Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

A chromosome-scale genome of Rhus chinensis Mill. provides new insights into plant-insect interaction and gallotannins biosynthesis.

Rhus chinensis Mill., an economically valuable Anacardiaceae species, is parasitized by the galling aphid Schlechtendalia chinensis, resulting in the formation of the Chinese gallnut (CG). Here, we report a chromosomal-level genome assembly of R. chinensis, with a total size of 389.40 Mb and scaffold N50 of 23.02 Mb. Comparative genomic and transcriptome analysis revealed that the enhanced structure of CG and nutritional metabolism contribute to improving the adaptability of R. chinensis to S. chinensis by supporting CG and galling aphid growth. CG was observed to be abundant in hydrolysable tannins (HT), particularly gallotannin and its isomers. Tandem repeat clusters of dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) and serine carboxypeptidase-like (SCPL) and their homologs involved in HT production were determined as specific to HT-rich species. The functional differentiation of DQD/SDH tandem duplicate genes and the significant contraction in the phenylalanine ammonia-lyase (PAL) gene family contributed to the accumulation of gallic acid and HT while minimizing the production of shikimic acid, flavonoids, and condensed tannins in CG. Furthermore, we identified one UDP glucosyltransferase (UGT84A), three carboxylesterase (CXE), and six SCPL genes from conserved tandem repeat clusters that are involved in gallotannin biosynthesis and hydrolysis in CG. We then constructed a regulatory network of these genes based on co-expression and transcription factor motif analysis. Our findings provide a genomic resource for the exploration of the underlying mechanisms of plant-galling insect interaction and highlight the importance of the functional divergence of tandem duplicate genes in the accumulation of secondary metabolites.

Construction and validation of a SASP-related prognostic signature in patients with acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML.

Significance of Epitaxial Growth of PtO2 on Rutile TiO2 for Pt/TiO2 Catalysts.

TiO2-supported Pt species have been widely applied in numerous critical reactions involving photo-, thermo-, and electrochemical-catalysis for decades. Manipulation of the state of the Pt species in Pt/TiO2 catalysts is crucial for fine-tuning their catalytic performance. Here, we report an interesting discovery showing the epitaxial growth of PtO2 atomic layers on rutile TiO2, potentially allowing control of the states of active Pt species in Pt/TiO2 catalysts. The presence of PtO2 atomic layers could modulate the geometric configuration and electronic state of the Pt species under reduction conditions, resulting in a spread of the particle shape and obtaining a Pt/PtO2/TiO2 structure with more positive valence of Pt species. As a result, such a catalyst exhibits exceptional electrocatalytic activity and stability toward hydrogen evolution reaction, while also promoting the thermocatalytic CO oxidation, surpassing the performance of the Pt/TiO2 catalyst with no epitaxial structure. This novel epitaxial growth of the PtO2 structure on rutile TiO2 in Pt/TiO2 catalysts shows its potential in the rational design of highly active and economical catalysts toward diverse catalytic reactions.

Multivariate analysis compares and evaluates drought and flooding tolerances of maize germplasm.

Drought and flooding are the two most important environmental factors limiting maize (Zea mays L.) production globally. This study aimed to investigate the physiological mechanisms and accurate evaluation indicators and methods of maize germplasm involved in drought and flooding stresses. The twice replicated pot experiments with 60 varieties, combined with the field validation experiment with 3 varieties, were conducted under well-watered, drought, and flooding conditions. Most varieties exhibited stronger tolerance to drought than flooding due to higher antioxidant enzyme activities, osmotic adjustment substances, and lower reactive oxygen species. In contrast, flooding stress resulted in higher levels of reactive oxygen species (particularly O2-), ascorbate peroxidase, catalase, peroxidase, and soluble sugars but lower levels of superoxide dismutase, proline, and soluble protein compared with well-watered conditions. Superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, proline, soluble sugars, and protein contents, in addition to plant height, leaf area/plant, and stem diameter, were accurate and representative indicators for evaluating maize tolerance to drought and flooding stresses and could determine a relatively high mean forecast accuracy of 100.0% for the comprehensive evaluation value. A total of 4 principal components were extracted, in which different principal components played a vital role in resisting different water stresses. Finally, the accuracy of the 3 varieties screened by multivariate analysis was verified in the field. This study provides insights into the different physiological mechanisms and accurate evaluation methods of maize germplasm involved in drought and flooding stresses, which could be valuable for further research and breeding.

Exploring the pathogenicity of Mycoplasma pneumoniae: Focus on community-acquired respiratory distress syndrome toxins.

Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX) is a unique exotoxin produced by Mycoplasma pneumoniae (MP) and has been confirmed to possess ADP-ribosyltransferase (ART) and vacuolating activities. CARDS TX binds to receptors on the surfaces of mammalian cells followed by entry into the cells through clathrin-mediated endocytosis, and exerts cytotoxic effects by undergoing retrograde transport and finally cleavage on endosomes and cellular organelles. In addition, CARDS TX can trigger severe inflammatory reactions resulting in airway dysfunction, producing allergic inflammation and asthma-like conditions. As a newly discovered virulence factor of MP, CARDS TX has been extensively studied in recent years. As resistance to macrolide drugs has increased significantly in recent years and there is no vaccine against MP, the development of a vaccine targeting CARDS TX is considered a potential preventive measure. This review focuses on recent studies and insights into this toxin, providing directions for a better understanding of MP pathogenesis and treatment. IMPORTANCE: A serious hazard to worldwide public health in recent years, Mycoplasma pneumoniae (MP) is a prominent bacterium that causes community-acquired pneumonia (CAP) in hospitalized children. Due to their high prevalence and fatality rates, MP infections often cause both respiratory illnesses and extensive extrapulmonary symptoms. It has recently been shown that MP produces a distinct exotoxin known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). Mycoplasma pneumoniae pneumonia (MPP)-like tissue injury is caused by this toxin because it has both ADP-ribosyltransferase and vacuolating properties. A better knowledge of MP etiology and therapy is provided by this review, which focuses on latest research and insights into this toxin.

Associations of sleep disorders with serum neurofilament light chain levels in Parkinson's disease.

BACKGROUND: Sleep disorders are a prevalent non-motor symptom of Parkinson's disease (PD), although reliable biological markers are presently lacking. OBJECTIVES: To explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD. METHODS: The study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models. RESULTS: In baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors (ß = 0.033; P = 0.042) and movements of arms or legs during sleep (ß = 0.027; P = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep (ß = 0.038; P = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score (ß = 0.002; P = 0.011) or who were considered as probable RBD (ß = 0.012; P = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score (ß = 0.001; P = 0.012) or who were regarded to have EDS (ß = 0.013; P = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels. CONCLUSION: Sleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes.

Catalytic Hydrolysis-Oxidation of Halogenated Methanes over Phase- and Defect-Engineered CePO4: Halogenated Byproduct-Free and Stable Elimination.

Catalytic elimination of halogenated volatile organic compound (HVOC) emissions was still a huge challenge through conventional catalytic combustion technology, such as the formation of halogenated byproducts and the destruction of the catalyst structure; hence, more efficient catalysts or a new route was eagerly desired. In this work, crystal phase- and defect-engineered CePO4 was rationally designed and presented abundant acid sites, moderate redox ability, and superior thermal/chemical stability; the halogenated byproduct-free and stable elimination of HVOCs was achieved especially in the presence of H2O. Hexagonal and defective CePO4 with more structural H2O and Brønsted/Lewis acid sites was more reactive and durable compared with monoclinic CePO4. Based on the phase and defect engineering of CePO4, in situ diffuse reflectance infrared Fourier transform spectra (DRIFTS), and kinetic isotope effect experiments, a hydrolysis-oxidation pathway characterized by the direct involvement of H2O was proposed. Initiatively, an external electric field (5 mA) significantly accelerated the elimination of HVOCs and even 90% conversion of dichloromethane could be obtained at 170 °C over hexagonal CePO4. The structure-performance-dependent relationships of the engineered CePO4 contributed to the rational design of efficient catalysts for HVOC elimination, and this pioneering work on external electric field-assisted catalytic hydrolysis-oxidation established an innovative HVOC elimination route.

Reducing Indoor Particulate Air Pollution Improves Student Test Scores: A Randomized Double-Blind Crossover Study.

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.

Robust Ru/Ce@Co Catalyst with an Optimized Support Structure for Propane Oxidation.

Short carbon chain alkanes, as typical volatile organic compounds (VOCs), have molecular structural stability and low molecular polarity, leading to an enormous challenge in the catalytic oxidation of propane. Although Ru-based catalysts exhibit a surprisingly high activity for the catalytic oxidation of propane to CO2 and H2O, active RuOx species are partially oxidized and sintered during the oxidation reaction, leading to a decrease in catalytic activity and significantly inhibiting their application in industrial processes. Herein, the Ru/Ce@Co catalyst is synthesized with a specific structure, in which cerium dioxide is dispersed in a thin layer on the surface of Co3O4, and Ru nanoparticles fall preferentially on cerium oxide with high dispersity. Compared with the Ru/CeO2 and Ru/Co3O4 catalysts, the Ru/Ce@Co catalyst demonstrates excellent catalytic activity and stability for the oxidation of propane, even under severe operating conditions, such as recycling reaction, high space velocity, a certain degree of moisture, and high temperature. Benefiting from this particular structure, the Ru/Ce@Co (5:95) catalyst with more Ce3+ species leads to the Ru species being anchored more firmly on the CeO2 surface with a low-valent state and has a strong potential for adsorption and activation of propane and oxygen, which is beneficial for RuOx species with high activity and stability. This work provides a novel strategy for designing high-efficiency Ru-based catalysts for the catalytic combustion of short carbon alkanes.

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.

A sequencing electroreduction-electrooxidation system driven by atomic hydrogen for enhancing 2,4-dichloronitrobenzene removal from wastewater.

The sequencing electroreduction-electrooxidation process has emerged as a promising approach for the degradation of the chloronitrobenzenes (CNBs) due to its elimination of electro-withdrawing groups in the reduction process, facilitating further removal in the subsequent oxidation process. Herein, we developed a cathode consisting of atom Pd on a Ti plate, which enabled the electro-generation of atomic hydrogen (H*) and the efficient electrocatalytic activation of H2O2 to hydroxyl radical (•OH). Cyclic voltammetry (CV) curves and electron spin resonance (ESR) spectra verified the existence of H* and •OH. The electroreduction-electrooxidation system achieved 94.7% of 20 mg L-1 2,4-DCNB removal with a relatively low H2O2 addition (5 mM). Moreover, the inhibition rate of Photobacterium phosphoreum in the effluent decreased from 95% to 52% after the sequencing electroreduction-electrooxidation processes. It was further revealed that the H* dominated the electroreduction process and triggered the electrooxidation process. Our work sheds light on the effective removal of electron-withdrawing groups substituted aromatic contaminants from water and wastewater.

Genetic Variability and Evolutionary Dynamics of Papaya Ringspot Virus and Papaya Leaf Distortion Mosaic Virus Infecting Feral Papaya in Hainan Island.

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence (P=0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Associations between abnormal sleep behavior and indoor environmental risk factors among children with a chronic cough in Wuxi, China: a cross-sectional study.

BACKGROUND: Indoor environmental factors, such as pet ownership, presence of cockroaches, mattress quality, fuel usage (gas or electricity), use of biomass for cooking and heating, exposure to tobacco smoke or household molds can significantly affect the sleep quality of children with chronic cough. However, data regarding the effects of indoor environmental conditions on sleep in this population are limited. This study aimed to assess the prevalence of abnormal sleep behaviors and to establish associations between indoor environmental factors and sleep behaviors among children with chronic cough in Wuxi, China. METHODS: A cross-sectional design was employed in this study, involving children aged 3-18 years. Data on sociodemographic factors, allergies, home environmental exposures, and sleep characteristics of the participants were collected using paper-based questionnaires. The association between indoor environmental factors and sleep behaviors in children with chronic cough was analyzed using logistic regression models. RESULTS: The findings demonstrated that the prevalence of chronic cough among children in Wuxi was 15.50%. The chronic cough group exhibited a significantly higher incidence of eczema, wheezing, rhinitis, food allergy, and nasosinusitis than the non-chronic cough group. In addition, children with chronic cough also tended to have a family history of sleep disorders and adenoid hypertrophy (P < 0.01). After adjusting for confounding factors, a significant association was observed between bruxism (teeth grinding) and chronic cough (sometimes: odds ratio [OR] = 1.04; confidence interval [CI] = 1.01-1.08; always: OR = 1.11; CI = 1.04-1.19; P < 0.01). Among children with chronic cough, recent home decoration was associated with sleepwalking (OR = 1.04; CI = 1.00-1.07; P < 0.05), mold exposure was associated with bruxism (OR = 1.15; CI = 1.0-1.31; P < 0.05), and carpet use at home was associated with apnea (OR = 1.09; CI = 1.02-1.17; P < 0.05), twitching during sleep (OR = 1.13; CI = 1.00-1.27; P < 0.01) and morning headache (OR = 1.14; CI = 1.05-1.23; P < 0.01). CONCLUSION: Children with chronic cough are more prone to some abnormal sleep behaviors than children without chronic cough. Household decoration within a year, household mold exposure, and carpet use were all significantly positively associated with abnormal sleep behaviors in children with chronic cough. Our study provides novel insights into the impact of the indoor environment on children's sleep and the occurrence of chronic cough, offering guidance for tailored health promotion programs for families.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.

Effects of probiotic supplementation on 12 min run performance, mood management, body composition and gut microbiota in amateur marathon runners: A double-blind controlled trial.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Modulation of Rac1/PAK1/connexin43-mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma.

Connexin43 (Cx43) is a major gap junction protein in glial cells. Mutations have been found in the gap-junction alpha 1 gene encoding Cx43 in glaucomatous human retinas, suggestive of the involvement of Cx43 in the pathogenesis of glaucoma. However, how Cx43 is involved in glaucoma is still unknown. We showed that increased intraocular pressure in a glaucoma mouse model of chronic ocular hypertension (COH) downregulated Cx43, which was mainly expressed in retinal astrocytes. Astrocytes in the optic nerve head where they gather and wrap the axons (optic nerve) of retinal ganglion cells (RGCs) were activated earlier than neurons in COH retinas and the alterations in astrocytes plasticity in the optic nerve caused a reduction in Cx43 expression. A time course showed that reductions of Cx43 expression were correlated with the activation of Rac1, a member of the Rho family. Co-immunoprecipitation assays showed that active Rac1, or the downstream signaling effector PAK1, negatively regulated Cx43 expression, Cx43 hemichannel opening and astrocyte activation. Pharmacological inhibition of Rac1 stimulated Cx43 hemichannel opening and ATP release, and astrocytes were identified to be one of the main sources of ATP. Furthermore, conditional knockout of Rac1 in astrocytes enhanced Cx43 expression and ATP release, and promoted RGC survival by upregulating the adenosine A3 receptor in RGCs. Our study provides new insight into the relationship between Cx43 and glaucoma, and suggests that regulating the interaction between astrocytes and RGCs via the Rac1/PAK1/Cx43/ATP pathway may be used as part of a therapeutic strategy for managing glaucoma.

Targeting CB2R in astrocytes for Parkinson's disease therapy: unraveling the Foxg1-mediated neuroprotective mechanism through autophagy-mediated NLRP3 degradation.

BACKGROUND: Inflammasomes in astrocytes have been shown to play a crucial role in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Cannabinoid Receptor 2(CB2R), a G protein-coupled receptor (GPCR), is considered a promising therapeutic target in inflammation-related disorders. This study aims to explore the role of CB2R in regulating NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated neuroinflammation in astrocytes. METHODS: In an in vivo animal model, specific targeting of astrocytic CB2R was achieved by injecting CB2R-specific adenovirus (or fork head box g1(foxg1) adenovirus) to knock down CB2R or administering CB2R agonists, inhibitors, etc., in the substantia nigra pars compacta (SNc) of mice. A PD mouse model was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induction. Animal behavioral tests, western blot, immunofluorescence, and other experiments were performed to assess the loss of midbrain tyrosine hydroxylase (TH) neurons, activation of astrocytes, and activation of the NLRP3 pathway. Primary astrocytes were cultured in vitro, and NLRP3 inflammasomes were activated using 1-methyl-4-phenylpyridinium (MPP+) or lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Western blot and ELISA experiments were conducted to assess the release of inflammatory factors. Transcriptomic sequencing and CUT&RUN techniques were employed to study the CB2R regulation of the foxg1 binding site on the autophagy molecule microtubule-associated protein 1 light chain 3 beta (MAP1LC3B). RESULTS: Astrocytic CB2R knockdown impaired the motor abilities of MPTP-induced mice, exacerbated the loss of TH neurons, and induced activation of the NLRP3/Caspase-1/interleukin 1 (IL-1ß) pathway. Activation of CB2R significantly alleviated motor impairments in mice while reducing NLRP3 deposition on astrocytes. In vitro cell experiments showed that CB2R activation attenuated the activation of the NLRP3/Caspase-1/IL-1ß pathway induced by LPS + ATP or MPP+. Additionally, it inhibited the binding of foxg1 to MAP1LC3B, increased astrocytic autophagy levels, and facilitated NLRP3 degradation through the autophagy-lysosome pathway. CONCLUSION: Activation of CB2R on astrocytes effectively mitigates NLRP3-mediated neuroinflammation and ameliorates the disease characteristics of PD in mice. CB2R represents a potential therapeutic target for treating PD.