The increasing frequency of compound extreme events under ongoing climate change threatens global food security.Compared to individual extreme events,the simultaneous occurrence of multiple extreme events can exacerba...The increasing frequency of compound extreme events under ongoing climate change threatens global food security.Compared to individual extreme events,the simultaneous occurrence of multiple extreme events can exacerbate crop yield reductions,yet comprehensive assessments of these compound effects remain limited.To bridge this gap,we applied a linear mixed-effects model to quantify the impacts of individual extreme events(cold days(CD)and killing degree days(KDD))and triple compound extreme events(heatwave and low precipitation(HWLP)and hot-dry-windy(HDW))on the global yields of winter wheat,soybeans,and maize from 1982 to 2016.Our analysis indicated that regions severely impacted by extreme events(exceeding the 95%threshold)experienced total crop yield losses of more than 9.16,24.89,26.69,and 7.12%due to CD,KDD,HWLP,and HDW,respectively.The adverse effects of compound events were particularly pronounced during critical growth stages.HWLP results in yield losses of 9.4%for winter wheat and 6.8%for maize per 10 hours of exposure during the heading to harvesting stages,while soybean yields declined by 8.8%per 10 hours during the planting to three-true-leaf stage.Similarly,KDD caused a 7.4%yield reduction in winter wheat per 10°C day during the heading to harvesting stages,a 9.5%reduction in maize per 10°C day during the planting to jointing stages,and a 3.8%reduction in soybean per 10°C day during the planting to three-true-leaf stages.These findings underscore the substantial contribution of compound extreme events,which are often overlooked in existing risk assessments,in determining the global yields of major staple crops.展开更多
UV-B application enhances the aroma quality of oolong tea;however,the underlying regulatory mechanism remains unclear.This study investigates the regulatory role of UV-B in the biosynthesis of a-farnesene,an important...UV-B application enhances the aroma quality of oolong tea;however,the underlying regulatory mechanism remains unclear.This study investigates the regulatory role of UV-B in the biosynthesis of a-farnesene,an important floral and fruity characteristic aroma.UV-B treatment significantly improved the aroma quality of‘Foshou’and‘Yuquan’oolong teas,increasing a-farnesene levels by 1.8-and 1.4-fold,respectively.The a-farnesene synthase(CsAFS),ELONGATED HYPOCOTYL 5(CsHY5),and myelocytomatosis protein 2(CsMYC2)exhibited a highly correlated expression pattern closely associated with a-farnesene accumulation.Single-factor treatment revealed that CsAFS expression was induced by both UV-B and mechanical wounding,with CsHY5 predominantly responding to UV-B radiation,while CsMYC2 primarily responded to tumbling-induced mechanical wounding signal.Transient suppression of CsHY5 in tea leaves reduced the expression of both CsAFS and CsMYC2 whereas CsMYC2 suppression decreased CsAFS expression.G-box motifs were identified in promoters of CsMYC2 and CsAFS,and the dual-luciferase reporter assay(LUC)and electrophoretic mobility shift assays(EMSA)demonstrated direct binding functions of CsHY5 to CsAFS and CsMYC2 promoters,as well as CsMYC2 to the CsAFS promoter.Based on sensory evaluation,odourant quantification,gene expression,and molecular functional analysis,we propose that UV-B radiation and tumbling-induced wounding signals synergistically regulate a-farnesene biosynthesis through a coordinated interaction of CsHY5 and CsMYC2 during oolong tea processing.These findings improve our understanding of flavour formation during oolong tea production and also provide novel insights into artificial light application in tea manufacturing.展开更多
Information-carrying capacity has become an important factor in the development of encryption and anti-counterfeiting.Herein,a hydrogen-bonded organic framework(HOF-PyTTA)was developed as novel anti-counterfeiting ink...Information-carrying capacity has become an important factor in the development of encryption and anti-counterfeiting.Herein,a hydrogen-bonded organic framework(HOF-PyTTA)was developed as novel anti-counterfeiting ink without rare metals and a smartphone-based APP was written for encryption and anti-counterfeiting.We found that the fluorescence of HOF-PyTTA can be quenched by Fe^(3+)ions and recovered by the addition of ascorbic acid.And the fluorescence of HOF-PyTTA can be enhanced by the increasing concentrations of ethanol.Based on these stimulus-response properties,four anti-counterfeiting models with gradually increased security were studied.Mode one was printed by HOFs ink and decrypted by UV light.Mode two was based on HOF-PyTTA and CsPbBr_(3)inks(or HOF-PyTTA-Fe^(3+))which are used to separately print the genuine and pirated information.A decryption reagent was applied to get the genuine information.Furthermore,we successfully construct a dynamic information encryption anti-counterfeiting model using a fluorescence array in combination with an information encryption anticounterfeiting APP.The circular array is printed by several concentrations of HOF-PyTTA ink and different RGB thresholds are set with the help of the information encryption anti-counterfeiting APP,to obtain distinct encrypted anti-counterfeiting information,thus accomplishing a high information-carrying capacity.展开更多
High-performance MXene-based polymer nanocomposites are well-suited for various industrial applications owing to their excellent mechanical,thermal,and other properties.However,the fabrication of flame-retardant polym...High-performance MXene-based polymer nanocomposites are well-suited for various industrial applications owing to their excellent mechanical,thermal,and other properties.However,the fabrication of flame-retardant polymer/MXene nanocom-posites remains challenging owing to the limited flame-retardant properties of MXene itself.This study prepared a novel MXene@Ag@PA hybrid material via radiation modification and complexation reaction.This material was used to further enhance the key properties of ethylene-vinyl acetate(EVA),such as its mechanical properties,thermal conductivity,flame retardancy,and electromagnetic shielding.The addition of two parts of this hybrid material increased the thermal conduc-tivity of EVA by 44.2%and reduced its peak exothermic rate during combustion by 30.1%compared with pure EVA.The material also significantly reduced smoke production and increased the residue content.In the X-band,the electromagnetic shielding effectiveness of the EVA composites reached 20 dB.Moreover,the MXene@Ag@PA hybrid material could be used to further enhance the mechanical properties of EVA composites under electron-beam irradiation.Thus,this study contributes to the development of MXene-based EVA advanced materials that are fire-safe,have high strength,and exhibit good electromagnetic shielding performance for various applications.展开更多
Studies on plant diversity are usually based on the total number of species in a community.However,few studies have examined species richness(SR)of different plant life forms in a community along largescale environmen...Studies on plant diversity are usually based on the total number of species in a community.However,few studies have examined species richness(SR)of different plant life forms in a community along largescale environmental gradients.Particularly,the relative importance(RIV)of different plant life forms in a community and how they vary with environmental variables are still unclear.To fill these gaps,we determined plant diversity of ephemeral plants,annual herbs,perennial herbs,and woody plants from 187 sites across drylands in China.The SR patterns of herbaceous plants,especially perennial herbs,and their RIV in plant communities increased with increasing precipitation and soil nutrient content;however,the RIV of annual herbs was not altered along these gradients.The SR and RIV of ephemeral plants were affected mainly by precipitation seasonality.The SR of woody plants had a unimodal relationship with air temperature and exhibited the highest RIV and SR percentage in plant communities under the harshest environments.An obvious shift emerged in plant community composition,SR and their critical impact factors at 238.5 mm of mean annual precipitation(MAP).In mesic regions(>238.5 mm),herbs were the dominant species,and the SR displayed a relatively slow decreasing rate with increasing aridity,which was mediated mainly by MAP and soil nutrients.In arid regions(<238.5 mm),woody plants were the dominant species,and the SR displayed a relatively fast decreasing rate with increasing aridity,which was mediated mainly by climate variables,especially precipitation.Our findings highlight the importance of comparative life form studies in community structure and biodiversity,as their responses to gradients differed substantially on a large scale.展开更多
Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,wh...Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.展开更多
Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase alle...Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase allele mining using six updated FNP marker systems,the functional haplotypes at Pit,Pib,and Pi63 strictly diverged into the X-populations and were defined as X-R loci,while those at Pi54,Pi37,and Pi36 into the G-populations as G-R loci.The genic diversity at the three X-R loci(16 alleles)was twofold higher than that at the three G-R loci(8 alleles),and the allelic diversity in the Southern region(21 alleles)was nearly double that in the Northeastern region(11 alleles).Both observations reflect a significant difference in genetic diversity between X-and G-populations,and indicate that the effective R-genes mainly originated from X-subspecies.Based on the allelic structures characterized by a set of 10 parameters,8 and 16 alleles were respectively recognized as favorable and promising ones for the regional breeding programs.The genotypic structures of the two regional populations were almost different,indicating that the diverged alleles have been further assembled into two series of regional genotypes through long-term breeding programs,despite the presence of one-third of region-common alleles.The genotypic diversity in the Southern region(55 genotypes)was nearly twice as high as that in the Northeastern region(28),which perfectly reflects the aforementioned differences in both genic and allelic diversities.After analyzing the genotypic structures using a set of 13 parameters,4 and 23 genotypes,respectively,can be recommended as the favorable and promising ones for the regional breeding programs.The case study serves as a concrete sample of how to identify the favorable and promising alleles and genotypes,and beneficial parents based their comprehensive population structures for gene-designed breeding.展开更多
Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group deve...Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.展开更多
<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many co...<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>展开更多
Groundwater is the main water supply source in the Tarim Basin in China.Endemic disease caused by high iodine(I)groundwater in the Tarim Basin was reported previously.Therefore,it is crucial to systematically identify...Groundwater is the main water supply source in the Tarim Basin in China.Endemic disease caused by high iodine(I)groundwater in the Tarim Basin was reported previously.Therefore,it is crucial to systematically identify the distribution and genesis of groundwater I.Based on hydrochemical analysis of 717 groundwater samples collected in 2015–2018,spatial distribution and hydrogeochemistry characteristic of high I groundwater in different aquifers were analyzed.Results showed that groundwater I ranged between<10.00 and 4000.00μg/L(mean of 53.71μg/L).High I groundwater(I>100.00μg/L)accounted for 7.25%of the total samples.Horizontally,groundwater I significantly increased from recharge zone(RZ)to transition zone(TZ)and to evaporation zone(EZ).Vertically,groundwater in shallow confined aquifer(SCA)had the greatest I concentration,followed by single-structure phreatic aquifer(SSPA),phreatic aquifer in confined groundwater area(PACGA),while groundwater in deep confined aquifer(DCA)generally had low I concentration.Groundwater I enrichment in SSPA was mainly affected by organic matter(OM)decomposition and that in SCA was mainly affected by evaporite mineral dissolution,OM decomposition under alkaline environment.While I enrichment in groundwater of PACGA was restrained under neutral environment.Lacustrine sedimentary environment was crucial for I enrichment in groundwater.Besides,fine-grained lithology of aquifer,smooth topographic slope,shallow buried depth of groundwater,weak alkaline and reducing environment,reductive dissolution of iron oxide/hydroxide minerals and OM decomposition were advantageous to I enrichment in groundwater.展开更多
Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvas...Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.展开更多
Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegeta...Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegetation phenology and physiology,the effectiveness of satellite-derived indicators in capturing these variations has not been fully evaluated.This study develops and evaluates the satellite-derived phenology and physiology indicators for modeling AGPP variability.We assessed the performance of satellite-derived metrics,including solar-induced chlorophyll fluorescence(SIF),leaf area index(LAI),and enhanced vegetation index(EVI),in capturing AGPP variations.Among these,SIF-based indicators exhibited the highest accuracy(Pearson's r=0.79;root mean square error=414.7 gC·m^(-2)·year^(-1)),outperforming LAI-and EVI-based indicators.To further investigate the mechanisms driving AGPP variability,we used a structural equation model based on in situ observations to quantify the direct and indirect effects of climate on AGPP through phenology and physiology.Our results reveal that vegetation physiology,particularly the seasonal maximum gross primary production,plays a more dominant role in regulating AGPP than phenology.Furthermore,we found that globally,SIF-derived phenology indicators tend to be lower than those from LAI and EVI,whereas SIF-derived physiology indicators are elevated in tropical regions and the Southern Hemisphere.These findings highlight the potential of satellite-derived indicators in advancing AGPP modeling and emphasize the predominant role of vegetation physiology in regulating ecosystem carbon uptake.This study contributes to a refined understanding of global carbon cycle dynamics and provides insights for improving large-scale carbon assessments in the context of climate change.展开更多
In high-frequency electrical energy systems,polyimide(PI)composite insulation materials need to possess a low dielectric constant,sufficient thermal conductivity,and robust interfacial adhesion to ensure reliable perf...In high-frequency electrical energy systems,polyimide(PI)composite insulation materials need to possess a low dielectric constant,sufficient thermal conductivity,and robust interfacial adhesion to ensure reliable performance under elevated temperatures and pressures.These aspects are crucial for preventing local overheating and electrical breakdown,thereby ensuring reliable equipment operation.Traditional PI insulation materials often exhibit high dielectric constants and pronounced dielectric losses,compromising their insulation efficiency.In this study,molecular dynamics simulations were employed to incorporate polyhedral oligomeric silsesquioxanes(POSS)into PI through physical blending and chemical bonding to enhance dielectric properties.Key parameters of the PI/POSS composite system,including dielectric constant,thermal conductivity,glass transition temperature,Young’s modulus,Poisson’s ratio,and interfacial adhesion energy,were systematically evaluated for both doping methods.The degradation behavior of the PI composites under high-temperature and electric field conditions was also simulated to elucidate degradation pathways and product distributions,providing insights for designing low-dielectric insulation materials.Doping with POSS significantly reduces the dielectric constant of PI,thereby improving insulation performance,thermal stability,mechanical strength,and interfacial adhesion.At an optimal POSS doping ratio,the thermal conductivity of PI is enhanced.Compared with the physical blending system,the chemical bonding system yields more substantial improvements across all evaluated properties.Under high-temperature and strong electric field conditions,POSS doping enhances interfacial adhesion and thermal stability,effectively suppressing the cleavage of key chemical bonds,reducingCOemissions,and increasing the formation of oxygen-containing intermediates and water molecules,which contributes to improved environmental sustainability.展开更多
Although cisplatin is a widely used chemotherapeutic agent,it is severely toxic and causes irreversible hearing loss,restricting its application in clinical settings.This study aimed to determine the molecular mechani...Although cisplatin is a widely used chemotherapeutic agent,it is severely toxic and causes irreversible hearing loss,restricting its application in clinical settings.This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity.Here,we established in vitro and in vivo ototoxicity models of cisplatininduced hair cell loss,and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death.In addition,we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA,which may act as a critical linker between the cyclic GMP-AMP synthesis−stimulator of interferon genes(cGASSTING)pathway and the pathogenesis of cisplatin-induced hearing loss.H-151,a specific inhibitor of STING,reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo.This study underscores the role of cGASSTING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.展开更多
BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but th...BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.展开更多
Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based...Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis,but its colonizing and therapeutic efficacy after oral administration are limited.Here,we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein(MMPB)with the famous probiotic bacteria Lactobacillus plantarum(Lac)and Bifidobacterium animalis subsp.lactis(Bif).The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein.Owing to presence of the artificial protein on the MMPB surface,the nanodrug strongly bound and cross-linked the probiotic cells,forming the Lac+Bif+MMPB co-assembly.During co-incubation with the kanamycin-resistant E.coli strain(Ecka),the co-assembly strongly reduced the viability of Ecka,leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2.After oral administration of the co-assembly to themice pre-colonized by Ecka,Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine,and led to 2-3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif.More importantly,in the mice suffering from enteritis caused by drug-resistant S.Tm,the co-assembly remarkably recovered the mouse body weight,reduced intestine colonization of S.Tm cells,and decreased the levels of pro-inflammatory cytokines in both serum and colons.This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.展开更多
基金supported by the National Natural Science Foundation of China(42371483,and 42401573)the Guangdong Basic and Applied Basic Research Foundation,China(2022B1515130001)+2 种基金the Natural Science Foundation of Guangdong Province,China(2024A1515012081 and 2025A1515010770)the Guangzhou Basic and Applied Basic Research Project,China(202201011666)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZB20240880).
文摘The increasing frequency of compound extreme events under ongoing climate change threatens global food security.Compared to individual extreme events,the simultaneous occurrence of multiple extreme events can exacerbate crop yield reductions,yet comprehensive assessments of these compound effects remain limited.To bridge this gap,we applied a linear mixed-effects model to quantify the impacts of individual extreme events(cold days(CD)and killing degree days(KDD))and triple compound extreme events(heatwave and low precipitation(HWLP)and hot-dry-windy(HDW))on the global yields of winter wheat,soybeans,and maize from 1982 to 2016.Our analysis indicated that regions severely impacted by extreme events(exceeding the 95%threshold)experienced total crop yield losses of more than 9.16,24.89,26.69,and 7.12%due to CD,KDD,HWLP,and HDW,respectively.The adverse effects of compound events were particularly pronounced during critical growth stages.HWLP results in yield losses of 9.4%for winter wheat and 6.8%for maize per 10 hours of exposure during the heading to harvesting stages,while soybean yields declined by 8.8%per 10 hours during the planting to three-true-leaf stage.Similarly,KDD caused a 7.4%yield reduction in winter wheat per 10°C day during the heading to harvesting stages,a 9.5%reduction in maize per 10°C day during the planting to jointing stages,and a 3.8%reduction in soybean per 10°C day during the planting to three-true-leaf stages.These findings underscore the substantial contribution of compound extreme events,which are often overlooked in existing risk assessments,in determining the global yields of major staple crops.
基金supported by the National Natural Science Foundation of China(Grant No.32072623)the National Key Research and Development Program of China(Grant No.2021YFD1601103).
文摘UV-B application enhances the aroma quality of oolong tea;however,the underlying regulatory mechanism remains unclear.This study investigates the regulatory role of UV-B in the biosynthesis of a-farnesene,an important floral and fruity characteristic aroma.UV-B treatment significantly improved the aroma quality of‘Foshou’and‘Yuquan’oolong teas,increasing a-farnesene levels by 1.8-and 1.4-fold,respectively.The a-farnesene synthase(CsAFS),ELONGATED HYPOCOTYL 5(CsHY5),and myelocytomatosis protein 2(CsMYC2)exhibited a highly correlated expression pattern closely associated with a-farnesene accumulation.Single-factor treatment revealed that CsAFS expression was induced by both UV-B and mechanical wounding,with CsHY5 predominantly responding to UV-B radiation,while CsMYC2 primarily responded to tumbling-induced mechanical wounding signal.Transient suppression of CsHY5 in tea leaves reduced the expression of both CsAFS and CsMYC2 whereas CsMYC2 suppression decreased CsAFS expression.G-box motifs were identified in promoters of CsMYC2 and CsAFS,and the dual-luciferase reporter assay(LUC)and electrophoretic mobility shift assays(EMSA)demonstrated direct binding functions of CsHY5 to CsAFS and CsMYC2 promoters,as well as CsMYC2 to the CsAFS promoter.Based on sensory evaluation,odourant quantification,gene expression,and molecular functional analysis,we propose that UV-B radiation and tumbling-induced wounding signals synergistically regulate a-farnesene biosynthesis through a coordinated interaction of CsHY5 and CsMYC2 during oolong tea processing.These findings improve our understanding of flavour formation during oolong tea production and also provide novel insights into artificial light application in tea manufacturing.
基金financial support from the National Natural Science Foundation(No.22164005)the Natural Science Foundation of Guangxi(No.2022GXNSFAA035475)+1 种基金the Student Innovation Training Program(No.202110602062)the BAGUI Scholar Program。
文摘Information-carrying capacity has become an important factor in the development of encryption and anti-counterfeiting.Herein,a hydrogen-bonded organic framework(HOF-PyTTA)was developed as novel anti-counterfeiting ink without rare metals and a smartphone-based APP was written for encryption and anti-counterfeiting.We found that the fluorescence of HOF-PyTTA can be quenched by Fe^(3+)ions and recovered by the addition of ascorbic acid.And the fluorescence of HOF-PyTTA can be enhanced by the increasing concentrations of ethanol.Based on these stimulus-response properties,four anti-counterfeiting models with gradually increased security were studied.Mode one was printed by HOFs ink and decrypted by UV light.Mode two was based on HOF-PyTTA and CsPbBr_(3)inks(or HOF-PyTTA-Fe^(3+))which are used to separately print the genuine and pirated information.A decryption reagent was applied to get the genuine information.Furthermore,we successfully construct a dynamic information encryption anti-counterfeiting model using a fluorescence array in combination with an information encryption anticounterfeiting APP.The circular array is printed by several concentrations of HOF-PyTTA ink and different RGB thresholds are set with the help of the information encryption anti-counterfeiting APP,to obtain distinct encrypted anti-counterfeiting information,thus accomplishing a high information-carrying capacity.
文摘High-performance MXene-based polymer nanocomposites are well-suited for various industrial applications owing to their excellent mechanical,thermal,and other properties.However,the fabrication of flame-retardant polymer/MXene nanocom-posites remains challenging owing to the limited flame-retardant properties of MXene itself.This study prepared a novel MXene@Ag@PA hybrid material via radiation modification and complexation reaction.This material was used to further enhance the key properties of ethylene-vinyl acetate(EVA),such as its mechanical properties,thermal conductivity,flame retardancy,and electromagnetic shielding.The addition of two parts of this hybrid material increased the thermal conduc-tivity of EVA by 44.2%and reduced its peak exothermic rate during combustion by 30.1%compared with pure EVA.The material also significantly reduced smoke production and increased the residue content.In the X-band,the electromagnetic shielding effectiveness of the EVA composites reached 20 dB.Moreover,the MXene@Ag@PA hybrid material could be used to further enhance the mechanical properties of EVA composites under electron-beam irradiation.Thus,this study contributes to the development of MXene-based EVA advanced materials that are fire-safe,have high strength,and exhibit good electromagnetic shielding performance for various applications.
基金supported by the National Key Research and Development Program of China(2023YFF0805602)National Natural Science Foundation of China(32225032,32001192,32271597)+1 种基金the Innovation Base Project of Gansu Province(2021YFF0703904)the Science and Technology Program of Gansu Province(24JRRA515,22JR5RA525,23JRRA1157).
文摘Studies on plant diversity are usually based on the total number of species in a community.However,few studies have examined species richness(SR)of different plant life forms in a community along largescale environmental gradients.Particularly,the relative importance(RIV)of different plant life forms in a community and how they vary with environmental variables are still unclear.To fill these gaps,we determined plant diversity of ephemeral plants,annual herbs,perennial herbs,and woody plants from 187 sites across drylands in China.The SR patterns of herbaceous plants,especially perennial herbs,and their RIV in plant communities increased with increasing precipitation and soil nutrient content;however,the RIV of annual herbs was not altered along these gradients.The SR and RIV of ephemeral plants were affected mainly by precipitation seasonality.The SR of woody plants had a unimodal relationship with air temperature and exhibited the highest RIV and SR percentage in plant communities under the harshest environments.An obvious shift emerged in plant community composition,SR and their critical impact factors at 238.5 mm of mean annual precipitation(MAP).In mesic regions(>238.5 mm),herbs were the dominant species,and the SR displayed a relatively slow decreasing rate with increasing aridity,which was mediated mainly by MAP and soil nutrients.In arid regions(<238.5 mm),woody plants were the dominant species,and the SR displayed a relatively fast decreasing rate with increasing aridity,which was mediated mainly by climate variables,especially precipitation.Our findings highlight the importance of comparative life form studies in community structure and biodiversity,as their responses to gradients differed substantially on a large scale.
基金supported by the National Natural Science Foundation of China(32170484 and 32300384)the Fundamental Research Funds for the Central Universities(2572022DQ07 and 2572020AW04).
文摘Hematopoiesis is crucial for organismal health,and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates.In larvae,hematopoiesis primarily occurs in the lymph gland,which contains distinct zones,including the cortical zone,intermediate zone,medullary zone,and posterior signaling center(PSC).Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules,yet its role in hematopoietic homeostasis is not fully understood.This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells.Rab1 impairment disrupts the endosomal trafficking of β-integrin,leading to its abnormal localization on cell membranes,which promotes lamellocyte differentiation and alters progenitor dynamics in circulating hemocytes and lymph glands,respectively.We also show that the mislocalization of β-integrin is dependent on the adhesion protein DE-cadherin.The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation.Furthermore,Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17(Syx17).Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.
基金funded by grants from the National Key R&D Project(2023YFD1400201-02,2023YFD1400203-02)the National Natural Science Foundation of China(31870137)+1 种基金the National Transgenic Research Project(2015ZX08001-002)the Key R&D Project of Guangdong Province(2022B0202060005).
文摘Asian rice comprises two major subspecies:Xian(X)and Geng(G),and the diverged resistance genes(R)have provided a foundation for breeding improved cultivars to control rice blast disease.After conducting two-phase allele mining using six updated FNP marker systems,the functional haplotypes at Pit,Pib,and Pi63 strictly diverged into the X-populations and were defined as X-R loci,while those at Pi54,Pi37,and Pi36 into the G-populations as G-R loci.The genic diversity at the three X-R loci(16 alleles)was twofold higher than that at the three G-R loci(8 alleles),and the allelic diversity in the Southern region(21 alleles)was nearly double that in the Northeastern region(11 alleles).Both observations reflect a significant difference in genetic diversity between X-and G-populations,and indicate that the effective R-genes mainly originated from X-subspecies.Based on the allelic structures characterized by a set of 10 parameters,8 and 16 alleles were respectively recognized as favorable and promising ones for the regional breeding programs.The genotypic structures of the two regional populations were almost different,indicating that the diverged alleles have been further assembled into two series of regional genotypes through long-term breeding programs,despite the presence of one-third of region-common alleles.The genotypic diversity in the Southern region(55 genotypes)was nearly twice as high as that in the Northeastern region(28),which perfectly reflects the aforementioned differences in both genic and allelic diversities.After analyzing the genotypic structures using a set of 13 parameters,4 and 23 genotypes,respectively,can be recommended as the favorable and promising ones for the regional breeding programs.The case study serves as a concrete sample of how to identify the favorable and promising alleles and genotypes,and beneficial parents based their comprehensive population structures for gene-designed breeding.
基金The National Natural Science Foundation of China(no.82204006)the Science and Technology of Project of Hebei Education Department(QN2022009)+1 种基金the Provincial Graduate Student Innovation Funding Project of Hebei Province(CXZZBS2022104)the National Natural Science Foundation of Hebei Province(H2020209292).
文摘Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.
文摘<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>
基金financially supported by the National Natural Science Foundation of China(Nos.42067035 and 42007161)Water Conservancy Engineering Key Discipline Project of Xinjiang Agricultural University(No.SLXK2019-10)the Opening Project of Xinjiang Key Laboratory of Hydraulic Engineering Security and Water Disasters Prevention in 2021(No.ZDSYS-JS-2021-10)。
文摘Groundwater is the main water supply source in the Tarim Basin in China.Endemic disease caused by high iodine(I)groundwater in the Tarim Basin was reported previously.Therefore,it is crucial to systematically identify the distribution and genesis of groundwater I.Based on hydrochemical analysis of 717 groundwater samples collected in 2015–2018,spatial distribution and hydrogeochemistry characteristic of high I groundwater in different aquifers were analyzed.Results showed that groundwater I ranged between<10.00 and 4000.00μg/L(mean of 53.71μg/L).High I groundwater(I>100.00μg/L)accounted for 7.25%of the total samples.Horizontally,groundwater I significantly increased from recharge zone(RZ)to transition zone(TZ)and to evaporation zone(EZ).Vertically,groundwater in shallow confined aquifer(SCA)had the greatest I concentration,followed by single-structure phreatic aquifer(SSPA),phreatic aquifer in confined groundwater area(PACGA),while groundwater in deep confined aquifer(DCA)generally had low I concentration.Groundwater I enrichment in SSPA was mainly affected by organic matter(OM)decomposition and that in SCA was mainly affected by evaporite mineral dissolution,OM decomposition under alkaline environment.While I enrichment in groundwater of PACGA was restrained under neutral environment.Lacustrine sedimentary environment was crucial for I enrichment in groundwater.Besides,fine-grained lithology of aquifer,smooth topographic slope,shallow buried depth of groundwater,weak alkaline and reducing environment,reductive dissolution of iron oxide/hydroxide minerals and OM decomposition were advantageous to I enrichment in groundwater.
基金supported the National Natural Science Foundation of China(81930113).
文摘Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
基金support from the National Natural Science Foundation of China(Nos.42450226,42371483,and 42171308)the Natural Science Foundation of Guangdong Province,China(No.2025A1515010770)the Postdoctoral Fellowship Program of CPSF(No.GZB20240880).
文摘Vegetation annual gross primary production(AGPP),the total yearly carbon assimilation via photosynthesis,serves as a key indicator of ecosystem carbon uptake.While AGPP variations are jointly influenced by both vegetation phenology and physiology,the effectiveness of satellite-derived indicators in capturing these variations has not been fully evaluated.This study develops and evaluates the satellite-derived phenology and physiology indicators for modeling AGPP variability.We assessed the performance of satellite-derived metrics,including solar-induced chlorophyll fluorescence(SIF),leaf area index(LAI),and enhanced vegetation index(EVI),in capturing AGPP variations.Among these,SIF-based indicators exhibited the highest accuracy(Pearson's r=0.79;root mean square error=414.7 gC·m^(-2)·year^(-1)),outperforming LAI-and EVI-based indicators.To further investigate the mechanisms driving AGPP variability,we used a structural equation model based on in situ observations to quantify the direct and indirect effects of climate on AGPP through phenology and physiology.Our results reveal that vegetation physiology,particularly the seasonal maximum gross primary production,plays a more dominant role in regulating AGPP than phenology.Furthermore,we found that globally,SIF-derived phenology indicators tend to be lower than those from LAI and EVI,whereas SIF-derived physiology indicators are elevated in tropical regions and the Southern Hemisphere.These findings highlight the potential of satellite-derived indicators in advancing AGPP modeling and emphasize the predominant role of vegetation physiology in regulating ecosystem carbon uptake.This study contributes to a refined understanding of global carbon cycle dynamics and provides insights for improving large-scale carbon assessments in the context of climate change.
基金financially supported by the Natural Science Foundation of Shandong Province(No.ZR2021ME011)State Key Laboratory of Alternate Electrical Power System with Renewable Energy Sources(No.LAPS20001)。
文摘In high-frequency electrical energy systems,polyimide(PI)composite insulation materials need to possess a low dielectric constant,sufficient thermal conductivity,and robust interfacial adhesion to ensure reliable performance under elevated temperatures and pressures.These aspects are crucial for preventing local overheating and electrical breakdown,thereby ensuring reliable equipment operation.Traditional PI insulation materials often exhibit high dielectric constants and pronounced dielectric losses,compromising their insulation efficiency.In this study,molecular dynamics simulations were employed to incorporate polyhedral oligomeric silsesquioxanes(POSS)into PI through physical blending and chemical bonding to enhance dielectric properties.Key parameters of the PI/POSS composite system,including dielectric constant,thermal conductivity,glass transition temperature,Young’s modulus,Poisson’s ratio,and interfacial adhesion energy,were systematically evaluated for both doping methods.The degradation behavior of the PI composites under high-temperature and electric field conditions was also simulated to elucidate degradation pathways and product distributions,providing insights for designing low-dielectric insulation materials.Doping with POSS significantly reduces the dielectric constant of PI,thereby improving insulation performance,thermal stability,mechanical strength,and interfacial adhesion.At an optimal POSS doping ratio,the thermal conductivity of PI is enhanced.Compared with the physical blending system,the chemical bonding system yields more substantial improvements across all evaluated properties.Under high-temperature and strong electric field conditions,POSS doping enhances interfacial adhesion and thermal stability,effectively suppressing the cleavage of key chemical bonds,reducingCOemissions,and increasing the formation of oxygen-containing intermediates and water molecules,which contributes to improved environmental sustainability.
基金supported by grants from the National Natural Science Foundation of China(82222017,82271183,and 81970883)the Key Research and Development Program of Hubei Province(2022BCA046)funding from the Fundamental Research Funds for the Central Universities(2042022kf0059).
文摘Although cisplatin is a widely used chemotherapeutic agent,it is severely toxic and causes irreversible hearing loss,restricting its application in clinical settings.This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity.Here,we established in vitro and in vivo ototoxicity models of cisplatininduced hair cell loss,and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death.In addition,we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA,which may act as a critical linker between the cyclic GMP-AMP synthesis−stimulator of interferon genes(cGASSTING)pathway and the pathogenesis of cisplatin-induced hearing loss.H-151,a specific inhibitor of STING,reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo.This study underscores the role of cGASSTING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
基金Supported by the Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,No.2023D009+1 种基金the Natural Science Foundation of Xiamen City,No.3502Z202373104 and No.3502Z20227162Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005。
文摘BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.
基金supported by National Natural Science Foundation of China(32170102)Natural Science Foundation of Tianjin(25JCLMJC00400)the Fundamental Research Funds for the Central Universities(63253191).
文摘Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis,but its colonizing and therapeutic efficacy after oral administration are limited.Here,we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein(MMPB)with the famous probiotic bacteria Lactobacillus plantarum(Lac)and Bifidobacterium animalis subsp.lactis(Bif).The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein.Owing to presence of the artificial protein on the MMPB surface,the nanodrug strongly bound and cross-linked the probiotic cells,forming the Lac+Bif+MMPB co-assembly.During co-incubation with the kanamycin-resistant E.coli strain(Ecka),the co-assembly strongly reduced the viability of Ecka,leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2.After oral administration of the co-assembly to themice pre-colonized by Ecka,Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine,and led to 2-3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif.More importantly,in the mice suffering from enteritis caused by drug-resistant S.Tm,the co-assembly remarkably recovered the mouse body weight,reduced intestine colonization of S.Tm cells,and decreased the levels of pro-inflammatory cytokines in both serum and colons.This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.
