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Cyber-slacking interrupts classroom teaching and learning activities and is associated with poor academic performance. Based on the theory of planned behavior (TPB), this study aimed to investigate whether both cognitive (i.e., attitudes, perceived norms, and perceived behavioral control) and affective (i.e., fear of missing out [FoMO]) factors contribute to classroom cyber-slacking intention and behavior among Chinese university students. We recruited a convenience sample of 431 undergraduate students (M = 19.34, SD = 1.08; 66.4% female; 33.6% male) from mainland China who completed an online survey (i.e., items measured cognitive factors of cyber-slacking, cyber-slacking behavior, FoMO, and demographic information). The findings of correlational, hierarchical multiple regression, and path analysis with bootstrapping approach showed that both cognitive and affective factors were positive correlates of cyber-slacking intention and behavior and explained the variance in cyber-slacking intention. Moreover, attitudes, perceived norms, perceived behavioral control, and FoMO had statistically significant indirect effects (via intention) on cyber-slacking behaviors, whereas perceived behavioral control alone has a direct impact on cyber-slacking behaviors. The findings not only lend more credence to TPB, suggesting that cognitive factors are reliable correlates of both classroom cyber-slacking intention and behavior, but also showed affective factors, such as FoMO, can be used to reduce students' cyber-slacking intention and, subsequently, their behavior. Based on these findings, interventions for reducing classroom cyber-slacking are discussed.

Abstract Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.

The effectiveness of AI-driven drug discovery can be enhanced by pretraining on small molecules. However, the conventional masked language model pretraining techniques are not suitable for molecule pretraining due to the limited vocabulary size and the non-sequential structure of molecules. To overcome these challenges, we propose FragAdd, a strategy that involves adding a chemically implausible molecular fragment to the input molecule. This approach allows for the incorporation of rich local information and the generation of a high-quality graph representation, which is advantageous for tasks like virtual screening. Consequently, we have developed a virtual screening protocol that focuses on identifying estrogen receptor alpha binders on a nucleus receptor. Our results demonstrate a significant improvement in the binding capacity of the retrieved molecules. Additionally, we demonstrate that the FragAdd strategy can be combined with other self-supervised methods to further expedite the drug discovery process.

Abstract To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P

Abstract Reuse and recycling of retired electric vehicle (EV) batteries offer a sustainable waste management approach but face decision-making challenges. Based on the process-based life cycle assessment method, we present a strategy to optimize pathways of retired battery treatments economically and environmentally. The strategy is applied to various reuse scenarios with capacity configurations, including energy storage systems, communication base stations, and low-speed vehicles. Hydrometallurgical, pyrometallurgical, and direct recycling considering battery residual values are evaluated at the end-of-life stage. For the optimized pathway, lithium iron phosphate (LFP) batteries improve profits by 58% and reduce emissions by 18% compared to hydrometallurgical recycling without reuse. Lithium nickel manganese cobalt oxide (NMC) batteries boost profit by 19% and reduce emissions by 18%. Despite NMC batteries exhibiting higher immediate recycling returns, LFP batteries provide superior long-term benefits through reuse before recycling. Our strategy features an accessible evaluation framework for pinpointing optimal pathways of retired EV batteries.

AIM: To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor (IOIP) patients with orbital wall bone destruction (OWBD) and to propose an expanded classification system that includes bone destruction. METHODS: The study retrospectively reviewed clinical presentations, imaging findings, treatment modalities, and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren Hospital, Capital Medical University between October 2018 and June 2021. RESULTS: Over two years, 6 (10%) of 60 IOIP patients at our hospital exhibited OWBD, but this may overrepresent severe cases. The cohort consisted of three men and three women, aged 17 to 60y (mean 35.5±16.1y). Presenting symptoms included proptosis, eyelid swelling, decreased visual acuity with pain, and palpable mass. Imaging revealed multiple anatomical structures involved with the medial wall being the most common site of bone destruction. Histopathological examination showed classic type in five patients and sclerosing type in one patient. All patients underwent surgical resection followed by methylprednisolone treatment. Follow-up (mean 30.3±3.1mo) indicated three patients had no recurrence, while others had varying degrees of symptom persistence or recurrence. CONCLUSION: IOIP with bone destruction is a rare but significant subtype that mimics malignancy, leading to potential diagnostic and therapeutic challenges. Our findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable outcomes. However, larger-scale studies are needed to further optimize therapeutic approaches.

Abstract The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced kidney injury. Trimethylamine N-oxide (TMAO) is a gut-derived metabolite linked to many diseases, but its role in I/R-induced kidney injury remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels and postoperative kidney injury in patients after post-cardiopulmonary bypass surgery. By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) and dietary supplementation of choline to modulate TMAO levels, we found that TMAO aggravated acute kidney injury through the triggering of endoplasmic reticulum (ER) stress and worsened subsequent renal fibrosis through TGFβ/Smad signaling activation. Together, our study underscores the negative role of TMAO in I/R-induced kidney injury and highlights the therapeutic potential through the modulation of TMAO levels by targeting FMO3, thereby mitigating acute kidney injury and preventing subsequent renal fibrosis.

Abstract Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Abstract Objectives To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0–6 months old). Methods The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. Results Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. Conclusions The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

Abstract LLC series resonant converter (LLC‐SRC) has attracted much attention due to its simple circuit structure and easy realization of soft‐switching. To get a better efficiency, rectifier stage can be realized by the active switches instead of the diodes. Meanwhile, more control variables can be selected besides the switching frequency, such as single phase shifted (SPS) angle, dual phase shifted (DPS) angle, and extended phase shifted (EPS) angle. Considering the simplicity of the implementation of the control strategy, this paper focused on the converter model with frequency and SPS control. Different from the common modelling method with the Fundamental Harmonic Approximation (FHA), the precise time‐domain mathematic model is built. By a comparison between the two modelling results, it can be proved the FHA model may be failure in some operating condition while the proposed time‐domain model can still show a good accuracy. According to the proposed model, two simple fixed‐frequency SPS control strategies are proposed. The first one can realize infinite soft‐switching margin with no restrictions on the transformer magnetizing inductance. The second one can greatly improve the efficiency of the converter. All the theoretical results are verified by a 1‐kW experiment prototype.

Abstract Background Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. Methods Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. Results The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p

Objective: To develop and evaluate a Chinese version of the Symptom Questionnaire for Visual Dysfunctions (CSQVD) to quantify visual dysfunction symptoms in school-age children with various eye diseases, and to explore the relationship between ophthalmological disorders and visual dysfunction symptoms. Methods: Following standard scale adaptation procedures, the Symptom Questionnaire for Visual Dysfunctions (SQVD) was translated into Chinese (CSQVD). We employed random sampling to survey 198 outpatients aged 7–18 to assess the psychometric properties of the CSQVD. Using the reliable and validated questionnaire, we evaluated the determinants of visual dysfunction symptoms among 406 school-age patients at an eye center. The CSQVD scores were correlated with demographic and clinical variables, including gender, age, eye position, refractive power, and best-corrected visual acuity. Univariate analysis identified potential risk factors, followed by binary logistic regression and multiple linear regression analysis on factors with a P-value

Elderly patients with type 2 diabetes mellitus often face the problems of multimorbidity and multiple medications, and these conditions often lead to irrational or inappropriate medication use, significantly affecting patient outcomes and quality of life, making early and effective medication decisions particularly important. As an important supplement to medication support information, decision support tools, including electronic health record-based systems, mobile applications, online health platforms, etc., provide personalized, evidence-based medical information to help patients understand medication regimens, assist patients and healthcare professionals in making more rational medication decisions, enhance the appropriateness and safety of medication, and reduce the risk of drug interactions, thereby improving the overall treatment of patients and reducing the risk of drug interactions. The application of medication management in elderly patients with type 2 diabetes mellitus has made significant progress, thus improving the overall outcome and quality of life of patients. This article summarizes the current situation of medication use in elderly patients with type 2 diabetes mellitus, the influencing factors, types, application methods and their roles of decision aids, aiming to provide reference for the development of medication decision aids for this population in China.

Abstract Background Insulin resistance (IR) and arthritis are strongly associated, and the triglyceride–glucose (TyG) index combinations with obesity indicators [including TyG–BMI (glucose triglyceride–body mass index), TyG–WC (glucose triglyceride–waist circumference), and TyG–WHtR (glucose triglyceride–waist height ratio)] has recently been recognized as a more effective indicator for assessing IR. However, there is a lack of research on its association with arthritis, and it is also important to assess in different populations. Methods The analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and the National Health and Nutrition Examination Survey (NHANES). Arthritis diagnosis relied on self-reporting confirmed by physicians. The association of TyG–BMI, TyG–WC, and TyG–WHtR with arthritis was analyzed through weighted logistic regression models, and exploring nonlinear effects with restricted cubic spline (RCS) models. Secondary and sensitivity analyses included receiver operating characteristic curve (ROC) analysis, comparisons of z score-related odds ratios, subgroup analyses, and multiple imputation. Results The study involved 6141 CHARLS participants and 17,091 NHANES participants. Adjusting for confounding variables, TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both CHARLS (TyG–BMI: OR = 1.02, 95% CI 1.00–1.04; TyG–WHtR: OR = 1.13, 95% CI 1.03–1.24) and NHANES (TyG–BMI: OR = 1.07, 95% CI 1.06–1.08; TyG–WHtR: OR = 1.50, 95% CI 1.40–1.60). RCS regression analysis demonstrated a significant nonlinear association. ROC analysis indicated that TyG–BMI and TyG–WHtR were superior to TyG for the diagnosis of arthritis in both CHARLS and NHANES. Conclusions TyG–BMI and TyG–WHtR demonstrate a positive correlation with arthritis prevalence in both Chinese and the U.S. populations, displaying superior diagnostic relevance compared to TyG.

Abstract Objective The aim of this study is to evaluate the clinical efficacy of injectable cemented hollow pedicle screw (CICPS) in the treatment of osteoporotic lumbar degenerative diseases through a large sample long-term follow-up study. Additionally, we aim to explore the risk factors affecting interbody fusion. Methods A total of 98 patients who underwent CICPS for transforaminal lumbar interbody fusion (TLIF) for osteoporotic lumbar degenerative disease from March 2011 to September 2017 were analyzed. X-ray and electronic computed tomography (CT) imaging data were collected during preoperative, postoperative, and follow-up periods. The data included changes in intervertebral space height (ΔH), screw failure, cement leakage (CL), and intervertebral fusion. The patients were divided into two groups based on their fusion status one year after surgery: satisfied group A and dissatisfied group B. Surgical data such as operation time, intraoperative bleeding volume and surgical complications were recorded, and visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the improvement of lumbar and leg pain. Results The mean follow-up time was 101.29 months (ranging from 70 to 128 months). A total of 320 CICPS were used, with 26 screws (8.13%) leaking, 3 screws (0.94%) experiencing cement augmentation failure, and 1 screw (0.31%) becoming loose and breaking. The remaining screws were not loose or pulled out. Female gender, decreased bone density, and CL were identified as risk factors affecting interbody fusion (P

Abstract Mutations in the Cockayne Syndrome group B (CSB) gene cause cancer in mice, but premature aging and severe neurodevelopmental defects in humans. CSB, a member of the SWI/SNF family of chromatin remodelers, plays diverse roles in regulating gene expression and transcription-coupled nucleotide excision repair (TC-NER); however, these functions do not explain the distinct phenotypic differences observed between CSB-deficient mice and humans. During investigating Cockayne Syndrome-associated genome instability, we uncover an intrinsic mechanism that involves elongating RNA polymerase II (RNAPII) undergoing transient pauses at internal T-runs where CSB is required to propel RNAPII forward. Consequently, CSB deficiency retards RNAPII elongation in these regions, and when coupled with G-rich sequences upstream, exacerbates genome instability by promoting R-loop formation. These R-loop prone motifs are notably abundant in relatively long genes related to neuronal functions in the human genome, but less prevalent in the mouse genome. These findings provide mechanistic insights into differential impacts of CSB deficiency on mice versus humans and suggest that the manifestation of the Cockayne Syndrome phenotype in humans results from the progressive evolution of mammalian genomes.

Abstract Myeloid cells are vital components of the immune system and have pivotal functions in orchestrating immune responses. Understanding their functions within the tumor microenvironment and their interactions with tumor-infiltrating lymphocytes presents formidable challenges across diverse cancer types, particularly with regards to cancer immunotherapies. Here, we explore tumor-infiltrating myeloid cells (TIMs) by conducting a pan-cancer analysis using single-cell transcriptomics across eight distinct cancer types, encompassing a total of 192 tumor samples from 129 patients. By examining gene expression patterns and transcriptional activities of TIMs in different cancer types, we discern notable alterations in abundance of TIMs and kinetic behaviors prior to and following immunotherapy. We also identify specific cell-cell interaction targets in immunotherapy; unique and shared regulatory profiles critical for treatment response; and TIMs associated with survival outcomes. Overall, our study illuminates the heterogeneity of TIMs and improves our understanding of tissue-specific and cancer-specific myeloid subsets within the context of tumor immunotherapies.

Abstract To explore complex biological questions, it is often necessary to access various data types from public data repositories. As the volume and complexity of biological sequence data grow, public repositories face significant challenges in ensuring that the data is easily discoverable and usable by the biological research community. To address these challenges, the National Center for Biotechnology Information (NCBI) has created NCBI Datasets. This resource provides straightforward, comprehensive, and scalable access to biological sequences, annotations, and metadata for a wide range of taxa. Following the FAIR (Findable, Accessible, Interoperable, and Reusable) data management principles, NCBI Datasets offers user-friendly web interfaces, command-line tools, and documented APIs, empowering researchers to access NCBI data seamlessly. The data is delivered as packages of sequences and metadata, thus facilitating improved data retrieval, sharing, and usability in research. Moreover, this data delivery method fosters effective data attribution and promotes its further reuse. This paper outlines the current scope of data accessible through NCBI Datasets and explains various options for exploring and downloading the data.

Abstract The fusion rules and operator product expansion (OPE) serve as crucial tools in the study of operator algebras within conformal field theory (CFT). Building upon the vision of using entanglement to explore the connections between fusion coefficients and OPE coefficients, we employ the replica method and Schmidt decomposition method to investigate the time evolution of entanglement entropy (EE) and pseudo entropy (PE) for linear combinations of operators in rational conformal field theory (RCFT). We obtain a formula that links fusion coefficients, quantum dimensions, and OPE coefficients. We also identify two definition schemes for linear combination operators. Under one scheme, the EE captures information solely for the heaviest operators, while the PE retains information for all operators, reflecting the phenomenon of pseudo entropy amplification. Irrespective of the scheme employed, the EE demonstrates a step-like evolution, illustrating the effectiveness of the quasiparticle propagation picture for the general superposition of locally excited states in RCFT. From the perspective of quasiparticle propagation, we observe spontaneous block-diagonalization of the reduced density matrix of a subsystem when quasiparticles enter the subsystem.

Abstract Background The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia. Methods This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed. Results A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P

Abstract Ferroptosis is an iron-dependent cell death that was discovered recently. For beneficial microbes to establish mutualistic relationships with hosts, precisely controlled cell death in plant cells is necessary. However, whether ferroptosis is involved in the endophyte‒plant system is poorly understood. Here, we reported that endophytic Streptomyces hygroscopicus OsiSh-2, which established a sophisticated and beneficial interaction with host rice plants, caused ferroptotic cell death in rice characterized by ferroptosis- and immune-related markers. Treatments with ferroptosis inhibitors and inducers, different doses of OsiSh-2, and the siderophore synthesis-deficient mutant ΔcchH revealed that only moderate ferroptosis induced by endophytes is essential for the establishment of an optimal symbiont to enhance plant growth. Additionally, ferroptosis involved in a defence-primed state in rice, which contributed to improved resistance against rice blast disease. Overall, our study provides new insights into the mechanisms of endophyte‒plant interactions mediated by ferroptosis and suggests new directions for crop yield promotion.

Abstract Background Chronic myeloid leukemia (CML) is a common hematological malignancy, and tyrosine kinase inhibitors (TKIs) represent the primary therapeutic approach for CML. Activation of metabolism signaling pathway has been connected with BCR::ABL1-independent TKIs resistance in CML cells. However, the specific mechanism by which metabolism signaling mediates this drug resistance remains unclear. Here, we identified one relationship between glutamine synthetase (GS) and BCR::ABL1-independent Imatinib resistance in CML cells. Methods GS and PXN-AS1 in bone marrow samples of CML patients with Imatinib resistance (IR) were screened and detected by whole transcriptome sequencing. GS expression was upregulated using LVs and blocked using shRNAs respectively, then GS expression, Gln content, and cell cycle progression were respectively tested. The CML IR mice model were established by tail vein injection, prognosis of CML IR mice model were evaluated by Kaplan–Meier analysis, the ratio of spleen/body weight, HE staining, and IHC. PXN-AS1 level was blocked using shRNAs, and the effects of PXN-AS1 on CML IR cells in vitro and in vivo were tested the same as GS. Several RNA-RNA tools were used to predict the potential target microRNAs binding to both GS and PXN-AS1. RNA mimics and RNA inhibitors were used to explore the mechanism through which PXN-AS1 regulates miR-635 or miR-635 regulates GS. Results GS was highly expressed in the bone marrow samples of CML patients with Imatinib resistance. In addition, the lncRNA PXN-AS1 was found to mediate GS expression and disorder cell cycle in CML IR cells via mTOR signaling pathway. PXN-AS1 regulated GS expression by binding to miR-635. Additionally, knockdown of PXN-AS1 attenuated BCR::ABL1-independent Imatinib resistance in CML cells via PXN-AS1/miR-635/GS/Gln/mTOR signaling pathway. Conclusions Thus, PXN-AS1 promotes GS-mediated BCR::ABL1-independent Imatinib resistance in CML cells via cell cycle signaling pathway. Graphic Abstract

Abstract Objectives To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs). Methods In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model’s performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA). Results From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48–65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52–69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53–69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000). Conclusion The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility. Critical relevance statement In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment. Key Points The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility. Graphical Abstract

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (m6A) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by m6A methylation. Methods Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the m6A methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis. Results LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 m6A modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels. Conclusion WTAP-mediated m6A modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.

Abstract Background With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. Objective With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers’ stigma, increasing their knowledge, willingness to intervene, and perceived competence. Methods Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. Conclusions The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.

Abstract The brain presents age-related structural and functional changes in the human life, with different extends between subjects and groups. Brain age prediction can be used to evaluate the development and aging of human brain, as well as providing valuable information for neurodevelopment and disease diagnosis. Many contributions have been made for this purpose, resorting to different machine learning methods. To solve this task and reduce memory resource consumption, we develop a mini architecture of only 10 layers by modifying the deep residual neural network (ResNet), named ResNet mini architecture. To support the ResNet mini architecture in brain age prediction, the brain age dataset (OpenNeuro #ds000228) that consists of 155 study participants (three classes) and the Alzheimer MRI preprocessed dataset that consists of 6400 images (four classes) are employed. We compared the performance of the ResNet mini architecture with other popular networks using the two considered datasets. Experimental results show that the proposed architecture exhibits generality and robustness with high accuracy and less parameter number.

Abstract Accurate preoperative differentiation of the chronic rhinosinusitis (CRS) endotype between eosinophilic CRS (eCRS) and non-eosinophilic CRS (non-eCRS) is an important topic in predicting postoperative outcomes and administering personalized treatment. To this end, we have constructed a sinus CT dataset, which comprises CT scan data and pathological biopsy results from 192 patients of chronic rhinosinusitis with nasal polyps (CRSwNP), treated at the Second Affiliated Hospital of Shantou University Medical College between 2020 and 2022. To differentiate CRSwNP endotype on preoperative CT and improve efficiency at the same time, we developed a multi-view fusion model that contains a mini-architecture with each network of 10 layers by modifying the deep residual neural network. The proposed model is trained on a training set and evaluated on a test set. The multi-view deep learning fusion model achieved the area under the receiver-operating characteristics curve (AUC) of 0.991, accuracy of 0.965 and F1-Score of 0.970 in test set. We compared the performance of the mini-architecture with other lightweight networks on the same Sinus CT dataset. The experimental results demonstrate that the developed ResMini architecture contribute to competitive CRSwNP endotype identification modeling in terms of accuracy and parameter number.

The effects of different cooking methods (raw, microwave, steaming and frying) on the volatile components of Ctenopharyngodon idella were analyzed by gas chromatography-mass spectrometry, electronic nose technique and sensory evaluation. The results of gas chromatography-mass spectrometry showed that 78 volatiles were detected in 4 cooking methods, mainly olefin, alkanes, aldehydes, esters and other volatile compounds, and the number and content of components in frying methods were higher than those in other processing groups. The electronic nose and principal component analysis showed that, compared with raw fish, the volatiles of fish was closer between steaming and microwave, and fried one had a greater effect on the volatiles. The results of sensory evaluation showed that the fish smell in four treatments all had a certain fishy and grassy taste, but the fried one was mainly manifested in burnt and greasy taste. In addition, the special volatile compounds such as trans, trans-2,4-decenal, 2-furanaldehyde and 2-amyl furan produced during frying give the smell of roast meat, which could cover the off-odor such as fishy and grassy. In summary, the volatiles of Ctenopharyngodon idella were mainly aldehydes and esters, and compared with raw fish, frying had the greatest impact on the volatile components, which could better reduce the fishy off-flavor, the results would provide a theoretical basis for the development of deep processing technology for Ctenopharyngodon idella meat.

Abstract The impact of aging on diabetic retinopathy (DR) remains underestimated. The current study aimed to investigate the association between biological aging and DR, in contrast to chronological age (CA). Using the National Health and Nutrition Survey data from 2005 to 2008. Biological aging was evaluated through the biological age (BA) and phenotypic age (PA), which were calculated from clinical markers. DR was identified in participants with diabetes mellitus (DM) when they exhibited one or more retinal microaneurysms or retinal blot hemorrhages under retinal imaging, with or without the presence of more severe lesions. Survey-weighted multivariable logistic regression was performed, and the regression model was further fitted using restricted cubic splines. The discriminatory capability and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Based on weighted analyses, of the 3100 participants included in this study, of which 162 had DR. In the adjusted model, BA (odds ratio [OR] = 1.12, 95% CI, 1.06–1.18) and PA (OR = 1.11, 95% CI, 1.07–1.14) were associated with DR, while CA was not significantly (OR = 1.01, 95% CI, 0.99–1.03). Narrowing the analysis to DM participants and adjusting for factors like insulin showed similar results. ROC and DCA analyses indicate that BA/PA predicted DR better than CA and offer greater clinical utility. The positive association between BA/PA and DR was consistent across subgroups despite potential interactions. Biological aging heightens DR risk, with BA/PA showing a stronger association than CA. Our findings underscored the importance of timely anti-aging interventions for preventing DR.

Abstract In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.

This research examined the impact of defatted coconut flour (DCF)-based oleogels on the quality of surimi. Microscopic analysis indicated that the dietary fiber present in DCF could act as the main structure of the oleogels network. The formation of the oleogels network primarily relies on the tensile intramolecular or intermolecular hydrogen bonds between DCF and corn oil. The oleogels displayed oil binding capacity of up to 96.95% and exhibited favorable mechanical and rheological properties. Efforts were undertaken to integrate the acquired oleogels into silver carp surimi to create oil-fortified surimi products. Adding oleogels significantly enhanced the gel strength, texture, and water-holding capacity of surimi compared to adding corn oil. Especially, oleogels containing 5.0 % (w/v) DCF concentration elevated the lipid content in the surimi and preserved the gel and texture properties. Therefore, incorporating oleogels in surimi presents a potential solution for enhancing the nutritional content of surimi products.

Accurately predicting agricultural yields is crucial for developing adaptative strategies to ensure food security. Unmanned aerial vehicle (UAV) remote sensing equipped with portable multispectral sensors are commonly applied to acquire high temporal and spatial resolutions of remote sensing data. The vegetation indices (VIs) extracted from multispectral images are conducted for agricultural yield prediction. However, existing VIs often suffered from saturation problems when the canopy coverage is high. Integrating UAV-derived canopy height data with spectral indices holds the potential to solve saturation problem. However, this method is still at the infant stage and requires further validation. Here, we have newly proposed a multispectral-based canopy volumetric vegetation index (MSCVI) that integrates RGB-based volumetric index (VCI) and multispectral images derived VIs from UAV platform for predicting irrigated maize yields for three years (2019, 2020, and 2021). To test the stability of the proposed method, the maize was well managed and different levels of fertilizers were applied in each plot. The results using regression analysis showed the MSCVI outperformed the single adoption of VIs and VCI, and the MSCVI at reproductive growth stages was more strongly correlated with maize yields. Two commonly applied machine learning approaches: backpropagation neural network (BP) and random forest (RF) were applied for predicting maize yield. The R2 between actual maize yield and predicted maize yield using BP increased from 0.81 to 0.86 (RMSE decreased from 0.93 to 0.67 t/ha). The R2 between actual maize yield and predicted maize yield using RF increased from 0.91 to 0.94 (RMSE decreased from 0.65 to 0.42 t/ha). The robustness of the proposed model was further evaluated using data updating strategies, and results implied that the models was stable across sensors and different years. Overall, this study revealed the proposed MSCVI obtain high potential for predicting agricultural yields, and the proposed model was robust and stable when tested using data updating strategy.

Problematic smartphone use (PSU) and its negative consequences among adolescents are so commonly observed that they have become a matter of public concern. Utilizing life history (LH) theory, this study aims to examine how childhood risks (i.e., childhood harshness and unpredictability) would be associated with adolescent PSU via cognitive and emotional processes of LH strategy and psychological distress. A sample of 459 Chinese high school students aged from 14 to 18 (M = 16.90) participated in this study and voluntarily completed an anonymous survey. The results showed that childhood unpredictability and psychological distress were positively correlated with PSU, whereas childhood harshness and the two processes of LH strategy were negatively correlated with PSU. Path analysis further supported a partial mediation model, in which childhood unpredictability increased PSU, via serial mediators of the emotional process of LH strategy and psychological distress. The findings support the efficacy of LH theory in elucidating the development of behavioral addiction. However, the direct and negative association of childhood harshness with PSU was unexpected. It implicates the complexity of childhood environment on adolescent behavioral addictions and warrants further investigation.

Objective Concerns regarding sleep problems in emerging adults and their antecedents, such as problematic smartphone use (PSU), have been growing. This study tested the association between PSU and sleep problems and further investigated the mechanisms of this relationship based on the theory of compensatory health beliefs (CHBs). Methods This study included 999 participants (74.87% female) in China, aged 17 to 25 years (M = 21.16; standard deviation = 1.60), who voluntarily filled in an anonymous survey. Results The findings showed positive correlations between sleep problems and PSU, sleep-related CHBs, and bedtime procrastination ( r s = .25–.52, p

ObjectiveThis study aimed to explore the combination effects of prenatal exposure to environment tobacco smoke (ETS) and nutrients supplement during pregnancy on childhood obesity in preschoolers.MethodsA cross-sectional study was conducted with 58,814 child-mother dyads from 235 kindergartens in Longhua District of Shenzhen, China in 2021. A self-administered structured questionnaire was completed by mothers to collect socio-demographic characteristics, prenatal ETS exposure, and nutrients supplement in pregnancy, and preschoolers' heights and weights were measured at the same time. After controlling for potential confounding variables, logistic regression models and cross-analyses were used to examine the independent and combination effects of maternal prenatal ETS exposure and nutrients supplementation during pregnancy on obesity in preschool children.ResultsThe results of our study showed that prenatal ETS exposure increased the risk of childhood obesity (AOR = 1.22, 95% CI = 1.11–1.34) in preschoolers. In addition, risk of childhood obesity was significantly higher when mothers didn't take supplements of multivitamins (AOR = 1.12, 95% CI = 1.05–1.20), folic acid (AOR = 1.23, 95% CI = 1.10–1.37) and iron (AOR = 1.11, 95% CI = 1.04–1.19) during pregnancy. The cross-over analysis showed that the combination of prenatal ETS exposure with mothers taking no multivitamins (AOR = 1.40, 95% CI = 1.21–1.62), no folic acid (AOR = 1.55, 95% CI = 1.12–2.14) and no iron (AOR = 1.38, 95% CI = 1.19–1.59) during pregnancy also increased the risk of obesity among Chinese preschoolers. We also discovered additive interactive effects between prenatal ETS exposure and no maternal multivitamin, folic acid and iron supplementation in pregnancy on the risk of obesity in preschoolers.ConclusionThe combination of prenatal exposure to ETS with no supplementation of these nutrients might jointly increase the risk of childhood obesity. Public health interventions are needed to reduce prenatal exposure to ETS and to encourage mothers to take appropriate multivitamin, folic acid and iron supplements during pregnancy.

Summary: Cancer cells with mitochondrial dysfunction can be rescued by cells in the tumor microenvironment. Using human adenoid cystic carcinoma cell lines and fibroblasts, we find that mitochondrial transfer occurs not only between human cells but also between human and mouse cells both in vitro and in vivo. Intriguingly, spontaneous cell fusion between cancer cells and fibroblasts could also emerge; specific chromosome loss might be essential for nucleus reorganization and the post-hybrid selection process. Both mitochondrial transfer through tunneling nanotubes (TNTs) and cell fusion “selectively” revive cancer cells, with mitochondrial dysfunction as a key motivator. Beyond mitochondrial transfer, cell fusion significantly enhances cancer malignancy and promotes epithelial-mesenchymal transition. Mechanistically, mitochondrial dysfunction in cancer cells causes L-lactate secretion to attract fibroblasts to extend TNTs and TMEM16F-mediated phosphatidylserine externalization, facilitating TNT formation and cell-membrane fusion. Our findings offer insights into mitochondrial transfer and cell fusion, highlighting potential cancer therapy targets.

It has been well acknowledged that maternal exposure to fine particulate matters (PM2.5) might lead to poor pregnancy outcomes including the intrauterine growth restriction (IUGR) by interfering with the placental development. Our previous studies have demonstrated that maternal PM2.5 exposure induces IUGR, accompanied with increased maternal circulating TNFα level and impaired extravillous trophoblast cells (EVTs) invasion in mice. In this study, HTR8/SVneo cells, the immortalized human EVTs line, were used to assess effects and the underlying molecular mechanisms of nicotinamide on the impaired EVTs invasion. Our results showed that, the placental FLT1 protein level was significantly increased whereas maternal serum nicotinamide concentration was remarkably decreased in PM2.5-exposured pregnant mice at GD17.5 (vaginal plug day=GD0.5), compared to that in normal GD17.5 pregnant mice. FLT1 expression in HTR8/SVneo cells was significantly up-regulated by TNFα treatment, and the down-regulated FLT1 expression effectively abated the inhibitory effects of TNFα on HTR8/SVneo cells migration and invasion. Meanwhile, TNFα promoted reactive oxygen species (ROS) production and NF-κB signaling pathway activation in HTR8/SVneo cells in a dose-dependent manner. Nicotinamide treatment significantly reversed the effects of TNFα on cell migration and invasion, as well as the FLT1 expression, ROS production and NF-κB pathway activation. In summary, increased TNFα induced by PM2.5 exposure inhibits EVTs invasion by activating the ROS/NF-κB/FLT1 signaling pathway, and this adverse effect could be attenuated by nicotinamide treatment, suggesting a potential application in the clinical intervention of PM2.5-induced IUGR.

Abstract As a highly organized system, endo‐lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo‐lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo‐lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll‐like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48‐linked polyubiquitination of LAMP‐1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP‐1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP‐1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs.

Summary: Prioritizing electric power system decarbonization is crucial for meeting global carbon neutrality targets. However, the role of energy technology cost reduction driven by innovation in advancing carbon neutrality in the electric power system has not been well studied. To fill this gap, an integrated investment planning and operation model is developed to simulate the carbon neutral pathway in the electric power system over a 30-year period from 2020 to 2050. The learning curves with different learning rates are incorporated into the model to represent different energy technology innovation scenarios. According to our results, the advanced innovation scenario is projected to achieve carbon neutrality in the electric power system five years earlier compared with the conservative innovation scenario, with a cost savings of 465 billion CNY. In addition, both inter-regional and intra-regional collaboration facilitate the achievement of carbon neutrality in the electric power system at a reduced cost. Science for society: Reducing carbon emissions and achieving carbon neutrality is a critical global challenge. Previous studies have formulated pathways for energy transition in the electric power system to meet carbon reduction targets. However, many of them overlook the role of energy technology cost reduction driven by innovation in advancing carbon neutrality in the electric power system. In this study, an integrated investment planning and operation model is developed to simulate the transition pathway in the electric power system from 2020 to 2050 toward carbon neutrality under different innovation scenarios. Our results reveal that carbon neutrality can be achieved earlier and more cost effectively in the advanced energy technology innovation scenario. Furthermore, expanding both inter-regional and intra-regional transmission capacities can facilitate the achievement of carbon neutrality in the electric power system at a reduced cost.

Prostate cancer (PC) is the third most common male cancer in the world, which occurs due to various mutations leading to the loss of chromatin structure. There are multiple treatments for this type of cancer, of which chemotherapy is one of the most important. Sometimes, a combination of different treatments, such as chemotherapy, radiotherapy, and surgery, are used to prevent tumor recurrence. Among other treatments, androgen deprivation therapy (ADT) can be mentioned, which has had promising results. One of the drawbacks of chemotherapy and ADT treatments is that they are not targeted to the tumor tissue. For this reason, their use can cause extensive side effects. Treatments based on nanomaterials, known as nanomedicine, have attracted much attention today. Nanoparticles (NPs) are one of the main branches of nanomedicine, and they can be made of different materials such as polymer, metal, and carbon, each of which has distinct characteristics. In addition to NPs, nanovesicles (NVs) also have therapeutic applications in PC. In treating PC, synthetic NVs (liposomes, micelles, and nanobubbles) or produced from cells (exosomes) can be used. In addition to the role that NPs and NVs have in treating PC, due to being targeted, they can be used to diagnose PC and check the treatment process. Knowing the characteristics of nanomedicine-based treatments can help design new treatments and improve researchers’ understanding of tumor biology and its rapid diagnosis. In this study, we will discuss conventional and nanomedicine-based treatments. The results of these studies show that the use of NPs and NVs in combination with conventional treatments has higher efficacy in tumor treatment than the individual use of each of them.

PurposeGiven the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke.Methods and materialsThe Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends.ResultsGlobally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS.ConclusionThe burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

Alanine is the most abundant chiral amino acid that exists into the D-alanine or L-alanine forms with diverse applications in the biomedical, pharmaceutical, plastics, and food industries. D/L-alanine production can be carried out through chemical, microbial fermentation, and biocatalytic methods and not much effective due to complicated processes or purification issues and is still challenging to achieve a higher yield. In the present study, biobrick method was utilized for efficient production of D/L-alanine in the recombinant Escherichia coli BL21(DE3) with tandem three-gene co-expression plasmid. Firstly, the co-expression plasmid pET-22bNS-DadX-Ald-Gdh containing three genes, alanine dehydrogenase (ald), alanine racemase (dadX), and glucose dehydrogenase (gdh) from Bacillus pseudofirmus OF4 were successfully constructed and introduced into the E. coli BL21(DE3) strain. Then, under optimized conditions in the whole-cell biocatalytic reaction [20 mM Na2CO3-NaHCO3 (pH 10.1), 200 mM D-glucose, 200 mM sodium pyruvate, and 200 mM ammonium chloride], the concentration of D-alanine and L-alanine reached the maximum value (6.48 g/L and 7.05 g/L) after 3.0 h reaction time at 37°C under 180 rpm rotation. Meanwhile, promoter replacement experiments and Western blot analysis revealed that the expression level of protein OF4Ald had a significant effect on the production of D/L-alanine, indicating that alanine dehydrogenase might be the rate-limiting enzyme for D/L-alanine synthesis. This study provides a simple, feasible, and efficient biosynthesis process of D/L-alanine, which could explore emerging applications for large-scale production of industrial bioproducts.

Abstract Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia–reperfusion (I/R) injury, we found that the prophylactic administration of a well‐known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R‐induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro‐inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen‐glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R‐induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Due to its advantages of high spatiotemporal resolution, long-term stable observation, and historical retrospective data, satellite remote sensing has extensive application in the dynamic monitoring of water quality in coastal and inland waters. However, constructing generic satellite inversion models for water quality indicators, especially non-optically active parameters such as nutrients, remains challenging due to the varying pollution sources in different inland waters. This study aims to address this challenge from a data-driven perspective. Based on Sentinel-2 satellite images and in situ data from 311 automatic monitoring stations in Zhejiang Province, China, a large volume of matchups between satellite-derived water spectra and in situ water quality parameter concentrations were constructed, including the permanganate index (CODMn, N=8760, from 0.08 to 9.88 mg/L), total nitrogen (TN, N=7434, from 0.01 to 9.30 mg/L), total phosphorus (TP, N=8845, from 0.001 to 0.991 mg/L), ammonia nitrogen (NH3-N, N=8642, from 0.001 to 1.980 mg/L) and water turbidity (TUB, N=7913, from 0.1 to 1994 NTU). Satellite retrieval models for the five water quality parameters were constructed utilizing the extreme gradient boosting tree algorithm (XGBoost), which can be applied to diverse inland waters. The models showed robust performance on the additional independent dataset, with correlation coefficients (r) of 0.74, 0.79, 0.84, 0.72, and 0.87, and root mean square errors (RMSEs) of 0.73 mg/L, 0.56 mg/L, 0.18 mg/L, 0.24 mg/L, and 0.29 NTU for CODMn, TN, TP, NH3-N, and TUB, respectively. Comparisons between satellite-retrieved and in situ values showed good consistency in both spatial and temporal distributions. By applying these models to inland waters in Zhejiang Province, the monthly distributions of major rivers and reservoirs with a 10 m resolution for the five water quality parameters were obtained. The patterns of the five water quality parameters across the rivers typically indicated elevated values in the downstream regions and diminished values in the upstream areas, except for those of the Yongjiang River and Cao’e River. Compared to rivers, reservoirs had good water quality. However, for some water quality parameters, the temporal variations in the average values over the whole reservoir and the values at specific sites had opposite trends. Our research provides a practical reference for the construction of satellite retrieval models for determining the water quality parameters of inland waters, as well as robust technical support for dynamic remote sensing surveillance of inland water quality.