RESUMO
Evidence for reciprocal comorbidity of schizophrenia (SCZ) and body mass index (BMI) has grown in recent years. However, little is known regarding the shared genetic architecture or causality underlying the phenotypic association between SCZ and BMI. Leveraging summary statistics from the hitherto largest genome-wide association study (GWAS) on each trait, we investigated the genetic overlap and causal associations of SCZ with BMI. Our study demonstrated a genetic correlation between SCZ and BMI, and the correlation was more evident in local genomic regions. The cross-trait meta-analysis identified 27 significant SNPs shared between SCZ and BMI, most of which had the same direction of influence on both diseases. Mendelian randomization analysis showed the causal association of SCZ with BMI, but not vice versa. Combining the gene expression information, we found that the genetic correlation between SCZ and BMI is enriched in six regions of brain, led by the brain frontal cortex. Additionally, 34 functional genes and 18 specific cell types were found to have an impact on both SCZ and BMI within these regions. Taken together, our comprehensive genome-wide cross-trait analysis suggests a shared genetic basis including pleiotropic loci, tissue enrichment, and shared function genes between SCZ and BMI. This work provides novel insights into the intrinsic genetic overlap of SCZ and BMI, and highlights new opportunities and avenues for future investigation.
Assuntos
Esquizofrenia , Humanos , Esquizofrenia/genética , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Encéfalo , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Predisposição Genética para Doença/genéticaRESUMO
To investigate whether high cognitive task load (CTL) for aircraft pilots can be identified by analysing heart-rate variability, electrocardiograms were recorded while cadet pilots (n = 68) performed the plane tracking, anti-gravity pedalling, and reaction tasks during simulated flight missions. Data for standard electrocardiogram parameters were extracted from the R-R-interval series. In the research phase, low frequency power (LF), high frequency power (HF), normalised HF, and LF/HF differed significantly between high and low CTL conditions (p < .05 for all). A principal component analysis identified three components contributing 90.62% of cumulative heart-rate variance. These principal components were incorporated into a composite index. Validation in a separate group of cadet pilots (n = 139) under similar conditions showed that the index value significantly increased with increasing CTL (p < .05). The heart-rate variability index can be used to objectively identify high CTL flight conditions.Practitioner summary: We used principal component analysis of electrocardiogram data to construct a composite index for identifying high cognitive task load in pilots during simulated flight. We validated the index in a separate group of pilots under similar conditions. The index can be used to improve cadet training and flight safety.Abbreviations: ANOVA: a one-way analysis of variance; AP: anti-gravity pedaling task; CTL: cognitive task load; ECG: electrocardiograms; HR: heart rate; HRV: heart-rate variability; HRVI: heart-rate variability index; PT: plane-tracking task; RMSSD: root-mean square of differences between consecutive R-R intervals; RT: reaction task; SDNN: standard deviation of R-R intervals; HF: high frequency power; HFnu: normalized HF; LF: low frequency power; LFnu: normalized LF; PCA: principal component analysis.
Assuntos
Cognição , Eletrocardiografia , Humanos , Frequência Cardíaca/fisiologia , Análise de Componente PrincipalRESUMO
In the soil, plant roots associated with fungi often encounter uneven distribution of nitrate (NO3- )/ammonium (NH4+ ) patches, but the mechanism underlying N form-influenced plant-fungal interactions remains limited. We inoculated Arabidopsis with a root endophyte Phomopsis liquidambaris, and evaluated the effects of P. liquidambaris on plant performance under NO3- or NH4+ nutrition. Under NO3- nutrition, P. liquidambaris inoculation promoted seedling growth, whereas under NH4+ nutrition, P. liquidambaris suppressed seedling growth. Under high NH4+ conditions, fungus-colonized roots displayed increased NH4+ accumulation and NH4+ efflux, similar to the effect of ammonium stress caused by elevated NH4+ levels. Notably, this fungus excluded NH4+ during interactions with host roots, thereby leading to increased NH4+ levels at the plant-fungal interface under high NH4+ conditions. A nitrite reductase-deficient strain that excludes NO3- but absorbs NH4+ , decreased NH4+ levels in Arabidopsis shoots and rescued plant growth and nitrogen metabolism under high NH4+ levels. Transcriptomic analysis highlighted that P. liquidambaris had altered transcriptional responses associated with plant response to inorganic N forms. Our results demonstrate that fungus-regulated NO3- /NH4+ dynamics at the plant-fungal interface alters plant response to NO3- /NH4+ nutrition. This study highlights the essential functions of root endophytes in plant adaptation to soil nitrogen nutrients.
Assuntos
Compostos de Amônio , Arabidopsis , Compostos de Amônio/metabolismo , Arabidopsis/metabolismo , Endófitos/metabolismo , Fungos , Nitratos/metabolismo , Nitrogênio/metabolismo , Raízes de Plantas/metabolismo , SoloRESUMO
AIMS: This study evaluated the control effect of the endophytic fungus Phomopsis liquidambaris B3 against rice bakanae disease (RBD) caused by Fusarium proliferatum and the disease control result of different inoculation times of beneficial micro-organisms. METHODS AND RESULTS: Rice seedlings preinoculated, coinoculated and noninoculated with B3 were exposed to F. proliferatum stress and grown under controlled conditions. Greenhouse experimental results showed that rice preinoculation with B3 significantly reduced rice bakanae disease by 21.45%, inhibited the colonization of F. proliferatum, increased defence-related enzyme activities, upregulated the expression of defence genes and promoted plant photosynthesis. However, bakanae disease in rice coinoculation with B3 increased by 11.45%, resulted in excessive reactive oxygen species (ROS) bursts and plant cell death. CONCLUSIONS: Preinoculation with the endophytic fungus P. liquidambaris B3 significantly reduced rice bakanae disease by triggering the SA-dependent defence pathways of plants, and promoted plant growth. However, coinoculatiton with P. liquidambaris B3 activated excessive defence responses, resulting in plants cell death and aggravation of bakanae disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicated that P. liquidambaris B3 was an effective method for agricultural control against rice bakanae disease caused by F. proliferatum, and provides an experimental basis for the development of sustainable endophytic fungal resources to effectively control plant diseases caused by pathogenic fungi, and suggests that precise application of beneficial micro-organisms may be become a key factor in farmland crop disease management.
Assuntos
Ascomicetos , Fusarium , Micoses , Oryza , Ascomicetos/genética , Fusarium/metabolismo , Oryza/microbiologiaRESUMO
BACKGROUND: Rice spikelet rot disease (RSRD) is an emerging disease that significantly reduces rice yield and quality. In this study, we evaluated the potential use of the broad-spectrum endophytic fungus Phomopsis liquidambaris B3 as a biocontrol agent against RSRD. We also compared the control effects of different treatments, including chemical fungicides and treatment with multiple strains and single strains in combination or individually, against RSRD. The objective of this study was to find an effective and environmentally friendly control strategy to reduce the occurrence of RSRD and improve the rice yield. RESULTS: In pot experiments, the effect of B3 alone was better than that of fungicide or combined measures. The results showed that root colonization by B3 significantly reduced the incidence and disease index of RSRD by 41.0% and 53.8%, respectively. This was related to enhanced superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activity, and to significantly upregulated expression levels of OsAOX, OsLOX, OsPAL, and OsPR10 in rice. Moreover, B3 improved the diversity of the bacterial community rather than the fungal community in the rice rhizosphere. It also led to a decrease in Fusarium proliferatum colonization and fumonisin content in the grain. Finally, root development was markedly promoted after B3 inoculation, and the yield improved by 48.60%. The result of field experiments showed that the incidence of RSRD and the fumonisin content were observably reduced in rice receiving B3, by 24.41% and 37.87%, respectively. CONCLUSION: The endophytic fungus Phomopsis liquidambaris B3 may become an effective tool to relieve rice spikelet rot disease. © 2020 Society of Chemical Industry.
Assuntos
Endófitos/fisiologia , Fusarium/fisiologia , Oryza/crescimento & desenvolvimento , Phomopsis/fisiologia , Doenças das Plantas/imunologia , Catecol Oxidase/genética , Catecol Oxidase/imunologia , Resistência à Doença , Fumonisinas/metabolismo , Oryza/genética , Oryza/imunologia , Oryza/microbiologia , Peroxidase/genética , Peroxidase/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Raízes de Plantas/genética , Raízes de Plantas/imunologia , Raízes de Plantas/microbiologia , Superóxido Dismutase/genética , Superóxido Dismutase/imunologiaRESUMO
The role of flowering in root-fungal symbiosis is not well understood. Because flowering and fungal symbionts are supported by carbohydrates, we hypothesized that flowering modulates root-beneficial fungal associations through alterations in carbohydrate metabolism and transport. We monitored fungal colonization and soluble sugars in the roots of Arabidopsis thaliana following inoculation with a mutualistic fungus Phomopsis liquidambari across different plant developmental stages. Jasmonate signalling of wild-type plants, sugar transport, and root invertase of wild-type and jasmonate-insensitive plants were exploited to assess whether and how jasmonate-dependent sugar dynamics are involved in flowering-mediated fungal colonization alterations. We found that flowering restricts root-fungal colonization and activates root jasmonate signalling upon fungal inoculation. Jasmonates reduce the constitutive and fungus-induced accumulation of root glucose and fructose at the flowering stage. Further experiments with sugar transport and metabolism mutant lines revealed that root glucose and fructose positively influence fungal colonization. Diurnal, jasmonate-dependent inhibitions of sugar transport and soluble invertase activity were identified as likely mechanisms for flowering-mediated root sugar depletion upon fungal inoculation. Collectively, our results reveal that flowering drives root-fungus cooperation loss, which is related to jasmonate-dependent root soluble sugar depletion. Limiting the spread of root-fungal colonization may direct more resources to flower development.
Assuntos
Ascomicetos/fisiologia , Ciclopentanos/metabolismo , Flores/fisiologia , Oxilipinas/metabolismo , Raízes de Plantas/microbiologia , Açúcares/metabolismo , Simbiose/fisiologia , Arabidopsis/microbiologia , Ascomicetos/crescimento & desenvolvimento , Transporte Biológico , Ritmo Circadiano/fisiologia , Frutose/metabolismo , Glucose/metabolismo , Floema/metabolismo , Raízes de Plantas/enzimologia , Transdução de Sinais , Solubilidade , beta-Frutofuranosidase/metabolismoRESUMO
A triplicate volcanic rock matrix-Bacillus thuringiensis-laccase WlacD (VRMs-Bt-WlacD) dye decolorization system was developed. WlacD was displayed on the B. thuringiensis MB174 cell surface to prepare a whole-cell laccase biocatalyst by using two repeat N-terminal domains of autolysin Mbg (Mbgn)2 as the anchoring motif. Immunofluorescence microscopic assays confirmed that the fusion protein (Mbgn)2-WlacD was anchored on the surface of the recombinant B. thuringiensis MB174. After optimization by a single factor test, L 9(34)-orthogonal test, Plackett-Burman test, steepest ascent method, and Box-Behnken response surface methodology, the whole-cell specific laccase activity of B. thuringiensis MB174 was improved to 555.2 U L-1, which was 2.25 times than that of the primary culture condition. Optimized B. thuringiensis MB174 cells were further adsorbed by VRMs to prepare VRMs-Bt-WlacD, an immobilized whole-cell laccase biocatalyst. Decolorization capacity of as-prepared VRMs-Bt-WlacD toward an initial concentration of 500 mg L-1 of an textile dye reactive blue 19 (RB19) aqueous solution reached 72.36% at a solid-to-liquid ratio of 10 g-100 mL. Repeated decolorization-activation operations showed the high decolorization capacity of VRMs-Bt-WlacD and have the potential for large-scale or continuous operations.
Assuntos
Antraquinonas/química , Bacillus thuringiensis/enzimologia , Células Imobilizadas/enzimologia , Corantes/metabolismo , Lacase/metabolismo , Têxteis , Bacillus thuringiensis/genética , Bacillus thuringiensis/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Reatores Biológicos , Células Imobilizadas/microbiologia , Corantes/síntese química , Ensaios Enzimáticos , Enzimas Imobilizadas/genética , Enzimas Imobilizadas/metabolismo , Fermentação , Expressão Gênica , Genes Bacterianos , Lacase/genética , Microscopia Eletrônica de Varredura , Proteínas Recombinantes/metabolismo , Propriedades de Superfície , Indústria TêxtilRESUMO
An avian infectious bronchitis virus (IBV) was isolated and identified from a commercial layer flock vaccinated with live attenuated H120 vaccine in China, designed as ck/CH/IBTZ/2012. To determine the origination and evolution of this isolated strain, we have carried out a complete genome sequencing of this strain. The genome of the ck/CH/IBTZ/2012 strain is 27,691 nucleotides in length and includes more than 10 open reading frames. Sequence comparison and phylogenetic analysis based on the full-length genomic sequences showed that ck/CH/IBTZ/2012 is mostly related to the LX4-like strains. However, sequence analysis based on the spike protein (S) gene sequences revealed that ck/CH/IBTZ/2012 possesses a distinct S gene setting it apart from the Massachusetts-type strains and LX4-type strains. The cleavage site within the spike protein (S) of ck/CH/IBTZ/2012 is HRRKR, which is different from the majority of the IBVs in China for their cleavage sits are HRRRR. Recombination analysis showed that ck/CH/IBTZ/2012 is a chimeric virus with a LX4-like backbone except S gene which might be from an unknown strain. Based on the data presented in this paper, it can be concluded that genetic changes due to adaptive evolution and recombination both contributed to the origin of strain ck/CH/IBTZ/2012, which belongs to a new genotype.
Assuntos
Genoma Viral , Vírus da Bronquite Infecciosa/genética , RNA Viral/genética , Análise de Sequência de DNA , Glicoproteína da Espícula de Coronavírus/genética , Animais , Galinhas , China , Análise por Conglomerados , Vírus da Bronquite Infecciosa/isolamento & purificação , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Recombinação Genética , Homologia de SequênciaRESUMO
INTRODUCTION: Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence. AREAS COVERED: Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety. EXPERT OPINION: Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.
Assuntos
Antibacterianos , Infecções por Clostridium , Doenças Inflamatórias Intestinais , Probióticos , Humanos , Infecções por Clostridium/terapia , Infecções por Clostridium/microbiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/microbiologia , Probióticos/administração & dosagem , Antibacterianos/administração & dosagem , Fatores de Risco , Transplante de Microbiota Fecal , Clostridioides difficile/isolamento & purificação , Microbioma Gastrointestinal , Prebióticos/administração & dosagem , Coinfecção , Imunoterapia/métodos , Criança , Prevalência , Índice de Gravidade de Doença , Fatores Etários , IdosoRESUMO
Infectious bronchitis virus (IBV) restricts cell tropism. Except for the Beaudette strain, other IBVs cannot infect mammalian cell lines. The limited cell tropism of other IBVs has hindered IBV vaccine development and research on the mechanisms of IBV infection. A novel Vero cell-adapted strain, HV80, has been previously reported. In this study, we constructed recombinants expressing the chimeric S glycoprotein, S1 or S2 subunit of strain H120 and demonstrated that mutations on S2 subunit are associated with the strain HV80 Vero cell adaptation. R687P or P687R substitution recombinants were constructed with the genome backbone of strains HV80 or H120. We found that the RRRR690/S motif at the S2' cleavage site is crucial to the Vero cell adaptation of strain HV80. Another six amino acid substitutions in the S2 subunit of the recombinants showed that the Q855H mutation induced syncytium formation. A transient transfection assay demonstrated the S glycoprotein with the PRRR690/S motif at the S2' cleavage site induced low-level cell-cell fusion, while H855Q substitution hindered cell-cell fusion and blocked cleavage event with S20 product. This study provides a basis for the construction of IBV recombinants capable of replicating in Vero cells, thus contributing to the advancement in the development of genetically engineered cell-based IBV vaccines.
Assuntos
Vírus da Bronquite Infecciosa , Mutação , Tropismo Viral , Animais , Vírus da Bronquite Infecciosa/genética , Vírus da Bronquite Infecciosa/fisiologia , Chlorocebus aethiops , Células Vero , Glicoproteína da Espícula de Coronavírus/genética , Substituição de Aminoácidos , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterináriaRESUMO
Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC-derived extracellular vesicles (MSCs-EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs-EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs-EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs-EVs in cancer treatment, along with the challenges they face.
RESUMO
Campylobacter is a major cause of bacterial foodborne diarrhea worldwide. Consumption of raw or undercooked chicken meat contaminated with Campylobacter is the most common causative agent of human infections. Given the high prevalence of contamination in poultry meat and the recent rise of multi-drug-resistant (MDR) Campylobacter strains, an effective intervention method of reducing bird colonization is needed. In this study, the Campylobacter-specific lytic phage CP6 was isolated from chicken feces. Phage CP6 exhibited a broad host range against different MDR Campylobacter isolates (97.4% of strains were infected). Some biological characteristics were observed, such as a good pH (3-9) stability and moderate temperature tolerance (<50 â). The complete genome sequence revealed a linear double-stranded DNA (178,350 bp, group II Campylobacter phage) with 27.51% GC content, including 209 predicted open reading frames, among which only 54 were annotated with known functions. Phylogenetic analysis of the phage major capsid protein demonstrated that phage CP6 was closely related to Campylobacter phage CPt10, CP21, CP20, IBB35, and CP220. CP6 phage exerted good antimicrobial effects on MDR Campylobacter in vitro culture and reduced CFUs of the host cells by up to 1-log compared with the control in artificially contaminated chicken breast meat. Our findings suggested the potential of CP6 phage as a promising antimicrobial agent for combating MDR Campylobacter in food processing.
Assuntos
Bacteriófagos , Infecções por Campylobacter , Campylobacter jejuni , Campylobacter , Humanos , Animais , Aves Domésticas/microbiologia , Galinhas/microbiologia , Filogenia , Carne/microbiologia , Infecções por Campylobacter/microbiologia , Infecções por Campylobacter/veterinária , Antibacterianos/farmacologia , Microbiologia de AlimentosRESUMO
Infectious bronchitis virus (IBV) has restricted cell and tissue tropism. IBVs, except the Beaudette strain, can infect and replicate in chicken embryos, primary chicken embryo kidneys, and primary chicken kidney cells, only. The limited viral cell tropism of IBV substantially hinders in vitro cell-based research on pathogenic mechanisms and vaccine development. Herein, the parental H120 vaccine strain was serially passaged for five generations in chicken embryos, 20 passages in CK cells and 80 passages in Vero cells. This passaging yielded a Vero cell-adapted strain designated HV80. To further understand viral evolution, serial assessments of infection, replication, and transmission in Vero cells were performed for the viruses obtained every tenth passage. The ability to form syncytia and the replication efficiency significantly after the 50th passage (strain HV50). HV80 also displayed tropism extension to DF-1, BHK-21, HEK-293 T, and HeLa cells. Whole genome sequencing of viruses from every tenth generation revealed a total of 19 amino acid point mutations in the viral genome by passage 80, nine of which occurred in the S gene. The second furin cleavage site appeared in viral evolution and may be associated with cell tropism extension of HV80.
Assuntos
Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Vacinas Virais , Chlorocebus aethiops , Embrião de Galinha , Animais , Humanos , Células Vero , Vírus da Bronquite Infecciosa/genética , Células HeLa , Células HEK293 , Galinhas , Infecções por Coronavirus/veterináriaRESUMO
Background: There is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA. Methods: Using public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR). Results: We found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA. Conclusions: Our investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions.
Assuntos
Artrite Reumatoide , Hipotireoidismo , Humanos , Estudo de Associação Genômica Ampla , Teorema de Bayes , Artrite Reumatoide/genética , Transcriptoma , Hipotireoidismo/genética , Hipotireoidismo/complicaçõesRESUMO
In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.
Assuntos
Inteligência Artificial , Mpox , Humanos , Mpox/tratamento farmacológico , Mpox/epidemiologia , Mpox/prevenção & controle , Anticorpos , Surtos de Doenças , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
AmpC ß-lactamase genes are clinically important because they often confer resistance to most ß-lactams other than 4th-generation cephalosporins and carbapenems. However, traditional and existing detection methods are expensive, labor-intensive and range-limited. We established an efficient multiplex PCR method to simultaneously identify six families of ampC ß-lactamase genes, ACC, EBC, CIT, DHA, MOX and FOX, and evaluated the sensitivity and specificity of this assay. The multiplex method could accurately identify ACC, EBC, CIT, DHA, MOX and FOX variants among a total of 175 ampC ß-lactamase genes. The minimum concentration of genomic DNA that could be detected was 1.0×103 copies/µL. We subsequently used this method to analyze 2 Salmonella spp. with carrying CMY-2 and DHA-1, and 167 Enterobacteriaceae isolates in blinded PCR testing. Positive isolates produced bright bands that corresponded with their genotype. Results were in concordance with those of the traditional method but showed increased sensitivity and accuracy. This indicates that the newly developed multiplex PCR system could be used as a diagnostic tool to accurately distinguish the six families of ampC ß-lactamase genes with high efficiency, wide range, easy operation and good discrimination.
RESUMO
The complex environments of plants force them to prioritize their immune responses to stimuli occurring simultaneously, including colonization by microbes or nutrient availability. Little is known about how the interplay between endophytes and nutrient status affects the immune responses of both plants and fungi. We primarily monitored immune responses in rice following inoculation with the endophytic fungus Phomopsis liquidambaris under different nitrogen (N) conditions. Ph. liquidambaris promoted plant growth under low N (LN) conditions, concomitant with higher root colonization. Plant production of oxidative signals, including hydrogen peroxide and nitric oxide, was activated by Ph. liquidambaris colonization under LN conditions, while salicylic acid (SA) was maintained at high levels and was involved in controlling rice-fungal interactions. High N (HN) conditions enhanced the ability of Ph. liquidambaris in suppressing plant cell death and the ability of roots to degrade Ph. liquidambaris cell walls. Furthermore, under both LN and HN conditions, the activity of plant defence-associated enzymes and fungal antioxidases was not affected in the interactive association. Our data reveal the alteration of plant immunity, including oxidative signalling and plant cell death, by fungal colonization in response to external N conditions and identify SA signalling as a potential controller for rice-Ph. liquidambaris interaction.
Assuntos
Ascomicetos , Oryza , Ascomicetos/metabolismo , Endófitos/metabolismo , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Nitrogênio/metabolismo , Imunidade Vegetal , Raízes de Plantas/microbiologia , Plantas/metabolismo , Ácido Salicílico/metabolismoRESUMO
Loop-mediated isothermal amplification (LAMP) was designed for detection of Listeria monocytogenes, which is an important food-borne kind of pathogenic bacteria causing human and animal disease. The primers set for the hlyA gene consist of six primers targeting eight regions on specific gene. The LAMP assay could be performed within 40 min at 65°C in a water bath. Amplification products were visualized by calcein and manganous ion and agarose gel electrophoresis. Sensitivity of the LAMP assay for detection of L. monocytogenes in pure cultures was 2.0 CFU per reaction. The LAMP assay was 100-fold higher sensitive than that of the conventional PCR assay. Taking this way, 60 chicken samples were investigated for L. monocytogenes. The accuracy of LAMP was shown to be 100% when compared to the "gold standard" culture-biotechnical, while the PCR assay failed to detect L. monocytogenes in two of the positive samples. It is shown that LAMP assay can be used as a sensitive, rapid, and simple detection tool for the detection of L. monocytogenes and will facilitate the surveillance for contamination of L. monocytogenes in food.
Assuntos
Toxinas Bacterianas/genética , Microbiologia de Alimentos , Proteínas de Choque Térmico/genética , Proteínas Hemolisinas/genética , Listeria monocytogenes/isolamento & purificação , Carne/microbiologia , Animais , Galinhas , DNA Bacteriano/análise , Listeria monocytogenes/genética , Listeriose/prevenção & controle , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e EspecificidadeRESUMO
Campylobacter is a major food-borne pathogen in humans, and previous studies reported a high prevalence of gentamicin-resistant Campylobacter isolates from food-producing animals in China. This study aimed to investigate the aminoglycoside resistance of Campylobacter isolated from chicken and swine in Jiangsu province, China and understand the possible mechanisms responsible for aminoglycoside resistance. One hundred and eighty-five Campylobacter isolates of chicken and swine origins in 2017 and 2018 were analyzed for gentamicin and kanamycin resistance. Some aminoglycoside resistance genes were selected for PCR detection in all strains. The genomic DNAs of two strains with high resistance to gentamicin were used as donors to subject C. jejuni NCTC11168 to natural transformation. The transformants were investigated by whole-genome sequencing and analyzed comparatively with C. jejuni NCTC11168. In total, 30.5% (29/95) of C. jejuni isolates and 42.2% (38/90) of C. coli isolates were resistant to gentamicin and kanamycin. The prevalence of the aph(2")-If gene and aac(6')-Ie/aph(2")-Ia gene was 65.4% (121/185) and 36.2% (67/185) in Campylobacter isolates, respectively. The aadE-sat4-aphA-3 cluster was identified in 8.7% (8/92) and 20.4% (19/93) of all Campylobacter isolates in each year. With each donor DNA, aminoglycoside-resistant transformants were obtained. The transformants showed ≥128-fold increases in the MICs of gentamicin, kanamycin, and tobramycin. A 5200-bp segment was found to be inserted between the highly conserved genes Cj0299 and panB of Campylobacter. A total of 9.7% (18/185) strains showing high resistance to aminoglycosides had this segment by PCR detection. The genetic diversity of the insertion-fragment positive strains was determined by MLST, and seven sequence types were identified for these strains.
RESUMO
In agroecosystems, drought stress severely threatens crops development. Although potassium (K) is required in amounts by crops under drought stress, the mobilization and availablity of K are limited by the soil water status. Arbuscular mycorrhizal (AM) fungi can form mutualistic associations with most crops and play direct or indirect roles in the host drought resistance. Considering that the glomalin generated by living AM fungal hyphae can sequester multiple minerals, however, the function of mineral-sequestering glomalin in the crop drought resistance remains unclear. In this study, peanuts cultivated in the sterilized soil with a history of AM fungi inoculation showed significantly enhanced leaf K accumulation, drought resistance and pod yield under drought stress. Through the collection of different types of mineral-sequestering glomalin from living AM fungal hyphae, the peanut drought resistance was improved only when K-sequestering glomalin was added. Moreover, we found that peanut root exudates could prime the dissociation of glomalin-bound K and further satisfy the K requirement of crops. Our study is the first report that K-sequestering glomalin could improve drought performance and peanut pod yield, and it helps us to understand the ecological importance of improving AM symbiosis to face agricultural challenges.