Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In ...Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.展开更多
Targeting Chang'E-8 mission'in-situ resource utilization(ISRU)for sustainable lunar habitats,laser powder bed fusion(LPBF)provides a viable pathway for in-situ additive manufacturing of lunar regolith.To eluci...Targeting Chang'E-8 mission'in-situ resource utilization(ISRU)for sustainable lunar habitats,laser powder bed fusion(LPBF)provides a viable pathway for in-situ additive manufacturing of lunar regolith.To elucidate mission relevant mechanical behavior and failure mechanisms of LPBF fabricated lunar regolith simulants,mare type and highland type simulant specimens were produced.Microstructural characterization,mechanical test coupled with three-dimensional digital image correlation(3D-DIC),and an energy-dissipation framework were employed for comprehensive analysis.The pristine highland specimens achieved 5.79 MPa and a peak strain of 0.13(50 mm×50 mm×30 mm),significantly outperforming their mare counterparts.Wire-cutting to 20 mm×20 mm×20 mm lowered strength by~20%and peak strain to 0.04,indicating cutting-induced defects reduce ductility.All specimens displayed multipeaked stress–strain curves.3D-DIC revealed band-type strain localization in pristine highland samples,diffuse strain patterns in cut highland samples,and highly tortuous,network-type bands in mare samples;the anisotropy index was also quantified.Fragmented particles exhibited fractal dimensions ranging from 1.6 to 2.0(size 1.25–9 mm).Energy evolution progressed through three distinct stages:elastic energy storage,progressive energy dissipation delaying crack propagation,and final unstable collapse.An energy-based damage model was established and validated.The data and methods developed support Chang'E-8 missions'ISRU demonstrations and establish a transferable framework toward sustainable lunar habitats.展开更多
Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid com...Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.展开更多
Alien species from the Asteraceae family frequently invade native plant communities.This study aims to determine how the number of Asteraceae species(i.e.,Erigeron canadensis,E.annuus,and Solidago canadensis)in a co-i...Alien species from the Asteraceae family frequently invade native plant communities.This study aims to determine how the number of Asteraceae species(i.e.,Erigeron canadensis,E.annuus,and Solidago canadensis)in a co-invasion affects plant taxonomic diversity and invasibility in plant communities in China.We found that co-invasions by one or two Asteraceae species decreased plant diversity and increased community invasibility.However,co-invasion by three Asteraceae species increased plant diversity and community invasibility.We also found that plant taxonomic diversity was negatively correlated with total coverage of invasive Asteraceae species.Conversely,community invasibility was positively correlated with total coverage of invasive Asteraceae species.These findings indicate that the number of Asteraceae invasive species positively correlates with total coverage,diversity,dominance,evenness,and invasibility.Our study shows that co-invasion by three IAS may increase plant taxonomic diversity but also community invasibility,which may further facilitate subsequent invasion.展开更多
The dynamic continuous cooling transformation（CCT）diagram and phase transformation rules of 510 MPa automobile beam steel,which is produced by a continuous casting of thin slab of FTSR technology in Tangshan Iron an...The dynamic continuous cooling transformation（CCT）diagram and phase transformation rules of 510 MPa automobile beam steel,which is produced by a continuous casting of thin slab of FTSR technology in Tangshan Iron and Steel Co.Ltd.,are researched by thermal simulation experiment.The microstructure characteristics of the beam steel under different test conditions are studied by means of optical microscope and scanning electron microscope.The test results show that the critical temperatures of phase transformation Ar3 and Ar1 will all decrease with the increase of the cooling rate.When the cooling rate is lower than 20 ℃·s-1,the ferrite and pearlite phase transformations are the main parts;when the cooling rate is higher than 20 ℃·s-1,the bainite phase appears.Moreover,the microstructures of 510 MPa automobile beam steel produced by FTSR technology are also studied,and the results are basically in accordance with the CCT diagram gained from the test.展开更多
<b>Introduction:</b> <i>Burkholderia cepacia</i> is a non-fermenting emergent bacterium common in nosocomial infections and can cause life-threatening infections whose multidrug resistance make...<b>Introduction:</b> <i>Burkholderia cepacia</i> is a non-fermenting emergent bacterium common in nosocomial infections and can cause life-threatening infections whose multidrug resistance makes them a serious threat in hospitals. The aim of this study was to determine the prevalence of <i>B. cepacia</i> infections during nosocomial infections at Libreville University teaching hospital. <b>Methodology:</b> In this cross-sectional study, lasting 19 months, 412 blood cultures were analyzed. The BacT/ALERT 3D (Biomerieux, France) was used to detect the positivity of blood culture flasks and the Viteck 2 compact (Biomerieux, France) for the identification of germs and the study of their susceptibility to antibiotics. <b>Results:</b> Our study population consisted of 412 patients. The sex-ratio M/F was 1.06 in favor of the male gender (n = 201, 51%). The age of the patients varied between 0 and 82 years. The bacteremia of <i>B. cepacia</i> mainly affected children under 15 years of age with a prevalence of 7% (n = 28). The pediatric ward was more represented with a frequency of 36% (n = 10). The antibiotic sensitivity profile showed high resistance of 100% for aminoglycosides (amikacin, tobramycin, and gentamycin), tetracycline, beta-lactams (Amoxicillin, Imipenem, Ticarcillin, Cefoxitin and Cefotaxime), and ciprofloxacin. However, four molecules were active on <i>B. cepacia</i> (Levofloxacin 100%, Trimethoprim + sulfamethoxazole 92.3%, ceftazidime 80% and cefepime 35%). <b>Conclusion:</b> Ultimately, infection and multi-resistance due to <i>Burkholderia cepacia</i> calls for a review of hospital hygiene in the pediatric ward and a review of antibiotic therapy in young children.展开更多
Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vi...Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vironment and intensify carbon emissions.However,the use of microbially induced calcium carbonate pre-cipitation(MICP)to obtain bio-cement is a novel technique with the potential to induce soil stability,providing a low-carbon,environment-friendly,and sustainable integrated solution for some geotechnical engineering pro-blems in the environment.This paper presents a comprehensive review of the latest progress in soil improvement based on the MICP strategy.It systematically summarizes and overviews the mineralization mechanism,influ-encing factors,improved methods,engineering characteristics,and current field application status of the MICP.Additionally,it also explores the limitations and correspondingly proposes prospective applications via the MICP approach for soil improvement.This review indicates that the utilization of different environmental calcium-based wastes in MICP and combination of materials and MICP are conducive to meeting engineering and market demand.Furthermore,we recommend and encourage global collaborative study and practice with a view to commercializing MICP technique in the future.The current review purports to provide insights for engineers and interdisciplinary researchers,and guidance for future engineering applications.展开更多
2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-...2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.展开更多
Whole wheat flour is a food raw material rich in macronutrients,but its application in baking industry is limited due to the existence of a large amount of insoluble dietary fiber in bran.In order to make full use of ...Whole wheat flour is a food raw material rich in macronutrients,but its application in baking industry is limited due to the existence of a large amount of insoluble dietary fiber in bran.In order to make full use of this resource,we first screened twelve cellulase-producing strains,and then extracted soluble dietary fiber(SDF)from whole wheat flour after fermentation with 3 strains of Aspergillus sp.and 2 strains of Bacillus sp.,respectively.The effects of different strains on nutritional characteristics,SDF yield,structure improvement,and antioxidant activity of whole wheat flour were compared.The results showed that fermentation of whole wheat significantly increased the yield of SDF,the content of nutritive active substances,and improved the physicochemical structure and antioxidant activity of SDF in vitro.Scanning electron microscopy(SEM),X-ray diffraction and liquidity characteristics show that the fermentation to make whole wheat SDF has more porous microstructure and crystallinity of lower molecular weight.Fourier transform infrared spectrum showed that there were differences in functional group types between soluble dietary fiber in control group(C-SDF)and soluble dietary fiber in the fermentation group(F-SDF).These changes together improved the hydration performance and antioxidant activity of whole wheat SDF,including water holding capacity,oil holding capacity,cholesterol adsorption,1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and hydroxyl radical scavenging,and lipase activity inhibition.Bacillus sp.SH and Aspergillus oryzae Y21 are ideal strains for fermentation of improved whole wheat,which has the potential of antioxidant properties while improving nutritional properties and food quality.展开更多
Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids...Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids(BAs)can act not only as fat emulsifiers but also as signaling molecules to regulate body metabolism.Although BAs have been used to some extent in monogastric and aquatic animals,their role in ruminants,particularly in transition cows,remains unclear.Therefore,this study aimed to determine the effects of BAs on the production performance,milk and plasma fatty acid and BA composition,and fecal microbiota in transition dairy cows.Results Forty-six healthy transition Holstein dairy cows with similar conditions were randomly divided into two groups and supplemented with 0 or 20 g/d of BAs from 21 d before the expected calving to 21 d after calving.The production performance was tracked until 60 d after calving.The results indicated that BA supplementation significantly improved postpartum milk fat content and yields as well as the yields of unsaturated fatty acids,monounsaturated fatty acids,and polyunsaturated fatty acids in milk.There was a significant increase in the concentration of triglyceride and the proportion of C≤16 fatty acids in the plasma of cows supplemented with BAs,while the concentration of β-hydroxybutyrate and the proportion of C>16 fatty acids in the plasma decreased significantly.BA supplementation significantly altered the composition of the fecal bacterial community and increased the relative abundance of bacteria beneficial for BA metabolism and transformation(Romboutsia,Clostridium sensu_stricto_6,and Clostridium sensu_stricto_1).Functional prediction analysis showed that the relative abundance of bile salt hydrolase,7 α-hydroxysteroid dehydrogenase,and BA inducible E as well as the pathways related to BA metabolism also significantly increased in cows supplemented BAs.In addition,BA supplementation significantly altered the composition of plasma and fecal BAs,particularly increasing circulating secondary BA concentration,which might induce the complete oxidation of fatty acids in the liver and further reduce the concentration of β-hydroxybutyrate.Conclusions These findings highlight the potential benefits of BA supplementation in improving milk yields and quality,as well as influencing metabolic pathways in transition dairy cows.Meanwhile,further studies are needed to elucidate the underlying mechanisms and explore the broader implications of these results by using more tissue samples.展开更多
Background Formolase(FLS)is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone(DHA).FLS lays the foundation for s...Background Formolase(FLS)is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone(DHA).FLS lays the foundation for several artificial carbon fixation and valorization pathways,such as the artificial starch anabolic pathway.However,the application of FLS is limited by its low catalytic activity and product promiscuity.Findings FLS,designed and engineered based on benzoylformate decarboxylase from Pseudomonas putida,was selected as a candidate for modification.To evaluate its catalytic activity,25 residues located within an 8Ådistance from the active center were screened using single-point saturation mutagenesis.A screening approach based on the color reaction of the DHA product was applied to identify the desired FLS variants.After screening approximately 5,000 variants(approximately 200 transformants per site),several amino acid sites that were not identified by directed evolution were found to improve DHA formation.The serine-to-phenylalanine substitution at position 236 improved the activity towards DHA formation by 7.6-fold.Molecular dynamics simulations suggested that the mutation increased local hydrophobicity at the active site,predisposing the cofactor-C2 intermediate to nucleophilic attack by the third formaldehyde molecule for subsequent DHA generation.Conclusions This study provides improved FLS variants and valuable information into the influence of residues adjacent to the active center affecting catalytic efficiency,which can guide the rational engineering or directed evolution of FLS to optimize its performance in artificial carbon fixation and valorization.展开更多
Wind tunnel experiment and CFD(computational fluid dynamics)simulation with LES(large eddy simulation)have been conducted to investigate the characteristics of peak wind force coefficients of porous panels mounted on ...Wind tunnel experiment and CFD(computational fluid dynamics)simulation with LES(large eddy simulation)have been conducted to investigate the characteristics of peak wind force coefficients of porous panels mounted on the roofs of high-rise buildings.First,aerodynamic modelling of porous panels was discussed.The relation between pressure loss coefficient and porosity was obtained.Then,a wind tunnel experiment was conducted to measure the wind forces(net wind pressures)acting on solid and porous panels mounted on the roof of a high-rise building.Because it was difficult to measure the pressures on both sides of thin,porous panel at the same location simultaneously,we proposed to use the roof edge pressures near the panel for the panel’s inside-surface pressures.This experimental method was validated by a CFD simulation reproducing the wind tunnel experiment.The characteristics of peak wind force coefficients of porous panels mounted on the roofs of high-rise buildings were made clear.Finally,positive and negative peak wind force coefficients for designing the rooftop porous panels were proposed.展开更多
Sulfur autotrophic denitrification technology is a low-carbon and environmentally friendly wastewater treatment technology.The effects of factors such as pH,temperature,S/N and salinity on the efficiency of sulfur aut...Sulfur autotrophic denitrification technology is a low-carbon and environmentally friendly wastewater treatment technology.The effects of factors such as pH,temperature,S/N and salinity on the efficiency of sulfur autotrophic denitrification reactions were discussed,and the community characteristics of microorganisms were summarized.This article also introduced the future research and development directions of this process.展开更多
Compared to refined wheat flour,whole wheat flour contains higher nutrients,but its high content of dietary fiber can have a significant impact on the quality of the final product.Therefore,how to enable consumers to ...Compared to refined wheat flour,whole wheat flour contains higher nutrients,but its high content of dietary fiber can have a significant impact on the quality of the final product.Therefore,how to enable consumers to obtain health benefits from whole wheat flour and improve the processing performance of whole wheat products has become a concern.The purpose of this study is to apply 2 strains Bacillus sp.SH and Aspergillus oryzae Y21 with cellulase production capacity and study their adaptability in whole wheat dough.The results indicate that the addition of cellulase-producing strains enhanced the acid production ability of whole wheat dough,rapidly reduced its pH value and insoluble dietary fiber content,and significantly increased the water-soluble arabinoxylan and water-soluble dietary fiber content.During the fermentation process,the viscoelasticity of the dough decreased,free sulfhydryl content increased,wet gluten content decreased,and the degree of reduction was consistent with the degree of acidification.Moreover,the proteolytic activity of the dough was increased,and the hydrolysis of gliadin was the most extensive.SH showed a higher advantage and has been used in whole wheat bread making.Increasing the proportion of strain SH in whole wheat bread can improve the structural characteristics and texture of the bread.When SH(5×10~7 CFU/g)is added to whole wheat bread,its hardness,elasticity,chewiness,and resilience can be similar to those of bread made from control group wheat flour,far exceeding that of whole wheat bread without adding SH.The addition of cellulase producing strains has obvious advantages in the development of whole-wheat dough,and also promote the development of whole wheat fermented foods as staple foods.展开更多
For the treatment of the mixed flue gas desulfurization wastewater with high salinity by the biological fluidized bed process,the optimum temperature was 25-35℃,and the optimum hydraulic retention time was 10 h.When ...For the treatment of the mixed flue gas desulfurization wastewater with high salinity by the biological fluidized bed process,the optimum temperature was 25-35℃,and the optimum hydraulic retention time was 10 h.When the influent quality was stable,the average concentration of COD,NH_(4)^(+)-N and TN in the inlet water was 210,11 and 16.3 mg/L,respectively,and their average concentration in the effluent was 54,0.32 and 4.09 mg/L,respectively.The treatment effect was good.When the incoming water quality of flue gas desulfurization wastewater fluctuated greatly,the effluent quality was still relatively stable after being treated by the biological fluidized bed,indicating that the biological fluidized bed process had a good ability to resist the impact of water quality in the treatment of high-salinity flue gas desulfurization wastewater.At the same time,the biological fluidized bed process provides a reference for high-salinity wastewater that is difficult to be biologically treated.展开更多
Lunar in-situ construction using additive manufacturing(AM)technology has emerged as a critical pathway for sustainable extraterrestrial exploration.This review systematically evaluates two dominant AM paradigms for l...Lunar in-situ construction using additive manufacturing(AM)technology has emerged as a critical pathway for sustainable extraterrestrial exploration.This review systematically evaluates two dominant AM paradigms for lunar regolith processing:low-temperature deposition forming(material extrusion and binder jetting),and high-energy beam additive manufacturing(powder bed fusion and directed energy deposition).Low-temperature methods achieve moderate compressive strength with low energy consumption but face challenges such as binder dependency and vacuum instability.By contrast,high-energy beam techniques enable binder-free fabrication with better compatibility for in-situ resource utilization,though they suffer from porosity,high energy intensity,and geometric limitations.In the context of lunar in-situ resource utilization(ISRU),low-temperature methods offer near-term feasibility for small-scale infrastructure,while high-energy approaches show promise for large-scale,autonomous construction by leveraging solar energy and raw regolith.Future advancements will hinge on hybrid systems that integrate material efficiency,energy sustainability,and robotic adaptability to overcome extreme environmental challenges.This review consolidates technological progress,identifies interdisciplinary synergies,and provides strategic insights into guiding the transition from Earth-dependent prototypes to self-sufficient lunar habitats,ultimately advancing the capability of humanity for a long-term extraterrestrial presence.展开更多
Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and mol...Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and molecular changes remain unclear.This study investigated platelet-derived growth factor receptor beta-positive(Pdgfrb+)pericyte dynamics and reprogramming in GBM vasculature.Methods:We generated GL261-Luc and GL261-CFP glioblastoma cells via lentiviral transduction and established two transgenic models.(1)For pericyte labeling,Ai14 reporter mice was crossed with PDGFRβ-P2A-CreERT2mice for td Tomato-specific lineage tracing(PT mice).(2)For conditional ablation,we generated inducible Pdgfrb-expressing cell ablation models(PT mice was crossed with ROSA-DTA mice).An intravital imaging platform(FITC-dextran/CFP/td Tomato+two-photon microscopy)tracked pericytes,vessels,and tumor cells,while FACSsorted Pdgfrb+cells from GBM and normal brain were analyzed by LC-MS/MS proteomics.Results:Cre-mediated ablation of Pdgfrb-expressing cells revealed stage-dependent effects on GBM growth:early ablation inhibited progression while late ablation promoted it.Pericytes undergo dual spatial reorganization in GBM:regional enrichment with pre-sprouting accumulation at the tumor-brain interface,and focal positioning with preferential localization at vascular branch points.Concurrently,GBM vasculature displayed simplified branching,dilation,and pericyte remodeling(shorter processes,higher density).Proteomics revealed 1426 altered proteins,with upregulated proliferation pathways(e.g.,matrix metallopeptidase 14[Mmp14],lysyl oxidase like 2[Loxl2])and downregulated homeostasis functions(e.g.,transforming growth factor beta 1[Tgfb1]),validated by scRNA-seq in human GBM.Conclusions:This study demonstrates that during early GBM progression,pericytes actively drive tumor angiogenesis through molecular reprogramming toward proliferative and pro-angiogenic phenotypes,with the integrated imaging-proteomics framework revealing potential therapeutic targets for disrupting pericyte-mediated vascular remodeling.展开更多
Electrocatalytic CO_(2)reduction for the synthesis of high value-added multi-carbon(C_(2)+)products is a promising strategy to achieve energy storage and carbon neutrality.However,to acquire high selectivity of C_(2)+...Electrocatalytic CO_(2)reduction for the synthesis of high value-added multi-carbon(C_(2)+)products is a promising strategy to achieve energy storage and carbon neutrality.However,to acquire high selectivity of C_(2)+products remains a challenge.Herein,Ag NCs@Ag-MOF with highly dispersed Ag nanoclusters(NCs)and Cu-O_(2)N2-COF with Cu-O_(2)N2active sites were designed,synthesized and then coupled for the conversion of CO_(2)to liquid C_(2)products(ethanol and acetate).Faradaic efficiency(FE)of the liquid C_(2)products was 90.9% at-0.98 V(vs.RHE),which is 1.9 times that of Cu-O_(2)N2-COF in direct CO_(2)electroreduction and the highest liquid C_(2)products selectivity reported so far.The current density reached 324.8 mA·cm^(-2)at-1.2 V(vs.RHE).In situ infrared spectroscopy and density functional theory calculations showed that the tandem catalytic system significantly enhanced the accumulation of*CO on the catalyst and promoted*CO-*CO coupling,thus significantly improving the selectivity of liquid C_(2)products.展开更多
Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new trea...Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new treatments.An optimal animal model for studies on hypertension must well mimic human-like hemodynamics and pathophysiological structural modification,showing human disease features and complications timely or even ahead of time.A review of the most frequently used hypertensive animal models available,including small and large animals,induced and genetic models,would provide an insight into the appropriate targets to be addressed in the development of different hypertensive animal models.Another focus of the review are the processes of target-organs injury caused by high blood pressure,which mainly influences human health.展开更多
Seed storage proteins and their abundance are closely related to the formation of rice quality and grain size.A better understanding of the molecular basis of seed storage proteins will provide important information f...Seed storage proteins and their abundance are closely related to the formation of rice quality and grain size.A better understanding of the molecular basis of seed storage proteins will provide important information for developing new rice breeding strategies.In this study,we report that a seed storage protein albumin,named OsRAL5,positively regulates rice quality and grain size.OsRAL5 is specifically expressed during the grain-filling stage,suggesting its key role in regulating seed development.Gene editing of OsRAL5 using the CRISPR/Cas9 system diminished grain size and weight,resulting in the development of white-core endosperm and a reduction in eating and cooking quality(ECQ).Conversely,the endosperm appearance became transparent,and both grain weight and ECQ improved in the OsRAL5 over-expressed lines.The major seed storage components differed significantly between the OsRAL5-edited(dOsRAL5-TS)and OsRAL5-overexpressed(OsRAL5-OE)lines compared with the wild type.The protein and total lipid contents both decreased in the dOsRAL5-TS lines and increased in the OsRAL5-OE lines.Collectively,the over-expression of OsRAL5 significantly increased nutritional content and simultaneously improved yield and ECQ.These results imply that OsRAL5 might be a promising candidate gene for breeding super rice varieties with increased yield potential and superior quality.展开更多
文摘Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.
基金supported by the Young Student Project of National Natural Science Foundation of China(No.525B2139)the National Key Research and Development Program of China(Nos.2023YFB3711300 and 2021YFF0500301)the Space Application System of China Manned Space Program(No.KJZ-YYWCL404)。
文摘Targeting Chang'E-8 mission'in-situ resource utilization(ISRU)for sustainable lunar habitats,laser powder bed fusion(LPBF)provides a viable pathway for in-situ additive manufacturing of lunar regolith.To elucidate mission relevant mechanical behavior and failure mechanisms of LPBF fabricated lunar regolith simulants,mare type and highland type simulant specimens were produced.Microstructural characterization,mechanical test coupled with three-dimensional digital image correlation(3D-DIC),and an energy-dissipation framework were employed for comprehensive analysis.The pristine highland specimens achieved 5.79 MPa and a peak strain of 0.13(50 mm×50 mm×30 mm),significantly outperforming their mare counterparts.Wire-cutting to 20 mm×20 mm×20 mm lowered strength by~20%and peak strain to 0.04,indicating cutting-induced defects reduce ductility.All specimens displayed multipeaked stress–strain curves.3D-DIC revealed band-type strain localization in pristine highland samples,diffuse strain patterns in cut highland samples,and highly tortuous,network-type bands in mare samples;the anisotropy index was also quantified.Fragmented particles exhibited fractal dimensions ranging from 1.6 to 2.0(size 1.25–9 mm).Energy evolution progressed through three distinct stages:elastic energy storage,progressive energy dissipation delaying crack propagation,and final unstable collapse.An energy-based damage model was established and validated.The data and methods developed support Chang'E-8 missions'ISRU demonstrations and establish a transferable framework toward sustainable lunar habitats.
基金supported by Huhhot Science&Technology Plan(2021-National Center of Technology innovation for Dairy-4)Innovation Consortium Project(2023RC Consortium-7)+3 种基金National Key Research and Development Program(2023YFF1104502)Ganpo Juncai supports the plan(20232BCJ22046)Nanchang University Jiangxi Financial Science and Technology Special Project(ZBG20230418011)Free Exploration Project of State Key Laboratory(SKLF-ZZB-202317).
文摘Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.
基金funded by the following sources:State Key Research Development Program of China(2024YFF1307500)Open Science Research Fund of Key Laboratory of Ocean Space Resource Management Technology,Marine Academy of Zhejiang Province,China(KF-2024-112)+2 种基金Special Research Project of School of Emergency Management,Jiangsu University(KY-C-01)Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment(no grant number)Research project on the application of invasive plants in soil ecological restoration in Jiangsu(20240110).
文摘Alien species from the Asteraceae family frequently invade native plant communities.This study aims to determine how the number of Asteraceae species(i.e.,Erigeron canadensis,E.annuus,and Solidago canadensis)in a co-invasion affects plant taxonomic diversity and invasibility in plant communities in China.We found that co-invasions by one or two Asteraceae species decreased plant diversity and increased community invasibility.However,co-invasion by three Asteraceae species increased plant diversity and community invasibility.We also found that plant taxonomic diversity was negatively correlated with total coverage of invasive Asteraceae species.Conversely,community invasibility was positively correlated with total coverage of invasive Asteraceae species.These findings indicate that the number of Asteraceae invasive species positively correlates with total coverage,diversity,dominance,evenness,and invasibility.Our study shows that co-invasion by three IAS may increase plant taxonomic diversity but also community invasibility,which may further facilitate subsequent invasion.
基金Item Sponsored by National Natural Science Foundation of China(50334010)FOK YING TUNG Education Foundation(104017)
文摘The dynamic continuous cooling transformation（CCT）diagram and phase transformation rules of 510 MPa automobile beam steel,which is produced by a continuous casting of thin slab of FTSR technology in Tangshan Iron and Steel Co.Ltd.,are researched by thermal simulation experiment.The microstructure characteristics of the beam steel under different test conditions are studied by means of optical microscope and scanning electron microscope.The test results show that the critical temperatures of phase transformation Ar3 and Ar1 will all decrease with the increase of the cooling rate.When the cooling rate is lower than 20 ℃·s-1,the ferrite and pearlite phase transformations are the main parts;when the cooling rate is higher than 20 ℃·s-1,the bainite phase appears.Moreover,the microstructures of 510 MPa automobile beam steel produced by FTSR technology are also studied,and the results are basically in accordance with the CCT diagram gained from the test.
文摘<b>Introduction:</b> <i>Burkholderia cepacia</i> is a non-fermenting emergent bacterium common in nosocomial infections and can cause life-threatening infections whose multidrug resistance makes them a serious threat in hospitals. The aim of this study was to determine the prevalence of <i>B. cepacia</i> infections during nosocomial infections at Libreville University teaching hospital. <b>Methodology:</b> In this cross-sectional study, lasting 19 months, 412 blood cultures were analyzed. The BacT/ALERT 3D (Biomerieux, France) was used to detect the positivity of blood culture flasks and the Viteck 2 compact (Biomerieux, France) for the identification of germs and the study of their susceptibility to antibiotics. <b>Results:</b> Our study population consisted of 412 patients. The sex-ratio M/F was 1.06 in favor of the male gender (n = 201, 51%). The age of the patients varied between 0 and 82 years. The bacteremia of <i>B. cepacia</i> mainly affected children under 15 years of age with a prevalence of 7% (n = 28). The pediatric ward was more represented with a frequency of 36% (n = 10). The antibiotic sensitivity profile showed high resistance of 100% for aminoglycosides (amikacin, tobramycin, and gentamycin), tetracycline, beta-lactams (Amoxicillin, Imipenem, Ticarcillin, Cefoxitin and Cefotaxime), and ciprofloxacin. However, four molecules were active on <i>B. cepacia</i> (Levofloxacin 100%, Trimethoprim + sulfamethoxazole 92.3%, ceftazidime 80% and cefepime 35%). <b>Conclusion:</b> Ultimately, infection and multi-resistance due to <i>Burkholderia cepacia</i> calls for a review of hospital hygiene in the pediatric ward and a review of antibiotic therapy in young children.
基金funded by the National Natural Science Foundation of China(No.41962016)the Natural Science Foundation of NingXia(Nos.2023AAC02023,2023A1218,and 2021AAC02006).
文摘Soil improvement is one of the most important issues in geotechnical engineering practice.The wide application of traditional improvement techniques(cement/chemical materials)are limited due to damage ecological en-vironment and intensify carbon emissions.However,the use of microbially induced calcium carbonate pre-cipitation(MICP)to obtain bio-cement is a novel technique with the potential to induce soil stability,providing a low-carbon,environment-friendly,and sustainable integrated solution for some geotechnical engineering pro-blems in the environment.This paper presents a comprehensive review of the latest progress in soil improvement based on the MICP strategy.It systematically summarizes and overviews the mineralization mechanism,influ-encing factors,improved methods,engineering characteristics,and current field application status of the MICP.Additionally,it also explores the limitations and correspondingly proposes prospective applications via the MICP approach for soil improvement.This review indicates that the utilization of different environmental calcium-based wastes in MICP and combination of materials and MICP are conducive to meeting engineering and market demand.Furthermore,we recommend and encourage global collaborative study and practice with a view to commercializing MICP technique in the future.The current review purports to provide insights for engineers and interdisciplinary researchers,and guidance for future engineering applications.
基金financially supported by the National Key Research and Development Program of China(2022YFF1100402)National Center of Technology Innovation for Dairy(2022-Open subject-11)+1 种基金Young Elite Scientist Sponsorship Program by CAST(YESS20200271)the National Natural Science Foundation of China(32101919)。
文摘2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.
基金supported by National Natural Science Foundation of China(32330081).
文摘Whole wheat flour is a food raw material rich in macronutrients,but its application in baking industry is limited due to the existence of a large amount of insoluble dietary fiber in bran.In order to make full use of this resource,we first screened twelve cellulase-producing strains,and then extracted soluble dietary fiber(SDF)from whole wheat flour after fermentation with 3 strains of Aspergillus sp.and 2 strains of Bacillus sp.,respectively.The effects of different strains on nutritional characteristics,SDF yield,structure improvement,and antioxidant activity of whole wheat flour were compared.The results showed that fermentation of whole wheat significantly increased the yield of SDF,the content of nutritive active substances,and improved the physicochemical structure and antioxidant activity of SDF in vitro.Scanning electron microscopy(SEM),X-ray diffraction and liquidity characteristics show that the fermentation to make whole wheat SDF has more porous microstructure and crystallinity of lower molecular weight.Fourier transform infrared spectrum showed that there were differences in functional group types between soluble dietary fiber in control group(C-SDF)and soluble dietary fiber in the fermentation group(F-SDF).These changes together improved the hydration performance and antioxidant activity of whole wheat SDF,including water holding capacity,oil holding capacity,cholesterol adsorption,1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and hydroxyl radical scavenging,and lipase activity inhibition.Bacillus sp.SH and Aspergillus oryzae Y21 are ideal strains for fermentation of improved whole wheat,which has the potential of antioxidant properties while improving nutritional properties and food quality.
基金supported by the National Center of Technology Innovation for Dairy(No.2024-JSGG-021)the National Natural Science Foundation of China(No.32102570)the Key Research and Development Project of Ningxia(No.2024BBF01006).
文摘Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids(BAs)can act not only as fat emulsifiers but also as signaling molecules to regulate body metabolism.Although BAs have been used to some extent in monogastric and aquatic animals,their role in ruminants,particularly in transition cows,remains unclear.Therefore,this study aimed to determine the effects of BAs on the production performance,milk and plasma fatty acid and BA composition,and fecal microbiota in transition dairy cows.Results Forty-six healthy transition Holstein dairy cows with similar conditions were randomly divided into two groups and supplemented with 0 or 20 g/d of BAs from 21 d before the expected calving to 21 d after calving.The production performance was tracked until 60 d after calving.The results indicated that BA supplementation significantly improved postpartum milk fat content and yields as well as the yields of unsaturated fatty acids,monounsaturated fatty acids,and polyunsaturated fatty acids in milk.There was a significant increase in the concentration of triglyceride and the proportion of C≤16 fatty acids in the plasma of cows supplemented with BAs,while the concentration of β-hydroxybutyrate and the proportion of C>16 fatty acids in the plasma decreased significantly.BA supplementation significantly altered the composition of the fecal bacterial community and increased the relative abundance of bacteria beneficial for BA metabolism and transformation(Romboutsia,Clostridium sensu_stricto_6,and Clostridium sensu_stricto_1).Functional prediction analysis showed that the relative abundance of bile salt hydrolase,7 α-hydroxysteroid dehydrogenase,and BA inducible E as well as the pathways related to BA metabolism also significantly increased in cows supplemented BAs.In addition,BA supplementation significantly altered the composition of plasma and fecal BAs,particularly increasing circulating secondary BA concentration,which might induce the complete oxidation of fatty acids in the liver and further reduce the concentration of β-hydroxybutyrate.Conclusions These findings highlight the potential benefits of BA supplementation in improving milk yields and quality,as well as influencing metabolic pathways in transition dairy cows.Meanwhile,further studies are needed to elucidate the underlying mechanisms and explore the broader implications of these results by using more tissue samples.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDC0110201)the National Natural Science Foundation of China(32222004 and 32070083)+3 种基金the Major Program and Innovation Fund of Haihe Laboratory of Synthetic Biology(22HHSWSS00003 and 22HHSWSS00017)the CAS Project for Young Scientists in Basic Research(YSBR-072)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2021177)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-008).
文摘Background Formolase(FLS)is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone(DHA).FLS lays the foundation for several artificial carbon fixation and valorization pathways,such as the artificial starch anabolic pathway.However,the application of FLS is limited by its low catalytic activity and product promiscuity.Findings FLS,designed and engineered based on benzoylformate decarboxylase from Pseudomonas putida,was selected as a candidate for modification.To evaluate its catalytic activity,25 residues located within an 8Ådistance from the active center were screened using single-point saturation mutagenesis.A screening approach based on the color reaction of the DHA product was applied to identify the desired FLS variants.After screening approximately 5,000 variants(approximately 200 transformants per site),several amino acid sites that were not identified by directed evolution were found to improve DHA formation.The serine-to-phenylalanine substitution at position 236 improved the activity towards DHA formation by 7.6-fold.Molecular dynamics simulations suggested that the mutation increased local hydrophobicity at the active site,predisposing the cofactor-C2 intermediate to nucleophilic attack by the third formaldehyde molecule for subsequent DHA generation.Conclusions This study provides improved FLS variants and valuable information into the influence of residues adjacent to the active center affecting catalytic efficiency,which can guide the rational engineering or directed evolution of FLS to optimize its performance in artificial carbon fixation and valorization.
文摘Wind tunnel experiment and CFD(computational fluid dynamics)simulation with LES(large eddy simulation)have been conducted to investigate the characteristics of peak wind force coefficients of porous panels mounted on the roofs of high-rise buildings.First,aerodynamic modelling of porous panels was discussed.The relation between pressure loss coefficient and porosity was obtained.Then,a wind tunnel experiment was conducted to measure the wind forces(net wind pressures)acting on solid and porous panels mounted on the roof of a high-rise building.Because it was difficult to measure the pressures on both sides of thin,porous panel at the same location simultaneously,we proposed to use the roof edge pressures near the panel for the panel’s inside-surface pressures.This experimental method was validated by a CFD simulation reproducing the wind tunnel experiment.The characteristics of peak wind force coefficients of porous panels mounted on the roofs of high-rise buildings were made clear.Finally,positive and negative peak wind force coefficients for designing the rooftop porous panels were proposed.
文摘Sulfur autotrophic denitrification technology is a low-carbon and environmentally friendly wastewater treatment technology.The effects of factors such as pH,temperature,S/N and salinity on the efficiency of sulfur autotrophic denitrification reactions were discussed,and the community characteristics of microorganisms were summarized.This article also introduced the future research and development directions of this process.
基金supported by National Natural Science Foundation of China(32330081)。
文摘Compared to refined wheat flour,whole wheat flour contains higher nutrients,but its high content of dietary fiber can have a significant impact on the quality of the final product.Therefore,how to enable consumers to obtain health benefits from whole wheat flour and improve the processing performance of whole wheat products has become a concern.The purpose of this study is to apply 2 strains Bacillus sp.SH and Aspergillus oryzae Y21 with cellulase production capacity and study their adaptability in whole wheat dough.The results indicate that the addition of cellulase-producing strains enhanced the acid production ability of whole wheat dough,rapidly reduced its pH value and insoluble dietary fiber content,and significantly increased the water-soluble arabinoxylan and water-soluble dietary fiber content.During the fermentation process,the viscoelasticity of the dough decreased,free sulfhydryl content increased,wet gluten content decreased,and the degree of reduction was consistent with the degree of acidification.Moreover,the proteolytic activity of the dough was increased,and the hydrolysis of gliadin was the most extensive.SH showed a higher advantage and has been used in whole wheat bread making.Increasing the proportion of strain SH in whole wheat bread can improve the structural characteristics and texture of the bread.When SH(5×10~7 CFU/g)is added to whole wheat bread,its hardness,elasticity,chewiness,and resilience can be similar to those of bread made from control group wheat flour,far exceeding that of whole wheat bread without adding SH.The addition of cellulase producing strains has obvious advantages in the development of whole-wheat dough,and also promote the development of whole wheat fermented foods as staple foods.
文摘For the treatment of the mixed flue gas desulfurization wastewater with high salinity by the biological fluidized bed process,the optimum temperature was 25-35℃,and the optimum hydraulic retention time was 10 h.When the influent quality was stable,the average concentration of COD,NH_(4)^(+)-N and TN in the inlet water was 210,11 and 16.3 mg/L,respectively,and their average concentration in the effluent was 54,0.32 and 4.09 mg/L,respectively.The treatment effect was good.When the incoming water quality of flue gas desulfurization wastewater fluctuated greatly,the effluent quality was still relatively stable after being treated by the biological fluidized bed,indicating that the biological fluidized bed process had a good ability to resist the impact of water quality in the treatment of high-salinity flue gas desulfurization wastewater.At the same time,the biological fluidized bed process provides a reference for high-salinity wastewater that is difficult to be biologically treated.
基金supported by National Key Research and Development Program of China(Grant Nos.2023YFB3711300,2021YFF0500300)Space Application System of China Manned Space ProgramStrategic Research and Consulting Project of the Chinese Academy of Engineering(Grant No.2023-JB-09-10)。
文摘Lunar in-situ construction using additive manufacturing(AM)technology has emerged as a critical pathway for sustainable extraterrestrial exploration.This review systematically evaluates two dominant AM paradigms for lunar regolith processing:low-temperature deposition forming(material extrusion and binder jetting),and high-energy beam additive manufacturing(powder bed fusion and directed energy deposition).Low-temperature methods achieve moderate compressive strength with low energy consumption but face challenges such as binder dependency and vacuum instability.By contrast,high-energy beam techniques enable binder-free fabrication with better compatibility for in-situ resource utilization,though they suffer from porosity,high energy intensity,and geometric limitations.In the context of lunar in-situ resource utilization(ISRU),low-temperature methods offer near-term feasibility for small-scale infrastructure,while high-energy approaches show promise for large-scale,autonomous construction by leveraging solar energy and raw regolith.Future advancements will hinge on hybrid systems that integrate material efficiency,energy sustainability,and robotic adaptability to overcome extreme environmental challenges.This review consolidates technological progress,identifies interdisciplinary synergies,and provides strategic insights into guiding the transition from Earth-dependent prototypes to self-sufficient lunar habitats,ultimately advancing the capability of humanity for a long-term extraterrestrial presence.
基金The National Key Research and Development Program of China,Grant/Award Number:2022YFF0710700Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01。
文摘Background:Glioblastoma(GBM)is a highly aggressive brain tumor characterized by aberrant angiogenesis and an immunosuppressive microenvironment.Pericytes are aberrantly recruited but their spatiotemporal roles and molecular changes remain unclear.This study investigated platelet-derived growth factor receptor beta-positive(Pdgfrb+)pericyte dynamics and reprogramming in GBM vasculature.Methods:We generated GL261-Luc and GL261-CFP glioblastoma cells via lentiviral transduction and established two transgenic models.(1)For pericyte labeling,Ai14 reporter mice was crossed with PDGFRβ-P2A-CreERT2mice for td Tomato-specific lineage tracing(PT mice).(2)For conditional ablation,we generated inducible Pdgfrb-expressing cell ablation models(PT mice was crossed with ROSA-DTA mice).An intravital imaging platform(FITC-dextran/CFP/td Tomato+two-photon microscopy)tracked pericytes,vessels,and tumor cells,while FACSsorted Pdgfrb+cells from GBM and normal brain were analyzed by LC-MS/MS proteomics.Results:Cre-mediated ablation of Pdgfrb-expressing cells revealed stage-dependent effects on GBM growth:early ablation inhibited progression while late ablation promoted it.Pericytes undergo dual spatial reorganization in GBM:regional enrichment with pre-sprouting accumulation at the tumor-brain interface,and focal positioning with preferential localization at vascular branch points.Concurrently,GBM vasculature displayed simplified branching,dilation,and pericyte remodeling(shorter processes,higher density).Proteomics revealed 1426 altered proteins,with upregulated proliferation pathways(e.g.,matrix metallopeptidase 14[Mmp14],lysyl oxidase like 2[Loxl2])and downregulated homeostasis functions(e.g.,transforming growth factor beta 1[Tgfb1]),validated by scRNA-seq in human GBM.Conclusions:This study demonstrates that during early GBM progression,pericytes actively drive tumor angiogenesis through molecular reprogramming toward proliferative and pro-angiogenic phenotypes,with the integrated imaging-proteomics framework revealing potential therapeutic targets for disrupting pericyte-mediated vascular remodeling.
基金financially supported by the National Natural Science Foundation of China(No.22233006,22273018)the Natural Science Foundation of Henan Province(232300421081)+1 种基金Key Research Projects of Higher Education Institutions in Henan Province(25B150004)111 Project(D17007)。
文摘Electrocatalytic CO_(2)reduction for the synthesis of high value-added multi-carbon(C_(2)+)products is a promising strategy to achieve energy storage and carbon neutrality.However,to acquire high selectivity of C_(2)+products remains a challenge.Herein,Ag NCs@Ag-MOF with highly dispersed Ag nanoclusters(NCs)and Cu-O_(2)N2-COF with Cu-O_(2)N2active sites were designed,synthesized and then coupled for the conversion of CO_(2)to liquid C_(2)products(ethanol and acetate).Faradaic efficiency(FE)of the liquid C_(2)products was 90.9% at-0.98 V(vs.RHE),which is 1.9 times that of Cu-O_(2)N2-COF in direct CO_(2)electroreduction and the highest liquid C_(2)products selectivity reported so far.The current density reached 324.8 mA·cm^(-2)at-1.2 V(vs.RHE).In situ infrared spectroscopy and density functional theory calculations showed that the tandem catalytic system significantly enhanced the accumulation of*CO on the catalyst and promoted*CO-*CO coupling,thus significantly improving the selectivity of liquid C_(2)products.
基金National Natural Science Foundation of China,Grant/Award Number:82270289Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CAMS),Grant/Award Number:2021-I2M-1-035the National key research and development program,Grant/Award Number:2022YFF0710600。
文摘Although hypertension is a frequently seen chronic condition across the world,its exact cause remains unclear.Animal models are beneficial for clarifying the pathogenic mechanism of hypertension and examining new treatments.An optimal animal model for studies on hypertension must well mimic human-like hemodynamics and pathophysiological structural modification,showing human disease features and complications timely or even ahead of time.A review of the most frequently used hypertensive animal models available,including small and large animals,induced and genetic models,would provide an insight into the appropriate targets to be addressed in the development of different hypertensive animal models.Another focus of the review are the processes of target-organs injury caused by high blood pressure,which mainly influences human health.
基金supported by the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20211137)China Agriculture Research System(Grant No.CARS-01)。
文摘Seed storage proteins and their abundance are closely related to the formation of rice quality and grain size.A better understanding of the molecular basis of seed storage proteins will provide important information for developing new rice breeding strategies.In this study,we report that a seed storage protein albumin,named OsRAL5,positively regulates rice quality and grain size.OsRAL5 is specifically expressed during the grain-filling stage,suggesting its key role in regulating seed development.Gene editing of OsRAL5 using the CRISPR/Cas9 system diminished grain size and weight,resulting in the development of white-core endosperm and a reduction in eating and cooking quality(ECQ).Conversely,the endosperm appearance became transparent,and both grain weight and ECQ improved in the OsRAL5 over-expressed lines.The major seed storage components differed significantly between the OsRAL5-edited(dOsRAL5-TS)and OsRAL5-overexpressed(OsRAL5-OE)lines compared with the wild type.The protein and total lipid contents both decreased in the dOsRAL5-TS lines and increased in the OsRAL5-OE lines.Collectively,the over-expression of OsRAL5 significantly increased nutritional content and simultaneously improved yield and ECQ.These results imply that OsRAL5 might be a promising candidate gene for breeding super rice varieties with increased yield potential and superior quality.
