Root rot is a prevalent soil-borne fungal disease in citrus.Citron C-05(Citrus medica)stands out as a germplasm within Citrus spp.due to its complete resistance to citrus canker and favorable characteristics such as s...Root rot is a prevalent soil-borne fungal disease in citrus.Citron C-05(Citrus medica)stands out as a germplasm within Citrus spp.due to its complete resistance to citrus canker and favorable characteristics such as single embryo and easy rooting.However,Citron C-05 was found to be highly susceptible to root rot during cultivation,with the specific pathogens previously unknown.In this study,four candidate fungal species were isolated from Citron C-05 roots.Sequence analysis of ITS,EF-1a,RPB1,and RPB2 identified two Fusarium solani strains,Rr-2 and Rr-4,as the candidates causing root rot in Citron C-05.Resistance tests showed these two pathogens increased root damage rate from 10.30%to 35.69%in Citron C-05,sour orange(Citrus aurantium),sweet orange(Citrus sinensis)and pummelo(Citrus grandis).F.solani exhibited the weak pathogenicity towards trifoliate orange(Poncirus trifoliata).DAB staining revealed none of reddish-brown precipitation in the four susceptible citrus germplasm after infection with F.solani,while trifoliate orange exhibited significant H2O2 accumulation.Trypan blue staining indicated increased cell death in the four susceptible citrus germplasm following infection with these two pathogens but not in trifoliate orange.These findings provide a comprehensive understanding of citrus root rot and support future research on the mechanisms of root rot resistance in citrus.展开更多
Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and m...Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation,deregulated signaling pathways,genomic instability,and the release of parasite-derived exosomes that reshape the tumor microenvironment.These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better.The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities.We examine pathogens such as Schistosoma haematobium,Opisthorchis viverrini,Toxoplasma gondii,Plasmodium falciparum,and Leishmania spp.,detailing their roles in chronic inflammation,immune modulation,and interactions with tumor-associated immune cells.The review further discusses parasite-induced immunosuppression,coinfections,and their cumulative impact on cancer risk.Additionally,we explore novel therapeutic approaches,including pathway inhibitors,epigenetic drugs,microbiome modulation,and engineered parasites.Future perspectives emphasize parasite-based immunotherapies,long-term epigenetic consequences of infection,and AI-driven multiomics strategies for identifying oncogenic signatures.This review integrates advances from parasitology and oncology to provide new insights into biomarkers,targeted therapies,and mechanisms of infection-induced tumorigenesis.The literature search covered studies indexed in PubMed,Scopus,and Web of Science up to July 2025.展开更多
The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurologica...The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.展开更多
Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivar...Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.展开更多
The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of famil...The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.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
Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracel...Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracellular NLR receptors that recognize pathogen effectors(Jones et al.,2024).The nucleoporin CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5(CPR5)is a key negative regulator of ETI.CPR5 integrates nuclear transport,cell cycle control,and RNA processing to suppress immune signaling(Wang et al.,2014;Gu et al.,2016;Peng et al.,2022).Recent work revealed that CPR5 also modulates immunity through another nucleoporin,GUANYLATE-BINDING PROTEIN-LIKE 3(GBPL3),which interaCtS with PWWP-DOMAIN INTERACTOR OF POLYCOMBS1(PWO1),a key component of the chromatin-associated methyltransferase POLYCOMB REPRESSIVE COMPLEX 2(PRC2)(Reimann et al.,2023;Pan et al.,2025).These findings suggest unexplored roles for chromatin remodeling in the CPR5-mediated immunity.展开更多
Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contribu...Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].展开更多
NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-l...NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-like PRRSV evolved,named the L1A variant.The phylogenetics,epidemic status,and pathogenicity of the LA variants were subsequently comprehensively evaluated.Based on the results of the ORF5 phylogenetic analysis,the L1A variants were classified as NADC34-like PPRSV.All the strains had the same discontinuous 131-aa deletion in the NSP2 region(similar to that in the NADC30).Recombination analysis revealed that the L1A variants were recombinant viruses that contained an NADC30-like PRRSV skeleton,a nonstructural protein-encoding gene region obtained in part from JXA1-like PRRSV and a ORF2-ORF6 gene region partly obtained from NADC34-like PRRSV and that exhibited similar recombination patterns.We successfully isolated the L1A variant TZJ2756 from PAMs and Marc-145 cells.In animal experiments,TZJ2756 exhibited moderate pathogenicity in piglets,causing obvious clinical symptoms,namely,persistent fever,significantly reduced body weight,interstitial edema and severe interstitial pneumonia in the lungs,and prolonged high-load viremia.L1A variants have been detected in at least 12 provinces in China and share many similar epidemiological characteristics with the American L1C variant.This research will enhance our understanding of the prevalence of L1A variants and furnish valuable data for the ongoing monitoring of NADC34-like PRRSV in China.展开更多
Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more ...Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.展开更多
Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dyn...Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.展开更多
Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and ...Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).展开更多
BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicat...BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.展开更多
Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative...Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative antimicrobial strategies.This study presents a structure-function approach to antimicrobial peptide(AMP)design through the strategic integration of a cationic backbone with a hydrophobic core.This dual-domain architecture enables robust hydrophobic and electrostatic interactions,promoting spontaneous self-assembly and efficient membrane engagement.The lead peptide,Tryptolycin(TRPY),formed stable,monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity,with minimum inhibitory concentrations≤1μmol/L against multiple strains of MRSA and K.pneumoniae,while exerting minimal cytotoxicity toward mammalian cells.TRPY achieved rapid bacterial elimination,eradicating 99.9%of both planktonic and persister populations within minutes.Mechanistic investigations revealed that TRPY induced membrane permeabilization,promoted reactive oxygen species(ROS)production,and inhibited biofilm formation.In murine infection models,TRPY effectively eradicated established infections,reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations.Collectively,these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,...Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.展开更多
The risk of new pathogen emergence is constantly increasing due to several factors,including the expansion and exploration of previously uninhabited regions,increased global trade,tourism,climate change and others.Rec...The risk of new pathogen emergence is constantly increasing due to several factors,including the expansion and exploration of previously uninhabited regions,increased global trade,tourism,climate change and others.Recently,monkeypox(mpox)cases have been increasing,causing alarm as the cases are reported from countries where the disease is not endemic.Mpox virus is an emerging pathogen responsible for human mpox.展开更多
The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple d...The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.展开更多
Non-O1/non-O139 Vibrio cholerae(NOVC)has multiple pathogenic pathways in humans.The cause of disease in influenced by the virulence genes carried by the infecting strain and the health condition of the host.[1-2]When ...Non-O1/non-O139 Vibrio cholerae(NOVC)has multiple pathogenic pathways in humans.The cause of disease in influenced by the virulence genes carried by the infecting strain and the health condition of the host.[1-2]When seafood,food and water sources are contaminated with feces,people are prone to gastroenteritis,and direct exposure to contaminated water may cause wound infection.展开更多
Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by t...Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.展开更多
基金supported by Joint Funds of the National Natural Science Foundation of China(Grant No.U21A20228).
文摘Root rot is a prevalent soil-borne fungal disease in citrus.Citron C-05(Citrus medica)stands out as a germplasm within Citrus spp.due to its complete resistance to citrus canker and favorable characteristics such as single embryo and easy rooting.However,Citron C-05 was found to be highly susceptible to root rot during cultivation,with the specific pathogens previously unknown.In this study,four candidate fungal species were isolated from Citron C-05 roots.Sequence analysis of ITS,EF-1a,RPB1,and RPB2 identified two Fusarium solani strains,Rr-2 and Rr-4,as the candidates causing root rot in Citron C-05.Resistance tests showed these two pathogens increased root damage rate from 10.30%to 35.69%in Citron C-05,sour orange(Citrus aurantium),sweet orange(Citrus sinensis)and pummelo(Citrus grandis).F.solani exhibited the weak pathogenicity towards trifoliate orange(Poncirus trifoliata).DAB staining revealed none of reddish-brown precipitation in the four susceptible citrus germplasm after infection with F.solani,while trifoliate orange exhibited significant H2O2 accumulation.Trypan blue staining indicated increased cell death in the four susceptible citrus germplasm following infection with these two pathogens but not in trifoliate orange.These findings provide a comprehensive understanding of citrus root rot and support future research on the mechanisms of root rot resistance in citrus.
文摘Parasitic infections are increasingly recognized as contributors to cancer development,yet the underlying oncogenic mechanisms remain insufficiently understood.Growing evidence from molecular oncology,immunology,and microbiome research suggests that chronic parasitic infections may drive tumorigenesis through sustained inflammation,deregulated signaling pathways,genomic instability,and the release of parasite-derived exosomes that reshape the tumor microenvironment.These insights underscore the need to integrate parasitology with cancer biology to understand infection-associated malignancies better.The aim of this narrative review is to synthesize current knowledge on how selected parasites contribute to cancer development and to highlight emerging therapeutic and diagnostic opportunities.We examine pathogens such as Schistosoma haematobium,Opisthorchis viverrini,Toxoplasma gondii,Plasmodium falciparum,and Leishmania spp.,detailing their roles in chronic inflammation,immune modulation,and interactions with tumor-associated immune cells.The review further discusses parasite-induced immunosuppression,coinfections,and their cumulative impact on cancer risk.Additionally,we explore novel therapeutic approaches,including pathway inhibitors,epigenetic drugs,microbiome modulation,and engineered parasites.Future perspectives emphasize parasite-based immunotherapies,long-term epigenetic consequences of infection,and AI-driven multiomics strategies for identifying oncogenic signatures.This review integrates advances from parasitology and oncology to provide new insights into biomarkers,targeted therapies,and mechanisms of infection-induced tumorigenesis.The literature search covered studies indexed in PubMed,Scopus,and Web of Science up to July 2025.
基金funded by the Ministerio de Ciencia e Innovación Spain(PID2020-113388RB-I00,AEI/10.13039/501100011033)Consellería de Innovación,Universidades,Ciencia y Sociedad Digital,Generalitat Valenciana(CIPROM/2021/082)+2 种基金co-funded with European Regional Development Funds(ERDF)(PID2020-113388RB-I00,and CIPROM/2021/082)PID2022-136874OB-C33 from MCIN/AEI/10.13039/501100011033by the European Union NextGenerationEU/PRTR(to VF).
文摘The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.
基金provided by the National Natural Sciences Foundation of China (82270979)High-Level Hospital Construction Project (0224C001,0224C050)Cultivation Program for Reserve Talents for Academic Leaders (2023A208) of Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University。
文摘Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.
基金supported by the Natural Science Foundation of Beijing,Nos.7244428(to WZ)and 7222215(to JH)the Peking University Medicine Sailing Program forYoung Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+4 种基金the National Natural Science Foundation of China,Nos.81873784,82071426(to DF),and81974197(to JH)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)Beijing Physician-Scientist TrainingProgram,No.BJPSTP-2024-03(to JH)the China Postdoctoral Science Foundation,Nos.2022TQ0014(to LX),2022M720284(to LX)the E-Town Cooperation&Development Foundation,No.YCXJ-JZ-2023-017(to LX).
文摘The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.
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supported by grants from the National Natural Science Foundation of China(32270290)the Shanghai Engineering Research Center of Plant Germplasm Resources(17DZ2252700).
文摘Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracellular NLR receptors that recognize pathogen effectors(Jones et al.,2024).The nucleoporin CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5(CPR5)is a key negative regulator of ETI.CPR5 integrates nuclear transport,cell cycle control,and RNA processing to suppress immune signaling(Wang et al.,2014;Gu et al.,2016;Peng et al.,2022).Recent work revealed that CPR5 also modulates immunity through another nucleoporin,GUANYLATE-BINDING PROTEIN-LIKE 3(GBPL3),which interaCtS with PWWP-DOMAIN INTERACTOR OF POLYCOMBS1(PWO1),a key component of the chromatin-associated methyltransferase POLYCOMB REPRESSIVE COMPLEX 2(PRC2)(Reimann et al.,2023;Pan et al.,2025).These findings suggest unexplored roles for chromatin remodeling in the CPR5-mediated immunity.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(2022YFD1800400).
文摘Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].
基金supported by grants from the National Natural Science Foundation of China(32172890 and 32002315)the National Key Research and Development Program of China(2022YFF0711004)+3 种基金the Natural Science Foundation of Heilongjiang Province,China(YQ2022C042)the State Key Laboratory of Veterinary Biotechnology Foundation of China(SKLVBF202208)the Postdoctoral Fellowship Program of CPSF,China(GZC20233062)the National Center of Technology Innovation for Pigs,China(NCTIP-XD/C09)。
文摘NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-like PRRSV evolved,named the L1A variant.The phylogenetics,epidemic status,and pathogenicity of the LA variants were subsequently comprehensively evaluated.Based on the results of the ORF5 phylogenetic analysis,the L1A variants were classified as NADC34-like PPRSV.All the strains had the same discontinuous 131-aa deletion in the NSP2 region(similar to that in the NADC30).Recombination analysis revealed that the L1A variants were recombinant viruses that contained an NADC30-like PRRSV skeleton,a nonstructural protein-encoding gene region obtained in part from JXA1-like PRRSV and a ORF2-ORF6 gene region partly obtained from NADC34-like PRRSV and that exhibited similar recombination patterns.We successfully isolated the L1A variant TZJ2756 from PAMs and Marc-145 cells.In animal experiments,TZJ2756 exhibited moderate pathogenicity in piglets,causing obvious clinical symptoms,namely,persistent fever,significantly reduced body weight,interstitial edema and severe interstitial pneumonia in the lungs,and prolonged high-load viremia.L1A variants have been detected in at least 12 provinces in China and share many similar epidemiological characteristics with the American L1C variant.This research will enhance our understanding of the prevalence of L1A variants and furnish valuable data for the ongoing monitoring of NADC34-like PRRSV in China.
基金supported by the National Natural Science Foundational of China,Nos.U24A20692(to CJZ),82371355(to CJZ),and 82101414(to MH)National NaturalScience Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)+5 种基金Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovationand Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’sHospital,No.30420230005Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(toCJZ)Sichuan Science and Technology Support Project,No.2023YFS0212(to BH)Project of Sichuan Provincial Health Commission,No.19PJ265(to LD).
文摘Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.
基金supported by the Key Research and Development Program of Shandong Province,China(No 2021CXGC010803)Pan’an County Chinese Medicine Industry Project(No.PZYF202103).
文摘Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.
基金supported by Zhejiang Province Science and Technology Cooperation Project of“Three Rural and Nine Parties”(grant number 2023SNJF059).
文摘Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).
文摘BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.
基金supported by the National Key Research and Development Program of China(2022YFC2105003,2022YFC2602500)National Natural Science Foundation of China(92469103,32400769,32300404)+6 种基金Chinese Academy of Sciences(YSBR-111,SAJC202402)Yunnan Provincial Science and Technology Department(202305AH340007,202301AT070343,202502AA310005)Yunnan Characteristic Plant Extraction Laboratory(2025YKZY002)Kunming Science and Technology Bureau(2022SCP007)New Cornerstone Investigator Program from Shenzhen New Cornerstone Science Foundation(NCI202238)Tianfu Jincheng Laboratory Foundation(TFJC2023010007)Chinese Academy of Sciences and World Academy of Sciences(CAS-TWAS)President’s Fellowship Program(2019A8010415001)。
文摘Effective countermeasures against multidrug-resistant nosocomial pathogens,such as carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus(MRSA),require the development of innovative antimicrobial strategies.This study presents a structure-function approach to antimicrobial peptide(AMP)design through the strategic integration of a cationic backbone with a hydrophobic core.This dual-domain architecture enables robust hydrophobic and electrostatic interactions,promoting spontaneous self-assembly and efficient membrane engagement.The lead peptide,Tryptolycin(TRPY),formed stable,monodisperse nanoparticles and demonstrated broad-spectrum bactericidal activity,with minimum inhibitory concentrations≤1μmol/L against multiple strains of MRSA and K.pneumoniae,while exerting minimal cytotoxicity toward mammalian cells.TRPY achieved rapid bacterial elimination,eradicating 99.9%of both planktonic and persister populations within minutes.Mechanistic investigations revealed that TRPY induced membrane permeabilization,promoted reactive oxygen species(ROS)production,and inhibited biofilm formation.In murine infection models,TRPY effectively eradicated established infections,reducing bacterial burden across target organs by 3-to 5-fold without significant cytotoxicity at therapeutic concentrations.Collectively,these findings establish TRPY as a promising therapeutic agent for clinical translation in the treatment of refractory bacterial infections.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金Supported by National Natural Science Foundation of China,No.82374323and Hunan Graduate Research Innovation Project,No.2023CX15.
文摘Helicobacter pylori-associated gastritis(HPAG)is a common condition of the gastrointestinal tract.However,extensive and long-term antibiotic use has resulted in numerous adverse effects,including increased resistance,gastrointestinal dysfunction,and increased recurrence rates.When these concerns develop,traditional Chinese medicine(TCM)may have advantages.TCM is based on the concept of completeness and aims to eliminate pathogens and strengthen the body.It has the potential to prevent this condition while also boosting the rate of Helicobacter pylori eradication.This review elaborates on the mechanism of TCM treatment for HPAG based on cellular signalling pathways,which reflects the flexibility of TCM in treating diseases and the advantages of multi-level,multipathway,and multi-target treatments for HPAG.
文摘The risk of new pathogen emergence is constantly increasing due to several factors,including the expansion and exploration of previously uninhabited regions,increased global trade,tourism,climate change and others.Recently,monkeypox(mpox)cases have been increasing,causing alarm as the cases are reported from countries where the disease is not endemic.Mpox virus is an emerging pathogen responsible for human mpox.
基金supported by the National KeyR&DProgramof China(2022YFF0710500)the National Natural Science Foundation of China(32172853 and 32373013)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001).
文摘The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other groups.In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic(including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.
基金supported by the National Natural Science Foundation(82372206)the Jiangsu Provincial Health Commission(H2023107)the project of basic and clinical research on cardiac arrest in the Emergency and Critical Care Department of the Second Affiliated Hospital of Soochow University(XKTJ-XK202408-2).
文摘Non-O1/non-O139 Vibrio cholerae(NOVC)has multiple pathogenic pathways in humans.The cause of disease in influenced by the virulence genes carried by the infecting strain and the health condition of the host.[1-2]When seafood,food and water sources are contaminated with feces,people are prone to gastroenteritis,and direct exposure to contaminated water may cause wound infection.
基金funded by the Deanship of Scientific Research,Vice Presidency for Graduate Studies and Scientific Research,King Faisal University,Saudi Arabia,for supporting this work for work through grant number KFU242134.
文摘Coffee wilt represents one of the most devastating diseases of Arabica coffee(Coffea arabica L.)plantations in the primary coffee-producing regions.In this study,coffee trees manifesting wilt symptoms accompanied by the defoliation and drying of the whole tree were observed in the Jazan,El Baha,Najran,and Asir regions.The purpose of this investigation was to isolate and identify the Fusarium species recovered from symptomatic coffee trees.The developed fungi were initially characterized based on their morphological features followed by molecular phylogenetic multi-locus analysis of the combined sequences of ITS,TEF1-α,RPB2,and CaM.Twenty-five isolates were recovered from 28 samples.All fungal isolates were categorized morphologically under the genus Fusarium.Phylogenetic analysis positioned all the representative 15 isolates into one cluster grouping together with Neocosmospora falciformis(formerly F.falciforme)confirming their taxonomic position.Pathogenicity tests of the N.falciformis isolates were subsequently conducted on coffee seedlings,and the results revealed that all isolates induced wilt symptoms resembling those recorded in the field,and the incidence was 100%.The fungicide sensitivity test of seven investigated fungicides revealed that Maxim XL^(®) followed by Moncut^(®) exhibited the highest inhibitory effect against N.falciformis KSA 24-14,reaching 93.33%and 91.67%,respectively.To our knowledge,N.falciformis is a new causal pathogen of coffee wilt in Saudi Arabia.Remarkably,these results offer important insights for devising effective approaches to monitor and control such diseases.
