Cytogenetic Analysis of a Patient with Turner Syndrome (45,X/47,XXX/48,XXXX/46,XX).

BACKGROUND: Turner syndrome (TS) is a female genetic disorder. Most patients with TS have a 45,X haplotype, but a small proportion have low nonholic chimerism. We here report a rare case of chimeric Turner syndrome in an individual with no phenotype aside from difficulties in conception, which may have been due to TS-associated decreased ovarian function. METHODS: A 41-year-old female presented with no family history of TS, normal facial build, normal intelligence, and no other common clinical features of TS. The patient experienced spontaneous puberty, regular menstruation of a normal volume, bilateral fallopian tube blockage, and multiple cervical cysts. RESULTS: Karyotype analysis showed 45,X/47,XXX/46,XX cells, whereas fluorescence in situ hybridization also revealed the presence of 48,XXX cells. CONCLUSIONS: There is growing evidence that ovarian function declines with age among those with chimeric TS, reducing their chances of conception. Fluorescence in situ hybridization should be recommended among those with difficulties conceiving to detect those with atypical chimeric TS, who may experience ovarian failure at an early age, to enable timely fertility interventions.

Self-limiting multimerization of α-synuclein on membrane and its implication in Parkinson's diseases.

α-Synuclein (α-syn), a crucial molecule in Parkinson's disease (PD), is known for its interaction with lipid membranes, which facilitates vesicle trafficking and modulates its pathological aggregation. Deciphering the complexity of the membrane-binding behavior of α-syn is crucial to understand its functions and the pathology of PD. Here, we used single-molecule imaging to show that α-syn forms multimers on lipid membranes with huge intermultimer distances. The multimers are characterized by self-limiting growth, manifesting in concentration-dependent exchanges of monomers, which are fast at micromolar concentrations and almost stop at nanomolar concentrations. We further uncovered movement patterns of α-syn's occasional trapping on membranes, which may be attributed to sparse lipid packing defects. Mutations such as E46K and E35K may disrupt the limit on the growth, resulting in larger multimers and accelerated amyloid fibril formation. This work emphasizes sophisticated regulation of α-syn multimerization on membranes as a critical underlying factor in the PD pathology.

Predictive Value of CCQ and its Subdomains for Hospitalized Exacerbations in Chronic Obstructive Pulmonary Disease: A 3-Year Observational Prospective Study.

BACKGROUND: The prediction capacity of the Clinical COPD Questionnaire (CCQ) and its functional, symptom, and mental subdomain for COPD hospitalized exacerbation were rarely studied. OBJECTIVE: To examine the prognostic capacity of the total CCQ and its three subdomains for 3-year COPD hospitalized exacerbations. METHODS: We analyzed the predictive ability of total CCQ score and its subdomains for hospitalized exacerbations in an observational cohort of 987 subjects with stable COPD from the RealDTC, an ongoing multicenter prospective study. Hospitalized exacerbations were prospectively collected every 6 month for a maximum of 3 years. RESULTS: The total CCQ and its functional and symptom domain, but not the mental domain, were significantly associated with 3-year hospitalized exacerbations by multivariate Cox regression analysis. The predictive capacity of functional domain was similar to that of the total CCQ, but significantly stronger than the symptom and mental domain by ROC analysis (P < 0.05). ROC curves also showed that the AUC of exacerbation history combined with CCQ functional domain was larger than that of exacerbation history alone (P < 0.0001). Additionally, the predictive value of multivariable models that contains CCQ functional domain was significantly better than the corresponding model without CCQ functional domain (P < 0.05). CONCLUSIONS: The total CCQ and its functional and symptom domain were independent risk factors of 3-year hospitalized exacerbations. The prognostic capacity of the functional domain was similar to that of total CCQ, and was significantly stronger than the symptom and mental domain. The CCQ functional domain was able to increase the predictive power of exacerbation history and other multivariable prediction models, indicating it may have an important role in the multivariable prediction tool for hospitalized exacerbation, and its combination with other clinical variables might be used as a low-cost approach for assessments of the disease severity and severe exacerbation in COPD patients in the future.

PWWP3A deficiency accelerates testicular senescence in aged mice.

BACKGROUND: The PWWP domain-containing proteins are involved in chromatin-associated biological processes, including transcriptional regulation and DNA repair, and most of them are significant for gametogenesis and early embryonic development in mammals. PWWP3A, one of the PWWP domain proteins, is a reader of H3K36me2/H3K36me3 and a response factor to DNA damage. However, the physiological role of PWWP3A in spermatogenesis and fertility remains unclear. OBJECTIVE: The goal of this study was to explore the function and mechanism of PWWP3A in the process of spermatogenesis. MATERIALS AND METHODS: We generated V5-Pwwp3a KI mice and PWWP3A polyclonal antibody to observe the localization of PWWP3A in vivo. Meanwhile, Pwwp3a KO mice was used to explore the function in spermatogenesis. RESULTS: We reported that PWWP3A is a predominant expression in the testis of mice. During spermatogenesis, PWWP3A exhibits the temporal expression from early-pachytene to the round spermatids. The results of spermatocyte spreading and immunostaining showed that PWWP3A aggregated on the XY body, which then diffused as the XY chromosome separated at late-diplotene. Although the depletion of PWWP3A had no obvious reproductive defects in young male mice, there were observed morphological abnormalities in sperm heads. Immunoprecipitation demonstrated the interaction of PWWP3A with DNA repair proteins SMC5/6; however, PWWP3A deficiency did not result in any meiotic defects. Notably, the testes of aged male Pwwp3a KO mice displayed pronounced degeneration, and were characterized by the presence of vacuolated seminiferous tubules. Furthermore, RNA-seq analysis revealed an upregulation in the expression of genes which may be involving in immunoregulatory and inflammatory response pathways in aged Pwwp3a KO mice with testicular degeneration. CONCLUSIONS: Our study showed that PWWP3A was highly enriched in the mouse testis, and the Pwwp3a KO mice were fertile. However, the aged Pwwp3a KO male mice displayed testicular atrophy that may be due to changes in the immune micro-environment or abnormal repair of DNA damage.

Proactive employees perceive coworker ostracism: The moderating effect of team envy and the behavioral outcome of production deviance.

As the workplace becomes more team based, interpersonal relationships at work are a central topic that affects both employees and the organization. Despite ample evidence showing the detrimental effects of workplace ostracism on employees' health and productivity, why someone is ostracized by others at work warrants more research. Based on social comparison theory, we predict that task proactivity could be perceived negatively and can elicit ostracism from team members; this effect is dependent upon the boundary condition of team envy. Furthermore, perceived coworker ostracism explains why task proactivity may turn into production deviance. We tested these predictions based on data from 630 employees in 131 teams collected in various industries in China. The results showed that individual-level task proactivity positively predicted coworker ostracism perceived by the proactive employee, and this relationship was moderated by team envy. Task proactivity was indirectly and positively related to production deviance via perceived coworker ostracism, especially in teams with high levels of team envy. Based on these results, we suggest that proactive employees need to be aware of possible unexpected interpersonal consequences in the workplace, given that proactive work behaviors may elicit unwanted and unintended treatment from team members. Managers should monitor team contextual factors, which may affect the extent to which good soldiers turn into bad apples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dynamic changes, cycling and downward fate of dissolved carbon and nitrogen photosynthetically-derived from glaciers in Upper Indus River Basin.

Glaciers play key roles in capturing, storing, and transforming global carbon and nitrogen, thereby contributing markedly to their cycles. However, an integrated mechanistic approach is still lacking regarding glacier's primary producers (PP), in terms of stable dissolved inorganic carbon isotope (δ13C-DIC) and its relationship with dissolved carbon and nitrogen transformation dynamic changes/cycling. Here, we sampled waters from glaciers, streams, tributaries, and the Indus River (IR) mainstream in the Upper IR Basin, Western Himalaya. Dissolved organic matter (DOM) appears to increase, on average, by ∼2.5-23.4% with fluctuations when passing from glaciers to streams-tributaries-IR mainstream (the upper and lower parts, respectively) continuum, implying that DOM originates from glaciers PP and is subsequently degraded. The corresponding fluctuations are observed for fluorescent DOM (FDOM), dissolved organic nitrogen (8.0‒106.8%), NO3‒-N (‒13.5/+16.6%), NH4+-N (‒8.8/+13.0%), and NO2‒-N (70.7-217.5%). These variations are associated with overall DOM/FDOM transformations, with the production of ending byproducts (e.g. CO2/DIC). The δ13C-DIC values fluctuated from glaciers (-5.3±2.5‰) to streams (-4.4±2.1‰), tributaries (-4.3±1.6‰), and IR mainstream (-4.2±1.3‰). The δ13C-DIC data are consistent with C transformations that involve lighter CO2 emission into the atmosphere, whereas highly depleted DIC/CO2 is the signature of DOM degradation after its fresh production from glaciers PP which originated by photosynthetic activities (e.g. uptake/sink of atmospheric CO2: ‒8.4‰). Finally, glacier-fed meltwaters would simultaneously contribute to the biogeochemical characteristics of downward margins and specific ecosystems (lake/pond/groundwater/hot springs) via transformation dynamics/cycling of dissolved C and N with high photo/microbial lability. Our results highlight the substantial contribution of western Himalayan glaciers-derived DOM to the global C and N cycles.

Different charged biopolymers induce α-synuclein to form fibrils with distinct structures.

The aggregation of α-synuclein (α-syn) into amyloid fibrils, a key process in the development of Parkinson's disease (PD) and other synucleinopathies, is influenced by a range of factors such as charged biopolymers, chaperones, and metabolites. However, the specific impacts of different biopolymers on α-syn fibril structure are not well understood. In our work, we found that different polyanions and polycations, such as polyphosphate (polyP), polyuridine (polyU), and polyamines (including putrescine, spermidine, and spermine), markedly altered the fibrillation kinetics of α-syn in vitro. Furthermore, seeding assay revealed distinct cross-seeding capacities across different biopolymer-induced α-syn fibrils, suggesting the formation of structurally distinct strains under different conditions. Utilizing cryo-electron microscopy (cryo-EM), we further examined the detailed structural configuration of α-syn fibrils formed in the presence of these biopolymers. Notably, we found that while polyamines do not change the atomic structure of α-syn fibrils, polyU and polyP induce the formation of distinct amyloid fibrils, exhibiting a range of structural polymorphs. Our work offers valuable insights into how various charged biopolymers affect the aggregation process and the resultant structures of α-syn fibrils, thereby enhancing our understanding of the structural variations in α-syn fibrils across different pathological conditions.

Quantitative analysis of construction risks in shallowly buried biased tunnel portal section.

To address the prominent problem of collapse instability in shallow buried soft ground tunnels, a non-invasive stochastic finite element method was introduced. Taking Fujian Puyan Wenbishan tunnel as the background project, ABAQUS finite element software was used to analyze the tunnel excavation mechanics and parameter sensitivity. And developed the software interface program based on Python to output explicit limit state equation for the key mechanical indexes of the tunnel, so as to evaluate the tunnel reliability under different excavation methods, quantitatively. Study results show a significant improvement in efficiency and accuracy when calculating the probability of failure in tunnel excavation by the non-invasive stochastic finite element method. The maximum displacement monitoring points for the Wenbishan tunnel portal section were all vault settlement, with displacements of 33.6 mm, 30.2 mm, and 25.3 mm, respectively, using the annular retained core soil method, single sidewall guide pit and double sidewall guide pit method, with probabilities of failure of 36.11%, 28.03%, and 20.02%. It is found that the reliability of the tunnel is mainly determined by the geotechnical weight, elastic modulus and cohesion of the weak sandy soil layer, which can provide ideas for this type of engineering researches.

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.

BACKGROUND: The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. METHODS: Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. RESULTS: Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted ß were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). CONCLUSIONS: Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Association between nighttime sleep duration and quality with low back pain in middle-aged and older Chinese adults.

BACKGROUND: This study aims to investigate the association between sleep duration, sleep quality, and the risk of low back pain (LBP) among middle-aged and elderly individuals in China. METHODS: Utilizing data from the China Health and Retirement Longitudinal Study spanning 2011 to 2020, we categorized sleep duration into long, medium, and short categories, and sleep quality into good, fair, and poor levels. LBP status was determined based on self-reported information by participants. Multivariable logistic regression analysis was employed to assess the relationship between sleep duration, sleep quality, with the risk of LBP. RESULTS: A total of 6750 individuals were included in the longitudinal study. After 9 years of follow-up, the prevalence of LBP was 25.69 %. In the fully adjusted model, compared to individuals with medium sleep duration, those with short sleep duration had a 28 % increased risk of developing LBP (OR = 1.28, 95%CI: 1.12, 1.46). Additionally, when compared to individuals with good sleep quality, those with fair and poor sleep quality had a 35 % (OR = 1.35, 95%CI: 1.19, 1.54) and 33 % (OR = 1.33, 95%CI: 1.12, 1.58) increased risk of LBP, respectively. Joint analysis of both factors revealed that individuals with poor sleep quality and short sleep duration had the highest risk of LBP. CONCLUSION: Among middle-aged and elderly individuals in China, short sleep duration and poor sleep quality were associated with an increased risk of LBP. Future studies should further explore the mechanisms underlying this association and validate the findings through randomized controlled trials.

A subpellicular microtubule dynein transport machinery regulates ookinete morphogenesis for mosquito transmission of Plasmodium yoelii.

The cortical cytoskeleton of subpellicular microtubules (SPMTs) supports the Plasmodium ookinete morphogenesis during mosquito transmission of malaria. SPMTs are hypothesized to function as the cytoskeletal tracks in motor-driven cargo transport for apical organelle and structure assembly in ookinetes. However, the SPMT-based transport motor has not been identified in the Plasmodium. The cytoplasmic dynein is the motor moving towards the minus end of microtubules (MTs) and likely be responsible for cargo transport to the apical part in ookinetes. Here we screen 7 putative dynein heavy chain (DHC) proteins in the P. yoelii and identify DHC3 showing peripheral localization in ookinetes. DHC3 is localized at SPMTs throughout ookinete morphogenesis. We also identify five other dynein subunits localizing at SPMTs. DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection of Plasmodium. The DHC3-deficient ookinetes display defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, likely functioning as the receptors for the cargoes driven by SPMT-dynein. Disturbing Rab11A or Rab11B phenocopies DHC3 deficiency in ookinete morphogenesis. Our study reveals an SPMT-based dynein motor driving the transport of Rab11A- and Rab11B-labeled cargoes in the ookinete morphogenesis of Plasmodium.

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Effective microorganisms (EM) might alleviate deterioration of soil environmental quality and yield decline of pepper (Capsicum annuum) caused by continuous replanting and imbalanced fertilizer application in Xinjiang. We investigated the effects of applying EM microbial agent on the growth of pepper plants, yield, soil nutrient content, soil enzyme activity, and rhizosphere eukaryotic community. The results showed that the application of EM microbial agent increased plant height, stem diameter, leaf length, leaf width and root length by 22.6%, 35.3%, 33.3%, 29.7% and 15.1%, respectively. It also increased fruit width, individual fruit weight, and yield by 5.3%, 42.9%, and 74.7%, respectively. After the application of EM microbial agent, the levels of soil available nitrogen increased by 10.2% and 5.8% during the flowering and maturity stages, respectively. Similarly, available phosphorus increased by 10.4% and 13.4%, respectively. The soil sucrase activity was increased by 40.7%, 14.6%, and 9.3% during the seedling, flowering, and maturity stages, respectively. Urease activity was also increased by 7.9%, 10.2%, and 11.5%, respectively. Furthermore, the application of EM microbial agent increased soil peroxidase activity by 16.8% and 44.6% at flowering and maturity stages, respectively. The application of microbial agent significantly altered the ß-diversity of the rhizosphere eukaryotic community in pepper plants. Specifically, microbial agent increased the relative abundances of populations belonging to Enchytraeus and Sminthurides genera, which could contribute to soil improvement and nutrient cycling. Compared to the CK, the relative abundance of pathogenic microorganisms including Olpidium and Aplanochytrium genera decreased by 98.0% and 89.3%, and the relative abundance of the Verticillium decreased to 0. These results demonstrated that EM microbial agent could increase soil nutrient content, enhance soil enzyme activity, and reduce soil pathogenic fungi in the pepper cultivation areas of Xinjiang, thus achieving beneficial effects on pepper growth and fruit yield.

Intervention effect of exercise on working memory in patients with depression: a systematic review.

Background: This article aims to systematically evaluate the intervention effect of exercise on working memory in patients with depression. Methods: Six Chinese and English databases were searched for randomized controlled trials (RCTs) about exercise on working memory in patients with depression. PEDro scale was adopted to evaluate the methodological quality of the included articles, GRADEpro scale was employed to evaluate the level of evidence for outcomes, and the Metafor Package in R 4.4.1 was used to analyze the combined effect size, subgroup analyses and publication bias. Results: A total of 15 studies were included. The meta-analysis indicated that exercise had a statistically significant effect on working memory in patients with depression, with an effect size of 0.16 (95% CI [0.03-0.28], p = 0.02). Exercise type (F(3,34) = 1.99, p = 0.13), intervention content (F(1,36) = 1.60, p = 0.22), and exercise duration (F(1,36) = 0.05, p = 0.83) did not moderate the effect, whereas exercise intensity showed a moderating effect (F(2,35) = 8.83, p < 0.01). There was evidence of publication bias in the study results (t = 2.52, p = 0.02). Conclusion: Exercise can improve the working memory of patients with depression, and its moderating effect is the best when having low-intensity and moderate-intensity. Research plan was registered in international system evaluation platform PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) (CRD42023475325).

Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. METHODS: A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018-2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. RESULTS: A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January-April and October-December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P < 0.05). Furthermore, compared to the pre-COVID-19 group, the post-COVID-19 group displayed higher rates of SLRTI and mechanical ventilation, with a longer length of hospital stay (all P < 0.05). Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6 were the shared independent risk factors for RSV-related SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group. CONCLUSIONS: An off-season RSV endemic was observed in Yunnan during the post-COVID-19 era, with changed clinical features and increased severity. Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6, seizures, and co-infection were the risk factors for RSV-related SLRTI in the post-COVID-19 era.

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

BACKGROUND: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. METHODS: To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. RESULTS: MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10-6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, -0.041 to -0.015; P = 1.31 × 10-5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. CONCLUSION: Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

A naturaly attenuated largemouth bass ranavirus strain provided protection for Micropterus salmoides by immersion immunization.

Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.

Toll-Like Receptor 2 Deficiency Exacerbates Dextran Sodium Sulfate-Induced Intestinal Injury through Marinifilaceae-Dependent Attenuation of Cell Cycle Signaling.

BACKGROUND: Ulcerative colitis (UC) is an intestinal disorder marked by chronic, recurring inflammation, yet its underlying mechanisms have not been fully elucidated. METHODS: The current research dealt with examining the biological impacts of toll-like receptor 2 (TLR2) on dextran sulfate sodium (DSS)-triggered inflammation in the intestines of wild-type (WT) and TLR2-knockout (TLR2-KO) colitis mouse models. To elucidate the protective function of TLR2 in DSS-triggered colitis, RNA-sequencing (RNA-Seq) was carried out to compare the global gene expression data in the gut of WT and TLR2-KO mice. Further, 16S rRNA gene sequencing revealed notable variations in gut microbiota composition between WT and TLR2-KO colitis mice. RESULTS: It was revealed that TLR2-KO mice exhibited increased susceptibility to DSS-triggered colitis. RNA-Seq results demonstrated that cell cycle pathway-related genes were notably downregulated in TLR2-KO colitis mice (enrichment score = 30, p < 0.001). 16S rRNA gene sequencing revealed that in comparison to the WT colitis mice, the relative abundance of Marinifilacea (p = 0.006), Rikenellacea (p = 0.005), Desulfovibrionaceae (p = 0.045), Tannerellaceae (p = 0.038), Ruminococcaceae (p = 0.003), Clostridia (p = 0.027), and Mycoplasmataceae (p = 0.0009) was significantly increased at the family level in the gut of TLR2-KO colitis mice. In addition, microbiome diversity-transcriptome collaboration analysis highlighted that the relative abundance of Marinifilaceae was negatively linked to the expression of cell cycle signaling-related genes (p values were all less than 0.001). CONCLUSION: Based on these findings, we concluded that TLR2-KO exacerbates DSS-triggered intestinal injury by mitigating cell cycle signaling in a Marinifilaceae-dependent manner.

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

Characteristics of Endemic Mycoses Talaromyces marneffei Infection Associated with Inborn Errors of Immunity.

BACKGROUND: Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children. OBJECTIVE: We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies. METHODS: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected. RESULTS: Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals. CONCLUSIONS: The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes.

Enhanced Photocatalytic Hydrogen Evolution Activity Driven by the Synergy Between Surface Vacancies and Cocatalysts: Surface Reaction Matters.

The incorporation of defects and cocatalysts is known to be effective in improving photocatalytic activity, yet their coupled contribution to the photocatalytic hydrogen evolution process has not been well-explored. In this study, We demonstrate that the incorporation of S vacancies and NiSe can contribute to the improvement of charge separation efficiency via the formation of a strong electric field within the bulk ZnIn2S4 (ZIS) and on its surface. More importantly, We also demonstrate that the synergy of S vacancies and NiSe benefits the overall hydrogen evolution activity by facilitating the H2O adsorption and dissociation process. This is particularly important for hydrogen evolution taking place under alkaline conditions where the proton concentration is low, allowing ZISv-NiSe (containing abundant S vacancies) to outperform ZIS-NiSe under alkaline conditions. In contrast, under acid conditions, since there are already sufficient amounts of protons available for reaction, the hydrogen evolution activity became governed by the hydrogen adsorption/desorption process rather than the H2O dissociation process. This leads to ZIS-NiSe exhibiting higher activity than ZISv-NiSe due to its more favorable hydrogen adsorption energy. The findings thus provide insights into how defect and cocatalyst modification strategies can be tailor-made to improve hydrogen evolution activity under different pH conditions.