Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive dise...Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive disease on lichi,litchi downy blight.PlM90 was reported as a key oosporogenesis regulator.Here,we identified an MFS transporter gene PlMFS1,which is up-regulated during oospore formation at the late infection stage,while down-regulated in the PlM90 mutant.To investigate PlMFS1 function,we generated PlMFS1knockout mutants using CRISPR/Cas9-mediated genome editing technology.Compared with the wild-type strain SHS3,PlMFS1 deletion impaired mycelium growth,zoospore release,oospore production and pathogenicity.Furthermore,PlMFS1 deletion significantly affected P.litchii utilization of fructose,lactose and maltose,and may be the PlMFS1 mechanism involved in mycelial growth.PlMFS1 gene deletion also led to deceased laccase activity,laccase-encoding gene downregulation and impaired P.litchii pathogenicity.To our knowledge,this is the first report of an MFS transporter involved in sugar utilization,sexual reproduction,asexual reproduction and pathogenesis in oomycetes.展开更多
Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functio...Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.展开更多
Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseu...Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseudograminearum （Fp） was reported in wheat from Henan Province of China a couple of years ago. The wheat crown rot （CR） caused by this new pathogen is as an emerging severe disease of wheat, which has recently expanded to several provinces in China and is, therefore, under rapid investigation. Colonization of wheat tissue by Fp is accomplished though the formation of a septated foot-shaped appressoria and generation of a penetration peg to break through the internal cells of leaf sheath. The molecular mechanism by which Fp regulates the pathogenesis on wheat host is unclear. Here, we report FpPDE1, a P-type ATPase-encoding predicted PDE1 orthologue gene of Magnaporthe oryzae, belonging to the DRS2 subfamily of aminophospholipid translocases. The gene deletion of FpPDE1 with the split-marker approach did not obviously affect hyphae growth and conidiation, but led to an attenuated virulence on wheat base stem and root. Our finding indicates that the putative aminophospholipid translocases is not essential for the infectious hyphae development in Fp.展开更多
Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading f...Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.展开更多
Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to ...Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.展开更多
Pathogenesis-related(PR)proteins are one of the major and preliminary proteins accumulated as a defense against biotic stress.This defense response can be induced by using beneficial rhizobacteria,which has been studi...Pathogenesis-related(PR)proteins are one of the major and preliminary proteins accumulated as a defense against biotic stress.This defense response can be induced by using beneficial rhizobacteria,which has been studied in various host-pathogen interactions.In the present study,eleven Pseudomonas isolates were assessed for their potential to ferment sorbitol,reduce nitrate,and produce mycolytic enzymes,1-aminocyclopropane-l-carboxylic acid(ACC)deaminase,phenazine antibiotics,and N-acyl homoserine lactones(AHLs).All isolates were tested against the host-specific pathogen Fusarium oxysporum MTCC1755 in tomato under greenhouse conditions,and shortlisted isolates were tested for their rhizosphere competence.In-vitro test results showed that the isolates were able to produce mycolytic enzymes,including protease,lipase,chitinase,cellulase,and amylase,and the antibiotic phenazine and were negative for pyoluteorin.All the isolates except two were positive for ACC deaminase production.Greenhouse results showed that the isolates M80,M96,and T109 significantly reduced symptoms of Fusarium wilt.Extended greenhouse tests under autoclaved and unautoclaved soil conditions showed that M80,M96,and T109 were excellent rhizosphere competitors and were identified as Pseudomonas putida.In brief,the defense-specific biochemical variations in the host could describe the improved defense against Fusarium wilt occurring in the primed plants.These three Pseudomonas strains could be used as potential biocontrol agents,along with their rhizosphere competence.展开更多
Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functi...Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functions of Gyp8 in plant pathogenic fungi are still unknown. In this study, we investigated the roles of Fg Gyp8 in F. graminearum by genetic and pathological analyses. Through gene knockout and phenotypic analyses, we found that Fg Gyp8 is required for vegetative growth in F. graminearum. The conidiation, conidial size and number of septa per conidium of ΔFggyp8 mutant are significantly reduced when compared to the wild type PH-1. Furthermore, Fg Gyp8 is crucial for pathogenicity on wheat coleoptiles and wheat heads. Fg Gyp8 contains a conserved TBC domain. Domain deletion analysis showed that the TBC domain, C-and N-terminal regions of Fg Gyp8 are all important for its biological functions in F. graminearum. Moreover, we showed that Fg Gyp8 catalyzes the hydrolysis of the GTP on Fg Rab1 to GDP in vitro, indicating that Fg Gyp8 is a GTPase-activating protein(GAP) for Fg Rab1. In addition, we demonstrated that Fg Gyp8 is required for Fg Snc1-mediated fusion of secretory vesicles with the plasma membrane in F. graminearum. Finally, we showed that Fg Gyp8 has functional redundancy with another Fg Rab1 GAP, Fg Gyp1, in F. graminearum. Taken together, we conclude that Fg Gyp8 is required for vegetative growth, conidiogenesis, pathogenicity and acts as a GAP for Fg Rab1 in F. graminearum.展开更多
Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Metho...Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Methods Mice were infected with increasing virus titers.Viral load in the lungs and trachea was determined by EID50 assay.Pulmonary histopathology was assessed by hematoxylin‐eosin staining.Anti‐HI antibody titers and T‐cell responses to viral HA were determined by ELISPOT and confirmed by flow cytometry.Results Mice presented a mild syndrome after intranasal infection with A/Guangzhou/333/99 （H9N2） influenza virus.Virus was detected in the trachea and lungs of mice harvested on days 3,6,and 9 post‐infection.A T‐cell response to viral HA was detected on day 6 and H9 HA‐specific CD 4＋ T‐cells predominated.Seroconversion was detected after 14 days and antibody persisted for at least 28 weeks.Conclusion Our results suggest that H9N2 （A/Guangzhou/333/99） can replicate in the murine respiratory tract without prior adaptation,and both humoral and cell‐mediated immunity play an important role in the immune response.展开更多
Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)...Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)from 5 aspects:abnormal climate in"warm winter",unique geographical location,pathogenesis evolution of cold and dampness mixed with insidious dryness,transmission and change of"triple energizer"of toxic pathogens,and game between healthy Qi and toxic pathogens.Combined with the special treatment of traditional Chinese medicine(TCM),the purpose is to make a modest contribution to curbing the epidemic situation with TCM.展开更多
The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we...The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we showed by bio-informatic analysis that TdPR1.2 contains six cysteine residues that are conserved between all PR-1 proteins tested. Using ScanProsite tool, we found that TdPR1.2 structure has a CRISP family signature 1 and 2 located at the C-terminal part of the protein. Those two domains are conserved in many identified PR1.2 proteins in plants. Moreover, SignalIP-5.0 analysis revealed that TdPR1.2 contains a putative signal peptide formed by 25 amino acids at the N-terminal extremity. The presence of this signal peptide suggested that the mature proteins will be secreted after the cleavage of the signal sequence. Further, we investigate the role of the TdPR1.2 proteins in the growth of <i>Escherichia coli</i> transformants cells under different abiotic stresses. Our results showed that the full-length form of TdPR1.2 enhanced tolerance of <i>E. coli</i> against salt and osmotic stress but not to KCl. Moreover, TdPR1.2 protein confers bacterial tolerance to heavy metals in solid and liquid mediums. Based on these results, we suggest that the TdPR1.2 protein could play an important role in response to abiotic stress conditions.展开更多
Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and ...Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and thrive.However,the fungal proteins involved in proteostasis remain poorly characterized in the process of pathogenesis.In this study,we characterized the function of the nascent polypeptideassociated complex(NAC)in Fusarium graminearum(F.graminearum)(FgNAC),one of the top 10 fungal pathogens with predominant scientific/economic importance.We found that FgNACa,a subunit of FgNAC,manifests high structural and functional similarity to its homologous counterparts in yeast and other species.The mutants of F.graminearum lacking NACa are viable but suffer significant defects in vegetative growth,conidial production,and pathogenesis.In addition,we show here that FgNACa can interact with another subunit of NAC(FgNACb)in a yeast-two-hybrid assay.The subcellular localization results show that FgNACa and FgNACb are predominantly localized in the cytoplasm.Future studies should focus on deciphering the mechanism by which NAC orchestrates protein biogenesis and consequentially modulates development and pathogenesis.展开更多
Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and...Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.展开更多
Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusi...Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusitis,adenoid hypertrophy and other parts of the nose and pharynx.Professor Yin Dan believes that the main disease of upper airway cough syndrome is due to cold fluid retained in lung,blood stasis endogenous,compound feeling of wind evil.The pathogenesis is external wind evil and the hidden pathogen together to cause the disease.In the treatment,the warm cold fluid retention is the core,accompanied by the activation of blood and wind,so that the wind evil can go away,the cold evil can be warmed,the phlegm can be removed,and the blood stasis can be dispersed,so as to achieve the purpose of treating the upper airway cough syndrome of the children’s cold fluid retention in lung.展开更多
RXLR effectors are pathogenic factors secreted from oomycetes to manipulate the immunity of the host.Typical RXLR effectors contain an RXLR-dEER motif at the N-terminus,whereas atypical RXLRs show variations on this m...RXLR effectors are pathogenic factors secreted from oomycetes to manipulate the immunity of the host.Typical RXLR effectors contain an RXLR-dEER motif at the N-terminus,whereas atypical RXLRs show variations on this motif.The oomycete Phytophthora cactorum is known to infect over 200 plant species,resulting in significant agricultural economic losses.Although genome-wide identification and functional analyses of typical RXLRs from P.cactorum have been performed,little is known of atypical PcaRXLRs.Here,we identified RXLRs,both typical and atypical,in P.cactorum and compared them with those of other oomycete pathogens.Fewer RXLRs were identified in P.cactorum compared with other Phytophthora species,possibly due to fewer duplication events of RXLRs.In contrast,the percentage of atypical RXLRs was higher in P.cactorum than in other species,suggesting significant roles in P.cactorum pathogenesis.Analysis of RXLR gene expression showed that most were transcribed,suggesting their functionality.Transient expression of two atypical RXLRs in Nicotiana benthamiana showed that they induced necrosis dependent on host SGT1 and HSP90.Furthermore,two additional atypical RXLRs suppressed the defense response in N.benthamiana and promoted P.cactorum infection.These results demonstrate the vital role of atypical RXLRs in P.cactorum and provide valuable information on their evolutionary patterns and interactions with host plants.展开更多
Poplar canker,caused by the fungus Cytospora chrysosperma,results in tremendous losses in poplar plantations in China.Although NADPH oxidases(NOXs)play important roles in the development and pathogenicity of several p...Poplar canker,caused by the fungus Cytospora chrysosperma,results in tremendous losses in poplar plantations in China.Although NADPH oxidases(NOXs)play important roles in the development and pathogenicity of several pathogenic fungi,their roles in C.chrysosperma remain unclear.In this study,we characterized three NOX genes(CcNox1,CcNox2,and CcNoxR)in C.chrysosperma.All three genes were highly upregulated during poplar branch infection,and deletion of any of them severely reduced virulence on poplar branches.Furthermore,deletion of either CcNox1 or CcNoxR resulted in a significant increase in endogenous reactive oxygen species production in hyphae,enhanced influx of Ca^(2+),the disruption of redox homeostasis and compromised mitochondrial integrity.Moreover,biosynthesis and secretion of a known virulence factor oxalic acid was obviously defective and exogenous oxalic acid supplementation rescued the virulence of the mutants.Taken together,our findings reveal that NOXs play important roles in redox homeostasis,mitochondrial integrity and pathogenicity in C.chrysosperma.展开更多
Previous studies have sought to classify bladder cancer(BLCA)into different molecular subtypes to understand its pathogenic pathways and uncover specific treatments.1 These subtypes,often based on genetic,transcriptom...Previous studies have sought to classify bladder cancer(BLCA)into different molecular subtypes to understand its pathogenic pathways and uncover specific treatments.1 These subtypes,often based on genetic,transcriptomic,or proteomic profiles,aim to stratify patients for precision medicine and improve therapeutic outcomes.Despite these efforts,such classifications have rarely been applied in clinical practice due to challenges in standardization,reproducibility,and limited translational studies validating their utility.1 The treatment of BLCA predominantly relies on surgery,often combined with chemotherapy,immunotherapy,targeted therapy,or antibody-drug conjugates.Radical cystectomy remains the cornerstone for muscle-invasive bladder cancer(MIBC),while transurethral resection and intravesical therapy are common for non-muscle-invasive bladder cancer(NMIBC).2 However,the choice of its treatment modality still depends specifically on whether the disease is NMIBC or MIBC,rather than on the various molecular subtype classifications.3 Bridging the gap between molecular research and clinical application remains a significant challenge,highlighting the need for robust biomarker validation and the development of treatment algorithms that incorporate these subtypes to better guide personalized therapy.展开更多
Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The ae...Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.展开更多
Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as ...Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.展开更多
Background:Alzheimer’s disease(AD)is a fatal disease that threatens the quality of life of an aging population at a global scale.Various hypotheses on the etiology of AD have been developed over the years to guide ef...Background:Alzheimer’s disease(AD)is a fatal disease that threatens the quality of life of an aging population at a global scale.Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies.Main body:In this review,we focus on four AD hypotheses currently relevant to AD onset:the prevailing amyloid cascade hypothesis,the well-recognized tau hypothesis,the increasingly popular pathogen(viral infection)hypothesis,and the infection-related antimicrobial protection hypothesis.In briefly reviewing the main evidence supporting each hypothesis and discussing the questions that need to be addressed,we hope to gain a better understanding of the complicated multi-layered interactions in potential causal and/or risk factors in AD pathogenesis.As a defining feature of AD,the existence of amyloid deposits is likely fundamental to AD onset but is insufficient to wholly reproduce many complexities of the disorder.A similar belief is currently also applied to hyperphosphorylated tau aggregates within neurons,where tau has been postulated to drive neurodegeneration in the presence of pre-existing Aβplaques in the brain.Although infection of the central nerve system by pathogens such as viruses may increase AD risk,it is yet to be determined whether this phenomenon is applicable to all cases of sporadic AD and whether it is a primary trigger for AD onset.Lastly,the antimicrobial protection hypothesis provides insight into a potential physiological role for Aβpeptides,but how Aβ/microbial interactions affect AD pathogenesis during aging awaits further validation.Nevertheless,this hypothesis cautions potential adverse effects in Aβ-targeting therapies by hindering potential roles for Aβin anti-viral protection.Conclusion:AD is a multi-factor complex disorder,which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline.A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms,which may involve personalized treatment strategies for individual patients at varying stages of disease progression.展开更多
The disease caused by pathogenic fungi is the main cause of postharvest loss of fresh fruits.The formulation of disease control strategies greatly depends on the understanding of pathogenic mechanism of fungal pathoge...The disease caused by pathogenic fungi is the main cause of postharvest loss of fresh fruits.The formulation of disease control strategies greatly depends on the understanding of pathogenic mechanism of fungal pathogens and control strategy.In recent years,based on the application of various combinatorial research methods,some pathogenic genes of important postharvest fungal pathogens in fruit have been revealed,and their functions and molecular regulatory networks of virulence have been explored.These progresses not only provide a new perspective for understanding the molecular basis and regulation mechanism of pathogenicity of postharvest pathogenic fungi,but also are beneficial to giving theoretical guidance for the creation of new technologies of postharvest disease control.Here,we synthesized these recent advances and illustrated conceptual frameworks,and identified several issues on the focus of future studies.展开更多
基金funded by the Natural Science Foundation of Guangdong Province,China(Grant Nos.2023A1515012617,2022A1515010458 and 2023A1515030267)Guangzhou Science&Technology Program(Grant No.202201010410)the earmarked fund for CARS-32。
文摘Major facilitator superfamily(MFS)transporters are secondary active membrane transporters that play an important role in solute interchange and energy metabolism.Peronophythora litchii causes the most destructive disease on lichi,litchi downy blight.PlM90 was reported as a key oosporogenesis regulator.Here,we identified an MFS transporter gene PlMFS1,which is up-regulated during oospore formation at the late infection stage,while down-regulated in the PlM90 mutant.To investigate PlMFS1 function,we generated PlMFS1knockout mutants using CRISPR/Cas9-mediated genome editing technology.Compared with the wild-type strain SHS3,PlMFS1 deletion impaired mycelium growth,zoospore release,oospore production and pathogenicity.Furthermore,PlMFS1 deletion significantly affected P.litchii utilization of fructose,lactose and maltose,and may be the PlMFS1 mechanism involved in mycelial growth.PlMFS1 gene deletion also led to deceased laccase activity,laccase-encoding gene downregulation and impaired P.litchii pathogenicity.To our knowledge,this is the first report of an MFS transporter involved in sugar utilization,sexual reproduction,asexual reproduction and pathogenesis in oomycetes.
基金funded by the National Natural Science Foundation of China(32172364 to Shihong Zhang and 32272513 to Zonghua Wang)Fujian Agriculture and Forestry University scholarship,China for Wajjiha Batool。
文摘Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.
基金financially supported by the National Special Fund for Agro-scientific Research in the Public Interest of China(201503112)the Basic and Advance Technology Research Program in Henan Province,China(152300410073)the Talent Project of Henan Agricultural University,China(3600861)
文摘Wheat crown rot caused by Fusarium spp. is a common disease worldwide. Both Fusarium pseudograminearum and Fusarium graminearum infect wheat crown and produce mycotoxin leading to grain loss due to white head. F. pseudograminearum （Fp） was reported in wheat from Henan Province of China a couple of years ago. The wheat crown rot （CR） caused by this new pathogen is as an emerging severe disease of wheat, which has recently expanded to several provinces in China and is, therefore, under rapid investigation. Colonization of wheat tissue by Fp is accomplished though the formation of a septated foot-shaped appressoria and generation of a penetration peg to break through the internal cells of leaf sheath. The molecular mechanism by which Fp regulates the pathogenesis on wheat host is unclear. Here, we report FpPDE1, a P-type ATPase-encoding predicted PDE1 orthologue gene of Magnaporthe oryzae, belonging to the DRS2 subfamily of aminophospholipid translocases. The gene deletion of FpPDE1 with the split-marker approach did not obviously affect hyphae growth and conidiation, but led to an attenuated virulence on wheat base stem and root. Our finding indicates that the putative aminophospholipid translocases is not essential for the infectious hyphae development in Fp.
文摘Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.
文摘Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic roles.The goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic implications.English abstracts were identified in PubMed by multiple search terms,and bibliographies were developed.MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines.Diverse pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells emerge.Circulating MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver disease.This phenotype lacks disease-specificity,and it does not predict the biological effects.MAIT cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated cirrhosis.They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis.Local factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual diseases.Investigational manipulations of function are warranted to establish an association with disease severity and outcome.In conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and infection.Their pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.
基金The authors are thankful to JAIN(Deemed-to-be University),India and Department of Science and Technology-Science and Engineering Research Board(DST-SERB),India(No.YSS/2015/001905)for the financial and infrastructural supports.
文摘Pathogenesis-related(PR)proteins are one of the major and preliminary proteins accumulated as a defense against biotic stress.This defense response can be induced by using beneficial rhizobacteria,which has been studied in various host-pathogen interactions.In the present study,eleven Pseudomonas isolates were assessed for their potential to ferment sorbitol,reduce nitrate,and produce mycolytic enzymes,1-aminocyclopropane-l-carboxylic acid(ACC)deaminase,phenazine antibiotics,and N-acyl homoserine lactones(AHLs).All isolates were tested against the host-specific pathogen Fusarium oxysporum MTCC1755 in tomato under greenhouse conditions,and shortlisted isolates were tested for their rhizosphere competence.In-vitro test results showed that the isolates were able to produce mycolytic enzymes,including protease,lipase,chitinase,cellulase,and amylase,and the antibiotic phenazine and were negative for pyoluteorin.All the isolates except two were positive for ACC deaminase production.Greenhouse results showed that the isolates M80,M96,and T109 significantly reduced symptoms of Fusarium wilt.Extended greenhouse tests under autoclaved and unautoclaved soil conditions showed that M80,M96,and T109 were excellent rhizosphere competitors and were identified as Pseudomonas putida.In brief,the defense-specific biochemical variations in the host could describe the improved defense against Fusarium wilt occurring in the primed plants.These three Pseudomonas strains could be used as potential biocontrol agents,along with their rhizosphere competence.
基金National Natural Science Foundation of China (31970141)the Natural Science Foundation of Fujian Province, China (2020J06047)+1 种基金the Foundation of Minjiang University, China (MJY19019)the Foundation of Fujian Agriculture and Forestry University, China (KFb22050XA)。
文摘Fusarium graminearum is an important plant pathogenic fungus that causes disease and yield reduction in many cereal crops, such as wheat and barley. Gyp8 stimulates GTP hydrolysis on Ypt1 in yeast. However, the functions of Gyp8 in plant pathogenic fungi are still unknown. In this study, we investigated the roles of Fg Gyp8 in F. graminearum by genetic and pathological analyses. Through gene knockout and phenotypic analyses, we found that Fg Gyp8 is required for vegetative growth in F. graminearum. The conidiation, conidial size and number of septa per conidium of ΔFggyp8 mutant are significantly reduced when compared to the wild type PH-1. Furthermore, Fg Gyp8 is crucial for pathogenicity on wheat coleoptiles and wheat heads. Fg Gyp8 contains a conserved TBC domain. Domain deletion analysis showed that the TBC domain, C-and N-terminal regions of Fg Gyp8 are all important for its biological functions in F. graminearum. Moreover, we showed that Fg Gyp8 catalyzes the hydrolysis of the GTP on Fg Rab1 to GDP in vitro, indicating that Fg Gyp8 is a GTPase-activating protein(GAP) for Fg Rab1. In addition, we demonstrated that Fg Gyp8 is required for Fg Snc1-mediated fusion of secretory vesicles with the plasma membrane in F. graminearum. Finally, we showed that Fg Gyp8 has functional redundancy with another Fg Rab1 GAP, Fg Gyp1, in F. graminearum. Taken together, we conclude that Fg Gyp8 is required for vegetative growth, conidiogenesis, pathogenicity and acts as a GAP for Fg Rab1 in F. graminearum.
基金supported by the National Basic Research Program of China (973 program: 2005CB523006)
文摘Objective To investigate the pathogenesis and immunogenicity of H9N2 influenza virus A/Guangzhou/333/99 （a reassortant of G1 and G9 viruses isolated from a female patient in 1999） in a mouse model of infection.Methods Mice were infected with increasing virus titers.Viral load in the lungs and trachea was determined by EID50 assay.Pulmonary histopathology was assessed by hematoxylin‐eosin staining.Anti‐HI antibody titers and T‐cell responses to viral HA were determined by ELISPOT and confirmed by flow cytometry.Results Mice presented a mild syndrome after intranasal infection with A/Guangzhou/333/99 （H9N2） influenza virus.Virus was detected in the trachea and lungs of mice harvested on days 3,6,and 9 post‐infection.A T‐cell response to viral HA was detected on day 6 and H9 HA‐specific CD 4＋ T‐cells predominated.Seroconversion was detected after 14 days and antibody persisted for at least 28 weeks.Conclusion Our results suggest that H9N2 （A/Guangzhou/333/99） can replicate in the murine respiratory tract without prior adaptation,and both humoral and cell‐mediated immunity play an important role in the immune response.
基金the funding support from the National Natural Science Foundation of China(No.81774126)Hunan Provincial Innovation Foundation for Postgraduate(No.CX2018B481)Program for First-class Disciplines of Hunan Province in the Direction of Traditional Chinese and Western Medicine(No.2018ZXYJH20).
文摘Based on the characteristics of the epidemic situation and the authors’understanding of the related ancient books and documents,this paper explores the etiology and pathogenesis of Corona Virus Disease 2019(COVID-19)from 5 aspects:abnormal climate in"warm winter",unique geographical location,pathogenesis evolution of cold and dampness mixed with insidious dryness,transmission and change of"triple energizer"of toxic pathogens,and game between healthy Qi and toxic pathogens.Combined with the special treatment of traditional Chinese medicine(TCM),the purpose is to make a modest contribution to curbing the epidemic situation with TCM.
文摘The pathogenesis-related proteins 1 (PR-1) gene family play important roles in the plant metabolism in response to biotic and abiotic stresses. The wheat TdPR1.2 has been previously isolated and characterized. Here we showed by bio-informatic analysis that TdPR1.2 contains six cysteine residues that are conserved between all PR-1 proteins tested. Using ScanProsite tool, we found that TdPR1.2 structure has a CRISP family signature 1 and 2 located at the C-terminal part of the protein. Those two domains are conserved in many identified PR1.2 proteins in plants. Moreover, SignalIP-5.0 analysis revealed that TdPR1.2 contains a putative signal peptide formed by 25 amino acids at the N-terminal extremity. The presence of this signal peptide suggested that the mature proteins will be secreted after the cleavage of the signal sequence. Further, we investigate the role of the TdPR1.2 proteins in the growth of <i>Escherichia coli</i> transformants cells under different abiotic stresses. Our results showed that the full-length form of TdPR1.2 enhanced tolerance of <i>E. coli</i> against salt and osmotic stress but not to KCl. Moreover, TdPR1.2 protein confers bacterial tolerance to heavy metals in solid and liquid mediums. Based on these results, we suggest that the TdPR1.2 protein could play an important role in response to abiotic stress conditions.
基金This work was supported by the National Natural Science Foundation of China(31471737,31671984,and 31801691)the Advanced Programs of Guizhou Province for the Returned Overseas Scholars([2018]02).
文摘Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and thrive.However,the fungal proteins involved in proteostasis remain poorly characterized in the process of pathogenesis.In this study,we characterized the function of the nascent polypeptideassociated complex(NAC)in Fusarium graminearum(F.graminearum)(FgNAC),one of the top 10 fungal pathogens with predominant scientific/economic importance.We found that FgNACa,a subunit of FgNAC,manifests high structural and functional similarity to its homologous counterparts in yeast and other species.The mutants of F.graminearum lacking NACa are viable but suffer significant defects in vegetative growth,conidial production,and pathogenesis.In addition,we show here that FgNACa can interact with another subunit of NAC(FgNACb)in a yeast-two-hybrid assay.The subcellular localization results show that FgNACa and FgNACb are predominantly localized in the cytoplasm.Future studies should focus on deciphering the mechanism by which NAC orchestrates protein biogenesis and consequentially modulates development and pathogenesis.
基金Supported by the National Natural Science Foundation of China(No.82260001)Key Special Project Supported by the National Key R&D Plan of the Ministry of Science and Technology(No.2022YFC2305004)。
文摘Burkholderia pseudomallei is the pathogen that causes melioidosis.Melioidosis has a long duration of chronic infection,atypical clinical manifestations at acute onset,and is prone to life-threatening complications and poor prognosis.Understanding the pathogenesis and drug resistance mechanism of Burkholderia pseudomallei will effectively help the diagnosis and treatment of the disease and improve the prognosis.This review focuses on the extracellular movement of Burkholderia pseudomallei in host cells,the way of infecting host cells,virulence factors,and drug resistance mechanisms(efflux pumps,changes in target sites,etc.).This study provides a possible direction for the early diagnosis,treatment and control of melioidosis caused by this bacterium.
文摘Upper airway cough syndrome refers to a clinical syndrome with chronic cough as the main manifestation caused by the reverse flow of secretions from various upper airway diseases such as allergic rhinitis,rhino-sinusitis,adenoid hypertrophy and other parts of the nose and pharynx.Professor Yin Dan believes that the main disease of upper airway cough syndrome is due to cold fluid retained in lung,blood stasis endogenous,compound feeling of wind evil.The pathogenesis is external wind evil and the hidden pathogen together to cause the disease.In the treatment,the warm cold fluid retention is the core,accompanied by the activation of blood and wind,so that the wind evil can go away,the cold evil can be warmed,the phlegm can be removed,and the blood stasis can be dispersed,so as to achieve the purpose of treating the upper airway cough syndrome of the children’s cold fluid retention in lung.
基金funded by the Liaoning Applied Basic Research Program(2022JH2/101300284)Liaoning Agricultural Science and Technology Innovation Fund(2022XTCX0503 and 2023QN2417).
文摘RXLR effectors are pathogenic factors secreted from oomycetes to manipulate the immunity of the host.Typical RXLR effectors contain an RXLR-dEER motif at the N-terminus,whereas atypical RXLRs show variations on this motif.The oomycete Phytophthora cactorum is known to infect over 200 plant species,resulting in significant agricultural economic losses.Although genome-wide identification and functional analyses of typical RXLRs from P.cactorum have been performed,little is known of atypical PcaRXLRs.Here,we identified RXLRs,both typical and atypical,in P.cactorum and compared them with those of other oomycete pathogens.Fewer RXLRs were identified in P.cactorum compared with other Phytophthora species,possibly due to fewer duplication events of RXLRs.In contrast,the percentage of atypical RXLRs was higher in P.cactorum than in other species,suggesting significant roles in P.cactorum pathogenesis.Analysis of RXLR gene expression showed that most were transcribed,suggesting their functionality.Transient expression of two atypical RXLRs in Nicotiana benthamiana showed that they induced necrosis dependent on host SGT1 and HSP90.Furthermore,two additional atypical RXLRs suppressed the defense response in N.benthamiana and promoted P.cactorum infection.These results demonstrate the vital role of atypical RXLRs in P.cactorum and provide valuable information on their evolutionary patterns and interactions with host plants.
基金supported by the National Key R&D Program of China(2022YFD1401000).
文摘Poplar canker,caused by the fungus Cytospora chrysosperma,results in tremendous losses in poplar plantations in China.Although NADPH oxidases(NOXs)play important roles in the development and pathogenicity of several pathogenic fungi,their roles in C.chrysosperma remain unclear.In this study,we characterized three NOX genes(CcNox1,CcNox2,and CcNoxR)in C.chrysosperma.All three genes were highly upregulated during poplar branch infection,and deletion of any of them severely reduced virulence on poplar branches.Furthermore,deletion of either CcNox1 or CcNoxR resulted in a significant increase in endogenous reactive oxygen species production in hyphae,enhanced influx of Ca^(2+),the disruption of redox homeostasis and compromised mitochondrial integrity.Moreover,biosynthesis and secretion of a known virulence factor oxalic acid was obviously defective and exogenous oxalic acid supplementation rescued the virulence of the mutants.Taken together,our findings reveal that NOXs play important roles in redox homeostasis,mitochondrial integrity and pathogenicity in C.chrysosperma.
基金supported by the National Natural Science Foundation of China(No.82273065)Fundamental Research Funds for the Central Universities(China)(No.2042022dx0003)+1 种基金Research Fund of Zhongnan Hospital of Wuhan University(Wuhan,China)(No.YYXKNLJS2024001,PTPP2024001)The funders played no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Previous studies have sought to classify bladder cancer(BLCA)into different molecular subtypes to understand its pathogenic pathways and uncover specific treatments.1 These subtypes,often based on genetic,transcriptomic,or proteomic profiles,aim to stratify patients for precision medicine and improve therapeutic outcomes.Despite these efforts,such classifications have rarely been applied in clinical practice due to challenges in standardization,reproducibility,and limited translational studies validating their utility.1 The treatment of BLCA predominantly relies on surgery,often combined with chemotherapy,immunotherapy,targeted therapy,or antibody-drug conjugates.Radical cystectomy remains the cornerstone for muscle-invasive bladder cancer(MIBC),while transurethral resection and intravesical therapy are common for non-muscle-invasive bladder cancer(NMIBC).2 However,the choice of its treatment modality still depends specifically on whether the disease is NMIBC or MIBC,rather than on the various molecular subtype classifications.3 Bridging the gap between molecular research and clinical application remains a significant challenge,highlighting the need for robust biomarker validation and the development of treatment algorithms that incorporate these subtypes to better guide personalized therapy.
基金supported by the National Natural Science Foundation of China (81790624 and C-0052)Natural Science Foundation of Hubei Province (2020CFA016)。
文摘Myocarditis is an inflammatory cardiac disease characterized by the destruction of myocardial cells, infiltration of interstitial inflammatory cells, and fibrosis, and is becoming a major public health concern. The aetiology of myocarditis continues to broaden as new pathogens and drugs emerge. The relationship between immune checkpoint inhibitors, severe acute respiratory syndrome coronavirus 2, vaccines against coronavirus disease-2019, and myocarditis has attracted increased attention. Immunopathological processes play an important role in the different phases of myocarditis, affecting disease occurrence, development, and prognosis. Excessive immune activation can induce severe myocardial injury and lead to fulminant myocarditis,whereas chronic inflammation can lead to cardiac remodelling and inflammatory dilated cardiomyopathy. The use of immunosuppressive treatments, particularly cytotoxic agents, for myocarditis, remains controversial. While reasonable and effective immunomodulatory therapy is the general trend. This review focuses on the current understanding of the aetiology and immunopathogenesis of myocarditis and offers new perspectives on immunomodulatory therapies.
文摘Hodgkin lymphoma(HL)is a heterogenous lymphoproliferative disorder of B-cell origin and represents one of the most common malignancies in children and young adults.In addition to well-known underlying factors-such as Epstein-Barr virus infection-the familial aggregation demonstrated in large population studies suggested a genetic predisposition.First-degree relatives of patients with HL have an approximately threefold increased risk of developing the disease compared to the general population.These observations have recently prompted several whole-genome studies in affected families,identifying variants possibly implicated in lymphomagenesis,including alterations in DICER1(a member of the ribonuclease III family),POT1(protection of telomeres 1),KDR(kinase insert domain receptor),KLHDC8B(kelch domain-containing protein 8B),PAX5(paired box protein 5),GATA3(GATA binding protein 3),IRF7(interferon regulatory factor 7),EEF2KMT(eukaryotic elongation factor 2 lysine methyltransferase),and POLR1E(RNA polymerase I subunit E).In this article,we review current insights into the etiopathogenesis and risks of familial HL,and present case reports involving two sisters diagnosed with HL nearly 17 years apart.Recognizing the risk for first-degree relatives may potentially increase awareness of early symptoms among family members of HL patients,leading to earlier diagnosis and better outcomes.Conversely,understanding that the hereditary risk,though higher than in the general population,remains relatively low may provide reassurance for affected families.
基金National Institutes of Health(NIH)AG059217&AG061875 for TYHNIH AG062257,AG057509,AG054111,and AG020670 for HZNIH AG057981,BrightFocus Foundation A2016346F,Alzheimer Association AARG-17-500335,&Florida Department of Health 8AZ07 for CL.
文摘Background:Alzheimer’s disease(AD)is a fatal disease that threatens the quality of life of an aging population at a global scale.Various hypotheses on the etiology of AD have been developed over the years to guide efforts in search of therapeutic strategies.Main body:In this review,we focus on four AD hypotheses currently relevant to AD onset:the prevailing amyloid cascade hypothesis,the well-recognized tau hypothesis,the increasingly popular pathogen(viral infection)hypothesis,and the infection-related antimicrobial protection hypothesis.In briefly reviewing the main evidence supporting each hypothesis and discussing the questions that need to be addressed,we hope to gain a better understanding of the complicated multi-layered interactions in potential causal and/or risk factors in AD pathogenesis.As a defining feature of AD,the existence of amyloid deposits is likely fundamental to AD onset but is insufficient to wholly reproduce many complexities of the disorder.A similar belief is currently also applied to hyperphosphorylated tau aggregates within neurons,where tau has been postulated to drive neurodegeneration in the presence of pre-existing Aβplaques in the brain.Although infection of the central nerve system by pathogens such as viruses may increase AD risk,it is yet to be determined whether this phenomenon is applicable to all cases of sporadic AD and whether it is a primary trigger for AD onset.Lastly,the antimicrobial protection hypothesis provides insight into a potential physiological role for Aβpeptides,but how Aβ/microbial interactions affect AD pathogenesis during aging awaits further validation.Nevertheless,this hypothesis cautions potential adverse effects in Aβ-targeting therapies by hindering potential roles for Aβin anti-viral protection.Conclusion:AD is a multi-factor complex disorder,which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline.A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms,which may involve personalized treatment strategies for individual patients at varying stages of disease progression.
基金This research was funded by the National Natural Science Foundation of China(grant numbers 31930086,31530057,31671910,31722043).
文摘The disease caused by pathogenic fungi is the main cause of postharvest loss of fresh fruits.The formulation of disease control strategies greatly depends on the understanding of pathogenic mechanism of fungal pathogens and control strategy.In recent years,based on the application of various combinatorial research methods,some pathogenic genes of important postharvest fungal pathogens in fruit have been revealed,and their functions and molecular regulatory networks of virulence have been explored.These progresses not only provide a new perspective for understanding the molecular basis and regulation mechanism of pathogenicity of postharvest pathogenic fungi,but also are beneficial to giving theoretical guidance for the creation of new technologies of postharvest disease control.Here,we synthesized these recent advances and illustrated conceptual frameworks,and identified several issues on the focus of future studies.
