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Abstract Background Trastuzumab, a monoclonal antibody for breast cancer, faces global accessibility challenges, primarily due to high costs. This study examines how changes in medical insurance policies and price adjustments influence Trastuzumab utilization in China, focusing on implementation challenges and their impact on drug accessibility and affordability. Methods This retrospective study investigated Trastuzumab utilization among HER2-positive breast cancer patients at a tertiary hospital from May 2013 to December 2022 in JX, a prefecture-level city in eastern China. Patients were stratified based on their CerbB2 indicator, because those with a 2 + CerbB2 status require further FISH testing to confirm Trastuzumab eligibility. We analyzed the utilization rates of both FISH test and Trastuzumab using logistic regressions, identifying factors that influence their usage. Results 766 patients were included. The utilization rate of Trastuzumab among patients with CerbB2 3+ rose from 40.40 to 77.94% in September 2017 following the expansion of insurance coverage, and further increased to 90.41% after a price reduction in 2020. The FISH test was not covered by health insurance, and it was not available in the local hospital until Trastuzumab became available in JX city. For patients with CerbB2 2+, the proportion undergoing the FISH test increased dramatically from 8.89 to 82.08% after the price reduction in 2020. The mere inclusion into basic medical insurance, regardless of insurance types, significantly increased the utilization of Trastuzumab and the FISH test. However, rural patients in JX city are still facing financial burdens with Trastuzumab's out-of-pocket cost accounting for 62.9% of their annual disposable income in 2020. Conclusions Our findings indicate that insurance coverage and price reduction significantly increased Trastuzumab utilization. However, failure to improve the accessibility of the FISH test can pose challenges in enhancing the uptake of Trastuzumab among eligible patients. With the expiration of Trastuzumab's patent and the development of affordable biosimilars, there are now greater opportunities to enhance treatment access globally. These insights can inform policy makers of implementation guidance about providing financial support for breast cancer patients in other LMICs.

Abstract Background This prospective cohort study focused on the predictive value of frailty or pre-frailty assessed by Edmonton Frailty Scale (EFS) for postoperative delirium in spinal surgery patients. Methods The primary outcome measurement was postoperative delirium (POD) evaluated by Confusion Assessment Method at day 1, day 2, and day 3 after the surgery. Secondary outcomes included severity and duration of POD, severe postoperative pain measured by Faces Pain Scale-Revised. Patients scheduled for elective spinal surgery were enrolled and assessed for frailty by EFS before surgery. Demographic data, preoperative, intraoperative, and postoperative information were collected. Results 231 out of 325 patients were enrolled and analyzed in this study at last. The cohort with 36.8% being frail and 28.5% being vulnerable. Postoperative delirium was detected in 41 in 231 patients. Multivariate logistic regression analysis revealed that vulnerable to frailty (OR = 4.681, 95% CI: 1.199 to 18.271, P = 0.026), after adjusted duration of surgery more than 3 h, using flumazenil at the end of surgery, using butorphanol only in postoperative patient-controlled intravenous analgesia, moderate-to-severe pain at day 1 and 2, is a strong predictor of postoperative delirium. Frailty was associated with longer duration (frailty vs. fit, P = 0.364) and stronger severity of postoperative delirium in the first two days (P

Abstract Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS +/− ) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS +/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

Abstract Background Exposure of the hepatic artery is a fundamental step in many surgeries, during which iatrogenic hepatic artery injury may occur. Although the incidence of hepatic artery haemorrhage is low, its occurrence can lead to life-threatening haemorrhage. It is difficult and dangerous to accumulate clinical experience in laparoscopic hepatic artery repair in actual patients, and simulation training models for laparoscopic hepatic artery repair are currently lacking. In this study, a 3D printed model was designed to simulate the training curriculum for sudden hepatic artery haemorrhage, but whether training with the 3D printed model could yield superior skill improvement for surgeons remained to be determined. Methods A new 3D printed model was designed for this study. Surgeons from the General Surgery Department of Sir Run Run Shaw Hospital participated in this simulation training. The surgical performance of each model was compared, and the authenticity of the model was evaluated and mechanically tested. Results Experienced surgeons performed better on the 3D printed model. After repeated training, inexperienced surgeons showed significant improvement of their laparoscopic hepatic artery repair skills. The authenticity of the model was generally satisfactory, but shortcomings persisted in the mechanical testing of artery wall tearing, necessitating further improvement. Conclusions Few studies have investigated laparoscopic simulation training for sudden hepatic artery haemorrhage. This simulation model distinguishes surgeons with different levels of experience and allows those with less experience to improve their laparoscopic hepatic artery repair skills through training on the model.

Abstract Objective Empathy is crucial for patient health. The Balint group is a commonly used method for empathy training. However, the impact of Balint groups on empathy remains unclear. This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the impact of Balint groups on empathy training among medical and nursing students, as well as doctors and nurses. Methods This review involved searching multiple databases for relevant articles. Rigorous eligibility criteria were applied during the screening of titles and abstracts, and during the selection of records. Following a full-text eligibility evaluation, two reviewers independently extracted data from the final selection of studies, and a meta-analysis was conducted. The standardized mean difference (SMD) was calculated to assess the systematic outcomes. Results A total of 11 studies were included in this systematic review and meta-analysis. Participants in Balint groups demonstrated a significant increase in empathy than those in the control group (SMD = 1.46, 95% confidence interval [CI] 0.86–2.06; p

As Internet technology evolves, distance learning emerges as a pivotal mode of education. In music education, vocal teaching faces limitations in traditional face-to-face methods. This paper explores the advantages of Internet-based remote vocal music teaching and proposes a new mode leveraging an online platform, multimedia technology, and real-time interaction. The study assesses its impact on theoretical knowledge, vocal skills, singing proficiency, satisfaction, and improvement. Results demonstrate the effectiveness of Internet-based remote teaching, overcoming geographical barriers and providing flexible learning opportunities. Multimedia tools enhance skill demonstration, making learning more intuitive. The study reveals that Internet distance vocal teaching rivals traditional methods in improving singing skills and outperforms in teaching music theory. Moreover, students express higher satisfaction with this innovative approach, establishing it as a promising mode in vocal music education.

Ceramides, formed by the dehydration of long-chain fatty acids with phytosphingosine and its derivatives, are widely used in skincare, cosmetics, and pharmaceuticals. Due to the exceedingly low concentration of phytosphingosine in plant seeds, relying on the extraction method is highly challenging. Currently, the primary method for obtaining phytosphingosine is the deacetylation of tetraacetyl phytosphingosine (TAPS) derived from fermentation. Wickerhamomyces ciferrii, an unconventional yeast from the pods of Dipteryx odorata, is the only known microorganism capable of naturally secreting TAPS, which is of great industrial value. In recent years, research and applications focused on modifying W. ciferrii for TAPS overproduction have increased rapidly. This review first describes the discovery history, applications, microbial synthesis pathway of TAPS. Research progress in using haploid breeding, mutagenesis breeding, and metabolic engineering to improve TAPS production is then summarized. In addition, the future prospects of TAPS production using the W. ciferrii platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future researches are also emphasized.

Abstract Background Chemotherapy remains the standard first-line treatment for pancreatic adenocarcinoma, but with limited efficacy. We aimed to explore the feasibility of adding the PARP inhibitor fuzuloparib to mFOLFIRINOX in the locally advanced/metastatic (LA/M) setting. Methods This was the dose-escalation and -expansion, phase 1b portion of a phase 1b/2 study. Patients were given oral fuzuloparib at escalating doses starting at 30 mg twice daily (BID) plus intravenous mFOLFIRINOX q2w for 8–12 cycles, followed by maintenance fuzuloparib at 150 mg BID. Cohorts at the maximal tolerated dose (MTD) and lower dose of fuzuloparib were expanded. Primary endpoints were dose-limiting toxicity (DLT), MTD, and recommended phase 2 dose (RP2D). Results As of data cutoff on Jan 15, 2023, 39 patients were recruited. 12 patients were enrolled during dose escalation (30 mg [n = 4]; 60 mg [n = 6]; 100 mg [n = 2]). DLT occurred in 1 patient in 60 mg cohort and 1 patient in 100 mg cohort. 60 mg BID was determined to be the MTD, and then 60 and 30 mg cohorts were expanded to 22 and 15 patients, respectively. The most common grade ≥ 3 treatment-related adverse events were hematologic toxicities. Efficacy in 60 mg cohort seemed to be most favorable, with an objective response rate of 50.0% (95% CI, 26.0–74.0) and disease control rate of 94.4% (95% CI, 72.7–99.9). Conclusions First-line fuzuloparib plus mFOLFIRINOX followed by maintenance fuzuloparib was generally safe and showed encouraging anti-tumor activity in patients with LA/M pancreatic adenocarcinoma. The RP2D of fuzuloparib combination was 60 mg BID. Trial registration ClinicalTrials.gov, NCT04228601.

Abstract Background SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap. Methods Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs. Results SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients. Conclusion This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.

Listeria monocytogenes is capable of forming biofilms on the food contact surfaces, increasing the risk of food contamination by this pathogen. The disinfectant benzalkonium chloride (BC) is commonly used to control L. monocytogenes in the food industry. This study aimed to investigate effects of BC on L. monocytogenes biofilms. Biofilm biomass was measured by the microplate method with crystal violet staining. Results from the broth microdilution method showed that the minimum inhibitory concentration (MIC) of BC against L. monocytogenes 10403S was 8 μg.mL-1. Sub-MICs of BC inhibited the biofilm formation and lethal concentrations of BC removed mature biofilms of L. monocytogenes 10403S. The presence of BC reduced extracellular proteins and exopolysaccharides in biofilms. Additionally, upregulation of quorum sensing gene luxS and agrBDCA and downregulation of flagellum motility genes flaA, motA, and motB were observed in the presence of BC. The BC disinfectant has an excellent anti-biofilm activity against L. monocytogenes.

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) has become a routine endoscopic procedure that is essential for diagnosing and managing various conditions, including gallstone extraction and the treatment of bile duct and pancreatic tumors. Despite its efficacy, post-ERCP infections – particularly those caused by carbapenem-resistant Enterobacterales (CRE) – present significant risks. These risks highlight the need for accurate predictive models to enhance postprocedural care, reduce the mortality risk associated with post-ERCP CRE sepsis, and improve patient outcomes in the context of increasing antibiotic resistance. Objective This study aimed to examine the risk factors for 30-day mortality in patients with CRE sepsis following ERCP and to develop a nomogram for accurately predicting 30-day mortality risk. Methods Data from 195 patients who experienced post-ERCP CRE sepsis between January 2010 and December 2022 were analyzed. Variable selection was optimized via the least absolute shrinkage and selection operator (LASSO) regression model. Multivariate logistic regression analysis was then employed to develop a predictive model, which was evaluated in terms of discrimination, calibration, and clinical utility. Internal validation was achieved through bootstrapping. Results The nomogram included the following predictors: age > 80 years (hazard ratio [HR] 2.61), intensive care unit (ICU) admission within 90 days prior to ERCP (HR 2.64), hypoproteinemia (HR 4.55), quick Pitt bacteremia score ≥ 2 (HR 2.61), post-ERCP pancreatitis (HR 2.52), inappropriate empirical therapy (HR 3.48), delayed definitive therapy (HR 2.64), and short treatment duration (

Abstract Carbon materials with defect-rich structure are highly demanded for various electrochemical scenes, but encountering a conflict with the deteriorative intrinsic conductivity. Herein, we build a highway-mediated nanoarchitecture that consists of the ordered pseudographitic nanodomains among disordered highly nitrogen-doped segments through a supramolecular self-assembly strategy. The “order-in-disorder” nanosheet-like carbon obtained at 800 °C (O/D NSLC-800) achieves a tradeoff with high defect degree (21.9 at% of doped nitrogen) and compensated electrical conductivity simultaneously. As expected, symmetrical O/D NSLC-800 electrodes exhibit superior capacitive deionization (CDI) performance, including brackish water desalination (≈82 mgNaCl g−1 at a cell voltage of 1.6 V in a 1000 mg L−1 NaCl solution) and reusage of actual refining circulating cooling water, outperforming most of the reported state-of-the-art CDI electrodes. The implanted pseudographitic nanodomains lower the resistance and activation energy of charge transfer, which motivates the synergy of hosting sites of multiple nitrogen configurations. Our findings shed light on electrically conductive nanoarchitecture design of defect-rich materials for advanced electrochemical applications based on molecular-level modulation.

As an important part of rotating machinery, heat generation due to friction is inevitable during the rotating process of bearings. A large amount of heat causes the temperature of lubricating oil to increase, viscosity of lubricating oil to decrease, and lubricating performance decreases. Addressing the issue of inadequate lubrication between the rolling element and raceway due to increased lubricating oil temperature, this study focuses on full-ceramic ball bearings. It examines the impact of temperature fluctuations on the bearing's lubrication condition and investigates the vibration characteristics of the full-ceramic bearing. The variation in the viscosity of lubricating oil with respect to temperature is measured via a rotary viscometer. A dynamic model of the silicon nitride full-ceramic ball bearing, which considers the effects of elastohydrodynamic lubrication, is established. The impacts of changes in lubricating oil viscosity due to different temperatures on oil film pressure, oil film thickness, and bearing vibration are analyzed and then compared with experimental data. It is observed that under conditions of constant load and speed, the film thickness of the lubricating oil decreases as the viscosity decreases. Additionally, the second peak value of oil film pressure is reduced with the declining viscosity of the lubricating oil. As the viscosity decreases, the vibration of the bearing increases. The amplitude discrepancy between the simulated vibration signal and experimental vibration signal of the full-ceramic bearing is found to be less than 10 %, verifying the validity of the dynamic model.

With the rapid development of the economy and changes in dietary structure, there is an excessive intake of high sugar and high-fat foods. To address this issue, in this study, we grafted palmitic acid onto CNC in the form of ester groups and evaluated its adsorption performance. Research had found that among these three methods, the CDI catalytic method can successfully obtain esterification modified CNC while also taking into account its environmentally friendly and pollution-free characteristics. Compared with CNC, its adsorption capacity for oil had increased, with the maximum adsorption capacity increasing from 35.80 g/g to 46.91 g/g. Meanwhile, the degree of esterification substitution of esterification modified CNC was measured, and the result was 0.03. Especially, after adding CNC-PA, the hydrolysis of fat was significantly reduced during the simulated digestion in vitro, whilst the absorption of fat in the intestine was significantly inhibited. In vivo testing also confirmed that consuming a diet containing CNC-PA significantly reduced elevated levels of triglycerides (TG) compared to the high-fat control group while long-term feeding of a diet containing CNC-PA reduced weight and fat accumulation.

The 2A12 aluminum alloy, renowned for its exceptional mechanical properties, encounters significant limitations in applications involving abrasive environments or frequent contact with other surfaces due to its inadequate wear resistance. This shortcoming substantially reduces the service life of components and escalate maintenance costs, highlighting the urgent need for advanced surface modification techniques. This study meticulously investigates the influence of nanoceramic particle size and content on the wear resistance of micro-arc oxidation (MAO) coatings, a surface modification technique renowned for forming dense, adherent ceramic layers on aluminum alloys. The systematic experimentation revealed that the incorporation of 150 nm α-Al2O3 nanoparticles into the MAO matrix achieves an optimal dispersion, leading to a substantial enhancement in wear resistance. The sample with a 5 g/L concentration of 150 nm α-Al2O3 nanoparticles doping in the MAO electrolyte demonstrated the lowest mass loss, underscoring its enhanced wear resistance. The enhanced microstructure, enriched with hard ceramic phases such as α-Al2O3 and mullite, plays a pivotal role in withstanding wear. Moreover, this study identified that an optimal balance of surface roughness and coating thickness is essential for achieving enhanced wear resistance. The findings of this research provide a strategy for the design of wear-resistant coatings tailored for high-performance applications across aerospace, automotive, and general engineering industries. By optimizing the particle size and concentration in MAO coatings, this study paves the way for the development of durable materials capable of thriving in demanding environments, thereby extending the service life and reducing maintenance requirements of components.

In recent years, with rising concerns over food quality and safety, computer vision technology has gradually attracted attention and begun to be widely used in the field of food quality evaluation. Machine learning technologies such as artificial neural networks (ANN), convolutional neural networks (CNN), and support vector machines (SVM) allow automatic assessment and monitoring of food quality by training on large amounts of food images and related data. Particularly, with the development of deep learning, the computer is now able to more accurately recognize food features such as appearance, shape, and color, thereby allowing food classification, prediction and quality monitoring. In addition to its conventional application in food quality assessment, learning technologies also find application in more complex tasks such as defect detection, foreign object detection, and freshness assessment. These technologies not only improve the efficiency of food production and processing but also reduce errors caused by human factors, thereby ensuring food quality and safety. However, despite the significant progress in the application of learning technologies in food quality assessment, there are still challenges that need to be overcome. For instance, the high cost of acquiring and annotating food image datasets, as well as insufficient data quality and quantity, may affect the performance and generalization ability of models. Furthermore, the interpretability and transparency of models are important issues, especially when explaining or making decisions on food quality assessment results. Therefore, further research is needed to explore how to improve the quality and scale of datasets, optimize the robustness and interpretability of models, and develop more efficient and sustainable food quality assessment systems.

Abstract Exploring vegetation dynamics in arid areas and their responses to different natural and anthropogenic factors is critical for understanding ecosystems. Based on the monthly MOD13Q1 (250 m) remote sensing data from 2000 to 2019, this study analyzed spatio-temporal changes in vegetation cover in the Aksu River Basin and predicted future change trends using one-dimensional linear regression, the Mann–Kendall test, and the Hurst index. Quantitative assessment of the magnitude of anthropogenic and natural drivers was performed using the Geodetector model. Eleven natural and anthropogenic factors were quantified and analyzed within five time periods. The influence of the driving factors on the changes in the normalized difference vegetation index (NDVI) in each period was calculated and analyzed. Four main results were found. (1) The overall vegetation cover in the region significantly grew from 2000 to 2019. The vegetation cover changes were dominated by expected future improvements, with a Hurst index average of 0.45. (2) Land use type, soil moisture, surface temperature, and potential vapor dispersion were the main drivers of NDVI changes, with annual average q-values above 0.2. (3) The driving effect of two-factor interactions was significantly greater than that of single factors, especially land use type interacts with other factors to a greater extent on vegetation cover. (4) The magnitude of the interaction between soil moisture and potential vapor dispersion and the magnitude of the interaction between anthropogenic factors and other factors showed an obvious increasing trend. Current soil moisture and human activities had a positive influence on the growth of vegetation in the area. The findings of this study are important for ecological monitoring and security as well as land desertification control.

The core-shell structure Fe3O4@C magnetic nanoparticles were synthesized with superparamagnetic Fe3O4 nanosphere as a magnetic core, and soluble starch resin as a carbon source via a solvothermal method. Silica-iron oxide and Fe3O4@C carriers with a core-shell structure were prepared by carbonization of organic material on the surface of Fe3O4 nanoparticles, Fe3O4@C supported Pd were processed into magnetic nano-catalysts with core-shell structure, and their catalytic properties were investigated. The resulting environmentally friendly magnetic material can be used to degrade dye wastewater. The structure of magnetic nanoparticles was characterized using TEM, XRD and VSM. The effects of preparation conditions in the structure of the Fe3O4@C magnetic nanoparticles were taken out. The results indicate that from XRD, the magnetic nano particles Fe3O4@C synthesized of carbon sources have amorphous carbon diffraction peak except for all the characteristic peaks of Fe3O4. The saturation magnetization Fe3O4, Fe3O4@SiO2 and Fe3O4@C – 59.14 emu/g, 49.12 emu/g and 27.95 emu/g, respectively.

IntroductionWearable exoskeletons are emerging technologies for providing movement assistance and rehabilitation for people with motor disorders. In this study, we focus on the specific gait pathology dropfoot, which is common after a stroke. Dropfoot makes it difficult to achieve foot clearance during swing and heel contact at early stance and often necessitates compensatory movements.MethodsWe developed a soft ankle exoskeleton consisting of actuation and transmission systems to assist two degrees of freedom simultaneously: dorsiflexion and eversion, then performed several proof-of-concept experiments on non-disabled persons. The actuation system consists of two motors worn on a waist belt. The transmission system provides assistive force to the medial and lateral sides of the forefoot via Bowden cables. The coupling design enables variable assistance of dorsiflexion and inversion at the same time, and a force-free controller is proposed to compensate for device resistance. We first evaluated the performance of the exoskeleton in three seated movement tests: assisting dorsiflexion and eversion, controlling plantarflexion, and compensating for device resistance, then during walking tests. In all proof-of-concept experiments, dropfoot tendency was simulated by fastening a weight to the shoe over the lateral forefoot.ResultsIn the first two seated tests, errors between the target and the achieved ankle joint angles in two planes were low; errors of

PurposeThis meta-analysis aimed to compare the safety and efficacy of aspirin and indobufen in patients with coronary heart disease. The primary focus was on the incidence of cardiovascular events, bleeding events, and gastrointestinal reactions. Given the relatively limited research on indobufen, this study utilized aspirin as a control drug and employed meta-analysis to integrate existing clinical studies. The goal was to provide a reference for the clinical use of indobufen and to suggest directions for further largescale, multicenter prospective studies.MethodsThis review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a comprehensive search of the PubMed, EMBASE, WOS, and Cochrane Library databases to identify all relevant literature on indobufen. A total of nine trials met the inclusion criteria, encompassing seven randomized controlled trails (RCTs) and two retrospective studies. Categorical variables were analyzed using odds ratio and random effects models.ResultsThe meta-analysis included nine trials, comprising seven RCTs and two retrospective studies. The pooled results indicated that indobufen significantly reduced the incidence of minor bleeding events, and gastrointestinal discomfort compared to aspirin. However, both drugs had similar effects on the incidence of recurrent angina pectoris, myocardial infarction and mortality due to coronary heart disease.ConclusionIndobufen was associated with fewer gastrointestinal reactions and a low risk of bleeding, making it a viable option for patients with high-risk factors for bleeding and gastric ulcers. Despite this, indobufen's short history and limited evidence base compared to aspirin highlight the need for further research. Aspirin remains widely available, cost-effective, and the preferred drug for the primary and secondary prevention of cardiovascular and cerebrovascular diseases. Indobufen or other antiplatelet agents should only be considered when aspirin is not tolerated or contraindicated. Further clinical trials are necessary to determine whether indobufen can replace aspirin.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier [CRD42024523477].

Summary: Stress granules (SGs), membrane-less cellular organelles formed via liquid-liquid phase separation, are central to how cells adapt to various stress conditions, including endoplasmic reticulum stress, nutrient scarcity, and hypoxia. Recent studies have underscored a significant link between SGs and the process of tumorigenesis, highlighting that proteins, associated components, and signaling pathways that facilitate SG formation are often upregulated in cancer. SGs play a key role in enhancing tumor cell proliferation, invasion, and migration, while also inhibiting apoptosis, facilitating immune evasion, and driving metabolic reprogramming through multiple mechanisms. Furthermore, SGs have been identified as crucial elements in the development of resistance against chemotherapy, immunotherapy, and radiotherapy across a variety of cancer types. This review delves into the complex role of SGs in cancer development and resistance, bringing together the latest progress in the field and exploring new avenues for therapeutic intervention.

Optically spatial displacement and material modification hold great potential for the appealing applications in nanofabrication and reconfiguration of functional optical devices. Here, we propose and demonstrate a scheme to achieve simultaneous deformation and phase change in vanadium dioxide (VO2)/Si3N4/Au hybrid nanostructures by laser stimuli. Low triggering threshold and significant deformation characteristics of VO2, based on controllable phase transition, are demonstrated in microscale cantilevers. The plasmonic properties of the nanostructure array are further utilized to achieve a polarization-selective dynamic response. The persistence of deformation and dynamical optical modulation are further demonstrated. Such high-precision fabrication methods and non-contact reconfiguration methods are useful for future applications in dynamic optical manipulation.

Abstract Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

K subgroup of Avian leukemia virus (ALV-K), as the latest reported exogenous ALV subgroup, can cause severe immunosuppression and tumorigenesis in infected chickens and bring serious threats to the poultry. Culling the positive chickens from breeder flocks is the most effective measurement for controling its infection at present. To setup a specific and rapid method for detecting ALV-K, an immunochromatographic strip (ICS) based on colloidal gold nanoparticles and double monoclonal antibodies (MAbs) immunochemical reaction was successfully developed. The solution containing colloidal gold particles (colloidal 20 nm) was prepared by sodium citrate reduction, and the ascites MAbs against ALV-K were purified and identified. The antibody concentration of the colloidal gold-MAb complex reaction system was 9.6 μg/mL, and the optimum pH was 7.5. The optimum coating concentrations of the captured antibody and quality control antibody on the NC membrane were 1.2 mg/mL and 0.6 mg/mL, respectively. The results showed that the prepared ICS could specifically detect ALV-K and had no cross reaction with exogenous ALV-A/B/J strains. Its sensitivity was 64 TCID50/mL against ALV-K and 0.25 μg/mL against ALV-K gp85 protein. The ICS stored at 4 °C for 180 d, at 25 °C for 45 d, and at 37 °C for 15 d could stably detect ALV-K in the samples. In comparision detection of 128 clinical samples, the coincidence rates in cloacal swab samples, serum samples, egg albumen samples and tissue homogenate samples between the ICS and the commercial ALV p27 antigen ELISA kit were 100 %, 100 %, 96.7 % and 96.9 %, respectively; moreover, the prepared ICS in operations was simpler and more convenient. This study supplies a new specific and rapid method for detecting ALV-K in clinics. This is the first report on the application of nano-colloidal gold ICS in ALV-K differential detection.

Background: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. Methods: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. Results: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. Conclusions: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

This study aims to evaluate airborne transmission risk in university towns during the COVID-19 pandemic based on surveys of indoor environmental quality (IEQ). Both on-site measurements and questionnaire surveys were carried out in public buildings in university towns in Changsha, China. Air temperature, relative humidity, and CO2 concentration in one library, ten classrooms, eight canteens, seven restaurants, and sixteen malls were measured. 2220 valid questionnaires concerning occupants’ sensation on thermal environment, air movement, and indoor air quality were collected. A 3-level evaluation method of airborne transmission risk that is dependent on building type and indoor CO2 concentration was developed. Excessive CO2 concentration is found in library (1045 ppm), classrooms (1151 ppm), restaurants (1242 ppm), and malls (1057 ppm). The percentage time of “high risk” accounts for 18–100% in these buildings. The results reveal a serious problem: numerous public buildings in China and probably other resource limited countries are not basically prepared and equipped to cope with airborne transmission. This fact should be taken into account when developing guidelines and formulating mitigation measures. Real-time monitoring and displaying IEQ and thus the transmission risk level should be an important way to be widely implemented in public buildings.

Printed circuit boards present several challenges to the detection of defects, including targets of insufficient size and distribution, a high level of background noise, and a variety of complex types. These factors contribute to the difficulties encountered by PCB defect detection networks in accurately identifying defects. This paper proposes a less-parametric model, YOLO-RRL, based on the improved YOLOv8 architecture. The YOLO-RRL model incorporates four key improvement modules: The following modules have been incorporated into the proposed model: Robust Feature Downsampling (RFD), Reparameterised Generalised FPN (RepGFPN), Dynamic Upsampler (DySample), and Lightweight Asymmetric Detection Head (LADH-Head). The results of multiple performance metrics evaluation demonstrate that YOLO-RRL enhances the mean accuracy (mAP) by 2.2 percentage points to 95.2%, increases the frame rate (FPS) by 12%, and significantly reduces the number of parameters and the computational complexity, thereby achieving a balance between performance and efficiency. Two datasets, NEU-DET and APSPC, were employed to evaluate the performance of YOLO-RRL. The results indicate that YOLO-RRL exhibits good adaptability. In comparison to existing mainstream inspection models, YOLO-RRL is also more advanced. The YOLO-RRL model is capable of significantly improving production quality and reducing production costs in practical applications while also extending the scope of the inspection system to a wide range of industrial applications.

The control system of PMa-SynRMs (Permanent Magnet-assisted Synchronous Reluctance Machines) exhibit susceptibility to external disturbances, thereby emphasizing the utmost significance of employing an observer to effectively observe and suppress system disturbances. Meanwhile, disturbances in load are sensitive to control system noise, which may be introduced from current sensors, hardware circuit board systems, sensor-less control, and analog position sensors. To tackle these problems, this paper proposes an A-DESO (anti-disturbance extended state observer) to improve the dynamic performance, noise suppression, and robustness of PMa-SynRMs in both the constant torque and FW (flux weakening) regions. With the proposed A-DESO, lumped disturbance in torque could be detected, and speed could be extracted in position with unmeasurable noise. Thanks to the merits of the small observation error in the low-frequency region and the excellent anti-disturbance performance in the high-frequency region of the proposed A-DESO, the control of the PMa-SynRM features the advantages of a fast response and good noise immunity ability within the same observation error range. The proposed A-DESO presents a shorter convergence time and a better noise suppression ability, which leads to a better dynamic response of the PMa-SynRM when encountering an unknown load disturbance compared to the traditional ESO-based control, according to simulations and experiments.

The integration of advanced technologies is revolutionizing classrooms, significantly enhancing their intelligence, interactivity, and personalization. Central to this transformation are sensor technologies, which play pivotal roles. While numerous surveys summarize research progress in classrooms, few studies focus on the integration of sensor and AI technologies in developing smart classrooms. This systematic review classifies sensors used in smart classrooms and explores their current applications from both hardware and software perspectives. It delineates how different sensors enhance educational outcomes and the crucial role AI technologies play. The review highlights how sensor technology improves the physical classroom environment, monitors physiological and behavioral data, and is widely used to boost student engagements, manage attendance, and provide personalized learning experiences. Additionally, it shows that combining sensor software algorithms with AI technology not only enhances the data processing and analysis efficiency but also expands sensor capabilities, enriching their role in smart classrooms. The article also addresses challenges such as data privacy protection, cost, and algorithm optimization associated with emerging sensor technologies, proposing future research directions to advance educational sensor technologies.

Abstract The templating method holds great promise for fabricating surface nanopatterns. To enhance the manufacturing capabilities of complex surface nanopatterns, it is important to explore new modes of the templates beyond their conventional masking and molding modes. Here, we employed the metal-organic framework (MOF) microparticles assembled monolayer films as templates for metal electrodeposition and revealed a previously unidentified guiding growth mode enabling the precise growth of metallic films exclusively underneath the MOF microparticles. The guiding growth mode was induced by the fast ion transportation within the nanochannels of the MOF templates. The MOF template could be repeatedly used, allowing for the creation of identical metallic surface nanopatterns for multiple times on different substrates. The MOF template-guided electrochemical growth mode provided a robust route towards cost-effective fabrication of complex metallic surface nanopatterns with promising applications in metamaterials, plasmonics, and surface-enhanced Raman spectroscopy (SERS) sensing fields.

Abstract Identifying the primary site of metastatic cancer is critical to guiding the subsequent treatment. Approximately 3–9% of metastatic patients are diagnosed with cancer of unknown primary sites (CUP) even after a comprehensive diagnostic workup. However, a widely accepted molecular test is still not available. Here, we report a method that applies formalin-fixed, paraffin-embedded tissues to construct reduced representation bisulfite sequencing libraries (FFPE-RRBS). We then generate and systematically evaluate 28 molecular classifiers, built on four DNA methylation scoring methods and seven machine learning approaches, using the RRBS library dataset of 498 fresh-frozen tumor tissues from primary cancer patients. Among these classifiers, the beta value-based linear support vector (BELIVE) performs the best, achieving overall accuracies of 81-93% for identifying the primary sites in 215 metastatic patients using top-k predictions (k = 1, 2, 3). Coincidentally, BELIVE also successfully predicts the tissue of origin in 81-93% of CUP patients (n = 68).

To make the polyimide (PI) composite material having both heat resistance and magnetic permeability, Fe3O4/PI magnetic polyimide composite powder was synthesized by one-step solvothermal method. 4,4'-diaminodiphenyl ether (ODA) as monomers, ether anhydride polyamic acid (PAA) was designed and prepared by Fe3+ and polyimide precursor-polyamic acid triethylamine salt (PAAS) was reacted in a reactor, and the PI/Fe3O4 composite powders were synthesized under the condition of high temperature and high pressure. The obtained PI/Fe3O4 composite powders were analyzed by infrared spectroscopy, microscopic morphology and thermal properties. The morphology and structure of the samples were both characterized by scanning electron microscopy (SEM) and infrared spectroscopy (IR). The thermal properties of the composite microspheres were studied via thermogravimetric analysis (TGA) and the magnetic properties were determined by a vibrating sample magnetometer (VSM). The saturation magnetization decreases gradually, increasing the polyimide content, with a saturation magnetization of PI/Fe3O4 determined to be 20.29 emu/g.

Abstract Background The osteogenic differentiation capacity of periodontal mesenchymal stem cells (PDLSCs) can be influenced by different levels of static mechanical strain (SMS) in an inflammatory microenvironment. Long non-coding RNAs (lncRNAs) are involved in various physiological processes. However, the mechanisms by which lncRNAs regulate the osteogenic differentiation of PDLSCs remain unclear. Methods We investigated the responses of PDLSCs obtained from periodontitis patients and healthy people to 8% and 12%SMS. Gene microarray and bioinformatics analyses were implemented and identified lncRNA00638 as a target gene for the osteogenesis of PDLSCs from periodontitis patients under SMS. Competing endogenous RNA (ceRNA) network analysis was applied and predicted interactions among lncRNA00638, miRNA-424-5p, and fibroblast growth factor receptor 1 (FGFR1). Gene expression levels were regulated by lentiviral vectors. Cell Counting Kit-8 assays, alkaline phosphatase assays, and Alizarin Red S staining were used to examine the osteogenic potential. RT-qPCR and Western blot were performed to detect the expression levels of related genes and proteins. Results We found that 8% and 12% SMS exerted distinct effects on HPDLSCs and PPDLSCs, with 12% SMS having the most significant effect. By microarray analysis, we detected differentially expressed lncRNAs/mRNAs between 12% SMS strained and static PPDLSCs, among which lncRNA00638 was detected as a positive target gene to promote the osteogenic differentiation of PPDLSCs under SMS loading. Mechanistically, lncRNA00638 may act as a ceRNA for miR-424-5p to compete with FGFR1. In this process, lncRNA00638 and miR-424-5p suppress each other and form a network to regulate FGFR1. Conclusions Our findings demonstrate that the lncRNA00638/miRNA-424-5p/FGFR1 regulatory network is actively involved in the regulation of PDLSC osteogenic differentiation from periodontitis patients under SMS loading, which may provide evidence for optimizing orthodontic treatments in patients with periodontitis.

White Etching Layer (WEL) and Brown Etching Layer (BEL) always form on the surface of rails and bearings subjected to rolling cyclic contact stress. Because of the different properties between WEL/BEL and matrix, the cracks initiate and propagate easily, leading to failure ultimately. The WEL and BEL found on pearlite rail, have been widely investigated, but WEL and BEL on bainite rail and martensite bearing have not been further studied. Especially the BEL on martensite bearing raceways has rarely been reported. This study investigates the features of WEL and BEL found on martensite bearing raceway. The BEL locates in the middle of WEL and matrix, but its hardness values are the highest, which is different from the general results reported: WEL > BEL > matrix. The WEL is mainly consisted of austenite with coarse grains, ferrite and retained tempered martensite. The mainly composition of BEL is quenched martensite. Thermal effect is the main formation mechanism of the WEL and BEL in this study. BEL forms because the surface temperature exceeds Acm point, and then rapidly decreases. The formation of WEL may originate from two processes: (1) The austenitizing and slowly cooling process again of BEL; (2) The austenitizing and slowly cooling process of the matrix. WEL and BEL forming processes are closely related to the diffusion and redistribution of carbon. The contributory heat conduction and diffusion mechanism in the confined spaces of grease lubricated bearings have been also discussed in this study.

China’s rural residents have basically solved the problem of subsistence, but due to aging, the prevalence of sarcopenia (abbreviated as sarcopenia) has been increasing year by year, especially the skeletal muscle health of the rural older residents has not been sufficiently paid attention to, so analyses of the impact of income level on the skeletal muscle health of the older people in rural areas of China are of great practical significance. Based on the annual data of the China Health and Nutrition Survey (CHNS) in 2006, 2009, and 2011, we introduced the mediator variable of dietary knowledge and used the Probit model regression, mediation effect model, and instrumental variable regression to assess the skeletal muscle health status of the rural older people in China and explore the mechanism of the influence of the income level on the skeletal muscle health of the rural older residents in China. The primary objectives of this study were to evaluate the impact of income level on the skeletal muscle health status of older adults living in rural areas of China and to investigate the underlying mechanisms. By analyzing the findings of this study, our aim is to establish a correlation between the economic status and skeletal muscle health of older adults in rural communities, as well as elucidate the influence of income level and dietary knowledge on their skeletal muscle health. Through the attainment of these objectives, we hope to provide valuable insights and recommendations for enhancing skeletal muscle health among the rural older population in China. Based on our research findings, it can be inferred that there was a significant association between the financial status of rural older adults and their skeletal muscle health. Additionally, the prevalence of sarcopenia was lower among individuals with higher income levels, and there was a negative correlation between the prevalence of sarcopenia and the level of dietary knowledge among rural older individuals. The knowledge of dietary knowledge level of rural older people plays a mediating role in the income level and the prevalence of sarcopenia. Moreover, with the change in income level and the increase in age, the change in skeletal muscle health status showed obvious heterogeneity, in which the effect on the relatively younger (65–70 years old) samples was greater. Therefore, sustained income growth remains an effective way to improve the skeletal muscle health of older rural residents. At the same time, improving dietary knowledge and dietary quality among the older people is important in preventing a decline in muscle strength and physical function and in preventing the onset of sarcopenia.

Diabetic encephalopathy (DE) is a common central nervous system complication of diabetes mellitus without effective therapy currently. Recent studies have highlighted synaptic mitochondrial damages as a possible pathological basis for DE, but the underlying mechanisms remain unclear. Our previous work has revealed that phosphatidate phosphatase Lipin1, a critical enzyme involved with phospholipid synthesis, is closely related to the pathogenesis of DE. Here, we demonstrate that Lipin1 is significantly down-regulated in rat hippocampus of DE. Knock-down of Lipin1 within hippocampus of normal rats induces dysregulation of homeostasis in synaptic mitochondrial dynamics with an increase of mitochondrial fission and a decrease of fusion, then causes synaptic mitochondrial dysfunction, synaptic plasticity deficits as well as cognitive impairments, similar to that observed in response to chronic hyperglycemia exposure. In contrast, an up-regulation of Lipin1 within hippocampus in the DE model ameliorates this cascade of dysfunction. We also find that the effect of Lipin1 that regulating mitochondrial dynamics results from maintaining appropriate phospholipid components in the mitochondrial membrane. In conclusion, alterations in hippocampal Lipin1 contribute to hippocampal synaptic mitochondrial dysfunction and cognitive deficits observed in DE. Targeting Lipin1 might be a potential therapeutic strategy for the clinical treatment of DE.

ObjectiveTo examine the association between various sociodemographic factors with alcohol and tobacco use behaviors during the COVID-19 pandemic.MethodsParticipants from Ohio and Indiana were asked to participate in the 'Impact of COVID-19 on the Cancer Continuum Consortium' study (N = 32,989) from June-November 2020. Those who completed the survey and responded to key study questions were included (n = 5,374). Participants were asked about the frequency and type of alcohol and tobacco product used. Multivariable logistic regression was conducted to determine factors associated with the impact of COVID-19 on change in alcohol and/or tobacco use.ResultsMean age was 57 years old, 68% were female, 90% non-Hispanic white, 75% married, and 31% lived in rural counties. Out of 5,374 participants, 53% used alcohol-only (n = 2,833), 5% used tobacco-only (n = 255), 7% used both alcohol and tobacco (n = 395), and 35% used neither alcohol nor tobacco (n = 1,891). Urban county of residence (vs. rural) was associated with an increase in alcohol-use (p = 0.0001), change in alcohol products (p = 0.023), and an increase in tobacco use (p = 0.05). Among alcohol-only users, those who were younger (OR = 0.97), female (OR = 1.58), married (OR = 1.69), of high socioeconomic status (OR = 1.99), residing in urban counties (OR = 1.65), and had elevated financial (OR = 1.06) and employment concerns (OR = 1.28) were significantly more likely to report increased alcohol-use. Similarly, among tobacco users, those who were younger (OR = 0.97), female (OR = 2.79), married (OR = 2.16) or divorced (OR = 2.83), and had higher levels of neighborhood disadvantage (OR = 2.19) were significantly more likely to report increased tobacco-use.ConclusionsFindings suggest targeted intervention and prevention strategies for young, female participants with elevated financial and employment concerns during the COVID-19 pandemic are necessary to mitigate risks associated with higher odds of alcohol and tobacco use. Our findings on alcohol and tobacco use may be a result of the unique social and economic influence of the pandemic on women.