing strain,DRX by LRGBs is enhanced gradually under high strain rates;the“pinch-off”effect is enhanced at low strain rates,which was conducive to the formation of a uniform and fine microstructure.展开更多
Heat stress hinders the growth and productivity of sweetpotato plants,predominantly through oxidative damage to cellular membranes.Therefore,the development of efficient approaches for mitigating heat-related impairme...Heat stress hinders the growth and productivity of sweetpotato plants,predominantly through oxidative damage to cellular membranes.Therefore,the development of efficient approaches for mitigating heat-related impairments is essential for the long-term production of sweetpotatoes.Melatonin has been recognised for its capacity to assist plants in dealing with abiotic stress conditions.This research aimed to investigate how different doses of exogenous melatonin influence heat damage in sweetpotato plants.Heat stress drastically affected shoot and root fresh weight by 31.8 and 44.5%,respectively.This reduction resulted in oxidative stress characterised by increased formation of hydrogen peroxide(H_(2)O_(2))by 804.4%,superoxide ion(O_(2)^(·-))by 211.5%and malondialdehyde(MDA)by 234.2%.Heat stress also reduced chlorophyll concentration,photosystemⅡefficiency(F_v/F_m)by 15.3%and gaseous exchange.However,pre-treatment with 100μmol L^(-1)melatonin increased growth and reduced oxidative damage to sweetpotato plants under heat stress.In particular,melatonin decreased H_(2)O_(2),O_(2)^(·-)and MDA by 64.8%,42.7%and 38.2%,respectively.Melatonin also mitigated the decline in chlorophyll levels and improved stomatal traits,gaseous exchange and F_(v)/F_(m)(13%).Results suggested that the favorable outcomes of melatonin treatment can be associated with elevated antioxidant enzyme activity and an increase in non-enzymatic antioxidants and osmo-protectants.Overall,these findings indicate that exogenous melatonin can improve heat stress tolerance in sweetpotatoes.This stu dy will assist re searchers in further investigating how melatonin makes sweetpotatoes more resistant to heat stress.展开更多
BACKGROUND Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels,making its radical resection challenging.Multimodal treatment strategies,including neoadjuvant therapy,surger...BACKGROUND Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels,making its radical resection challenging.Multimodal treatment strategies,including neoadjuvant therapy,surgery,and postoperative adjuvant therapy,are contributing to a paradigm shift in the treatment of pancreatic cancer.This strategy is also promising in the treatment of pancreatic neckbody cancer.AIM To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.METHODS From January 2019 to December 2021,we reviewed the demographic characteristics,neoadjuvant and adjuvant treatment data,intraoperative and postoperative variables,and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital.This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.RESULTS A total of 11 patients with pancreatic neck-body cancer were included in this study,of whom 6 patients were borderline resectable and 5 were locally advanced.Through multidisciplinary team discussion,all patients received neoadjuvant therapy,of whom 8(73%)patients achieved a partial response and 3 patients maintained stable disease.After multidisciplinary team reassessment,all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection.Postoperatively,two patients(18%)developed ascites,and two patients(18%)developed pancreatic fistulae.The median length of stay of the patients was 11 days(range:10-15 days).All patients received postoperative adjuvant therapy.During the follow-up,three patients experienced tumor recurrence,with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.CONCLUSION A multimodal treatment strategy combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy,and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.展开更多
AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding ei...AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.展开更多
BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebr...BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control b^ood pressure together with other cardiovascular risk factors. OBJECTIVE: The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group (anti-hypertensive drugs plus Yiqi Huaju Formula, CHF) and the control group (anti-hypertensive drugs plus placebo). The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES: Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin (HbAlc), fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), fasting plasma insulin, serum lipid, etc. RESULTS: Compared with the control group, the CHF group had significant improvement (P〈0.01) in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION: This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER: ChiCTR-TRC-11001633.展开更多
BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to ...BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbAlc), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P〈0.05), WC (P〈0.01) and WHR (P〈0.01). Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P〈0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P〈0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P〉0.05), whereas it significantly increased with CHF treatment (P〈0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P〈0.01). However, there was no significant difference between the two groups (P〉0.05). CONCLUSION: Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.展开更多
AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylate...AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.展开更多
Novel dual-ionic imidazolium salts are shown to display excellent catalytic activity for cycloaddition of carbon dioxide and epoxides under room temperature and atmospheric pressure(0.1 MPa)without any solvent and co-...Novel dual-ionic imidazolium salts are shown to display excellent catalytic activity for cycloaddition of carbon dioxide and epoxides under room temperature and atmospheric pressure(0.1 MPa)without any solvent and co-catalyst leading to 96.1%product yield.It can be reused five times to keep the product yield over 90%.These intriguing results are attributed to a new reaction mechanism,which is supported by theoretical calculations along with the measurements of ^(13)C NMR spectrum and Fourier transform infrared spectroscopy(FT-IR).The excellent catalytic activity can be traced to a CO_(2)-philic group along with an electrophilic hydrogen atom.Our work shows that incorporation of CO_(2)-philic group is an feasible pathway to develop the new efficient ionic liquids.展开更多
Background:Sophora flavescens,a traditional Chinese herb medicine,has been used to prevent and cure type 2 diabetes mellitus(T2DM)both in folk medicine and medical institutions.Modern pharmacological studies have also...Background:Sophora flavescens,a traditional Chinese herb medicine,has been used to prevent and cure type 2 diabetes mellitus(T2DM)both in folk medicine and medical institutions.Modern pharmacological studies have also demonstrated that the flavonoids obtained from Sophora flavescens ethyl acetate extract(SFE)exhibited potential anti-diabetic activity.Our previous study elucidated that SFE exerts anti-T2DM effects by regulating the host-microbial metabolic axis.In the present study,we further explored the pharmacodynamic effect and the potential targets of the anti-T2DM activity of SFE by integrating network pharmacology and pharmacological evaluations.Methods:The diabetic rat model was created by streptozotocin and oral administration with SFE for 8 weeks.Then,the T2DM-related index was estimated to assess the interventional effect of SFE.Network pharmacology was applied to identify the likely targets and the pathways modulated by SFE components.Furthermore,Western blotting was applied to verify the prediction.Results:Pharmacological evaluation in vivo revealed that SFE could markedly improve the blood glucose,serum insulin secretion,insulin resistance,liver glycogen synthesis,and the liver tissue structure in T2DM rats.Through network pharmacology analysis,101 active compounds of SFE and 114 targets belonging to 128 pathways were identified.The insulin,TNF,IL-6,and PI3K/Akt pathway may be the key targets and pathway.Based on the results of network pharmacology analysis,IRS/PI3K/Akt and IKK/NF-κB/TNF pathways were selected for further validation.Subsequently,experimental results of Western blotting confirmed that SFE may exert anti-T2DM effects by modulating the IRS/PI3K/Akt and IKK/NF-κB/TNF pathways.Conclusion:SFE may protect the T2DM rats by relieving the insulin resistance and inflammation through regulating the IRS/PI3K/Akt and IKK/NF-κB/TNF pathways.The results of the present study would improve the comprehension of the pharmacological basis of SFE against T2DM and provide a theoretical basis for the clinical use of Sophora flavescens.展开更多
Objective:To establish a co-culture model of colon cancer cells or mesenchymal stem cells with normal colon epithelial cells in vitro for simulating the tumor microenvironment in vitro,and to investigate the effect of...Objective:To establish a co-culture model of colon cancer cells or mesenchymal stem cells with normal colon epithelial cells in vitro for simulating the tumor microenvironment in vitro,and to investigate the effect of colon cancer cells or mesenchymal stem cells on the migration and epithelial-mesenchymal transformation(EMT)of normal colon epithelial cells in the co-culture environment.Method:Co-culture model of colon cancer cell line SW480 or human umbilical cord mesenchymal stem cells(hUC-MSCs)with human normal colon epithelial cells(NCM460)was established.Morphological changes of NCM460 after co-culture were evaluated by microscopic observation,and migration ability of NCM460 was measured by wound healing and Transwell assay.Meanwhile,Western blot was used to detect the EMT markers of NCM460.Results:There was no significant change in cell morphology of NCM460.Transwell assay results showed that when hUC-MSC or SW480 were co-cultured with NCM460,there is a trend of enhancement of the migration ability of NCM460,and the expression of Vimentin was up-regulated to some extent(P<0.05),E-cadherin and wound healing ability were not significantly changed(P>0.05).When NCM460 were cocultured with MSCs and SW480 at the same time,NCM460's wound healing ability and migration ability were significantly enhanced,meanwhile Vimentin protein expression was significantly up-regulated and E-cadherin protein was significantly down-regulated significantly(P<0.05).Conclusion:Colon cancer cells can increase the migration ability of normal colon epithelial cells and upregulate the expression of EMT markers.Mesenchymal stem cells may play a role in this process.展开更多
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in...A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.展开更多
Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different ...Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.展开更多
Owing to the intrinsically sluggish kinetics of urea oxidation reaction(UOR)involving a six-electron transfer process,developing efficient UOR electrocatalyst is a great challenge remained to be overwhelmed.Herein,by ...Owing to the intrinsically sluggish kinetics of urea oxidation reaction(UOR)involving a six-electron transfer process,developing efficient UOR electrocatalyst is a great challenge remained to be overwhelmed.Herein,by taking advantage of 2-Methylimidazole,of which is a kind of alkali in water and owns strong coordination ability to Co^(2+)in methanol,trace Co(1.0 mol%)addition was found to induce defect engineering onα-Ni(OH)_(2)in a dual-solvent system of water and methanol.Physical characterization results revealed that the synthesized electrocatalyst(WM-Ni_(0.99)Co_(0.01)(OH)_(2))was a kind of defective nanosheet with thickness around 5-6 nm,attributing to the synergistic effect of Co doping and defect engineering,its electron structure was finely altered,and its specific surface a rea was tremendously enlarged from 68 to 172.3 m^(2)g^(-1).With all these merits,its overpotential to drive 10 mA cm^(-2)was reduced by 110 mV.Besides,the interfacial behavior of UOR was also well deciphered by operando electrochemical impedance spectroscopy.展开更多
基金Supported by TCM Administration Bureau of Shannxi Province,China, No. 199704
文摘AIM: To study the inhibitory effects of Fuzheng Yiliuyin (Decoction for Suppressing Tumors by Strengthening the Body Resistance) in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS: Fuzheng Yiliuyin (ZY) combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains, then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytorneter was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope. RESULTS: Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with tluorouracil, etoposide and cisplatin (EFP) chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803. CONCLUSION: ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
基金supported by the National Key R&D Program of China(2022YFF0504400)the National Natural Science Foundation of China(42188101,42274195,42174193)+2 种基金the International Partnership Program Of Chinese Academy of Sciences(Grant No.183311KYSB20200003)the USTC Research Funds of the Double First-Class Initiative(YD2080002013)the Joint Open Fund of Mengcheng National Geophysical Observatory(MENGO-202408).
文摘Statistical characteristics and the classification of the topside ionospheric mid-latitude trough are systemically analyzed,using observations from the Defense Meteorological Satellite Program F18(DMSP-F18)satellite.The data was obtained at an altitude of around 860 km in near polar orbit,throughout 2013.Our study identified the auroral boundary based on the in-situ electron density and electron spectrum,allowing us to precisely determine the location of the mid-latitude trough.This differs from most previous works,which only use Total Electron Content(TEC)or in-situ electron density.In our study,the troughs exhibited a higher occurrence rate in local winter than in summer,and extended to lower latitudes with increasing geomagnetic activity.It was found that the ionospheric mid-latitude trough,which is associated with temperature changes or enhanced ion drift,exhibited distinct characteristics.Specifically,the ionospheric mid-latitude troughs related to electron temperature(Te)peak were located more equatorward of auroral oval boundary in winter than in summer.The ionospheric mid-latitude troughs related to Te-maximum were less frequently observed at 60−70°S magnetic latitude and 90−240°E longitude.Furthermore,the troughs related to ion temperature(Ti)maximums were observed at relatively higher latitudes,occurring more frequently in winter.In addition,the troughs related to ion velocity(Vi)maximums could be observed in all seasons.The troughs with the maximum-Ti and maximum-Vi were located closer to the equatorward boundary of the auroral oval at the nightside,and in both hemispheres.This implies that enhanced ion drift velocity contributes to increased collisional frictional heating and enhanced ion temperatures,resulting in a density depletion within the trough region.
基金financial supports from the National Natural Science Foundation of China(Nos.52161023,51901204)Science and Technology Project of Yunnan Precious Metal Laboratory,China(No.YPML-2023050208)+1 种基金Yunnan Science and Technology Planning Project,China(Nos.202201AU070010,202301AT070276,202302AB080008,202303AA080001)Postgraduate Research and Innovation Foundation of Yunnan University,China(No.2021Y338).
文摘The hot deformation behavior of Pt−10Ir alloy was studied under a wide range of deformation parameters.At a low deformation temperature(950−1150℃),the softening mechanism is primarily dynamic recovery.In addition,dynamic recrystallization by progressive lattice rotation near grain boundaries(DRX by LRGBs)and microshear bands assisted dynamic recrystallization(MSBs assisted DRX)coordinate the deformation.However,it is difficult for the dynamic softening to offset the stain hardening due to a limited amount of DRXed grains.At a high deformation temperature(1250−1350℃),three main DRX mechanisms associated with strain rates occur:DRX by LRGBs,DRX by a homogeneous increase in misorientation(HIM)and geometric DRX(GDRX).With increasing strain,DRX by LRGBs is enhanced gradually under high strain rates;the“pinch-off”effect is enhanced at low strain rates,which was conducive to the formation of a uniform and fine microstructure.
基金supported jointly by the earmarked fund for CARS-10-GW2the key research and development program of Hainan Province(Grant No.ZDYF2020226)+1 种基金Collaborative innovation center of Nanfan and high-efficiency tropical agriculture,Hainan University(Grant No.XTCX2022NYC21)funding of Hainan University[Grant No.KYQD(ZR)22123]。
文摘Heat stress hinders the growth and productivity of sweetpotato plants,predominantly through oxidative damage to cellular membranes.Therefore,the development of efficient approaches for mitigating heat-related impairments is essential for the long-term production of sweetpotatoes.Melatonin has been recognised for its capacity to assist plants in dealing with abiotic stress conditions.This research aimed to investigate how different doses of exogenous melatonin influence heat damage in sweetpotato plants.Heat stress drastically affected shoot and root fresh weight by 31.8 and 44.5%,respectively.This reduction resulted in oxidative stress characterised by increased formation of hydrogen peroxide(H_(2)O_(2))by 804.4%,superoxide ion(O_(2)^(·-))by 211.5%and malondialdehyde(MDA)by 234.2%.Heat stress also reduced chlorophyll concentration,photosystemⅡefficiency(F_v/F_m)by 15.3%and gaseous exchange.However,pre-treatment with 100μmol L^(-1)melatonin increased growth and reduced oxidative damage to sweetpotato plants under heat stress.In particular,melatonin decreased H_(2)O_(2),O_(2)^(·-)and MDA by 64.8%,42.7%and 38.2%,respectively.Melatonin also mitigated the decline in chlorophyll levels and improved stomatal traits,gaseous exchange and F_(v)/F_(m)(13%).Results suggested that the favorable outcomes of melatonin treatment can be associated with elevated antioxidant enzyme activity and an increase in non-enzymatic antioxidants and osmo-protectants.Overall,these findings indicate that exogenous melatonin can improve heat stress tolerance in sweetpotatoes.This stu dy will assist re searchers in further investigating how melatonin makes sweetpotatoes more resistant to heat stress.
基金Supported by the Hunan Province Clinical Medical Technology Innovation Guidance Project,No.2020SK50912Annual Scientific Research Plan Project of Hunan Provincial Health Commission,No.C2019057Hunan Provincial Natural Science Foundation of China,No.2023JJ40381.
文摘BACKGROUND Pancreatic cancer involving the pancreas neck and body often invades the retroperitoneal vessels,making its radical resection challenging.Multimodal treatment strategies,including neoadjuvant therapy,surgery,and postoperative adjuvant therapy,are contributing to a paradigm shift in the treatment of pancreatic cancer.This strategy is also promising in the treatment of pancreatic neckbody cancer.AIM To evaluate the feasibility and effectiveness of a multimodal strategy for the treatment of borderline/locally advanced pancreatic neck-body cancer.METHODS From January 2019 to December 2021,we reviewed the demographic characteristics,neoadjuvant and adjuvant treatment data,intraoperative and postoperative variables,and follow-up outcomes of patients who underwent multimodal treatment for pancreatic neck-body cancer in a prospectively collected database of our hospital.This investigation was reported in line with the Preferred Reporting of Case Series in Surgery criteria.RESULTS A total of 11 patients with pancreatic neck-body cancer were included in this study,of whom 6 patients were borderline resectable and 5 were locally advanced.Through multidisciplinary team discussion,all patients received neoadjuvant therapy,of whom 8(73%)patients achieved a partial response and 3 patients maintained stable disease.After multidisciplinary team reassessment,all patients underwent laparoscopic subtotal distal pancreatectomy and portal vein reconstruction and achieved R0 resection.Postoperatively,two patients(18%)developed ascites,and two patients(18%)developed pancreatic fistulae.The median length of stay of the patients was 11 days(range:10-15 days).All patients received postoperative adjuvant therapy.During the follow-up,three patients experienced tumor recurrence,with a median disease-free survival time of 13.3 months and a median overall survival time of 20.5 months.CONCLUSION A multimodal treatment strategy combining neoadjuvant therapy,laparoscopic subtotal distal pancreatectomy,and adjuvant therapy is safe and feasible in patients with pancreatic neck-body cancer.
基金Supported by The Fok Ying-Tong Education Foundation, China, No. 114036Leading Academic Discipline Project of Shanghai Municipal Education Commission, No. J50307State Administration of Traditional Chinese Medicine
文摘AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone group.Age-matched NPD-fed rats served as controls.YQZMT or rosiglitazone were administered for 8 wk.Intraperitoneal glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin sensitivity.Serum levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also analyzed.RESULTS:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control group.Administration of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic rats.After the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group,with a significant reduction in serum glucose(12.16 ± 1.00 mmol/L vs 17.65 ± 2.22 mmol/L,P < 0.01),homeostasis model assessment of basal insulin resistance(22.68 ± 2.37 vs 38.79 ± 9.02,P < 0.05),triglyceride(0.87 ± 0.15 mmol/L vs 1.99 ± 0.26 mmol/L,P < 0.01),TC(3.31 ± 0.52 mmol/L vs 6.50 ± 1.04 mmol/L,P < 0.01) and LDL-c(2.47 ± 0.50 mmol/L vs 6.00 ± 1.07 mmol/L,P < 0.01),and a signif icant increase in HDL-c(0.84 ± 0.08 mmol/L vs 0.50 ± 0.03 mmol/L,P < 0.01).But the body weight was not changed signif icantly.CONCLUSION:YQZMT,which ameliorates insulin resistance and does not cause increase in body weight,may be a suitable therapeutic adjunct for the treatment of type 2 diabetes.
基金supported by grants from the National Traditional Chinese Medicine Administration Bureau, Chinathe project of Science and Technology Commission of Shanghai Municipality(No.08dj 1400600),Shanghaithe National Natural Science Foundation(No.81001574)
文摘BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control b^ood pressure together with other cardiovascular risk factors. OBJECTIVE: The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group (anti-hypertensive drugs plus Yiqi Huaju Formula, CHF) and the control group (anti-hypertensive drugs plus placebo). The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES: Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin (HbAlc), fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), fasting plasma insulin, serum lipid, etc. RESULTS: Compared with the control group, the CHF group had significant improvement (P〈0.01) in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION: This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER: ChiCTR-TRC-11001633.
基金supported by Ministry of Education 211 Project,Fudan UniversityProject of Innovation of Shanghai Municipal Committee of Science and Technology (No.08dj1400600)+6 种基金National Natural Science Foundation of China(No.81001574)Leading Medical Projects at Science and Technology Commission of Shanghai Municipality (No.12401905100)Three-year Projects to Promote Traditional Chinese Medicine,Shanghai(No.ZYSNXD-CC-ZDYJ050)Project of Shanghai Cerebrated TCM Doctor Workshop (No.ZYSNXD-CC-MZY034)Shanghai Association of Chinese Integrative Medicine(No.zxyQ-1245)The Fok Ying-Tong Education Foundation for Young Teacher of University(No.114036)the Foundation of Leading Academic Discipline Project of Shanghai Municipal Education Commission(No.J50307)
文摘BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbAlc), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P〈0.05), WC (P〈0.01) and WHR (P〈0.01). Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P〈0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P〈0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P〉0.05), whereas it significantly increased with CHF treatment (P〈0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P〈0.01). However, there was no significant difference between the two groups (P〉0.05). CONCLUSION: Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.
基金Supported by National Natural Science Foundation of China (No.81100649)
文摘AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.
基金supported by the National Natural Science Foundation of China(21975064)Program of Henan Center for Outstanding Overseas Scientists(GZS2020011)+1 种基金Henan University's first-class discipline science and technology research project(2018YLTD07,2018YLZDYJ11,2019YLZDYJ09)the Excellent Foreign Experts Project of Henan University。
文摘Novel dual-ionic imidazolium salts are shown to display excellent catalytic activity for cycloaddition of carbon dioxide and epoxides under room temperature and atmospheric pressure(0.1 MPa)without any solvent and co-catalyst leading to 96.1%product yield.It can be reused five times to keep the product yield over 90%.These intriguing results are attributed to a new reaction mechanism,which is supported by theoretical calculations along with the measurements of ^(13)C NMR spectrum and Fourier transform infrared spectroscopy(FT-IR).The excellent catalytic activity can be traced to a CO_(2)-philic group along with an electrophilic hydrogen atom.Our work shows that incorporation of CO_(2)-philic group is an feasible pathway to develop the new efficient ionic liquids.
基金supported by the National Natural Science Foundation of China(No.NSFC 81872980,NSFC 81673556,NSFC 82073982)the Guangdong Basic and Applied Basic Research Special Fund,Guangdong Natural Science Fund(No.2017A030313753).
文摘Background:Sophora flavescens,a traditional Chinese herb medicine,has been used to prevent and cure type 2 diabetes mellitus(T2DM)both in folk medicine and medical institutions.Modern pharmacological studies have also demonstrated that the flavonoids obtained from Sophora flavescens ethyl acetate extract(SFE)exhibited potential anti-diabetic activity.Our previous study elucidated that SFE exerts anti-T2DM effects by regulating the host-microbial metabolic axis.In the present study,we further explored the pharmacodynamic effect and the potential targets of the anti-T2DM activity of SFE by integrating network pharmacology and pharmacological evaluations.Methods:The diabetic rat model was created by streptozotocin and oral administration with SFE for 8 weeks.Then,the T2DM-related index was estimated to assess the interventional effect of SFE.Network pharmacology was applied to identify the likely targets and the pathways modulated by SFE components.Furthermore,Western blotting was applied to verify the prediction.Results:Pharmacological evaluation in vivo revealed that SFE could markedly improve the blood glucose,serum insulin secretion,insulin resistance,liver glycogen synthesis,and the liver tissue structure in T2DM rats.Through network pharmacology analysis,101 active compounds of SFE and 114 targets belonging to 128 pathways were identified.The insulin,TNF,IL-6,and PI3K/Akt pathway may be the key targets and pathway.Based on the results of network pharmacology analysis,IRS/PI3K/Akt and IKK/NF-κB/TNF pathways were selected for further validation.Subsequently,experimental results of Western blotting confirmed that SFE may exert anti-T2DM effects by modulating the IRS/PI3K/Akt and IKK/NF-κB/TNF pathways.Conclusion:SFE may protect the T2DM rats by relieving the insulin resistance and inflammation through regulating the IRS/PI3K/Akt and IKK/NF-κB/TNF pathways.The results of the present study would improve the comprehension of the pharmacological basis of SFE against T2DM and provide a theoretical basis for the clinical use of Sophora flavescens.
基金Fund Project:Key Research and Development Project of Guangxi Science and Technology Plan(No.AB18221086AB16380202)Youth Fund Project of Guangxi Natural Science Foundation(No.GXNSFBA138033)。
文摘Objective:To establish a co-culture model of colon cancer cells or mesenchymal stem cells with normal colon epithelial cells in vitro for simulating the tumor microenvironment in vitro,and to investigate the effect of colon cancer cells or mesenchymal stem cells on the migration and epithelial-mesenchymal transformation(EMT)of normal colon epithelial cells in the co-culture environment.Method:Co-culture model of colon cancer cell line SW480 or human umbilical cord mesenchymal stem cells(hUC-MSCs)with human normal colon epithelial cells(NCM460)was established.Morphological changes of NCM460 after co-culture were evaluated by microscopic observation,and migration ability of NCM460 was measured by wound healing and Transwell assay.Meanwhile,Western blot was used to detect the EMT markers of NCM460.Results:There was no significant change in cell morphology of NCM460.Transwell assay results showed that when hUC-MSC or SW480 were co-cultured with NCM460,there is a trend of enhancement of the migration ability of NCM460,and the expression of Vimentin was up-regulated to some extent(P<0.05),E-cadherin and wound healing ability were not significantly changed(P>0.05).When NCM460 were cocultured with MSCs and SW480 at the same time,NCM460's wound healing ability and migration ability were significantly enhanced,meanwhile Vimentin protein expression was significantly up-regulated and E-cadherin protein was significantly down-regulated significantly(P<0.05).Conclusion:Colon cancer cells can increase the migration ability of normal colon epithelial cells and upregulate the expression of EMT markers.Mesenchymal stem cells may play a role in this process.
基金financially supported by the National Natural Science Foundation of China,No.32002235(to MT)the Science and Technology Foundation of Taian of Shandong Province,No.2020NS216(to XL)。
文摘A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.
基金supported by the Local Financial Funds of National Agricultural Science and Technology Center,Chengdu,China(NASC2021KR01)the Agricultural Science and Technology Innovation Program(ASTIP-IUA-2022002)。
文摘Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.
基金supported by the Central South University Scientific Research Foundation for Post-doctor(Grant No.:140050052)the National Natural Science Foundation of China(Grant No.:52204325)
文摘Owing to the intrinsically sluggish kinetics of urea oxidation reaction(UOR)involving a six-electron transfer process,developing efficient UOR electrocatalyst is a great challenge remained to be overwhelmed.Herein,by taking advantage of 2-Methylimidazole,of which is a kind of alkali in water and owns strong coordination ability to Co^(2+)in methanol,trace Co(1.0 mol%)addition was found to induce defect engineering onα-Ni(OH)_(2)in a dual-solvent system of water and methanol.Physical characterization results revealed that the synthesized electrocatalyst(WM-Ni_(0.99)Co_(0.01)(OH)_(2))was a kind of defective nanosheet with thickness around 5-6 nm,attributing to the synergistic effect of Co doping and defect engineering,its electron structure was finely altered,and its specific surface a rea was tremendously enlarged from 68 to 172.3 m^(2)g^(-1).With all these merits,its overpotential to drive 10 mA cm^(-2)was reduced by 110 mV.Besides,the interfacial behavior of UOR was also well deciphered by operando electrochemical impedance spectroscopy.