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Abstract Heart failure (HF) remains a significant global health concern with limited effective treatments available. C1q/TNF‐related protein 6 (CTRP6) is a member of the CTRP family analogous to adiponectin and its role in HF pathogenesis remains unclear. Here, we investigated the impact of CTRP6 on HF progression. To mimic heart failure with reduced ejection fraction (HFrEF), we used isoproterenol injection in mice and administered adenovirus vectors expressing CTRP6 (Ad‐CTRP6) via tail vein injection. We assessed cardiac function through echocardiography and histology. CTRP6's effects on hypertrophy, fibrosis, apoptosis, oxidative stress and mitochondrial function were analysed. Downstream pathways (phosphorylated AMP‐activated protein kinase (p‐AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator‐activated receptor γ coactivator 1‐α (PGC‐1α) were studied in heart tissues. In vitro, isoproterenol‐stimulated H9c2 cardiomyocytes were treated with CTRP6 to examine viability, apoptosis, F‐actin and signalling proteins. Compound C was used to assess AMPK involvement. CTRP6 expression was lower in the plasma of HF patients. In an isoproterenol‐induced HFrEF mouse model, adenovirus‐mediated overexpression of CTRP6 ameliorated cardiac dysfunction and reduced cardiomyocyte apoptosis, oxidative stress, inflammation and myocardial injury markers. Mechanistically, CTRP6 activation of the AMPK/SIRT1/PGC‐1α signalling pathway restored mitochondrial homeostasis, evidenced by reduced mitochondrial reactive oxygen species levels, increased ATP content, and enhanced mitochondrial complex I/III activities in cardiac tissues. In vitro studies using isoproterenol‐stimulated H9c2 cardiomyocytes corroborated these findings, demonstrating that CTRP6 upregulation attenuated hypertrophy, apoptosis, oxidative stress and mitochondrial dysfunction. Furthermore, these effects were partially reversed by the AMPK inhibitor Compound C, implicating the involvement of the AMPK pathway in CTRP6‐mediated cardioprotection. CTRP6 alleviates HF progression through the AMPK/SIRT1/PGC‐1α signalling pathway.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Camelids produce both conventional tetrameric antibodies (Abs) and dimeric heavy-chain antibodies (HCAbs). Although B cells that generate these two types of Abs exhibit distinct B cell receptors (BCRs), whether these two B cell populations differ in their phenotypes and developmental processes remains unclear. Here, we performed single-cell 5′ RNA profiling of peripheral blood mononuclear cell samples from Bactrian camels before and after immunization. We characterized the functional subtypes and differentiation trajectories of circulating B cells in camels, and reconstructed single-cell BCR sequences. We found that in contrast to humans, the proportion of T-bet+ B cells was high among camelid peripheral B cells. Several marker genes of human B cell subtypes, including CD27 and IGHD, were expressed at low levels in the corresponding camel B cell subtypes. Camelid B cells expressing variable genes of HACbs (VHH) were widely present in various functional subtypes and showed highly overlapping differentiation trajectories with B cells expressing variable genes of conventional Abs (VH). After immunization, the transcriptional changes in VHH+ and VH+ B cells were largely consistent. Through structure modeling, we identified a variety of scaffold types among the reconstructed VHH sequences. Our study provides insights into the cellular context of HCAb production in camels and lays the foundation for developing single-B cell-based camelid single-domain Ab screening.

Abstract Background DNA methylation is a crucial epigenetic mechanism that regulates gene expression during plant growth and development. However, the role of DNA methylation in regulating the organ-specific functions of the invasive weed Mikania micrantha remains unknown. Results Here, we generated DNA methylation profiles for M. micrantha and a local congeneric species, Mikania cordata, in three vegetative organs (root, stem, and leaf) using whole-genome bisulfite sequencing. The results showed both differences and conservation in methylation levels and patterns between the two species. Combined with transcriptome data, we found that DNA methylation generally inhibited gene expression, with varying effects depending on the genomic region and sequence context (CG, CHG, and CHH). Genes overlapping with differentially methylated regions (DMRs) were more likely to be differentially expressed between organs, and DMR-associated upregulated differentially expressed genes (DEGs) were enriched in organ-specific pathways. A comparison between photosynthetic (leaf) and non-photosynthetic (root) organs of M. micrantha further confirmed the regulatory role of DNA methylation in leaf-specific photosynthesis. Integrating small RNA-Seq data revealed that 24-nt small interfering RNAs (siRNAs) were associated with CHH methylation in gene-rich regions and regulated CHH methylation in the flanking regions of photosynthesis-related genes. Conclusion This study provides insights into the complex regulatory role of DNA methylation and siRNAs in organ-specific functions and offers valuable information for exploring the invasive characteristics of M. micrantha from an epigenetic perspective.

Abstract Electrocatalytic nitrite reduction to the valuable ammonia is a green and sustainable alternative to the conventional Haber-Bosch method for ammonia synthesis, while the activity and selectivity for ammonia production remains poor at low nitrite concentrations. Herein, we report a nanoporous intermetallic single-atom alloy CuZn (np/ISAA-CuZn) catalyst with completely isolated Cu-Zn active-sites, which achieves neutral nitrite reduction reaction with a remarkable NH3 Faradaic efficiency over 95% and the highest energy efficiency of ≈ 59.1% in wide potential range from −0.2 to −0.8 V vs. RHE. The np/ISAA-CuZn electrocatalyst was able to operate stably at 500 mA cm−2 for 220 h under membrane electrode assembly conditions with a stabilized NH3 Faraday efficiency of ~80% and high NO2 ‒ removal rate of ~100%. A series of in situ experimental studies combined with density functional theory calculations reveal that strong electronic interactions of isolated Cu-Zn active-sites altered the protonation adsorption species, effectively alleviating the protonation barrier of *NO2 and thus greatly facilitating the selective reduction of NO2 − into NH3.

Abstract Non-equilibrium quantum transport is crucial to technological advances ranging from nanoelectronics to thermal management. In essence, it deals with the coherent transfer of energy and (quasi-)particles through quantum channels between thermodynamic baths. A complete understanding of quantum transport thus requires the ability to simulate and probe macroscopic and microscopic physics on equal footing. Using a superconducting quantum processor, we demonstrate the emergence of non-equilibrium steady quantum transport by emulating the baths with qubit ladders and realising steady particle currents between the baths. We experimentally show that the currents are independent of the microscopic details of bath initialisation, and their temporal fluctuations decrease rapidly with the size of the baths, emulating those predicted by thermodynamic baths. The above characteristics are experimental evidence of pure-state statistical mechanics and prethermalisation in non-equilibrium many-body quantum systems. Furthermore, by utilising precise controls and measurements with single-site resolution, we demonstrate the capability to tune steady currents by manipulating the macroscopic properties of the baths, including filling and spectral properties. Our investigation paves the way for a new generation of experimental exploration of non-equilibrium quantum transport in strongly correlated quantum matter.

Abstract Background When compared to open surgery, laparoscopic common bile duct exploration (LCBDE) is known to cause less discomfort and a faster recovery. This study examines the effect of the Enhanced Recovery After Surgery (ERAS) strategy on LCBDE outcomes. Methods In March 2021 to May 2024, 400 patients with LCBDE participated in randomized research. The six patient groups were: Multimodal Pain Management (n = 50), Standard Pain Management (n = 50), ERAS (n = 50), Preoperative Assessment (n = 100), Standard Preoperative Assessment (n = 100), and Standard Care (n = 50). The patient’s satisfaction, long-term recovery, pain, anxiety, and complication rates were among the outcomes that were measured. Results After the intervention, the mean anxiety level of the ERAS group was significantly lower (P

Abstract Aim Explore the effects of mitochondrial transplantation (MT) after cardiopulmonary resuscitation (CPR) on the polarization of microglia/macrophages (MG/MΦ) and neurological function. Methods Seventy-five Sprague-Dawley rats were randomly divided into five groups: sham, normal saline (NS), vehicle, mitochondria (Mito), and non-functional mitochondria (N-Mito) group. Rats in sham group underwent surgical procedures without cardiac arrest, while the other four groups underwent cardiac arrest and CPR, and then received NS, respiration buffer, mitochondrial suspension or non-functional mitochondria, immediately after the restoration of spontaneous circulation (ROSC). The number of mitochondria in the hippocampus, the morphology and structure of mitochondria in MG/MΦ, the phenotype of MG/MΦ, and hippocampal tissue injury, neuroinflammation, and neuronal apoptosis were detected on days 1 and 3 after ROSC. Neurodeficit score (NDS) was performed on days 1, 3, 7, 15 and 30 after ROSC. Results Compared with other groups, the number of mitochondria in the hippocampus was increased, and the morphology and structure of mitochondria in MG/MΦ were significantly improved in the Mito group. Our results show higher expression of M2-type markers in MG/MΦ and decreased hippocampal tissue damage in the Mito group. Levels of NSE and S100β in serum, and TNF-α, IL-6 in the hippocampus were decreased, while the levels of TGF-β and IL-10 were increased in the Mito group. Apoptosis rate of neurons in the Mito group was decreased and the NDS of the Mito group was higher than the other groups. Conclusions Exogenous MT can improve neurological function after CPR by promoting the polarization of MG/MΦ to M2-type cells, and this could be a potential method for brain protection after CPR.

Abstract This study explores the relationship between surface roughness and characteristic scale through theoretical analyses and experimental data. Considering the concavity and convexity of cycloidal gear tooth profile curvatures, a curved surface contact coefficient model suitable for both inner and outer contacts, with either equal or unequal curvatures, has been developed. Moreover, a fractal contact model is constructed for cycloidal pinwheels. This model considers scale correlation and analyzes the influence of microscopic parameters on the elastic-plastic critical grade and the behavior of the contact area. Additionally, the influence of the micro-convex body frequency index on surface contact performance is explored to provide theoretical insights for improving the elastic contact ratio and reducing wear on contact surfaces.

Abstract Background Assessing the methodological quality of case reports and case series is challenging due to human judgment variability and time constraints. We evaluated the agreement in judgments between human reviewers and GPT-4 when applying a standard methodological quality assessment tool designed for case reports and series. Methods We searched Scopus for systematic reviews published in 2023–2024 that cited the appraisal tool by Murad et al. A GPT-4 based agent was developed to assess the methodological quality using the 8 signaling questions of the tool. Observed agreement and agreement coefficient were estimated comparing published judgments of human reviewers to GPT-4 assessment. Results We included 797 case reports and series. The observed agreement ranged between 41.91% and 80.93% across the eight questions (agreement coefficient ranged from 25.39 to 79.72%). The lowest agreement was noted in the first signaling question about selection of cases. The agreement was similar in articles published in journals with impact factor

Abstract Background Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.

High-repetition-rate free-electron lasers impose stringent requirements on the thermal deformation of beamline optics. The Shanghai HIgh-repetition-rate XFEL aNd Extreme light facility (SHINE) experiences high average thermal power and demands wavefront preservation. To deeply study the thermal field of the first reflection mirror M1 at the FEL-II beamline of SHINE, thermal analysis under a photon energy of 400 eV was executed by fluid and solid heat transfer method. According to the thermal analysis results and the reference cooling water temperature of 30 °C, the temperature of the cooling water at the flow outlet is raised by 0.15 °C, and the wall temperature of the cooling tube increases by a maximum of 0.5 °C. The maximum temperature position of the footprint centerline in the meridian direction deviates away from the central position, and this asymmetrical temperature distribution will directly affect the thermal deformation of the mirror and indirectly affect the focus spot of the beam at the sample.

Abstract In multiple physical fields, the mutual influence among these fields can significantly impact material elastoplasticity. This paper proposes a thermodynamic-based constitutive model that incorporates the mutual influence of multiple physical fields. Rather than treating physical field characteristics as adjustable “parameters” affecting material coefficients, the proposed model employs a thermodynamic dissipation potential derived from the Onsager reciprocity relations, accounting for thermodynamic forces coupling. This dissipation potential ensures that the thermodynamic flow in the stress field is influenced by both stress field and other physical fields thermodynamic forces, which describes the plastic flow under multiple physical fields, while preserving thermodynamic duality. The paper begins with the formulation of a generalized thermodynamic model applicable to diverse materials and types of coupled fields, which is then degraded to a specific model for AA5182-O AlMg alloy under the influence of temperature and strain rate fields coupling. Given the universal applicability of the generalized model, such degradation provides a structured approach framework for developing thermodynamics-based constitutive models. For different materials encountered in practical engineering, new thermodynamic forces can be introduced to describe their unique mechanical properties while preserving the overarching thermodynamics-based model framework, thereby facilitating model scalability. The paper concludes with a validation example, showing that within the Portevin-Le Chatelie (PLC) regime, the plastic flow stress of AA5182-O AlMg alloy decreases with increasing strain rate at low temperatures but increases at high temperatures. The accurate simulation of these distinct strain rate effects crucially relies on integrating the mutual influence of temperature field and strain rate field.

Abstract Background The current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses. Methods We retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003–2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles. Results The analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P

Very low frequency(VLF) electromagnetic wave provides a reliable method for cross-medium communication in polar sea environments due to its ability to penetrate seawater. In order to solve the problem of polar VLF electromagnetic wave propagation across the ice layer, a multilayer dielectric propagation model based on the transmission matrix was established in this paper. The attenuation characteristics of VLF electromagnetic waves in air-ice layer-seawater and the influence of incident angle were studied by using the two-port network equivalent circuit method. Through simulation and field experiment data, the attenuation law of VLF electromagnetic wave field intensity in the ice layer was quantified for the first time, revealing the important discovery that the attenuation of VLF electromagnetic wave field intensity in the ice layer was less than 1 dB per meter. The effect of sea ice on VLF communication in polar regions was evaluated. The results show that sea ice had less loss on VLF electromagnetic waves and was not the main factor affecting VLF communication.

Abstract Introduction Noninvasive ventilation (NIV) is widely used for sequential extubation in patients with chronic obstructive pulmonary disease (COPD). However, NIV may cause many adverse events such as claustrophobia, facial skin compression, air leakage, bloating, and even reflux aspiration, resulting in poor patient compliance/tolerance and high failure rate, especially for older adults who are at high risk of communication difficulties and consciousness disorder. High-flow nasal cannula (HFNC) oxygen therapy is a new alternative support to NIV, but whether it can effectively reduce the rate of re-intubation after extubation in elderly patients with COPD remains controversial. The purpose of this study is to explore the safety and efficacy of HFNC versus NIV for elderly COPD patients after extubation. Methods and analysis This study is an investigator-initiated, single-center, prospective, non-inferior, randomized controlled trial. Elderly patients (age > 65 years) who have received invasive ventilation and was diagnosed with COPD will be randomly assigned to HFNC group or NIV group immediately after extubation with a planned enrollment of 168 patients. The primary outcomes will be reintubation rates at 72 h and 7 days after extubation. Secondary outcomes will include treatment failure, post-extubation vital signs and arterial blood gases, the scores of compliance and comfort of patients, duration of respiratory support after extubation, respiratory support related adverse events, sleep quality scores, usage of sedative and analgesic drugs after extubation, and the incidence of delirium. Additionally, clinical outcomes such as ventilator-free days at 28 days post-randomization, tracheotomy rate, duration of intensive care unit (ICU) and hospital stay, ICU and hospital mortality will be evaluated. Ethics and dissemination This study has been approved by the Ethics Committee of West China Hospital of Sichuan University (2023–2284). Informed consent is required. It is expected that a follow-up randomized controlled trial will be conducted. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration The study was retrospectively registered at ClinicalTrials.gov (ChiCTR2400087312).

Abstract Background Elucidating the dynamics of gene expression across developmental stages, including the genomic characteristics of brain expression during infancy, is pivotal in deciphering human psychiatric and neurological disorders and providing insights into developmental disorders. Results Leveraging comprehensive human GWAS associations with temporal and spatial brain expression data, we discovered a distinctive co-expression cluster comprising 897 genes highly expressed specifically during infancy, enriched in functions related to the neuronal system. This gene cluster notably harbors the highest ratio of genes linked to psychiatric and neurological disorders. Through computational analysis, MYT1L emerged as a potential central transcription factor governing these genes. Remarkably, the infancy-specific expressed genes, including SYT1, exhibit prominent colocalization within human accelerated regions. Additionally, chromatin state analysis unveiled prevalent epigenetic markers associated with enhancer-specific modifications. In addition, this cluster of genes has demonstrated to be specifically highly expressed in cell-types including excitatory neurons, medial ganglionic eminence and caudal ganglionic eminence. Conclusions This study comprehensively characterizes the genomics and epigenomics of genes specifically expressed during infancy, identifying crucial hub genes and transcription factors. These findings offer valuable insights into early detection strategies and interventions for psychiatric and neurological disorders.

Abstract Background Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs’ fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism? Results In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine. Conclusions We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10−4, OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10−3, OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10−4, OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome’s roles in respiratory diseases’ clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.

Abstract Recent advancements of quantum technologies have triggered tremendous interest in exploring practical quantum advantage. The simulation of fluid dynamics, a highly challenging problem in classical physics but vital for practical applications, emerges as a potential direction. Here, we report an experiment on the digital simulation of unsteady flows with a superconducting quantum processor. The quantum algorithm is based on the Hamiltonian simulation using the hydrodynamic formulation of the Schrödinger equation. With the median fidelities of 99.97% and 99.67% for parallel single- and two-qubit gates respectively, we simulate the dynamics of a two-dimensional (2D) compressible diverging flow and a 2D decaying vortex with ten qubits. Note that the former case is an inviscid potential flow, and the latter one is an artificial vortical flow with an external body force. The experimental results well capture the temporal evolution of averaged density and momentum profiles, and qualitatively reproduce spatial flow fields with moderate noises. This work demonstrates the potential of quantum computing in simulating more complex flows, such as turbulence, for practical applications.

Abstract Background Reference intervals, which define an interval in which a specific proportion of measurements from a healthy population are expected to fall, are commonly used in medical practice. Synthesizing information from multiple studies through meta-analysis can provide a more precise and representative reference interval than one derived from a single study. However, the current approaches for estimating the reference interval from a meta-analysis mainly rely on aggregate data and require parametric distributional assumptions that cannot always be checked. Methods With the availability of individual participant data (IPD), non-parametric methods can be used to estimate reference intervals without any distributional assumptions. Furthermore, patient-level covariates can be introduced to estimate personalized reference intervals that may be more applicable to specific patients. This paper introduces quantile regression as a method to estimate the reference interval from an IPD meta-analysis under the fixed effects model. Results We compared several non-parametric bootstrap methods through simulation studies to account for within-study correlation. Under fixed effects model, we recommend keeping the studies fixed and only randomly sampling subjects with replacement within each study. Conclusion We proposed to use the quantile regression in the IPD meta-analysis to estimate the reference interval. Based on the simulation results, we identify an optimal bootstrap strategy for estimating the uncertainty of the estimated reference interval. An example of liver stiffness measurements, a clinically important diagnostic test without explicitly established reference range in children, is provided to demonstrate the use of quantile regression in estimating both overall and subject-specific reference intervals.

Abstract Exploring the impact of physical exercise on adolescent insomnia and the chained mediating role of psychological inflexibility and stress between them. In September 2023, a questionnaire survey was conducted among 416 adolescents in Xiangxi Prefecture, collecting data on physical activity, insomnia, psychological inflexibility, stress, and related variables. Statistical analysis was performed, involving 215 boys and 201 girls with an average age of 15.37 ± 0.54 years. (1) Adolescent physical exercise showed significant negative correlations with stress (r =−0.329, P

Abstract Topologically ordered phases of matter elude Landau’s symmetry-breaking theory, featuring a variety of intriguing properties such as long-range entanglement and intrinsic robustness against local perturbations. Their extension to periodically driven systems gives rise to exotic new phenomena that are forbidden in thermal equilibrium. Here, we report the observation of signatures of such a phenomenon—a prethermal topologically ordered time crystal—with programmable superconducting qubits arranged on a square lattice. By periodically driving the superconducting qubits with a surface code Hamiltonian, we observe discrete time-translation symmetry breaking dynamics that is only manifested in the subharmonic temporal response of nonlocal logical operators. We further connect the observed dynamics to the underlying topological order by measuring a nonzero topological entanglement entropy and studying its subsequent dynamics. Our results demonstrate the potential to explore exotic topologically ordered nonequilibrium phases of matter with noisy intermediate-scale quantum processors.

Highlights Single-atom Fe–N4 sites embedded into graphene were successfully synthesized to exert the dielectric properties of graphene. The absorption mechanisms of metal-nitrogen doping reduced graphene oxide mainly include enhanced dipole polarization, interface polarization, conduction loss and defect-induced polarization. Excellent reflection loss of − 74.05 dB (2.0 mm) and broad effective absorption bandwidth of 7.05 GHz (1.89 mm, with filler loading only 1 wt%) were obtained.

Abstract Translation, a fundamental process regulating cellular growth and proliferation, relies on functional ribosomes. As sessile organisms, plants have evolved adaptive strategies to maintain a delicate balance between growth and stress response. But the underlying mechanisms, particularly on the translational level, remain less understood. In this study, we revealed the mechanisms of AtPRMT3-RPS2B in orchestrating ribosome assembly and managing translational regulation. Through a forward genetic screen, we identified PDCD2-D1 as a suppressor gene restoring abnormal development and ribosome biogenesis in atprmt3-2 mutants. Our findings confirmed that PDCD2 interacts with AtPRMT3-RPS2B, and facilitates pre-ribosome transport through nuclear pore complex, finally ensuring normal ribosome translation in the cytoplasm. Additionally, the dysfunction of AtPRMT3-RPS2B was found to enhance freezing tolerance. Moreover, we revealed that AtPRMT3-RPS2B promotes the translation of housekeeping mRNAs while concurrently repressing stress-related mRNAs. In summary, our study sheds light on the regulatory roles of AtPRMT3-RPS2B in ribosome assembly and translational balance, enabling the trade-off between growth and stress.

Abstract Greenberger-Horne-Zeilinger (GHZ) states, also known as two-component Schrödinger cats, play vital roles in the foundation of quantum physics and the potential quantum applications. Enlargement in size and coherent control of GHZ states are both crucial for harnessing entanglement in advanced computational tasks with practical advantages, which unfortunately pose tremendous challenges as GHZ states are vulnerable to noise. Here we propose a general strategy for creating, preserving, and manipulating large-scale GHZ entanglement, and demonstrate a series of experiments underlined by high-fidelity digital quantum circuits. For initialization, we employ a scalable protocol to create genuinely entangled GHZ states with up to 60 qubits, almost doubling the previous size record. For protection, we take a different perspective on discrete time crystals (DTCs), originally for exploring exotic nonequilibrium quantum matters, and embed a GHZ state into the eigenstates of a tailor-made cat scar DTC to extend its lifetime. For manipulation, we switch the DTC eigenstates with in-situ quantum gates to modify the effectiveness of the GHZ protection. Our findings establish a viable path towards coherent operations on large-scale entanglement, and further highlight superconducting processors as a promising platform to explore nonequilibrium quantum matters and emerging applications.

Abstract Microplastics (MPs) have emerged as a significant food‐related risk factor, posing potential threats to human health through dietary intake and the food chain. This review comprehensively analyses the impact of MPs as a novel food safety risk factor on human health (in particular on the gastrointestinal route). Furthermore, we explore the potential mechanisms by which dietary fibers (DFs) may alleviate the health risks associated with MPs. The impact of DFs on human health is intricately linked to factors such as their size, concentration, and composition. We characterize current knowledge and highlight gaps. Although DFs may be a potential strategy to reduce the impact of MPs on organism health, more in‐depth studies are needed to determine their practical effects and application prospects. In particular, research on MPs that actively reduce intake in vivo remains relatively limited and needs to receive more attention from the scientific community.

Abstract Background To investigate the values of apparent diffusion coefficient (ADC) for the treatment response evaluation in pancreatic cancer (PC) patients receiving neoadjuvant therapy (NAT). Methods This study included 103 NAT patients with histologically proven PC. ADC maps were generated using monoexponential diffusion-weighted imaging (b values: 50, 800 s/mm2). Tumors’ minimum, maximum, and mean ADCs were measured and compared pre- and post-NAT. Variations in ADC values measured between pre- and post-NAT completion for NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0–2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analyzed. Results The minimum, maximum, and mean ADC values all increased dramatically after NAT, rising from 23.4 to 25.4% (all p

Abstract Riboswitches are structured RNA elements that regulate gene expression upon binding to small molecule ligands. Understanding the mechanisms by which small molecules impact riboswitch activity is key to developing potent, selective ligands for these and other RNA targets. We report the structure-informed design of chemically diverse synthetic ligands for PreQ1 riboswitches. Multiple X-ray co-crystal structures of synthetic ligands with the Thermoanaerobacter tengcongensis (Tte)-PreQ1 riboswitch confirm a common binding site with the cognate ligand, despite considerable chemical differences among the ligands. Structure probing assays demonstrate that one ligand causes conformational changes similar to PreQ1 in six structurally and mechanistically diverse PreQ1 riboswitch aptamers. Single-molecule force spectroscopy is used to demonstrate differential modes of riboswitch stabilization by the ligands. Binding of the natural ligand brings about the formation of a persistent, folded pseudoknot structure, whereas a synthetic ligand decreases the rate of unfolding through a kinetic mechanism. Single round transcription termination assays show the biochemical activity of the ligands, while a GFP reporter system reveals compound activity in regulating gene expression in live cells without toxicity. Taken together, this study reveals that diverse small molecules can impact gene expression in live cells by altering conformational changes in RNA structures through distinct mechanisms.

Abstract Given the surpassing of the Shockley-Quiesser efficiency limit in conventional p-n junction photovoltaic effect, bulk photovoltaic effect (BPVE) has garnered significant research interest. However, the BPVE primarily focuses on a narrow wavelength range, limiting its potential applications. Here we report a giant infrared bulk photovoltaic effect in tellurene (Te) for broad-spectrum neuromodulation. The generated photocurrent in uniformly illuminated Te excludes other photoelectric effects and is attributed to the BPVE. The bulk photovoltaic wavelength in Te spans a wide range from the ultraviolet (390 nm) to the mid-infrared (3.8 µm). Moreover, the photocurrent density of 70.4 A cm−2 under infrared light simulation outperforms that in previous ultraviolet and visible semiconductors as well as infrared semimetals. Te attached to the dendrites or somata of the cortical neurons successfully elicit action potentials under broad-spectrum light irradiation. This work lays the foundation for the further development of infrared BPVE in narrow bandgap materials.

Abstract Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and biocompatibility. In the field of sports medicine, their application opens up new possibilities for the prevention and treatment of sports‐related diseases. The authors will introduce the existing theoretical models of friction in the locomotor system, the characteristics and advantages of biomimetic lubrication materials and discuss in depth their applications in the field of sports medicine. The development of bionic lubrication materials opens up unprecedented opportunities for sports medicine to provide more effective and long‐lasting treatment options for patients.

Abstract Although the critical path method (CPM) is effective for the integrated scheduling of small-batch orders, its overemphasis on vertical process relationships and neglect of horizontal parallel relationships have imposed limitations on scheduling, often leading to suboptimal outcomes in terms of the total product completion time. This study introduces an innovative algorithm designed to overcome these limitations and further optimize the total processing time of products. We propose a strategy of "exchanging adjacent processes on the same device", which operates based on the scheduling results of the CPM. By swapping adjacent and interchangeable processes within the constraints of the problem, this algorithm generates multiple new scheduling schemes, effectively expanding the solution space. This expansion enables the discovery of optimized solutions that leverage "horizontal parallel relationships", which is crucial for reducing the "total processing time of products". Finally, the effectiveness of the proposed algorithm is verified through experiments.

Abstract Background Skin conditions are common in patients on maintenance hemodialysis and those with pancreatitis. However, there is a lack of research on dermatological issues in patients who have both hemodialysis and pancreatitis concurrently. Case presentation A 62-year-old male patient with a 4-year history of maintenance hemodialysis (MHD) presented with pain and was diagnosed with acute pancreatitis and gallbladder stones. Markedly elevated blood amylase, creatine kinase, and myoglobin were noted, alongside a purplish-red skin discoloration. Treatment included inhibition of digestive fluid secretion, anti-infection measures, blood purification, fasting, rehydration, and symptomatic care. Notably, continuous renal replacement therapy (CRRT) combined with hemoperfusion (HP) was employed. The patient’s dialysis effluent initially appeared red. Upon examination of the patient’s peripheral blood smear, red blood cell debris was not observed. The dialysis effluent (on Day 0) was analyzed, revealing no hemoglobin (0 g/L) but an elevated myoglobin concentration of 80.4 U/L. After the therapeutic intervention, the indicators, including the blood amylase, C-reactive protein, total bilirubin, creatine kinase, and myoglobin were improved. The patient experienced resolution of sternal and upper abdominal pain within two days. After four consecutive days of CRRT and HP treatment, the skin color returned to normal, alongside improved clarity of the dialysis effluent. Subsequently, the patient’s method of blood purification was reverted to conventional hemodialysis. On the eighth day of hospitalization, the patient resumed normal diet and was discharged. Conclusions In the case of the current patient with acute pancreatitis undergoing MHD, it is noteworthy to report the observation of a unique purplish-red skin discoloration. This phenomenon may be attributable to inflammation resulting from acute pancreatitis, and the retention of myoglobin within the body.

Abstract Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U18U19G20-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment. Graphical Abstract

Abstract This study proposes a frequency coupling suppression strategy for voltage source converters (VSCs) with DC‐link dynamics to address the challenges posed by the asymmetric system structures for system modelling and control design. The strategy introduces a reshaping outer loop into the q‐axis, which eliminates the conjugate voltages and currents induced by the DC‐link dynamics, to achieve decoupling of the DC‐link voltage control (DVC). Therefore, the VSC is modelled as a single‐input single‐output (SISO) admittance model, which provides clear physical insights for the analysis of admittance characteristics. Compared with the admittance matrix, the SISO model reveals the dominance of each control dynamics on VSC admittance in different frequency bands. This insight facilitates the exploration of optimized control strategies to improve the system stability margin. Based on the SISO model, a virtual admittance for compensating the negative resistive effect of the PLL is designed to illustrate the advantages of the proposed method in providing design‐oriented analysis. Experimental results verify the effectiveness of the proposed control strategy.

Abstract This article introduces a Wasserstein distance‐based distributionally robust optimization model to address the transmission expansion planning considering renewable‐based microgrids (MGs) under the impact of uncertainties. The primary objective of the presented methodology is to devise a robust expansion strategy that accounts for both long‐term uncertainty and short‐term variability over the planning horizon from the perspective of a central planner. In this framework, the central planner fosters the construction of appropriate transmission lines and the deployment of optimal MG‐based generating units among profit‐driven private investors. The Wasserstein distance uncertainty set is used to characterize the long‐term uncertainty associated with future load demand. Short‐term uncertainties, stemming from variations in load demands and production levels of stochastic units, are modeled through operating conditions. To ensure the tractability of the proposed planning model, the authors introduce a decomposition framework embedded with a modified application of Bender's method. To validate the efficiency and highlight the potential benefits of the proposed expansion planning methodology, two case studies based on simplified IEEE 6‐bus and IEEE 118‐bus systems are included. These case studies assess the effectiveness of the presented approach, its ability to navigate uncertainties, and its capacity to effectively optimize expansion decisions.

Plasma arc additive manufacturing (PAAM) was applied to fabricate TC4 and Ti48Al (gamma titanium aluminide) bimetals in this work. The impact of deposition sequence on the microstructure and mechanical properties of two groups of bimetals (TC4-Ti48Al, first deposited TC4, then Ti48Al; Ti48Al-TC4, first deposited Ti48Al, then TC4) was investigated. The results show that the ultimate tensile strengths of two groups of bimetals exhibit significant differences, with 158.4 MPa for TC4-Ti48Al and 232.3 MPa for Ti48Al-TC4, the reason for this disparity is the difference in microstructure at the transition zone, which is attributed to heat input and Marangoni convection. The phase transformation evolution of TC4-Ti48Al transition zone is (major α2 + minor α)→ (major α2 + minor γ) → (major γ + minor α2), and (major α2 + minor α) → (major α + minor α2) for Ti48Al-TC4. The formation mechanism of transition zones and relationship between the microstructure characteristics and mechanical properties of two groups of bimetals were further discussed. Overall, the property of Ti48Al-TC4 was superior, and this work provides a promising new method for the preparation of TC4 and Ti48Al bimetals.

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients’ life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P

Abstract The highly polygenic nature of human longevity renders pleiotropy an indispensable feature of its genetic architecture. Leveraging the genetic correlation between aging-related traits (ARTs), we aimed to model the additive variance in lifespan as a function of the cumulative liability from pleiotropic segregating variants. We tracked allele frequency changes as a function of viability across different age bins and prioritized 34 variants with an immediate implication on lipid metabolism, body mass index (BMI), and cognitive performance, among other traits, revealed by PheWAS analysis in the UK Biobank. Given the highly complex and non-linear interactions between the genetic determinants of longevity, we reasoned that a composite polygenic score would approximate a substantial portion of the variance in lifespan and developed the integrated longevity genetic scores (iLGSs) for distinguishing exceptional survival. We showed that coefficients derived from our ensemble model could potentially reveal an interesting pattern of genomic pleiotropy specific to lifespan. We assessed the predictive performance of our model for distinguishing the enrichment of exceptional longevity among long-lived individuals in two replication cohorts (the Scripps Wellderly cohort and the Medical Genome Reference Bank (MRGB)) and showed that the median lifespan in the highest decile of our composite prognostic index is up to 4.8 years longer. Finally, using the proteomic correlates of iLGS, we identified protein markers associated with exceptional longevity irrespective of chronological age and prioritized drugs with repurposing potentials for gerotherapeutics. Together, our approach demonstrates a promising framework for polygenic modeling of additive liability conferred by ARTs in defining exceptional longevity and assisting the identification of individuals at a higher risk of mortality for targeted lifestyle modifications earlier in life. Furthermore, the proteomic signature associated with iLGS highlights the functional pathway upstream of the PI3K-Akt that can be effectively targeted to slow down aging and extend lifespan.

Abstract Mycoplasma bovis (M. bovis) is capable of causing a range of diseases in cattle, encompassing calf pneumonia, arthritis, conjunctivitis, meningitis, and mastitis. It is widely recognized as one of the predominant pathogens posing a significant threat to the global cattle industry. Therefore, accurate and sensitive methods are urgently needed to detect M. bovis. This study aims to detect M. bovis by combining colloidal gold with biotin-labeled oligonucleotides to improve detection sensitivity and form a chromogenic detection probe based on signal amplification technology. Here, we developed a sensitive and specific polymerase chain reaction-lateral flow dipstick assay (PCR-LFD) strip for efficient nucleic acid detection of M. bovis. A pair of specific primers with 5’ ends labeled with biotin and digoxigenin probes was designed for PCR experiments. Colloidal gold particles-labeled anti-digoxigenin IgG coated gold-labeled test strip was prepared, streptavidin was used as the detection probe, and nitrocellulose membrane coated goat anti-mouse IgG was used as the control line. Our results showed that the detection limit of the PCR-LFD was 89 fg/µL for the M. bovis DNA. The results from the test strip were highly consistent with those from real-time qPCR. This assay were highly specific for M. bovis, as there were no cross-reactions with other microorganisms tested and the detection sensitivity of the test was also relatively high (97.67%). The novel strips present a promising tool for the cost-effective and sensitive diagnosis of M. bovis.

Abstract Background Airway pressure release ventilation (APRV) has become increasingly popular for the management of acute respiratory distress syndrome (ARDS); however, its clinical impact remains a topic of debate. Furthermore, there is a gap between the guidelines and the actual clinical practices in mechanical ventilation management for ARDS. This survey aimed to explore the utilization of APRV and mechanical ventilation strategies for ARDS in Chinese intensive care unit (ICU) clinicians. Methods A comprehensive 34‐item survey was distributed online platforms amongst ICU clinicians across mainland China from June to August 2019. Results A total of 420 valid responses were collected, with 57.4% (241) originating from academic hospitals and 42.6% (179) from non‐academic hospitals. Of the respondents, 98.6% (414) recognized the significance of low tidal volume ventilation for ARDS prognosis, 85.2% adhered to a tidal volume below 8 mL/kg predicted body weight, and most (46.4%) selected the initial positive end‐expiratory pressure within the range of 5–10 cmH2O based on experience. Among the respondents, 62.1% (261) reported familiarity with APRV and 41.9% (176) had implemented APRV. Of those who had utilized APRV, 93.2% (164) believed in its effectiveness for ARDS patients and 69.3% (122) advocated for early application of APRV. Substantial variations were noted regarding APRV initiation settings and the preservation of spontaneous breathing during APRV. Academic hospitals exhibited higher usage rates of lung recruitment, neuromuscular blockade, prone ventilation, and acquaintance with and utilization of APRV compared to non‐academic hospitals (all p values ≤ 0.001). Conclusions Our findings highlight opportunities for improvement in mechanical ventilation management for ARDS, particularly in non‐academic hospitals. Additionally, a significant proportion of clinicians demonstrated limited knowledge of APRV, and there was a lack of consensus on its application. Further training and larger‐scale clinical trials are required to validate the efficacy and utilization of APRV in managing ARDS.

Abstract The Chinese government has introduced a carbon neutral policy to cope with the rapid changes in the global climate. It is not clear what impact this policy will have on wildlife. Therefore, this study analyzed the suitable habitat distribution of China’s unique leopard subspecies in northern Shaanxi, and simulated the potential suitable habitat distribution under different carbon emission scenarios at two time points of future carbon peak and carbon neutralization. We found that in the future SSPs 126 scenario, the suitable habitat area and the number of suitable habitat patches of North China leopard will continue to increase. With the increase of carbon emissions, it is expected that the suitable habitat of North China leopard will continue to be fragmented and shifted. When the annual average temperature is lower than 8 °C, the precipitation seasonality is 80–90 mm and the precipitation of the warmest quarter is greater than 260 mm, the probability of occurrence of North China leopard is higher. The increase in carbon emissions will lead to the reduction, migration, and fragmentation of the suitable habitat distribution of the North China leopard. Carbon neutrality policies can protect suitable wild habitats. In the future, the impact of carbon neutrality policies on future wildlife habitat protection should be carried out in depth to effectively promote the construction of wildlife protection projects.

Abstract Background Reticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections. Methods To further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control. Results In the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens. Conclusion In this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV.

Abstract Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor and signal central to cell metabolisms. Disrupting NAD homeostasis in plant alters growth and stress resistance, yet the underlying mechanisms remain largely unknown. Here, by combining genetics with multi-omics, we discover that NAD+ deficiency in qs-2 caused by mutation in NAD+ biosynthesis gene-Quinolinate Synthase retards growth but induces biosynthesis of defense compounds, notably aliphatic glucosinolates that confer insect resistance. The elevated defense in qs-2 is resulted from activated jasmonate biosynthesis, critically hydroperoxidation of α-linolenic acid by the 13-lipoxygenase (namely LOX2), which is escalated via the burst of chloroplastic ROS-singlet oxygen (1O2). The NAD+ deficiency-mediated JA induction and defense priming sequence in plants is recapitulated upon insect infestation, suggesting such defense mechanism operates in plant stress response. Hence, NAD homeostasis is a pivotal metabolic checkpoint that may be manipulated to navigate plant growth and defense metabolism for stress acclimation.

Marine creatures have an abundance of polysaccharides, active proteins, active peptides, and amino acids. With advancements in separation extraction and structure-activity relationship analysis technology, marine animal polysaccharides, as important components of marine animal active ingredients, are shown to exhibit a variety of biological activities such as immune regulation, hypoglycemic activities, antioxidant effects, lipid-lowering processes, and anticancer properties. This article examines the different types, biological activities, and applications of polysaccharides in biomedicine, aquaculture, food, cosmetics, and proposes potential research directions for pursuit by providing theoretical reference to promote the high-value and ecological development and utilization of marine animals.

The in-situ TEM irradiation experiments of zirconium alloy were conducted at 573 K, 673 K, and 773 K utilizing a 400 keV Kr + single beam and a 400 keV Kr+ and 30 keV He + dual beam. The results show that a large number of dislocation loops have been characterized in the matrix of the zirconium alloy under irradiation. With increasing the irradiation damage dose, some dislocation loops have reacted with one another to form a larger dislocation loop, which has finally formed dislocation lines or other defect structures. In zirconium alloys irradiated with Kr + single beam and Kr+ and He + dual-beam radiation, the proportion of type dislocation loops with different Burgers vectors is essentially the same at low damage doses, but the proportion of interstitial type dislocation loops with the same Burgers vectors is obviously different. The amorphization of the second phase and the dissolution of the small-sized second phase were also pointed out. With the increase in temperature, the density of the dislocation loop in zirconium alloy gradually decreases, and the size of dislocation loop first increases and then decreases. Kr+ and He + dual beam irradiation increases the size of dislocation loops but decreases their density as compared with Kr + single beam irradiation.

Let $ G = (V(G), E(G)) $ be a simple connected graph with vertex set $ V(G) $ and edge set $ E(G) $. The atom-bond sum-connectivity (ABS) index was proposed recently and is defined as $ ABS(G) = \sum_{uv\in E(G)}\sqrt{\frac{d_{G}(u)+d_{G}(v)-2}{d_{G}(u)+d_{G}(v)}} $, where $ d_{G}(u) $ represents the degree of vertex $ u\in V(G) $. A connected graph $ G $ is called a unicyclic graph if $ |V(G)| = |E(G)| $. In this paper, we determine the maximum ABS index of unicyclic graphs with given diameter. In addition, the corresponding extremal graphs are characterized.

Abstract Background Mobility limitations (e.g., using wheelchair) have been closely linked to diminished functional independence and quality of life in older adults. The regulation of mobility is pertaining to multiple neurophysiologic and sociodemographic factors. We here aimed to characterize the relationships of these factors to the risk of restricted mobility in older adults. Methods In this longitudinal study, 668 older adults with intact mobility at baseline completed the baseline assessments of clinical characteristics, cognitive function, sleep quality, activities of daily living (ADL), walking performance, beat-to-beat blood pressure, and structural MRI of the brain. Then 506 of them (mean age = 70.7 ± 7.5 years) responded to the follow-up interview on the mobility limitation (as defined by if using wheelchair, cane, or walkers, or being disabled and lying on the bed) after 18 ± 3.5 months. Logistic regression analyses were performed to examine the relationships between the baseline characteristics and the follow-up mobility restriction. Results At baseline, compared to intact-mobility group (n = 475), restricted-mobility group (n = 31) were older, with lower score of ADL and the Montreal Cognitive Assessment (MoCA), greater score of Pittsburgh Sleep Quality Index (PSQI), poorer cardio- and cerebral vascular function, and slower walking speeds (ps

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions: Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.