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The informatization of education is the key area of the current education reform. Physical exercise is not only a compulsory course in schools but also very important to people's health. With the outbreak of the COVID-19 epidemic, online courses have begun to appear frequently. With the gradual increase of various online learning platforms, digital platforms emerge as the times require, which lays the foundation for the provision of physical education online. The digital platform can make online physical education teaching more complete and efficient and gradually form an independent and efficient system. However, the development of digital-physical education platforms has not made a big breakthrough. In response to the above problems, this paper will conduct data analysis and research on the role and development of digital platforms in physical education based on the Internet of Things (IoT) technology. The research results showed that the Random Forest (RF) algorithm can achieve 99% accuracy in gesture recognition when the number of features is 4. This provided new methods and aids for physical education on digital platforms.

In this article, we discuss the significance of English in the internationalization of higher education and international student mobility, using Kachru's (1985) Three Circles Model of World English. As education is one of the major forms of migration (Liu-Farrer, 2022; Borlongan, 2023) in the so-called 'age of migration' (cf. de Haas, Castles, & Miller, 2020), more and more students are motivated to study abroad to complete their tertiary education. First, we discuss motivating factors both for the internationalization of higher education and international student mobility. Second, we point out how English has been playing a very central role in the internationalization of higher education institutions and international student mobility (Philipson, 2010; Jenkins, 2017) among these factors. Then, we present the dynamics of international student mobility by looking at their global flow, English-medium programs, and English language proficiency requirements. While Inner Circle countries are still the most attractive destinations for most international students, Expanding Circle countries, where English is not an institutionalized medium of instruction in higher education, also value English by expanding English-medium degree programs and requiring English proficiency test scores to admission. Finally, we end the article by reiterating the dominance and utility of English in the internationalization of higher education and international student mobility and its stable position as the language of educational migration.

Abstract The COVID-19 pandemic has led to a surge in medical waste generation, posing hazards to both the environment and global health. The impacts of the COVID-19 pandemic’s medical waste hazard may persist long after the pandemic itself subsides. Improper disposal of medical waste can contaminate environment, posing risks to ecosystems and public health. Discarded medical rubber gloves, for example, can become a source of infection, improper disposal of these gloves can escalate the spread of infectious diseases and increase the risk of transmission of the virus to the general public. This study proposes an innovative and sustainable method to reinforce cement mortar by adding recycled glove rubber as an additive to cement mortar to increase its resistance to impact loads. This study conducted uniaxial compression tests, separating hopkinson pressure bar (SHPB) experiments and SEM observations to evaluate the quasi-static compressive strength and dynamic stress of recycled rubber fiber mortar (RRFM) with varying recycled rubber fiber (RRF) contents (0, 1%, 2%, 3%). Strain curves, dynamic increase factor (DIF), energy absorption rules, failure modes, and microstructure of RRFM mixtures. The experimental results demonstrate that with the addition of RRF, the dynamic stress-strain curve flattens and the peak strain gradually increases. The RRFM sample shows stronger toughness. In comparison to regular cement mortar (NM), RRFM has a higher DIF and specific absorbed energy, a faster increase in dynamic compressive strength, and the ability to absorb more energy per unit volume. Under the same impact load, RRFM has fewer and smaller cracks than NM. Scanning electron microscopy (SEM) testing also observed that RRF formed a strong connection pattern with the cement mortar matrix.

Abstract Background Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow’s triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling. Results This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood. Conclusion Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow’s triad in the context of CVC.

Abstract Immune checkpoint blockade (ICB) is a promising cancer therapy; however, resistance frequently develops. To explore ICB resistance mechanisms, we develop Immunotherapy Resistance cell-cell Interaction Scanner (IRIS), a machine learning model aimed at identifying cell-type-specific tumor microenvironment ligand-receptor interactions relevant to ICB resistance. Applying IRIS to deconvolved transcriptomics data of the five largest melanoma ICB cohorts, we identify specific downregulated interactions, termed resistance downregulated interactions (RDI), as tumors develop resistance. These RDIs often involve chemokine signaling and offer a stronger predictive signal for ICB response compared to upregulated interactions or the state-of-the-art published transcriptomics biomarkers. Validation across multiple independent melanoma patient cohorts and modalities confirms that RDI activity is associated with CD8 + T cell infiltration and highly manifested in hot/brisk tumors. This study presents a strongly predictive ICB response biomarker, highlighting the key role of downregulating chemotaxis-associated ligand-receptor interactions in inhibiting lymphocyte infiltration in resistant tumors.

Abstract Background Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. Methods This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. Discussion Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. Trial registration Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Abstract Objective The objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs. Methods The study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed. Results Based on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P

Abstract Objectives Women exposed to occupational noise experience adverse pregnancy outcomes. Therefore, we initiated a large, population-based, cross-sectional study to further investigate the effects of occupational noise on hearing and blood pressure among female workers of childbearing age. Study design and setting A total of 6981 childbearing-aged female workers were selected for this cross-sectional study. Basic characteristics of participants were analyzed by comparing the exposed and control groups. Logistic regression models were employed to calculate the odds ratios (ORs) and 95% confidences intervals (CIs) for the associations of occupational noise with levels of hearing loss and blood pressure. The associations were further explored through stratification by age and duration of noise exposure. Results Compared with participants not exposed to occupational noise, increasing years of occupational noise exposure were independently associated with an elevated risk of hypertension after adjustment of age, industry classification, enterprise size and economic type. Compared to participants not exposed to occupational noise, only the prevalence of bilateral hearing loss was significantly higher after adjustments for age, industry classification, enterprise size and economic type. Compared with those with normal hearing, the ORs and 95% CIs were 1.97 (0.95–4.07), 2.22 (1.05–4.68) and 1.29 (1.06–1.57) for bilateral, unilateral and any ear hearing loss, respectively. Conclusions Occupational noise exposure is positively associated with both hypertension and bilateral hearing loss among female workers of childbearing age. Those exposed to occupational noise show an increased risk of hypertension after adjusting for potential confounders.

Objective To investigate the value of real-time tissue elastography (RTE) in evaluating donor liver quality and postoperative early allograft dysfunction (EAD) in liver transplantation patients. Methods A total of 58 patients who received liver transplantation in Organ Transplantation Center of our hospital from October 2020 to January 2022 were enrolled, and according to the recovery of liver function in the early stage after surgery, the patients were divided into EAD group and non-EAD group. The two groups were compared in terms of the indicators such as the routine ultrasound examination and RTE measurement of donor liver before liver transplantation, liver function and coagulation function of recipients before and after liver transplantation, and preoperative Model for End-Stage Liver Disease (MELD) score. The logistic regression analysis was performed for the indicators with significant differences, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC) and assess the performance of related factors. Results Compared with the non-EAD group, the EAD group had significantly higher liver fibrosis (LF) index of donor liver and MELD score of recipients (t=4.822, 2.902,P1.645 was a risk factor for EAD after liver transplantation, and the ROC curve analysis showed that donor liver LF index had an AUC of 0.840 in predicting EAD after surgery, with a sensitivity of 82.4%, a specificity of 73.2%, and a cut-off value of 1.645. Conclusion High LF index of donor liver before liver transplantation is a risk factor for EAD in recipients after liver transplantation, and RTE measurement for LF index of donor liver before li-ver transplantation has a certain value in assessing the quality of donor liver and predicting the onset of EAD.

Abstract Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

Abstract Background One of the challenges of physical training in extreme condition is frostbite, especially in Northeast China. In this study, we aimed to construct a risk prediction model for frostbite among soldiers in Northeast China, and verify its effect. Methods 698 participants were selected via convenience sampling from Northeast China from December 2021 to January 2022 (winter). They were randomly divided into a training set (N = 479) and a testing set (N = 202) in a ratio of 7:3. All participants completed a researcher-made questionnaire on frostbite. The prediction model was constructed through the use of Logistic regression analysis, which was used to predict the independent risk factors for frostbite formation and screen significant indicators. The model’s performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) to evaluate the prediction efficiency and goodness of fit. Results The incidence of frostbite in the training set was 19.83% (95 people), all of which were first-degree frostbite. Among them, frostbite in multiple parts was the most common (58.95%), followed by singular body parts like hands (24.21%), ears (11.58%) and feet (5.26%). Single factor logistic regression analyses showed that ambient temperature, ambient wind speed, outdoor stationary time, stationary status, and history of frostbite are independent risk factors that affect the occurrence of frostbite. Furthermore, we constructed the frostbite risk prediction model for soldiers in the northeastern region of China. The area under the receiver operating characteristic curve (AUC) for the risk of frostbite in the training set and testing set was 0.816 (95% CI, 0.770 ~ 0.862) and 0.787 (95% CI, 0.713 ~ 0.860), respectively. The Hosmer-Lemeshow test of the model showed χ 2 = 11.328 and P = 0.184 (> 0.05). The DCA curve indicated that most of the clinical net benefits of the model are greater than 0, demonstrating good clinical usefulness. Conclusion The constructed frostbite prediction model can effectively identify soldiers with a higher risk of frostbite. It provided theoretical support for commanders to take preventive measures to reduce the incidence of frostbite among soldiers and was of great clinical guiding significance.

Powder bed fusion titanium alloys， as an important metallic material， are widely used in aerospace， medical devices and automotive industries.However， due to their unique material properties and processing methods， surface quality and performance remainone of key issues that constrain their application.In this paper， the research progress on surface polishing techniques for powder bed fusion titanium alloys was reviewed.The advancements in chemical polishing， electrochemical polishing， plasma electrolytic polishing， laser polishing and mechanical polishing were introduced.These techniques have provided options for achieving surface quality and performance that meet various application needs for powder bed fusion titanium alloys.Additionally， the development of composite polishing technologies and related advancements were also prospected.

Abstract Background Ovarian cancer (OC) is the predominant primary tumor in the human reproductive system. Abnormal sialylation has a significant impact on tumor development, metastasis, immune evasion, angiogenesis, and treatment resistance. B4GALT5, a gene associated with sialylation, plays a crucial role in ovarian cancer, and may potentially affect clinicopathological characteristics and prognosis. Methods We conducted a comprehensive search across TIMER, GEPIA2, GeneMANIA, and Metascape to obtain transcription profiling data of ovarian cancer from The Cancer Genome Atlas (TCGA). The expression of B4GALT5 was test by immunohistochemistry. To investigate the impact of B4GALT5 on growth and programmed cell death in OC cells, we performed transwell assays and western blots. Results The presence of B4GALT5 was strongly associated with an unfavorable outcome in OC. B4GALT5 significantly promoted the proliferation of OC cells. Upon analyzing gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was discovered that B4GALT5 played a crucial role in the extracellular matrix, particularly in collagen-containing structures, and exhibited correlations with ECM-receptor interactions, transcriptional dysregulation in cancer, as well as the interleukin-1 receptor signaling pathway. Furthermore, there is a clear link between B4GALT5 and the tumor immune microenvironment in OC. Moreover, B4GALT5 exhibits favorable expression levels across various types of cancers, including CHOL, KIRC, STAD and UCES. Conclusion In conclusion, it is widely believed that B4GALT5 plays a pivotal role in the growth and progression of OC, with its heightened expression serving as an indicator of unfavorable outcomes. Moreover, B4GALT5 actively participates in shaping the cancer immune microenvironment within OC. This investigation has the potential to contribute significantly to a deeper understanding of the substantial involvement of B4GALT5 in human malignancies, particularly OCs.

Abstract Background The impact of weather on human health has been proven, but the impact of extreme weather events on cardiometabolic multimorbidity (CMM) needs to be urgently explored. Objectives Investigating the impact of extreme temperature, relative humidity (RH), and laboratory testing parameters at admission on adverse events in CMM hospitalizations. Designs Time-stratified case-crossover design. Methods A distributional lag nonlinear model with a time-stratified case-crossover design was used to explore the nonlinear lagged association between environmental factors and CMM. Subsequently, unbalanced data were processed by 1:2 propensity score matching (PSM) and conditional logistic regression was employed to analyze the association between laboratory indicators and unplanned readmissions for CMM. Finally, the previously identified environmental factors and relevant laboratory indicators were incorporated into different machine learning models to predict the risk of unplanned readmission for CMM. Results There are nonlinear associations and hysteresis effects between temperature, RH and hospital admissions for a variety of CMM. In addition, the risk of admission is higher under low temperature and high RH conditions with the addition of particulate matter (PM, PM2.5 and PM10) and O3_8h. The risk is greater for females and adults aged 65 and older. Compared with first quartile (Q1), the fourth quartile (Q4) had a higher association between serum calcium (HR = 1.3632, 95% CI: 1.0732 ~ 1.7334), serum creatinine (HR = 1.7987, 95% CI: 1.3528 ~ 2.3958), fasting plasma glucose (HR = 1.2579, 95% CI: 1.0839 ~ 1.4770), aspartate aminotransferase/ alanine aminotransferase ratio (HR = 2.3131, 95% CI: 1.9844 ~ 2.6418), alanine aminotransferase (HR = 1.7687, 95% CI: 1.2388 ~ 2.2986), and gamma-glutamyltransferase (HR = 1.4951, 95% CI: 1.2551 ~ 1.7351) were independently and positively associated with unplanned readmission for CMM. However, serum total bilirubin and High-Density Lipoprotein (HDL) showed negative correlations. After incorporating environmental factors and their lagged terms, eXtreme Gradient Boosting (XGBoost) demonstrated a more prominent predictive performance for unplanned readmission of CMM patients, with an average area under the receiver operating characteristic curve (AUC) of 0.767 (95% CI:0.7486 ~ 0.7854). Conclusions Extreme cold or wet weather is linked to worsened adverse health effects in female patients with CMM and in individuals aged 65 years and older. Moreover, meteorologic factors and environmental pollutants may elevate the likelihood of unplanned readmissions for CMM.

Abstract Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract Background With orthopedic surgery increasing year on year, the main challenges in bone drilling are thermal damage, mechanical damage, and drill skid. The need for new orthopedic drills that improve the quality of surgery is becoming more and more urgent. Methods Here, we report the skidding mechanism of drills at a wide range of inclination angle and propose two crescent drills (CDTI and CDTII). The anti-skid performance and drilling damage of the crescent drills were analyzed for the first time. Inclined bone drilling experiments were carried out with crescent drills and twist drills and real-time drilling forces and temperatures were collected. Results The crescent drills are significantly better than the twist drill in terms of anti-skid, reducing skidding forces, thrust forces and temperature. The highest temperature is generated close to the upper surface of the workpiece rather than at the hole exit. Finally, the longer crescent edge with a small and negative polar angle increases the rake angle of the cutting edge and reduces thrust forces but increases skidding force and temperature. This study can promote the development of high-quality orthopedic surgery and the development of new bone drilling tools. Conclusion The crescent drills did not skid and caused little drilling damage. In comparison, the CDTI performs better in reducing the skidding force, while the CDTII performs better in reducing the thrust force.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract Background Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation. The diagnosis of FCD is challenging. We generated a radiomics nomogram based on multiparametric magnetic resonance imaging (MRI) to diagnose FCD and identify laterality early. Methods Forty-three patients treated between July 2017 and May 2022 with histopathologically confirmed FCD were retrospectively enrolled. The contralateral unaffected hemispheres were included as the control group. Therefore, 86 ROIs were finally included. Using January 2021 as the time cutoff, those admitted after January 2021 were included in the hold-out set (n = 20). The remaining patients were separated randomly (8:2 ratio) into training (n = 55) and validation (n = 11) sets. All preoperative and postoperative MR images, including T1-weighted (T1w), T2-weighted (T2w), fluid-attenuated inversion recovery (FLAIR), and combined (T1w + T2w + FLAIR) images, were included. The least absolute shrinkage and selection operator (LASSO) was used to select features. Multivariable logistic regression analysis was used to develop the diagnosis model. The performance of the radiomic nomogram was evaluated with an area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration and clinical utility. Results The model-based radiomics features that were selected from combined sequences (T1w + T2w + FLAIR) had the highest performances in all models and showed better diagnostic performance than inexperienced radiologists in the training (AUCs: 0.847 VS. 0.664, p = 0.008), validation (AUC: 0.857 VS. 0.521, p = 0.155), and hold-out sets (AUCs: 0.828 VS. 0.571, p = 0.080). The positive values of NRI (0.402, 0.607, 0.424) and IDI (0.158, 0.264, 0.264) in the three sets indicated that the diagnostic performance of Model-Combined improved significantly. The radiomics nomogram fit well in calibration curves (p > 0.05), and decision curve analysis further confirmed the clinical usefulness of the nomogram. Additionally, the contrast (the radiomics feature) of the FCD lesions not only played a crucial role in the classifier but also had a significant correlation (r = -0.319, p

Abstract Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract Aims/Introduction The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. Materials and Methods The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet β‐cell function, insulin resistance and comprehensive management measures. Results Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0–4.0 years). The baseline HbA1c was 11.2% (IQR 9.2–12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3–6.1%]) in the half‐year course group and the highest in the 4‐year course group (9.0 [IQR 6.8%–11.3%]). Compared with the group with a disease duration 4 years group had a lower proportion of patients with HbA1c

Ectopic transplantation of the hand remains a rare, innovative yet valuable operation in select cases of trauma and amputation. We aim to describe a novel technique of complex hand reconstruction using a two‐stage ectopic implantation of the contralateral upper limb. A male patient with a near complete avulsion amputation of the right upper limb at the level of the mid‐forearm and a crushing injury to his left hand was admitted after a farming accident. The right palm was ectopically transplanted to the left lower limb and both upper limbs underwent debridement with vacuum assisted dressings (VACs). There was eventual dieback of the left thumb, ring and little finger with a large palmar soft tissue defect that was eventually reconstructed using segments of the ectopically transplanted limb in two separate operations. The patient made an uneventful postoperative recovery and managed to regain protective sensation and gross motor function of his reconstructed hand.

In order to clarify the differences of postharest quality and volatile substances of different tomato varieties, the volatile substances of different tomato varieties ('567' 'Provence' 'Youshi No.3' 'Warrior 808' 'Meiqi') were determined by gas chromatography-ion mobility spectroscopy (GC-IMS), and the quality indexes were discussed. '567' tomato fruit was round-shaped. The 'Provence' tomato was near-round and had the highest titrable acid content. 'Youshi No.3' tomato fruit was round-shaped, whose soluble solid content and fruit firmness was the highest. 'Warrior 808' tomato was a near-round fruit. 'Meiqi' tomato fruit was near-round, whose the skin color was the most shiny, which contained the most red color and the highest vitamin C content. A total of 57 volatile substances were detected in 5 varieties of tomato fruits, of which 51 volatile substances were identified, including 18 aldehydes, 11 esters, 8 ketones, 8 alcohols, 2 furans, 3 terpenes and 1 others. There were differences in the main volatiles of different varieties of tomatoes. The volatiles present in all five varieties of tomatoes were ethyl butyrate (apple flavour), trans-2-hexenal (green banana). Hexanol (fruity flavour), propionic acid (sour flavour), and hexyl acetate (fruity flavour) were the main odour substances of 'Meiqi' tomato. Basilene (tropical citrus flavour), ethyl acetyl propionate (fruity flavour), ethyl isobutyrate (sweet flavour) were the main odour substances of '567' tomato. And 2-methylbutyl acetate (sweet banana flavour) was the main odour substance of 'Provence' tomato. Moreover, (Z)-4-heptenal (creamy flavour) was the main odour substance of 'Warrior 808' tomato. Lastly, 1-octen-3-one (mushroom flavour) was the main odour substance of 'Youshi No.3' tomato. In light of this, the differences of postharvest quality of different varieties of tomato fruits were identified in this experiment, and gas chromatography-ion mobility spectroscopy can effectively evaluate the differences of volatile substances.

Introduction: Herbicide application is a highly efficiency method of weed control that boots agricultural output and assures food security. The development of novel herbicides focuses on improved bioactivity and new modes of action. The amino acid biosynthesis was validated as a promising novel mode of action for herbicidal compounds. However, the amino acid biosynthesis enzyme remains largely unexplored for herbicidal targets. Objectives: Serine hydroxymethyl transferase (SHMT) is an essential enzyme in the photorespiratory cycle. The study aims to explore Conyza canadensis SHMT1 (CcSHMT1) as a promising target for herbicide discovery. Methods: Structure determination of CcSHMT1 was resolved by X-ray crystallography. Virtual screening docking experiments were performed with Glide version 5.5. Novel derivatives of dimethyl 2-acetamido terephthalate were further designed, synthesized, and bioassay. The druggability of the inhibitor was evidenced by ultrastructural changes in mitochondria, in vivo and vitro enzyme activity assays, and genetics analysis. Results: CcSHMT1 has a typical PLP-dependent enzyme 3D structure. The dimethyl 2-acetamido terephthalate-containing compounds had herbicidal activity. Dimethyl 2-(2-(4-(2-(4-bromo-2-chlorophenoxy) acetyl)piperazin-1-yl)acetamido) terephthalate (Compound 9ay, EC50 = 193.8 g a.i./ ha) exhibited the highest herbicidal activity on tested weed among the synthesized compounds. Compound 9ay had no obvious adverse effect on the growth of maize and honeybees. Compound 9ay was verified to target CcSHMT1 as an herbicide candidate. Conclusion: A first-in-class CcSHMT1 inhibitor that could be developed as a potent herbicide with a new mode of action and provide an avenue for discovering novel inhibitors of pyridoxal-5-phosphate-dependent enzymes.

Background Chromosomal abnormalities are one of the common causes of birth defects, and karyotype analysis is still an important method for prenatal diagnosis of chromosomal abnormalities as well as an effective way to prevent and control birth defects. However, karyotype analysis, especially chromosomal image segmentation and classification mainly depends on manual work at present, which is laborious and time-consuming. As an emerging approach to karyotype analysis, it is of great significance to investigate the application value of artificial intelligence (AI) in prenatal chromosomal karyotype diagnosis. Objective To investigate the application effect and clinical value of AI in prenatal karyotype diagnosis. Methods A total of 1 000 pregnant women who received interventional prenatal diagnosis and karyotype analysis of amniotic fluid cells in the department of medical genetics and prenatal diagnosis of Wuxi Maternity and Child Health Care Hospital between 2020 and 2022 were selected as the study subjects. The karyotype analysis of all cases was performed using two-line mode, the results of the AI reading were reviewed by one geneticist in the first line, and another geneticist analyzed the karyotypes by Ikaros karyotype analysis workstation in the second line, the diagnostic results and time were recorded respectively. The final diagnosis of the samples were based on the manual review of the first line and the manual reading of the second line. Results Among the 1 000 amniotic fluid samples, 735 cases were diagnosed as normal karyotype, 233 cases as aneuploidy, 0 case as structural abnormality and 32 cases as mosaicism by AI. The numbers of normal karyotype, aneuploidy, structural abnormality and mosaicism assessed by AI-assisted geneticist were 689, 233, 45 and 33, which were completely consistent with those evaluated by geneticist using Ikaros system. Compared with AI-assisted geneticist, AI-based diagnosis had strong consistency (Kappa=0.895, 95%CI=0.866-0.924, P

Museums are traditionally considered public service settings with educational functions and practical learning resources for students. Early childhood teachers' intention to implement class visits to museums is still very low. This paper synthesizes the theory of planned behavior model (TPB) and core determinants of the technology acceptance model (TAM) to hypothesize an extended TPB model to explain preschool teachers' perceptions and intentions to implement museum visits. The results revealed that early childhood teachers' intention of implementing class visits to museums was significantly influenced by attitude, perceived usefulness, and perceived behavioral control. The implications of this study are provided.

Generative artificial intelligence (AI) is widely recognized as one of the most influential technologies for the future, having sparked a paradigm shift in scientific research. The field of education has also been greatly impacted by this transformative technology, with researchers exploring the applications of generative AI, particularly ChatGPT, in education. However, existing research primarily focuses on generating text from text, and there remains a relative scarcity of studies on leveraging multimodal generation capabilities to address key challenges in multimodal data supported instruction. In this article, we present a technical framework for generating Tang poetry situational videos, emphasizing the utilization of generative AI to address the need for multimedia teaching resources. Our framework comprises three main modules: textual situational comprehension, image creation, and video generation. Moreover, we have developed a situational video generation system that incorporates various technologies, including text-to-text generation models, text-to-image generation models, image interpolation, text-to-speech synthesis, and video synthesis. To ascertain the efficacy of the modules within the Tang poetry situational video generation system, we undertook a comparative analysis utilizing the prevalent text-to-image and text-to-video generation models. The empirical findings indicate that our approach is capable of generating images that exhibit greater semantic similarity with the poems, thereby enabling a better comprehension of the poem's connotations and its key components. Concurrently, the Tang poetry videos generated can significantly contribute to the reduction of cognitive load and the enhancement of understanding during the learning process. Our research showcases the potential of generative AI in the education field, specifically in the domain of multimodal teaching resources.

Abstract: Given the threat of fossil fuel depletion, it is essential to proactively strive for carbon neutrality and promote clean, low-carbon and efficient energy use. This study used ERA5 reanalysis data to assess wind energy resources in the Pacific Northwest region. By analyzing key indicators such as wind power density, effective wind speed occurrence, and energy level occurrence, climate statistics and Empirical Orthogonal Function analysis (EOF) were used to examine the spatial distribution and long-term trend of offshore wind energy resources in the Northwest Pacific. The results suggest that there are abundant wind energy resources in this region, which are beneficial for the development of offshore wind energy. The rich areas are the East China Sea, Taiwan islands and reefs in the South China Sea and east of Japan, with prevailing wind power density (500 ∼ 2500 W/m2) and effective wind speed occurrence (80–90%) and energy level occurrence (60% ∼ 90%). Offshore wind energy resources in the Pacific Northwest are more abundant in fall and winter than in summer. The time coefficient of the first mode shows that the offshore wind energy in the Northwest Pacific has no obvious change trend, and the wind energy resources are relatively stable.

ABSTRACT: α-Lactalbumin (α-lac), a natural food-sourced protein, exhibits high biocompatibility as delivery systems for small bioactive molecules or RNA. However, their potential clinical application as a delivery system is greatly limited due to the lack of targeting to desired tissues, such as tumors. Here, a delivery system/nanocarrier of nanotube (NT) was fabricated by the self-assembly of peptides hydrolyzed from α-lac. Among the loading of anti-tumor agents of doxorubicin (Dox) and siRNA, NTs were conjugated with the tLyp-1 peptide to specifically target the neuropilin 1 receptor, which exists on the membrane of MDA-MB-231 cancer cells. The micromorphology of NTs was not affected during the processes of loading and targeting modification. Additionally, no significant changes in the size and zeta potential of the tLyp-1/NTs/Dox/siRNA nanocarrier were observed when stored in phosphate buffered saline for 7 days, indicating outstanding stability. Moreover, both the cellular uptake efficiency and tumor accumulation effects of NTs on MDA-MB-231 breast cancer cells were significantly improved after modification with tLyp-1. The relative viability of MDA-MB-231 cells was decreased by 70.1% in vitro after treatment with tLyp-1/NTs/Dox/siRNA (5 μg/mL Dox). Finally, a synergistic anticancer effect of Dox and siRNA co-loaded in tLyp-1/NTs was achieved in the anticancer treatment of MDA-MB-231 tumor-bearing mice. These findings indicate that food-sourced protein α‑lac nanocarriers could be used for the co-delivery of bioactive molecules and RNA, achieving synergistic and efficient therapeutic effects.

Background and objective Neoantigen reactive T cell (NRT) has the ability to inhibit the growth of tumors expressing specific neoantigens. However, due to the difficult immune infiltration and the inhibition of tumor microenvironment, the therapeutic effect of NRT in solid tumors is limited. In this study, we designed NRT cells (7×19 NRT) that can express both interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19) in mouse lung cancer cells, and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells. Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma (LLC), prepared RNA vaccine, cultured NRT cells, constructed retroviral vectors encoding IL-7 and CCL19, transduced NRT cells and IL-7 and CCL19 were successfully expressed, and 7×19 NRT was successfully obtained. The anti-tumor effect was evaluated in vivo and in vitro in mice. Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19, achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice. The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment. In addition, both 7×19 NRT treatment and conventional NRT treatment were safe. Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19, which is a safe and effective genetic modification of NRT.

Abstract Considering the key role of myeloid cell differentiation—related genes in the tumor microenvironment (TME), we aimed to build a prognostic risk model using these genes for Lung adenocarcinoma (LUAD). The mRNA gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were downloaded as the training and validation sets. Then, “edgeR” R package was applied to screen out the differentially expressed genes (DEGs) and univariate cox regression, backward stepwise selection analyses were performed to construct a prognostic model for LUAD. ESTIMATE, TIMER, XCELL, CIBERSORT abs, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT algorithms were conducted to access the association of risk levels with the stromal and immune cell infiltration levels in LUAD. Six genes (F2RL1, PRKDC, TNFSF11, INHA, PLA2G3 and TUBB1) were utilized to construct the prognostic model. The risk model showed excellent prognostic performance for LUAD in both TCGA and GEO datasets. Also, compared to the low-risk patients, the high-risk patients had higher expression of immune checkpoint molecules and showed a lower IC50 value to the chemotherapy agents. Our findings provided a myeloid cell differentiation—related gene signature that could effectively predict prognosis and guide treatment strategies for LUAD patients.

Abstract Background Despite the use of targeted therapeutic approaches, T-cell acute lymphoblastic leukemia (T-ALL) is still associated with a high incidence of complications and a poor prognosis. Indisulam (also known as E7070), a newly identified molecular glue compound, has demonstrated increased therapeutic efficacy in several types of cancer through the rapid degradation of RBM39. This study aimed to evaluate the therapeutic potential of indisulam in T-ALL, elucidate its underlying mechanisms and explore the role of the RBM39 gene. Methods We verified the anticancer effects of indisulam in both in vivo and in vitro models. Additionally, the construction of RBM39-knockdown cell lines using shRNA confirmed that the malignant phenotype of T-ALL cells was dependent on RBM39. Through RNA sequencing, we identified indisulam-induced splicing anomalies, and proteomic analysis helped pinpoint protein changes caused by the drug. Comprehensive cross-analysis of these findings facilitated the identification of downstream effectors and subsequent validation of their functional roles. Results Indisulam has significant antineoplastic effects on T-ALL. It attenuates cell proliferation, promotes apoptosis and interferes with cell cycle progression in vitro while facilitating tumor remission in T-ALL in vivo models. This investigation provides evidence that the downregulation of RBM39 results in the restricted proliferation of T-ALL cells both in vitro and in vivo, suggesting that RBM39 is a potential target for T-ALL treatment. Indisulam’s efficacy is attributed to its ability to induce RBM39 degradation, causing widespread aberrant splicing and abnormal translation of the critical downstream effector protein, THOC1, ultimately leading to protein depletion. Moreover, the presence of DCAF15 is regarded as critical for the effectiveness of indisulam, and its absence negates the ability of indisulam to induce the desired functional alterations. Conclusion Our study revealed that indisulam, which targets RBM39 to induce tumor cell apoptosis, is an effective drug for treating T-ALL. Targeting RBM39 through indisulam leads to mis-splicing of pre-mRNAs, resulting in the loss of key effectors such as THOC1.

Abstract Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.

Abstract Z-DNA binding protein 1 (ZBP1) is a crucial player in the intracellular recognition of Z-form nucleic acids (Z-NAs) through its Zαβ domain, initiating downstream interactions with RIPK1 and RIPK3 via RHIM domains. This engagement leads to the assembly of PANoptosomes, ultimately inducing programmed cell death to curb pathogen dissemination. How Zαβ and RHIM domain cooperate to trigger Z-NAs recognition and signal transduction remains unclear. Here, we show that ZBP1 condensate formation facilitates Z-NAs binding and antiviral signal transduction. The ZBP1 Zαβ dimerizes in a concentration-dependent manner, forming characteristic condensates in solutions evidenced by DLS and SAXS methods. ZBP1 exhibits a binding preference for 10-bp length CG (10CG) DNA and Z-RNA ligand, which in turn enhanced Zαβ dimerization, expediting the formation of droplet condensates in vitro and amyloid-like puncta in cells. Subsequent investigations reveal that Zαβ could form condensates with liquid-liquid phase separation property upon HSV and IAV infections, while full-length ZBP1 forms amyloid-like puncta with or without infections. Furthermore, ZBP1 RHIM domains show typical amyloidal fibril characterizations and cross-polymerize with RIPK1 depending on the core motif of 206IQIG209, while mutated ZBP1 could impede necroptosis and antiviral immunity in HT-29 cells. Thus, ZBP1 condensate formation facilitates the recognition of viral Z-NAs and activation of downstream signal transduction via synergic action of different domains, revealing its elaborated mechanism in innate immunity.

Due to the numerous and interconnected quality influencing parameters, the production process propagation and evolution of abnormal factors are complex, which can affect the stability of quality characteristics from multiple perspectives. This paper addresses the problem of identifying the quality fluctuations sources and proposes a variable-weighted reconstruction analysis-based method for identifying abnormal sources of quality fluctuations in the spinning process. The method monitors the degree of quality fluctuations by constructing information entropy statistics and reconstructs the weighted parameters of abnormal quality processes. On this basis, abnormal contribution ranking is performed based on the degree of change in quality characteristics before and after weight reconstruction, which achieves the identification of the abnormal source. The proposed method is validated using a spinning process dataset. It reveals that the method could accurately identify the quality fluctuation abnormal source, which indicates its practicability and feasibility and will provide a theoretical basis for the quality stability control.

Abstract At present, the multi‐object tracking method based on transformer generally uses its powerful self‐attention mechanism and global modelling ability to improve the accuracy of object tracking. However, most existing methods excessively rely on hardware devices, leading to an inconsistency between accuracy and speed in practical applications. Therefore, a lightweight transformer joint position awareness algorithm is proposed to solve the above problems. Firstly, a joint attention module to enhance the ShuffleNet V2 network is proposed. This module comprises the spatio‐temporal pyramid module and the convolutional block attention module. The spatio‐temporal pyramid module fuses multi‐scale features to capture information on different spatial and temporal scales. The convolutional block attention module aggregates channel and spatial dimension information to enhance the representation ability of the model. Then, a position encoding generator module and a dynamic template update strategy are proposed to solve the occlusion. Group convolution is adopted in the input sequence through position encoding generator module, with each convolution group responsible for handling the relative positional relationships of a specific range. In order to improve the reliability of the template, dynamic template update strategy is used to update the template at the appropriate time. The effectiveness of the approach is validated on the MOT16, MOT17, and MOT20 datasets.

Abstract In this paper, we investigate, in the framework of the topological approach to black hole thermodynamics, using the generalized off-shell Helmholtz free energy, the topological numbers of the static multi-charge AdS black holes in four- and five-dimensional gauged supergravities. We find that the topological number of the static-charged AdS black holes in four-dimensional Kaluza-Klein (K-K) gauged supergravity theory is W = 0, while that of the static-charged AdS black holes in four-dimensional gauged –iX 0 X 1-supergravity and STU gauged supergravity theories, and five-dimensional Einstein-Maxwell-dilaton-axion (EMDA) gauged supergravity and STU gauged supergravity, and five-dimensional static-charged AdS Horowitz-Sen black hole are both W = 1. Furthermore, we observe a novel temperature-dependent thermodynamic topological phase transition that can happen in the four-dimensional static-charged AdS black hole in EMDA gauged supergravity theory, the four-dimensional static-charged AdS Horowitz-Sen black hole, and the five-dimensional static-charged AdS black hole in K-K gauged supergravity theory. We believe that the novel temperature-dependent thermodynamic topological phase transition could help us better understand black hole thermodynamics and, further, shed new light on the fundamental nature of gauged supergravity theories.

Abstract Background Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. Methods Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. Results Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. Conclusions The study suggest that the ketogenic diet had an unfavorable risk–benefit trade-off and may compromise metabolic homeostasis in obese mice.

Abstract Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome‐driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

Abstract The demand for larger and lighter mechanisms for next-generation space missions necessitates using deployable structures. High-strain fiber polymer composites show considerable promise for such applications due to their exceptional strength-to-weight ratio, manufacturing versatility, packaging efficiency, and capacity for self-deployment using stored strain energy. However, a significant challenge in using composite deployable structures for space applications arises from the unavoidable extended stowage periods before they are deployed into their operational configuration in orbit. During the stowage period, the polymers within the composites experience material degradation due to their inherent viscoelastic and/or plastic properties, causing stress relaxation and accumulation of plastic strains, thereby reducing the deployment capability and resulting in issues related to recovery accuracy. This paper aims to give a state-of-the-art review of recent advances in the design, modeling, and manufacturing of high-strain composites for deployable structures in space applications, emphasizing the long-term stowage effects. This review is intended to initiate discussion of future research to enable efficient, robust, and accurate design of composite deployable structures that account for the enduring challenges posed by long-term stowage effects.

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic–chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.

Nature seamlessly integrates multiple functions for energy conversion, utilizing solar energy and salinity gradients as the primary drivers for ionic power generation. The creation of artificial membranes capable of finely controlling ion diffusion within nanoscale channels, driven by diverse forces, remains a challenging endeavor. In this study, we present an innovative approach: an ionic covalent-organic framework (COF) membrane constructed using chromophoric porphyrin units. The incorporation of ionic groups within these nanoconfined channels imparts the membrane with exceptional charge screening capabilities. Moreover, the membrane exhibits photoelectric responsivity, enhancing the ion conductivity upon exposure to light. As a result, this leads to a substantial increase in the output power density. In practical terms, when subjected to a salinity gradient of 0.5/0.01 M NaCl and exposed to light, the device achieved an outstanding peak power density of 18.0 ± 0.9 W m–2, surpassing the commercial benchmark by 3.6-fold. This innovative membrane design not only represents a significant leap forward in materials science but also opens promising avenues for advancing sustainable energy technologies.

Based on the engineering background of the wide-width single cable-stayed bridge, the shear lag effects of the cross-section of these bridge box girders under the action of the eccentric load were experimentally studied. The behavior of shear lag effects in the horizontal and longitudinal bridge directions under eccentric load in the operational stage of a single cable-stayed bridge was analyzed by a model testing method and a finite element (FE) analytical method. The results showed that the plane stress calculation under unidirectional live load was similar to the results from spatial FE analysis and structural calculations performed according to the effective flange width described in the design specification. At the position of the main beam near the cable force point of action, the positive stress at its upper wing edge was greatest. At a distance from the cable tension point, the maximum positive stress position trend showed that from the center of the top flange to the junction of the top flange and the middle web to the junction of the top flange and the middle web and the side web. Under eccentric load, the positive and negative shear lag effects on the end fulcrum existed at the same time, and the shear lag coefficient on the web plate was larger than the shear lag coefficient on the unforced side. Due to the influence of constraint at the middle fulcrum near the middle pivot point, positive and negative shear lag effects were significant, and the coefficient variation range was large, resulting in large tensile stress on the roof plate in this area. According to FE analytical results, stress and shear forces of a single box three-chamber box girder under eccentric load were theoretically analyzed, the bending load decomposed into the accumulation of bending moment and axial force, using the bar simulation method, and the overall shear lag effect coefficient λ was obtained and verified.

BACKGROUND: Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and is responsible for a high worldwide mortality rate. OBJECTIVE: Investigate whether corticosteroids could benefit clinical outcomes in adult with ARDS. METHODS: A comprehensive search of electronic databases Ovid MEDLINE, Ovid EMbase, and Cochrane Library from their inception to 7 May 2023 was conducted to identify studies that met the eligibility criteria, including only randomized controlled trials. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methods of trial sequential analysis. MAIN OUTCOME MEASURES: Mortality rates, including including the 14-, 28-, 45-, and 60-day mortality, hospital mortality, and intensive care unit (ICU) mortality. SAMPLE SIZE: 17 studies with 2508 patients. RESULTS: Data relating to mortality at 14, 28, 45, and 60 days were not significantly different when treatments with corticosteroids and placebo were compared. In terms of hospital and ICU mortality, the mortality of those who had received corticosteroids was significantly lower than that of those who had not. ARDS patients who received assisted ventilation benefited from corticosteroid therapy, as revealed by the significant difference in outcome days between those who received assisted ventilation and those who did not. Corticosteroid had significantly more days free from mechanical ventilation, ICU-free days, and MODS-free days during the first 28 days, but not more organ support-free days up to day 28. CONCLUSION: Although corticosteroid therapy did not reduce mortality rates at different observation periods, it significantly reduced hospital and ICU mortality. Administering corticosteroids to ARDS patients significantly decreased the days of assisted ventilation and time cost consumption. This study confirmed that long-term use of low-dose glucocorticoids may have a positive effect on early ARDS. LIMITATION: Risk of bias due to the differences in patient characteristics.