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
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
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
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
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
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: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
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
Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune press...Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.展开更多
Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue a...Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.展开更多
The Northeast region is the main producer of guava in Brazil,generating employment and income.However,water availability means that producer’s resort to using water with high salinity,which harms plant development,es...The Northeast region is the main producer of guava in Brazil,generating employment and income.However,water availability means that producer’s resort to using water with high salinity,which harms plant development,especially during the seedling formation phase.The adoption of techniques that mitigate the deleterious effect of salinity is increasingly necessary,such as the use of elicitors such as ascorbic acid.The purpose of this study was to analyze the morphophysiology of guava seedlings under saline and ascorbic acid levels.The study was carried out by applying treatments composed of five saline levels(SL=0.3;1.3;2.3;3.3 and 4.3 dS m^(-1))and four levels of ascorbic acid—AA(0,200,400,and 600 mg L^(-1)),in a 5×4 factorial arrangement,adopting a randomized block design.Gas exchange and growth of guava seedlings are limited from 0.3 dS m^(-1).Using 400 mg L^(-1)of AA reduces damage from salinity on stomatal conductance,transpiration,and net assimilation rate up to the estimated SL of 1.80 dS m^(-1).In contrast,AA level 412 mg L^(-1)increased instantaneous water use efficiency up to the salinity of 2.3 dS m^(-1).AA level of 600 mg L^(-1)attenuated salt stress effects on leaf area and height/stem diameter ratio up to SL of 2.05 dS m^(-1).The number of leaves and the absolute and relative growth rates were stimulated by AA under the lowest saline level.展开更多
The forming quality of metal bipolar plate(BPP)flow channels in proton exchange membrane fuel cells(PEMFCs)is a key factor affecting battery performance.A flow channel with straight sidewalls and a low thinning rate c...The forming quality of metal bipolar plate(BPP)flow channels in proton exchange membrane fuel cells(PEMFCs)is a key factor affecting battery performance.A flow channel with straight sidewalls and a low thinning rate can enhance battery output.Roll forming,as a new technology for BPP production,offers advantages such as a low thinning rate and high efficiency.However,existing roll curve design methods struggle to accommodate both low thinning rates and straight sidewall angles simultaneously.This study aims to develop flow channels with right-angled sidewalls,which provide benefits such as a low thinning rate,reduced residual stress,and high accuracy.A roller tooth profile was designed to achieve a flow channel with right-angled sidewalls and minimal thinning.Simulations and experiments were conducted to validate the feasibility of this novel design method for the roll forming process.The study investigated the effects of roller tooth parameters on sidewall angle,thinning rate,and residual stress.A multifactor evaluation method was developed to optimize the tip fillet radius and the tooth profile backlash of the roller.The results indicated that the tip fillet radius and the tooth profile backlash were negatively correlated with the sidewall angle.As the tip fillet radius and tooth profile backlash increased,the thinning rate and residual stress decreased.With a tip fillet radius of 0.25 mm and a tooth profile backlash of 0.19 mm,the flow channel achieved an approximately right-angled sidewall,a maximum thinning rate of 7.7%,a 29.6%reduction in maximum residual stress,and maximum and average residual stress imbalance values of 7.1%and 3.2%,respectively.This study proposes a new design method for a right-angled sidewall runner roller gear profile,facilitating the roll forming of metal BPPs with right-angled sidewalls and minimal thinning.This method provides theoretical support for the large-scale application of roll forming in the manufacture of PEMFC BPPs.展开更多
Development of clean desulfurization process that combines both efficient and environmentally friendly remains a significant challenge for diesel production.The photocatalytic oxidation desulfurization technology is r...Development of clean desulfurization process that combines both efficient and environmentally friendly remains a significant challenge for diesel production.The photocatalytic oxidation desulfurization technology is regarded as a promising process depending on the superior electron transfer and visible light utilization of photocatalyst.Herein,the nonstoichiometry MoO_(3-x)with outstanding photoresponse ability is prepared and modified by imidazole-based ionic liquid[C_(12)mim]Cl to upgrade electronic structure.The interface H-bonding between MoO_(3-x)and[C_(12)mim]Cl regard as electronic transfer channel and the recombination of e^(-)-h^(+)pairs is effectively inhibited with the modification of[C_(12)mim]Cl.Deep desulfurization rate of 96.6%can be reached within 60 min and the MoO_(3-x)/[C_(12)mim]Cl(MoC_(12))photocatalyst demonstrated outstanding cyclic stability within 7 cycles in an extraction coupled photocatalytic oxidation desulfurization(ECPODS)system.The study provides a new perspective on enhancing photocatalytic desulfurization through defect engineering and surface modification.展开更多
Photocatalytic technology has been proven to be a simple and effective method for degrading recalcitrant organic pollutants.In this study,a series of Z-scheme heterojunction nanocomposites composed of CeO_(2)and terep...Photocatalytic technology has been proven to be a simple and effective method for degrading recalcitrant organic pollutants.In this study,a series of Z-scheme heterojunction nanocomposites composed of CeO_(2)and terephthalic acid-modified WO_(3) was prepared and further used as photocatalysts for perfluorobutane sulfonate(PFBS)degradation.In this design,terephthalic acid was used as an electron recombination center and heterojunction mediator,which effectively enhances the migration ability of electron-hole pairs and the physicochemical stability of the catalyst.In addition,in situ synthesis of CeO_(2)onto the WO_(3) surface by the coordinate bond between terephthalic acid and Ce ions can avoid CeO_(2)agglomeration.As a result,the CeO_(2)@WO_(3) photocatalyst exhibits excellent PFBS degradation ability(94%for CeO_(2)@WO_(3) vs.19%for CeO_(2)).After the fifth cyclic degradation experiment,the CeO_(2)@WO_(3) photocatalyst still maintains stable degradation efficiency.Furthermore,the reaction mechanism of the PFBS in CeO_(2)@WO_(3) photocatalytic process was analyzed by free radical trapping experiment and liquid chromatography tandem mass spectrometry(LC-MS)technique.This study provides new insights for constructing Z-scheme heterojunction and demonstrates that CeO_(2)@WO_(3) photocatalysts possess a promising prospect for degrading PFBS pollutants.展开更多
Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer t...Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms.Methods In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods(GNRs) and tetrahedral framework nucleic acids(tFNA) loaded with the anti-tumor drug doxorubicin(DOX).Results Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation.Conclusion This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.展开更多
Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orth...Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.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 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.
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.
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 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.
基金National Science and Technology Infrastructure of China,Grant/Award Number:National Pathogen Resource Center-NPRC-32National Key Research and Development Program of China,Grant/Award Number:2023YFF0724800CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
文摘Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
基金Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-035 and 2022-I2M-1-011。
文摘Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.
基金supported by CNPq(National Council for Scientific and Technological Development—Processo:151057/2024-9),CAPES(Coordination for the Improvement of Higher Education Personnel)financial code—001,and UFCG(Universidade Federal de Campina Grande).
文摘The Northeast region is the main producer of guava in Brazil,generating employment and income.However,water availability means that producer’s resort to using water with high salinity,which harms plant development,especially during the seedling formation phase.The adoption of techniques that mitigate the deleterious effect of salinity is increasingly necessary,such as the use of elicitors such as ascorbic acid.The purpose of this study was to analyze the morphophysiology of guava seedlings under saline and ascorbic acid levels.The study was carried out by applying treatments composed of five saline levels(SL=0.3;1.3;2.3;3.3 and 4.3 dS m^(-1))and four levels of ascorbic acid—AA(0,200,400,and 600 mg L^(-1)),in a 5×4 factorial arrangement,adopting a randomized block design.Gas exchange and growth of guava seedlings are limited from 0.3 dS m^(-1).Using 400 mg L^(-1)of AA reduces damage from salinity on stomatal conductance,transpiration,and net assimilation rate up to the estimated SL of 1.80 dS m^(-1).In contrast,AA level 412 mg L^(-1)increased instantaneous water use efficiency up to the salinity of 2.3 dS m^(-1).AA level of 600 mg L^(-1)attenuated salt stress effects on leaf area and height/stem diameter ratio up to SL of 2.05 dS m^(-1).The number of leaves and the absolute and relative growth rates were stimulated by AA under the lowest saline level.
基金Supported by Major Special Projects of Public Bidding in Shanxi Province of China(Grant No.20201101020)Central Guidance on Local Science and Technology Development Fund Project of China(Grant No.YDZJSX2022A053)Open Fund Subjectof National Key Laboratory of Material Forming and Mold Technology of China(Grant No.P2024-002)。
文摘The forming quality of metal bipolar plate(BPP)flow channels in proton exchange membrane fuel cells(PEMFCs)is a key factor affecting battery performance.A flow channel with straight sidewalls and a low thinning rate can enhance battery output.Roll forming,as a new technology for BPP production,offers advantages such as a low thinning rate and high efficiency.However,existing roll curve design methods struggle to accommodate both low thinning rates and straight sidewall angles simultaneously.This study aims to develop flow channels with right-angled sidewalls,which provide benefits such as a low thinning rate,reduced residual stress,and high accuracy.A roller tooth profile was designed to achieve a flow channel with right-angled sidewalls and minimal thinning.Simulations and experiments were conducted to validate the feasibility of this novel design method for the roll forming process.The study investigated the effects of roller tooth parameters on sidewall angle,thinning rate,and residual stress.A multifactor evaluation method was developed to optimize the tip fillet radius and the tooth profile backlash of the roller.The results indicated that the tip fillet radius and the tooth profile backlash were negatively correlated with the sidewall angle.As the tip fillet radius and tooth profile backlash increased,the thinning rate and residual stress decreased.With a tip fillet radius of 0.25 mm and a tooth profile backlash of 0.19 mm,the flow channel achieved an approximately right-angled sidewall,a maximum thinning rate of 7.7%,a 29.6%reduction in maximum residual stress,and maximum and average residual stress imbalance values of 7.1%and 3.2%,respectively.This study proposes a new design method for a right-angled sidewall runner roller gear profile,facilitating the roll forming of metal BPPs with right-angled sidewalls and minimal thinning.This method provides theoretical support for the large-scale application of roll forming in the manufacture of PEMFC BPPs.
基金supports from National Natural Science Foundation of China(Nos.22172066,22378176)supported by State Key Laboratory of Heavy Oil Processing.Supported by Jiangsu Collaborative Innovation Center of TechnologyMaterial of Water Treatment,Suzhou University of Science and Technology.
文摘Development of clean desulfurization process that combines both efficient and environmentally friendly remains a significant challenge for diesel production.The photocatalytic oxidation desulfurization technology is regarded as a promising process depending on the superior electron transfer and visible light utilization of photocatalyst.Herein,the nonstoichiometry MoO_(3-x)with outstanding photoresponse ability is prepared and modified by imidazole-based ionic liquid[C_(12)mim]Cl to upgrade electronic structure.The interface H-bonding between MoO_(3-x)and[C_(12)mim]Cl regard as electronic transfer channel and the recombination of e^(-)-h^(+)pairs is effectively inhibited with the modification of[C_(12)mim]Cl.Deep desulfurization rate of 96.6%can be reached within 60 min and the MoO_(3-x)/[C_(12)mim]Cl(MoC_(12))photocatalyst demonstrated outstanding cyclic stability within 7 cycles in an extraction coupled photocatalytic oxidation desulfurization(ECPODS)system.The study provides a new perspective on enhancing photocatalytic desulfurization through defect engineering and surface modification.
基金Project supported by the National Natural Science Foundation of China(52300206)the Natural Science Foundation of Jiangsu Province(BK20230705)+2 种基金Industry-University Research Cooperation Project of Jiangsu Province,China(BY20221227)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB610014)the Talent-Recruiting Program of Nanjing Institute of Technology(YKJ202124)。
文摘Photocatalytic technology has been proven to be a simple and effective method for degrading recalcitrant organic pollutants.In this study,a series of Z-scheme heterojunction nanocomposites composed of CeO_(2)and terephthalic acid-modified WO_(3) was prepared and further used as photocatalysts for perfluorobutane sulfonate(PFBS)degradation.In this design,terephthalic acid was used as an electron recombination center and heterojunction mediator,which effectively enhances the migration ability of electron-hole pairs and the physicochemical stability of the catalyst.In addition,in situ synthesis of CeO_(2)onto the WO_(3) surface by the coordinate bond between terephthalic acid and Ce ions can avoid CeO_(2)agglomeration.As a result,the CeO_(2)@WO_(3) photocatalyst exhibits excellent PFBS degradation ability(94%for CeO_(2)@WO_(3) vs.19%for CeO_(2)).After the fifth cyclic degradation experiment,the CeO_(2)@WO_(3) photocatalyst still maintains stable degradation efficiency.Furthermore,the reaction mechanism of the PFBS in CeO_(2)@WO_(3) photocatalytic process was analyzed by free radical trapping experiment and liquid chromatography tandem mass spectrometry(LC-MS)technique.This study provides new insights for constructing Z-scheme heterojunction and demonstrates that CeO_(2)@WO_(3) photocatalysts possess a promising prospect for degrading PFBS pollutants.
基金supported by the PLAGH Innovation Funds,(Grant No.22QNFC080)the Sichuan Science and Technology Program(Grant No.2023ZYD0064 and 2023YFG0220)+2 种基金the Fundamental Research Funds for the Central Universities(Grant No.YJ202242)the Research Funding from West China School/Hospital of Stomatology, Sichuan University(Grant No.QDJF2022-2)National Undergraduate Training Program for Innovation(Grant No.C2024129736)。
文摘Objective Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms.Methods In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods(GNRs) and tetrahedral framework nucleic acids(tFNA) loaded with the anti-tumor drug doxorubicin(DOX).Results Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation.Conclusion This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2023-I2M-2-001National Key Research and Development Project of China,Grant/Award Number:2022YFC2304100 and 2023YFC2309000+1 种基金National Natural Science Foundation of China,Grant/Award Number:82241068 and 82222041Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.
