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Abstract Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78–0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65–0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients’ early risk stratification.

Genetic algorithm (GA) and particle swarm optimization (PSO) were used to optimize the back propagation（BP） neural network to establish the prediction model of Mooney viscosity of ethylene-propylene-diene monomer (EPDM) compound, and the error of the prediction results was compared and analyzed. The results showed that the predicted va-lues of the BP neural network model optimized by the two algorithms all maintained a high degree of fit and correlation with the measured values. Compared with the single BP neural network, the accuracy of the GA-BP neural network prediction model increased by 58.9% and the accuracy of the PSO-BP model increased by 3.57%, which indicated that the prediction accuracy of the prediction model optimized by the two algorithms, especially the BP neural network prediction model optimized by GA, improved significantly Mooney viscosity of EPDM compound.

Abstract Background Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. Methods Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. Results Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P

Interleukin-37 (IL-37), previously known as IL-1F7, is a member of the IL-1 family of cytokines. There are five basic subtypes of IL-37, including IL-37a, IL-37b, IL-37c, IL-37d, and IL-37e. Like other members of the IL-1 family, IL-37 is initially expressed as an immature precursor protein that needs to be processed enzymatically by caspase-1 to generate the bioactive protein. However, unlike most other members of the IL-1 family, IL-37 induces anti-inflammatory activities in IL-37 receptor-positive target cells. IL-37 functions as an extracellular protein by binding to the IL-18 receptor, IL-18R, and an intracellular protein via its interaction with SMAD family member-3 (SMAD-3). This article reviews recent findings regarding the IL-37 protein maturation process and the biological functions mediated by this cytokine.

Abstract Background Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. Results The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. Conclusions These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.

Abstract Food crops are attacked by microbial pathogens and insect pests, leading to significant yield reductions and economic losses. Conventional disease diagnosis and management approaches often fail to provide rapid and eco-friendly solutions. In the current situation, nanomaterials (NMs) serve a valuable role in both managing emerging pathogens and monitoring overall plant health. Nanotechnology has transformed the biotechnology industry including agriculture with specific applications such as nano-fungicides, nano-bactericides, and nano-pesticides. This review focuses on the use of various nanomaterials, including inorganic materials such as Ag, ZnO, CuO, and CeO, as well as carbon-based nanoparticles, nanotubes, nanowires, and nano-capsules. The application of NMs holds the potential to address various challenges in food security through novel applications like advanced nano-biosensors for rapid pathogen detection and targeted disease management strategies. This includes the potential to minimize reliance on chemical inputs and contribute to more sustainable agricultural practices. Nanomaterials (NMs) promise to deliver plant hormones and signaling molecules to plants, enhancing resistance inducers against major crop pathogens. NMs against newly arising pathogens through reactive oxygen generation, membrane damage, and biochemical interference are also reviewed. However, challenges regarding the stability, toxicity, and environmental impacts of NMs are discussed, along with recommendations on green synthesis and functionalization approaches. This article aims to investigate the role of nanomaterials (NMs) in managing emerging pathogens and monitoring overall crop health offering an insightful outlook for future generations. Further biosafety aspects and larger-scale validation of NM-based applications could enable their commercialization for improving global food security. Graphical Abstract

Abstract Wound infection is a worldwide health issue that not only brings large detrimental effects to people’s physical and mental health, but also causes substantial economic burdens to society. By using traditional surgical debridement and antibiotic therapy, patients generally suffer more pain and are at risk of recurring infections. Thus, the development of non-antibiotic treatment methods is desperately needed. Currently, the emerging of flexible wound dressings with physiological signal detection, inactivated infectious pathogen, and wound-healing promoting properties has exhibited immense potential for the treatment of infected wound. Among various dressings, MXene‐based flexible electronic materials as wound dressings with special electroactive, mechanical, photophysical, and biological performances possess a broad application prospect in healthcare. In this review, the challenges of infected wound management are introduced. Next, the types of MXene-based flexible materials and wound infection features are outlined. Then the recent advance of MXene-based flexible materials for infected wound detection and treatment is summarized. Lastly, the predicaments, prospects, and future directions of MXene-based flexible materials for infected wound management are discussed.

Avian metapneumovirus (aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation. The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16 (wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4+ T lymphocytes, and the Th1 (IFN-γ) and Th2 (IL-4 and IL-6) cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

Abstract Background Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. Methods We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. Results There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, − 1.88; 95% CI = − 2.60 to − 1.15), azithromycin (MD, − 1.74; 95% CI = − 2.52 to − 0.95), doxycycline (MD, − 1.53; 95% CI = − 2.05 to − 1.00), ceftriaxone (MD, − 1.22; 95% CI = − 1.89 to − 0.55), penicillin (MD, − 1.22; 95% CI = − 1.80 to − 0.64), and penicillin or ampicillin (MD, − 0.08; 95% CI = − 1.01 to − 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch–Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). Conclusions Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. Systematic review registration PROSPERO CRD42022354938.

Abstract Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Abstract Background The outbreak of Corona Virus Disease (COVID-19) in 2019 has continued until now, posing a huge threat to the public’s physical and mental health, resulting in different degrees of mental health problems. As a vulnerable segment of the public, anxiety is one of the most common mental health problems among COVID-19 patients. Excessive anxiety aggravates the physical and psychological symptoms of COVID-19 patients, which is detrimental to their treatment and recovery, increases financial expenditure, affects family relations, and adds to the medical burden. Objective This study aimed to explore the role of psychological capital and self-esteem in the relationship between insomnia and anxiety, thereby shedding light on the mechanism of the effect of insomnia on anxiety in COVID-19 patients. Methods A cross-sectional study was conducted from April to May 2022 in Fangcang hospital in Shanghai, China. The self-administered questionnaires were distributed to 718 COVID-19 patients via cell phone using the Internet platform “Questionnaire Star”, which included Athens Insomnia Scale, Psychological Capital Questionnaire, Self-esteem Scale, Self-Rating Anxiety Scale, gender, age, marital status, education. Data analysis was performed using descriptive analysis, independent-samples t-test, one-way analysis of variance, Pearson correlation analysis, ordinary least-squares regression, and bootstrap method. Results Education background had significant impact on anxiety in COVID-19 patients (F = 7.70, P

ABSTRACT: Background: Virtual simulation (VS) technology has been widely utilised in various aspects of oral education. This study aimed to evaluate the impact of VS technology in a scaling and root planing (SRP) teaching programme and explore an effective teaching approach. Method: A total of 98 fourth-year undergraduates from Guanghua School of Stomatology at Sun Yat-sen University were enrolled in this study and randomly assigned to either the VS teaching group or the traditional teaching (TT) group. All participants received SRP training before undergoing an operational examination. Subsequently, questionnaires were administered to both students and teachers involved in the programme to assess the teaching effect and fidelity of the VS training system. Unpaired Student t test was used to analyse the final test scores and residual rates amongst students. Results: The overall residual rate of the calculus in the VS group was significantly lower than that in the TT group (48.81% ± 13.50% vs 56.89% ± 13.68%, P

The exposure of organic UV filters has been increasingly confirmed to induce adverse effects on humans. However, the critical exposure pathway and the vulnerable population of organic UV filters are not clearly identified. This paper attempts to evaluate the health risk of commonly used organic UV filters from various exposure routes based on comprehensive analysis strategy. The estimated daily intakes (EDI) and hazard quotient (HQ) values of organic UV filters through four pathways (dermal exposure, indoor dust, indoor air, and drinking water) for various age groups were determined. Although the total HQ values (0.01–0.4) from comprehensive exposure of organic UV filters were below risk threshold (1.0), infants were identified as the most vulnerable population, with EDI (75.71 ng/kg-bw/day) of 2–3 times higher than that of adults. Additionally, the total EDI values of individual exposure pathways were estimated and ranked as follows: indoor air (138.44 ng/kg-bw/day) > sunscreen application (37.2 ng/kg-bw/day) > drinking water (21.87 ng/kg-bw/day) > indoor dust (9.24 ng/kg-bw/day). Moreover, we successfully tailored the Sankey diagram to depict the EDI proportion of individual organic UV filters from four exposure pathways. It was noted that EHMC (ethylhexyl methoxycinnamate) and EHS (ethylhexyl salicylate) dominated the contribution of EDI (72 %) via indoor air exposure routes. This study serves as a crucial reference for enhancing public health risk awareness concerning organic UV filters, with a special focus on the vulnerable populations such as infants and children.

Not available.

Head and neck malignancies are a significant global health concern, with head and neck squamous cell carcinoma (HNSCC) being the sixth most common cancer worldwide accounting for > 90% of cases. In recent years, there has been growing recognition of the potential role of alternative splicing (AS) in the etiology of cancer. Increasing evidence suggests that AS is associated with various aspects of cancer progression, including tumor occurrence, invasion, metastasis, and drug resistance. Additionally, AS is involved in shaping the tumor microenvironment, which plays a crucial role in tumor development and response to therapy. AS can influence the expression of factors involved in angiogenesis, immune response, and extracellular matrix remodeling, all of which contribute to the formation of a supportive microenvironment for tumor growth. Exploring the mechanism of AS events in HNSCC could provide insights into the development and progression of this cancer, as well as its interaction with the tumor microenvironment. Understanding how AS contributes to the molecular changes in HNSCC cells and influences the tumor microenvironment could lead to the identification of new therapeutic targets. Targeted chemotherapy and immunotherapy strategies tailored to the specific AS patterns in HNSCC could potentially improve treatment outcomes and reduce side effects. This review explores the concept, types, processes, and technological advancements of AS, focusing on its role in the initiation, progression, treatment, and prognosis of HNSCC.

Abstract In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human‐relevant criterion for determining undernutrition weight‐for‐age z‐score (WAZ), with a cutoff point of ≤ −1.83 is established as the benchmark for identifying undernourished nonhuman primates (U‐NHPs). In U‐NHPs, pathological anomalies in multi‐organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U‐NHPs. Mitochondria dysfunction is typified by reduced mito‐number, accumulated long‐chain fatty acids, and disruption of OXPHOS complexes. Soy peptide‐treated U‐NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U‐NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re‐establish lipid metabolism balance and mitigated undernutrition.

Common bunt caused by Tilletia laevis Kühn is one of the most serious fungal diseases of wheat. The root–microbial associations play key roles in protecting plants against biotic and abiotic factors. Managing these associations offers a platform for improving the sustainability and efficiency of agriculture production. Here, by using high throughput sequencing, we aimed to identify the bacterial and fungal associations in wheat, alfalfa, and oat crops cultivated in different years in the Gansu province of China. Soil samples (0–6 cm below the surface) from infected wheat by T. laevis had significantly more bacterial and fungal richness than control samples as per the Chao1 analysis. We found some dominant fungi and bacterial phyla in infected wheat by T. laevis, such as Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Ascomycota, Basidiomycota, and Mortierello mycota. We also analyzed the chemical and enzymatic properties of soil samples after T. laevis inoculation. The total nitrogen, total kalium (TK), ammonium nitrogen, available kalium, organic carbon, invertase, phosphatase, and catalase were more in T. laevis-infected samples as compared to the control samples, while pH, total phosphorus, nitrate nitrogen, available phosphorus, and urease were more in control samples compared to T. laevis-infected samples. The results of this study will contribute to the control of wheat common bunt by candidate antagonistic microorganisms and adverse properties of soil.

IntroductionGalactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. MethodsBy running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified.ResultsThe IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738–0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN.ConclusionOur data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.

Introduction Ixodes ticks are pivotal in transmitting diseases like Lyme disease and human granulocytic anaplasmosis, caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. These pathogens not only affect humans through single or multiple tick bites but also pose risks to animal hosts, leading to potential coinfections. Despite regional studies indicating significant prevalence, their global coinfection data remain sparse. This study aims to bridge this gap through a systematic review and meta-analysis of B. burgdorferi and A. phagocytophilum coinfections in Ixodes ticks worldwide. Addressing data limitations and study variability, it seeks to provide a nuanced understanding of coinfection patterns, their epidemiological implications and inform targeted prevention strategies.Methods and analysis Following Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015 guidelines and PROSPERO registration, this study will undertake a thorough database search without constraints on language or publication date, using standardised screening and data extraction protocols. The quality and bias of studies will be evaluated using Joanna Briggs Institute tools. In the statistical analysis phase, conducted in R, we will initially determine the use of fixed or random-effects models based on the assessment of data heterogeneity. This choice will guide the framework for subsequent analyses. Within the selected model’s framework, we will perform subgroup analyses and meta-regression to investigate the effects of various factors, ensuring that each step is tailored to the initial model selection to maintain analytical consistency.Ethics and dissemination As this study does not involve clinical research or data collection from subjects, ethical approval is not required. We will uphold ethical standards in synthesising and reporting data. Study outcomes will be published in peer-reviewed journals, communicating findings to the scientific community and contributing to the understanding of Ixodes tickborne diseases.PROSPERO registration number CRD42023449735.

Ethylene glycol is odorless and harmful to humans. Each year, a large number of fatal cases are caused by ethylene glycol poisoning. Therefore, rapid identification of ethylene glycol is crucial. In this study, clay-like Ti3C2Tx MXene exhibits a larger interlayer spacing compared to accordion-like Ti3C2Tx MXene, which enhances the gas diffusion channels. Nitrogen doping can increase the active sites of clay-like Ti3C2Tx MXene. The introduction of nitrogen-doped carbon nanotubes into N-Ti3C2Tx was carried out to enhance selectivity towards ethylene glycol, leading to the formation of N-Ti3C2Tx MXene/N-CNTs. The N-Ti3C2Tx MXene/N-CNTs exhibits significant selectivity towards the ethylene glycol at room temperature. Meanwhile, the detection limit was 0.3484 ppm, with a shortened response/recovery time of 10.57/6.29 s. Meanwhile, the ethylene glycol sensor device has been prepared through custom-made circuit boards and sensing programs. Moreover, the adsorption and oxidation process of ethylene glycol on N-Ti3C2Tx MXene/N-CNTs was explored through in-situ infrared spectroscopy testing. This study revealed that the oxygen vacancies on the surface of N-Ti3C2Tx MXene/N-CNTs play a crucial role in the oxidative catalytic detection of ethylene glycol. The strategy of N-Ti3C2Tx MXene/N-CNTs provides a new avenue for the detection of ethylene glycol.

The presence of trace organic pollutants in the effluent of wastewater treatment plants (WWTPs) poses considerable risks to aquatic organisms and human health. A large-scale survey of 302 trace organic pollutants in the effluent of 46 Chinese WWTPs was conducted to gain an improved understanding of their occurrence and ecological risks. The survey data showed that 216 compounds in 11 chemical classes had been detected in effluents. The sum concentrations of the trace contaminants in effluent ranged from 1,392 ng/L to 35,453 ng/L, with the maximum concentration of perfluoroalkyl substances (PFASs) recorded as the highest (30,573 ng/L), which was markedly less than the reported 185,000 ng/L for the 38 American WWTPs. The concentration of bisphenol analogs (BPs) was up to 4,422 ng/L, significantly higher than those reported in France, Germany, Japan, Korea, and the U.S. PFASs and BPs were the major pollutants, accounting for 59% of the total pollution. Additionally, a total of 119 contaminants were found to have ecological risks (RQ > 0.01). Among these, 23 contaminants (RQ > 1.0) warrant higher attention and should be prioritized for removal. This study lists valuable information for controlling contaminants with higher priority in WWTP effluent in China.

Abstract Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.

The multitemporal polarimetric SAR (PolSAR) data contains the scattering change information during the growth of crops. However, the current classification methods usually directly use the addition of features extracted at single-temporal or use the temporal and spatial variations of certain features, not really exploring the complete scattering variation information. The specific data representation models for multitemporal PolSAR data should combine time with polarimetry to characterize the scattering variations. However, the characterization and utilization of such kind of models are inadequate. In this article, we construct data representation model based on the power form of coherence matrix to comprehensively represent all kinds of scattering mechanism variation, which is full-rank positive semidefinite Hermitian matrix. We extract new time-variant scattering features and design vision transformer classifier accordingly for crop classification. Experiment results on RADARSAT-2 datasets show that the proposed power representation model outperforms other models.

Abstract Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin’s ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.

Abstract Background This study aimed to compare the efficacy of three different techniques, namely virtual simulation technology (VS), traditional pathological typodont (TT), and quail egg (QE), in pre-clinical training of periodontal ultrasonic scaling. It also aimed to propose an integrated teaching approach for ultrasonic scaling teaching. Methods This single-blind randomized multi-arm trial enrolled 108 fourth-year students from Guanghua School of Stomatology at Sun Yat-sen University. The participants were randomly, evenly assigned to VS, TT, or QE group. First, the participants received theoretical review on ultrasonic scaling and demonstrative teaching. Then in the 90-minute operation training by group, students used traditional typodont equipped in head-simulators, raw quail eggs, or scaling module of the UniDental VS system respectively. Then all participants practiced on pathological models for 30 min. In the final operation examination, participants were instructed to remove the supra- and sub-gingival calculi pre-set on designated teeth by ultrasonic scalers within 30 min. Their performances were evaluated by residual calculus rate and a multi-perspective scoring scale. After the examination, questionnaires were provided to assess the teaching effects of each method and the fidelity of VS. Statistical analysis was carried out using one-way, two-way ANOVA, and multiple t-test. Results Students in VS group had significant higher total test scores than QE group (87.89 ± 6.81, 83.53 ± 8.14) and TT group (85.03 ± 6.81). VS group scored higher in several dimensional comparisons with the other two groups, especially in difficult situations. QE group had higher scores particularly in force application and supra-gingival scaling. TT group scored the highest in pivot stability practice and body position training. Students gave higher scores when assessing the fidelity of VS than experienced teachers. Conclusion The study highlights the importance of specialized pre-clinical training on ultrasonic scaling for dental students. The methods adopted in current study (VS, TT and QE) each offered unique advantages in education, which can be combined to create an integrative teaching procedure. This procedure aims to provide an effective, advisable and normative pre-clinical training procedure for ultrasonic scaling. By utilizing the strengths of each method, dental educators can deliver high-quality training and ensure that students are well-prepared for clinical practice.

Mycoplasma pneumoniae (MP) is the cause of Mycoplasma pneumoniae pneumonia (MPP) in children and adolescents, with the clinical manifestations highlighted by intermittent irritating cough, accompanied by headache, fever and muscle pain. This paper aimed to study the research status and focal points in MP infection, especially the common laboratory diagnostic methods and clinical treatment of Mycoplasma pneumoniae. Laboratory diagnostic methods include molecular assay, serological antibody detection, rapid antigen detection and isolation and culture. Polymerase chain reaction (PCR) is the gold standard with high sensitivity and specificity. The serological antibody can detect various immune antibodies qualitatively or quantitatively in serum. Rapid antigen can be detected faster, with no equipment environment requirements, which can be used for the early diagnosis of MP infection. While the culture growth cycle is long and insensitive, not recommended for routine diagnosis. Macrolides were the preferred drug for children with MPP, while the drug resistance rate was rising in China. Tetracycline can be substituted but was not recommended for children under 8 years of age, quinolone drugs are not necessary, severe MPP can be combined with glucocorticoids, involving the nervous or immune system can choose gamma globulin. Other treatments for MPP including symptomatic treatment which can alleviate symptoms, improve lung function and improve prognosis. A safe and effective vaccine needed to be developed which can provide protective immunity to children and will reduce the incidence of MPP.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

ABSTRACT: Probiotics are increasingly recognized for their capacity to combat pathogenic bacteria. In this study, we isolated a strain of Ligilactobacillus salivarius XP132 from the gut microbiota of healthy chickens. This strain exhibited resistance to low pH and bile salts, auto-aggregation capabilities, and the ability to co-aggregate with pathogenic Salmonella. The in vitro antibacterial activity of Ligilactobacillus salivarius XP132 was tested using an Oxford cup antibacterial test, and the results showed that Ligilactobacillus salivarius XP132 exhibited broad-spectrum antibacterial activity, with especially strong antibacterial activity against Salmonella. In animal experiments with white feather broilers and specific-pathogens-free (SPF) chickens, we orally administered 1 × 109 CFU XP132 live bacteria per chicken per day, and detected the content of Salmonella in the liver, spleen, intestinal contents, and eggs of the chickens by RT-qPCR. Oral administration of Lactobacillus salivarius XP132 group significantly reduced the levels of Salmonella in chicken liver, spleen, intestinal contents and eggs, and the oral administration of Ligilactobacillus salivarius XP132 significantly inhibited the horizontal and vertical transmission of Salmonella in SPF chickens and white-feathered broilers. After oral administration of XP132, the production of chicken serum anti-infective cytokine IFN-γ was also significantly up-regulated, thereby enhancing the host's ability to resist infection. In addition, the production of various serum inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α, was down-regulated, leading to significant amelioration of the inflammatory response induced by S. Pullorum in chickens. These findings suggest that Ligilactobacillus salivarius XP132 possesses potent antibacterial and immunomodulatory properties that effectively prevent both horizontal and vertical transmission of Salmonella Pullorum, highlighting its potential as a valuable tool for the prevention and control of Salmonella disease.

Protein phosphorylation in sweat metabolites plays a key role in nerve activity, muscle contraction, and other activities, and abnormal protein phosphorylation may lead to diseases such as neurodegenerative disorders. Real-time non-invasive monitoring of changes in phosphorylated protein levels in sweat facilitates the development of prevention of human degenerative neurological diseases. Here, an electrochemical sensor for the detection of trace phosphoproteins in sweat was constructed by exploiting the selective enrichment ability of the TiZr dual active center in the TiO2 NPs@UiO-66 structure for phosphoproteins. The common phosphoprotein α-Casein was selected as a demonstration sample to show the functionality of the designed sensing platform. The sensor exhibited excellent selectivity, repeatability, reproducibility and stability with a detection limit as low as 0.659 μmol/L and a detection range of 1–10 μmol/L. In addition, the low biotoxicity of the prepared materials was verified by biological experiments on SD rats and volunteers, which can meet the needs of skin-friendly biosensors. The detection of phosphoproteins in human sweat at rest and during exercise verified the performance for practical applications. This work realizes the goal of non-invasive and continuous detection of phosphoproteins in sweat in wearable devices.

BackgroundCongenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) syndrome (OMIM #616266) is an autosomal dominant hereditary disease that can lead to the congenital contracture of the limbs and face, hypotonia, and developmental delay. In addition, it may result in growth retardation and present various clinical symptoms, such as brain atrophy, a small pituitary gland, musculoskeletal abnormalities, abnormal breathing, abdominal hernia, and abnormal facial features. Herein, we describe a novel de novo missense genetic variant in the sodium leak channel, non-selective (NALCN) gene that is associated with CLIFAHDD syndrome.Case descriptionThis study describes a patient with varus deformities in both feet, deviation of the ulnar side of the fingers, and severe hypotonia. This patient was subsequently confirmed to have CLIFAHDD syndrome through genetic testing, which also revealed a novel missense de novo genetic variant in the NALCN gene (c.3553G > A, p.Ala1185Thr).ConclusionsOur findings further enrich the known variant spectrum of the NALCN gene and may expand the range of clinical options for treating NALCN-related disorders.

Diabetic nephropathy (DN) is a severe complication of prolonged diabetes, impacting millions worldwide with an increasing incidence. This study investigates the role of tribbles pseudokinase 3 (TRIB3), a protein implicated in the progression of DN, focusing on its mechanisms underlying glomerular damage. Through analysis of the Gene Expression Omnibus (GEO) database, we identified TRIB, among differentially expressed genes (DEGs) in streptozotocin (STZ)-treated C57BL/6J mice. Both in vitro and in vivo experiments were conducted to examine the effects of TRIB3 inhibition on high glucose (HG)-induced damage in podocytes and DN mouse models. The results demonstrated that TRIB3 inhibition reduced inflammatory responses and extracellular matrix (ECM) production inMPC5 cells, mediated by the downregulation of DNA damage-inducible transcript 3 (DDIT3) - a critical regulator of proinflammatory cytokine secretion and ECM synthesis. Inhibiting TRIB3 decreased inflammatory factors and ECM deposition in diabetic mice in vivo, confirming its pivotal role in DN pathogenesis. These findings indicate that TRIB3 and its interaction with DDIT3 contribute significantly to DN by promoting inflammatory cascades and ECM accumulation, presenting potential therapeutic targets for managing the disease.

As an important carrier of culture, poetry plays a significant role in deepening language learners' understanding of the target language culture as well as enhancing their language skills; however, the effect of the target language culture on language learners' enjoyment of poetry remains unclear. The study served as an attempt to shed light on the point of whether the target language culture has different effects on high- and low-level Chinese Arabic learners' fondness for Arabic poetry with the use of pictures related to Arabic culture and those not related to Arabic culture. In the current study, 40 Arabic learners (20 high-level and 20 low-level) scored the Arabic poem line based on their fondness for it after viewing two kinds of picture with electroencephalogram (EEG) recording. Frontal alpha asymmetry index as a correlate of approach and avoidance related motivation measured by EEG power in the alpha band (8-13 Hz) was calculated for examining whether the behavioral results of Arabic learners' fondness for poetry are in line with the results of changes in the related EEG components. Behavioral results illustrated that low-level subjects showed significantly less liking for Arabic poetry after viewing pictures related to Arabic culture compared to those not related to Arabic culture. The high-level subjects did not show a significant difference in the level of liking for Arabic poetry between the two cases. FAA results demonstrated that low-level subjects presented a significant avoidance-related responses to Arabic poetry after viewing pictures related to Arabic culture in comparison to viewing pictures not related to Arabic culture; while the FAA values did not differ significantly between the two cases in high-level subjects, which is in line with behavioral results. The findings of this research can benefit teachers in motivating students to learn poetry in foreign language curriculum and also contribute to the literature on the effect of target language culture on language learners' enjoyment of poetry.

Abstract Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.

Abstract Sepsis is a life‐threatening condition that requires urgent medical attention. In this study, we investigated the potential of soybean‐derived peptides (soy peptides) as an anti‐inflammatory supplement for patients with sepsis. Cynomolgus monkeys were induced with sepsis by intravenous administration of three different concentrations of Escherichia coli (6.3 × 103, 6.3 × 105, and 6.3 × 107 CFU/kg). Changes in body weight and inflammatory markers were analyzed, and the high dose of 6.3 × 107 CFU/kg was found to be the most appropriate for sepsis modeling. Controlled enzymatic hydrolysis was then used to release bioactive soy peptides from soy protein isolate, which were administered to monkeys with sepsis. The results showed that soy peptide supplementation significantly suppressed inflammatory responses and improved coagulation abnormalities in the monkeys. Our findings suggest that soy peptides could be an effective clinical nutritional supplement for patients with sepsis, with potential benefits for reducing inflammation and improving coagulation. These results provide a foundation for further research into the development of novel nutritional supplements for patients with sepsis.

Abstract Global wind power expansion raises concerns about its potential impact on plant biomass production (PBP). Using a high-dimensional fixed effects model, this study reveals significant PBP reduction due to wind farm construction based on 2404 wind farms, 108,361 wind turbines, and 7,904,352 PBP observations during 2000–2022 in China. Within a 1–10 km buffer, the normalized differential vegetation and enhanced vegetation indices decrease from 0.0097 to 0.0045 and 0.0075 to 0.0028, respectively. Similarly, absorbed photosynthetically active radiation and gross primary productivity decline from 0.0094 to 0.0034% and 0.0003–0.0002 g*C/m2 within a 1–7 km buffer. Adverse effects last over three years, magnified in summer and autumn, and are more pronounced at lower altitudes and in plains. Forest carbon sinks decrease by 12,034 tons within a 0–20 km radius, causing an average economic loss of $1.81 million per wind farm. Our findings underscore the balanced mitigation strategies for renewable energy transition when transiting from fossil fuels.

Abstract Background Disruption of the BBB is a harmful event after intracranial hemorrhage (ICH), and this disruption contributes to a series of secondary injuries. We hypothesized that FGF21 may have protective effects after intracranial hemorrhage (ICH) and investigated possible underlying molecular mechanisms. Methods Blood samples of ICH patients were collected to determine the relationship between the serum level of FGF21 and the $$\Delta$$ Δ GCS%. Wild-type mice, SIRT6flox/flox mice, endothelial-specific SIRT6-homozygous-knockout mice (eSIRT6−/− mice) and cultured human brain microvascular endothelial cells (HCMECs) were used to determine the protective effects of FGF21 on the BBB. Results We obtained original clinical evidence from patient data identifying a positive correlation between the serum level of FGF21 and $$\Delta$$ Δ GCS%. In mice, we found that FGF21 treatment is capable of alleviating BBB damage, mitigating brain edema, reducing lesion volume and improving neurofunction after ICH. In vitro, after oxyhemoglobin injury, we further explored the protective effects of FGF21 on endothelial cells (ECs), which are a significant component of the BBB. Mitochondria play crucial roles during various types of stress reactions. FGF21 significantly improved mitochondrial biology and function in ECs, as evidenced by alleviated mitochondrial morphology damage, reduced ROS accumulation, and restored ATP production. Moreover, we found that the crucial regulatory mitochondrial factor deacylase sirtuin 6 (SIRT6) played an irreplaceable role in the effects of FGF21. Using endothelial-specific SIRT6-knockout mice, we found that SIRT6 deficiency largely diminished these neuroprotective effects of FGF21. Then, we revealed that FGF21 might promote the expression of SIRT6 via the AMPK–Foxo3a pathway. Conclusions We provide the first evidence that FGF21 is capable of protecting the BBB after ICH by improving SIRT6-mediated mitochondrial homeostasis.

Highlights The electrochemical principles/mechanism of Li–S batteries and origin of the shuttle effect have been discussed. The efficient strategies have been summarized to inhibit the shuttle effect. The recent advances of inhibition of shuttle effect in Li–S batteries for all components from anode to cathode.

Abstract Objective This study aimed to investigate the genetic etiologies of fetuses with single atria and/or ventricle (SA or/and SV) using different genetic detection methods in a Chinese prenatal cohort. Methods In this retrospective study, the various genetic results of 44 fetuses with SA and/or SV were analyzed. All 44 cases were tested by chromosomal microarray analysis (CMA) and karyotyping simultaneously, and 8 underwent whole exome sequencing (WES). Data on the pregnancy outcomes and neonatal prognoses were collected from medical records and postnatal follow-up. Results The whole cohort of 44 fetuses included 14 SA cases (31.8%), 12 SV cases (27.3%), and 18 SA and SV cases (40.9%). A total of 9 pathogenic genetic results were detected by conventional karyotyping, CMA and trio-WES, indicating an overall detection rate of 20.5% (9/44). Six pathogenic chromosomal abnormalities were identified by CMA among the 44 cases, showing a detection rate of 13.6% (6/44). Two microdeletions being missed by karyotyping were diagnosed by CMA, showing an additional diagnostic yield of 4.5% for CMA in present cohort(2/44). Three pathogenic variants in two fetuses were identified by WES, indicating an incremental diagnostic yield of 4.5%(2/44) for WES in fetuses with SA or/and SV. Conclusion In this study, WES achieved an additional diagnostic yield of 4.5% in fetuses with SA or/and SV. WES is valuable for fetal prognosis assessment and could add diagnostic value for fetuses with SA and/or SV when CMA is negative. It would be a valuable technique for the identification of underlying pathogenic variants in prenatal cohorts.

Abstract Background Ulcerative colitis (UC) represents a clinically challenging condition characterized by persistent damage to the colonic epithelial mucosa as the principal pathological feature. Polyvinyl alcohol (PVA) solution, primarily composed of glue, is a biodegradable polymer material that has found utility in the medical field. This research endeavors to investigate the therapeutic potential of PVA water solution in ameliorating UC in mice. Methods UC was induced in 48 C57BL/6 mice by administering 2.5% DSS in their diet for 6 days. Mice were treated with different concentrations of PVA (0.1 mg/ml PVA, 0.3 mg/ml PVA, 1 mg/ml PVA, 3 mg/ml PVA, 10 mg/ml PVA) enemas (n = 6). Disease Activity Index (DAI) and histologic score were evaluated for inflammation degree. Furthermore, mouse colon organoids were cultured, which were used to assess the effects of PVA on expansion in vitro. Results PVA aqueous solutions (1 mg/ml and 3 mg/ml) were able to alleviate the DAI in mice. By DAY 6, there was a significant 3/5-fold decrease in DAI within the 1 mg/ml PVA group (p = 0.02). Histopathology scores demonstrated improvements, while the levels of inflammatory factors in the intestinal mucosal tissue were reduced. Additionally, it was confirmed that PVA could promote the expansion of colonic organoids in vitro. Conclusions In summary, our investigation has yielded findings indicating that PVA holds the potential to ameliorate symptoms associated with colitis in murine subjects afflicted by DSS-induced colitis, primarily through its facilitation of intestinal stem cell expansion. This study might provide a new candidate for the clinical treatment of ulcerative colitis.

Abstract Background During the course of their illness, people with Parkinson’s disease may see changes in their insulin-like growth factor (IGF-1) and serum homocysteine (Hcy) indices. In this study, patients with intermediate to severe Parkinson’s disease were examined for how Resagiline and levodopa and benserazide hydrochloride affected their motor performance, serum levels of homocysteine (Hcy), and insulin-like growth factor (IGF-1). Methods From June 2020 to December 2021, a total of 100+ cases of Parkinson’s patients over 60 years old in the middle and late stages of Parkinson’s were seen in the outpatient and inpatient departments of the Third People’s Hospital of Chengdu City and had a detailed observation record, and according to the inclusion criteria, the patients who met the criteria were randomly grouped into a clinical observation group and a control group. The subjects in the control group received only levodopa and benserazide hydrochloride treatment, while the observation group was treated with Resagiline in combination with the clinical control group. The total treatment observation period was 1 year for both groups, and the motor function and serum Hcy and IGF-1 indexes of both groups were compared after the end of treatment. Results We randomly and evenly grouped 64 patients who met the requirements of the inclusion criteria into a clinical observation group and a control group, each with 32 patients, from among 168 patients over 60 years of age with detailed observation records in the middle and late stages of Parkinson’s. After the 1-year observation period, we found that the total effective rate after treatment in the clinical observation group (93.75%) and significantly higher than that in the control group (68.75%) (P

Abstract Introduction Periodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis. Methods A polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer’s-related changes, and nisin’s therapeutic potential in this context. Results 16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1β/IL-1 β, Interleukin 6/IL-6, and Tumor Necrosis Factor α/TNF-α) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-β 42 (Aβ42), total Tau, and Tau (pS199) (445.69 ± 120.03, 1420.85 ± 331.40, 137.20 ± 36.01) were significantly higher in the infection group compared to the control group (193.01 ± 31.82, 384.27 ± 363.93, 6.09 ± 10.85), respectively. Nisin treatment markedly reduced the Aβ42 (261.80 ± 52.50), total Tau (865.37 ± 304.93), and phosphorylated Tau (82.53 ± 15.77) deposition in the brain of the infection group. Discussion Nisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal–dysbiosis-related AD.

Truncated singular value decomposition (TSVD) is a popular recovery algorithm for multimode fiber single-pixel imaging (MMF-SPI), and it uses truncation thresholds to suppress noise influences. However, due to the sensitivity of MMF relative to stochastic disturbances, the threshold requires frequent re-determination as noise levels dynamically fluctuate. In response, we design an adaptive truncation threshold determination (ATTD) method for TSVD-based MMF-SPI in disturbed environments. Simulations and experiments reveal that ATTD approaches the performance of ideal clairvoyant benchmarks, and it corresponds to the best possible image recovery under certain noise levels and surpasses both traditional truncation threshold determination methods with less computation—fixed threshold and Stein’s unbiased risk estimator (SURE)—specifically under high noise levels. Moreover, target insensitivity is demonstrated via numerical simulations, and the robustness of the self-contained parameters is explored. Finally, we also compare and discuss the performance of TSVD-based MMF-SPI, which uses ATTD, and machine learning-based MMF-SPI, which uses diffusion models, to provide a comprehensive understanding of ATTD.

Periodontitis-related oral microbial dysbiosis is thought to contribute to adverse pregnancy outcomes (APOs), infertility, and female reproductive inflammation. Since probiotics can modulate periodontitis and oral microbiome dysbiosis, this study examined the effects of a probiotic bacteriocin, nisin, in modulating the reproductive microbiome and inflammation triggered by periodontitis. A total of 24 eight-week-old BALB/cByJ female mice were randomly divided into four treatment groups (control, infection, nisin, and infection+nisin group), with 6 mice per group. A polymicrobial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) mouse model of periodontal disease was used to evaluate the effects of this disease on the female reproductive system, with a focus on the microbiome, local inflammation, and nisin’s therapeutic potential in this context. Moreover, 16s RNA sequencing was used to evaluate the changes in the microbiome and RT-PCR was used to evaluate the changes in inflammatory cytokines. Periodontal pathogen DNA was detected in the reproductive organs, and in the heart and aorta at the end of the experimental period, and the DNA was especially elevated in the oral cavity in the infection group. Compared to the control groups, only P. gingivalis was significantly higher in the oral cavity and uterus of the infection groups, and T. forsythia and F. nucleatum were significantly higher in the oral cavity of the infection groups. The infection and nisin treatment group had significantly lower levels of P. gingivalis, T. forsythia, and F. nucleatum in the oral cavity compared with the infection group. Since periodontal pathogen DNA was also detected in the heart and aorta, this suggests potential circulatory system transmission. The polymicrobial infection generally decreased the microbiome diversity in the uterus, which was abrogated by nisin treatment. The polymicrobial infection groups, compared to the control groups, generally had lower Firmicutes and higher Bacteroidota in all the reproductive organs, with similar trends revealed in the heart. However, the nisin treatment group and the infection and nisin group, compared to the control or infection groups, generally had higher Proteobacteria and lower Firmicutes and Bacteroidota in the reproductive organs and the heart. Nisin treatment also altered the microbiome community structure in the reproductive tract to a new state that did not mirror the controls. Periodontal disease, compared to the controls, triggered an increase in inflammatory cytokines (IL-6, TNF-α) in the uterus and oral cavity, which was abrogated by nisin treatment. Polymicrobial periodontal disease alters the reproductive tract’s microbial profile, microbiome, and inflammatory status. Nisin modulates the microbial profile and microbiome of the reproductive tract and mitigates the elevated uterine inflammatory cytokines triggered by periodontal disease.

Premature ovarian insufficiency (POI) is defined as the depletion of ovarian function before the age of 40 years. The global prevalence of POI is 3.5%. To date, genetic factors account for 23.5% of the etiology of POI. Herein, a previously uncharacterized pathogenic homozygous variant of the chromosome segregation–1–like gene (CSE1L) was identified in POI patients via targeted panel sequencing. It is reported that dysregulated iron metabolism is involved in many reproductive endocrine disorders; however, its precise role in POI remains obscure. In this study, we identified CSE1L as a potential candidate gene that plays an important role in maintaining iron homeostasis. Deficiency of CSE1L led to ferroptosis in human granulosa cells, which was confirmed by transmission electron microscopy. Mechanistically, coimmunoprecipitation identified the direct interaction between CSE1L and FoxO1. Inhibition of CSE1L led to the excessive accumulation of FoxO1 in the nucleus via nucleocytoplasmic transport. Then, FoxO1 bound to the promoter region of NCOA4 and promoted its transcription, which was verified by a chromatin immunoprecipitation assay. Moreover, inhibition of CSE1L in cumulus cell monolayer could impede oocyte maturation, which might be associated with oxidative stress. Consequently, our study first revealed that CSE1L participated in ferroptosis in human ovarian granulosa cells via nucleocytoplasmic transportation, which might be helpful in revealing the molecular mechanism of CSE1L in the development of POI. Importantly, these findings might provide new insights into the application of ferroptosis inhibitors in the treatment of POI.

IntroductionGut microbiota are closely related to the nutrition, immunity, and metabolism of the host and play important roles in maintaining the normal physiological activities of animals. Cranes are important protected avian species in China, and they are sensitive to changes in the ecological environment and are thus good environmental indicators. There have been no reports examining gut fungi or the correlation between bacteria and fungi in wild Demoiselle cranes (Grus virgo) and Common cranes (Grus grus). Related research can provide a foundation for the protection of rare wild animals.Methods16S rRNA and ITS high-throughput sequencing techniques were used to analyze the gut bacterial and fungal diversity of Common and Demoiselle cranes migrating to the Yellow River wetland in Inner Mongolia.ResultsThe results revealed that for gut bacteria α diversity, Chao1 index in Demoiselle cranes was remarkably higher than that in Common cranes (411.07 ± 79.54 vs. 294.92 ± 22.38), while other index had no remarkably differences. There was no remarkable difference in fungal diversity. There were marked differences in the gut microbial composition between the two crane species. At the phylum level, the highest abundance of bacteria in the Common crane and Demoiselle crane samples was Firmicutes, accounting for 87.84% and 74.29%, respectively. The highest abundance of fungi in the guts of the Common and Demoiselle cranes was Ascomycota, accounting for 69.42% and 57.63%, respectively. At the genus level, the most abundant bacterial genus in the Common crane sample was Turicibacter (38.60%), and the most abundant bacterial genus in the Demoiselle crane sample was Catelicoccus (39.18%). The most abundant fungi in the Common crane sample was Penicillium (6.97%), and the most abundant fungi in the Demoiselle crane sample was Saccharomyces (8.59%). Correlation analysis indicated that there was a significant correlation between gut bacteria and fungi.DiscussionThis study provided a research basis for the protection of cranes. Indeed, a better understanding of the gut microbiota is very important for the conservation and management of wild birds, as it not only helps us to understand their life history and related mechanisms, but also can hinder the spread of pathogenic microorganisms.

ABSTRACT Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The “host shutoff,” a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.

Background and aims To explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated liver disease (ALD)-related HCC risk.Methods A database of 136 571 inpatients in the Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018 with chronic liver disease was established. Data were collected by medical records review. Multivariate logistic regression was used to identify the independent high-risk factors associated with HCC, and then were incorporated into a novel nomogram. Afterward, the new established model was validated using external cohort by receiver operating characteristic curves analysis. For external cohort, 1646 patients with ALD admitted to our hospital from 2019 to 2021 were included. ALD was diagnosed on the basis of a history of sustained heavy alcohol intake greater than 40 g/day for men and 20 g/day for women for >5 years, clinical evidence of liver disease and supporting laboratory abnormalities.Results Over the last 17 years, trends showed obviously increases in ALD. ALD-related HCC experienced a significant increase from 5.8% to 30.7%, whereas hepatitis B virus (HBV)-related HCC declined from 77.6% to 52.0%. In patients with ALD-related HCC (5119), 3816 (74.54%) cases had HBV infection, 493 (9.63%) cases had hepatitis C virus (HCV) infection, 71 (1.39%) cases were coinfected with both HBV and HCV, and 739 (14.44%) cases had neither HBV nor HCV infection. Drinking years (OR 1.009, 95% CI (1.000 to 1.017)), age (OR 1.060, 95% CI (1.051 to 1.069)), diabetes mellitus (OR 1.314, 95% CI (1.123 to 1.538)), HBV infection (OR 4.905, 95% CI (4.242 to 5.671)), liver cirrhosis (OR 4.922, 95% CI (3.887 to 6.232)) and male sex (OR 17.011, 95%CI (2.296 to 126.013)) were associated with increased risk of HCC in patients with ALD. A nomogram had a concordance index of 0.786 (95% CI 0.773 to 0.799) and had well-fitted calibration curves. These results were successfully validated both in the internal cohort and external cohort.Conclusion The prevalence of ALD and ALD-related HCC has been increased dramatically. The nomogram model established here with its high accuracy and easy-to-use features achieved an optimal prediction of HCC development in patients with ALD, which can help clinicians to develop an individualised and precise treatment strategy.

The subgroup J avian leukosis virus (ALV-J), a retrovirus, uses its gp85 protein to bind to the receptor, the chicken sodium hydrogen exchanger isoform 1 (chNHE1), facilitating viral invasion. ALV-J is the main epidemic subgroup and shows noteworthy mutations within the receptor-binding domain (RBD) region of gp85, especially in ALV-J layer strains in China. However, the implications of these mutations on viral replication and transmission remain elusive. In this study, the ALV-J layer strain JL08CH3-1 exhibited a more robust replication ability than the prototype strain HPRS103, which is related to variations in the gp85 protein. Notably, the gp85 of JL08CH3-1 demonstrated a heightened binding capacity to chNHE1 compared to HPRS103-gp85 binding. Furthermore, we showed that the specific N123I mutation within gp85 contributed to the enhanced binding capacity of the gp85 protein to chNHE1. Structural analysis indicated that the N123I mutation primarily enhanced the stability of gp85, expanded the interaction interface, and increased the number of hydrogen bonds at the interaction interface to increase the binding capacity between gp85 and chNHE1. We found that the N123I mutation not only improved the viral replication ability of ALV-J but also promoted viral shedding in vivo. These comprehensive data underscore the notion that the N123I mutation increases receptor binding and intensifies viral replication.

Abstract Although 2D material van der Waals heterostructures (vdWHs) exhibit many novel properties and applications, 2D homojunctions have unique advantages in interface lattice matching, band continuity, and charge transfer efficiency. However, the rectification performances of 2D homojunction diodes are severely limited by the small junction barrier, mainly due to inefficient charge doping. In this work, an ultrahigh‐rectification‐ratio WSe2 homojunction diode achieved by the semi‐floating gate doping of graphdiyne oxide (GDYO) is reported. Utilizing the WSe2/GDYO direct charge trapping mode can free the inhibition of charge capturing efficiency by removing conventional insulating barriers and thus improve the rectification ratio. The C─C(sp) and oxygen‐containing functional groups in the GDYO layer can provide outstanding charge‐trapping ability due to their unsaturation. Furthermore, the oxygen plasma treatment used for oxidizing graphdiyne (GDY) into GDYO can make GDYO a flatter surface, thus creating strong‐coupling WSe2/GDYO interfaces to improve the charge transfer efficiency and enhance the electrostatic doping effect. Besides, the WSe2/GDYO interfaces are confirmed to possess a higher junction barrier than that of the WSe2/GDY interfaces. This research proposes a brand‐new approach to building p–n junctions via charge trapping and the homojunction diode with a record‐highest rectification ratio of up to 106 is obtained.