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Abstract The expression of TRIM47, a member of the TRIM protein and E3 ubiquitin ligase families, is elevated in various cancers, such as non-small cell lung cancer and colorectal cancer, and is linked to poor prognosis. This study aimed to investigate the role of TRIM47 in gastric cancer development. Using The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset and analysis of 20 patient samples from our center, TRIM47 was found to be significantly up-regulated in gastric cancer tissues and associated with advanced N-stage and poor prognosis. We constructed stable TRIM47 knockdown and overexpressing gastric cancer cell lines. CCK8, EDU, colony formation, wound healing, and Transwell tests were used to evaluate the effects on cell proliferation, invasion, and migration. The results showed that TRIM47 knockdown inhibited the proliferation, migration and invasion of gastric cancer cells, while TRIM47 overexpression promoted these behaviors. These results were further confirmed in vivo. In the mechanism part, we found that TRIM47 interacts with CYLD protein. Moreover, TRIM47 promotes K48-linked ubiquitination, leading to the degradation of CYLD by the proteasome, thereby activating the NF-κB pathway and regulating the biological behavior of gastric cancer cells. Taken together, our study demonstrated that TRIM47 is involved in the proliferation and metastasis of gastric cancer through the CYLD/NF-κB pathway.

Abstract Chronic rhinosinusitis (CRS) is a prevalent inflammatory airway disease affecting over 10% of the global population, leading to considerable socio-economic impacts, especially in developing countries. The pathogenesis of CRS is multifactorial, involving potential contributions from both genetic and environmental factors. While the influence of allergic and autoimmune diseases on CRS has been observed, the causal relationships between these diseases and CRS remain unclear. We extracted data from large-scale genome-wide association studies (GWAS) and utilized a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between CRS and ten autoimmune and allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), psoriasis, type 1 diabetes (T1D), hypothyroidism, celiac disease (CeD), multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Additionally, we conducted colocalization analysis to determine whether the allergic/autoimmune diseases showing statistical causal relationships with CRS are driven by the same genetic variants. The MR analysis identified that AR (OR = 1.30; 95% CI = 1.21–1.40; P = 3.26E−13), asthma (OR = 1.35; 95% CI = 1.25–1.45; P = 1.35E−14), and AD (OR = 1.17; 95% CI = 1.06–1.30; P = 0.003) were significantly associated with an increased risk of developing CRS. Interestingly, psoriasis (OR = 0.05; 95% CI = 0.01–0.37; P = 0.004) appeared to have a protective effect against CRS. Associations for T1D and hypothyroidism were also suggestive as potential risk factors for CRS. No significant associations in the reverse MR analysis, suggesting a one-directional relationship. Colocalization analysis indicated that asthma (PP.H4 = 0.99) shared the same genetic variant (IL-33 rs3939286) with CRS. In conclusion, our study confirmed the causal relationships between allergic and autoimmune diseases (AR, asthma, AD, and psoriasis) and CRS. Notably, we identified a shared genetic variant, rs3939286 in the IL-33 gene, between asthma and CRS, suggesting that targeting the IL-33 pathway may provide a therapeutic strategy for both diseases.

Abstract Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of various diseases, such as infectious diseases, autoimmune disorders, metabolic diseases, and cancers. In this context, IRFs display a dichotomous nature, functioning as both tumor suppressors and promoters, contingent upon the specific disease milieu. Post-translational modifications of IRFs, including phosphorylation and ubiquitination, play a crucial role in modulating their function, stability, and activation. As prospective biomarkers and therapeutic targets, IRFs present promising opportunities for disease intervention. Further research is needed to elucidate the precise mechanisms governing IRF regulation, potentially pioneering innovative therapeutic strategies, particularly in cancer treatment, where the equilibrium of IRF activities is of paramount importance.

Abstract This project utilized both field experiment and laboratory analyses to address the gap in understanding regarding the alterations in properties and functions of biochar, and the impact of heavy metal passivation in soil over long-term natural field aging. The study aimed to examine the changes in the physical and chemical characteristics of biochar over an extended period of natural aging. Additionally, it sought to analyze the impact and mechanisms of biochar in reducing of the harmful effects of the heavy metal cadmium (Cd) during the aging process. Both original and aged biochar conformed to the pseudo-second-order kinetics model and the Langmuir model. The aging process enhanced the adsorption of Cd by biochar and mitigated the leaching of Cd2+ into the soil. These findings provide a scientific basis for evaluating biochar’s environmental behavior and its potential use in the remediation of soil contaminated with heavy metals.

Abstract Pediatric trauma plays a crucial role in pediatric mortality, with traffic injuries and falls frequently cited as leading causes of significant injuries among children. A comprehensive investigation, including geographical factors, is essential for developing effective strategies to prevent injuries and alleviate the burden of pediatric trauma. This study involved a retrospective analysis of clinical data from pediatric patients admitted to our hospital’s intensive care unit (ICU) due to trauma over a 10-year period. Comprehensive analyses were conducted to elucidate trends, demographics, injury patterns, and risk factors associated with these admissions. This retrospective study included 951 pediatric patients (mean age: 4.79 ± 3.24 years; mean weight: 18.45 ± 9.02 kg; median time to ICU admission post-injury: 10.86 ± 14.95 h). Among these patients, 422 (44.4%) underwent emergency surgery, and 466 (49%) required mechanical ventilation support, with a mean duration of 70.19 ± 146.62 h. The mean duration of ICU stay was 6.24 ± 8.01 days, and the overall mean hospitalization duration was 16.08 ± 15.56 days. The predominant cause of unintentional injury was traffic accidents (47.9%), followed by falls (42.5%) and burns/scalds (5.3%). Most incidents involved children aged 0–6 years (70.7%), with males comprising 60.0% of patients. Injury incidents predominantly occurred between 12 and 6 PM (44.5%) and on non-workdays (37.6%). The most common locations where injuries occurred were roadsides (49%) and rural areas (64.35%). Single-site injuries (58.78%) were more prevalent than multiple-site injuries (41.22%), and head injuries were the most common among single-site injuries (81.57%). At ICU admission, the mean injury severity score was 18.49 ± 8.86. Following active intervention, 871 patients (91.59%) showed improvement, while 80 (8.41%) succumbed to their injuries. Traffic injuries remain the primary cause of pediatric trauma leading to ICU admission, underscoring the importance of using appropriate child restraint systems and protective gear as fundamental preventive measures. The increased incidence of injuries among children aged

To date, computed tomography experiments, carried-out at synchrotron radiation facilities worldwide, pose a tremendous challenge in terms of the breadth and complexity of the experimental datasets produced. Furthermore, near real-time three-dimensional reconstruction capabilities are becoming a crucial requirement in order to perform high-quality and result-informed synchrotron imaging experiments, where a large amount of data is collected and processed within a short time window. To address these challenges, we have developed and deployed a synchrotron computed tomography framework designed to automatically process online the experimental data from the synchrotron imaging beamlines, while leveraging the high-performance computing cluster capabilities to accelerate the real-time feedback to the users on their experimental results. We have, further, integrated it within a modern unified national authentication and data management framework, which we have developed and deployed, spanning the entire data lifecycle of a large-scale scientific facility. In this study, the overall architecture, functional modules and workflow design of our synchrotron computed tomography framework are presented in detail. Moreover, the successful integration of the imaging beamlines at the Shanghai Synchrotron Radiation Facility into our scientific computing framework is also detailed, which, ultimately, resulted in accelerating and fully automating their entire data processing pipelines. In fact, when compared with the original three-dimensional tomography reconstruction approaches, the implementation of our synchrotron computed tomography framework led to an acceleration in the experimental data processing capabilities, while maintaining a high level of integration with all the beamline processing software and systems.

Umami peptides, the flavor compounds mainly derived from natural proteins, provide a pleasant taste for humans and exhibit a variety of biological activities, such as antioxidant and lipid-lowering properties. Marine proteins, which serve as excellent sources of umami peptides, have become a focal point of research. This review introduces the research progress on reported marine umami peptides. Firstly, it discusses the structural characteristics of umami peptides and the mechanism behind their formation to create an umami taste. It then presents several commonly used techniques for preparing and regulating umami peptides while summarizing the advantages and disadvantages of each technique. Finally, this review describes the potential application prospects for core technologies within Industry 4.0—such as molecular simulation, artificial intelligence, big data analysis, cloud computing, and blockchain technology—which could bring new opportunities for the development of marine umami peptides.

Abstract Background The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. Results We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. Conclusions Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Abstract Background Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. Results Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. Conclusions This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish. Video Abstract

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I–expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

Abstract Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

Abstract Objective This cross‐sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID‐19 in China. Methods This study was conducted by 45 tertiary Grade‐A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID‐19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self‐reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions The incidence of dysosmia and dysgeusia following infection with the SARS‐CoV‐2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS‐CoV‐2 vaccination, history of head‐facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Targeted protein degradation (TPD) represented by proteolysis targeting chimeras (PROTACs) marks a significant stride in drug discovery. A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond degradation. Non-small-molecule-based approaches play an irreplaceable role in this field. A wide variety of agents spanning a broad chemical spectrum, including peptides, nucleic acids, antibodies, and even vaccines, which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing paradigms. Herein we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs, including three major trajectories, to provide insights for the design strategies based on novel paradigms.

Background: Schizophrenia (SCZ) is a prevalent and serious mental disorder, and the exact pathophysiology of this condition is not fully understood. In previous studies, it has been proven that ferroprotein levels are high in SCZ. It has also been shown that this inflammatory response may modify fibromodulin. Accumulating evidence indicates a strong link between metabolism and ferroptosis. Therefore, the present study aims to identify ferroptosis‐linked hub genes to further investigate the role that ferroptosis plays in the development of SCZ. Material and methods: From the GEO database, four microarray data sets on SCZ (GSE53987, GSE38481, GSE18312, and GSE38484) and ferroptosis‐linked genes were extracted. Using the prefrontal cortex expression matrix of SCZ patients and healthy individuals as the control group from GSE53987, weighted gene co‐expression network analysis (WGCNA) was performed to discover SCZ‐linked module genes. From the feed, genes associated with ferroptosis were retrieved. The intersection of the module and ferroptosis-linked genes was done to obtain the hub genes. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were conducted. The SCZ diagnostic model was established using logistic regression, and the GSE38481, GSE18312, and GSE38484 data sets were used to validate the model. Finally, hub genes linked to immune infiltration were examined. Results: A total of 13 SCZ module genes and 7 hub genes linked to ferroptosis were obtained: DECR1, GJA1, EFN2L2, PSAT1, SLC7A11, SOX2, and YAP1. The GO/KEGG/GSEA study indicated that these hub genes were predominantly enriched in mitochondria and lipid metabolism, oxidative stress, immunological inflammation, ferroptosis, Hippo signaling pathway, AMP‐activated protein kinase pathway, and other associated biological processes. The diagnostic model created using these hub genes was further confirmed using the data sets of three blood samples from patients with SCZ. The immune infiltration data showed that immune cell dysfunction enhanced ferroptosis and triggered SCZ. Conclusion: In this study, seven critical genes that are strongly associated with ferroptosis in patients with SCZ were discovered, a valid clinical diagnostic model was built, and a novel therapeutic target for the treatment of SCZ was identified by the investigation of immune infiltration.

Abstract Repair and preservation of the injured meniscus has become paramount in clinical practice. However, the complexities of various clinic stitching techniques for meniscus repair pose challenges for grassroots doctors. Hence, there is a compelling interest in innovative therapeutic strategies such as bioadhesives. An ideal bioadhesive must cure quickly in aqueous and blood environments, bind strongly, endure arthroscopic washing pressures, and degrade appropriately for tissue regeneration. Here, we present a tetra‐poly (ethylene glycol) (PEG)‐based hydrogel bioadhesive, boasting high biocompatibility, ultrafast gelation, facile injectable operation, and favorable mechanical strength. In view of the synergistic effects of chemical anchor and physical chain entanglement to tightly bind the meniscus, a seamless interface was formed between the surrounding meniscal tissues and hydrogels, enabling the longitudinal tear of the meniscus fused in situ to withstand large tensile force with the adhesive strength of 541.5 ± 31.4 kPa and arthroscopic washout resistance of 29.4 kPa. Superior to existing commercial adhesives, ours allows sutureless application and arthroscopic assistance, without requiring specialized clinical skills. This research is expected to significantly impact our understanding of meniscal healing and ultimately promote a simpler process for achieving functional and structural recovery in torn menisci.

Abstract Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi‐C mapping, whole‐genome Bisulfite Sequencing (BS‐Seq), long‐read isoform sequencing (Iso‐Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein‐coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)‐including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full‐length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family.

Osteoporosis (OP), the most prevalent bone degenerative disease, has become a significant public health challenge globally. Current therapies primarily target inhibiting osteoclast activity or stimulating osteoblast activation, but their effectiveness remains suboptimal. This paper introduced a “three birds, one stone” therapeutic approach for osteoporosis, employing upconversion nanoparticles (UCNPs) to create a dual-gas storage nanoplatform (UZPA-CP) targeting bone tissues, capable of concurrently generating carbon monoxide (CO) and hydrogen sulfide (H2S). Through the precise modulation of 808 nm near-infrared (NIR) light, the platform could effectively control the release of CO and H2S in the OP microenvironment, and realize the effective combination of promoting osteogenesis, inhibiting osteoclast activity, and improving the immune microenvironment to achieve the therapeutic effect of OP. High-throughput sequencing results further confirmed the remarkable effectiveness of the nanoplatform in inhibiting apoptosis, modulating inflammatory response, inhibiting osteoclast differentiation and regulating multiple immune signaling pathways. The gas storage nanoplatform not only optimized the OP microenvironment with the assistance of NIR, but also restored the balance between osteoblasts and osteoclasts. This comprehensive therapeutic strategy focused on improving the bone microenvironment, promoting osteogenesis and inhibiting osteoclast activity provides an ideal new solution for the treatment of metabolic bone diseases.

Background: Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide. JEV exhibits significant neuroinvasiveness and neurotoxicity, resulting in considerable damage to the nervous system. Japanese encephalitis is associated with high morbidity and mortality rate, seriously harming both human health and livestock production. The current lack of specific antiviral drugs means that the development of new therapeutic agents for JEV has become urgent. Methods: Anti-JEV drugs were screened from 111 inhibitors of neurotransmitter receptor-related molecules by high content technology. The antiviral effects of clomipramine HCl were evaluated through plaque assay, real-time quantitative PCR, immunofluorescence assay and western blotting assay. Bioinformatic tools were utilized to cluster the altered signaling pathway members after clomipramine HCl treatment. Finally, the anti-JEV mechanism was deeply resolved in vivo via such molecular biology and virological detection techniques. Results: In this study, we screened nine compounds with significant anti-JEV activity, of which clomipramine HCl demonstrated the most potent antiviral effect and exhibited dose-dependent activity. Mechanistically, clomipramine HCl may activate endoplasmic reticulum stress and modulate the unfolded protein response, thus inhibiting the assembly stage of JEV infection. Conclusion: This study highlights the importance of clomipramine HCl as a promising approach for JEV infection protection, which may lead to new host-directed antiviral approaches to such mosquito-borne viruses.

ObjectivesThis study aimed to investigate the psychological stress experienced by frontline medical staff during the Yangbi Earthquake and to understand how coping strategies and social support influence stress responses.MethodsFrom days 3 to 14 post-earthquake, online questionnaires were administered to frontline medical staff to assess perceived social support, coping strategies, and psychological stress responses using the Perceived Social Support Scale (PSSS), Trait Coping Strategies Questionnaire (TCSQ), and Stress Response Questionnaire (SRQ). Data analysis included correlation analysis to explore relationships between variables, multiple linear regression to identify key predictors of stress, and path analysis to determine direct and indirect effects.ResultsA total of 253 valid questionnaires were analyzed, with a participant composition of 81.82% females and 18.18% males, and the majority being nurses (62.06%). Psychological stress responses varied by gender and age, with females and older age groups showing higher physical stress responses (P < 0.05). Correlation and regression analyses indicated that negative coping and lower levels of social support were associated with increased stress responses (P < 0.05). Path analysis revealed that intra-family and extra-family support influenced stress responses directly and indirectly through coping strategies (P < 0.05).ConclusionThis study suggests that perceived social support directly influences stress responses in frontline medical personnel during disasters, with coping strategies mediating this effect. Future research should explore these dynamics over time through longitudinal studies.

BackgroundMitochondrial dysfunction is an important factor in the pathogenesis of schizophrenia. However, the relationship between mitophagy and schizophrenia remains to be elucidated.MethodsSingle-cell RNA sequencing datasets of peripheral blood and brain organoids from SCZ patients and healthy controls were retrieved. Mitophagy-related genes that were differentially expressed between the two groups were screened. The diagnostic model based on key mitophagy genes was constructed using two machine learning methods, and the relationship between mitophagy and immune cells was analyzed. Single-cell RNA sequencing data of brain organoids was used to calculate the mitophagy score (Mitoscore).ResultsWe found 7 key mitophagy genes to construct a diagnostic model. The mitophagy genes were related to the infiltration of neutrophils, activated dendritic cells, resting NK cells, regulatory T cells, resting memory T cells, and CD8 T cells. In addition, we identified 12 cell clusters based on the Mitoscore, and the most abundant neurons were further divided into three subgroups. Results at the single-cell level showed that Mitohigh_Neuron established a novel interaction with endothelial cells via SPP1 signaling pathway, suggesting their distinct roles in SCZ pathogenesis.ConclusionWe identified a mitophagy signature for schizophrenia that provides new insights into disease pathogenesis and new possibilities for its diagnosis and treatment.

Introduction: Trauma is a significant global public health concern and the leading cause of morbidity and mortality in children. This study aimed to assess the independent predictors of trauma severity as well as mortality in pediatric patients admitted to the intensive care unit (ICU). Methods: In this cross-sectional study, following the STROBE checklist, we retrospectively analyzed the clinical and baseline characteristics of pediatric patients with trauma injuries admitted to the ICU of Children’s Hospital of Zhejiang University School of Medicine, China, over a decade. Results: 951 pediatric patients with a mean age of 4.79 ± 3.24 years (60.78% Boys) were studied (mortality rate 8.41%). Significant associations were observed between ISS and place of residence (p = 0.021), location of the injury (p = 0.010), year of injury (p

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in “photosynthesis” and “photosynthesis, light reaction” in Sedum alfredii Hance leaves. Moreover, the “plant hormone signal transduction” pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer's disease, Parkinson's disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing Terf2 in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, Terf2 overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of Terf2 downregulation on excitotoxicity involves Sirt3 repression leading to mitochondrial dysfunction. We propose that increasing the level of Terf2 expression is a potential strategy to reduce post-hypoxic stress damages.

Abstract Japanese encephalitis virus (JEV) is a neurotropic pathogen that causes lethal encephalitis. The high susceptibility and massive proliferation of JEV in neurons lead to extensive neuronal damage and inflammation within the central nervous system. Despite extensive research on JEV pathogenesis, the effect of JEV on the cellular composition and viral tropism towards distinct neuronal subtypes in the brain is still not well comprehended. To address these issues, we performed single-cell RNA sequencing (scRNA-seq) on cells isolated from the JEV-highly infected regions of mouse brain. We obtained 88,000 single cells and identified 34 clusters representing 10 major cell types. The scRNA-seq results revealed an increasing amount of activated microglia cells and infiltrating immune cells, including monocytes & macrophages, T cells, and natural killer cells, which were associated with the severity of symptoms. Additionally, we observed enhanced communication between individual cells and significant ligand-receptor pairs related to tight junctions, chemokines and antigen-presenting molecules upon JEV infection, suggesting an upregulation of endothelial permeability, inflammation and antiviral response. Moreover, we identified that Baiap2-positive neurons were highly susceptible to JEV. Our findings provide valuable clues for understanding the mechanism of JEV induced neuro-damage and inflammation as well as developing therapies for Japanese encephalitis.

Based on the textual-analyzed data covering 2148 IPO firms in China’s stock market during the 2007–2018 period, the authors’ purpose is to examine the influence of anti-takeover provision (ATP) adoption on initial public offerings (IPO) underpricing and identify the reducing effect of the former. The authors examine the sample consisting of Chinese A-share listed IPO firms between 2007 and 2018 from China Stock Market Accounting Research and Chinese Research Data Services, with ATP data collected from the IPO firm chapters. Specifically, the authors use text analysis to identify whether there are ATPs in the IPO firm chapters, as well as the number of ATPs. H1: IPO underpricing is less severe for firms adopting ATPs. H2: The effect of ATP adoption on IPO underpricing is more salient for firms in worse information environments. The authors examine the influence of ATP adoption on IPO underpricing and identify the reducing effect of the former. This effect can be explained by the fact that adopting ATPs in IPO firm chapters can reduce information asymmetry to a large extent by helping external investors obtain more private information, which alleviates IPO underpricing. The authors also find that the reducing effect is more significant in the worsened information environment. Furthermore, the authors explore the influence of adopting ATPs on other IPO characteristics and find positive effects on IPO over-subscription, funds raised and trading activity and negative effects on listing fees. This study mainly contributes to the literature from the following two aspects. First, the study enriches the literature about the influencing factors of IPO underpricing. Second, the study also enriches the literature about the economic consequences of ATP adoption. This study also has important policy implications. With the coming of the era of decentralized ownership in China’s capital market, ATP adoption has become more important and attracted more attention. Also, investors focus more on pricing efficiency. The findings in this paper provide a more comprehensive understanding of the relationship between ATP adoption and IPO underpricing.

Summary: R-loops play diverse functional roles, but controversial genomic localization of R-loops have emerged from experimental approaches, posing significant challenges for R-loop research. The development and application of an accurate computational tool for studying human R-loops remains an unmet need. Here, we introduce DeepER, a deep learning-enhanced R-loop prediction tool. DeepER showcases outstanding performance compared to existing tools, facilitating accurate genome-wide annotation of R-loops and a deeper understanding of the position- and context-dependent effects of nucleotide composition on R-loop formation. DeepER also unveils a strong association between certain tandem repeats and R-loop formation, opening a new avenue for understanding the mechanisms underlying some repeat expansion diseases. To facilitate broader utilization, we have developed a user-friendly web server as an integral component of R-loopBase. We anticipate that DeepER will find extensive applications in the field of R-loop research.

Abstract Biochar application is widely recognized as an effective approach for increasing soil organic carbon (SOC) and mitigating climate change in agroecosystems. However, the effects of biochar application on net accumulations and relative contributions of different SOC sources remain unclear. Here, we explored the effects of biochar application on plant‐derived (PDC) and microbial necromass C (MNC) in a 10‐year experimental rice–wheat rotation field receiving four different intensities of biochar application (0, 2.25, 11.5, and 22.5 t ha−1 for each crop season), using phospholipid fatty acids (PLFAs), lignin phenols and amino sugars as biomarkers of microbial biomass, PDC and MNC, respectively. Our results showed that biochar application increased SOC content and stock by 32.6%–203% and 26.4%–145%, respectively. Higher biochar application (11.5 and 22.5 t ha−1) increased soil pH, total nitrogen (TN), total phosphorus (TP), SOC/TN, and root biomass. In addition, higher biochar application enhanced bacterial, fungal, and total microbial biomass. Plant lignin phenols and MNC contents significantly increased, whereas their contributions to SOC significantly decreased with the increase in biochar application rates due to the disproportionate increase in PDC and MNC, and SOC. Fungal necromass had a greater contribution to SOC than bacterial necromass. The fungal/bacterial necromass decreased from 2.56 to 2.26 with increasing biochar application rates, because of the higher abundances of bacteria than that of fungi as indicated by PLFAs under higher biochar application rates. Random forest analyses revealed that pH, TP, and SOC/TN were the main factors controlling plant lignin and MNC accumulation. Structural equation modeling revealed that biochar application increased lignin phenols by stimulating root biomass, whereas enhanced MNC accumulation was primarily from increased microbial biomass and lignin phenols. Overall, our findings suggest that biochar application increases the accumulation of the two SOC sources but decreases their contributions to SOC in paddy soils.

Cobalt-based amorphous alloys (Co-MG) demonstrate ultra-high permeability and remarkably-low power loss, positioning them as promising candidates for shielding (near-) static magnetic fields and addressing accuracy limitations in extremely-weak magnetic measurements. However, the brittleness and poor understanding about magnetic performance below 100 Hz have impeded their widespread adoption. To integrate satisfied processing, magnetic and mechanical performances, polystyrene-grafted Co-MG composites are developed. Compared with permalloy-1J85, Co-MG-(g-PS_35 %) composite exhibits 40 % increase in initial permeability, 48 % increase in saturation magnetization, 71 % reduction in remanence within shielding area. In contrast to Mn–Zn ferrite, Co-MG-(g-PS_35 %) composite demonstrates the power loss and μ″/μ′2 values lower by an order of magnitude, resulting in magnetic noises 85 % lower at 1 Hz. Furthermore, the resultant composite maintains similar processing-rheological behaviors and mechanical properties compared with bulk polystyrene. It provides an innovative solution to expand real-world applications for biomagnetic detection, and overcome the sensitivity limitation of extremely-weak magnetic measurement.

Abstract Background Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. Methods Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. Results In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among “Mild P-A” at baseline, 32.0% converted to no-pain, 12.8% progressed to “Mild P-R-A”, and 53.2% remained. Approximately 46.1% of “Mild P-R-A” and 54.5% of “Mod P-R-A” at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. Conclusions We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

Abstract Background Allergic diseases exert a considerable impact on global health, thus necessitating investigations into their etiology and pathophysiology for devising effective prevention and treatment strategies. This study employs a Mendelian randomization (MR) analysis and meta-analysis to identify metabolite targets potentially associated with allergic diseases. Methods A two-sample MR analysis was conducted to explore potential causal relationships between circulating and urinary metabolites and allergic diseases. Exposures were derived from a genome-wide association study (GWAS) of 486 circulating metabolites and a GWAS of 55 targeted urinary metabolites. Outcome data for allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, were obtained from the FinnGen biobank in Europe (cohort 1) and the Biobank Japan in Asia (cohort 2). MR results from both cohorts were combined using a meta-analysis. Results MR analysis identified 50 circulating metabolites and 6 urinary metabolites in cohort 1 and 54 circulating metabolites and 2 urinary metabolites in cohort 2 as potentially causally related to allergic diseases. A meta-analysis of the MR results revealed stearoylcarnitine (OR 8.654; 95% CI 4.399−17.025; P = 4.06E-10) and 1-arachidonoylglycerophosphoinositol (OR 2.178; 95% CI 1.388−3.419; P = 7.15E-04) as the most reliable causal circulating metabolites for asthma and AR, respectively. Further, histidine (OR 0.734; 95% CI: 0.594−0.907; P = 0.004), tyrosine (OR 0.601; 95% CI: 0.380−0.952; P = 0.030), and alanine (OR 0.280; 95% CI: 0.125−0.628; P = 0.002) emerged as urinary metabolites with the greatest protective effects against asthma, AD, and AR, respectively. Conclusions Imbalances in numerous circulating and urinary metabolites may be implicated in the development and progression of allergic diseases. These findings have significant implications for the development of targeted strategies for the prevention and treatment of allergic diseases.

Traditional nonlinear elements of the electromagnetic transient simulation program (EMTP) use the numerical integration method, often employing the trapezoidal integration method as an implicit algorithm. However, when the number of nonlinear elements is high, the iterative format becomes computationally cumbersome. The semi-implicit format algorithms, based on the Rosenbrock real-time integration method, do not require iterations and can be applied directly in a recursive manner. However, as the number of nonlinear elements increases, it becomes necessary to invert the matrix that contains the Jacobian matrix, resulting in an increase of both algorithmic computation and inversion time with the dimensionality of the system. In this paper, a new numerical solution method is adopted, which combines the precise integration method. Specifically, the Calahan algorithm, with 2-stage and 3-order, is used to numerically integrate the Duhamel integration terms, and the accuracy of the Calahan algorithm is enhanced through Richardson extrapolation. The new algorithm can avoid the inverse of the matrix containing the Jacobian matrix, and the computational efficiency is equivalent to an explicit method, which greatly improves the computational efficiency of the Rosenbrock integration algorithm. The results verify the effectiveness and accuracy of the algorithm for typical power system nonlinear element electromagnetic transient simulation cases.

Abstract Background Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. Case presentation A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. Conclusion This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

Abstract Quantum vortices in Bose–Einstein condensates (BECs) are essential phenomena in condensed matter physics, and precisely locating their positions, especially the vortex core, is a precondition for studying their properties. With the rise of machine learning, there is a possibility to expedite the localization process and provide accurate predictions. However, traditional machine learning requires particular considerable amount of manual data annotation, leading to uncontrollable accuracy. In this paper, we utilize the U-Net method to detect vortex positions accurately at the pixel level and propose an Automatic Correction Labeling (ACL) approach to optimize the acquisition of data sets for vortex localization in BECs. This approach addresses inaccuracies in the labeled vortex positions and improves the accuracy of vortex localization, especially the vortex core positions, while enhancing the tolerance for human mislabeling. The main process involves Rough Labeling $$\rightarrow $$ → Machine Learning $$\rightarrow $$ → Probability Region Search $$\rightarrow $$ → Data Relabeling $$\rightarrow $$ → Machine Learning again. The objective of ACL is to secure more accurate labeled data for model retraining. Through vortex localization experiments conducted in a two-dimensional Bose-Einstein condensate, our results establish the following: 1. Even under conditions of biased and missing manual annotations, U-Net can still accurately locate vortex positions; 2. Vortices exhibit certain regularities, and training U-Net with a small number of samples yields excellent predictive consequences; 3. The machine learning vortex locator based on the ACL method effectively corrects errors in manually annotated data, significantly improving the model’s performance metrics, thus enhancing the precision and metrics of vortex localization. This substantial advancement in the application of machine learning in vortex localization provides an effective way for vortex dynamics localization. Furthermore, this method of obtaining more accurate positions of approximate human labels through machine learning offers new insights for machine learning in other types of image recognition problems.

Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Seed aging is a complex process that involves various physiological and biochemical changes leading to a decline in seed viability during storage. However, the specific biomarkers for assessing the degree of seed aging in rice remain elusive. In this study, we isolated a golden hull mutant, gh15, from the indica rice Z15 by employing a radiation mutagenesis technique. Compared with the wild type (WT) Z15, the mutant gh15 displayed a golden hue in the hull, stem, and internodes, while no significant differences were observed in the key agronomic traits. A genetic analysis showed that the gh15 phenotype is regulated by a single recessive gene, which possibly encodes cinnamyl alcohol dehydrogenase OsCAD2. Significant differences of seed aging tolerance were observed between gh15 and WT after six months of natural storage and artificial aging treatment, with gh15 exhibiting a markedly lower aging tolerance compared to the WT. Haplotype assays indicated that the Hap2 of OsCAD2 was significantly associated with the dark coloration of the hull and lower seed aging tolerance. The molecular marker of OsCAD2 associated with seed color was explored in rice. These findings demonstrate that the golden hull serves as a potential biomarker for the rapid assessment of seed aging tolerance in rice.

Polycentric development facilitates urban–rural spatial reshaping and land use/land cover (LULC) protection. Previous studies have predominantly focused on urban areas, with spatial delineation methods biased towards the macro-level, lacking a holistic perspective that situates them within the urban–rural spatial framework. This study proposes a spatial delineation framework that is applicable to the polycentric structure, taking into account the social, economic, and natural characteristics of urbanization. It employs semivariance analysis and spatial continuous wavelet transform (SCWT) to analyze the effects of polycentric development on the urban–rural space of Wuhan from 2012 to 2021 and applies a land use transition matrix, landscape indices, and bivariate spatial autocorrelation to quantify the responses and differences of LULC within urban–rural space. The results indicate that 600m×600m is the best scale for exhibiting the multidimensional characterization of urbanization. The polycentric structure alleviates the compact development of the central city, and it drives rapid expansion at the urban–rural fringe, exacerbating the spatial heterogeneity in LULC change pattern, spatial configuration, and urbanization response within urban–rural spaces. The overall effects of urbanization on LULC are relatively weak along the urban–rural gradient, experiencing a transition from positive to negative and back to positive. This study employs a novel spatial delineation framework to depict the polycentric transformation of metropolitan areas and provides valuable insights for regional planning and ecological conservation in the urban–rural fringe.

BackgroundEnteric glia are essential components of the enteric nervous system. Previously believed to have a passive structural function, mounting evidence now suggests that these cells are indispensable for maintaining gastrointestinal homeostasis and exert pivotal influences on both wellbeing and pathological conditions. This study aimed to investigate the global status, research hotspots, and future directions of enteric glia.MethodsThe literature on enteric glia research was acquired from the Web of Science Core Collection. VOSviewer software (v1.6.19) was employed to visually represent co-operation networks among countries, institutions, and authors. The co-occurrence analysis of keywords and co-citation analysis of references were conducted using CiteSpace (v6.1.R6). Simultaneously, cluster analysis and burst detection of keywords and references were performed.ResultsA total of 514 publications from 36 countries were reviewed. The United States was identified as the most influential country. The top-ranked institutions were University of Nantes and Michigan State University. Michel Neunlist was the most cited author. “Purinergic signaling” was the largest co-cited reference cluster, while “enteric glial cells (EGCs)” was the cluster with the highest number of co-occurring keywords. As the keyword with the highest burst strength, Crohns disease was a hot topic in the early research on enteric glia. The burst detection of keywords revealed that inflammation, intestinal motility, and gut microbiota may be the research frontiers.ConclusionThis study provides a comprehensive bibliometric analysis of enteric glia research. EGCs have emerged as a crucial link between neurons and immune cells, attracting significant research attention in neurogastroenterology. Their fundamental and translational studies on inflammation, intestinal motility, and gut microbiota may promote the treatment of some gastrointestinal and parenteral disorders.

Despite significant progress in targeted therapy for acute myeloid leukemia (AML), clinical outcomes are disappointing for elderly patients, patients with less fit disease characteristics, and patients with adverse disease risk characteristics. Over the past 10 years, adaptive T-cell immunotherapy has been recognized as a strategy for treating various malignant tumors. However, it has faced significant challenges in AML, primarily because myeloid blasts do not contain unique surface antigens. The preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is abnormally expressed in AML and does not exist in normal hematopoietic cells. Accumulating evidence has demonstrated that PRAME is a useful target for treating AML. This paper reviews the structure and function of PRAME, its effects on normal cells and AML blasts, its implications in prognosis and follow-up, and its use in antigen-specific immunotherapy for AML.

Abstract Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin‐1 (MaR1), one of metabolites from Omega‐3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)‐infused mouse model. In addition, MaR1‐treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin‐dependent protein kinase II/nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

Cardiovascular diseases have been identified as vital factors in global morbidity and mortality in recent years. The available evidence suggests that various cytokines and pathological proteins participate in these complicated and changeable diseases. The thrombospondin (TSP) family is a series of conserved, multidomain calcium-binding glycoproteins that cause cell-matrix and cell-cell effects via interactions with other extracellular matrix components and cell surface receptors. The TSP family has five members that can be divided into two groups (Group A and Group B) based on their different structures. TSP-1, TSP-2, and TSP-4 are the most studied proteins. Among recent studies and findings, we investigated the functions of several family members, especially TSP-5. We review the basic concepts of TSPs and summarize the relevant molecular mechanisms and cell interactions in the cardiovascular system. Targeting TSPs in CVD and other diseases has a remarkable therapeutic benefit.

Neoagarooligosaccharides (NAOS), possessing a variety of bioactivities, are mainly produced by β-agarases cleaving the β-1,4-glycosidic bond of agar or agarose. Previous study indicated that NAOS has antioxidant effect, however, the NAOS monomers on the activity of scavenging ROS has not been deeply clarified till now. In this study, the protective effects of NAOS especially neoagarotetraose (NA4) against H2O2-stimulated oxidative damage in HepG2 cells and their underlying molecular mechanism were investigated. The results indicated that NA4 could inhibit the production of reactive oxygen species (ROS) and enhance the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in H2O2-induced HepG2 cells. Moreover, NA4 activated the mRNA and protein expression levels of the nuclear factor erythroid-2-related factor 2 (Nrf2), which further up-regulated the mRNA and protein expression of the downstream antioxidant enzymes including heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), indicating that NA4 could attenuate H2O2-induced oxidative damage through Nrf2 pathway in HepG2 cells. The study suggested that NA4 could be an effective antioxidant candidate and it may be developed as a promising component in healthy food exerting antioxidation effect.

Reducing sedentary behavior has become a public health priority due to significantly increased prevalence of leisure-time sedentary behaviors among people; promoting physical activity and interrupting sedentary time are among common interventions on sedentary behaviors. The built environment, as one of determinants of sedentary behavior, is increasingly being investigated and relevant studies have indicated that environmental interventions on sedentary behavior may be a more cost-effective and appropriate approach; however, few studies have specified the extent and mechanism of a distinct built environment’s impact on sedentary behavior. In this review, we summarize researches on the association of characteristics of built environment with sedentary behavior, related measurement tools, and environmental interventions on sedentary behaviors to provide references to domestic studies in this field.

Abstract Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs. In this study, we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulation-specific gene expression between cartilage with macroscopically confirmed osteoarthritis (n = 5) and cartilage without osteoarthritis (n = 5) from the interphalangeal joints of five donors. Of 105 142 cells, we identified 13 subpopulations, including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes. Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage. Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage. In these two subpopulations from osteoarthritic cartilage, the ferroptosis pathway was enriched, and expression of iron overload-related genes, e.g., FTH1, was elevated. To verify these findings, we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study. Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis (odds ratio = 1.07, 95% confidence interval: 1.02–1.11) among participants (n = 332 668) in UK Biobank. High levels of serum ferritin (encoded by FTH1), a biomarker of body iron overload, were significantly associated with a high prevalence of hand osteoarthritis among participants (n = 1 241) of Xiangya Osteoarthritis Study (P-for-trend = 0.037). In conclusion, our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis, providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.

Abstract Background Puberty marks the end of childhood and achieve sexual maturation and fertility. The role of hypothalamic proteins in regulating puberty onset is unclear. We performed a comprehensive differential proteomics and phosphoproteomics analysis in prepubertal and pubertal goats to determine the roles of hypothalamic proteins and phosphoproteins during the onset of puberty. Results We used peptide and posttranslational modifications peptide quantification and statistical analyses, and identified 69 differentially expressed proteins from 5,057 proteins and 576 differentially expressed phosphopeptides from 1574 phosphorylated proteins. Combined proteomic and phosphoproteomics, 759 correlated proteins were identified, of which 5 were differentially expressed only at the protein level, and 201 were only differentially expressed at the phosphoprotein level. Pathway enrichment analyses revealed that the majority of correlated proteins were associated with glycolysis/gluconeogenesis, Fc gamma R-mediated phagocytosis, focal adhesion, GABAergic synapse, and Rap1 signaling pathway. These pathways are related to cell proliferation, neurocyte migration, and promoting the release of gonadotropin-releasing hormone in the hypothalamus. CTNNB1 occupied important locations in the protein-protein interaction network and is involved in focal adhesion. Conclusion The results demonstrate that the proteins differentially expression only at the protein level or only differentially expressed at the phosphoprotein level and their related signalling pathways are crucial in regulating puberty in goats. These differentially expressed proteins and phosphorylated proteins may constitute the proteomic backgrounds between the two different stages.

Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

Abstract Background Oxidation Resistance 1 (OXR1) gene is a highly conserved gene of the TLDc domain-containing family. OXR1 is involved in fundamental biological and cellular processes, including DNA damage response, antioxidant pathways, cell cycle, neuronal protection, and arginine methylation. In 2019, five patients from three families carrying four biallelic loss-of-function variants in OXR1 were reported to be associated with cerebellar atrophy. However, the impact of OXR1 on cellular functions and molecular mechanisms in the human brain is largely unknown. Notably, no human disease models are available to explore the pathological impact of OXR1 deficiency. Results We report a novel loss-of-function mutation in the TLDc domain of the human OXR1 gene, resulting in early-onset epilepsy, developmental delay, cognitive disabilities, and cerebellar atrophy. Patient lymphoblasts show impaired cell survival, proliferation, and hypersensitivity to oxidative stress. These phenotypes are rescued by TLDc domain replacement. We generate patient-derived induced pluripotent stem cells (iPSCs) revealing impaired neural differentiation along with dysregulation of genes essential for neurodevelopment. We identify that OXR1 influences histone arginine methylation by activating protein arginine methyltransferases (PRMTs), suggesting OXR1-dependent mechanisms regulating gene expression during neurodevelopment. We model the function of OXR1 in early human brain development using patient-derived brain organoids revealing that OXR1 contributes to the spatial–temporal regulation of histone arginine methylation in specific brain regions. Conclusions This study provides new insights into pathological features and molecular underpinnings associated with OXR1 deficiency in patients.

Abstract Background Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. Methods Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. Results Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. Conclusion Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. Graphic abstract

Anticipating changes in system inertia is crucial for maintaining the stability and reliability of new power systems. While machine learning prediction models can be effective in this regard, many of these models are “black-box” models that lack interpretability, making it difficult to understand the factors that contribute to changes in system inertia. In order to address this issue, we propose a short-term prediction method for power system inertia using eXtreme Gradient Boosting (XGBoost) and examine its interpretability. Our method involves using XGBoost to create a prediction model based on operational data from the power system as input features. The XGBoost explanation mechanism utilizes the SHAP attribution method to decompose prediction results into various dimensions, allowing us to examine the influence of various features on the predicted inertia value. By utilizing this method, we are able to gain a better understanding of how the prediction was made and how each feature contributed to the final result. We conduct simulations on a realistic photovoltaic system and find that the proposed method is effective in explaining the influence of input features on short-term predicted inertia values and providing clear explanations for the model’s prediction results on individual samples. By accurately predicting changes in system inertia and understanding the factors that contribute to these changes, we can take proactive measures to prevent potential weaknesses in the system and ensure its overall stability and reliability.