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To reveal the microstructure forming mechanism of laser/ultra-high frequency (UHF) induction deposition, this paper developed a microscopic phase-field (PF) model to numerically investigate dendrite growth during solidification. The macroscopic model of molten pool evolution is adopted to provide the solidification conditions for the microscopic PF model. The dendrite growth during laser deposition is simulated to evaluate the effect of UHF induction heat on the dendrite growth. Results show that because of the high temperature gradient and cooling rate, the PDAS of laser-UHF induction hybrid deposited layer is less than that of the laser deposited layer. The UHF induction heat also leads to a high flow velocity of the molten metal during laser-UHF induction hybrid deposition. The high flow velocity contributes to the decrease in PDAS by inhibiting the interdendritic enrichment of solute. During laser-UHF induction hybrid deposition, a higher solute gradient is present in the tip region of dendrite arm, leading to a faster dendrite growth rate. The UHF induction heat also increases the solute distribution coefficient during deposition, which further inhibits the element segregation. Under the action of UHF induction heat, a low interdendritic solute gradient and an evenly distributed solute can be obtained, thus helping increase interdendritic undercooling degrees and decreasing the PDAS. The simulated PDAS and solute distribution have good consistency with the experimental results. The spectral analysis of EDS line detection indicates that the laser-UHF induction hybrid deposited layer has a more refined microstructure and weaker element segregation than the laser deposited layer does.

Abstract Background T-cell leukemia homeobox protein 1 (TLX1) has been revealed as a hub transcription factor in leukemia, while its function in hepatocellular carcinoma (HCC) has not been well described. Here, we investigated the regulation and function of TLX1 in HCC. Methods TLX1 and its possible upstream and downstream molecules in HCC were identified using bioinformatics tools, which were then verified by RT-qPCR assay. CCK-8, wound healing, and Transwell invasion assays were performed to detect the effects of TLX1 knockdown on HCC cells. The interactions between TLX1 and trafficking protein particle complex subunit 9 (TRAPPC9) or Zinc finger protein 69 homolog B (ZFP69B) were further probed by ChIP and luciferase reporter assays. Rescue experiments were finally conducted in vitro and in vivo. Results TLX1 was highly expressed in HCC cells, and the knockdown of TLX1 led to reduced malignant biological behavior of HCC cells. TLX1 bound to the promoter region of TRAPPC9, thereby promoting TRAPPC9 expression. Overexpression of TRAPPC9 attenuated the effect of TLX1 reduction on suppressing malignant behavior of HCC cells. ZFP69B was also highly expressed in HCC cells and bound to the promoter region of TLX1 to induce TLX1 expression. Knockdown of ZFP69B inhibited the viability and mobility of HCC cells in vitro and tumor growth in vivo, and overexpression of TLX1 rescued this inhibition. Conclusion These findings suggest that ZFP69B promotes the proliferation of HCC cells by directly upregulating the expression of TLX1 and the ensuing TRAPPC9.

Abstract Background Understanding the impact of environmental factors on physical activity (PA) and physical fitness (PF) is crucial for promoting a healthy lifestyle among children and adolescents. This study examines how awareness of sports policies, school, family, and community environments influence PA and PF in Chinese youth. Methods A cross-sectional study was conducted with 2747 children and adolescents (mean age 12.90 ± 2.49; 48.2% male) from 17 schools across five Chinese cities. Environmental factors were assessed via questionnaires, and PA levels were measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). PF metrics, including BMI, waist-to-height ratio, grip strength, vertical jump, and 20-m shuttle run test (20-mSRT), were measured onsite. Structural Equation Modeling (SEM) was used to explore relationships between environmental factors and PA/PF outcomes. Results The school environment scored highest (78.0 ± 9.5), while the community environment scored lowest (38.7 ± 18.0). Family environment positively influenced low-intensity PA (LPA) (β = 0.102, P

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

SiC-based composites are widely used as electromagnetic wave absorbers due to their excellent dielectric properties. However, the constraints associated with structural design and the intricacies of the preparation process hinder their broader application. In this study, novel mullite anti-gyroid/SiC gyroid metastructures are designed to integrate the mechanical and electromagnetic wave (EMW) absorption properties of composite materials. Mullite anti-gyroid/SiC gyroid composites are fabricated utilizing a combination of digital light processing (DLP) three-dimensional (3D) printing and precursor infiltration and pyrolysis (PIP) processes. Through the modulation of structural units, the electromagnetic parameters can be effectively regulated, thus improving the impedance matching characteristics of the composites. The structural composites show outstanding EMW absorption properties, with a minimum reflection loss of −54 dB at a thickness of 1.9 mm and an effective absorption bandwidth of 3.20 GHz at a thickness of 2.2 mm. Furthermore, the PIP process significantly enhances the mechanical properties of the composites; compared with those of the mullite/SiC ceramics, the flexural strength of the composites is improved by 3.69–5.85 times (13.28±1.15 MPa vs. (49.05±1.07)–(77.78±3.72) MPa), and the compressive strength is improved by 4.59–13.58 times (8.55±0.90 MPa vs. (39.02±1.63)–(116.13±2.58) MPa). This approach offers a novel and effective method for fabricating structural composites with an expanded range of higher electromagnetic wave absorption properties and improved mechanical properties.

By benchmarking with the iteration of drilling technology, fracturing technology and well placement mode for shale oil and gas development in the United States and considering the geological characteristics and development difficulties of shale oil in the Jiyang continental rift lake basin, East China, the development technology system suitable for the geological characteristics of shale oil in continental rift lake basins has been primarily formed through innovation and iteration of the development, drilling and fracturing technologies. The technology system supports the rapid growth of shale oil production and reduces the development investment cost. By comparing it with the shale oil development technology in the United States, the prospect of the shale oil development technology iteration in continental rift lake basins is proposed. It is suggested to continuously strengthen the overall three-dimensional development, improve the precision level of engineering technology, upgrade the engineering technical indicator system, accelerate the intelligent optimization of engineering equipment, explore the application of complex structure wells, form a whole-process integrated quality management system from design to implementation, and constantly innovate the concept and technology of shale oil development, so as to promote the realization of extensive, beneficial and high-quality development of shale oil in continental rift lake basins.

Abstract Background There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures. Methods We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient’s vertebral body was determined. Results In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p

Abstract In this paper, we propose a deformed Reuleaux-triangle resonator (RTR) to form exceptional point (EP) which results in the detection sensitivity enhancement of nanoparticle. After introducing single nanoparticle to the deformed RTR at EP, frequency splitting obtains an enhancement of more than 6 times compared with non-deformed RTR. In addition, EP induced a result that the far field pattern of chiral mode responses significantly to external perturbation, corresponding to the change in internal chirality. Therefore, single nanoparticle with far distance of more than 4000 nm can be detected by measuring the variation of far field directional emission. Compared to traditional frequency splitting, the far field pattern produced in deformed RTR provides a cost-effective and convenient path to detect single nanoparticle at a long distance, without using tunable laser and external coupler. Our structure indicates great potential in high sensitivity sensor and label-free detector. Graphical Abstract

Abstract Three-dimensional (3D) learning resources are increasingly being integrated into classrooms and becoming important teaching tools. Learning resilience is a crucial factor affecting learning outcomes. However, the impact of 3D learning resources on learning resilience has not been received sufficient academic attention. This study constructs a structural equation model based on the broaden-and-build theory and cognitive load theory to examine the impact of 3D learning resources on learning resilience. To examine the mechanism of this impact, including the mediating roles of positive emotion and cognitive load, we collected 963 valid questionnaires from college students in Shandong Province, China. The results indicate that 3D learning resources are significantly positively correlated with positive emotion and learning resilience and negatively correlated with cognitive load. Moreover, cognitive load is negatively correlated with learning resilience. Positive emotion and cognitive load serve as mediators in the relationship between 3D learning resources and learning resilience. Therefore, developing high-quality 3D learning resources, cultivating positive emotions among students and reducing cognitive load can enhance college students’ learning resilience and mitigate academic risks.

Abstract Background Klebsiella pneumoniae is a zoonotic opportunistic pathogen, and also one of the common pathogenic bacteria causing mink pneumonia. The aim of this study was to get a better understanding of the whole-genome of multi-drug resistant Klebsiella pneumoniae with K2 serotype in China. This study for the first time to analyze Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, resistance and virulence genes of Klebsiella pneumoniae in mink. Results The isolate was Klebsiella pneumoniae with serotype K2 and ST6189 by PCR method. The string test was positive and showed high mucus phenotype. There was one plasmid with IncFIB replicons in the genome. The virulence factors including capsule, lipopolysaccharide, adhesin, iron uptake system, urease, secretory system, regulatory gene (rcsA, rcsB), determinants of pili adhesion, enolase and magnesium ion absorption related genes. The strain was multi-drug resistant. A total of 26 resistance genes, including beta-lactam, aminoglycosides, tetracycline, fluoroquinolones, sulfonamides, amide alcohols, macrolides, rifampicin, fosfomycin, vancomycin, diaminopyrimidines and polymyxin. Multidrug-resistant efflux protein AcrA, AcrB, TolC, were predicted in the strain. Conclusion It was the first to identify that serotype K2 K. pneumonia with ST6189 isolated from mink in China. The finding indicated that hypervirulent and multi-drug resistant K. pneumoniae was exist in Chinese mink. The whole-genome of K. pneumoniae isolates have importance in mink farming practice.

Objective Uniportal full‐endoscopic foraminotomy offers a promising alternative to conventional surgical methods for individuals afflicted by lumbar foraminal stenosis. This study aims to evaluate the efficacy and clinical outcomes of uniportal full‐endoscopic foraminotomy in patients diagnosed with lumbar foraminal stenosis. Methods A comprehensive retrospective analysis was conducted on individuals who underwent full‐endoscopic foraminotomy in our medical center, between January 2018 and December 2019. The investigation encompassed the demographic data of patients and key clinical metrics such as the visual analogue scale of leg (VAS‐L) and back pain (VAS‐B), Oswestry disability index (ODI) scores, the Short Form‐36 Health Survey physical component summary (SF‐36 PCS) and the mental component summary (SF‐36 MCS), as well as modified MacNab grades, were systematically assessed and compared. Furthermore, radiological parameters: Coronal Cobb angle (CCA), Intervertebral angle changes (IAC), Disc height index (DHI), the foraminal cross‐sectional area (FCSA) and the FCSA enlargement ratio were also compared. A variety of statistical analyses including Student t‐test, chi‐square tests, Fisher's exact tests, Pearson's and Spearman's correlation analyses, and Interclass Correlation Coefficients (ICCs) were employed. Results 64 patients, including 34 males and 30 females were enrolled. The mean follow‐up period extended to 22.66 ± 7.05 months. Distribution by affected segments revealed 26.6% at L4‐5, 67.1% at L5‐S1 level, and 6.25% at both L4‐L5 and L5‐S1 levels. At the final follow‐up, VAS‐L decreased from 7.26 ± 1.19 to 1.37 ± 1.25, while VAS‐B decreased from 6.95 ± 0.54 to 1.62 ± 1.13 (p < 0.001). ODI score also demonstrated a substantial decrease from 74.73 ± 8.68 to 23.27 ± 8.71 (p < 0.001). Both SF‐36 PCS and SF‐36 MCS scores improved significantly (p < 0.001). Modified MacNab criteria revealed 58 excellent‐good patients (90.7%), and 6 fair‐poor patients (9.3%). No significant differences were founded in the CCA (p = 0.1065), IAC (p = 0.5544), and DHI (p = 0.1348) between pre‐operation and the final follow‐up. However, the FCSA significantly increased from 73.41 ± 11.75 to 173.40 ± 18.62 mm2 (p < 0.001), and the enlargement ratio was 142.9% ± 49.58%. Notably, the final follow‐up FCSA and the FCSA enlargement ratio were found to be larger in the excellent and good group compared to the fair and poor group, according to the modified MacNab criteria. Conclusion The utilization of uniportal full‐endoscopic foraminotomy has demonstrated its safety and efficacy in addressing lumbar foraminal stenosis. The clinical success of this procedure appears to be closely associated with the radiological decompression of the intervertebral foramen area. Importantly, the application of this technology does not seem to compromise the overall stability of the lumbar region.

Abstract Background Gibberella ear rot (GER) is one of the most devastating diseases in maize growing areas, which directly reduces grain yield and quality. However, the underlying defense response of maize to pathogens infection is largely unknown. Results To gain a comprehensive understanding of the defense response in GER resistance, two contrasting inbred lines ‘Nov-82’ and ‘H10’ were used to explore transcriptomic profiles and defense-related phytohormonal alterations during Fusarium graminearum infection. Transcriptomic analysis revealed 4,417 and 4,313 differentially expressed genes (DEGs) from the Nov-82 and H10, respectively, and 647 common DEGs between the two lines. More DEGs were obviously enriched in phenylpropanoid biosynthesis, secondary metabolites biosynthesis, metabolic process and defense-related pathways. In addition, the concentration of the defense-related phytohormones, jasmonates (JAs) and salicylates (SAs), was greatly induced after the pathogen infection. The level of JAs in H10 was more higher than in Nov-82, whereas an opposite pattern for the SA between the both lines. Integrated analysis of the DEGs and the phytohormones revealed five vital modules based on co-expression network analysis according to their correlation. A total of 12 hub genes encoding fatty acid desaturase, subtilisin-like protease, ethylene-responsive transcription factor, 1-aminocyclopropane-1-carboxylate oxidase, and sugar transport protein were captured from the key modules, indicating that these genes might play unique roles in response to pathogen infection, Conclusions Overall, our results indicate that large number DEGs related to plant disease resistance and different alteration of defensive phytohormones were activated during F. graminearum infection, providing new insight into the defense response against pathogen invasion, in addition to the identified hub genes that can be further investigated for enhancing maize GER resistance.

Abstract Background TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. Methods The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. Results We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. Conclusion MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.

Abstract Hydrogen sulfide (H2S) has emerged as a novel endogenous gas signaling molecule, joining the ranks of nitric oxide (NO) and carbon monoxide (CO). Recent research has highlighted its involvement in various physiological processes, such as promoting root organogenesis, regulating stomatal movement and photosynthesis, and enhancing plant growth, development, and stress resistance. Tobacco, a significant cash crop crucial for farmers’ economic income, relies heavily on root development to affect leaf growth, disease resistance, chemical composition, and yield. Despite its importance, there remains a scarcity of studies investigating the role of H2S in promoting tobacco growth. This study exposed tobacco seedlings to different concentrations of NaHS (an exogenous H2S donor) − 0, 200, 400, 600, and 800 mg/L. Results indicated a positive correlation between NaHS concentration and root length, wet weight, root activity, and antioxidant enzymatic activities (CAT, SOD, and POD) in tobacco roots. Transcriptomic and metabolomic analyses revealed that treatment with 600 mg/L NaHS significantly effected 162 key genes, 44 key enzymes, and two metabolic pathways (brassinosteroid synthesis and aspartate biosynthesis) in tobacco seedlings. The addition of exogenous NaHS not only promoted tobacco root development but also potentially reduced pesticide usage, contributing to a more sustainable ecological environment. Overall, this study sheds light on the primary metabolic pathways involved in tobacco root response to NaHS, offering new genetic insights for future investigations into plant root development.

Abstract Edible oil adulteration is a mostly practiced phenomenon. However, the traditional discriminant methods fail to detect oil adulteration involving more than one adulterant. Recently, one‐class classifiers were built for food or oil authentication. Unfortunately, as it is hard to determine the application domain of the one‐class classifier, high prediction error was obtained for real samples in market surveillance. In this study, a new method was developed based on one‐class classification and outlier detection for edible oil adulteration detection in market surveillance. The model population was constructed using Monte Carlo sampling of unidentified inspected samples to select the plateau region exhibiting the highest accumulated absolute centered residual (ACR) values. Subsequently, the number of models in the plateau region was validated by the theoretical ones calculated by the classical probability model. The models in the plateau region with the highest cumulative accumulated ACR values were used to identify adulterated oils. Furthermore, the cross‐validation was conducted by comparing identification results from two different Monte Carlo sampling ratios to ensure the accuracy of our method. Both single adulteration and multiple adulteration of peanut oils were prepared to validate our method. Moreover, this method was used to detect adulteration of sesame oils, which have already been identified by the markers in our previous study. The validation results of three datasets indicated that this method could effectively identify adulterated samples and therefore provide a novel solution for inspecting potential adulteration in practice.

The key to a Battery Management System (BMS) is the accurate and real-time prediction of the State of Charge (SOC) of the power battery. Currently, there is relatively little research on the construction methods of battery models within a wide temperature range. A second-order RC equivalent circuit is selected to establish an Improved Equivalent Circuit Model (IECM) based on temperature compensation. The identification of IECM parameters is completed by using the multi strategy improvement of Artificial Bee Colony (MSIABC) algorithm combining with pulse discharge experimental data under different temperature conditions (-20 °C to 60 °C). Based on the experimental data of the UDDS condition and the hybrid dynamic condition under low temperature, high temperature, and time-varying temperature environments, the battery SOC is estimated by combining the IECM and Adaptive Extended Kalman Filtering (AEKF) algorithm. The experimental results show that compared with the conventional ECM-AEKF estimation method, IECM-AEKF has higher SOC estimation accuracy and environmental temperature adaptability.

AbstractContext Diabetic kidney disease (DKD) is a prominent complication arising from diabetic microangiopathy, and its prevalence and renal impact have placed it as the primary cause of end-stage renal disease. Traditional Chinese Medicine (TCM) has the distinct advantage of multifaceted and multilevel therapeutic attributes that show efficacy in improving clinical symptoms, reducing proteinuria, protecting renal function, and slowing DKD progression. Over recent decades, extensive research has explored the mechanisms of TCM for preventing and managing DKD, with substantial studies that endorse the therapeutic benefits of TCM compounds and single agents in the medical intervention of DKD.Objective This review lays the foundation for future evidence-based research efforts and provide a reference point for DKD investigation.Methods The relevant literature published in Chinese and English up to 30 June 2023, was sourced from PubMed, Cochrane Library, VIP Database for Chinese Technical Periodicals (VIP), Wanfang Data, CNKI, and China Biology Medicine disc (CBM). The process involved examining and summarizing research on TCM laboratory tests and clinical randomized controlled trials for DKD treatment.Results and conclusions The TCM intervention has shown the potential to inhibit the expression of inflammatory cytokines and various growth factors, lower blood glucose levels, and significantly affect insulin resistance, lipid metabolism, and improved renal function. Furthermore, the efficacy of TCM can be optimized by tailoring personalized treatment regimens based on the unique profiles of individual patients. We anticipate further rigorous and comprehensive clinical and foundational investigations into the mechanisms underlying the role of TCM in treating DKD.

Wholly defined ex vivo expansion conditions for biliary tree stem cell (BTSC) organoids were established, consisting of a defined proliferative medium (DPM) used in combination with soft hyaluronan hydrogels. The DPM consisted of commercially available Kubota's Medium (KM), to which a set of small molecules, particular paracrine signals, and heparan sulfate (HS) were added. The small molecules used were DNA methyltransferase inhibitor (RG108), TGF- β Type I receptor inhibitor (A83-01), adenylate cyclase activator (Forskolin), and L-type Ca2+ channel agonist (Bay K8644). A key paracrine signal proved to be R-spondin 1 (RSPO1), a secreted protein that activates Wnts. Soluble hyaluronans, 0.05 % sodium hyaluronate, were used with DPM to expand monolayer cultures. Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology [G*] of less than 100 Pa. The combination is called the BTSC-Expansion-Glycogel-System (BEX-gel system) for expanding BTSCs as a monolayer or as organoids. The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors. Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/- mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions. The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.

Abstract Background Colorectal cancer (CRC) is a serious global health burden because of its high morbidity and mortality rates. Hypoxia and massive lactate production are hallmarks of the CRC microenvironment. However, the effects of hypoxia and lactate metabolism on CRC have not been fully elucidated. This study aimed to develop a novel molecular subtyping based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs) and construct a signature to predict the prognosis of patients with CRC and treatment efficacy. Methods Bulk and single-cell RNA-sequencing and clinical data of CRC were downloaded from the TCGA and GEO databases. HRGs and LMRGs were obtained from the Molecular Signatures Database. The R software package DESeq2 was used to perform differential expression analysis. Molecular subtyping was performed using unsupervised clustering. A predictive signature was developed using univariate Cox regression, random forest model, LASSO, and multivariate Cox regression analyses. Finally, the sensitivity of tumor cells to chemotherapeutic agents before and after hypoxia was verified using in vitro experiments. Results We classified 575 patients with CRC into three molecular subtypes and were able to distinguish their prognoses clearly. The C1 subtype, which exhibits high levels of hypoxia, has a low proportion of CD8 + T cells and a high proportion of macrophages. The expression of immune checkpoint genes is generally elevated in C1 patients with severe immune dysfunction. Subsequently, we constructed a predictive model, the HLM score, which effectively predicts the prognosis of patients with CRC and the efficacy of immunotherapy. The HLM score was validated in GSE39582, GSE106584, GSE17536, and IMvigor210 datasets. Patients with high HLM scores exhibit high infiltration of CD8 + exhausted T cells (Tex), especially terminal Tex, and oxidative phosphorylation (OXPHOS)−Tex in the immune microenvironment. Finally, in vitro experiments confirmed that CRC cell lines were less sensitive to 5-fluorouracil, oxaliplatin, and irinotecan under hypoxic conditions. Conclusion We constructed novel hypoxia- and lactate metabolism-related molecular subtypes and revealed their immunological and genetic characteristics. We also developed an HLM scoring system that could be used to predict the prognosis and efficacy of immunotherapy in patients with CRC.

Abstract Background Fear overgeneralization constitutes a susceptibility factor contributing to the development and maintenance of anxiety spectrum disorders. Extant research has demonstrated that exposure to positive and supportive social relationships attenuates fear acquisition and promotes the extinction of conditioned fear responses. However, the literature lacks investigation into the effect of secure attachment priming on inhibiting the generalization of conditioned fear. Methods In this study, college students were recruited via online platforms to voluntarily engage in the experimental procedures, resulting in 57 subjects whose data were deemed suitable for analysis. The experimental protocol consisted of four consecutive phases: pre-acquisition, acquisition, priming, and generalization. The priming phase consisted of two experimental conditions: secure attachment priming (experimental group) and positive emotion priming (control group). This study adopted the perceptual discrimination fear conditioning paradigm, employing subjective expectancy of shock ratings and skin conductance responses as primary assessment indices. Individual difference variables were measured using corresponding psychological measurement scales. Results In terms of generalization degree, a notable divergence surfaced in the skin conductance responses across various generalization materials between the secure attachment priming group and the control group. Similarly, during generalization extinction, a significant disparity emerged in the skin conductance responses across different generalization phases between the secure attachment priming group and the control group. In addition, individual differences analyses revealed that the inhibitory effect of secure attachment priming on fear generalization was not affected by intolerance of uncertainty and attachment orientations. Conversely, slope analyses confirmed that as intolerance of uncertainty increased, the inhibitory effect of positive emotion priming on fear generalization was attenuated. Conclusion The findings suggest that activating participants' representations of secure attachment via imagination effectively attenuates the generalization of perceptual fear at the physiological level. The inhibitory effect of secure attachment priming appears to be distinct from positive emotional modulation and remains unaffected by individual trait attachment styles. These results offer novel insights and avenues for the prevention and clinical intervention of anxiety spectrum disorders.

Abstract The risk of cholangitis after ERCP implantation in malignant obstructive jaundice patients remains unknown. To develop models based on artificial intelligence methods to predict cholangitis risk more accurately, according to patients after stent implantation in patients’ MOJ clinical data. This retrospective study included 218 patients with MOJ undergoing ERCP surgery. A total of 27 clinical variables were collected as input variables. Seven models (including univariate analysis and six machine learning models) were trained and tested for classified prediction. The model’ performance was measured by AUROC. The RFT model demonstrated excellent performances with accuracies up to 0.86 and AUROC up to 0.87. Feature selection in RF and SHAP was similar, and the choice of the best variable subset produced a high performance with an AUROC up to 0.89. We have developed a hybrid machine learning model with better predictive performance than traditional LR prediction models, as well as other machine learning models for cholangitis based on simple clinical data. The model can assist doctors in clinical diagnosis, adopt reasonable treatment plans, and improve the survival rate of patients.

Abstract Accurately controlling the product selectivity in syngas conversion, especially increasing the olefin selectivity while minimizing C1 byproducts, remains a significant challenge. Epsilon Fe2C is deemed a promising candidate catalyst due to its inherently low CO2 selectivity, but its use is hindered by its poor high-temperature stability. Herein, we report the successful synthesis of highly stable ε-Fe2C through a N-induced strategy utilizing pyrolysis of Prussian blue analogs (PBAs). This catalyst, with precisely controlled Mn promoter, not only achieved an olefin selectivity of up to 70.2% but also minimized the selectivity of C1 byproducts to 19.0%, including 11.9% CO2 and 7.1% CH4. The superior performance of our ε-Fe2C-xMn catalysts, particularly in minimizing CO2 formation, is largely attributed to the interface of dispersed MnO cluster and ε-Fe2C, which crucially limits CO to CO2 conversion. Here, we enhance the carbon efficiency and economic viability of the olefin production process while maintaining high catalytic activity.

Abstract Background Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation. Methods In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium. Results Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR

Abstract Background Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose–response relationship between overall and specific types of exercise with depression symptoms in older adults. Methods This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). Results A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose–response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. Conclusions In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.

Abstract Aim The most common type of cancer that leads to death worldwide is lung cancer. Despite significant surgery and chemotherapy improvements, lung cancer patient’s survival rate is still poor. The RNA polymerase I subunit D (POLR1D) gene can induce various cancers. A current study reported that POLR1D plays a vital role in cancer prognosis. However, its biological function in the development of lung cancer remains unclear. Methods Reverse transcription PCR (RT-PCR) measured the relative POLR1D protein expression level in lung cancer cell lines. Lung cancer cell proliferation, migration, and invasion were analyzed by performing cell counting kit-8 (CCK-8), and transwell. The phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway-related protein expressions were examined by Western blotting assay. Results POLR1D protein expression was elevated in lung cancer. Lung cancer cell loss-of-function tests showed that POLR1D silencing could attenuate cell viability both in SK-MES-1 and in H2170 cells. Furthermore, silencing POLR1D inhibited SK-MES-1 and H2170 cells proliferation, migration, and invasion. Moreover, SK-MES-1 and H2170 cells’ migration and invasion capacity were potentially suppressed by the knockdown of POLR1D. The progression of multiple cancers has been implicated in the PI3K/AKT pathway. Here, we observed that POLR1D silencing suppressed lung cancer progression by inhibition of the PI3K-Akt pathway. Conclusions The study speculated that POLR1D might provide a new potential therapeutic possibility for treating lung cancer patients via targeting PI3K/AKT.

Abstract Objective Research the dose–response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. Design Systemic and Bayesian Model-Based Network Meta-Analysis. Methods In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD. Results Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362). Conclusion Nonlinear dose–response relationship between exercise and cognitive improvement in Alzheimer’s disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.

The combat domain of modern warfare is becoming increasingly multidimensional. It is important to evaluate the resilience of the air-ground cooperative network for defending against attack threats and recovery performance. First, a resilience analysis model was proposed to effectively analyze and evaluate the resilience of the air-ground cooperative network. Then, considering the available resources, three dynamic reconfiguration strategies were given from the global perspective to help the air-ground cooperative network quickly recover performance and enhance combat capabilities. Finally, a typical 50-node network was taken as an example to prove the effectiveness and feasibility of the proposed model. The proposed method can provide scientific guidance for improving the air-ground cooperative network combat capabilities.

Abstract Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.

Abstract Background To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits. Methods A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR. Results The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P

Abstract Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. This study aimed to investigate the functional significance of aryl hydrocarbon receptor nuclear translocator (ARNT) in the pathogenesis of GBM. Analysis of public datasets revealed ARNT is upregulated in GBM tissues compared to lower grade gliomas or normal brain tissues. Higher ARNT expression correlated with the mesenchymal subtype and poorer survival in GBM patients. Silencing ARNT using lentiviral shRNAs attenuated the proliferative, invasive, and stem-like capabilities of GBM cell lines, while ARNT overexpression enhanced these malignant phenotypes. Single-cell RNA sequencing uncovered that ARNT is highly expressed in a stem-like subpopulation and is involved in regulating glycolysis, hypoxia response, and stress pathways. Mechanistic studies found ARNT activates p38 mitogen-activated protein kinase (MAPK) signaling to promote chemoresistance in GBM cells. Disrupting the ARNT/p38α protein interaction via the ARNT PAS-A domain restored temozolomide sensitivity. Overall, this study demonstrates ARNT functions as an oncogenic driver in GBM pathogenesis and represents a promising therapeutic target.

Ephedroid macrofossils have been widely documented in Cretaceous deposits, including numerous from the Lower Cretaceous Yixian Formation of NE China. However, few ephedroid macrofossils have been reported from South America. Herein, we describe a new plant of the family Ephedraceae, Arlenea delicata gen. et sp. nov., from the Lower Cretaceous Crato Formation of the Araripe Basin, Northeast Brazil, based on the vegetative and reproductive structures. It has the typical morphological characteristics of ephedroid plants, including fertile reproductive branches, opposite phyllotaxy, terminal female cones, a sympodial branching system, longitudinally striated internodes, and swollen nodes. Our new finding is unusual in having inner chlamydosperms subtended by two pairs of bracts, reproductive units connected to branches through swollen receptacles and a smooth seed surface. This new ephedroid taxon from the Crato Formation increases our understanding of plant diversity of this group during the Early Cretaceous. Furthermore, the general morphology (fleshy bracts and enlarged receptacles) of this new fossil discovery indicates that seeds of this plant may have been dispersed by animals such as pterosaurs (mainly the Tapejaridae) and birds (Enantiornithes and Ornituromorpha). If true, this would explain the cosmopolitan distribution of Ephedraceae in the Lower Cretaceous.

ABSTRACTDigital Light Processing (DLP) technology is a highly effective molding method for creating complex structural parts. However, the low solid content of SiC stereolithography slurry has been found to diminish the mechanical properties of the ceramic, regardless of whether it is sintered by Reactive Melt Infiltration (RMI) or Precursor Infiltration and Pyrolysis (PIP). This poses a significant challenge in improving the mechanical properties of SiC ceramics manufactured through DLP additive manufacturing. In response to this challenge, a novel method of RMI combined with infiltration is proposed in this study. The process involves the filling of the pores of the green body with pyrolytic carbon from PR or pyrolytic SiC from LHBPCS through circular infiltration, effectively increasing the content of SiC in the ceramics after reaction. Notably, the elastic modulus of RM-P2 and RM-L2 samples increased by 37.39% and 33.91%, respectively, demonstrating the potential of this method for preparing ceramics with high SiC content through stereolithography additive manufacturing. This innovative approach holds promise for overcoming the limitations previously associated with SiC ceramics produced through DLP additive manufacturing, opening up new possibilities for the development of high-performance SiC-based components.

Frozen ground (FG) plays an important role in global and regional climates and environments through changes in land freeze‒thaw processes, which have been conducted mainly in different regions. However, the changes in land surface freeze‒thaw processes under climate change on a global scale are still unclear. Based on ERA5-Land hourly land skin temperature data, this study evaluated changes in the global FG area, global land surface first freeze date (FFD), last freeze date (LFD) and frost-free period (FFP) from 1950 to 2020. The results show that the current FG areas (1991–2020 mean) in the Northern Hemisphere (NH), Southern Hemisphere (SH), and globe are 68.50 × 106, 9.03 × 106, and 77.53 × 106 km2, which account for 72.4%, 26.8%, and 60.4% of the exposed land (excluding glaciers, ice sheets, and water bodies) in the NH, SH and the globe, respectively; further, relative to 1951–1980, the FG area decreased by 1.9%, 8.8%, and 2.8%, respectively. Seasonally FG at lower latitudes degrades to intermittently FG, and intermittently FG degrades to non-frozen ground, which caused the global FG boundary to retreat to higher latitudes from 1950 to 2020. The annual FG areas in the NH, SH, and globe all show significant decreasing trends (p

Abstract Hard carbons are emerging as the most viable anodes to support the commercialization of sodium-ion (Na-ion) batteries due to their competitive performance. However, the hard carbon anode suffers from low initial Coulombic efficiency (ICE), and the ambiguous Na-ion (Na+) storage mechanism and interfacial chemistry fail to give a reasonable interpretation. Here, we have identified the time-dependent ion pre-desolvation on the nanopore of hard carbons, which significantly affects the Na+ storage efficiency by altering the solvation structure of electrolytes. Consummating the pre-desolvation by extending the aging time, generates a highly aggregated electrolyte configuration inside the nanopore, resulting in negligible reductive decomposition of electrolytes. When applying the above insights, the hard carbon anodes achieve a high average ICE of 98.21% in the absence of any Na supplementation techniques. Therefore, the negative-to-positive capacity ratio can be reduced to 1.02 for full cells, which enables an improved energy density. The insight into hard carbons and related interphases may be extended to other battery systems and support the continued development of battery technology.

Abstract Background Resolvin D1 (RvD1), a specialized pro-resolving lipid mediator (SPM), is derived from docosahexaenoic acid (DHA). It plays a key role in actively resolving inflammatory responses, which further reduces small intestinal damage. However, its regulation of the apoptosis triggered by endoplasmic reticulum (ER) stress in intestinal epithelial cells is still poorly understood. The intestinal porcine epithelial cells (IPEC-J2) were stimulated with tunicamycin to screen an optimal stimulation time and concentration to establish an ER stress model. Meanwhile, RvD1 (0, 1, 10, 20, and 50 nM) cytotoxicity and its impact on cell viability and the effective concentration for reducing ER stress and apoptosis were determined. Finally, the effects of RvD1 on ER stress and associated apoptosis were furtherly explored by flow cytometry analysis, AO/EB staining, RT-qPCR, and western blotting. Results The ER stress model of IPEC-J2 cells was successfully built by stimulating the cells with 1 µg/mL tunicamycin for 9 h. Certainly, the increased apoptosis and cell viability inhibition also appeared under the ER stress condition. RvD1 had no cytotoxicity, and its concentration of 1 nM significantly decreased cell viability inhibition (p= 0.0154) and the total apoptosis rate of the cells from 14.13 to 10.00% (p= 0.0000). RvD1 at the concentration of 1 nM also significantly reduced the expression of glucose-regulated protein 78 (GRP-78, an ER stress marker gene) (p= 0.0000) and pro-apoptotic gene Caspase-3 (p= 0.0368) and promoted the expression of B cell lymphoma 2 (Bcl-2, an anti-apoptotic gene)(p= 0.0008). Conclusions Collectively, the results shed light on the potential of RvD1 for alleviating apoptosis triggered by ER stress, which may indicate an essential role of RvD1 in maintaining intestinal health and homeostasis.

Dolichandrone spathacea is a mangrove associate with high medicinal and ecological values. However, due to the dual-pressure of climate change and human activities, D. spathacea has become endangered in China. Moreover, misidentification between D. spathacea and its terrestrial relative D. cauda-felina poses further challenges to field protection and proper medicinal usage of D. spathacea. Thus, to address these problems, we sequenced and assembled mitochondrial (mt) and chloroplast (cp) genomes for both D. spathacea and D. cauda-felina. Comparative analysis revealed apparently different size and scaffold number between the two mt genomes, but a high similarity between the cp genomes. Eight regions with high sequence divergence were identified between the two cp genomes, which might be used for developing candidate DNA markers for distinguishing the two species. The splitting between D. spathacea and D. cauda-felina was inferred to occur at ~6.8 - 7.7 million years ago (Mya), which may be driven by the environment fluctuations in late Miocene. In the cp genome, 12 genes related to the expression of photosynthesis-associated proteins were detected with signatures of positive selection, which may contribute to the origin and evolutionary adaptation of Dolichandrone mangrove species. These new findings do not only enrich organelle genomic resources of Dolichandrone species, but also provide important genetic clues for improving the conservation and proper usage of endangered mangrove associate D. spathacea.

BackgroundStress urinary incontinence (SUI) is a common condition characterized by urethral sphincter failure and urine leakage. Its prevalence in women is higher than in men, and estimates of crude prevalence rates vary widely due to factors such as research methodologies, study populations, and underreporting by patients. This variability hinders research and impacts patient diagnosis, treatment, and quality of life. The complex etiology of SUI is not fully understood, and previous studies have primarily focused on non-invasive indicators. While emerging observational research suggests a correlation between SUI in women and abnormalities in lipid and blood metabolism, the underlying biological mechanisms and causal relationships require further investigation. This study aims to explore the causalities between SUI in women and lipid and blood metabolism.MethodsUsing bidirectional univariate Mendelian randomization (MR), we investigated the causal association between SUI liability in women (case/control = 5,924/399,509) from UK Biobank and lipid and glucose metabolism, indicated by total cholesterol (TC, N = 61,166), low-density lipoproteins (LDL, N = 58,381), high-density lipoproteins (HDL, N = 60,812), triglycerides (TG, N = 60,027), fasting glucose (FG, N = 19,745), and fasting insulin (FI, N = 38,238) from ENGAGE consortium. To account for potential confounding effects, multivariable MR (MVMR) analyses were performed, adjusting for body mass index (BMI) and separately among lipid and glucose metabolism.ResultsWe found that increased genetically proxied TC, LDL, and HDL levels were associated with an elevated risk of SUI in women (OR: 1.090–1.117, all P < 0.05), These associations were further supported by MVMR analyses with adjustment for BMI (OR: 1.087–1.114, all P < 0.05). Conversely, increased FG and FI were associated with reduced SUI reliability in women (OR: 0.731–0.815, all P < 0.05). When adjusting among lipid and glucose metabolism, only HDL and FI demonstrated causal effects. Reverse MR analyses provided no genetic evidence supporting the causal effect of SUI in women on lipid and blood metabolism (all P > 0.05).ConclusionsOur results reported that increased TC, LDL, and HDL are linked to higher SUI susceptibility in women, while higher FG and FI levels have a protective effect. In overweight/obese women with metabolic abnormalities, the positive associations between TC, LDL, and HDL levels and SUI indicate a higher risk.

BackgroundDue to the rising standard of living and advances in public health and medical care in recent years in China, the health-related quality of life (HRQoL) has been increasingly acknowledged as an important part of health management of adults. This study aimed to analyze the HRQoL of Chinese adults and identify the influencing factors, proposing specific recommendations for improvement.MethodsA cross-sectional study was conducted among 1,291 selected adults from four provinces spanning different regions in China aged ≥18 years from July 2021 and January 2022. The EuroQol-5D-5L (EQ-5D-5L) was used to conduct the HRQoL survey, and a general questionnaire was administered to collect demographic characteristics, general information, and health behaviors of participants. The health utility value was measured, and one-way analysis of variance was performed. The Tobit regression model was employed to analyze the factors influencing the HRQoL of Chinese adults.ResultsThe mean health utility values and visual analog scale scores for adults were 0.9400 ± 0.1197 and 84.09 ± 14.392, respectively. Notably, 60.3% of respondents reported no difficulties in any of the five dimensions of EQ-5D. However, a substantial proportion faced challenges in anxiety/depression (27%) and pain/discomfort (26.2%). Tobit regression model revealed that age, marital status, educational level, diet, sleep, mental state, mood, and chronic diseases significantly impact the HRQoL of Chinese adults.ConclusionThe HRQoL among Chinese adults is generally satisfactory, but pay particular attention on areas such as pain, psychological anxiety, chronic diseases, and negative emotions is needed. The factors such as stress associated with marriage and the demands of high-skilled occupations might influence the overall health of the population. According to our findings, public health strategies to improve HRQoL should be developed to promote relatively healthy environments and lifestyles for older adults. Moreover, proactive measures are crucial for mitigating the potential health impacts associated with marital stress and high-skilled employment.

Fusarium is a soil-borne pathogen that poses a serious threat to the quality and yield of hundreds of crops worldwide, particularly tobacco production. Using metabolomics technology, we investigated natural metabolites from disease-conducting soil (DCS) and disease-suppressing soil (DSS) of tobacco rhizosphere as fungicides to control tobacco Fusarium wilt (TFW), which is mainly caused by Fusarium oxysporum. Furthermore, the antifungal mechanisms of these natural metabolites were preliminarily elucidated through various assessments, including antifungal activity determination, chemotaxis effect tests, PI staining experiments, and measurements of extracellular conductivity and protein content. Metabolomics results showed that the DCS with three different disease grades (G1, G5 and G9 groups) had significantly higher levels of 15, 14 and 233 differential rhizosphere metabolites (DRMs) and significantly lower levels of 72, 152 and 170 DRMs compared to the DSS (G0 group). According to KEGG pathway analysis, these DRMs were found to be enriched in the caffeine metabolism, biosynthesis of phenylpropanoids, galactose metabolism and tyrosine metabolism, etc. Linustatin, scopoletin and phenylpropiolic acid were picked out from these DRMs and found to have suppressive activity against F. oxysporum through correlation analysis and antifungal experiments. The three DRMs showed strong inhibitory effects on the growth and spore germination of F. oxysporum at concentrations of 0.5 mM or higher in each test period. Furthermore, F. oxysporum showed a phobotaxis effect against these three DRMs at concentrations as low as 0.25 mM. Finally, we found that the three DRMs had an inhibitory effect on F. oxysporum by destroying the integrity of the cell membrane and increasing the membrane permeability of F. oxysporum. This study firstly reports the inhibition activity of phenylpropiolic acid and linustatin on F. oxysporum, providing a practical and environmentally friendly method for biocontrol of TFW by using natural fungicides.

The key to managing urban heat island (UHI) is identifying and cooling the core areas of UHI. Studies have shown that spatial differences in urban green space (UGS) indicators have a significant impact on spatial differences in land surface temperature (LST). However, previous studies have mainly explored UGS and LST in the entire region, with few focusing on the urban core area. In this study, we extracted the urban core area based on the Point of Interest (POI) and kernel density methods. Correlation and regression analyses were then used to investigate the correlation between UGS indicators and seasonal LST in the urban core area. Our results confirm the significant cooling effect of UGS at the urban core scale. The effects of UGS landscape composition and configuration on LST varied across seasons and across urban green space ratio (UGSR) gradients. In the warm season, increasing the UGSR proved to be the most effective way to mitigate the urban thermal environment. In urban core areas where expanding UGS is not possible or in cores with high UGSR, designing UGS with complex shapes and clusters can better achieve the cooling effect. These results suggest that the influence of UGS landscape features on the urban surface thermal environment at the urban core area scale is very complex. Therefore, implementing urban greening to mitigate the UHI problem requires considering the premise of multifactorial analysis.

Objective About 2 billion people have caries in permanent teeth, and 514 million children have caries in primary teeth worldwide. Regional disparities in caries prevalence are evident in various areas of China. A comprehensive understanding of the status of dental caries and its associated risk factors is essential for developing effective dental health policies in economically disadvantaged regions. Thus, this study aims to examine the prevalence of dental caries and its risk factors among students aged 12–15 in Xide County, a remote mountainous area in China.Design In this cross-sectional study, dental health surveys were conducted using self-administered questionnaires and the Decayed-Missing-Filled Tooth (DMFT) Index. An oral clinical examination was carried out by the criteria and guidelines set forth by WHO.Setting Xide County, Liangshan prefecture, China in 2022.Participants 558 students aged 12–15 years completed the survey.Results The study conducted in Xide County found a dental caries prevalence of 42.5% among 12–15 year-old students, with a mean DMFT of 1.50 (SD=2.25). Multivariable logistic regression analysis identified several significant risk factors for dental caries (p

The prevalence and severity of overactive bladder increase with age, and mirabegron is an approved treatment for this condition. This meta-analysis systematically evaluated the efficacy and safety of mirabegron compared with placebo for overactive bladder treatment. We searched PubMed and the Cochrane Library (30 October 2023) for relevant articles (source: MEDLINE, EMBASE, ClinicalTrials.gov, ICTRP, CINAHL). We included randomized controlled trials involving adults with overactive bladder syndrome that compared mirabegron with placebo treatment. Data were analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions [Review Manager (computer program) Version 5.4]. Nine parallel-group trials (10 articles) were included. The evaluation included a total of 8,527 adults, including 6,445 women and 2,082 men, of whom 5,726 were White, 2,462 were Asian, and 161 were Black. The mean age of the participants ranged from 53.4 to 60.3 years. This evaluation involved three specifications of mirabegron: 25 mg, 50 mg, and 100 mg. In all trials, patients were enrolled in a 12-week double-blind treatment period, and the dose was once daily. The review of trials found that on average, people taking mirabegron had about 13 ml more volume voided per micturition, five fewer micturitions, and four fewer incontinence episodes every week, with moderate improvements in quality of life. About one in five people taking the drug reported TRAEs. Mirabegron treatment is well tolerated, with the risk of adverse events similar to that of a placebo. For best results, a dose of 50 mg once daily is recommended for long-term use. It is unclear whether any benefits are sustained after treatment discontinuation.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023430737).

Introduction: Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and a high mortality rate. Therefore, it is essential to understand the role and mechanism of key genes in RCC development and progression. This study aimed to analyze the role of zinc fingers and homeoboxes 2 (ZHX2) in RCC and the underlying mechanism. Methods: RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein expression was analyzed by western blotting assay and immunohistochemistry assay. Cell viability was evaluated using CCK-8 assay, and cell proliferation was assessed by EdU assay. The rate of cell apoptosis was quantified by flow cytometry. Transwell assays were conducted to analyze cell migration and invasion. The sphere formation assay was performed to assess the formation of microspheres. Additionally, m6A RNA immunoprecipitation assay and RNA immunoprecipitation assay were utilized to investigate the relationship between ZHX2 and two proteins, methyltransferase like 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1). The stability of ZHX2 mRNA was analyzed through the Actinomycin D assay. Furthermore, a xenograft mouse model assay was conducted to analyze the effect of ZHX2 overexpression and METTL3 silencing on RCC cell tumor properties in vivo. Results: ZHX2 expression was upregulated in both RCC tissues and cells when compared with healthy renal tissues and human renal cortex proximal convoluted tubule epithelial cells. Depletion of ZHX2 inhibited RCC cell proliferation, migration, invasion and spheroid-forming capacity but promoted cell apoptosis. Moreover, it was found that METTL3 mediated m6A methylation of ZHX2 and IGF2BP1 also stabilized ZHX2 through m6A methylation modification. Furthermore, ZHX2 overexpression showed a potential for attenuating the effects induced by METTL3 silencing and counteracted the inhibitory effect of METTL3 depletion on tumor formation in vivo. Conclusion: METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

Abstract Epigenetic mechanisms such as DNA methylation and hydroxymethylation play a significant role in depression. This research has shown that Ten‐eleven translocation 2 (Tet2) deficiency prompts depression‐like behaviors, but Tet2's transcriptional regulation remains unclear. In the study, bioinformatics is used to identify nuclear receptor subfamily 2 group E member 3 (Nr2e3) as a potential Tet2 regulator. Nr2e3 is found to enhance Tet2's transcriptional activity by binding to its promoter region. Nr2e3 knockdown in mouse hippocampus leads to reduced Tet2 expression, depression‐like behaviors, decreased hydroxymethylation of synaptic genes, and downregulation of synaptic proteins like postsynaptic density 95 KDa (PSD95) and N‐methy‐d‐aspartate receptor 1 (NMDAR1). Fewer dendritic spines are also observed. Nr2e3 thus appears to play an antidepressant role under stress. In search of potential treatments, small molecule compounds to increase Nr2e3 expression are screened. Azacyclonal (AZA) is found to enhance the Nr2e3/Tet2 pathway and exhibited antidepressant effects in stressed mice, increasing PSD95 and NMDAR1 expression and dendritic spine density. This study illuminates Tet2's upstream regulatory mechanism, providing a new target for identifying early depression biomarkers and developing treatments.

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.

Objectives Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. Results A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training ( P < 0.0001), testing ( P = 0.016), and total ( P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. Conclusion The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.

Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10 mg/kg or 20 mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1β, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.

The reliable and consistent operations of modular multilevel converters (MMCs) under fault conditions are crucial for high-voltage and high-power applications. To strengthen the performances of MMCs under submodule (SM) faults, a fault- tolerant strategy based on the nearest level modulation (NLM) is proposed in this paper. According to the changed AC component in the faulty arm voltage, this method adds a corrector in NLM, which remedies the faulty arm voltage by adjusting the number of inserted SMs for the faulty arm. Then, the faulty operation can be recovered to the normal. The corrector is simple to realize and can effectively suppress the odd-order circulating currents. Under the proposed method, only the ripples of the capacitor voltages in the faulty arm rise. The average voltage stress on each capacitor is the same as that in normal operation since the rated capacitor voltage in the faulty arm has no rise. No measure and influence impose on healthy arms. With features of simplicity, low voltage stress and little influence scope, the proposed strategy is fit for high-voltage MMCs. The feasibility of the proposed strategy is verified by the simulation results with the professional tool Matlab/Simulink.

Abstract The observation errors in precipitation gauges contribute to diminished precision in precipitation data sets. To reduce the impact of these errors, the World Meteorological Organization Solid Precipitation Intercomparison Experiments recommended the Double Fence Intercomparison Reference as a reference standard for precipitation measurements. This study proposed a new rain, snow, and mixed precipitation adjustment method for national standard precipitation gauges, using DFIR‐measured precipitation as the standard values. This method was used to adjust for systematic errors, including wind‐induced errors, wetting loss, and trace precipitation, in precipitation data collected by 785 stations in China from 1961 to 2020. After bias adjustment, the annual precipitation increased by 6.1–177.9 mm (with an average of 52.7 mm), accounting for 3.3%–52.1% (8.9%) of the total precipitation. The average annual error‐adjustment amounts for wind‐induced error, wetting loss, and trace precipitation were 21.9 (3.6% of total precipitation), 26.6 (4.7%), and 4.2 mm (1.3%), respectively. The adjustment percentage in winter was higher than that in summer, with the high‐adjusted‐percentage regions predominantly located in areas with drought, high proportion of snowfall, and strong wind speeds. Additionally, the annual average error‐adjustment amounts for rain, snow, and mixed precipitation respectively accounted for 5.2%, 38.2%, and 17.1% of their corresponding total amounts, indicating the significance of bias adjustment, particularly for snow and mixed precipitation, in the northern and Qinghai‐Tibet Plateau regions. Therefore, bias adjustment is necessary to enhance the accuracy of the precipitation data set in China.