Epoxy resin is widely used in electronic packaging due to its exceptional performance,particularly the low-temperature curable thiol/epoxy system,which effectively minimizes thermal damage to sensitive electronic comp...Epoxy resin is widely used in electronic packaging due to its exceptional performance,particularly the low-temperature curable thiol/epoxy system,which effectively minimizes thermal damage to sensitive electronic components.However,the majority of commercial thiol curing agents contain hydrolysable ester bonds and lack rigid structures,which induces most of thiol/epoxy systems still suffering from unsatisfactory heat resistance and hygrothermal resistance,significantly hindering their application in electronic packaging.In this study,we synthesized a tetrafunctional thiol compound,bis[3-(3-sulfanylpropyl)-4-(3-sulfanylpropoxy)phenyl]sulfone(TMBPS)with rigid and ester-free structures to replace traditional commercial thiol curing agents,pentaerythritol tetra(3-mercaptopropionate)(PETMP).Compared to the PETMP/epoxy system,the TMBPS/epoxy system exhibited superior comprehensive properties.The rigid structures of bisphenol S-type tetrathiol enhanced the heat resistance and mechanical properties of TMBPS/epoxy resin cured products,outperforming those of PETMP/epoxy resin cured products.Notably,the glass transition temperature of TMBPS/epoxy resin cured products was 74.2℃which was 11.8°C higher than that of PETMP cured products.Moreover,the ester-free structure in TMBPS contributed to its enhanced resistance to chemicals and hygrothermal conditions.After undergoing 1000 h of hightemperature and high-humidity aging,the tensile strength and adhesion strength of TMBPS-cured products were 73.33 MPa and 3.39 MPa,respectively exceeding 100%and 40%of their initial values,while PETMP-cured products exhibited a complete loss of both tensile strength and adhesion strength.This study provides a strategy for obtaining thermosetting polymers that can be cured at low temperatures and exhibit excellent comprehensive properties.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic repro...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.展开更多
Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise o...Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.展开更多
To improve the high-temperature service properties of coppery tuyere,Co06 coating with a Ni60A interlayer was prepared on copper by plasma cladding.Ni60A interlayer acted as a bridge to promote the element diffusion,t...To improve the high-temperature service properties of coppery tuyere,Co06 coating with a Ni60A interlayer was prepared on copper by plasma cladding.Ni60A interlayer acted as a bridge to promote the element diffusion,thus achieving metallurgical bonding.Due to the strengthening effect ofγ-Co,Cr_(23)C_(6)and Cr_(7)C_(3)phases,the wear resistance of Co06–Ni60A coating was much higher than that of copper substrate.As the temperature increased,the wear resistance of coating decreased first and then increased.The coating exhibited better wear resistance at 600℃ due to the oxidation wear mechanism.Compared with copper substrate and Ni60A,the oxidation resistance of Co06 was increased by 6.0 and 1.9 times,respectively.For melting loss resistance,Co06–Ni60A coating was superior to Ni60A single-layer coating,but the molten iron can still form a micro-metallurgical bonding with the coating surface.展开更多
Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially ...Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.展开更多
BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatm...BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.展开更多
Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pne...Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.展开更多
Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(S...Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].展开更多
Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment proc...Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.展开更多
The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets wit...The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets with a sandwich structure.Characterization tests including SEM,XPS,SPM,and XRD confirmed the successful preparation of IBP nanosheets with robust structural stability and antioxidation.Subsequently,a water-based epoxy resin(WEP)coating containing IBP nanosheets was prepared.Test results revealed that the composite coating containing 0.4 wt.%IBP nanosheets exhibited outstanding anti-corrosion,wear-resistant,and flame-retardant properties.After 42 days of immersion in a 3.5 wt.%NaCl solution,the Rct value of the 4-IBP/WEP coating was 1.79×10^(9)Ωcm^(2),surpassing the Pure WEP coating by more than 3 orders of magnitude.Additionally,the peak heat release rate(PHRR)and wear rate of the 4-IBP/WEP coating decreased by 19.29%and 90.97%compared to the Pure WEP coating.This research presents a novel idea for the utilization of BP nanosheets in multifunctional coatings.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,a...Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,as well as the wear resistance of the coatings.Besides,the effect of changing the laser melting process on the coatings was also investigated.The oxidation mass gain at 800–1200℃and the high-temperature oxidation behavior during high-temperature treatment for 1 h of two coated Zr alloy samples were studied.Results show that the Co coating and the Co-T800 coating have better resistance against high-temperature oxidation.After oxidizing at 1000℃for 1 h,the thickness of the oxide layer of the uncoated sample was 241.0μm,whereas that of the sample with Co-based coating is only 11.8–35.5μm.The friction wear test shows that the depth of the abrasion mark of the coated sample is only 1/2 of that of the substrate,indicating that the hardness and wear resistance of the Zr substrate are greatly improved.The disadvantage of Co-based coatings is the inferior corrosion resistance in 3.5wt%NaCl solution.展开更多
Plutella xylostella,a major pest of cruciferous vegetables worldwide,has developed resistance to diamide insecticides.Thiotraniliprole,a novel synthetic diamide insecticide,exhibits excellent activity against P.xylost...Plutella xylostella,a major pest of cruciferous vegetables worldwide,has developed resistance to diamide insecticides.Thiotraniliprole,a novel synthetic diamide insecticide,exhibits excellent activity against P.xylostella.In the present study,we aimed to confirm the resistance risk,cross-resistance,and mechanisms of resistance to thiotraniliprole in P.xylostella.After 40 consecutive generations of thiotraniliprole selection,we obtained a thiotraniliprole-resistance P.xylostella strain with a 5141.58-fold resistance ratio(RR)to thiotraniliprole.The overall realized heritability(h^(2))value of resistance was estimated as 0.9 using threshold trait analysis,indicating that the risk of developing resistance to thiotraniliprole is high in P.xylostella.The thiotraniliprole-resistant(TR)strain showed noticeable cross-resistance to chlorantraniliprole(RR=44670.05),cyantraniliprole(RR=7038.58),and tetrachlorantraniliprole(RR=1506.01),but no cross-resistance to tolfenpyrad,indoxacarb,diafenthiuron,or abamectin compared with the susceptible(S)strain.The enzyme assay data showed that the activities of glutathione-S transferase(GST),carboxylesterase(CarE),and the content of cytochrome P450 monooxygenase(P450s)were significantly higher in the TR strain than in the S strain.Sequencing of the full-length PxRyR cDNA revealed the gene site I4790K in the TR strain with a 100%frequency.This mutation in PxRyR likely underlies the high-level cross-resistance between thiotraniliprole and three other diamide insecticides.These findings provide valuable information for optimizing resistance management strategies to delay thiotraniliprole resistance development and ensure sustainable control of P.xylostella.展开更多
This is a review on resistant starch(RS),resistant dextrin(RD),and polydextrose(PDX),focusing on their similarities and differences.RS refers to the starch(or a portion of)that cannot be digested in the small intestin...This is a review on resistant starch(RS),resistant dextrin(RD),and polydextrose(PDX),focusing on their similarities and differences.RS refers to the starch(or a portion of)that cannot be digested in the small intestine,but can be partially fermented in the colon.The enzyme resistance of RS is mainly due to either its crystalline/granular structure or its interaction with other components.RD is produced by pyrodextrinization of starch,while PDX is produced by polycondensation of glucose and sorbitol.Both RD and PDX contain glycosidic linkages that are not digestible by the enzymes in the small intestine.RS is not soluble in water,whereas RD and PDX are soluble,mainly due to their molecular structures and other structural features.The major health benefits of RS,RD,and PDX are quite similar,including gut health,prebiotic effects,glycemic control,weight management,and prevention of cardiovascular disease.However,the efficacies can be different among them,for example,the degree and rate of gut fermentation.This review compares the definitions,functional properties,and health benefits of RS,RD,and PDX with the underlying mechanisms,which can be useful for their incorporation in food formulations to improve human health and wellness.展开更多
Southern corn leaf blight(SCLB)caused by Cochliobolus heterostrophus,is a widespread foliar disease that has a substantial impact on maize yield in the Huang-Huai-Hai Region of China.Pydiflumetofen(Pyd),a new succinat...Southern corn leaf blight(SCLB)caused by Cochliobolus heterostrophus,is a widespread foliar disease that has a substantial impact on maize yield in the Huang-Huai-Hai Region of China.Pydiflumetofen(Pyd),a new succinate dehydrogenase inhibitor(SDHI),has been found as a promising fungicide for the efficient control of SCLB,however,resistance of C.heterostrophus to Pyd has not been studied well.Here,five Pyd-resistant mutants were generated through fungicide adaptation.Sequence alignment analysis revealed that these mutants primarily mutated in ChSdhB and ChSdhD,with three genotypes:ChSdhB^(H277Y),ChSdhB^(I279T)and ChSdhD^(H133Y),exhibiting two distinct categories of resistance:high resistance(HR)and moderate resistance(MR),among which the resistance factors were 214.22 and 44.33-53.67,respectively.These mutants were more pathogenic than the wild-type parental strains,but there was a significant reduction in mycelial growth rate and sporulation in the resistant mutants,indicating a significant fitness cost associated with resistance to Pyd.In addition,this study revealed a positive cross-resistance between Pyd and another SDHI fungicide cyclobutrifluram.However,no cross-resistance was found between Pyd and other classes of fungicides,including prochloraz,fludioxonil,iprodione or pyraclostrobin.Homology modeling and molecular docking further confirmed that point mutations of ChSdhB^(H277Y),ChSdhB^(I279T),and ChSdhD^(H133Y)could reduce binding affinity between Pyd and its target subunits from-74.07,-74.07,-152.52 kcal mol^(-1)to-3.90,-4.95,-9.93 kcal mol^(-1),respectively.These findings not only provided valuable insights for managing SCLB caused by C.heterostrophus,but also enhanced our understanding of molecular mechanism underlying plant pathogen resistance to Pyd.展开更多
The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechan...The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.展开更多
BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated ...BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated the current status of antibiotic resistance of H.pylori in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of H.pylori infection.AIM To understand the antibiotic resistance of H.pylori in Hunan Province and provide guidance for the clinical treatment of H.pylori infection.METHODS This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023.The sensitivity of H.pylori to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline was detected using the Agar dilution method.RESULTS H.pylori strains from a total of 566 patients were isolated and identified.The resistance rates of H.pylori strains to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline were 49.2%,37.8%,76.1%,2.3%,1.4%,and 0.7%,respectively.The resistance rates to clarithromycin,levofloxacin,and metronidazole were high in the four regions of Hunan Province,and the overall resistance rates in central Hunan Province were higher than those in other regions.The resistance rates of H.pylori strains to clarithromycin and levofloxacin were significantly different among the different age groups(P<0.05),with the elderly group having a higher resistance rate than the young group.The resistance rate of H.pylori strains to clarithromycin was greater in patients with atrophic gastritis,and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers.CONCLUSION The resistance rate of H.pylori to amoxicillin,clarithromycin,and metronidazole is high in Hunan Province.Age,stomach disease,and H.pylori reinfection may affect the antibiotic resistance of H.pylori.展开更多
Cronobacter spp.has strong resistance to desiccation and high permeability in Enterobacteriaceae,and powdered infant formula(PIF)is one of the main contamination routes.In recent years,the contamination of Cronobacter...Cronobacter spp.has strong resistance to desiccation and high permeability in Enterobacteriaceae,and powdered infant formula(PIF)is one of the main contamination routes.In recent years,the contamination of Cronobacter spp.in PIF incidents occurs from time to time,causing infant serious diseases or death.In this investigation,matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to identify the phenotypes of 35 Cronobacter strains isolated from PIF and its processing environment.Subsequently,the isolates were evaluated for drying and osmotic pressure tolerance.The results showed that the deactivation rate of the strains ranged from 9.01%to 77.57%,and the highest osmotic pressure condition the strains could tolerate was 6 g/100 mL Na Cl.In addition,there was a positive correlation between biofilm formation ability and desiccation resistance.Combined with transcriptomics,Cronobacter spp.could activate biofilm synthesis,produce more trehalose,accumulate betaine and electrolytes to stabilize intracellular structure under the two treatment conditions.A total of 31 and 43 genes were found related to desiccation and permeability resistance,respectively.And some genes(cysM,thuF,ycjO,etc.)were found to be associated with two tolerances for the first time.展开更多
The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of...The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.展开更多
Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interacti...Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interaction dynamics between the cotton plant host and V.dahliae pathogen pose a crucial predicament for effectively managing cotton Verticillium wilt.Nevertheless,the most cost-effective approach to controlling this disease involves breeding and cul-tivating resistant cotton varieties,demanding a meticulous analysis of the mechanisms underlying cotton’s resistance to Verticillium wilt and the identification of pivotal genes.These aspects constitute focal points in disease-resistance breeding programs.In this review,we comprehensively discuss genetic inheritance associated with Verticillium wilt resistance in cotton,the advancements in molecular markers for disease resistance,the functional investiga-tion of resistance genes in cotton,the analysis of pathogenicity genes in V.dahliae,as well as the intricate interplay between cotton and this fungus.Moreover,we delve into the future prospects of cutting-edge research on cotton Verticillium wilt,aiming to proffer valuable insights for the effective management of this devastating fungus.展开更多
基金the support of the Science and Technology Commission of Shanghai Municipality(STCSM,No.20dz1203600)the Experimental Center of Materials Science and Engineering in Tongji University。
文摘Epoxy resin is widely used in electronic packaging due to its exceptional performance,particularly the low-temperature curable thiol/epoxy system,which effectively minimizes thermal damage to sensitive electronic components.However,the majority of commercial thiol curing agents contain hydrolysable ester bonds and lack rigid structures,which induces most of thiol/epoxy systems still suffering from unsatisfactory heat resistance and hygrothermal resistance,significantly hindering their application in electronic packaging.In this study,we synthesized a tetrafunctional thiol compound,bis[3-(3-sulfanylpropyl)-4-(3-sulfanylpropoxy)phenyl]sulfone(TMBPS)with rigid and ester-free structures to replace traditional commercial thiol curing agents,pentaerythritol tetra(3-mercaptopropionate)(PETMP).Compared to the PETMP/epoxy system,the TMBPS/epoxy system exhibited superior comprehensive properties.The rigid structures of bisphenol S-type tetrathiol enhanced the heat resistance and mechanical properties of TMBPS/epoxy resin cured products,outperforming those of PETMP/epoxy resin cured products.Notably,the glass transition temperature of TMBPS/epoxy resin cured products was 74.2℃which was 11.8°C higher than that of PETMP cured products.Moreover,the ester-free structure in TMBPS contributed to its enhanced resistance to chemicals and hygrothermal conditions.After undergoing 1000 h of hightemperature and high-humidity aging,the tensile strength and adhesion strength of TMBPS-cured products were 73.33 MPa and 3.39 MPa,respectively exceeding 100%and 40%of their initial values,while PETMP-cured products exhibited a complete loss of both tensile strength and adhesion strength.This study provides a strategy for obtaining thermosetting polymers that can be cured at low temperatures and exhibit excellent comprehensive properties.
基金supported in part by grants from the following sources:the National Natural Science Foundation of China(No.82090051,32371477,92168207)the National Key Research and Development Program of China(No.2022YFA1103400,2022YFC2406704)+1 种基金the Chief Scientist Research Project of Hubei Shizhen Laboratory(HSL2024SX0001)the Beijing Tsinghua Changgung Hospital Foundation(No.12025C01011).
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.
基金supported by National Natural Science Foundation of China(31860490)YNTC funds(2023530000241007 and 2017YN02)+1 种基金Yunnan Daguan Lab(YNDG202302ZY01)CLZ is supported by the Postdoctoral Fellowship Program of CPSF under grant number GZC20241527。
文摘Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.
基金supported by the University Synergy Innovation Program of Anhui Province(Grant Nos.GXXT-2023-025 and GXXT-2023-026)Natural Science Foundation of Anhui Province(Grant Nos.2008085ME149,2308085QE132 and 2308065ME171)Anhui University Scientific Research Project(Grant Nos.2022AH040247,2023AH051660,2023AH051670 and 2023AH051671).
文摘To improve the high-temperature service properties of coppery tuyere,Co06 coating with a Ni60A interlayer was prepared on copper by plasma cladding.Ni60A interlayer acted as a bridge to promote the element diffusion,thus achieving metallurgical bonding.Due to the strengthening effect ofγ-Co,Cr_(23)C_(6)and Cr_(7)C_(3)phases,the wear resistance of Co06–Ni60A coating was much higher than that of copper substrate.As the temperature increased,the wear resistance of coating decreased first and then increased.The coating exhibited better wear resistance at 600℃ due to the oxidation wear mechanism.Compared with copper substrate and Ni60A,the oxidation resistance of Co06 was increased by 6.0 and 1.9 times,respectively.For melting loss resistance,Co06–Ni60A coating was superior to Ni60A single-layer coating,but the molten iron can still form a micro-metallurgical bonding with the coating surface.
基金Supported by the Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417+2 种基金the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418the PERMANECER Programme of Pro-Rectory of Student Assistance at Federal University of Bahia,No.R8EZ-4V4W-6LQX-5LC8the CNPq Research Productivity Fellow,No.4357511882624145.
文摘Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
文摘BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.
基金supported by the National Natural Science Foundation of China(grant numbers 81991531 to M.W.,82102440 to J.J.,and 32400149 to J.Z.).
文摘Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.
基金Guangdong Basic and Applied Basic Research Foundation(grant number 2024A1515010319 to J.Q.)Science and Technology Program of Shenzhen(grant numbers KCXFZ20230731100901003 to J.Q.and L.L.,KJZD20230923115116032 to J.Q.,JCYJ20190809144005609 to J.Q.)+1 种基金Shenzhen Key Laboratory of Biochip(grant number ZDSYS201504301534057 to J.Q.)Shenzhen High-level Hospital Construction Fund(to J.Q.).
文摘Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].
基金supported by the National Natural Science Foundation of China (Nos.52100182 and 52300204)the the Science and Technology Innovation Program of Hunan Province (No.2023RC3122).
文摘Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.
基金supports from the Science and Technology Program of Guangzhou(No.2024A04J3710)the National Natural Science Foundation of China(No.22268025).
文摘The rapid development of industrialization requires the advancement of multifunctional coatings.In this study,successful self-assembly of iron porphyrin on BP nanosheets resulted in the synthesis of IBP nanosheets with a sandwich structure.Characterization tests including SEM,XPS,SPM,and XRD confirmed the successful preparation of IBP nanosheets with robust structural stability and antioxidation.Subsequently,a water-based epoxy resin(WEP)coating containing IBP nanosheets was prepared.Test results revealed that the composite coating containing 0.4 wt.%IBP nanosheets exhibited outstanding anti-corrosion,wear-resistant,and flame-retardant properties.After 42 days of immersion in a 3.5 wt.%NaCl solution,the Rct value of the 4-IBP/WEP coating was 1.79×10^(9)Ωcm^(2),surpassing the Pure WEP coating by more than 3 orders of magnitude.Additionally,the peak heat release rate(PHRR)and wear rate of the 4-IBP/WEP coating decreased by 19.29%and 90.97%compared to the Pure WEP coating.This research presents a novel idea for the utilization of BP nanosheets in multifunctional coatings.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
基金National Natural Science Foundation of China(52071126)Natural Science Foundation of Tianjin City,China(22JCQNJC01240)+2 种基金Central Guidance on Local Science and Technology Development Fund of Hebei Province(226Z1009G)Special Funds for Science and Technology Innovation in Hebei(2022X19)Anhui Provincial Natural Science Foundation(2308085ME135)。
文摘Co-based alloy coating was prepared on Zr alloy using laser melting and cladding technique to study the difference in the high-temperature oxidation behavior between pure metal Co coatings and Co-T800 alloy coatings,as well as the wear resistance of the coatings.Besides,the effect of changing the laser melting process on the coatings was also investigated.The oxidation mass gain at 800–1200℃and the high-temperature oxidation behavior during high-temperature treatment for 1 h of two coated Zr alloy samples were studied.Results show that the Co coating and the Co-T800 coating have better resistance against high-temperature oxidation.After oxidizing at 1000℃for 1 h,the thickness of the oxide layer of the uncoated sample was 241.0μm,whereas that of the sample with Co-based coating is only 11.8–35.5μm.The friction wear test shows that the depth of the abrasion mark of the coated sample is only 1/2 of that of the substrate,indicating that the hardness and wear resistance of the Zr substrate are greatly improved.The disadvantage of Co-based coatings is the inferior corrosion resistance in 3.5wt%NaCl solution.
基金Supported by the Zhejiang Provincial Public Welfare Technology Application Research Program(No:LGN21C140001).
文摘Plutella xylostella,a major pest of cruciferous vegetables worldwide,has developed resistance to diamide insecticides.Thiotraniliprole,a novel synthetic diamide insecticide,exhibits excellent activity against P.xylostella.In the present study,we aimed to confirm the resistance risk,cross-resistance,and mechanisms of resistance to thiotraniliprole in P.xylostella.After 40 consecutive generations of thiotraniliprole selection,we obtained a thiotraniliprole-resistance P.xylostella strain with a 5141.58-fold resistance ratio(RR)to thiotraniliprole.The overall realized heritability(h^(2))value of resistance was estimated as 0.9 using threshold trait analysis,indicating that the risk of developing resistance to thiotraniliprole is high in P.xylostella.The thiotraniliprole-resistant(TR)strain showed noticeable cross-resistance to chlorantraniliprole(RR=44670.05),cyantraniliprole(RR=7038.58),and tetrachlorantraniliprole(RR=1506.01),but no cross-resistance to tolfenpyrad,indoxacarb,diafenthiuron,or abamectin compared with the susceptible(S)strain.The enzyme assay data showed that the activities of glutathione-S transferase(GST),carboxylesterase(CarE),and the content of cytochrome P450 monooxygenase(P450s)were significantly higher in the TR strain than in the S strain.Sequencing of the full-length PxRyR cDNA revealed the gene site I4790K in the TR strain with a 100%frequency.This mutation in PxRyR likely underlies the high-level cross-resistance between thiotraniliprole and three other diamide insecticides.These findings provide valuable information for optimizing resistance management strategies to delay thiotraniliprole resistance development and ensure sustainable control of P.xylostella.
文摘This is a review on resistant starch(RS),resistant dextrin(RD),and polydextrose(PDX),focusing on their similarities and differences.RS refers to the starch(or a portion of)that cannot be digested in the small intestine,but can be partially fermented in the colon.The enzyme resistance of RS is mainly due to either its crystalline/granular structure or its interaction with other components.RD is produced by pyrodextrinization of starch,while PDX is produced by polycondensation of glucose and sorbitol.Both RD and PDX contain glycosidic linkages that are not digestible by the enzymes in the small intestine.RS is not soluble in water,whereas RD and PDX are soluble,mainly due to their molecular structures and other structural features.The major health benefits of RS,RD,and PDX are quite similar,including gut health,prebiotic effects,glycemic control,weight management,and prevention of cardiovascular disease.However,the efficacies can be different among them,for example,the degree and rate of gut fermentation.This review compares the definitions,functional properties,and health benefits of RS,RD,and PDX with the underlying mechanisms,which can be useful for their incorporation in food formulations to improve human health and wellness.
基金supported by the National Key Research and Development Program of China(2023YFD1401504)the Open Project of Anhui Province Key Laboratory of Pesticide Resistance Management on Grain and Vegetable Pests,China(PKLPRMGVP202402)+3 种基金the Programs for the Scientific Research Activities of Academic and Technical Leaders of Anhui Province,China(2020D251)the Development Fund for Talent Personnel of Anhui Agricultural University,China(rc342006)the University Synergy Innovation Program of Anhui Province,China(GXXT-2021-059)Anhui Province Agricultural Eco-Environmental Protection and Quality Safety Industry Technology System,China。
文摘Southern corn leaf blight(SCLB)caused by Cochliobolus heterostrophus,is a widespread foliar disease that has a substantial impact on maize yield in the Huang-Huai-Hai Region of China.Pydiflumetofen(Pyd),a new succinate dehydrogenase inhibitor(SDHI),has been found as a promising fungicide for the efficient control of SCLB,however,resistance of C.heterostrophus to Pyd has not been studied well.Here,five Pyd-resistant mutants were generated through fungicide adaptation.Sequence alignment analysis revealed that these mutants primarily mutated in ChSdhB and ChSdhD,with three genotypes:ChSdhB^(H277Y),ChSdhB^(I279T)and ChSdhD^(H133Y),exhibiting two distinct categories of resistance:high resistance(HR)and moderate resistance(MR),among which the resistance factors were 214.22 and 44.33-53.67,respectively.These mutants were more pathogenic than the wild-type parental strains,but there was a significant reduction in mycelial growth rate and sporulation in the resistant mutants,indicating a significant fitness cost associated with resistance to Pyd.In addition,this study revealed a positive cross-resistance between Pyd and another SDHI fungicide cyclobutrifluram.However,no cross-resistance was found between Pyd and other classes of fungicides,including prochloraz,fludioxonil,iprodione or pyraclostrobin.Homology modeling and molecular docking further confirmed that point mutations of ChSdhB^(H277Y),ChSdhB^(I279T),and ChSdhD^(H133Y)could reduce binding affinity between Pyd and its target subunits from-74.07,-74.07,-152.52 kcal mol^(-1)to-3.90,-4.95,-9.93 kcal mol^(-1),respectively.These findings not only provided valuable insights for managing SCLB caused by C.heterostrophus,but also enhanced our understanding of molecular mechanism underlying plant pathogen resistance to Pyd.
基金supported by the National Natural Science Foundation of China(82460111)the The First People’s Hospital of Yunnan Province Talent Project program(No.KHBS-2022013,KHYJ-2025-04-02,2022-KHRCBZ-B03)+4 种基金the Kunming Medical University Joint Special Project on Applied Basic Research(202301AY070001-210)Yunnan Provincial Key Laboratory of Clinical Virology(No.2023A4010403-04)Yunnan Foundmental basical research project(202301AT070034)the Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases(No.2022ZDKFKT001)the Open Project of Yunnan Provincial Clinical Medical Research Center for Elderly Diseases(No.:2023YJZX-LN03/13 of 202102AA3100692023).
文摘The efficacy of conventional antibiotics against multidrug-resistant pathogenic fungi is markedly limited.A study published in Nature by Wang et al.introduced mandimycin,a novel antifungal agent with a distinct mechanism of action,diverging from established polyene macrolide antibiotics that target ergosterol.The emergence of multidrug-resistant fungal pathogens poses substantial risks to patient health,healthcare infrastructures,and public health at large.The alarming increase in these pathogens is attributed to their capability to withstand numerous antifungal treatments,resulting in escalated morbidity and mortality rates among affected patients.The strategies employed by these pathogens to compromise patient health include modifications at drug target sites,improved efflux mechanisms,and biofilm formation,all of which complicate treatment protocols and extend hospital stays[1].This concerning trend accentuates the urgent need for ongoing monitoring and investigation into innovative antifungal agents and therapeutic approaches to address these resilient pathogens.
基金Supported by the National Natural Science Foundation of China,No.82270594the Independent Exploration and Innovation Project of Central South University,No.2024ZZTS0966.
文摘BACKGROUND Antibiotic resistance is a key factor influencing the treatment outcomes of Helicobacter pylori(H.pylori)infection.The antibiotic resistance spectrum of H.pylori varies in different regions.We investigated the current status of antibiotic resistance of H.pylori in Hunan Province and analyzed the factors related to such resistance to provide strategies for the accurate clinical treatment of H.pylori infection.AIM To understand the antibiotic resistance of H.pylori in Hunan Province and provide guidance for the clinical treatment of H.pylori infection.METHODS This study selected patients who underwent gastroscopy in five hospitals in Hunan Province from April 2022 to April 2023.The sensitivity of H.pylori to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline was detected using the Agar dilution method.RESULTS H.pylori strains from a total of 566 patients were isolated and identified.The resistance rates of H.pylori strains to clarithromycin,levofloxacin,metronidazole,amoxicillin,furazolidone,and tetracycline were 49.2%,37.8%,76.1%,2.3%,1.4%,and 0.7%,respectively.The resistance rates to clarithromycin,levofloxacin,and metronidazole were high in the four regions of Hunan Province,and the overall resistance rates in central Hunan Province were higher than those in other regions.The resistance rates of H.pylori strains to clarithromycin and levofloxacin were significantly different among the different age groups(P<0.05),with the elderly group having a higher resistance rate than the young group.The resistance rate of H.pylori strains to clarithromycin was greater in patients with atrophic gastritis,and the resistance rate to levofloxacin was the lowest in patients with peptic ulcers.CONCLUSION The resistance rate of H.pylori to amoxicillin,clarithromycin,and metronidazole is high in Hunan Province.Age,stomach disease,and H.pylori reinfection may affect the antibiotic resistance of H.pylori.
基金supported by the Joint Funds of the National Natural Science Foundation of China(U21A20272)。
文摘Cronobacter spp.has strong resistance to desiccation and high permeability in Enterobacteriaceae,and powdered infant formula(PIF)is one of the main contamination routes.In recent years,the contamination of Cronobacter spp.in PIF incidents occurs from time to time,causing infant serious diseases or death.In this investigation,matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to identify the phenotypes of 35 Cronobacter strains isolated from PIF and its processing environment.Subsequently,the isolates were evaluated for drying and osmotic pressure tolerance.The results showed that the deactivation rate of the strains ranged from 9.01%to 77.57%,and the highest osmotic pressure condition the strains could tolerate was 6 g/100 mL Na Cl.In addition,there was a positive correlation between biofilm formation ability and desiccation resistance.Combined with transcriptomics,Cronobacter spp.could activate biofilm synthesis,produce more trehalose,accumulate betaine and electrolytes to stabilize intracellular structure under the two treatment conditions.A total of 31 and 43 genes were found related to desiccation and permeability resistance,respectively.And some genes(cysM,thuF,ycjO,etc.)were found to be associated with two tolerances for the first time.
基金supported by the Northeast Asia Biodiversity Research Center(grant number 411147021003).
文摘The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.
基金supported by National Natural Science Foundation of China(32201752)Xinjiang Tianchi Talents Program (TCYC2023TP02)Key Project of the Natural Science Foundation of Xinjiang Production and Construction Corps (2024DA001)
文摘Verticillium wilt,caused by the infamous pathogen Verticillium dahliae,presents a primary constraint on cotton cul-tivation worldwide.The complexity of disease resistance in cotton and the largely unexplored interaction dynamics between the cotton plant host and V.dahliae pathogen pose a crucial predicament for effectively managing cotton Verticillium wilt.Nevertheless,the most cost-effective approach to controlling this disease involves breeding and cul-tivating resistant cotton varieties,demanding a meticulous analysis of the mechanisms underlying cotton’s resistance to Verticillium wilt and the identification of pivotal genes.These aspects constitute focal points in disease-resistance breeding programs.In this review,we comprehensively discuss genetic inheritance associated with Verticillium wilt resistance in cotton,the advancements in molecular markers for disease resistance,the functional investiga-tion of resistance genes in cotton,the analysis of pathogenicity genes in V.dahliae,as well as the intricate interplay between cotton and this fungus.Moreover,we delve into the future prospects of cutting-edge research on cotton Verticillium wilt,aiming to proffer valuable insights for the effective management of this devastating fungus.
