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Abstract Soft-magnetic fibers (SMFs) play a crucial role in energy conversion, transmission, and storage within electronic devices. However, conventional SMFs have poor plasticity and are therefore difficult to withstand long-term tensile, torsional, and shear deformation. A high fraction of grain boundaries could improve plastic deformability of conventional SMFs, but deteriorates the coercivity. This severely limits their applications in flexible electronics and multifunctional components. Herein, we propose a strategy to overcome this dilemma, which is realized by coarsening the grains of a Fe34Co29Ni29Al3Ta3Si2 high entropy alloy (HEA) fiber containing ordered coherent nanoprecipitates with small lattice misfit via a simple one-step in-rotating-water spinning method. This allows to reduce domain wall pinning and improve dislocation mobility. The resultant micron-diameter soft-magnetic HEA fiber has a tensile strength of 674 MPa at 23% elongation, a low coercivity of 8.1 Oe, a moderate magnetization of 116 emu/g at 10 kOe and a high Curie temperature of 770 K.

Organoids are expected to function as effective human organ models for precision cancer studies and drug development. Currently, primary tissue-derived organoids, termed non-engineered organoids (NEOs), are produced by manual pipetting or liquid handling that compromises organoid-organoid homogeneity and organoid-tissue consistency. Droplet-based microfluidics enables automated organoid production with high organoid-organoid homogeneity, organoid-tissue consistency, and a significantly improved production spectrum. It takes advantage of droplet-encapsulation of defined populations of cells and droplet-rendered microstructures that guide cell self-organization. Herein, we studied the droplet-engineered organoids (DEOs), derived from mouse liver tissues and human liver tumors, by using transcriptional analysis and cellular deconvolution on bulk RNA-seq data. The characteristics of DEOs are compared with the parental liver tissues (or tumors) and NEOs. The DEOs are proven higher reproducibility and consistency with the parental tissues, have a high production spectrum and shortened modeling time, and possess inter-organoid homogeneity and inter-tumor cell heterogeneity.

Abstract Promyelocytic leukemia protein (PML) nuclear bodies (NBs) are essential in regulating tumor suppression, antiviral response, inflammation, metabolism, aging, and other important life processes. The re-assembly of PML NBs might lead to an ~100% cure of acute promyelocytic leukemia. However, until now, the molecular mechanism underpinning PML NB biogenesis remains elusive due to the lack of structural information. In this study, we present the cryo-electron microscopy (cryo-EM) structure of the PML dimer at an overall resolution of 5.3 Å, encompassing the RING, B-box1/2 and part of the coiled-coil (RBCC) domains. The integrated approach, combining crosslinking and mass spectrometry (XL-MS) and functional analyses, enabled us to observe a unique folding event within the RBCC domains. The RING and B-box1/2 domains fold around the α3 helix, and the α6 helix serves as a pivotal interface for PML dimerization. More importantly, further characterizations of the cryo-EM structure in conjugation with AlphaFold2 prediction, XL-MS, and NB formation assays, help unveil an unprecedented octopus-like mechanism in NB assembly, wherein each CC helix of a PML dimer (PML dimer A) interacts with a CC helix from a neighboring PML dimer (PML dimer B) in an anti-parallel configuration, ultimately leading to the formation of a 2 µm membrane-less subcellular organelle.

Abstract Alkaline phosphatase (ALP) is a reliable biomarker for various diseases, making the development of new detection methods highly significant. Herein, we report a simple and accurate dual-signal optical detection strategy for measuring ALP activity across the entire clinical range in adults. Based on this, we designed a smartphone app to eliminate the limitations of large instruments, enabling real-time field detection. In this work, ALP catalyzes the conversion of the phosphate monoester of 2-phospho-L-ascorbic acid (PAA) into ascorbic acid (AA), a compound with strong reducing properties. AA facilitates the in-situ reduction of Ag+ to form Au@Ag core-shell nanoparticles, accompanied by significant changes in the ultraviolet-visible absorption spectra and color. These changes allow for the qualitative and quantitative detection of ALP activity. In UV absorption spectroscopy and colorimetric detection, the signal shows good linearity with ALP activity concentrations, with detection ranges of 0 U/L to 200 U/L (R2=0.9961) and 25 U/L to 250 U/L (R2=0.9771), respectively. Subsequent selective analysis and serum sample analysis demonstrated the high selectivity and accuracy of the proposed method, highlighting its potential for field application.

Abstract Background Over the past few years, the development of telerehabilitation has advanced rapidly. Patients with Parkinson's disease (PwPD) often have difficulty with mobility, making it challenging for them to perform centre-based exercise.This study aims to compare the effectiveness and adherence of home physical therapy (HPT) and telerehabilitation (TR) in mitigating motor symptoms and improving the quality of life in patients with mild to moderate Parkinson’s disease. Methods This randomized controlled trial included a total of 190 patients who underwent in-person eligibility assessment, with 100 allocated to the HPT group and 90 to the TR group. Both interventions consisted of home-based training sessions lasting 40–60 min and were conducted five times a week for 4 weeks. The primary outcome was the Unified Parkinson’s Disease Rating Scale motor section (UPDRS3) score. Secondary outcomes included balance function, assessed using the Berg Balance Scale (BBS); risk of fall, evaluated through the Timed Up-and-Go test (TUG) and the Five Times Sit-to-Stand test (FTSST); gait, measured using the Freezing of Gait Questionnaire (FOGQ) and IDEEA activity monitor; muscle strength, evaluated using the isokinetic dynamometry; motor aspects of experiences of daily living (UPDRS2); and quality of life, assessed by Parkinson's Disease Questionnaire-39 (PDQ-39). Results There was a significant difference in the UPDRS3, BBS, TUG, FTSST, FOGQ,step length, step velocity,preswing angle, UPDRS2 and PDQ-39 between baseline and 4 weeks in both groups. The decrease in the UPDRS3 score was significantly greater in the HPT group (-3.38 points) than in the RE group (-1.45 points) in the older age group (P = 0.021), but there was no significant between-group difference in the younger age group (P = 0.416). Similar changes favouring the HPT group were observed in the BBS, TUG, step velocity, and extension average torque. 7 (7%) patients in the HPT group and 12 (13%) patients in the TR group did not complete their daily exercise plan. Conclusions Both HPT and TR have demonstrated effectiveness, safety, and feasibility in PwPD. However, the HPT program exhibited greater effectiveness among older patients and higher patient compliance compared to TR. Trial registration Chictr.org.cn, ChiCTR2300071648. Registered on 22 May 2023—retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=196313 .

Abstract Introduction Although with increasing popularity due to aesthetic appeal and comfort, clear aligners (CAs) are facing challenges in efficacy and predictability. Advancement in the underlying biomechanical field is crucial to addressing these challenges. This paper endeavors to provide a comprehensive framework for understanding the biomechanics of CA and enlightening biomechanics-based improvements on treatment strategies. Methods A thorough review of the English-language literature accessible through PubMed and Google Scholar, without any publication year restrictions, was undertaken to unravel the biomechanical aspects of CA. Results This review presented an up-to-date understanding of aligner biomechanics arranged by the framework of the material-dependent mechanical characteristics of CA, the geometric characteristics-dependent force transmission of the CA system, methods for studying the biomechanics of CA, and the biomechanical analyses for different types of tooth movement. Conclusions Biomechanics should be the fundamental concern for concepts, methods and adjuncts attempting to enhance the accuracy and predictability of tooth movement induced by CA. Improvement on material properties and alteration of geometric design of CA are two main approaches to develop biomechanically optimized force system. Exploration of real-world force sensing and monitoring system would make substantial progresses in aligner biomechanics.

Abstract Agile and adaptive maneuvers such as fall recovery, high-speed turning, and sprinting in the wild are challenging for legged systems. We propose a Curricular Hindsight Reinforcement Learning (CHRL) that learns an end-to-end tracking controller that achieves powerful agility and adaptation for the legged robot. The two key components are (i) a novel automatic curriculum strategy on task difficulty and (ii) a Hindsight Experience Replay strategy adapted to legged locomotion tasks. We demonstrated successful agile and adaptive locomotion on a real quadruped robot that performed fall recovery autonomously, coherent trotting, sustained outdoor running speeds up to 3.45 m/s, and a maximum yaw rate of 3.2 rad/s. This system produces adaptive behaviors responding to changing situations and unexpected disturbances on natural terrains like grass and dirt.

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.

Antibacterial hydrogels not only provide a better environment for skin wounds to avoid infection but also accelerate wound healing. Herein, chitosan modified by a quaternary ammonium salt (CQ), and hyaluronic acid grafted with methacrylate (HM) were designed and synthesized to prepare an injectable photo-crosslinking hydrogel for wound dressing with inherent antibacterial and photothermal properties. CQ and HM exhibited excellent biocompatibility, improved water retention, and antibacterial activity, illustrating vast potential as an antibacterial material in various applications. MXene, a type of 2D nanomaterial, has been widely researched due to its photothermal properties. The CQ and HM polymer precursor could be mixed with Mxene and then crosslinked with 395 nm UV radiation under mild conditions to form a 3D network structure CQ-HM/MXene hydrogel. This hydrogel displayed an appropriate swelling ratio, elastic modulus, photothermal property and excellent biocompatibility. The injectable property of the hydrogel allowed it to easily cover the wound. In vitro and in vivo studies showed that the injectable hydrogel had low cytotoxicity and excellent antibacterial properties, which could help promote wound healing. In summary, this novel CQ-HA/MXene hydrogel has the potential for application in skin wound healing due to inherent antibacterial activity and photothermal effect.

Hardware Trojans (HTs) are a longstanding threat to secure computation. Among different threat models, it is the fabrication-time insertion of additional malicious logic directly into the layout of integrated circuits (ICs) that constitutes the most versatile, yet challenging scenario, for both attackers and defenders. Here, we present a large-scale, first-of-its-kind community effort through red-versus-blue teaming that thoroughly explores this threat. Four independently competing blue teams of 23 IC designers in total had to analyze and fix vulnerabilities of representative IC layouts at the pre-silicon stage, whereas a red team of 3 experts in hardware security and IC design continuously pushed the boundaries of these defense efforts through different HTs and novel insertion techniques. Importantly, we find that, despite the blue teams’ commendable design efforts, even highly-optimized layouts retained at least some exploitable vulnerabilities. Our effort follows a real-world setting for a modern 7nm technology node and industrygrade tooling for IC design, all embedded into a fully-automated and extensible benchmarking framework. To ensure the relevance of this work, strict rules that adhere to real-world requirements for IC design and manufacturing were postulated by the organizers. For example, not a single violation for timing and design-rule checks were allowed for defense techniques. Besides, in an advancement over prior art, neither red nor blue teams were allowed to use any so-called fillers and spares for trivial attack or defense approaches. Finally, we release all methods and artifacts: the representative IC layouts and HTs, the devised attack and defense techniques, the evaluation metrics and setup, the technology setup and commercial-grade reference flow for IC design, the encompassing benchmarking framework, and all best results. This full release enables the community to continue exploring this important challenge for hardware security, in particular to focus on the urgent need for further advancements in defense strategies.

Abstract BackgroundHealth-related rumors and misconceptions are spreading at an alarming rate, fueled by the rapid development of the internet and the exponential growth of social media platforms. This phenomenon has become a pressing global concern, as the dissemination of false information can have severe consequences, including widespread panic, social instability, and even public health crises. ObjectiveThe aim of the study is to compare the accuracy of rumor identification and the effectiveness of health science popularization between 2 generated large language models in Chinese (GPT-4 by OpenAI and Enhanced Representation through Knowledge Integration Bot [ERNIE Bot] 4.0 by Baidu). MethodsIn total, 20 health rumors and misconceptions, along with 10 health truths, were randomly inputted into GPT-4 and ERNIE Bot 4.0. We prompted them to determine whether the statements were rumors or misconceptions and provide explanations for their judgment. Further, we asked them to generate a health science popularization essay. We evaluated the outcomes in terms of accuracy, effectiveness, readability, and applicability. Accuracy was assessed by the rate of correctly identifying health-related rumors, misconceptions, and truths. Effectiveness was determined by the accuracy of the generated explanation, which was assessed collaboratively by 2 research team members with a PhD in nursing. Readability was calculated by the readability formula of Chinese health education materials. Applicability was evaluated by the Chinese Suitability Assessment of Materials. ResultsGPT-4 and ERNIE Bot 4.0 correctly identified all health rumors and misconceptions (100% accuracy rate). For truths, the accuracy rate was 70% (7/10) and 100% (10/10), respectively. Both mostly provided widely recognized viewpoints without obvious errors. The average readability score for the health essays was 2.92 (SD 0.85) for GPT-4 and 3.02 (SD 0.84) for ERNIE Bot 4.0 (PP ConclusionsERNIE Bot 4.0 demonstrated similar accuracy to GPT-4 in identifying Chinese rumors. Both provided widely accepted views, despite some inaccuracies. These insights enhance understanding and correct misunderstandings. For health essays, educators can learn from readable language styles of GLLMs. Finally, ERNIE Bot 4.0 aligns with Chinese expression habits, making it a good choice for a better Chinese reading experience.

Objective: Light exposure is thought to be associated with blood pressure (BP). However, the existing evidence is inconsistent, and the underlying mechanisms remain unclear. Methods: This cohort study enrolled over 300,000 participants from the UK Biobank. Information on the time spent in outdoor light during typical summer and winter days was collected using questionnaires. Cases of hypertension and hypotension were identified using the 10th edition of the International Classification of Diseases codes. Cox proportional hazards regression models were employed to estimate the lightBP associations, and restricted cubic splines were utilized to detect potential nonlinear associations. Subgroup analyses were conducted to identify effect modifiers, and causal mediation analyses were performed to explore potential mechanisms. Results: Using summer light exposure as an illustration, after a median follow-up of 13.4 years, each additional hour of summer light exposure was found to be associated with an increased risk of hypertension (hazard ratio [HR] 1.011, 95 % confidence interval [CI] 1.0061.017, P-nonlinear=0.803) and a decreased risk of hypotension (0.988, 0.9770.998, P-nonlinear=0.109). The lightBP association was found to be stronger in females (P=0.022), those with short sleep durations (P=0.049), and those with a high genetic risk of hypertension (P

The sett is a crucial resource for badgers, serving various functions and significantly influencing their spatial ecology. The selection of sett sites is also a complex behavior. While there have been extensive ecological studies on the European badger (Meles meles), little is known about the Asian badger (Meles leucurus), particularly in China, making it difficult to evaluate their current survival status and establish conservation strategies. Therefore, we conducted a pioneering ecological study on the Asian badger, focusing on local population density and habitat selection within the Northeast Tiger and Leopard National Park, NE China. First, we surveyed badger setts in the study area and set camera traps to capture videos of badgers and estimate the number of individuals. The estimated badger density based on the main sett distribution (1.40 sett /km2) and group size (average of 3.01 ± 1.82 individuals per sett) was 4.21 ± 2.55 badgers /km2. Second, we set up random points in the study area and measured 12 habitat factors of 67 random point quadrats and 67 badger sett quadrats to establish which factors affect the habitat selection of badgers. Statistical tests, random forest algorithm, and generalized linear model were used to explain the sett selection criteria of Asian badgers. Statistical tests indicated a highly significant difference in slope (p < 0.01) and a significant difference in tree distance and aspect (p < 0.05) between sett quadrats and random point quadrats. After correction for multiple testing according to Holm, we found that differences in tree distance and aspect lost their statistical significance. However, the random forest algorithm and generalized linear model showed that the selection of sett location was influenced by tree distance, slope, and aspect. We conclude that badgers exhibit a preference for setts located near trees, steep slopes, and orientations facing north and northwest (316–45°). This is the first assessment of the abundance and sett selection of the Asian badger at the local population scale from Chinese nature reserves, providing new insights into the population ecology and habitat selection of the Asian badger in China, and assisting in the development of relevant conservation strategies and management.

In vertical farms, the supplementation of far-red light has been widely applied to regulate plant growth and development. However, the relative contribution of far-red to photosynthesis and plant growth in indoor production systems is not sufficiently quantified. This study quantify the photosynthesis and growth responses under different levels of supplemental far-red in lettuce using a 3D modelling approach. Lettuce were cultivated under either white light or red to far-red (R:FR) ratio of 1.6 or 0.8. Measurements of plant morphological traits, leaf photosynthesis, and organ fresh and dry mass were taken and the 3D modelling approach was used to simulate plant photosynthesis and biomass accumulation. Results showed that leaf elevation angle, leaf expansion rate, and plant height significantly increased at each growth stage as the R:FR ratio decreased. Far-red light also promoted plant growth, leading to an increase in the dry and fresh weight of lettuce throughout the entire growth period. However, plants cultivated at low R:FR showed reduced maximum Rubisco carboxylation rate and maximum electron transport rate, which indicated that far-red light reduced the photosynthetic capacity in lettuce. Nevertheless, 3D model simulations demonstrated that plants exposed to enhanced far-red light exhibited increased light interception and whole-plant photosynthesis. The integrated analysis of photosynthetic parameters and plant morphological changes on the photosynthetic rate of the whole plant indicated that the positive effects of plant morphological changes outweighed the negative impacts of photosynthetic parameters. These results implied that far-red light-induced morphological changes enhanced light interception and whole-plant photosynthesis, thereby increased lettuce yield.

BackgroundOver the past 4 decades, obesity has escalated into a global epidemic, with its worldwide prevalence nearly tripling. Pharmacological treatments have evolved with the recent development of glucagon-like peptide 1 agonists, such as semaglutide. However, off-label use of drugs such as Ozempic for cosmetic weight loss has surged in popularity, raising concerns about potential misuse and the emergence of substandard and falsified products in the unregulated supply chain. ObjectiveThis study aims to conduct a multifactor investigation of product quality and patient safety risks associated with the unregulated online sale of semaglutide by examining product availability and vendor characteristics and assessing product quality through test purchases. MethodsWe used a complex risk and quality assessment methodology combining online market surveillance, search engine results page analysis, website content assessment, domain traffic analytics, conducting targeted product test purchases, visual quality inspection of product packaging, microbiological sterility and endotoxin contamination evaluation, and quantitative sample analysis using liquid chromatography coupled with mass spectrometry. ResultsWe collected and evaluated 1080 links from search engine results pages and identified 317 (29.35%) links belonging to online pharmacies, of which 183 (57.7%) led to legal pharmacies and 134 (42.3%) directed users to 59 unique illegal online pharmacy websites. Web traffic data for the period between July and September 2023 revealed that the top 30 domains directly or indirectly affiliated with illegal online pharmacies accumulated over 4.7 million visits. Test purchases were completed from 6 illegal online pharmacies with the highest number of links offering semaglutide products for sale without prescription at the lowest price range. Three injection vial purchases were delivered; none of the 3 Ozempic prefilled injection pens were received due to nondelivery e-commerce scams. All purchased vials were considered probable substandard and falsified products, as visual inspection indicated noncompliance in more than half (59%-63%) of the evaluated criteria. The semaglutide content of samples substantially exceeded labeled amounts by 28.56%-38.69%, although no peptide-like impurities were identified. The lyophilized peptide samples were devoid of viable microorganisms at the time of testing; however, endotoxin was detected in all samples with levels ranging between 2.1645 EU/mg and 8.9511 EU/mg. Furthermore, the measured semaglutide purity was significantly low, ranging between 7.7% and 14.37% and deviating from the 99% claimed on product labels by manufacturers. ConclusionsGlucagon-like peptide 1 agonist drugs promoted for weight loss, similar to erectile dysfunction medications more than 2 decades ago, are becoming the new blockbuster lifestyle medications for the illegal online pharmacy market. Protecting the pharmaceutical supply chain from substandard and falsified weight loss products and raising awareness regarding online medication safety must be a public health priority for regulators and technology platforms alike.

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

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

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.

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.

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.

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.

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.

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.