Search

Abstract The electrocatalytic reduction of nitrate toward ammonia under mild conditions addresses many challenges of the Haber-Bosch reaction, providing a sustainable method for ammonia synthesis, yet it is limited by sluggish reduction kinetics and multiple competing reactions. Here, the titanium hydride electrocatalyst is synthesized by electrochemical hydrogenation reconstruction of titanium fiber paper, which achieves a large ammonia yield rate of 83.64 mg h−1 cm−2 and a high Faradaic efficiency of 99.11% with an ampere-level current density of 1.05 A cm−2 at −0.7 V versus the reversible hydrogen electrode. Electrochemical evaluation and kinetic studies indicate that the lattice hydrogen transfer from titanium hydride promotes the electrocatalytic performance of nitrate reduction reaction and the reversible equilibrium reaction between lattice hydrogen and activate hydrogen not only improves the electrocatalytic activity of nitrate reduction reaction but also demonstrates notable catalytic stability. These finding offers a universal design principle for metal hydrides as catalysts for effectively electrochemical ammonia production, highlighting their potential for sustainable ammonia synthesis.

Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.

Abstract Background In supporting primary healthcare in delivering high-quality care for individuals with type 2 diabetes mellitus (T2DM), previous research emphasized strategies to facilitate communication and collaboration between primary healthcare providers and hospitals. This study aims to evaluate the effectiveness of case discussion conferences between specialists from hospitals and primary healthcare providers in China on the optimization of diabetes management and the improvement of patient health outcomes. Methods This study will be a parallel cluster randomized controlled trial in which primary healthcare institutions in Shouguang city and Shangsi County will be randomly allocated to the intervention and control groups. The intervention will involve regular case discussion conferences where attendants will meet to discuss complex cases with patients diagnosed with type 2 diabetes mellitus, exchange experiences, and seek and provide expert advice. Family doctor teams from primary healthcare institutions and specialists from secondary or tertiary hospitals will engage in these conferences. Data will be collected at baseline and at the 6- and 12-month follow-ups. The primary clinical outcome measures will focus on the changes in the HbA1c and FBG levels of patients under management. The secondary outcomes will include other physiological indicators, such as blood pressure, BMI, and cholesterol. The evaluation will extend to changes in the capabilities and behaviors of primary healthcare providers. Furthermore, the feasibility and adherence of this intervention will be thoroughly assessed. Discussion This study is designed to generate robust evidence on the effectiveness of case discussion conferences, an interprofessional collaboration strategy, in enhancing diabetes care delivery in primary healthcare, with the ultimate goal of improving patient health outcomes. Trial registration Chinese Clinical Trial Registry ChiCTR2300078829. Registered on December 19, 2023. https://www.chictr.org.cn/showproj.html?proj=210293

Abstract Malignant ovarian sex cord-stromal tumors are rare neoplasms that account for approximately 5–7% of all ovarian malignancies, and they are primarily treated with surgery. The prognosis of patients with different surgical extents remains controversial. Therefore, the effects of different surgical extents on the prognosis of patients were explored in this retrospective cohort study. Patients with malignant ovarian sex cord-stromal tumors who underwent surgical treatment from January 2000 to December 2019 were selected. Disease-free survival and overall survival rates were calculated by the Kaplan–Meier method and compared by the log-rank test. Prognosis factors were identified by Cox regression analysis. P

Abstract Background Immunotherapy faces a major challenge in treatment resistance, highlighting the need for efficacy biomarkers identification. The tumor microenvironment (TME) significantly influences treatment outcomes, necessitating molecular TME exploration to address immunotherapy resistance. Methods The study initially pinpointed IL7R as a pivotal TME gene and then examined its impact on TME’s CD8 + T cells at the single-cell level. Bulk-RNA analysis investigated IL7R function, immune cell infiltration related to IL7R in TCGA pan-cancer samples with its expression verified in clinical samples through immunohistochemistry. Genome instability and immune-related molecular expression associated with IL7R were also assessed. Furthermore, the clinical efficacy of IL7R was evaluated in various immunotherapy treatment cohorts. Results Our single-cell analyses and cell-cased experiment revealed that T cells with high IL7R expression tended to be non-terminal and correlated with favorable immunotherapy responses. High IL7R expression corresponded to increased immune and stromal cell signiture, immune pathway enrichment, and an immune-inflamed environment in Bulk-RNA analysis and immunohistochemistry verification. These patients exhibited higher proportions of memory T cells and M1 cells within the TME, along with frequent genome instability and immune molecular upregulation. While IL7R had varied prognostic impact across the TCGA dataset, patients with high IL7R expression showed extended survival under immunotherapy. Conclusion IL7R plays a critical role in shaping TME diversity across cancer types and holds promise as a relevant biomarker for predicting immunotherapy benefits.

Abstract Non-small cell lung cancer (NSCLC) constitutes a significant portion of lung cancers and cytotoxic drugs (e.g. cisplatin) are currently the first-line treatment. However, NSCLC has developed resistance to this drug, which limits the therapeutic effect and thus affects prognosis. NSCLC sc-RNA-seq data were downloaded from the GEO database and Ku Leuven Laboratory for Functional Epigenetics, and bulk RNA-seq data were obtained from the TCGA database. The “Seurat” package was employed for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were applied for downscaling and cluster identification. Use the FindAllMarkers function to find differential genes (DEGs) for tumor stem cells. Then, we performed univariate regression analyses on the DEGs to identify potential prognostic genes. We created a machine learning framework based on potential prognostic genes, which combines 10 machine learning methods and their 101 combinations to get the optimal prognostic risk model. The model was evaluated in the training set and validation set. A nomogram was developed to provide physicians with a quantitative tool for prognosis prediction. Finally, we evaluated the expression and functionality of SLC2A1. We discovered 22 cell clusters containing 218379 cells by examining single-cell RNA sequencing datasets (GSE148071, KU_lom, GSE131907, GSE136246, GSE127465). Tumour cells were isolated for subpopulation analysis and 162 differential genes from SOX2_cancer were obtained. After univariate Cox analysis, we found 23 genes with prognostic potential prognostic value and utilized them to develop 101‑combination machine learning computational framework. We eventually picked the best performing ‘StepCox[both] + RSF’, which includes 8 genes. The model has a relatively high prediction accuracy in both TCGA and GEO datasets. In in vitro investigations, targeted suppression of the SLC2A1 gene resulted in significant reductions in proliferation, invasion and migration in A549 cells. In addition, a significant reduction in cisplatin resistance was seen in A549/DDP cells. The outcomes demonstrated the precision and credibility of the prognostic model for NSCLC, highlighting its potential significance in the treatment and prognosis of individuals affected by this disease. SLC2A1 may become a promising prognostic marker and a potential therapeutic target, offering valuable insights to inform clinical treatment decisions.

Abstract Wearable ultrasound imaging technology has become an emerging modality for the continuous monitoring of deep-tissue physiology, providing crucial health and disease information. Fast volumetric imaging that can provide a full spatiotemporal view of intrinsic 3D targets is desirable for interpreting internal organ dynamics. However, existing 1D ultrasound transducer arrays provide 2D images, making it challenging to overcome the trade-off between the temporal resolution and volumetric coverage. In addition, the high driving voltage limits their implementation in wearable settings. With the use of microelectromechanical system (MEMS) technology, we report an ultrasonic phased-array transducer, i.e., a 2D piezoelectric micromachined ultrasound transducer (pMUT) array, which is driven by a low voltage and is chip-compatible for fast 3D volumetric imaging. By grouping multiple pMUT cells into one single drive channel/element, we propose an innovative cell–element–array design and operation of a pMUT array that can be used to quantitatively characterize the key coupling effects between each pMUT cell, allowing 3D imaging with 5-V actuation. The pMUT array demonstrates fast volumetric imaging covering a range of 40 mm × 40 mm × 70 mm in wire phantom and vascular phantom experiments, achieving a high temporal frame rate of 11 kHz. The proposed solution offers a full volumetric view of deep-tissue disorders in a fast manner, paving the way for long-term wearable imaging technology for various organs in deep tissues.

Abstract This study explores aerosol direct, indirect, and feedback effects on meteorology and fine particulate matter during heat waves of August 2022 over eastern China by using an online coupled regional climate–chemistry–aerosol model. In this period, aerosols exerted mean direct (DRE) and indirect (IRE) radiative effects of −3.9 Wm−2 and −2.4 Wm−2 at TOA, which totally caused a decrease in average surface air temperature by 0.3 °C over east China, accompanied by decreases in PBLH (planetary boundary layer height) and precipitation and an increase in PM2.5 concentration. With the anthropogenic emission reduction from 2013 to 2022, DRE apparently decreased while IRE changed little, leading to a decrease in total aerosol radiative effect (TRE) by 27% at TOA. The weakened TRE resulted in increases in surface air temperature and precipitation by 0.14 °C and 2.7 mm, respectively, on average over east China, with the maximum warming exceeding 0.5 °C in BTH (Beijing–Tianjin–Hebei province). This study highlights a warming trend due to weakened TRE, which may exacerbate heat wave, and an increasing importance of aerosol IRE relative to DRE due to weak sensitivity of cloud properties to aerosol change during the emission reduction.

Abstract Due to high energy density, clean combustion products and abundant resources, natural gas hydrates (NGHs) have been regarded as an important clean energy source with the potential for large-scale development and utilization. However, pilot tests in NGHs show that their production rates are far below commercial needs. Multilateral well technology may lead to a solution to this problem because it can dramatically expand the drainage area of production wells. This paper presents the practical rate transient analysis for multilateral horizontal wells in NGHs. In developing solution to the diffusivity equation of multilateral horizontal wells in NGHs, the superposition principle and reciprocity are applied. We wrote the governing equation in cylindrical coordinates to describe the NGH flow process. We used the moving boundaries and dissociation coefficients to model the solid-to-gas transition process in hydrates. To obtain solutions for flow in hydrate reservoirs, we used Laplace transforms and the Stehfest numerical inversion method. Superposition principle and Gaussian elimination are applied to obtain the desired solution for multilateral horizontal wells. We validated our proposed model with a commercial numerical simulator. By performing sensitivity analyses, effects on production behavior of the number of branches, dissociation coefficient, radius of the region with dissociated hydrate, and dispersion ratio are determined. A synthetic case study is conducted to show the typical production behaviors.

BackgroundThere are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. ObjectiveTo establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. MethodsCells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L−1 of the diluted NaClO (100 mmol·L−1) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L−1 NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca2+ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. ResultsCompared with 0 μmol·L−1, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L−1 NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L−1 NaClO, showing about 70% of normal cell viability (P

Abstract Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at −402 mA cm−2 and a high activity up to −1 A cm−2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at −100 mA cm−2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

Abstract This work introduces and discusses the impacts of the water bridge on gas adsorption and diffusion behaviors in a shale gas-bearing formation. The density distribution of the water bridge has been analyzed in micropores and meso-slit by molecular dynamics. Na+ and Cl− have been introduced into the system to mimic a practical encroachment environment and compared with pure water to probe the deviation in water bridge distribution. Additionally, practical subsurface scenarios, including pressure and temperature, are examined to reveal the effects on gas adsorption and diffusion properties, determining the shale gas transportation in realistic shale formation. The outcomes suggest carbon dioxide (CO2) usually has higher adsorption than methane (CH4) with a water bridge. Increasing temperature hinders gas adsorption, density distribution decreases in all directions. Increasing pressure facilitates gas adsorption, particularly as a bulk phase in the meso-slit, whereas it restricts gas diffusion by enhancing the interaction strength between gas and shale. Furthermore, ions make the water bridge distributes more unity and shifts to the slit center, impeding gas adsorption onto shale while encouraging gas diffusion. This study provides updated guidelines for gas adsorption and transportation characteristics and supports the fundamental understanding of industrial shale gas exploration and transportation.

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

Abstract Matching abbreviated names with their full names (full-abbr matching) plays a key role in data integration, address matching, information retrieval, and other fields. Traditional full-abbr matching technology often encounters issues related to near homophones and near homoglyphs. First, a near-homophone full-abbr matching model based on Simbert and VGG was first proposed, which integrates character and speech features, leveraging a speech recognition model and combining a brain-like cognitive learning dual-process mechanism which involves linguistic knowledge and neural network together. Second, to address the problem of near-homoglyph full-abbr matching in Chinese, a DenseNet-based model that fuses glyph structure and image features was proposed, in which statistical feature extractors are employed to extract feature vectors for glyphic features including stroke, Wubi and structural features separately. Lastly, the near-homophone model and the near-homoglyph model are coupled to work together in the full-abbr matching task, in which expert knowledge is used as a component of the feature optimizer. Experimental results showed that the integrated model significantly increased the matching accuracy to 87.5%, demonstrating a 12.3% improvement.

With the development of building seismic isolation technology and the official release of the Isolation Code in September 2021, seismic isolation design in China will now rely on two foundational codes: the Seismic Code and the Isolation Code. This paper take a ceramic jar storage of the RC frame structure as the research object, and carry out the seismic isolation design based on the separated calculation design method of the Seismic Code and the unitary calculation design method of the Isolation Code respectively, and clarify the control index of the Isolation Code is the story drift angle. The maximum displacement is reduced by 37.5%. In terms of material consumption, the Isolation Code leads to a 5.94% decrease in concrete usage, accompanied by a 13.97% increase in steel consumption, resulting in an overall cost increase of 4.98%. The findings indicate that seismic isolation design, guided by the Isolation Code, substantially mitigates the seismic response of the superstructure. The damage extent to structural members is reduced by 15–20%, promoting enhanced safety and repairability. The outcomes of this study offer valuable insights for future seismic isolation designs in RC frame structures.

Abstract Background Hydrogen gas (H2), a novel and beneficial gaseous molecule, plays a significant role in plant growth and development processes. Hydrogen-rich water (HRW) is regarded as a safe and easily available way to study the physiological effects of H2 on plants. Several recent research has shown that HRW attenuates stress-induced seed germination inhibition; however, the underlying modes of HRW on seed germination remain obscure under non-stress condition. Results In this current study, we investigated the possible roles of gibberellin (GA) and abscisic acid (ABA) in HRW-regulated seed germination in wax gourd (Benincasa hispida) through pharmacological, physiological, and transcriptome approaches. The results showed that HRW application at an optimal dose (50% HRW) significantly promoted seed germination and shortened the average germination time (AGT). Subsequent results suggested that 50% HRW treatment stimulated GA production by regulating GA biosynthesis genes (BhiGA3ox, BhiGA2ox, and BhiKAO), whereas it had no effect on the content of ABA and the expression of its biosynthesis (BhiNCED6) and catabolism genes (BhiCYP707A2) but decreased the expression of ABA receptor gene (BhiPYL). In addition, inhibition of GA production by paclobutrazol (PAC) could block the HRW-mediated germination. Treatment with ABA could hinder HRW-mediated seed germination and the ABA biosynthesis inhibitor sodium tungstate (ST) could recover the function of HRW. Furthermore, RNA-seq analysis revealed that, in the presence of GA or ABA, an abundance of genes involved in GA, ABA, and ethylene signal sensing and transduction might involve in HRW-regulated germination. Conclusions This study portrays insights into the mechanism of HRW-mediated seed germination, suggesting that HRW can regulate the balance between GA and ABA to mediate seed germination through ethylene signals in wax gourd.

Abstract Sclerotinia stem rot (SSR), caused by the necrotrophic fungus Sclerotinia sclerotiorum, is one of the most devastating diseases for several major oil-producing crops. Despite its impact, the genetic basis of SSR resistance in plants remains poorly understood. Here, through a genome-wide association study, we identify a key gene, BnaA07. MKK9, that encodes a mitogen-activated protein kinase kinase that confers SSR resistance in oilseed rape. Our functional analyses reveal that BnaA07.MKK9 interacts with BnaC03.MPK3 and BnaC03.MPK6 and phosphorylates them at the TEY activation motif, triggering a signaling cascade that initiates biosynthesis of ethylene, camalexin, and indole glucosinolates, and promotes accumulation of H2O2 and the hypersensitive response, ultimately conferring resistance. Furthermore, variations in the coding sequence of BnaA07.MKK9 alter its kinase activity and improve SSR resistance by ~30% in cultivars carrying the advantageous haplotype. These findings enhance our understanding of SSR resistance and may help engineer novel diversity for future breeding of oilseed rape.

To evaluate the degree of unsaturation of different varieties of Camellia oil, it was necessary to establish a rapid evaluation method with a narrow iodine value range (iodine value difference less than 10). In this study, a rapid quantitative prediction model for iodine value of oil in high-resolution Raman spectroscopy based on linear regression and gradient descent method was established. The Raman signals (785 nm) about 39 group of Camellia oil samples and 10 group of commercially oils were firstly collected. Then, the intensity ratio of peaks of 1656 cm−1 and 1440 cm−1 (I1656/1440) were selected through smoothing algorithm least squares smoothing filter (Savitzky-Golay), polynomial fitting and deconvolution algorithm Lorentzian. A credible model was obtained through correlation analysis with the iodine value of corresponding oil samples. The coefficient of determination (R2) of the test set of the constructed quantitative model was >0.82, the mean square error (MSE) was

Macrophages are the basic mediators and coordinators of various types of chronic inflammation and play a crucial role in the formation and development of atherosclerosis (AS). In the complex microenvironment of atherosclerotic plaques, macrophages of different sources are exposed to different signal stimuli and thus polarized into various subpopulations. Various types of macrophages with predominantly M1 and M2 phenotypes also play different regulatory roles in the initiation and progression of AS. Lipid-lowering drugs, mainly statins, are widely used in clinical practice, but the adverse reactions are obvious and there is a lack of personalized treatment. Emerging targeted macrophage and Traditional Chinese medicine (TCM)-related therapies can regulate the cellular microenvironment, inhibit the polarization of M1 macrophages, and promote the activation of M2 macrophages, providing new ideas for the prevention and treatment of AS.

BackgroundStress urinary incontinence (SUI), the most common form of urinary incontinence, is a condition that affects many women. It is characterized by involuntary urine leakage during activities that increase abdominal pressure, such as sneezing, coughing, or physical exertion, according to the International Continence Society. SUI affects patients’ quality of life and causes depression and emotional disorders, which negatively influences physical and mental health. The participants in the studies in this review comprised women with mild to moderate SUI, because there are more female patients than male patients, and most patients with severe SUI are treated surgically. Moreover, after retrieval, there were no systematic reviews or network meta-analyses (NMAs) of conservative treatments, such as electroacupuncture (EA), in women with mild to moderate SUI. ObjectiveThis study aims to investigate the efficacy of electroacupuncture among women with mild to moderate SUI using an NMA. MethodsRandomized clinical trials related to conservative treatments for SUI will be searched in 5 English and 3 Chinese literature databases: EMBASE, PubMed, Cochrane, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), WanFang, and the Chinese BioMedical Literature Database. The search period for these 8 electronic databases will be from 2002 to 2022. The PROSPERO database and the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) database will also be searched. Two reviewers will independently complete the research selection. After screening the studies, 2 other researchers will extract the data, and the quality of the included studies will be evaluated according to the quality standards specified in the Cochrane Collaboration Tool (version 2). The primary outcomes will be the change in urine leakage determined by a 1-hour pad test and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) scores at baseline and at the conclusion of the follow-up. The secondary outcomes will be 72-hour incontinence episodes, residual bladder volume, effective rate, urodynamic indexes, and other reported measurements. Stata (version 14.0; StataCorp) and Review Manager (RevMan version 5.3; Cochrane) will be implemented for data synthesis and meta-analysis. ResultsThe results are not yet accessible because this is a protocol for a systematic review and meta-analysis. The protocol was registered on INPLASY on February 22, 2023. By April 6, 2023, we had completed the literature search of the 8 databases and completed the selection and data extraction of the articles. ConclusionsThe results of this systematic review will demonstrate the efficacy of EA among women with mild to moderate SUI. The results will provide evidence for clinicians and guideline makers to choose suitable treatments for SUI. Trial RegistrationInternational Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) 202320098; https://inplasy.com/inplasy-2023-2-0098/ International Registered Report Identifier (IRRID)DERR1-10.2196/55870

Abstract Triboelectric nanogenerators (TENGs) have recently emerged as a promising technology for efficient water wave energy harvesting. However, there is a paucity of clear guidance regarding the optimal designs of TENGs and their shells to achieve efficient absorption and conversion of water wave energy in real random waves. Herein, from the perspective of wave‐body interaction and energy transfer, this paper proposes a structural quality factor (Qunit) for the quantitative evaluation of both the motion of floating triboelectric nanogenerator (Flo‐TENG) shells and their capability to absorb and convert water wave energy efficiently. The factor is further subdivided into the amplitude structural quality factor (Qacc), which characterizes shell motion amplitude, and the frequency structural quality factor (Qf), which describes shell motion frequency. This paper systematically investigates the impact of various shell parameters such as bow shapes, curvatures, inclinations, and immersion ratios on Qacc and Qf. The findings indicate that variations in shell shape result in distinct Qunit values along different axial directions of wave propagation. These variations directly influence energy absorption efficiency in these directions. These results provide fundamental guidance for the design of high‐performance Flo‐TENG shells and the selection of internal energy harvesting directions to enable more efficient energy conversion.

IntroductionAtherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS.MethodsApoE−/− mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content.ResultsThe results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality.ConclusionThese findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

Summary: Background: Cholelithiasis-induced acute cholangitis (CIAC) is an acute inflammatory disease with poor prognosis. This study aimed to create machine-learning (ML) models to predict the outcomes of patients with CIAC. Methods: In this retrospective cohort and ML study, patients who met the both diagnosis of ‘cholangitis’ and ‘calculus of gallbladder or bile duct’ according to the International Classification of Disease (ICD) 9th revision, or met the diagnosis of ‘calculus of bile duct with acute cholangitis with or without obstruction’ according to the ICD 10th revision during a single hospitalization were included from the Medical Information Mart for Intensive Care database, which records patient admissions to Beth Israel Deaconess Medical Center, MA, USA, spanning June 1, 2001 to November 16, 2022. Patients who were neither admitted in an emergency department nor underwent biliary drainage within 24 h after admission, had an age of less than 18, or lost over 20% of the information were excluded. Nine ML methods, including the Logistic Regression, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine, Adaptive Boosting, Decision Tree, Gradient Boosting Decision Tree, Gaussian Naive Bayes, Multi–Layer Perceptron, and Support Vector Machine were applied for prediction of in-hospital mortality, re-admission within 30 days after discharge, and mortality within 180 days after discharge. Patients from Zhongda Hospital affiliated to Southeast University in China between January 1, 2019 and July 30, 2023 were enrolled as an external validation set. The area under the receiver operating characteristic curve (AUROC) was the main index for model performance assessment. Findings: A total of 1156 patients were included to construct models. We performed stratified analyses on all patients, patients admitted to the intensive care unit (ICU) and those who underwent biliary drainage during ICU treatment. 13–16 features were selected from 186 variables for model training. The XGBoost method demonstrated the most optimal predictive efficacy, as evidenced by training set AUROC of 0.996 (95% CI NaN–NaN) for in-hospital mortality, 0.886 (0.862–0.910) for re-admission within 30 days after discharge, and 0.988 (0.982–0.995) for mortality within 180 days after discharge in all patients, 0.998 (NaN–NaN), 0.933 (0.909–0.957), and 0.988 (0.983–0.993) in patients admitted to the ICU, 0.987 (0.970–0.999), 0.908 (0.873–0.942), and 0.982 (0.971–0.993) in patients underwent biliary drainage during ICU treatment, respectively. Meanwhile, in the internal validation set, the AUROC reached 0.967 (0.933–0.998) for in-hospital mortality, 0.589 (0.502–0.677) for re-admission within 30 days after discharge, and 0.857 (0.782–0.933) for mortality within 180 days after discharge in all patients, 0.963 (NaN–NaN), 0.668 (0.486–0.851), and 0.864 (0.757–0.970) in patients admitted to the ICU, 0.961 (0.922–0.997), 0.669 (0.540–0.799), and 0.828 (0.730–0.925) in patients underwent biliary drainage during ICU treatment, respectively. The AUROC values of external validation set consisting of 61 patients were 0.741 (0.725–0.763), 0.812 (0.798–0.824), and 0.848 (0.841–0.859), respectively. Interpretation: The XGBoost models could be promising tools to predict outcomes in patients with CIAC, and had good clinical applicability. Multi-center validation with a larger sample size is warranted. Funding: The Technological Development Program of Nanjing Healthy Commission, and Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds.

Abstract This study employs similar simulation testing and discrete element simulation coupling to analyze the failure and deformation processes of a model coal seam's roof. The caving area of the overburden rock is divided into three zones: the delamination fracture zone, broken fracture zone, and compaction zone. The caving and fracture zones' heights are approximately 110 m above the coal seam, with a maximum subsidence of 11 m. The delamination fracture zone's porosity range is between 0.2 and 0.3, while the remainder of the roof predominantly exhibits a porosity of less than 0.1. In addition, the numerical model's stress analysis revealed that the overburden rock's displacement zone forms an 'arch-beam' structure starting from 160 m, with the maximum and minimum stress values decreasing as the distance of advancement increases. In the stress beam interval of the overburden rock, the maximum value changes periodically as the advancement distance increases. Based on a comparative analysis between observable data from on-site work and numerical simulation results, the stress data from the numerical simulation are essentially consistent with the actual results detected on-site, indicating the validity of the numerical simulation results.

Abstract Pentamidine and melarsoprol are primary drugs used to treat the lethal human sleeping sickness caused by the parasite Trypanosoma brucei. Cross-resistance to these two drugs has recently been linked to aquaglyceroporin 2 of the trypanosome (TbAQP2). TbAQP2 is the first member of the aquaporin family described as capable of drug transport; however, the underlying mechanism remains unclear. Here, we present cryo-electron microscopy structures of TbAQP2 bound to pentamidine or melarsoprol. Our structural studies, together with the molecular dynamic simulations, reveal the mechanisms shaping substrate specificity and drug permeation. Multiple amino acids in TbAQP2, near the extracellular entrance and inside the pore, create an expanded conducting tunnel, sterically and energetically allowing the permeation of pentamidine and melarsoprol. Our study elucidates the mechanism of drug transport by TbAQP2, providing valuable insights to inform the design of drugs against trypanosomiasis.

Much attention has been paid to the coating of energetic materials to improve their properties. However, the present coating technology has drawbacks, and it fails to meet the requirements of engineering applications. In this study, observation of the toad spawning process gave an idea for efficient preparation of millimeter-sized coated granules by directly using unrefined HMX. In this technique, the preparation device was cheaper and requirements were simpler. The mechanism of formation mechanism and curing of the coated granules were studied. The preparation process and its formula were continuously optimized during the exploration process. The morphologies and properties of the granules coated with different binders were studied by various techniques and the industrial productivity was evaluated. The coated granules showed regular and full morphology after optimization of the formula and were not easily deformed. Compared with unrefined HMX, the flowability was significantly improved, the mechanical sensitivity was reduced, the response time for ignition was shorter, and the flame intensity was higher. This method solved the problems of sedimentation of particulates and curing of large-sized droplets, while its high production efficiency and little wastage provided a new reference for producing large-sized high-energy coated granules for use in engineering applications.

The challenge of precisely regulating temperature during the photo-thermal bone promotion remains unresolved. Phase change material (PCM), capable of undergoing a phase transition at a specific temperature, offers a solution by photothermal temperature regulation through the storage and release of heat. This study incorporated biocompatible polyethylene glycol (PEG) with specific phase transition points as PCM. A phase change hydrogel scaffold was then synthesized through semi-crosslinking PEG with calcium-ion-chelated sodium alginate (SA) acting as the structural framework. Additionally, the newly developed graphene oxide (GO) modified composite scaffolds (GO-PHSC), featuring 0.5 wt% GO, not only demonstrated outstanding photothermal conversion efficiency and an optimal phase change temperature (42.2 °C) but also exhibited desirable values for latent enthalpy (100 J/g) and latent heat recovered (LHR) (93.3%). Moreover, the form-stability test demonstrated the PCM scaffolds' exceptional resistance to leakage and maintenance of shape stability even at elevated temperatures (70 °C). Beyond achieving passive temperature control in photothermal therapy, experimental findings highlighted that the phase change hydrogel, incorporating calcium ions and GO, met various requirements such as physicochemical properties, microstructure, mechanics, mineralization, biocompatibility, and cell affinity. These collective attributes suggest that GO-PHSC emerges as a promising scaffold composite candidate for temperature-controlled photothermal therapy in bone regeneration.

In order to address the issue of high development of hard overlying rock water-conducting fracture zones in deep coal mining and achieve water-preserved coal mining by reducing the height of water-conducting fracture zones, a new method is proposed in this study, which combines the techniques of pre-fracturing and weakening of hard main controlling overlying strata. This study comprehensively investigates the modification effect of pre-fracturing and weakening of hard main controlling overlying strata through laboratory experiments, theoretical analysis, and numerical simulation. The control mechanisms of different weakening layers on water-conducting fracture zones are elaborated and validated through field measurements. The results demonstrate that pre-existing fractures can induce the rock mass to shift its failure mode from intact rock fracturing to tension-shear failure controlled by pre-existing fractures, leading to a reduction in the severity of rock mass failure. The weakening effect of pre-existing fractures on the hard rock mass is revealed, and the damage variables coupled with stress and fractures are calculated. The relationship between the degree of weakening and the transformation of rock properties is qualitatively analyzed. It is found that the energy storage capacity of the rock mass is reduced while the dissipation capacity is enhanced after the modification. Numerical simulations are conducted to evaluate the control effect of different weakening layers on water-conducting fracture zones. By comparing the dynamic evolution of overlying rock failure modes, fracture counts, and failure heights, it is observed that the “saddle-shaped” failure mode gradually weakens with the increase of weakening layer height, and the evolution trend of fracture counts follows a pattern of “slow increase-sudden increase”. The dynamic evolution of failure height for unweakened and moderately to highly weakened overlying strata approximately exhibits an “S” shape, while the moderately weakened overlying strata exhibit a “semi-ejection” shape. Based on the analysis of the characteristics of failure in hard rock layers at different positions, the mechanisms of controlling the development of water-conducting fracture zones by different pre-fracturing weakening layers are revealed. Furthermore, using the borehole measurement method, the development height of the “two zones” under the condition of top plate fracturing in Mengcun mine is obtained. It is observed that the fracture extraction ratio is reduced under the condition of pre-fracturing weakening, thus preliminarily validating the inhibitory effect of top plate pre-fracturing weakening on the development of water-conducting fracture zones.It provides theoretical and scientific basis for coupling disaster prevention and control, water resources and ecological protection。

Glucose is a major energy substrate for porcine adipocytes and also serves as a regulatory signal for adipogenesis and lipid metabolism. In this study, we combined transcriptome and metabolome analyses to reveal the underlying regulatory mechanisms of high glucose (HG) on adipogenesis by comparing differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) identified in porcine adipocytes. Results showed that HG (20 mmol/L) significantly increased fat accumulation in porcine adipocytes compared to low glucose (LG, 5 mmol/L). A total of 843 DEGs and 365 DAMs were identified. Functional enrichment analyses of DEGs found that multiple pathways were related to adipogenesis, lipid metabolism, and immune-inflammatory responses. PPARγ, C/EBPα, ChREBP, and FOS were identified as the key hub genes through module 3 analysis, and PPARγ acted as a central regulator by linking genes involved in lipid metabolism and immune-inflammatory responses. Gene-metabolite networks found that PPARγ-13-HODE was the most important interaction relationship. These results revealed that PPARγ could mediate the cross-talk between adipogenesis and the immune-inflammatory response during adipocyte maturation. This work provides a comprehensive view of the regulatory mechanisms of glucose on adipogenesis in porcine adipocytes.

The majority of crack sensors do not offer simultaneously both a significant stretchability and an ultrahigh sensitivity. In this study, we present a straightforward and cost-effective approach to fabricate metal crack sensors that exhibit exceptional performance in terms of ultrahigh sensitivity and ultrahigh stretchability. This is achieved by incorporating a helical structure into the substrate through a modeling process and, subsequently, depositing a thin film of gold onto the polydimethylsiloxane substrate via sputter deposition. The metal thin film is then pre-stretched to generate microcracks. The sensor demonstrates a remarkable stretchability of 300%, an exceptional sensitivity with a maximum gauge factor reaching 107, a rapid response time of 158 ms, minimal hysteresis, and outstanding durability. These impressive attributes are attributed to the deliberate design of geometric structures and careful selection of connection types for the sensing materials, thereby presenting a novel approach to fabricating stretchable and highly sensitive crack-strain sensors. This work offers a universal platform for constructing strain sensors with both high sensitivity and stretchability, showing a far-reaching significance and influence for developing next-generation practically applicable soft electronics.

IntroductionThe prevalence of vitamin D deficiency and vitamin D levels in patients with epilepsy (PWE) were systematically evaluated, and the differences between subgroups were analyzed.MethodWe identified all articles investigating the prevalence of vitamin D deficiency in patients with epilepsy from the database established in March 2024 from PubMed, Web of Science, and Embase. We divided them into anti-seizure medication (ASM) interventions and non-ASM interventions according to whether or not someone used ASM.ResultsA total of 68 articles were included. The prevalence of newly diagnosed epilepsy was 50.2% (95% CI: 38.7–61.7%), and the prevalence after ASM intervention was 47.9% (95% CI: 40–55.9%), including 7,070 patients with epilepsy. Subgroup and meta-regression analyses were performed according to the diagnostic criteria, economic development level, region, age, ASM treatment, and other factors. The results showed that the differences were not significant. In addition, the vitamin D content of epilepsy patients (18.719 ng/mL) was lower than that of healthy people (20.295 ng/mL).ConclusionThe prevalence of vitamin D deficiency in patients with epilepsy is very high. Still, the related factors have little effect on the high prevalence of vitamin D in epilepsy, and ASM intervention can reduce the vitamin D content in patients with epilepsy. Therefore, it is emphasized that monitoring vitamin D levels is part of the routine management of patients with epilepsy.Systematic review registrationThe protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). (registration number CRD42023493896). https://www.crd.york.ac.uk/PROSPERO/ # myprospero.

ABSTRACT The Changle goose (CLG), a Chinese indigenous breed, is celebrated for its adaptability, rapid growth, and premium meat quality. Despite its agricultural value, the exploration of its genomic attributes has been scant. Our study entailed whole‐genome resequencing of 303 geese across CLG and five other Chinese breeds, revealing distinct genetic diversity metrics. We discovered significant migration events from Xingguo gray goose to CLG and minor gene flow between them. We identified genomic regions through selective sweep analysis, correlating with CLG's unique traits. An elevated inbreeding coefficient in CLG, alongside reduced heterozygosity and rare single nucleotide polymorphisms (RSNPs), suggests a narrowed genetic diversity. Genomic regions related to reproduction, meat quality, and growth were identified, with the GATA3 gene showing strong selection signals for meat quality. A non‐synonymous mutation in the Sloc2a1 gene, which is associated with reproductive traits in the CLG, exhibited significant differences in allelic frequency. The roles of CD82, CDH8, and PRKAB1 in growth and development, alongside FABP4, FAF1, ESR1, and AKAP12 in reproduction, were highlighted. Additionally, Cdkal1 and Mfsd14a may influence meat quality. This comprehensive genetic analysis underpins the unique genetic makeup of CLG, providing a basis for its conservation and informed breeding strategies.

Abstract The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi‐timepoint drug administration strategies across a wide range of drugs. Here, droplet‐engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici‐plate as an in vitro high‐throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time‐dependent variations are demonstrated in toxicity on the Chronotoxici‐plate, highlighting the importance of considering time‐dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing.

Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.

ObjectiveThe objective of this study was to develop a deep learning-and-radiomics-based ultrasound nomogram for the evaluation of axillary lymph node (ALN) metastasis risk in breast cancer patients ≥ 75 years.MethodsThe study enrolled breast cancer patients ≥ 75 years who underwent either sentinel lymph node biopsy or ALN dissection at Fudan University Shanghai Cancer Center. DenseNet-201 was employed as the base model, and it was trained using the Adam optimizer and cross-entropy loss function to extract deep learning (DL) features from ultrasound images. Additionally, radiomics features were extracted from ultrasound images utilizing the Pyradiomics tool, and a Rad-Score (RS) was calculated employing the Lasso regression algorithm. A stepwise multivariable logistic regression analysis was conducted in the training set to establish a prediction model for lymph node metastasis, which was subsequently validated in the validation set. Evaluation metrics included area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. The calibration of the model’s performance and its clinical prediction accuracy were assessed using calibration curves and decision curves respectively. Furthermore, integrated discrimination improvement and net reclassification improvement were utilized to quantify enhancements in RS.ResultsHistological grade, axillary ultrasound, and RS were identified as independent risk factors for predicting lymph node metastasis. The integration of the RS into the clinical prediction model significantly improved its predictive performance, with an AUC of 0.937 in the training set, surpassing both the clinical model and the RS model alone. In the validation set, the integrated model also outperformed other models with AUCs of 0.906, 0.744, and 0.890 for the integrated model, clinical model, and RS model respectively. Experimental results demonstrated that this study’s integrated prediction model could enhance both accuracy and generalizability.ConclusionThe DL and radiomics-based model exhibited remarkable accuracy and reliability in predicting ALN status among breast cancer patients ≥ 75 years, thereby contributing to the enhancement of personalized treatment strategies’ efficacy and improvement of patients’ quality of life.

Breast cancer (BrCa) is the most prevalent malignant tumor in women and one of the leading causes of female mortality. Its occurrence and progression are influenced by various factors, including genetics, environment, lifestyle, and hormones. In recent years, the gut microbiota has been identified as a significant factor affecting BrCa. The gut microbiota refers to the collective population of various microorganisms in the human gastrointestinal tract. Gut microbiota is closely associated with human health and disease development, participating in crucial physiological functions such as digestion, metabolism, immune response, and neural regulation. It has been found to influence the occurrence and treatment of BrCa through a variety of mechanisms. This article aims to review the immunomodulatory role of the gut microbiota in the development and treatment of BrCa.

IntroductionA variety of studies have shown a link between the gut microbiota and autoimmune diseases, but the causal relationship with Henoch-Schönlein purpura (HSP) and immune thrombocytopenic purpura (ITP) is unknown.MethodsThis study investigated the bidirectional causality between gut microbiota and HSP and ITP using Mendelian randomization (MR). Large-scale genetic data of gut microbiota at phylum to species level from the MiBioGen consortium and the Dutch Microbiome Project were utilized. Genome-wide association studies (GWAS) summary statistics for HSP and ITP came from FinnGen R10. Various MR methods were applied to infer causal relationships, including inverse variance weighted (IVW), maximum likelihood (ML), cML-MA, MR-Egger, weighted median, weighted model, and MR-PRESSO. Multiple sensitivity analyses and Bonferroni correction were conducted to enhance robustness and reliability.ResultsBased on the IVW estimates, 23 bacterial taxa were identified to have suggestive associations with HSP and ITP. Remarkably, after Bonferroni correction, family Alcaligenaceae (OR = 2.86, 95% CI = 1.52–5.37; IVW, p = 1.10 × 10−3, ML, p = 1.40 × 10−3) was significantly associated with ITP as a risk factor, while family Bacteroidales S24 7group (OR = 0.46, 95% CI = 0.29–0.74; IVW, p = 1.40 × 10−3) was significantly associated with ITP as a protective factor. No significant associations between HSP and ITP and gut microbiota were found in reverse analyses.ConclusionOur study provides evidence of causal effects of gut microbiota on HSP and ITP, highlighting the importance of further research to clarify the underlying mechanisms and develop targeted therapeutic interventions for these autoimmune diseases.

Microplastics (MPs), recognized as an emerging global environmental concern, have been extensively detected worldwide, with specific attention directed towards the Yangtze River Estuary (YRE) and East China Sea (ECS) regions. Despite their critical research significance, there remains a knowledge gap concerning the distribution of MPs in the benthic layer within this area, particularly regarding interactions governing their occurrence. Here we illuminate the distribution of MPs within the benthic layer and unravel the intricate interplay between bottom water and sediment in the YRE and ECS. We find that MPs are notably more abundant in bottom water, ranging from 8 to 175 times higher than in surface water. These MPs predominantly consist of polyester fibers, exhibit a size range between 0.5 and 5.0 mm, and display distinct coloration. Co-occurrence network analysis and Principal Coordinate Analysis confirm a robust correlation between MPs in bottom water and sediment, signifying the pivotal role of bottom water in mediating the distribution and transportation of MPs within the benthic layer. Furthermore, a positive correlation between MPs in sediment and bottom water turbidity underscores the impact of surface sediment resuspension and upwelling on MPs distribution. This study clarifies the intricate interactions within the benthic layer and highlights the crucial role of bottom water as a mediator in the vertical distribution of MPs, advancing our understanding of the “source-to-sink” transport processes governing MPs within water-sediment systems.

Reinforced concrete (RC) bent structures are widely used in single-story industrial buildings, with a considerable portion of them located in high-intensity seismic areas. Therefore, it is significant to study the seismic performance of the RC bent column while keeping construction costs in mind. To evaluate the seismic performance of the RC bent column from an economic perspective, pseudo-static tests combined with construction cost analysis were first carried out on three RC bent columns designed according to different versions of Chinese codes. A numerical simulation method based on the extended finite element method (XFEM) for the RC bent column was then established and verified. Subsequently, the relationship between the local damage index related to the apparent damage characteristics and the overall damage index was established by conducting numerical analysis on RC bent columns with different design parameters. Based on the established relationship between the local and overall damage indexes, a calculation method for the residual bearing capacity based on apparent damage was developed. The results show that, when compared to the constructional requirements in the Chinese code for seismic design of industrial and civil buildings published in 1978 (TJ11–78), the constructional requirements in the Chinese code for seismic design of buildings published in 1989 (GBJ11–89) can effectively reduce the stress concentration at the column bottom and delay the formation of the plastic hinge with minimal cost increase, while the constructional requirements in the Chinese code for seismic design of buildings published in 2016 (GB50011–2010) can further effectively reduce the damage to the upper column. Besides, the constructional requirements in GBJ11–89 and GB50011–2010 can improve the energy dissipation and maximum bearing capacity of the RC bent column while decrease the cost/ductility coefficient by more than 5.0 %. The proposed calculation method can effectively predict the residual bearing capacity of earthquake-damaged RC bent columns by comparing the calculation results to the test results.

BackgroundLianhua Qingwen (LHQW) granule, a botanical drug preparation, is frequently utilized as an adjuvant treatment for mycoplasma pneumoniae pneumonia (MPP). Nevertheless, the clinical efficacy and safety of this treatment remain uncertain.PurposeThis study aims to evaluate the efficacy and safety of LHQW granule combined with azithromycin (AZM) in treating MPP in children.MethodTo identify all randomized controlled trials (RCTs) of LHQW granule plus AZM, a search was conducted in eight Chinese and English databases (CNKI, Wan Fang, VIP, Sinomed, PubMed, Embase, Web of Science, and Cochrane Library) from their inception until 25 December 2023. Meta-regression and subgroup analysis were employed to investigate heterogeneity. Sensitivity analysis and trial sequential analysis (TSA) were conducted to assess the robustness of the findings. Additionally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was utilized to evaluate the quality of evidence.ResultsA total of 15 RCTs involving 1909 participants were included in this study. The meta-analysis results indicated combination therapy of LHQW granule and AZM is significant different from AZM alone in both efficacy and safety, which are specifically observed in the following outcomes: response rate (RR = 1.17, 95% CI: 1.12 to 1.22, p < 0.01), antipyretic time (MD = −1.32, 95% CI: −1.66 to −0.98, p < 0.01), cough disappearance time (MD = −1.76, 95% CI: −2.47 to −1.05, p < 0.01), pulmonary rale disappearance time (MD = −1.54, 95% CI: −2.06 to −1.02, p < 0.01), c-reactive protein (CRP) (MD = −5.50, 95% CI: −6.92 to −4.07, p < 0.01), procalcitonin (PCT) (MD = −0.31, 95% CI: −0.38 to −0.24, p < 0.01), interleukin 6 (IL-6) (MD = −5.97, 95% CI: −7.39 to −4.54, p

AimTo investigate the correlation between motor function and health-related quality of life (HrQOL) in early to mid-stage patients with Parkinson disease (PwP).MethodsThis cross-sectional study recruited PwP from April 2020 to December 2023 at the outpatient clinic of Peking Union Medical College Hospital in Beijing, China. The motor symptoms were assessed using Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part 3. Balance function was evaluated using the Berg Balance Scale (BBS), and the risk of fall using Timed Up-and-Go test (TUG), and Five Times Sit-to-Stand test (FTSST). Freezing of gait questionnaire (FOGQ) was used to evaluate the severity of gait. The Intelligent Device for Energy Expenditure and Physical Activity (IDEEA) recorded gait cycle parameters, and the isokinetic dynamometer measured muscle strength. The Parkinson’s Disease Questionnaire-39 (PDQ-39) was used to measure HrQOL. All assessments were tested during the on state. Spearman correlation was conducted to evaluate the correlation between motor function and HrQOL.Results243 patients with mean age of 69.33 years were enrolled. The PDQ-39 score was strongly correlated with FOG in H&Y stage III (r = 0.653, p

ObjectiveAutonomous docking is the key to the cooperative operation of unmanned underwater vehicles (UUVs). However, due to environmental complexity and object characteristics, it is very difficult to achieve precise guidance and docking. In order to improve the accuracy and robustness of underwater docking, this study proposes a vision-guided docking scheme which encompasses vision processing and 3D trajectory tracking control. MethodsFirst, the overall vision-guided docking scheme is designed in combination with an analysis of task and object characteristics. Second, the YOLOv5 neural network is designed to complete the target detection of the underwater docking station, and the online measurement of the relative position and attitude relationship between the docking station and UUV is realized by an efficient perspective-n-point (EPnP) algorithm. Next, combined with the visual measurement results, an effective 3D robust trajectory tracking controller is designed on the basis of the 3D LOS guidance law, radial basis function neural network (RBFNN) and terminal sliding mode control (TSMC). Finally, the validity of the proposed scheme is verified through numerical simulation and a tank test. ResultsIn the tank test, the proposed vision-guided control algorithm can effectively complete the online detection and relative positioning of the underwater docking station, thereby achieving precise underwater docking. ConclusionThe results of this study show that the proposed vision-guided 3D trajectory tracking control scheme is reasonable and efficient, and can lay a good foundation for UUV docking.

Large Language Models (LLMs) have demonstrated remarkable performance across various natural language tasks, marking significant strides towards general artificial intelligence. While general artificial intelligence is leveraged by developing increasingly large-scale models, there could be another branch to develop lightweight custom models that better serve certain domains, taking into account the high cost of training and deploying LLMs and the scarcity of resources. In this paper, we present MindLLM, a novel series of bilingual lightweight large language models, trained from scratch, alleviating such burdens by offering models with 1.3 billion and 3 billion parameters. A thorough account of experiences accrued during large model development is given, covering every step of the process, including data construction, model architecture, evaluation, and applications. Such insights are hopefully valuable for fellow academics and developers. MindLLM consistently matches or surpasses the performance of other open-source larger models on some public benchmarks. We also introduce an innovative instruction tuning framework tailored for smaller models to enhance their capabilities efficiently. Moreover, we explore the application of MindLLM in specific vertical domains such as law and finance, underscoring the agility and adaptability of our lightweight models.

Abstract Background To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression. Methods A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility. Results The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus. Conclusions This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.

Abstract Objective This study aims to investigate the relationship between abnormal vaginal microecology and human papillomavirus (HPV) infection, as well as the squamous intraepithelial lesions (SIL) progression. Methods A total of 383 patients diagnosed with HPV infection in our hospital between March 2017 and February 2022 were selected as the experimental group. In addition, several volunteers (n = 898) who underwent physical examination during the same period were randomly selected as the control group. Subsequently, we conducted several investigations, such as HPV detection and gene typing, examined vaginal microecological imbalances, and performed cytological examinations to analyze the correlation between microecological changes, different types of HPV infection, and SIL progression. Results HPV detection primarily included single and high-risk types of HPV infections. Moreover, significant disparities in the vaginal microecological environment between patients with persistent HPV infection and the control group, as well as patients with low-grade and high-grade SIL (LSIL and HSIL), were observed. The regression analysis revealed a correlation between LSIL and microflora density, diversity, bacteriological vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonas vaginalis (TV), sialidase, as well as Lactobacillus. In addition, we identified an association between HSIL and pH, flora density, diversity, BV, VVC, candida vaginitis (CV), leukocyte esterase, catalase, and Lactobacillus levels. Conclusion These findings revealed a significant association between abnormal vaginal microecology and both HPV infection and the SIL progression.

Irony detection aims to analyze and identify language expressions containing irony in texts, which can assist text sentiment analysis and opinion mining. Hyperbolic expressions are the unique language characteristics in Chinese ironic texts that often highlight the critics’ ironic intentions. Existing methods of irony domain lexicon construction ignore the hyperbolic expressions in the construction process, resulting in incomplete semantic information contained in the lexicon. Considering this problem, this paper proposes a method for constructing a hyperbolic representation lexicon to mine the language feature and improve the accuracy of irony detection. Firstly, we select the candidate words and word pairs of hyperbolic representation by Word2Vec combined with the K-means++ algorithm. Then, the information entropy is calculated to measure the correlation between candidate words and texts, so the seed word set with a high correlation with texts is obtained. Finally, we expand the seed word set using WoBERT to capture the text’s deep semantic information. Thus, the generalization ability of the hyperbolic representation lexicon is improved. The experimental results show that combining the lexicon constructed in this paper can effectively mine the language features of ironic texts, thereby improving the accuracy of irony detection. The experimental indicators Acc and F1-score have an average improvement of about 2.38% and 2.29%, respectively.

Abstract Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial–mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

Abstract Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. Atomic-resolution structures of metazoan RS and structures of axonemal complexes in ependymal cilia, whose rhythmic beating drives the circulation of cerebrospinal fluid, however, remain obscure. Here, we present near-atomic resolution cryo-EM structures of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic flexibility of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the cryo-ET and sub-tomogram averaging map of mouse ependymal cilia and build the models for RS1-3, IDAs, and N-DRC. Contrary to the conserved RS structure, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of Tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella, further exemplifying the structural diversity of mammalian motile cilia. Our findings shed light on the stepwise mammalian RS assembly mechanism, the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understanding on the etiology of ciliary dyskinesia-related ciliopathies and on the ependymal cilia in the development of hydrocephalus.

Abstract Upgrading ethanol to long-chain alcohols (LAS, C6+OH) offers an attractive and sustainable approach to carbon neutrality. Yet it remains a grand challenge to achieve efficient carbon chain propagation, particularly with noble metal-free catalysts in aqueous phase, toward LAS production. Here we report an unconventional but effective strategy for designing highly efficient catalysts for ethanol upgrading to LAS, in which Ni catalytic sites are controllably exposed on surface through sulfur modification. The optimal catalyst exhibits the performance well exceeding previous reports, achieving ultrahigh LAS selectivity (15.2% C6OH and 59.0% C8+OH) at nearly complete ethanol conversion (99.1%). Our in situ characterizations, together with theoretical simulation, reveal that the selectively exposed Ni sites which offer strong adsorption for aldehydes but are inert for side reactions can effectively stabilize and enrich aldehyde intermediates, dramatically improving direct-growth probability toward LAS production. This work opens a new paradigm for designing high-performance non-noble metal catalysts for upgrading aqueous EtOH to LAS.