Essentially clearing the structure-activity relationship between iron carbide catalysts involving multiple active centers to understand the reaction mechanism of CO hydrogenation conversion process is still a great ch...Essentially clearing the structure-activity relationship between iron carbide catalysts involving multiple active centers to understand the reaction mechanism of CO hydrogenation conversion process is still a great challenge.Here,two main micro-environment factors,namely electronic properties and geometrical effects were found to have an integrated effect on the mechanism of CO hydrogenation conversion,involving active sites on multiple crystal phases.The Bader charge of the surface Fe atoms on the active sites had a guiding effect on the CO activation pathway,while the spatial configuration of the active sites greatly affected the energy barriers of CO activation.Although the defective surfaces were more conducive to CO activation,the defective sites were not the only sites to dissociate CO,as CO always tended to dissociate in a wider area.This synergistic effect of the micro-environment also occurred during the CO conversion process.Surface C atoms on relatively flat configurations were more likely to form methane,while the electronic properties of the active sites could effectively describe the C-C coupling process,as well as distinguish the coupling mechanisms.展开更多
Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated wi...Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated with immune disorders that may affect the endometrial immune micro-environment.However,the effect of STRIGs on RIF remains unknown.Methods:Training(GSE111974)and validation(GSE106602)cohorts were acquired from the Gene Expression Omnibus database.STIRGs were extracted from the Molecular Signatures Database and relevant studies.Consensus clustering analysis was used to identify RIF molecular subtypes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and immune infiltration analyses were performed between RIF subtypes.Drug-related potential therapeutic target genes were discovered.Results:Two distinct molecular subtypes were discovered in both the training and validation groups according to STIRGs.In subtype C2,there was a notable decrease in the presence of different types of immune cells,such as natural killer cells and macrophages.Furthermore,the examination of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated a decrease in numerous immune-related biological processes within subtype C2.Finally,nine hub genes(CXCR4,POU5F1,PPARG,TLR2,EGFR,CSF1,BCL2A1,BTK,and SRGN)were identified as potential therapeutic targets for RIF.Conclusion:Based on STIRGs,we identified a new molecular subtype with significantly reduced immune infiltration in RIF.Nine genes might be potential therapeutic targets for RIF.展开更多
The irrigation method used in winter wheat fields affects micro-environment factors, such as relative humidity（RH） within canopy, soil temperature, topsoil bulk density, soil matric potential, and soil nutrients, an...The irrigation method used in winter wheat fields affects micro-environment factors, such as relative humidity（RH） within canopy, soil temperature, topsoil bulk density, soil matric potential, and soil nutrients, and these changes may affect plant root growth.An experiment was carried out to explore the effects of irrigation method on micro-environments and root distribution in a winter wheat field in the 2007–2008 and 2008–2009 growing seasons.The results showed that border irrigation（BI）, sprinkler irrigation（SI）, and surface drip irrigation（SDI） had no significant effects on soil temperature.Topsoil bulk density, RH within the canopy, soil available N distribution, and soil matric potential were significantly affected by the three treatments.The change in soil matric potential was the key reason for the altered root profile distribution patterns.Additionally, more fine roots were produced in the BI treatment when soil water content was low and topsoil bulk density was high.Root growth was most stimulated in the top soil layers and inhibited in the deep layers in the SDI treatment, followed by SI and BI, which was due to the different water application frequencies.As a result, the root profile distribution differed, depending on the irrigation method used.The root distribution pattern changes could be described by the power level variation in the exponential function.A good knowledge of root distribution patterns is important when attempting to model water and nutrient movements and when studying soil-plant interactions.展开更多
The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA...The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.展开更多
Three kinds of packaging bags composited with barrier film and moisture absorbents were designed in order to find out how to create an internal micro-environment with low O2content and relative humidity( RH). Peanuts ...Three kinds of packaging bags composited with barrier film and moisture absorbents were designed in order to find out how to create an internal micro-environment with low O2content and relative humidity( RH). Peanuts with different moisture contents were filled into packaging bags and stored in an environmental chamber for a certain period of time. An RH recorder was sealed in each bag and the RH inside the bag was recorded. The moisture contents of peanuts before and after storage were measured as well.It is found that peanuts with moisture content of 13% can reduce O2content inside the bag by the aerobic respiration,achieving the self modified atmosphere packaging( MAP) effect. A microenvironment with lower RH can be created by using super-absorbent fiber( SAF) or mineral bag as the moisture absorbent. The moisture contents of peanuts stored in the bags with SAF and mineral bag as moisture absorbent decreased from 13% to 10. 5%and 11. 3%,respectively. SAF is a promising material of packaging bags composited with barrier film,in which a low RH and high CO2content can be created.展开更多
A three-dimensional （3D） mathematical model of tumour growth at the avascular phase and vessel remodelling in host tissues is proposed with emphasis on the study of the interactions of tumour growth and hypoxic micr...A three-dimensional （3D） mathematical model of tumour growth at the avascular phase and vessel remodelling in host tissues is proposed with emphasis on the study of the interactions of tumour growth and hypoxic micro-environment in host tissues. The hybrid based model includes the continuum part, such as the distributions of oxygen and vascular endothelial growth factors （VEGFs）, and the discrete part of tumour cells （TCs） and blood vessel networks. The simulation shows the dynamic process of avascular tumour growth from a fewinitial cells to an equilibrium state with varied vessel networks. After a phase of rapidly increasing numbers of the TCs, more and more host vessels collapse due to the stress caused by the growing tumour. In addition, the consumption of oxygen expands with the enlarged tumour region. The study also discusses the effects of certain factors on tumour growth, including the density and configuration of pre- existing vessel networks and the blood oxygen content. The model enables us to examine the relationship between early tumour growth and hypoxic micro-environment in host tissues, which can be useful for further applications, such as tumour metastasis and the initialization of tumour angiogenesis.展开更多
Surface functionalization of Cu-based catalysts has demonstrated promising potential for enhancing the electrochemical CO_(2)reduction reaction(CO_(2)RR)toward multi-carbon(C2+)products,primarily by suppressing the pa...Surface functionalization of Cu-based catalysts has demonstrated promising potential for enhancing the electrochemical CO_(2)reduction reaction(CO_(2)RR)toward multi-carbon(C2+)products,primarily by suppressing the parasitic hydrogen evolution reaction and facilitating a localized CO_(2)/CO concentration at the electrode.Building upon this approach,we developed surface-functionalized catalysts with exceptional activity and selectivity for electrocatalytic CO_(2)RR to C_(2+)in a neutral electrolyte.Employing CuO nanoparticles coated with hexaethynylbenzene organic molecules(HEB-CuO NPs),a remarkable C_(2+)Faradaic efficiency of nearly 90%was achieved at an unprecedented current density of 300 mA cm^(-2),and a high FE(>80%)was maintained at a wide range of current densities(100-600 mA cm^(-2))in neutral environments using a flow cell.Furthermore,in a membrane electrode assembly(MEA)electrolyzer,86.14%FEC2+was achieved at a partial current density of 387.6 mA cm^(-2)while maintaining continuous operation for over 50 h at a current density of 200 mA cm^(-2).In-situ spectroscopy studies and molecular dynamics simulations reveal that reducing the coverage of coordinated K⋅H2O water increased the probability of intermediate reactants(CO)interacting with the surface,thereby promoting efficient C-C coupling and enhancing the yield of C_(2+)products.This advancement offers significant potential for optimizing local micro-environments for sustainable and highly efficient C_(2+)production.展开更多
A small English class can be called as a micro-environment for English study. In this small micro-environment, the relationship between teachers and students is subtle. How to achieve the good interaction and create a...A small English class can be called as a micro-environment for English study. In this small micro-environment, the relationship between teachers and students is subtle. How to achieve the good interaction and create a good micro-environment in English class between teachers and students is very important for developing students＇ learning ability. This thesis is based on Rogers＇ humanistic teaching theory, which uses questionnaires, inteview and comparative analysis to analyze the current situation of micro-environment in college English learning. It discusses the construction of micro-environment in college English learning based on Rogers＇ humanistic teaching theory and the ways to construct it from software conditions （roles of teachers and students, relationship between teachers and students, the classroom atmosphere） and hardware conditions（teaching resources, a classroom）.展开更多
BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secret...BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secretion through paracrine effects but are more susceptible to hypoxic injury post-transplant,while small islets offer better viability and insulin independence.In vivo studies suggest large islets are essential for maintaining euglycemia,though smaller islets are typically preferred in transplantation for better outcomes.AIM To document the impact of islet dimension on clinical and preclinical transplant outcomes to optimize procedures.METHODS PubMed,Scopus and EMBASE platforms were searched for relevant literature up to 9 April 2024.Articles reported on either glucose-stimulated insulin-secreting(GSIS)capacity,islet viability and engraftment,or insulin independence based on the islet dimension were included.The risk of bias was measured using the Appraisal Tool for Cross-Sectional Studies.Extracted data was analyzed via a narrative synthesis.RESULTS Nineteen studies were included in the review.A total of sixteen studies reported the GSIS,of which nine documented the increased insulin secretion in the small islet,where the majority reported insulin secretion per islet equivalent(IEQ).Seven studies documented increased GSIS in large-sized islets that measure insulin secretion per cell or islet.All the articles that compared small and large islets reported poor viability and engraftment of large islets.CONCLUSION Small islets with a diameter<125μm have desired transplantation outcomes due to their better survival following isolation.Large-sized islets receive blood supply directly from arterioles in vivo to meet their higher metabolic demands.The large islet undergoes central necrosis soon after the isolation(devascularization);failing to maintain the viability and glucose stimuli leads to a decline in GSIS and the overall function of the islet.Improved preservation of large islets after islet isolation,enhances the islet yield(IEQ),thereby reducing the likelihood of failed islet isolation and potentially improves transplant outcome.展开更多
Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be indu...BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,su...BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.展开更多
Type 1 diabetes(T1D)is a chronic,lifelong,autoimmune disease that is debilitating and life-threatening to those who suffer from severe hypoglycaemic events or the devastating chronic complications.Exogenous insulin re...Type 1 diabetes(T1D)is a chronic,lifelong,autoimmune disease that is debilitating and life-threatening to those who suffer from severe hypoglycaemic events or the devastating chronic complications.Exogenous insulin replacement,including the artificial pancreas,is the current mainstay of T1D therapy but cannot prevent the chronic vascular complications of the disease.They are also responsible for contributing to severe iatrogenic hypoglycaemia and impaired hypoglycaemic awareness.β-cell replacement with either pancreas or islet allotransplantation can reverse diabetes leading to better glycaemic control,prevention of hypoglycaemic events and improved quality of life for patients.The limited supply of cadaveric organ donors is a major barrier to this therapeutic option.Thus,alternative sources of islets are being actively explored,mainly human pluripotent stem-cell derived islets and xenogeneic porcine islets.Although these sources harbor their own risks and problems,various novel and innovative solutions are being perseveringly investigated across the globe to overcome these in the hopes that safe islet transplantation may one day be available to all T1D patients suffering from severe hypoglycaemic events.This review will concentrate on pre-clinical and clinical studies,in addition to the latest scientific discoveries relevant to T1D transplantation therapy using allogeneic or xenogeneic donor islet cells.展开更多
BACKGROUND Diabetes is characterized by insulin resistance as well as impaired insulin production,withβ-cell dysfunction playing a critical role in disease progression.Exercise is known to improve insulin sensitivity...BACKGROUND Diabetes is characterized by insulin resistance as well as impaired insulin production,withβ-cell dysfunction playing a critical role in disease progression.Exercise is known to improve insulin sensitivity,but its effects on pancreatic islet quality and function remain poorly understood.This work hypothesized that swimming training enhances glycemic control and insulin secretion by upregulating the insulin-like growth factor 1(IGF-1)/phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway in streptozotocin(STZ)-induced diabetic rats.AIM To investigate the effects of swimming on pancreatic islet quality and function in STZ-induced diabetic rats via the IGF-1/PI3K/AKT pathway.METHODS Twenty-six Sprague-Dawley rats were grouped into diabetic and control groups,with each group further split into exercise and sedentary subgroups.Diabetic rats were induced with STZ.The exercise groups underwent swimming training for 60 minutes/day,5 days/week,for 8 weeks.Body weight,food intake,blood glucose,insulin,lipids,and muscle glycogen were measured.Pancreatic islet morphology and the protein expression levels of IGF-1,PI3K,and AKT were analyzed.Data were analyzed using two-way repeated-measure ANOVA,followed by Tukey’s post-hoc test.RESULTS Exercise training significantly improved body weight[diabetic exercise group(D-Ex):390.66±50.14 g vs diabetic sedentary group(D-Sed):315.89±50.12 g,P<0.05],reduced blood glucose(D-Ex:12.21±4.43 mmol/L vs D-Sed:17.79±2.05 mmol/L,P<0.05),and increased insulin levels(D-Ex:53.50±15.31 pmol/L vs D-Sed:25.31±10.23 pmol/L,P<0.05)in diabetic rats.It also enhanced islet morphology,increased IGF-1 expression,and activated the PI3K/AKT pathway(P<0.05).In-vitro experiments confirmed that IGF-1 positively regulated insulin expression and inhibitedβ-cell apoptosis via the PI3K/AKT pathway.CONCLUSION Exercise training improves pancreatic islet quality and function in diabetic rats by modulating the IGF-1/PI3K/AKT pathway,highlighting its therapeutic potential for diabetes management.展开更多
目的探讨利拉鲁肽联合卡格列净治疗2型糖尿病(T2DM)的效果及对血清脂肪因子和炎症因子水平的影响。方法前瞻性选取2023年1月至2024年12月就诊于北京市垂杨柳医院的104例T2DM患者作为研究对象。按照随机数字表法将患者分为对照组与联合组...目的探讨利拉鲁肽联合卡格列净治疗2型糖尿病(T2DM)的效果及对血清脂肪因子和炎症因子水平的影响。方法前瞻性选取2023年1月至2024年12月就诊于北京市垂杨柳医院的104例T2DM患者作为研究对象。按照随机数字表法将患者分为对照组与联合组,每组各52例。对照组予以卡格列净治疗,联合组予以利拉鲁肽联合卡格列净治疗,两组均治疗3个月。治疗前、治疗3个月后,检测患者血糖指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(GHb)]、胰岛功能[空腹C肽、餐后2 h C肽(2 h CP)、稳态模型评估胰岛素抵抗指数(HOMA-IR)]、脂肪因子(鸢尾素、降脂素、瘦素)和炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平,并对比组间差异。结果治疗3个月后,两组患者的空腹血糖、2 h PPG和GHb均较治疗前显著降低,且联合治疗组的空腹血糖、2 h PPG和GHb均低于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的HOMA-IR均较治疗前显著降低,FCP和2 h CP水平均较治疗前上升,且联合治疗组的HOMA-IR低于对照组,CP和2 h CP水平均高于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的血清鸢尾素、降脂素水平均较治疗前显著提升,瘦素均较治疗前显著降低,且联合治疗组的血清鸢尾素、降脂素水平均高于对照组,瘦素低于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的血清IL-6、TNF-α水平均较治疗前显著降低,且联合治疗组的血清IL-6、TNF-α水平均低于对照组,差异均有统计学意义(P<0.05)。结论利拉鲁肽联合卡格列净用于血糖控制不佳的T2DM患者降糖治疗,可提升血糖控制效果,改善胰岛功能,其机制可能与调节脂肪因子和减轻炎症有关。展开更多
基金supported by the Research Fund for National Key Research and Development Program of China(2022YFA1503804,2021YFA1501403)the Natural Science Foundation of China(22208094,21922803,92034301,22008066 and 21776077)+2 种基金the China Postdoctoral Science Foundation(BX20190116)the Innovation Program of Shanghai Municipal Education Commission(17ZR1407300)the Program of Shanghai Academic/Technology Research Leader(21XD1421000).
文摘Essentially clearing the structure-activity relationship between iron carbide catalysts involving multiple active centers to understand the reaction mechanism of CO hydrogenation conversion process is still a great challenge.Here,two main micro-environment factors,namely electronic properties and geometrical effects were found to have an integrated effect on the mechanism of CO hydrogenation conversion,involving active sites on multiple crystal phases.The Bader charge of the surface Fe atoms on the active sites had a guiding effect on the CO activation pathway,while the spatial configuration of the active sites greatly affected the energy barriers of CO activation.Although the defective surfaces were more conducive to CO activation,the defective sites were not the only sites to dissociate CO,as CO always tended to dissociate in a wider area.This synergistic effect of the micro-environment also occurred during the CO conversion process.Surface C atoms on relatively flat configurations were more likely to form methane,while the electronic properties of the active sites could effectively describe the C-C coupling process,as well as distinguish the coupling mechanisms.
文摘Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated with immune disorders that may affect the endometrial immune micro-environment.However,the effect of STRIGs on RIF remains unknown.Methods:Training(GSE111974)and validation(GSE106602)cohorts were acquired from the Gene Expression Omnibus database.STIRGs were extracted from the Molecular Signatures Database and relevant studies.Consensus clustering analysis was used to identify RIF molecular subtypes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and immune infiltration analyses were performed between RIF subtypes.Drug-related potential therapeutic target genes were discovered.Results:Two distinct molecular subtypes were discovered in both the training and validation groups according to STIRGs.In subtype C2,there was a notable decrease in the presence of different types of immune cells,such as natural killer cells and macrophages.Furthermore,the examination of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated a decrease in numerous immune-related biological processes within subtype C2.Finally,nine hub genes(CXCR4,POU5F1,PPARG,TLR2,EGFR,CSF1,BCL2A1,BTK,and SRGN)were identified as potential therapeutic targets for RIF.Conclusion:Based on STIRGs,we identified a new molecular subtype with significantly reduced immune infiltration in RIF.Nine genes might be potential therapeutic targets for RIF.
基金the National Natural Science Foundation of China(51109214,31101074 and 51309211)the National Key Technology Research and Development Program of China(2011BAD32B)the Basic Scientific Research Foundation of National Non-Profit Scientific Institute of China(BSRF201303)
文摘The irrigation method used in winter wheat fields affects micro-environment factors, such as relative humidity（RH） within canopy, soil temperature, topsoil bulk density, soil matric potential, and soil nutrients, and these changes may affect plant root growth.An experiment was carried out to explore the effects of irrigation method on micro-environments and root distribution in a winter wheat field in the 2007–2008 and 2008–2009 growing seasons.The results showed that border irrigation（BI）, sprinkler irrigation（SI）, and surface drip irrigation（SDI） had no significant effects on soil temperature.Topsoil bulk density, RH within the canopy, soil available N distribution, and soil matric potential were significantly affected by the three treatments.The change in soil matric potential was the key reason for the altered root profile distribution patterns.Additionally, more fine roots were produced in the BI treatment when soil water content was low and topsoil bulk density was high.Root growth was most stimulated in the top soil layers and inhibited in the deep layers in the SDI treatment, followed by SI and BI, which was due to the different water application frequencies.As a result, the root profile distribution differed, depending on the irrigation method used.The root distribution pattern changes could be described by the power level variation in the exponential function.A good knowledge of root distribution patterns is important when attempting to model water and nutrient movements and when studying soil-plant interactions.
基金financially supported by National Natural Science Foundation of China(NSFC,Nos.81873921 and 51903174)Sino-German Cooperation Group Project(No.GZ1512)+2 种基金China Postdoctoral Science Foundation(No.2021M702772)Chengdu Science and Technology Program(No.2020-GH02-00007-HZ)Sichuan University Postdoctoral Interdisciplinary Innovation Startup Foundation and the Fundamental Research Funds for Central Universities(No.2021SCU12070)。
文摘The integrated lipopeptide(RVA)/gene complexes are fabricated with bi-directional regulation on tumor cells and micro-environment.After self-assembling and target coating modification,the poly(γ-glutamic acid)(γ-PGA)/RVA nano-vectors can sequentially respond to pH&redox stimuli,and guarantee efficient therapeutic gene delivery and control release of all-trans retinoic acid.The design provides a facile but promising strategy to treat refractory cancers.
文摘Three kinds of packaging bags composited with barrier film and moisture absorbents were designed in order to find out how to create an internal micro-environment with low O2content and relative humidity( RH). Peanuts with different moisture contents were filled into packaging bags and stored in an environmental chamber for a certain period of time. An RH recorder was sealed in each bag and the RH inside the bag was recorded. The moisture contents of peanuts before and after storage were measured as well.It is found that peanuts with moisture content of 13% can reduce O2content inside the bag by the aerobic respiration,achieving the self modified atmosphere packaging( MAP) effect. A microenvironment with lower RH can be created by using super-absorbent fiber( SAF) or mineral bag as the moisture absorbent. The moisture contents of peanuts stored in the bags with SAF and mineral bag as moisture absorbent decreased from 13% to 10. 5%and 11. 3%,respectively. SAF is a promising material of packaging bags composited with barrier film,in which a low RH and high CO2content can be created.
基金supported by the National 973 Basic Research Program of China(No.2013CB733800)the National Natural Science Foundation of China(Nos.11272091 and 11102113)
文摘A three-dimensional （3D） mathematical model of tumour growth at the avascular phase and vessel remodelling in host tissues is proposed with emphasis on the study of the interactions of tumour growth and hypoxic micro-environment in host tissues. The hybrid based model includes the continuum part, such as the distributions of oxygen and vascular endothelial growth factors （VEGFs）, and the discrete part of tumour cells （TCs） and blood vessel networks. The simulation shows the dynamic process of avascular tumour growth from a fewinitial cells to an equilibrium state with varied vessel networks. After a phase of rapidly increasing numbers of the TCs, more and more host vessels collapse due to the stress caused by the growing tumour. In addition, the consumption of oxygen expands with the enlarged tumour region. The study also discusses the effects of certain factors on tumour growth, including the density and configuration of pre- existing vessel networks and the blood oxygen content. The model enables us to examine the relationship between early tumour growth and hypoxic micro-environment in host tissues, which can be useful for further applications, such as tumour metastasis and the initialization of tumour angiogenesis.
基金supported by the National Natural Science Foundation of China(22101182)the Shenzhen Science and Technology Program(Nos.JCYJ20210324095202006,JCYJ20220531095813031,and JCYJ20230807140700001)Guangdong Basic and Applied Basic Research Foundation(2022A1515010318).
文摘Surface functionalization of Cu-based catalysts has demonstrated promising potential for enhancing the electrochemical CO_(2)reduction reaction(CO_(2)RR)toward multi-carbon(C2+)products,primarily by suppressing the parasitic hydrogen evolution reaction and facilitating a localized CO_(2)/CO concentration at the electrode.Building upon this approach,we developed surface-functionalized catalysts with exceptional activity and selectivity for electrocatalytic CO_(2)RR to C_(2+)in a neutral electrolyte.Employing CuO nanoparticles coated with hexaethynylbenzene organic molecules(HEB-CuO NPs),a remarkable C_(2+)Faradaic efficiency of nearly 90%was achieved at an unprecedented current density of 300 mA cm^(-2),and a high FE(>80%)was maintained at a wide range of current densities(100-600 mA cm^(-2))in neutral environments using a flow cell.Furthermore,in a membrane electrode assembly(MEA)electrolyzer,86.14%FEC2+was achieved at a partial current density of 387.6 mA cm^(-2)while maintaining continuous operation for over 50 h at a current density of 200 mA cm^(-2).In-situ spectroscopy studies and molecular dynamics simulations reveal that reducing the coverage of coordinated K⋅H2O water increased the probability of intermediate reactants(CO)interacting with the surface,thereby promoting efficient C-C coupling and enhancing the yield of C_(2+)products.This advancement offers significant potential for optimizing local micro-environments for sustainable and highly efficient C_(2+)production.
文摘A small English class can be called as a micro-environment for English study. In this small micro-environment, the relationship between teachers and students is subtle. How to achieve the good interaction and create a good micro-environment in English class between teachers and students is very important for developing students＇ learning ability. This thesis is based on Rogers＇ humanistic teaching theory, which uses questionnaires, inteview and comparative analysis to analyze the current situation of micro-environment in college English learning. It discusses the construction of micro-environment in college English learning based on Rogers＇ humanistic teaching theory and the ways to construct it from software conditions （roles of teachers and students, relationship between teachers and students, the classroom atmosphere） and hardware conditions（teaching resources, a classroom）.
文摘BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secretion through paracrine effects but are more susceptible to hypoxic injury post-transplant,while small islets offer better viability and insulin independence.In vivo studies suggest large islets are essential for maintaining euglycemia,though smaller islets are typically preferred in transplantation for better outcomes.AIM To document the impact of islet dimension on clinical and preclinical transplant outcomes to optimize procedures.METHODS PubMed,Scopus and EMBASE platforms were searched for relevant literature up to 9 April 2024.Articles reported on either glucose-stimulated insulin-secreting(GSIS)capacity,islet viability and engraftment,or insulin independence based on the islet dimension were included.The risk of bias was measured using the Appraisal Tool for Cross-Sectional Studies.Extracted data was analyzed via a narrative synthesis.RESULTS Nineteen studies were included in the review.A total of sixteen studies reported the GSIS,of which nine documented the increased insulin secretion in the small islet,where the majority reported insulin secretion per islet equivalent(IEQ).Seven studies documented increased GSIS in large-sized islets that measure insulin secretion per cell or islet.All the articles that compared small and large islets reported poor viability and engraftment of large islets.CONCLUSION Small islets with a diameter<125μm have desired transplantation outcomes due to their better survival following isolation.Large-sized islets receive blood supply directly from arterioles in vivo to meet their higher metabolic demands.The large islet undergoes central necrosis soon after the isolation(devascularization);failing to maintain the viability and glucose stimuli leads to a decline in GSIS and the overall function of the islet.Improved preservation of large islets after islet isolation,enhances the islet yield(IEQ),thereby reducing the likelihood of failed islet isolation and potentially improves transplant outcome.
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金Supported by the National Natural Science Foundation of China,No.82073908.
文摘BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.
基金Supported by National Natural Science Foundation of China,No.82000792General Project of Chongqing Natural Science Foundation,No.CSTB2023NSCQ-MSX0246 and No.CSTB2022NSCQ-MSX1271+1 种基金Research Project of the State Administration of Traditional Chinese Medicine on Collaborative Chronic Disease Management of Traditional Chinese Medicine and Western Medicine,No.CXZH2024087Science and Health Joint Project of Dazu District Science and Technology Bureau,No.DZKJ2024JSYJ-KWXM1002.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.
文摘Type 1 diabetes(T1D)is a chronic,lifelong,autoimmune disease that is debilitating and life-threatening to those who suffer from severe hypoglycaemic events or the devastating chronic complications.Exogenous insulin replacement,including the artificial pancreas,is the current mainstay of T1D therapy but cannot prevent the chronic vascular complications of the disease.They are also responsible for contributing to severe iatrogenic hypoglycaemia and impaired hypoglycaemic awareness.β-cell replacement with either pancreas or islet allotransplantation can reverse diabetes leading to better glycaemic control,prevention of hypoglycaemic events and improved quality of life for patients.The limited supply of cadaveric organ donors is a major barrier to this therapeutic option.Thus,alternative sources of islets are being actively explored,mainly human pluripotent stem-cell derived islets and xenogeneic porcine islets.Although these sources harbor their own risks and problems,various novel and innovative solutions are being perseveringly investigated across the globe to overcome these in the hopes that safe islet transplantation may one day be available to all T1D patients suffering from severe hypoglycaemic events.This review will concentrate on pre-clinical and clinical studies,in addition to the latest scientific discoveries relevant to T1D transplantation therapy using allogeneic or xenogeneic donor islet cells.
文摘BACKGROUND Diabetes is characterized by insulin resistance as well as impaired insulin production,withβ-cell dysfunction playing a critical role in disease progression.Exercise is known to improve insulin sensitivity,but its effects on pancreatic islet quality and function remain poorly understood.This work hypothesized that swimming training enhances glycemic control and insulin secretion by upregulating the insulin-like growth factor 1(IGF-1)/phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway in streptozotocin(STZ)-induced diabetic rats.AIM To investigate the effects of swimming on pancreatic islet quality and function in STZ-induced diabetic rats via the IGF-1/PI3K/AKT pathway.METHODS Twenty-six Sprague-Dawley rats were grouped into diabetic and control groups,with each group further split into exercise and sedentary subgroups.Diabetic rats were induced with STZ.The exercise groups underwent swimming training for 60 minutes/day,5 days/week,for 8 weeks.Body weight,food intake,blood glucose,insulin,lipids,and muscle glycogen were measured.Pancreatic islet morphology and the protein expression levels of IGF-1,PI3K,and AKT were analyzed.Data were analyzed using two-way repeated-measure ANOVA,followed by Tukey’s post-hoc test.RESULTS Exercise training significantly improved body weight[diabetic exercise group(D-Ex):390.66±50.14 g vs diabetic sedentary group(D-Sed):315.89±50.12 g,P<0.05],reduced blood glucose(D-Ex:12.21±4.43 mmol/L vs D-Sed:17.79±2.05 mmol/L,P<0.05),and increased insulin levels(D-Ex:53.50±15.31 pmol/L vs D-Sed:25.31±10.23 pmol/L,P<0.05)in diabetic rats.It also enhanced islet morphology,increased IGF-1 expression,and activated the PI3K/AKT pathway(P<0.05).In-vitro experiments confirmed that IGF-1 positively regulated insulin expression and inhibitedβ-cell apoptosis via the PI3K/AKT pathway.CONCLUSION Exercise training improves pancreatic islet quality and function in diabetic rats by modulating the IGF-1/PI3K/AKT pathway,highlighting its therapeutic potential for diabetes management.
文摘目的探讨利拉鲁肽联合卡格列净治疗2型糖尿病(T2DM)的效果及对血清脂肪因子和炎症因子水平的影响。方法前瞻性选取2023年1月至2024年12月就诊于北京市垂杨柳医院的104例T2DM患者作为研究对象。按照随机数字表法将患者分为对照组与联合组,每组各52例。对照组予以卡格列净治疗,联合组予以利拉鲁肽联合卡格列净治疗,两组均治疗3个月。治疗前、治疗3个月后,检测患者血糖指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(GHb)]、胰岛功能[空腹C肽、餐后2 h C肽(2 h CP)、稳态模型评估胰岛素抵抗指数(HOMA-IR)]、脂肪因子(鸢尾素、降脂素、瘦素)和炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平,并对比组间差异。结果治疗3个月后,两组患者的空腹血糖、2 h PPG和GHb均较治疗前显著降低,且联合治疗组的空腹血糖、2 h PPG和GHb均低于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的HOMA-IR均较治疗前显著降低,FCP和2 h CP水平均较治疗前上升,且联合治疗组的HOMA-IR低于对照组,CP和2 h CP水平均高于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的血清鸢尾素、降脂素水平均较治疗前显著提升,瘦素均较治疗前显著降低,且联合治疗组的血清鸢尾素、降脂素水平均高于对照组,瘦素低于对照组,差异均有统计学意义(P<0.05)。治疗3个月后,两组患者的血清IL-6、TNF-α水平均较治疗前显著降低,且联合治疗组的血清IL-6、TNF-α水平均低于对照组,差异均有统计学意义(P<0.05)。结论利拉鲁肽联合卡格列净用于血糖控制不佳的T2DM患者降糖治疗,可提升血糖控制效果,改善胰岛功能,其机制可能与调节脂肪因子和减轻炎症有关。
