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Abstract Long non-coding RNAs (lncRNAs) have a notable role in the diagnosis and prognosis of cancer. However, the associations between lncRNA-related hub genes (LRHGs) expression and the corresponding outcomes have not been fully understood in lung adenocarcinoma (LUAD). Here, a total of 71 patients diagnosed with LUAD and 60 healthy volunteers at The First Affiliated Hospital of Huzhou University from April, 2023 to December, 2023 were enrolled in the present study. A LRHGs model was established using least absolute shrinkage and selection operator analyses of The Cancer Genome Atlas-LUAD datasets. The underlying mechanisms of the LRHGs were investigated via Gene Set Enrichment Analysis and Gene Set Variation Analysis. Additionally, the diagnostic role of serum HOXD cluster antisense RNA 2 (HOXD-AS2) was assessed by receiver operating characteristic (ROC) curve analysis. Lastly, TCGA-LUAD samples were divided into high- and low-HOXD-AS2 expression groups based on the median expression. The associations between HOXD-AS2 expression and miR-4538 as well as Calmodulin-Dependent Protein Kinase Type II subunit Beta (CAMK2B) levels were conducted through Pearson correlation analysis. A comprehensive analysis identified 141 differentially expressed lncRNAs between 539 LUAD tissues and 59 normal samples. A prognostic marker for overall survival was established by constructing a predictive signature consisting of 9 LRHGs. Subsequently, 474 LUAD samples were categorized into a high or low-risk group based on the median of the risk score. An independent prognostic model was constructed to confirm the validity of this categorization. Further comparisons of the clinicopathological features and LRHG-related pathways were performed between the two groups. Examinations of LRHG expression in two LUAD clusters and of the association between LRHG expression and immune infiltration were also conducted. HOXD-AS2 expression was shown to be elevated in LUAD tissues compared with matched normal tissues, and the serum HOXD-AS2 level was also notably increased in LUAD samples compared with healthy controls. The results of the ROC analysis indicated that the sensitivity and specificity of HOXD-AS2 were higher than that of cytokeratin-19 fragment (CYFRA21-1), which is a serum marker for LUAD. Pearson analyses indicated that miR-4538 level was negatively associated with HOXD-AS2 expression, but CAMK2B level showed positive correlation in LUAD. The results of the present study therefore indicated that the constructed LRHG model, particularly HOXD-AS2, could independently diagnose and predict the prognosis of LUAD, which suggested the underlying mechanism of the HOXD-AS2/miR-4538/CAMK2B, and might offer efficient strategies for LUAD treatment.

Abstract Human‐machine cooperative control has become an important area of intelligent driving, where driver intention recognition and dynamic control authority allocation are key factors for improving the performance of cooperative decision‐making and control. In this paper, an online learning method is proposed for human‐machine cooperative control, which introduces a priority control parameter in the reward function to achieve optimal allocation of control authority under different driver intentions and driving safety conditions. Firstly, a two‐layer LSTM‐based sequence prediction algorithm is proposed to recognise the driver's lane change (LC) intention for human‐machine cooperative steering control. Secondly, an online reinforcement learning method is developed for optimising the steering authority to reduce driver workload and improve driving safety. The driver‐in‐the‐loop simulation results show that our method can accurately predict the driver's LC intention in cooperative driving and effectively compensate for the driver's non‐optimal driving actions. The experimental results on a real intelligent vehicle further demonstrate the online optimisation capability of the proposed RL‐based control authority allocation algorithm and its effectiveness in improving driving safety.

Abstract Boron, essential for plant growth, necessitates precise regulation due to its potential toxicity. This regulation is achieved by borate transporters (BORs), which are homologous to the SLC4 family. The Arabidopsis thaliana Bor1 (AtBor1) transporter from clade I undergoes slow regulation through degradation and translational suppression, but its potential for fast regulation via direct activity modulation was unclear. Here, we combine cryo-electron microscopy, mutagenesis, and functional characterization to study AtBor1, revealing high-resolution structures of the dimer in one inactive and three active states. Our findings show that AtBor1 is regulated by two distinct mechanisms: an autoinhibitory domain at the carboxyl terminus obstructs the substrate pathway via conserved salt bridges, and phosphorylation of Thr410 allows interaction with a positively charged pocket at the cytosolic face, essential for borate transport. These results elucidate the molecular basis of AtBor1’s activity regulation and highlight its role in fast boron level regulation in plants.

Neurokinin B (NKB) is a hypothalamic neuropeptide containing 10 amino acids and is an essential member of the tachykinin family. Based on studies in mammals, Kiss, NKB, and dynorphin A are located in the common neurons, named KNDy neurons, and NKB and Kiss can stimulate the GnRH pulses. In humans, the mutations of NKB and its receptor NK3R can lead to hypogonadotropic hypogonadism and infertility. NKB is also involved in many other physiological activities in mammals and has received increasing attention. NKB was first purified from porcine spinal cord extracts and named neurokinin B or neuromedin K. Subsequently, NKB has been identified in various species, and its encoding gene was named tac2 in ruminants and rodents, and tac3 in other mammals, birds, reptiles, amphibians, and fish. In teleosts, the NKB system was first identified in zebrafish by three laboratories in 2012; it was also found in grass carp, goldfish, Nile tilapia, European eel, orange-spotted grouper, and half-smooth tongue.As teleosts have experienced the third round of genome duplication (3R), the bony fish have two forms of tac3 genes, namely tac3a and tac3b. However, only tac3a is present in highly evolved fish species, such as Nile tilapia and orange-spotted grouper, whereas the tac3b gene has been lost. tac3 in fish and amphibians can encode two mature peptides, NKB and an NKB-related peptide (NKBRP), whereas there is only NKB in mammals, birds, and reptiles. NKB and NKBRP sequences are highly conserved, and sequence analysis showed that NKB and NKBRP share an identical -FXGLM motif at the C-terminus, and X is a hydrophobic or aromatic amino acid residue, which plays an important role in binding to homologous receptors.NKB exerts biological effects by activating the endogenous receptor NK3R. The NK3R receptor belongs to the G protein-coupled receptor family and has a typical seven-transmembrane structure. NK3R is encoded by the tacr3 gene. There are two tacr3 subtypes in teleosts: tacr3a and tacr3b. There was an additional gene, called tacr3a2, in the zebrafish and grass carp, and it was produced by local genome duplication of tacr3a1. The tissue distribution shows that tac3 and tacr3 are widely expressed in the central nervous system and peripheral tissues, indicating that they have essential physiological functions. The specific expression patterns vary depending on the species. They are mainly expressed in the brain, with high expression levels in the pituitary, intestine, and gonads. NKB may participate in regulating reproduction and feeding in teleosts.Currently, studies in teleosts mainly focus on reproductive and feeding regulation. Due to the existence of multiple forms of tac3 and tacr3 genes in teleosts, the action of the NKB system on reproduction control is more complex. Using different experiment methods, such as intraperitoneal injection, intramuscular injection, and incubation of pituitary cells or pituitaries, NKB affected the expression of gnrh, kiss, lhβ, and fshβ and the secretion of LH, FSH, and E2 in fish. The physiological effects varied depending on the gonadal development stages, species, sex, treatment methods, treatment time, and dose. In addition, NKB can act as an anorectic peptide to inhibit food intake and promote gastrointestinal motility. It could also affect the expression of growth-related genes. In summary, as a neurotransmitter or neuromodulator in the central nervous system and a major member of the brain-gut peptides, the NKB system plays an important role in teleosts.Tachykinins activate receptors by coupling to Gαs and Gαq proteins, transducing its signals via PKA and PKC pathways. NKB and NKBRP could activate the PKA/PKC pathway via cognate receptors in some teleosts. This could be verified because different pathway inhibitors could block the effects of NKB and NKBRP. Upon binding to NK3R, NKB induces the secretion of related neuropeptides and the expression of related genes through the AC/cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-Ⅱ cascades. The C-terminal motif of NKB is crucial to binding receptors; once it is changed, NKB cannot activate the downstream signaling of NK3R, indicating that the integrity of the NKB/NK3R system is essential for the normal functioning of NKB. There are many deficiencies in the research regarding the function of NKB in teleosts. The specific effects and mechanisms of regulating reproductive endocrinology remain unclear, and the functional and signaling interactions between NKB and other neuroendocrine factors such as Kiss, GnIH, and GnRH require further study. In addition, the physiological functions of NKB in fish are mainly focused on reproductive regulation, with less attention given to feeding regulation and other physiological effects.In conclusion, this review provides a summary of the research progress on the NKB system in teleosts, including the identification, tissue distribution, physiological functions, and signaling mechanisms of NKB and its receptors, to enhance the understanding of the NKB system in fish and provide a reference for future research.

With the continuous advancement in socioeconomic development and transportation infrastructure, the daily traffic volume on highways has been steadily increasing, resulting in the growing frequency of traffic congestion incidents. Thus, the accurate prediction of highway traffic flow is of great significance for implementing traffic congestion warnings, guiding traffic diversion, and developing the concept of intelligent highways. Traffic flow exhibits intricate spatial and temporal dependencies: in the spatial dimension, the relationships between various traffic nodes are not fixed, changing dynamically over time; in the temporal dimension, multiple temporal patterns of traffic flow sequences are entangled with each other. In addition, an efficient method for fusing spatiotemporal relationships is lacking, making the accurate prediction of traffic flow a challenging endeavor. In this regard, a methodology for forecasting highway traffic flow is proposed based on dynamic graph convolutional networks and spatiotemporal feature extraction modules. Given the challenge posed by the static nature of predefined graph structures in capturing dynamic spatial relationships among traffic nodes, a dynamic graph adjustment module is introduced. Initially, the spatial features of each traffic node are extracted. Subsequently, utilizing these extracted spatial features, spatial similarity scores between traffic nodes are computed. Based on these scores, a traffic network graph structure is adapted: connections between nodes with high similarity scores, previously unlinked, are established with a certain probability, while connections between nodes with low similarity scores, previously linked, are severed with a certain probability. Furthermore, by employing the spatiotemporal feature extraction module and leveraging the updated graph structure, spatial relationships are extracted through graph convolution. This is complemented by integrating a patch concept from temporal processing methodologies. Herein, a one-dimensional traffic flow sequence is decomposed and transformed into two-dimensional data. Through convolutional operations, temporal features within and between periods are simultaneously extracted before reverting the data back to its original dimensionality. This comprehensive approach enables the modeling of spatiotemporal dependencies within the traffic flow data. To validate the effectiveness of the proposed model, experiments were conducted on four highway traffic datasets, contrasting its performance with baseline models. The proposed model achieved the mean absolute error (MAE) values of 15.6, 19.7, 16.8, and 5.21 on the PeMS03, PeMS04, PeMS08, and Fuzhou Jingtai highway datasets, respectively. These results show that the proposed method reaches an advanced level in traffic flow forecasting. Lastly, to assess the efficacy of individual model components, ablative experiments were conducted, and their results were compared. These experiments validate the effectiveness of each component, thereby affirming the efficacy of the proposed model in highway traffic flow forecasting.

Abstract To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS

Abstract This study explored the molecular epidemiology and resistance mechanisms of 271 non-duplicate Salmonella enterica (S. enterica) strains, isolated mainly from adults (209/271) in a tertiary hospital in Hangzhou between 2020 and 2021. Through whole-genome sequencing and bioinformatics, the bacterial strains were classified into 46 serotypes and 54 sequence types (ST), with S. Enteritidis, S. 1,4,[5],12:i:-, and S. Typhimurium being the most prevalent serotypes and ST11, ST34, and ST19 the most common STs. The strains isolated from adults were primarily S. Enteritidis (59/209), while from children were mainly S. 1,4,[5],12:i:- (20/62). Worryingly, 12.55% strains were multi-drug resistant (MDR), with resistance rates to cefepime (FEP), ceftazidime (CAZ), ceftriaxone (CRO) and cefotaxime (CTX) of 7.38%, 9.23%, 15.87% and 16.24%, respectively, and resistance rates to levofloxacin (LEV) and ciprofloxacin (CIP) of 8.49% and 19.19%, respectively. It is worth noting that the resistance rates of CRO and CTX in children reached 30.65%. A total of 34 strains carried extended-spectrum β-lactamase (ESBL) genes, dominated by bla CTX-M-65 (13/34) and bla CTX-M-55 (12/34); it is notable that one strain of S. Saintpaul carried both bla CTX-M-27 and bla CTX-M-55. The resistance mechanism to cephalosporins was mainly due to ESBL genes (20/43), and other genes included AmpC and β-lactamase genes. The strains resistant to quinolones mainly carried qnrS1 (27/53), and others included qnrB6, aac(6′)-Ib-cr, and mutations in gyrA and parC. One strain did not carry common quinolone resistance genes but had a parC (p.T57S) mutation to cause CIP resistance. This research provides vital insights into the molecular epidemiology and resistance mechanisms of clinical S. enterica, implicating possible infection control strategies.

Abstract Background This study evaluates a three-dimensional (3D) visualisation design combined with customized surgical guides to assist anterior maxillary segmental distraction osteogenesis (AMSDO) in correcting maxillary hypoplasia in adolescents with cleft lip and palate (CLP), focusing on treatment outcomes, satisfaction and the validity of 3D planning. Methods This retrospective cohort study was conducted at a single hospital in China. Between January 2020 and December 2023, 12 adolescents with CLP with maxillary hypoplasia were included. An advanced 3D simulation was used to convey the treatment strategy to the patients and their families. A customized surgical guide and distraction osteogenesis device were designed. Cephalometric analysis evaluated AMSDO changes and long-term stability. Patient satisfaction was assessed. The Chinese version of the Child Oral Health Impact Profile was used to evaluate the children’s oral health-related quality of life before and after treatment. The postoperative outcomes were compared with the planned outcomes by superimposing the actual postoperative data onto the simulated soft tissue models and calculating the linear and angular differences between them. Results One patient experienced postoperative gingivitis, yielding an 8.33% complication rate. Most patients (83.33%) were highly satisfied with the target position, with the rest content. Cephalometric analysis showed significant improvements in various indices post-traction. Quality-of-life scores significantly improved post-treatment. The discrepancies in facial soft tissue between the simulated and actual results were within clinically satisfactory ranges. Conclusions Digitally designed surgical guides effectively treat maxillary hypoplasia in adolescents with CLP, ensuring stability, reducing complications, reducing dependency on operator experience, and enhancing satisfaction and health outcomes. Although the simulated results were clinically acceptable, it is important to inform patients of potential variations in the predicted soft tissue.

AIM: To develop a deep learning-based model for automatic retinal vascular segmentation, analyzing and comparing parameters under diverse glucose metabolic status (normal, prediabetes, diabetes) and to assess the potential of artificial intelligence (AI) in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes. METHODS: Retinal fundus photos from 200 normal individuals, 200 prediabetic patients, and 200 diabetic patients (600 eyes in total) were used. The U-Net network served as the foundational architecture for retinal artery-vein segmentation. An automatic segmentation and evaluation system for retinal vascular parameters was trained, encompassing 26 parameters. RESULTS: Significant differences were found in retinal vascular parameters across normal, prediabetes, and diabetes groups, including artery diameter (P=0.008), fractal dimension (P=0.000), vein curvature (P=0.003), C-zone artery branching vessel count (P=0.049), C-zone vein branching vessel count (P=0.041), artery branching angle (P=0.005), vein branching angle (P=0.001), artery angle asymmetry degree (P=0.003), vessel length density (P=0.000), and vessel area density (P=0.000), totaling 10 parameters. CONCLUSION: The deep learning-based model facilitates retinal vascular parameter identification and quantification, revealing significant differences. These parameters exhibit potential as biomarkers for prediabetes and diabetes.

As a widely spread Gram-negative bacteria, Klebsiella pneumoniae (KP) mainly causes acquired infections in hospitals, such as lung infections, urinary tract infections, and bloodstream infections. In recent years, the number of multidrug-resistant KP strains has increased dramatically, posing a great threat to human health. Carbapenem-resistant KP (CRKP) can be colonized in human body, especially in gastrointestinal tract, and some colonized patients can be infected during hospitalization, among which invasive operation, underlying disease, admission to intensive care unit, antibiotic use, severity of the primary disease, advanced age, operation, coma, and renal failure are common risk factors for secondary infection. Active screening and preventive measures can effectively prevent the occurrence of CRKP infection. Based on the epidemiological status, this study aims to discuss the correlation between colonization and secondary infection induced by CRKP and risk factors for their happening and provide some reference for nosocomial infection prevention and control.

The low-degree gravity field and rotation parameters of terrestrial planets are functions of the planet's interior structure, providing insights into their composition and evolution, which serves them as crucial targets throughout deep-space exploration. Particularly, the measurement of rotation state can directly reveal the density and size of most untouchable planetary core. With the accumulation of data and the recent high-precision deep-space missions, substantial scientific advances have been achieved in understanding the internal structure of terrestrial planets, especially the core, using the low-degree gravity field and rotation measurements. In this study, we provide a summary of the fundamental theory and method for determining the principal moment of inertia tensor of planets, and then the basic theory of planetary rotation dynamics and rotational normal modes closely related to internal structures, and the methods for solving principal moments of inertia tensors of planets using the low-degree gravitational potential coefficients. We review the up-to-date researches on determining the mean bulk density and mean moment of inertia factor through limited rotation observations and the low-degree gravity field measurements, and the basic approaches to invert interior structures. Finally, we present existing challenges in revealing interior structures from low-degree gravity field and rotation normal modes for terrestrial planets and asteroids with a hope to provide scientific references and theoretical support for Chinese future deep-space missions.

Objectives: To address the lack of research on the prevalence of carbapenem-resistant Enterobacterales (CREs) in Xinjiang, China, and elucidate the genomic characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) ST11-KL30. Methods: CREs were collected in Xinjiang from 2021 to 2023. The antimicrobial susceptibility testing of carbapenems was performed via agar dilution method. Whole-genome sequencing was completed on the Illumina platform, and subsequent genomic analyses of CRKP, such as sequencing typing, K-locus and O-locus identification, virulence score assessment, and phylogenetic analysis, were performed. The virulence of CRKP isolates was determined in vitro and in vivo, and biofilm formation was assessed by crystal violet staining. Additionally, the virulence plasmid was reconstructed, and the formation of CRKP ST11-KL30 was revealed based on genome data from public database. Results: Eighty-five CRE isolates were collected, among which CRKP was most prevalent (68/85). KPC was the most dominant carbapenemase (60/68) in CRKP, while NDM-type carbapenemase was more prevalent in other species. ST11 was the dominant CRKP clone and was phylogenetically divided into three clusters: ST11-KL64, ST11-KL47 and ST11-KL30. CRKP ST11-KL30 is a novel recombinant clone that harbours a pK2044-like virulence plasmid and can be derived from ST11-KL64 by obtaining an ∼57 kb region from ST29-KL30. Compared to ST11-KL47 and ST11-KL64, ST11-KL30 had lower virulence, but had enhanced biofilm formation. Conclusions: We describe the prevalence of CRE prevalence southern Xinjiang and report the emergence of a region-specific clone. Our findings underscore the potential dissemination of ST11-KL30, which warrants increased monitoring in the future.

Abstract During the COVID-19 pandemic, delirium became a major complication that worsened patient outcomes. However, the factors influencing the severity of delirium in patients with COVID-19 have not been determined. We conducted this study to detect influencing factors associated with subtypes of delirium in patients with COVID-19. We included 1774 adult inpatients with COVID-19 from January to February 2023 at 7 sites in China. And used the 3 min Confusion Assessment Method and the Richmond Agitation-Sedation Scale for site assessment to identify and classify subtypes of delirium. Laboratory data were obtained from the Hospital Information System. After multivariate analysis, hypoactive delirium was significantly associated with age, the serum albumin concentration, frailty and sarcopenia, and health and nutritional status. Mixed delirium was significantly associated with age, D-dimer level, sarcopenia, health status and nutritional status. Additionally, hyperactive delirium was significantly associated with age, procalcitonin levels, frailty status and health status. Our findings suggest that poor nutritional status and low serum albumin concentration can help detect patients at high risk of developing hypoactive and mixed delirium. Additionally, clinical staff should pay more attention to patients with inflammatory conditions to assess and detect delirium because many influencing factors are involved in the common pathological mechanism of inflammation.

Abstract The existing diagnostic methods of epilepsy have great limitations, and more reliable and less difficult diagnostic methods are needed. We collected serum samples of adult patients with first-diagnosed epilepsy (EPs) and seizure control patients (EPRs) for non-targeted metabolomics detection and found that they were both significantly altered, with increased expression of nicotine addiction, linoleic acid metabolism, purine metabolism, and other metabolic pathways. The diagnostic model based on 4 differential metabolites achieved a diagnostic efficiency of 99.4% in the training cohort and 100% in the validation cohort. In addition, the association analysis of oral flora, serum metabolism, and clinical indicators also provided a new angle to analyze the mechanism of epilepsy. In conclusion, this study characterized the serum metabolic characteristics of EPs and EPRs and the changes before and after epilepsy control based on a large cohort, demonstrating the potential of metabolites as non-invasive diagnostic tools for epilepsy.

Abstract Background Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood. Methods To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT–qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT–qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1’s regulation of autophagy in GC. Results Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo. Conclusion PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC. Graphical Abstract

Dendrobium is a traditional, valuable, and nourishing medicinal herb in China. It benefits the stomach, promotes fluid production, nourishes Yin, and clears heat. Polysaccharides are among the main active ingredients of Dendrobium. By reviewing literature over the past decade, the common structures and biological activities of Dendrobium polysaccharides are systematically summarized. The results illustrate that Dendrobium polysaccharides possess various effects, including antioxidant, antitumor, anti-inflammatory, and immunoregulatory effects, gut microbiota modulation, blood sugar reduction, and anticataract properties. The chemical structures of these polysaccharides are closely related to their biological activities. Previous studies suggest that polysaccharides rich in mannose and glucose exhibit stronger activity, whereas higher acetylation levels enhance immune activity. Higher uronic acid content corresponds to greater antioxidant ability, which may be due to the presence of (1→4)-α-D-Glcp and (1→4)-α-D-Manp on the main chain. Additionally, chemical modifications such as sulfation, selenization, and acetylation can enhance activity, whereas carboxymethylation decreases it. This article summarizes the research progress in recent years on the structure, biological activity, and product development of Dendrobium polysaccharides both home and abroad, elucidating the structure-activity relationship, aiming to provide important references for their in-depth development and application.

Abstract Background Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. Methods The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. Results DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein–protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. Conclusion This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.

Abstract The purpose of this study was to investigate the relationship between Inflammatory Prognostic Index (IPI) levels and Contrast-Induced Nephropathy (CIN) risk and postoperative clinical outcomes in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). A total of 3,340 consecutive patients who underwent CAG and/or PCI between May 2017 and December 2022 were enrolled in this study. Based on their baseline IPI levels, patients were categorized into four groups. Clinical characteristics and postoperative outcomes were compared among these groups. In-hospital outcomes focused on CIN risk, repeated revascularization, major bleeding, and major adverse cardiovascular events (MACEs), while the long-term outcome examined the all-cause readmission rate. Quartile analysis found a significant link between IPI levels and CIN risk, notably in the highest quartile (P

Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

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.

BackgroundRecent studies have investigated the epidemiological burden of sleep-disordered breathing (SDB) in patients with stroke; however, the results have been inconsistent, and the temporal trends of SDB after stroke remain unclear.ObjectiveTo perform a systematic review and meta-analysis of the prevalence and incidence of post-stroke SDB, evaluate demographic and clinical characteristic predictors of post-stroke SDB, and examine temporal trends in the overall burden of post-stroke SDB.MethodsWe searched PubMed, MEDLINE, Embase, Web of Science, CINAHL, and the Cochrane Library for studies reporting the burden of SDB in stroke patients published between 1 January 2010 and 30 December 2023. Two researchers independently screened the records for eligibility, extracted the data, and assessed the quality of the studies. Data were analyzed using random effects meta-analyses, and sources of heterogeneity were explored using subgroup analyses and meta-regression analyses.ResultsOut of the 8,799 references retrieved, none examined the incidence of SDB after stroke. However, 85 studies from 26 countries examined the prevalence of SDB and were included. The overall prevalence of SDB, mild SDB, and moderate to severe SDB were 60.0% (95% CI, 60.0–70.0%), 30.0% (95% CI, 23.0–37.0%), and 45.0% (95% CI, 33.0–57.0%), respectively. Meta-regression revealed that sex (p

Abstract gLiving materials can achieve unprecedented function by combining synthetic materials with the wide range of cellular functions. Of interest are situations where the critical properties of individual abiotic and biotic elements improve via their combination. For example, integrating electroactive bacteria into conjugated polyelectrolyte (CPE) hydrogels increases biocurrent production. One observes more efficient electrical charge transport within the CPE matrix in the presence of Shewanella oneidensis MR‐1 and more current per cell is extracted, compared to traditional biofilms. Here, the origin of these synergistic effects are examined. Transcriptomics reveals that genes in S. oneidensis MR‐1 related to bacteriophages and energy metabolism are upregulated in the composite material. Fluorescent staining and rheological measurements before and after enzymatic treatment identified the importance of extracellular biomaterials in increasing matrix cohesion. The synergy between CPE and S. oneidensis MR‐1 thus arises from initially unanticipated changes in matrix composition and bacteria adaption within the synthetic environment.

Today, firms face several environmental concerns, including but not limited to: decreasing natural resources, pollution management, and climate change. Little is known about the factors that motivate the many forms of environmental innovation or the effects of these endeavors on the financial success of businesses, despite the growing demand for eco-friendly goods and services. For the first time, this study introduces the core environmental determinants for China's 30 provinces covering the period of 2005–2022. In these determinants, this study considers foreign direct investment (FDI), financial development (FDI), natural resources (NRs), human capital (HC), and green energy (GE). However, to investigate the study objectives, the present study utilizes an advanced series of estimators that can overcome all panel data problems. In these estimators, the Augmented Mean Group (AMG), the Common Correlated Effect Mean Group (CCE-MG), and the Panel Quantile Regression (P-QR) are being considered. However, the results of the long-term investigation obtained interesting outcomes for selected provinces. For example, financial proxies such as economic development and foreign direct investment significantly increase the environmental innovations across the selected regions. Conversely, natural resources negatively affect environmental innovations and become a leading hurdle in the clean & green innovation process. Finally, empirical analysis finds a positive response of ecological regulations and green energy to an explained variable. This article outlined policy proposals for a low-carbon economy that would guarantee environmental innovation in certain provinces by reducing emissions; these proposals included increasing the use of renewable energy sources, sustainable technology, and environmentally friendly technology.

Seashore paspalum (Paspalum vaginatum) is a warm-season and perennial turfgrass and is known for its cadmium (Cd)-stress tolerance. Here, a Phosphoproteomics analysis was performed to examine the key proteins relating to Cd tolerance in seashore paspalum. Fructose 1,6-biphosphate aldolase, PvFBA1, was identified for its phosphorylated state after exposure to Cd stress. Specifically, the phosphorylation of PvFBA1 was enhanced in several metabolic pathways, including pentose phosphate pathway (PPP), carbon fixation and biosynthesis of amino acids under Cd stress. By transforming PvFBA1 into Arabidopsis, the PvFBA1-OE plants exhibited longer roots, greater FBA activity and higher soluble sugar content than WT under 100 µM CdCl2 treatment. By expressing the PvFBA1 in yeast, a serine 50 phosphorylation site was identified as functional site. By microscale thermophoresis experiment, we indicted that PvFBA1can bind Cd directly enhancing its phosphorylation level to alleviate the damage of Cd. This finding may provide new insights into the molecular mechanisms of plants Cd tolerance.

ObjectiveTo investigate how Chinese residents perceived changes in their protective behaviors in the early stage after the lifting of the dynamic zero-COVID policy, and to explore the associations between the overall perceived change and factors such as demographic and health-related information, COVID-19 related perceptions, negative emotions, and coping styles.MethodsThis cross-sectional study involved 798 Chinese residents who completed an online questionnaire between 16 and 25 December 2022. The questionnaire covered demographic and health-related information, COVID-19 related perceptions, negative emotions, coping styles, and perceived changes in protective behaviors. Multiple linear stepwise regression analysis was used to determine the factors associated with the overall perceived change in protective behaviors.ResultsThe mean score for perceived protective behavioral change among participants was 61.38 (SD = 10.20), which was significantly higher than the hypothesized no-change value of 49 (p

Herein, a TiVNb medium-entropy alloy was prepared via vacuum arc melting. The alloy maintained a body-centred cubic (BCC)-dominant phase following an annealing treatment at 1300 °C for 12 h. Although its structure was coarsened due to grain growth during annealing, the alloy developed a few Ti-rich nanobands and showed an increase in dislocations, resulting in its hardness increasing from 241.7 to 341.1 HV and strength increasing by tens of MPa relative to that of the as-melt TiVNb alloy. The tensile strength of the coarsened alloy reached 647 MPa at room temperature and 405 MPa at 800 °C. Further, the compressive yield strength reached 438 MPa at 800 °C, under which condition the alloy exhibited fewer cracks. Rapid softening was observed at 1200 °C, reducing the yield strength to ∼50 MPa. The coarsened TiVNb alloy showed weak dependence of its strength on temperature.

IntroductionFollicular thyroid carcinoma (FTC) is the second most common thyroid malignancy and is characterized by a higher risk of distant metastasis compared to papillary thyroid cancer. Intraoperative frozen section (IOFS) diagnosis of FTC is challenging due to its limited sensitivity and accuracy, leading to uncertainty in intraoperative surgical decision-making. In response, we developed a predictive model to assess the risk of follicular carcinoma in thyroid nodules identified as suspicious for follicular neoplasm by IOFS.MethodsThis model was derived from preoperative clinical and ultrasound data of 493 patients who underwent thyroid surgery at Ningbo Medical Center Lihuili Hospital. It identified five significant predictors of follicular carcinoma: nodule size, thyroglobulin (Tg) level, hypoechogenicity, lobulated or irregular margins, and thick halo.ResultsThe model demonstrated robust discrimination and calibration, with an area under the curve (AUC) of 0.83 (95% CI: 0.77-0.90) in the training set and 0.78 (95% CI: 0.68-0.88) in the validation set. In addition, it achieved a sensitivity of 81.63% (95% CI: 69.39-91.84) and 68.00% (95% CI: 48.00--4.00), a specificity of 77.42% (95% CI: 72.18-82.66) and 72.51% (95% CI: 65.50-78.96), an accuracy of 78.1% (95% CI: 73.4-82.4) and 71.9% (95% CI: 65.3-78.6), a positive predictive value (PPV) of 41. 67% (95% CI: 35.65-48.84) and 26.79% (95% CI: 19.40-34.33), respectively, and a negative predictive value (NPV) of 95.61% (95% CI: 92.86-97.99) and 94.07% (95% CI: 90.44-97.08) in the training and validation sets, respectively.ConclusionThe model can accurately rule out FTC in low-risk nodules, thereby providing surgeons with a practical tool to determine the necessary extent of surgical intervention for nodules flagged as suspicious by IOFS.

BackgroundEmergence agitation (EA) is a common complication in the pediatric population. This study aimed to investigate the effect of the prophylactic nalbuphine on EA in pediatric patients receiving sevoflurane anesthesia.MethodsThe children undergoing ear, nose, and throat (ENT) surgery were administered 0.2 mg/kg nalbuphine (the nalbuphine group) or the same volume of normal saline (the control group) 5 min before the end of the surgery. The extubating time, time to eye-opening and duration of the post-anesthesia care unit (PACU) were recorded. Heart rate and blood pressure were monitored before and 5 min after nalbuphine administration. Pain was assessed using Face Legs Activity Cry and Consolability (FLACC) scales, and the drug-related postoperative complications (e.g., EA, delayed awakening, nausea and vomiting, and respiratory depression) were recorded.ResultsOne-hundred and thirty pediatric patients were randomly divided into nalbuphine and control groups (n = 65). The nalbuphine group showed a significantly lower incidence of EA than the control group (20% vs. 46.2%, P = 0.002). No significant differences between the two groups were observed in heart rate and blood pressure 5 min after nalbuphine administration (P > 0.05). No significant differences were observed between the two groups regarding extubating time, time to eye-opening, and duration of PACU. The FLACC scales demonstrated lower values in the nalbuphine group than in the control group during the initial 4 h after the surgery. However, the FLACC scales showed similar values between 5 and 12 h after the surgery.ConclusionsIn summary, the results of this study demonstrated that prophylactic natbuphine could minimize the incidence of EA in pediatric patients following ENT surgery without increasing the extubating time and PACU duration.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier [ChiCTR2300070046].

Photocatalysis offers a sustainable means for the oxidative removal of low concentrations of NOx (NO, NO2, N2O, N2O5, etc.) from the atmosphere. Layered double hydroxides (LDHs) are promising candidate photocatalysts owing to their unique layered and tunable chemical structures and abundant surface hydroxide (OH−) moieties, which are hydroxyl radical (·OH) precursors. However, the practical applications of LDHs are limited by their poor charge-separation ability and insufficient active sites. Herein, we developed a facile N2H4-driven etching approach to introduce dual Ni2+ and OH− vacancies (Niv and OHv, respectively) into NiFe-LDH nanosheets (hereafter referred to as NiFe-LDH-et) to facilitate improved charge-carrier separation and active Lewis acidic site (Fe3+ and Ni2+ exposed at OHv) formation. In contrast to inert pristine LDH, NiFe-LDH-et actively removed NO under visible-light illumination. Specifically, Ni76Fe24-LDH-et etched with 1.50 mmol·L−1 N2H4 solution removed 32.8% of the NO in continuously flowing air (NO feed concentration: ∼500 parts per billion (ppb)) under visible-light illumination, thereby outperforming most reported catalysts. Experimental and theoretical data revealed that the dual vacancies promoted the production of reactive oxygen species (O2·− and ·OH) and the adsorption of NO on the LDH. In situ spectroscopy demonstrated that NO was preferentially adsorbed at Lewis acidic sites, particularly exposed Fe3+ sites, converted into NO+, and subsequently oxidized to NO3− without the notable formation of the more toxic intermediate NO2, thereby alleviating risks associated with its production and emission.

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photinia microphylla (J.E.Vidal) B.B.Liu and Weniomeles atropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

Abstract Background Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. Methods We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. Results We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. Conclusions Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC. Graphical abstract The mechanism of circ0003692 in suppressing metastasis of GC. FNDC3B-267aa encoded by circ0003692 interacted with c-Myc and promoted the proteasomal degradation of c-Myc, thereby down-regulated c-Myc-Snail/Slug axis and EMT pathway.

Abstract Conventional wind speed distribution methods (e.g., Rayleigh distribution and Weibull distribution) may not adequately capture complex characteristics of wind fields in mountainous areas. To address this problem, this study proposes a semi-parametric mix method for modeling the distribution of average wind speeds based on the combination of nonparametric Kernel Density Estimation (KDE) and Generalized Pareto Distribution (GPD). In the proposed method, KDE focuses on capturing the distribution in the main part of average wind speeds, while GPD aims at performing the distribution in terms of those in the extreme part. The segment point (i.e., the threshold) between KDE and GPD distributions is determined based on the combination of conditional mean excesses criterion and empirical rule. Meanwhile, the selection of modeling parameters should ensure that the mix distribution model is continuous and differentiable at the identified threshold point. Then, the commonly-used conditional probability model is further introduced to describe the wind direction distribution. Finally, a case study based on the measured 10-min average wind speeds at a mountainous bridge site is employed to demonstrate the effectiveness of the proposed method. The results indicate that: (1) the distribution of omnidirectional average wind speeds in the mountainous bridge site exhibits an obviously single-peak characteristic, while those considering wind directionality present a certain bimodal characteristic; (2) the proposed method can effectively describe wind speed distributions with different statistical characteristics, and the fitting accuracy outperforms the frequently-employed Weibull distribution model.

Abstract Holothuria scabra, a commercially valuable yet ecologically vulnerable tropical holothuroid, has experienced a severe decline in its wild populations, especially in China. Genomic resources are crucial for the development of effective genomic breeding projects and stock conservation strategies to restore these natural populations. Until now, a high-quality, chromosome-level reference genome for H. scabra has not been available. Here, we employed Oxford Nanopore and Hi-C sequencing technologies to assemble and annotate a high-quality, chromosome-level reference genome of H. scabra. The final genome comprised 31 scaffolds with a total length of 1.19 Gb and a scaffold N50 length of 53.52 Mb. Remarkably, 1,191.67 Mb (99.95%) of the sequences were anchored to 23 pseudo-chromosomes, with the longest one spanning 79.75 Mb. A total of 34,418 protein-coding genes were annotated in the final genome, with BUSCO analysis revealing 98.01% coverage of metazoa_odb10 genes, marking a significant improvement compared to the previous report. These chromosome-level sequences and annotations will provide an essential genomic basis for further investigation into molecular breeding and conservation management of H. scabra.

Abstract Background Soybean (Glycine max), a vital grain and oilseed crop, serves as a primary source of plant protein and oil. Soil salinization poses a significant threat to soybean planting, highlighting the urgency to improve soybean resilience and adaptability to saline stress. Melatonin, recently identified as a key plant growth regulator, plays crucial roles in plant growth, development, and responses to environmental stress. However, the potential of melatonin to mitigate alkali stress in soybeans and the underlying mechanisms remain unclear. Results This study investigated the effects of exogenous melatonin on the soybean cultivar Zhonghuang 13 under alkaline stress. We employed physiological, biochemical, transcriptomic, and metabolomic analyses throughout both vegetative and pod-filling growth stages. Our findings demonstrate that melatonin significantly counteracts the detrimental effects of alkaline stress on soybean plants, promoting plant growth, photosynthesis, and antioxidant capacity. Transcriptomic analysis during both growth stages under alkaline stress, with and without melatonin treatment, identified 2,834 and 549 differentially expressed genes, respectively. These genes may play a vital role in regulating plant adaptation to abiotic stress. Notably, analysis of phytohormone biosynthesis pathways revealed altered expression of key genes, particularly in the ARF (auxin response factor), AUX/IAA (auxin/indole-3-acetic acid), and GH3 (Gretchen Hagen 3) families, during the early stress response. Metabolomic analysis during the pod-filling stage identified highly expressed metabolites responding to melatonin application, such as uteolin-7-O-(2''-O-rhamnosyl)rutinoside and Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside, which helped alleviate the damage caused by alkali stress. Furthermore, we identified 183 differentially expressed transcription factors, potentially playing a critical role in regulating plant adaptation to abiotic stress. Among these, the gene SoyZH13_04G073701 is particularly noteworthy as it regulates the key differentially expressed metabolite, the terpene metabolite Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. WGCNA analysis identified this gene (SoyZH13_04G073701) as a hub gene, positively regulating the crucial differentially expressed metabolite of terpenoids, Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. Our findings provide novel insights into how exogenous melatonin alleviates alkali stress in soybeans at different reproductive stages. Conclusions Integrating transcriptomic and metabolomic approaches, our study elucidates the mechanisms by which exogenous melatonin ameliorates the inhibitory effects of alkaline stress on soybean growth and development. This occurs through modulation of biosynthesis pathways for key compounds, including terpenes, flavonoids, and phenolics. Our findings provide initial mechanistic insights into how melatonin mitigates alkaline stress in soybeans, offering a foundation for molecular breeding strategies to enhance salt-alkali tolerance in this crop.

Abstract This study explores the bidirectional association between multimorbidity and falls in Chinese middle-aged and elderly adults. Participants aged 45 and above from the China Health and Retirement Longitudinal Study were included. Binary logistic regression assessed the impact of chronic conditions on fall incidence (stage I), while multinomial logistic regression examined the relationship between baseline falls and multimorbidity (stage II). The fully adjusted odds ratios (ORs) for one, two, or three or more chronic conditions were 1.34, 1.65, and 2.02, respectively. Among participants without baseline falls, 28.61% developed two or more chronic conditions during follow-up, compared to 37.4% of those with a history of falls. Fully adjusted ORs for one, two, or three or more chronic conditions in those with a history of falls were 1.21, 1.38 and 1.70, respectively. The bidirectional relationship held in sensitivity and subgroup analyses. A bidirectional relationship exists between multimorbidity and falls in Chinese middle-aged and elderly adults. Strengthening chronic condition screening and treatment in primary healthcare may reduce falls risk, and prioritizing fall prevention and intervention in daily life is recommended.

Abstract Early warning of existing bridges is now predominated by deterministic methods. However, these methods face challenges in expressing uncertain factors (such as wind load, temperature load, and other variables, etc.). These problems directly impact the timeliness and accuracy of bridge early warning. This study develops an innovative method for bridge dynamic early warning with high versatility and accuracy. Long short-term memory network model (LSTM), expectation maximization (EM) and Gaussian mixture model (GMM) were employed in the proposed method. Firstly, the LSTM model is used to predict the measured monitoring data (such as deflection, strain, cable force, etc.) in real time to obtain the predicted results. Next, the number of clusters for the EM-GMM model is determined using the Calinski-Harabasz (CH) index. The method aims to comprehensively consider the internal cohesion of the clustering, ensuring accurate and reliable clustering results. Then, the EM-GMM model is used to cluster the random influence error and the predicted value, which can get the probabilistic prediction result of each corresponding random influence error. On this basis, the dynamic early warning interval under 95% confidence level is constructed. This facilitates early warning and decision-making for potential structural abnormalities. Finally, the accuracy and practicability of the method are verified by the comparison of engineering applications and existing specifications. The results demonstrate that the probabilistic early warning method considering the uncertain factors in the complex service environment can accurately achieve the dynamic early warning of bridges.

Endogenous retroviruses (ERVs), remnants of ancient viral invasions, make up a significant part of the mammalian genomes. ERVs are typically held in check by complex epigenetic mechanisms, which serve to limit their expansion and potential adverse effects on the genome. However, ERVs can become aberrantly activated in response to stressful challenges, contributing to progression in pathological conditions, including cancer, inflammation, auto-immune disorders, and aging, through various mechanisms. Notably, ERV activation is also detected in the brain and is increasingly recognized as an important factor in neuropsychiatric disorders. In this review, we encapsulate the general understanding of ERVs in both physiological and pathological states and compiled evidence for ERV activation across a spectrum of neuropsychiatric disorders, along with current studies exploring the underlying mechanisms. Despite the accumulating body of evidence, research in this field remains in its infancy and faces substantial challenges. Further studies are warranted to enhance our understanding of ERV activation mechanisms and their roles in neuropsychological conditions, potentially contributing to the development of innovative therapeutic interventions.

Purpose Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Abstract Background Coronary artery disease (CAD) patients who have undergone coronary artery bypass grafting (CABG) often experience a severe psychological burden for a long period of time, which can adversely affect their post-operative prognosis. Therefore, this study aimed to evaluate the effect of a web-based Information-Knowledge-Attitude-Practice (WIKAP) continuous intervention on the psychological status, medical compliance, and quality of life (QoL) in patients with CAD after CABG surgery. Methods A parallel randomized clinical trial enrolled 174 CAD patients who underwent CABG at our hospital between January 2018 and December 2019. The participants were randomly divided into the Control and WIKAP group and received intervention for 12 months. The scores for anxiety, depression, medical compliance, and QoL were assessed on the first day (M0), 3rd month (M3), 6th month (M6), 9th month (M9) and 12th month (M12) after discharge. Furthermore, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was analyzed using the Kaplan-Meier curve and Cox proportional regression models for an additional 24-month follow-up period without any intervention. Results After the 12-month intervention, the scores of anxiety and depression were significantly reduced in the WIKAP group at M9 and M12 compared to those in the Control group (all P 0.05). Cox proportional regression analysis also showed that the nursing intervention (Control vs. WKIAP) was not associated with the incidence of MACCE. Conclusion WIKAP nursing intervention effectively improved the psychological health, medical compliance, and QoL in CAD patients who underwent CABG operation, but it did not prolong MACCE-free survival. Trail registration The study is registered in isrctn.org: ISRCTN13653455.

Abstract What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.

Carbon materials (graphite or C/C composites) are widely used in aerospace applications due to their unique performance advantages, including low density, high specific strength and low coefficients of thermal expansion. However, carbon materials are highly susceptible to destructive oxidation in high-temperature oxygen-containing environments, limiting their application scope and service life. Coating technology is an effective approach for solving the above problem, and ceramic coatings are the most widely used protective system. In this review, the latest research progress regarding different types of silicon carbide-based antioxidation and anti-ablation ceramic coatings on the surfaces of carbon materials is described, and the protective properties and mechanism analysis of the SiC and modified SiC coatings by ultrahigh-temperature ceramic borides, carbides, silicides and other reinforcements are elucidated. In addition, the current main challenges of ceramic coatings are carefully analysed, and the perspectives for the future development of ceramic protection coatings are also discussed.

Leptin is a peptide hormone primarily produced by adipose tissue, which plays a crucial role in regulating energy balance by controlling appetite and energy expenditure. To better understand the intricate physiological functions of leptin in hepatocytes in tongue sole (Cynoglossus semilaevis), this study presents an integrated transcriptomic and metabolomic analysis of tongue sole hepatocytes following stimulation with lepA and lepB. Comparative analysis identified 2971 and 2900 upregulated differentially expressed genes (DEGs) and 1895 and 1821 downregulated DEGs in response to lepA and lepB stimulation, respectively. Notably, 5706 genes were commonly regulated by both stimulations, suggesting overlapping functional roles of these two leptin proteins. GO and KEGG enrichment analysis indicated significant enrichment in immune response (JAK-STAT signaling pathway, NF-κB signaling pathway, etc.) and lipid metabolism pathways, such as fatty acid synthesis, with similar findings for lepB. Metabolomic analysis demonstrated clear separation between treatment and control groups, with 34 medium- to long-chain fatty acids and numerous differentially expressed metabolites (DEMs) identified. KEGG analysis of the metabolome paralleled the transcriptomic findings, with shared pathways in lipid metabolism and immune function. Finally, joint analysis highlighted co-enrichment in linoleic acid metabolism and leishmaniasis pathways. Detailed mechanistic insights revealed the activation of JAK-STAT and NF-κB signaling pathways, modulation of arachidonic acid metabolism, and the influence on the MAPK signaling pathway. Additionally, lepA uniquely co-enriched in the fatty acid synthesis pathway, with specific gene regulation affecting the synthesis of various fatty acids. The study concluded that lepA and lepB exerted significant regulatory effects on lipid metabolism and immune responses in tongue sole hepatocytes through complex molecular networks. To our current knowledge, this represents the first direct evidence of leptin's role in immune function within teleost fish and offers valuable insights into the molecular mechanisms of lipid metabolism underlying the actions of lepA and lepB.

Background Patient safety incidents, such as adverse events and medical errors, are often caused by ineffective communication and collaboration. Interprofessional education is an effective method for promoting collaborative competencies and has attracted great attention in the context of patient safety. However, the effectiveness of interprofessional education interventions on patient safety remains unclear. This scoping review aimed to synthesize existing studies that focused on improving patient safety through interprofessional education interventions for healthcare professionals.Methods Six databases, including Medline (via PubMed), Embase, Cochrane Library, CINAHL (via EBSCO), Scopus and Web of Science, were last searched on 20 December 2023. The search records were independently screened by two researchers. The Joanna Briggs Institute Critical Appraisal Tool for Quasi-Experimental Studies was used for quality appraisal. The data were extracted by two researchers and cross-checked. Finally, a narrative synthesis was performed. The protocol for this scoping review was not registered.Results Thirteen quasi-experimental studies with moderate methodological quality were included. The results revealed that the characteristics of current interprofessional education interventions were diverse, with a strong interest in simulation-based learning strategies and face-to-face delivery methods. Several studies did not assess the reduction in patient safety incidents involving adverse events or medical errors, relying instead on the improvements in healthcare professionals’ knowledge, attitude or practice related to patient safety issues. Less than half of the studies examined team performance, based primarily on the self-evaluation of healthcare professionals and observer-based evaluation. There is a gap in applying newer tools such as peer evaluation and team-based objective structured clinical evaluation.Conclusion Additional evidence on interprofessional education interventions for improving patient safety is needed by further research, especially randomized controlled trials. Facilitating simulation-based interprofessional education, collecting more objective outcomes of patient safety and selecting suitable tools to evaluate teamwork performance may be the focus of future studies.

ABSTRACTTo investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-β-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harbouring plasmid contributed to the increased resistance to β-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

ABSTRACTCarbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to β-lactams, β-lactam/β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum β-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.

Abstract Background Extrachromosomal circular DNAs (eccDNAs), a type of double‐stranded DNAs (dsDNAs) that facilitate the activation of the DNA sensing machinery, have been implicated in the progression and prognosis of various diseases. While the roles of eccDNAs remain contentious, their significance in diffuse large B‐cell lymphoma (DLBCL) has not been reported. Methods Circular DNA sequencing (circle‐seq) was used to demonstrate the expression profile of eccDNAs in DLBCL, and atomic force microscopy to validate the presence of eccDNAs. CCK‐8 and scRNA‐seq techniques were employed to uncover the activation of eccDNA in the STING pathway, leading to enhanced cell proliferation. Chemotherapeutic drugs were used to test the hypothesis that DNA damage induces the production of eccDNA, thereby activating the STING pathway independent of cGAS. GEO databases were used for verification of the prognosis of the eccDNA‐related genes, and animal models were used to investigate the synergistic effects of DNA damage therapy in combination with STING inhibitors on anti‐tumour responses. Results EccDNAs were widely expressed in DLBCL and associated with the prognosis of patients. Elevated abundance of eccDNAs promoted the progression of DLBCL. Chemotherapeutic drugs‐induced DNA damage triggered the generation of eccDNAs, resulting in the activation of the STING signalling in a cGAS‐independent manner. Moreover, inhibition of STING exerted a synergistic anti‐tumour effect with cisplatin. Conclusions EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. This finding offers a rational therapeutic strategy combining chemotherapy with targeting STING. Highlights EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. The combined treatment of chemotherapeutic drugs with STING inhibitor significantly delayed the tumor progression, providing new insights into the therapeutic strategy for patients with DLBCL, particularly the relapsed and/or refractory (R/R) ones.

Sea-land relay transportation (SRT) is a key part of the “land-based greenhouse + offshore net cage” mariculture system for yellowtail kingfish. In this study, the physiological status of yellowtail kingfish during SRT was assessed by determining serum biochemical indexes (levels of cortisol, glucose, and malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and catalase (CAT)), the composition of intestinal microflora, and the liver transcriptome before (control), during, and after transportation (T1 and T2) and after recovery for 6 hours (6 h), 12 hours (12 h), 1 day (D1), 3 days (D3), and 7 days (D7). The results show that the serum cortisol and glucose levels, MDA level, and activities of SOD and CAT significantly increased during transportation, and decreased to similar levels to those in the control after 1 day of recovery. Bacteria including Acinetobacter, Enterobacter, and Comamonas accounted for more than 91 % of the microbial community in the gut of yellowtail kingfish, and these genera were associated with changes in serum glucose levels, indicating that they may help to alleviate the effects of transportation stress. Analyses of liver transcriptome data showed that significantly differentially expressed genes (DEGs) in the T2, D1, D3 and D7 groups were significantly enriched in the “Protein processing in the endoplasmic reticulum (ER)” pathway. At the end of transportation (T2 group), the ER-associated degradation (ERAD) pathway was activated, with up-regulation of hsp40, hsp70, and hsp90α. The transcript levels of these genes gradually returned to levels similar to those in the control during the recovery period. At the first day of recovery, the unfolded protein response imposed stress upon the ER, accompanied by significant down-regulation of PEPK and Calmin and significant up-regulation of CRT. The DEGs in the D3 group were enriched in the “ER”, “Steroid biosynthesis”, “Fatty acid degradation”, “PPAR signaling”, and “Fat digestion and absorption” pathways, whereas the number of DEGs related to lipid metabolism and stress pathways was significantly decreased in the D7 group. Our results indicate that hsp70 and hsp90α can be used as stress markers, and hsp40 can be used as a physio-metabolic recovery marker for yellowtail kingfish. These results show that, although serum indices recovered 24 hours after transportation, up to 3 days after transportation is an important period for recovery from transportation stress at the transcriptome level. “Protein processing in the ER pathway” is an important pathway regulating stress and recovery in yellowtail kingfish.