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Gradient triply periodic minimal surface (TPMS) structures are renowned for lightweight design and enhanced performance, but their complex and nonlinear configurations pose challenges in achieving targeted design goals. A new design methodology for the nonlinear gradient structure was proposed in this study, with the aim of achieving efficient and accurate modeling of complex and gradient sheet-based TPMS structures under specific performance objectives. This method utilized automated finite element (FE) simulations to obtain structure topology element densities under various boundary conditions. An artificial neural network (ANN) was then employed to efficiently predict the correspondence between these boundary conditions and topology element densities. A mapping was established between topology element densities and TPMS structural parameters, and the gradient structure was accurately constructed by using the voxel modeling technique. Taking a typical cantilever beam TPMS structure as an example of nonlinear gradient design, the results indicate that the error between the ANN-predicted and FE-simulated structure topology element densities is only 2.73 %, with prediction time being only 0.15 % of the simulation time. The thin regions of the gradient structure align with those geometrically removed in regular topology optimization scheme, achieving up to 65.45 % weight reduction, a 28.72 % improvement over the regular scheme, along with uniform structural stress transition and maximum stress reduction. TC4 alloy nonlinear gradient TPMS structures, printed by metal selective laser melting (SLM) technique, confirm the practical application value of this design method.

Abstract Background Preoperative oral carbohydrate intake can improve the postoperative recovery of fasting patients in many kinds of surgeries; however, the effect of carbohydrates on patients undergoing daytime oral surgery is still unclear. This study was designed to evaluate the effect of preoperative oral carbohydrate intake on the quality of recovery of patients undergoing daytime oral surgery using the quality of recovery-15 (QoR-15) questionnaire. Methods Ninety-two patients scheduled for daytime oral surgery were randomly allocated to the midnight fasting group (F group, n = 45) or the carbohydrate-Outfast loading group (O group, n = 47). Participants in the F group fasted from midnight the day before surgery. Patients in the O group also fasted but received the Outfast drink (4 ml/kg) 2–3 h before the induction of anesthesia. QoR-15 questionnaire, patient well-being, and satisfaction were assessed before anesthesia induction and 24 h after surgery. Perioperative blood glucose, postoperative exhaust time, and adverse events were also recorded. Results The QoR-15 scores were significantly higher in the O group than in the F group preoperatively and postoperatively. Seven parameters representing patient well-being evaluated on a numeric rating scale (NRS, 0–10) were lower in the O group than in the F group postoperatively, except for the hunger and sleep quality scores. Patient satisfaction scores on a 5-point scale were higher in the O group than in the F group preoperatively and postoperatively. Meanwhile, the postoperative exhaust time was significantly shorter in the O group compared to the F group, while there were no significant differences in blood glucose concentrations between two groups. Conclusions Preoperative oral carbohydrate intake could improve postoperative recovery quality, well-being, and satisfaction of patients undergoing daytime oral surgery 24 h after surgery, and may serve as a treatment option for patients undergoing daytime oral surgery. Trial registration This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2100053753) on 28/11/2021.

Abstract Background The airway should be thoroughly and accurately evaluated before anesthesia induction and endotracheal intubation. Awake direct laryngoscopy (ADL) can provide rapid, accurate, and intuitive airway assessment, especially for suspected difficult airways, and sometimes eliminates the need for fiberoptic intubation in some suspicious difficult airway cases. However, an optimal regimen has not been determined. Methods In this double-blind, controlled study, prior to ADL, 60 patients scheduled for general anesthesia were randomly allocated to receive 0.75 μg/kg of dexmedetomidine (Dex group, n = 20), 0.15 mg/kg of nalbuphine (Nal group, n = 20), or a placebo (control group, n = 20) intravenously over 10 min. At the same time, all study subjects received nebulized lidocaine for 15 min. The primary outcome was patient tolerance as assessed by a 5-point ADL comfort score, while secondary outcomes included satisfaction, coughing, pain, nausea and vital signs. Results Patients undergoing ADL in the Nal group had higher tolerance scores than those in the control and Dex groups [4 (3,4) vs. 3 (2,2.75), P

Abstract Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer’s disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD+-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPRmt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD+ metabolic profiles and improves MSR through the ATF4-dependent UPRmt pathway in AD-related cross-species models. At the organismal level, NAD+ repletion with NMN supplementation ameliorates mitochondrial proteotoxicity, decreases hippocampal synaptic disruption, decreases neuronal loss, and brain atrophy in mice model of AD. Remarkably, omics features of the hippocampus with NMN show that NMN leads to transcriptional changes of genes and proteins involved in MSR characteristics, principally within the astrocyte unit rather than microglia and oligodendrocytes. In brief, our work provides evidence that MSR has an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in AD mice aggravates the hallmarks of the disease; conversely, bolstering mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan.

Abstract In the area of online teacher training, asynchronous collaboration faces several challenges such as limited learner engagement and low interaction quality, thereby hindering its overall effectiveness. Drawing on social comparison theory, providing social comparison feedback to teacher-learners in online asynchronous collaborative learning offers benefits, but also has drawbacks. While social comparison has been explored in diverse fields, its role in education remains unclear. In this study, we selected 95 primary and secondary school teachers participating in an online training course. Using randomized controlled trial design, we provided the experimental group with social comparison feedback, while the control group received only self-referential feedback. We used epistemic network analysis, lag sequential analysis, and social network analysis to identify the impact of social comparison feedback on group-regulated focus, group-interactive behaviors, and social network structures. The results showed that social comparison feedback significantly enhanced teachers’ online asynchronous collaborative learning.

Abstract Adaptive governance has emerged as a prominent theoretical and methodological approach in environmental governance, recognized for its capacity to address evolving conditions and future uncertainties. Despite the extensive literature on adaptive governance since its inception in 2003, a comprehensive review of the literature spanning two decades remains to be conducted. This study addresses that gap by selecting 3274 articles from the Web of Science Core Collection and performing a global scientometric visualization analysis. Our analysis identifies the most productive institutions, authors, journals, publication trends, and research frontiers in adaptive governance research. The findings reveal that there has been a significant acceleration in global research on adaptive governance over the past two decades. Furthermore, the majority of contributions to the field of adaptive governance research have been made by scholars based in the United States, Australia, England, Canada, and the Netherlands. Additionally, existing studies in adaptive governance field focus mainly on subject categories of environmental studies, environmental sciences, and ecology. Finally, the concept of adaptive governance, environmental governance, social-ecological systems, climate change adaptation and social learning were identified as hot topics and emerging trends. This study provides researchers and practitioners with an extensive understanding of the salient research themes, trends, and patterns in global adaptive governance research in an intuitive manner.

Abstract In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority 3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

This study examines how COVID-induced and general attitudes toward Asians have changed over the course of the pandemic using nationally representative survey experiments in 2020 and 2022. First, we measured COVID-induced anti-Asian attitudes as the effect of a treatment reminding respondents of the pandemic on whether respondents would be willing to live or work with someone who is East or South Asian. The results suggest that the COVID-19 treatment worsened attitudes toward East and South Asians in the social domain and toward East Asians in the economic domain in 2020, but not in 2022. Second, we measured change in general attitudes toward Asians by comparing the control group responses in 2020 and 2022. The results demonstrate that, over the same period, general attitudes toward Asians have not improved despite growing attention toward anti-Asian biases. This finding underscores the persistence of general negative attitudes toward Asians beyond the immediate context of the pandemic and the ongoing imperative to actively address deeply ingrained biases against Asians.

Abstract Objective of the study Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related mortality globally. Metastasis, responsible for treatment failures, underscores the urgency to comprehend molecular drivers of invasion and migration. Central to the invasive and migratory processes underlying metastasis is the protein Talin1. However, the role and underlying mechanisms governing Talin1's involvement in HCC have remained elusive. Methods A total of 100 HCC specimens were collected from patients who underwent hepatectomy in our center. The expression level of talin1 was measured to evaluate the correlationship of talin1 and the development of HCC. In vitro and in vivo experiments were conducted to verify the characteristic of talin1 in HCC. RNA-seq and bioinformatics analysis were performed to identify the downstream signal pathway of talin1 and their impact on HCC development. Results Here, we reported elevated levels of Talin1 mRNA and protein in HCC tissues. Meanwhile, downregulation of Talin1 significantly reduced the HCC cell proliferation and metastasis in vitro and in vivo. Furthermore, elevating NRG-1, a downstream target of Talin1, enhanced metastasis of HCC cells. More importantly, attenuation of Talin1 inhibited HCC progression through decreasing the stabilization of NRG1 mRNA, consequently regulating the expression of NRG1 and its involvement in mediating the PI3K/AKT pathway. Conclusion Taken together, Talin1 regulates cellular proliferation, metastasis, and invasiveness by modulating NRG1/PI3K/AKT axis, suggesting that Talin1 emerges as a promising candidate for treating HCC.

Abstract Optical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.

Abstract Reservoir engineering is a powerful technique to autonomously stabilize a quantum state. Traditional schemes involving multi-body states typically function for discrete entangled states. In this work, we enhance the stabilization capability to a continuous manifold of states with programmable stabilized state selection using multiple continuous tuning parameters. We experimentally achieve 84.6% and 82.5% stabilization fidelity for the odd and even-parity Bell states as two special points in the manifold. We also perform fast dissipative switching between these opposite parity states within 1.8 μs and 0.9 μs by sequentially applying different stabilization drives. Our result is a precursor for new reservoir engineering-based error correction schemes.

Abstract Doped van der Waals heterostructures host layer-hybridized trions, i.e. charged excitons with layer-delocalized constituents holding promise for highly controllable optoelectronics. Combining a microscopic theory with photoluminescence (PL) experiments, we demonstrate the electrical tunability of the trion energy landscape in naturally stacked WSe2 bilayers. We show that an out-of-plane electric field modifies the energetic ordering of the lowest lying trion states, which consist of layer-hybridized $$\Lambda$$ Λ -point electrons and layer-localized K-point holes. At small fields, intralayer-like trions yield distinct PL signatures in opposite doping regimes characterized by weak Stark shifts in both cases. Above a doping-asymmetric critical field, interlayer-like species are energetically favored and produce PL peaks with a pronounced Stark red-shift and a counter-intuitively large intensity arising from efficient phonon-assisted recombination. Our work presents an important step forward in the microscopic understanding of layer-hybridized trions in van der Waals heterostructures and paves the way towards optoelectronic applications based on electrically controllable atomically-thin semiconductors.

This paper centers on stochastic Hopfield neural networks with variable coefficients and infinite delay. First, we propose an integral inequality that improves and extends some existing works. Second, by employing some inequalities and stochastic analysis techniques, some sufficient conditions for ensuring Pth moment generalized exponential stability are established. Our results do not necessitate the construction of a complex Lyapunov function or rely on the assumption of bounded variable coefficients, and our results expand some existing works. At last, to illustrate the efficacy of our result, we present several simulation examples.

Abstract Background Premature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy. Methods The study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36). Discussion The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice. Trial registration Clinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Objective: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). Methods: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. Conclusions: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Abstract This study presents a high-accuracy, all-fiber mode division multiplexing (MDM) reconstructive spectrometer (RS). The MDM was achieved by utilizing a custom-designed 3 × 1 mode-selective photonics lantern to launch distinct spatial modes into the multimode fiber (MMF). This facilitated the information transmission by increasing light scattering processes, thereby encoding the optical spectra more comprehensively into speckle patterns. Spectral resolution of 2 pm and the recovery of 2000 spectral channels were accomplished. Compared to methods employing single-mode excitation and two-mode excitation, the three-mode excitation method reduced the recovered error by 88% and 50% respectively. A resolution enhancement approach based on alternating mode modulation was proposed, reaching the MMF limit for the 3 dB bandwidth of the spectral correlation function. The proof-of-concept study can be further extended to encompass diverse programmable mode excitations. It is not only succinct and highly efficient but also well-suited for a variety of high-accuracy, high-resolution spectral measurement scenarios. Graphical Abstract

Abstract Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients’ therapy response and prognosis.

Abstract This study examined the effect of various clarification treatments on the physicochemical properties, volatile compounds, and sensory attributes of kiwi wines produced from five different kiwifruit (Actinidia deliciosa) varieties. The degree of clarification had a minimal impact on physicochemical parameters, including the content of residual sugar, ethanol, volatile acid, titratable acidity (except for the kiwifruit variety ‘Qinmei’), and the pH value. However, wines made from unclarified juices (muddy juice and pulp) displayed a higher glycerol content than those made from clarified juices. The cluster heat map and principal component analyses (PCA) demonstrated that kiwi wines produced from clarified kiwi juices possessed a higher ester content, whereas muddy juice and pulp wines contained elevated levels of higher alcohols. Quantitative descriptive analysis (QDA) indicated that clarified juice wines outperformed muddy juice and pulp wines in terms of purity, typicality, harmony, intensity, and freshness, with negligible differences in terms of palate acidity. Moreover, the clarified juice wines featured more characteristic kiwi wine aromas (kiwifruit, passionfruit, and pineapple) compared with that of the muddy juice and pulp wines, which exhibited an increased grassy flavour. Although the 100-NTU kiwifruit juice-fermented wine did not show an advantage in the cluster heat map and PCA, it presented better freshness, typicality, and intensity in the QDA, as well as a more passionfruit aroma. Based on the orthogonal partial least-squares discriminant analysis, A. deliciosa ‘Xuxiang’ was deemed to be the most suitable variety for vinification. This study provides crucial insights for enhancing the production of high-quality kiwi wine.

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

Accurate, rapid and sensitive detection of specific immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in human samples is crucial for preventing and assessing pandemics, especially in the case of recent COVID-19 outbreaks. However, simultaneous and efficient detection of IgG and IgM in a single system remains challenging. Herein, we developed a multicolor nanosystem capable of quantitatively analyzing anti-SARS-CoV-2 IgG and IgM with high sensitivity within 20 ​min. The detection system consists of core-shell upconversion nanoparticles (csUCNPs), secondary antibodies labeled with fluorescent dyes (sab), and magnetic nanocrystals (PMF). By leveraging the Förster resonance energy transfer (FRET) effect, the photoluminescence (PL) intensity of blue and green regions is restored for IgG and IgM detection, respectively. Inspiringly, owing to the introducing of PMF, the limits of detection (LODs) of IgG and IgM tested are improved to 89 ​fmol ​L−1 and 19.4 ​fmol ​L−1, representing about 416-folds and 487-folds improvement over only-dye dependent system, respectively. Mechanistic investigations reveal that the high collective effect and surface energy transfer efficiency from csUCNPs to PMF contribute to the enhanced detection sensitivity. The assay enables us to quantify clinical vaccinated samples with high specificity and precision, suggesting our multicolor platform can be a promising alternative for clinical point-of-care serological assay.

Microplastics (MPs) have attracted increasing attention worldwide owing to their widespread presence and potential risks to terrestrial and marine ecosystems. Estimating the pollution status and risk levels of MPs in coastal ecosystems is necessary; however, these are poorly understood in coastal megacities. Here, the abundance and characteristics of MPs in seawater, marine sediment, marine organisms, and beaches in the Shenzhen coastal ecosystems and land sources (river and sewage outfall) were simultaneously investigated, and the annual MPs load of rivers and MP-induced ecological risks were evaluated. The results showed that MPs pollution was prevalent in Shenzhen coastal ecosystems, with the average abundances of 2.40 ± 2.48 items/m3, 404.21 ± 431.48 items/kg, 1.66 ± 1.96 items/individual, and 1648.99 ± 1908.19 items/kg in seawater, marine sediment, marine organisms, and beach sands, respectively. The detected MPs were predominantly fibrous/granular, transparent/white, < 1 mm in size, and polyethylene terephthalate/polyethylene/polystyrene. The spatial distribution patterns of marine MPs are influenced mainly by anthropogenic activities and freshwater inflows (rivers and sewage outfalls). Pollution hotspots of MPs were identified in the Pearl River Estuary, which has a high population, gross domestic product, and river and wastewater discharge. Furthermore, the negative correlation between the abundance of MPs in seawater and salinity indicates that freshwater inflow carrying MPs to the sea is an important source of marine MPs pollution. It has been estimated that approximately 8320 billion MPs particles, weighing 274.55 tons, flow into the Shenzhen coast annually through river input. Based on the MPs polymer types and quantities, the ecological risk of MPs pollution in the Shenzhen coastal ecosystem is moderate and deserves further attention. These findings deepen the understanding of MPs pollution, sources, and ecological risks in the southern coastal region of China, and are helpful for employing effective management strategies to control marine MPs pollution.

Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration, subchondral sclerosis, synovitis, and osteophyte formation. OA is associated with disability and impaired quality of life, particularly among the elderly. Leptin, a 16-kD non-glycosylated protein encoded by the obese gene, is produced on a systemic and local basis in adipose tissue and the infrapatellar fat pad located in the knee. The metabolic mechanisms employed by leptin in OA development have been widely studied, with attention being paid to aging as a corroborative risk factor for OA. Hence, in this review, we have attempted to establish a potential link between leptin and OA, by focusing on aging-associated mechanisms and proposing leptin as a potential diagnostic and therapeutic target in aging-related mechanisms of OA that may provide fruitful guidance and emphasis for future research.

BACKGROUND Studying the professional commitment of a student in an 8-year medical training program of China, especially its association with academic performance, can enhance the understanding of professional loyalty in future doctors. This study aimed to investigate the self-efficacy, academic performance, professional commitment, and learning engagement of 8-year program medical students, and explore the mediating roles of professional commitment and learning engagement on the associations between self-efficacy and academic performance. METHODS We conducted a cross-sectional study in a Chinese medical university and collected the General Self-Efficacy Scale, Professional Commitment of Undergraduates Scales, and the Utrecht Work Engagement Scale-Student from self-reported students. Academic performance was ascertained using course examination scores in the most recent year. We conducted a structural equation model (SEM) analysis to examine the mediating roles of professional commitment and learning engagement on the relationship between self-efficacy and academic performance. RESULTS A total number of 402 medical students were included in this study. Students in the clinical practice stage had significantly lower professional commitment and learning engagement than students in the pre-medical and medical course stages. The professional commitment of students from low-income families was significantly lower than that of students from high-income families. Professional commitment and learning engagement were mediators in the relationship between self-efficacy and academic performance. CONCLUSIONS This study is the first to investigate professional commitment among students in the China 8-year medical program. Professional commitment plays an intermediary role between self-efficacy and academic performance.

This study explored the impact of varying nitrate to sulfide (N/S) ratios on nitrogen removal efficiency (NRE) in the sulfide-driven autotrophic denitrification and anammox (SDAD-anammox) system. Optimal nitrogen removal was observed at N/S ratios between 1.5 and 2.0. Isotope tracing results showed that the contribution of anammox to nitrogen removal was enhanced with increasing N/S ratios, reaching up to 37 % at the N/S ratio of 2.5. Additionally, complex nitrogen pathways were identified, including dissimilatory nitrate reduction to ammonium (DNRA). Furthermore, isotope tracing was innovatively applied to investigate N2O emissions, demonstrating that higher N/S ratios significantly reduced N2O emissions, with the lowest emissions at N/S ratio of 2.5. Gene expression analysis indicated that nitrogen and sulfide transformation genes decreased with increasing N/S ratios, while anammox-related genes first increased and then decreased, reflecting the system's microbial dynamics. These findings offer insights into nitrogen transformation pathways and N2O production mechanisms in the SDAD-anammox process.

Abstract Background Embryo implantation remains a critical barrier in assisted reproductive technologies. One of the main causes of unsuccessful embryo implantation is window of implantation (WOI) displacement, particularly in patients with recurrent implantation failure (RIF). Therefore, a reliable diagnostic tool for identifying the optimal WOI is essential. Previous data has suggested that a novel RNA-Seq-based endometrial receptivity testing (ERT) can diagnose WOI, guide personalized embryo transfer (pET), and improve pregnancy outcomes in patients with RIF compared to standard embryo transfer (sET). However, there is still a lack of evidence from randomized controlled trials (RCT) with sufficient power to determine whether pET based on ERT can increase the rate of live births as the primary outcome. Methods This trial is a prospective, single-blind, parallel-group RCT (1:1 ratio of pET versus sET). Infertile women with RIF who intend to undergo frozen-thawed embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) with the availability of at least one euploid blastocyst for transfer will be enrolled and assigned into two parallel groups randomly. Participants in the intervention group will undergo ERT and then pET based on the results of ERT, while those in the control group will undergo sET. The primary outcome is live birth rate. Discussion The findings of this study will provide evidence for the effect of pET guided by ERT on pregnancy outcomes in patients with RIF. Trial registration Chinese Clinical Trial Registry ChiCTR2100049041. Registered on 20 July 2021.

Abstract Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Abstract The performance of superconducting quantum circuits for quantum computing has advanced tremendously in recent decades; however, a comprehensive understanding of relaxation mechanisms does not yet exist. In this work, we utilize a multimode approach to characterizing energy losses in superconducting quantum circuits, with the goals of predicting device performance and improving coherence through materials, process, and circuit design optimization. Using this approach, we measure significant reductions in surface and bulk dielectric losses by employing a tantalum-based materials platform and annealed sapphire substrates. With this knowledge we predict the relaxation times of aluminum- and tantalum-based transmon qubits, and find that they are consistent with experimental results. We additionally optimize device geometry to maximize coherence within a coaxial tunnel architecture, and realize on-chip quantum memories with single-photon Ramsey times of 2.0 − 2.7 ms, limited by their energy relaxation times of 1.0 − 1.4 ms. These results demonstrate an advancement towards a more modular and compact coaxial circuit architecture for bosonic qubits with reproducibly high coherence.

Abstract The wide applications of liquid chromatography - mass spectrometry (LC-MS) in untargeted metabolomics demand an easy-to-use, comprehensive computational workflow to support efficient and reproducible data analysis. However, current tools were primarily developed to perform specific tasks in LC-MS based metabolomics data analysis. Here we introduce MetaboAnalystR 4.0 as a streamlined pipeline covering raw spectra processing, compound identification, statistical analysis, and functional interpretation. The key features of MetaboAnalystR 4.0 includes an auto-optimized feature detection and quantification algorithm for LC-MS1 spectra processing, efficient MS2 spectra deconvolution and compound identification for data-dependent or data-independent acquisition, and more accurate functional interpretation through integrated spectral annotation. Comprehensive validation studies using LC-MS1 and MS2 spectra obtained from standards mixtures, dilution series and clinical metabolomics samples have shown its excellent performance across a wide range of common tasks such as peak picking, spectral deconvolution, and compound identification with good computing efficiency. Together with its existing statistical analysis utilities, MetaboAnalystR 4.0 represents a significant step toward a unified, end-to-end workflow for LC-MS based global metabolomics in the open-source R environment.

Abstract Osteoporosis is usually caused by excessive bone resorption and energy metabolism plays a critical role in the development of osteoporosis. However, little is known about the role of energy metabolism-related genes in osteoporosis. This study aimed to explore the important energy metabolism-related genes involved in the development of osteoporosis and develop a diagnosis signature for osteoporosis. The GSE56814, GSE62402, and GSE7158 datasets were downloaded from the NCBI Gene Expression Omnibus. The intersection of differentially expressed genes between high and low levels of body mineral density (BMD) and genes related to energy metabolism were screened as differentially expressed energy metabolism genes (DE-EMGs). Subsequently, a DE-EMG-based diagnostic model was constructed and differential expression of genes in the model was validated by RT-qPCR. Furthermore, a receiver operating characteristic curve and nomogram model were constructed to evaluate the predictive ability of the diagnostic model. Finally, the immune cell types in the merged samples and networks associated with the selected optimal DE-EMGs were constructed. A total of 72 overlapped genes were selected as DE-EMGs, and a five DE-EMG based diagnostic model consisting B4GALT4, ADH4, ACAD11, B4GALT2, and PPP1R3C was established. The areas under the curve of the five genes in the merged training dataset and B4GALT2 in the validation dataset were 0.784 and 0.790, respectively. Moreover, good prognostic prediction ability was observed using the nomogram model (C index = 0.9201; P = 5.507e−14). Significant differences were observed in five immune cell types between the high- and low-BMD groups. These included central memory, effector memory, and activated CD8 T cells, as well as regulatory T cells and activated B cells. A network related to DE-EMGs was constructed, including hsa-miR-23b-3p, DANCR, 17 small-molecule drugs, and two Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways and pyruvate metabolism. Our findings highlighted the important roles of DE-EMGs in the development of osteoporosis. Furthermore, the DANCR/hsa-miR-23b-3p/B4GALT4 axis might provide novel molecular insights into the process of osteoporosis development.

Abstract Accurately placing very small amounts of electrolyte on tiny micro-supercapacitors (MSCs) arrays in close proximity is a major challenge. This difficulty hinders the development of densely-compact monolithically integrated MSCs (MIMSCs). To overcome this grand challenge, we demonstrate a controllable electrolyte directed assembly strategy for precise isolation of densely-packed MSCs at micron scale, achieving scalable production of MIMSCs with ultrahigh areal number density and output voltage. We fabricate a patterned adhesive surface across MIMSCs, that induce electrolyte directed assembly on 10,000 highly adhesive MSC regions, achieving a 100 µm-scale spatial separation between each electrolyte droplet within seconds. The resultant MIMSCs achieve an areal number density of 210 cells cm−2 and a high areal voltage of 555 V cm−2. Further, cycling the MIMSCs at 190 V over 9000 times manifests no performance degradation. A seamlessly integrated system of ultracompact wirelessly-chargeable MIMSCs is also demonstrated to show its practicality and versatile applicability.

The global prevalence of myopia is increasing year by year, leading to many ocular health issues and social problems. In recent years, it has been confirmed that peripheral defocus is closely related to the occurrence and development of myopia. Alteration of the state of peripheral defocus can significantly influence the progression of myopia and emmetropization, but the exact mechanisms are still unclear. At present, there is no method that can completely control myopia. Nowadays, the main controlling methods, including orthokeratology lens, peripheral defocus lens and multi-focal soft lens, have been confirmed to be closely related to peripheral defocus. In this paper, we will review and summarize the development and effect of these peripheral defocus relating control methods. In addition, the researches on the related mechanisms of peripheral retinal defocus and myopia prevention and control at home and abroad are reviewed, as well as the potential mechanisms of peripheral defocus, with a view to further improving the controlling effects of existing methods, developing new prevention and control methods and reducing the incidence and progression of myopia.

Abstract Unraveling the effect of spatially separated bifunctional sites on catalytic reactions is significant yet challenging. In this report, we investigate the role of spatial separation on the oxidation of methane in a series of Cu-exchanged aluminosilicate zeolites. Regulation of the bifunctional sites is done either through studying a physical mixture of Cu-exchanged zeolites and acidic zeolites or by systematically varying the Cu and acid density within a family of zeolite materials. We show that separated Cu and acid sites are beneficial for the formation of hydrocarbons while high-density Cu sites, which are closer together, facilitate the production of CO2. By contrast, a balance of the spatial separation of Cu and acid sites shows more favorable formation of methanol. This work will further guide approaches to methane oxidation to methanol and open an avenue for promoting hydrocarbon synthesis using methanol as an intermediate.

Black soldier fly (BSF) meal possesses a balanced nutritional profile, making it a promising substitute for fishmeal. Several studies have been conducted to investigate the effects of replacing fishmeal with BSF meal on fish immune response and antioxidant capacity. However, considering the varying effects of BSF meal on different fish species demonstrated in earlier studies, a meta-analysis study was imperative to determine the efficacy of BSF meal in aquafeed. This meta-analysis examined 38 studies on finfish. Subgroup analysis and meta-regression were conducted to investigate the source of heterogeneity in the immunostimulant and antioxidant efficacy of BSF meal. Categorical variables used in subgroup analysis included the BSF development stage (larvae versus prepupae or pupae), BSF processing method (full-fat versus defatted), and fish dietary habits. Two continuous variables were evaluated for meta-regression analysis: dietary BSF inclusion level and treatment duration. The datasets were assessed for publication bias using funnel plots and Egger's test with the Pustejovsky–Rodgers Approach. The results revealed that BSF meal influences immune performance and antioxidant ability. Subgroup analysis indicated that different BSF development stages significantly influence the immunostimulant and antioxidant efficacy of BSF meals, with BSF prepupae or pupae outperforming BSF larvae. In terms of processing, full-fat BSF was superior to defatted BSF. Furthermore, BSF meal demonstrated the highest efficacy in omnivorous fishes. Meta-regression outcomes revealed that a higher concentration of BSF meal may inhibit immune response and antioxidant ability and that treatment duration exerts little impact. In conclusion, the present meta-analysis demonstrated that BSF is a promising ingredient in aquafeed to improve fish immune response and antioxidant capacity.

Following the earthquake, prompt evaluation of the distribution of coseismic landslides and estimation of potential disaster losses are crucial for emergency response and resettlement planning. The Luding earthquake of 2022 offers a valuable opportunity to conduct a rapid assessment of coseismic landslides using various models. In this study, we utilize the Logistic Regression (LR)-based Xu2019 model, a new-generation model developed in China, alongside the Newmark model to perform the rapid hazard assessment of coseismic landslides. Assessing the accuracy and applicability of these two models based on the coseismic landslides from the Luding earthquake, we find that within intensity area of IX, the high probability area identified by the Newmark model aligns closely with the actual distribution of landslides. However, the Newmark model’s prediction is overestimated in the intensity area of VIII. For the Xu2019 model, the prediction results are in good agreement with the distribution of actual landslides. Most landslides are located in high probability areas, such as Detuo town, Wandong, and Xingfu villages, indicating that the model has a higher prediction accuracy. Overall, two models have good practical utility in emergency hazard assessment of coseismic landslides. However, the Newmark model requires multi-input parameters and the assignment of these parameters will increase the uncertainty and subjectivity in the practical application of the modeling assessment.

ObjectivesThe aim of this research is to discuss the research status, hotspots, frontiers, and development trends in the field of small bowel adenocarcinoma based on bibliometrics and visual analysis by CiteSpace software.MethodsThe relevant research articles on SBA from 1923 to 2023 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.ResultsThere were 921 articles included, and the number of articles published during 1923-2023 is increasing. The country with the highest number of articles published was the United States (443, 38.76%), followed by Japan (84, 9.12%) and France (72, 7.82%). The author with the highest number of publications is Ansell, Overman MJ (33, 3.58%), and the author with the highest co-citation frequency is Overman MJ (218). Journal of Clinical Oncology is the journal with the highest publication frequency. The top five cluster groups were “chemotherapy”, “inflammatory bowel disease”, “celiac disease”, “tumor” and “small intestine”. The related disease, chemotherapy drugs, and treatment regimens of SBA form the main research fields, and prognosis and diagnosis are the research hotspots and trends.ConclusionThe global research field in SBA has expanded in the past 100 years. The prognosis and new diagnosis of SBA are hotspots in this field and require further study in the future.

Background: Osteoporosis is a prevalent global health condition, primarily affecting the aging population, and several therapies for osteoporosis have been widely used. However, available drugs for osteoporosis are far from satisfactory because they cannot alleviate disease progression. This study aimed to explore potential drug targets for osteoporosis through Mendelian randomization analysis. Methods: Using cis-expression quantitative trait loci (cis-eQTL) data of druggable genes and two genome-wide association studies (GWAS) datasets related to osteoporosis (UK Biobank and FinnGen cohorts), we employed mendelian randomization (MR) analysis to identify the druggable genes with causal relationships with osteoporosis. Subsequently, a series of follow-up analyses were conducted, such as colocalization analysis, cell-type specificity analysis, and correlation analysis with risk factors. The association between potential drug targets and osteoporosis was validated by qRT-PCR. Results: Six druggable genes with causal relationships with osteoporosis were identified and successfully replicated, including ACPP, DNASE1L3, IL32, PPOX, ST6GAL1, and TGM3. Cell-type specificity analysis revealed that PPOX and ST6GAL1 were expressed in all cell types in the bone samples, while IL32, ACPP, DNASE1L3, and TGM3 were expressed in specific cell types. The GWAS data showed there were seven risk factors for osteoporosis, including vitamin D deficiency, COPD, physical activity, BMI, MMP-9, ALP and PTH. Furthermore, ACPP was associated with vitamin D deficiency and COPD; DNASE1L3 was linked to physical activity; IL32 correlated with BMI and MMP-9; and ST6GAL1 was related to ALP, physical activity, and MMP-9. Among these risk factors, only MMP-9 had a high genetic correlation with osteoporosis. The results of qRT-PCR demonstrated that IL32 was upregulated while ST6GAL1 was downregulated in peripheral blood of osteoporosis patients. Conclusion: Our findings suggested that those six druggable genes offer potential drug targets for osteoporosis and require further clinical investigation, especially IL32 and ST6GAL1.

Coastal wetlands are important areas with valuable natural resources and diverse biodiversity. Due to the influence of both natural factors and human activities, the landscape of coastal wetlands undergoes significant changes. It is crucial to systematically monitor and analyze the dynamic changes in coastal wetland cover over a long-term time series. In this paper, a long-term time series coastal wetland remote sensing classification process was proposed, which integrated feature selection and sample migration. Utilizing Google Earth Engine (GEE) and Landsat TM/ETM/OLI remote sensing image data, the selected feature set is combined with the sample migration method to generate the training sample set for each target year. The Simple Non-Iterative Clustering-Random Forest (SNIC-RF) model was ultimately employed to accurately map wetland classes in the Liaohe Estuary from 1985 to 2023 and quantitatively evaluate the spatio-temporal pattern change characteristics of wetlands in the study area. The findings indicate that: (1) After feature selection, the accuracy of the model reached 0.88, and the separation of the selected feature set was good. (2) After sample migration, the overall accuracy of sample classification in the target year ranged from 87 to 94%, along with Kappa coefficients of 0.84 to 0.92, thereby ensuring the validity of classification sample migration. (3) SNIC-RF classification results showed better performance of wetland landscape. Compared with RF classification, the overall classification accuracy was increased by 0.69–5.82%, and the Kappa coefficient was increased by 0.0087–0.0751. (4) From 1985 to 2023, there has been a predominant trend of natural wetlands being converted into artificial wetlands. In recent years, this transition has occurred more gently. Finally, this study offers valuable insights into understanding changes and trends in the surface ecological environment of the Liaohe Estuary. The research method can be extended to other types of wetland classification and the comprehensive application of coastal wetland in hydrology, ecology, meteorology, soil, and environment can be further explored on the basis of this research, laying strong groundwork for shaping policies on ecological protection and restoration.

The adoption and growth of functional magnetic resonance imaging (fMRI) technology, especially through the use of Pearson’s correlation (PC) for constructing brain functional networks (BFN), has significantly advanced brain disease diagnostics by uncovering the brain’s operational mechanisms and offering biomarkers for early detection. However, the PC always tends to make for a dense BFN, which violates the biological prior. Therefore, in practice, researchers use hard-threshold to remove weak connection edges or introduce l1-norm as a regularization term to obtain sparse BFNs. However, these approaches neglect the spatial neighborhood information between regions of interest (ROIs), and ROI with closer distances has higher connectivity prospects than ROI with farther distances due to the principle of simple wiring costs in resent studies. Thus, we propose a neighborhood structure-guided BFN estimation method in this article. In detail, we figure the ROIs’ Euclidean distances and sort them. Then, we apply the K-nearest neighbor (KNN) to find out the top K neighbors closest to the current ROIs, where each ROI’s K neighbors are independent of each other. We establish the connection relationship between the ROIs and these K neighbors and construct the global topology adjacency matrix according to the binary network. Connect ROI nodes with k nearest neighbors using edges to generate an adjacency graph, forming an adjacency matrix. Based on adjacency matrix, PC calculates the correlation coefficient between ROIs connected by edges, and generates the BFN. With the purpose of evaluating the performance of the introduced method, we utilize the estimated BFN for distinguishing individuals with mild cognitive impairment (MCI) from the healthy ones. Experimental outcomes imply this method attains better classification performance than the baselines. Additionally, we compared it with the most commonly used time series methods in deep learning. Results of the performance of K-nearest neighbor-Pearson’s correlation (K-PC) has some advantage over deep learning.

The antiviral agent amantadine is frequently detected in seawater and marine organisms. Because of increasing concentrations, amantadine has become a contaminant of emerging concern. This compound has toxic effects on the brown algae Laminaria japonica. The effects of amantadine on the biological processes of L. japonica and the corresponding toxic mechanisms remain unclear. In this study, amantadine toxicity on L. japonica was investigated using histopathological and physiological characteristics combined with metabolomics analysis. Changes in metabolites were determined by untargeted metabolomics after exposure to 107 ng/L amantadine for 72 h. The catalase activity in the exposure group slightly increased, whereas the superoxide dismutase activity greatly decreased. An increase in the malondialdehyde concentration was observed after amantadine exposure, which suggested that lipid peroxidation and cell damage occurred. Metabolomics analysis showed that there were 406 differentially expressed metabolites after amantadine exposure. These were mainly phospholipids, amino acids, purines, and their derivatives. Inhibition of the glycerophospholipid metabolism affected the lipid bilayer and cell structure, which was aligned with changes in histological observation. Changes in amino acids led to perturbation of protein synthesis and induced oxidative stress through interference with glutathione metabolism and tyrosine metabolism. Amantadine also interfered with energy metabolism in L. japonica by disturbing the tricarboxylic acid cycle and purine metabolism. The results of this study provide new insights into the mechanism of amantadine toxicity on L. japonica.

In order to investigate the effect of different water filling times on the compression deformation of filled gangue, a large-scale crushed gangue deformation testing system was utilized, and two sets of gradient loading experiments were designed. Through rigorous experimental analysis, distinct patterns of deformation during loading and constant load stages are elucidated, with a particular focus on the influence of water filling timing. Quantitative assessment reveals that early water filling induces rapid gangue deformation, primarily during loading stages, while later water filling stages exhibit a heightened impact on constant load stages. Moreover, the study identifies a stepped deformation phenomenon attributed to the irregularities in crushed gangue particles, shedding light on the underlying mechanisms governing gangue behavior under varying water filling conditions. Notably, an in-depth analysis of energy consumption patterns underscores the dominant role of strain, especially in later water filling stages, significantly influencing deformation characteristics. The study further explores the implications of water filling timing on mining subsidence effects, offering quantitative insights into the stability of gangue backfilling. Under the action of the cumulative deformation and concentrated filling effect, the equivalent filling height is slightly higher than that of the early water filling state, but this trend weakens with the increase of mining height. The conclusions of this study can provide experimental data for stability analysis of crushed gangue filling the abandoned mines with different water filling timing.

The corrosion of steel stirrups is recognized as a significant contributing factor to shear deterioration in reinforced concrete (RC) structures, leading to detrimental effects on structural performance and potential early failures during service. To investigate the effect of corrosion levels on the shear behavior of RC beams, a series of three-point bending tests were conducted in this study. Furthermore, finite element analyses were employed to duplicate the shear behavior and failure modes observed in the experiments. The numerical outcomes are aligned with experimental results, confirming the validity of the developed constitutive models. The findings reveal that a low corrosion level (5%) in steel stirrups exhibits a limited impact on the overall structural shear capacity (-4%-0.9%). However, a higher corrosion level (12%) in stirrups induces a more pronounced reduction in structural shear capacity. This reduction is particularly prominent in scenarios involving a high shear span-to-depth (av/d) ratio. The developed finite element model, incorporating comprehensive constitutive models for individual components, offers engineers a prospective approach for forecasting the long-term shear performance of corroded RC beams.

Carbon fiber-reinforced polymer (CFRP) is attractive to serve as reinforcements for concrete structures under harsh environmental conditions. Previous studies show that strip-shaped CFRP stirrups are satisfactory to replace conventional steel stirrups for concrete beams under shear, but the shear resistance mechanism of the strip-shape CFRP stirrups is not well understood. To fill this research gap, this study conducts a comparative analysis to examine the effects of different types of stirrups (CFRP or steel) on the distribution of shear cracks and the variation in shear resistance components of concrete beams with varying shear span-depth (a/d) ratios. A digital image correlation (DIC) technique is employed to capture the shear crack development of the beams. The results demonstrate that the strip-shaped CFRP stirrups (designed based on the principle of equal stiffness with steel stirrups) effectively restrain the propagation of individual shear crack, particularly at a large shear span (a/d=3.5). This enhanced crack restraint leads to a notable reduction in crack width and a significant increase in shear resistance component by 37.5% in the ultimate state when the strip-shaped CFRP stirrups are employed, compared to their steel stirrup counterparts at the same a/d ratio. These findings can facilitate the design and applications of concrete beams with CFRP stirrups.

To tackle the challenge of extracting residual coal resources in Zhangzhao Coal Mine while preventing floor water inrush, a strip filling mining method has been proposed. A two-step mining approach was designed to ensure roof stability and avoid floor water inrush. The first step involves mining and filling at 15 m intervals, leaving a 20 m strip coal pillar. In the second step, a 20 m strip coal pillar is mined and filled at intervals. To meet the filling mining requirements, tailings and industrial slag are used to create the filling body, designed using a paste ratio test. The optimal ratio for silt has been determined to be 1:5, with a mass concentration of 70 %. Simulation tests were conducted to determine the dynamic failure development of the floor under different advancing footage. The self-designed pressurized water sac was used in the simulation experiment, and the results showed that maximum floor damage occurred at 130 m. Additionally, monitoring stations were installed during mining to track the failure depth of the floor. The research revealed that filling mining significantly reduces the failure depth of the floor and prevents water bursting passages, demonstrating the potential of this method for use under similar conditions. This study provides useful references and recommendations for future mining efforts.

ObjectiveTo determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles.MethodsRetrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes.ResultsIn analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5–8.0) vs. 8.3 (7.0–10.0) mm, p

Messenger ribonucleic acid (mRNA) has emerged as a promising molecular preventive and therapeutic approach that opens new avenues for healthcare. Although the use of delivery systems, especially lipid nanoparticles (LNPs), greatly improves the efficiency and stability of mRNA, mRNA tends to accumulate in the liver and hardly penetrates physiological barriers to reach the target site after intravenous injection. Hence, the rational design of targeting strategies aimed at directing mRNA to specific tissues and cells remains an enormous challenge in mRNA therapy. High-throughput screening (HTS) is a cutting-edge targeted technique capable of synthesizing chemical compound libraries for the large-scale experiments to validate the efficiency of mRNA delivery system. In this review, we firstly provide an overview of conventional low-throughput targeting strategies. Then the latest advancements in HTS techniques for mRNA targeted delivery, encompassing optimizing structures of large-scale delivery vehicles and developing large-scale surface ligands, as well as the applications of HTS techniques in extrahepatic systemic diseases are comprehensively summarized. Moreover, we illustrate the selection of administration routes for targeted mRNA delivery. Finally, challenges in the field and potential solutions to tackle them are proposed, offering insights for future development toward mRNA targeted therapy.

PurposeQuantitative computed tomography (CT) analysis is an important method for diagnosis and severity evaluation of lung diseases. However, the association between CT-derived biomarkers and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear. We aimed to investigate its potential in predicting COPD exacerbations.MethodsPatients with COPD were consecutively enrolled, and their data were analyzed in this retrospective study. Body composition and thoracic abnormalities were analyzed from chest CT scans. Logistic regression analysis was performed to identify independent risk factors of exacerbation. Based on 2-year follow-up data, the deep learning system (DLS) was developed to predict future exacerbations. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic performance. Finally, the survival analysis was performed to further evaluate the potential of the DLS in risk stratification.ResultsA total of 1,150 eligible patients were included and followed up for 2 years. Multivariate analysis revealed that CT-derived high affected lung volume/total lung capacity (ALV/TLC) ratio, high visceral adipose tissue area (VAT), and low pectoralis muscle cross-sectional area (CSA) were independent risk factors causing COPD exacerbations. The DLS outperformed exacerbation history and the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, with an area under the ROC (AUC) value of 0.88 (95%CI, 0.82–0.92) in the internal cohort and 0.86 (95%CI, 0.81–0.89) in the external cohort. The DeLong test revealed significance between this system and conventional scores in the test cohorts (p

Mapping coastal wetlands' spatial distribution and spatiotemporal dynamics is crucial for ecological conservation and restoration efforts. However, the high hydrological dynamics and steep environmental gradients pose challenges for precise mapping. This study developed a new method for mapping coastal wetlands using time-series remote sensing images and a deep learning model. Precise mapping and change analysis were conducted in the Liaohe Estuary Reserve in 2017 and 2022. The results demonstrated the superiority of Temporal Optimize Features (TOFs) in feature importance and classification accuracy. Incorporating TOFs into the ResNet model effectively combined temporal and spatial information, enhancing coastal wetland mapping accuracy. Comparative analysis revealed ecological restoration trends, emphasizing artificial restoration's predominant role in salt marsh vegetation rehabilitation. These findings provide essential technical support for coastal wetland ecosystem monitoring and contribute to the study of sustainability under global climate change.

In this paper, foam concrete is modified using graphite and carbon fiber as absorbents. The mechanical properties are analyzed in conjunction with hydration products, pore size distribution based on XCT test. Additionally, the resistivity, complex permittivity and complex permeability are tested. The results demonstrate that carbon fiber enhances the proportion of pores with diameters less than 200 μm in foam concrete, thereby significantly enhancing its flexural strength. Furthermore, incorporating graphite helps offset the initial retardation of sulfoaluminate cement hydration induced by carbon fibers, leading to an increase in the average pore size and a reduction in compressive strength. The incorporation of carbon fibers at a concentration of 0.6 wt% achieves the percolation threshold, akin to scenarios with singular fiber incorporation. Exceeding 2 wt% graphite content results in negligible influence on the conductivity. The synergistic integration of graphite and carbon fibers significantly improves the electromagnetic wave absorption performance of the composite. At a thickness of 6 mm, the material exhibits an effective bandwidth where the reflection loss is less than −10 dB, extending up to 2.5 GHz, which constitutes 52.08 % of the tested frequency spectrum.

In recent years, ceramic membranes have received widespread focus in the area of liquid separation because of their high permeability, strong hydrophilicity, and good chemical stability. However, in practical applications, the surface of ceramic membranes is prone to be contaminated, which degrades the permeation flux of ceramic membranes during the separation process. Inspired by mussels, we imitate the biomimetic mineralization process to prepare a ceramic membrane of nano–silica on the pre-modified zirconia surface by co-deposited polydopamine/polyethyleneimine. The modified ceramic membranes were utilized for the purpose of oil–water separation. Separation performance has been tested using a disc ceramic membrane dynamic filtration device. The outcomes revealed an enhanced permeability in the modified membrane, measuring as 159 L m−2 h−1 bar−1, surpassing the separation flux of the unmodified membrane, which was 104 L m−2 h−1 bar−1. The permeation performance of the modified membrane was increased to 1.5 times. Modified ceramic membranes are highly resistant to fouling. From the beginning to the end of separation process, the oil rejection rate of the modified ceramic membrane is always higher than 99%. After a 2 h oil–water separation test run, modified ceramic membrane permeate flux can be restored to 91% after cleaning. It has an enormous capacity for application in the area of oil–water separation.