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Abstract The multi-lead electrocardiogram (ECG) is widely utilized in clinical diagnosis and monitoring of cardiac conditions. The advancement of deep learning has led to the emergence of automated multi-lead ECG diagnostic networks, which have become essential in the fields of biomedical engineering and clinical cardiac disease diagnosis. Intelligent ECG diagnosis techniques encompass Recurrent Neural Networks (RNN), Transformers, and Convolutional Neural Networks (CNN). While CNN is capable of extracting local spatial information from images, it lacks the ability to learn global spatial features and temporal memory features. Conversely, RNN relies on time and can retain significant sequential features. However, they are not proficient in extracting lengthy dependencies of sequence data in practical scenarios. The self-attention mechanism in the Transformer model has the capability of global feature extraction, but it does not adequately prioritize local features and cannot extract spatial and channel features. This paper proposes STFAC-ECGNet, a model that incorporates CAMV-RNN block, CBMV-CNN block, and TSEF block to enhance the performance of the model by integrating the strengths of CNN, RNN, and Transformer. The CAMV-RNN block incorporates a coordinated adaptive simplified self-attention module that adaptively carries out global sequence feature retention and enhances spatial–temporal information. The CBMV-CNN block integrates spatial and channel attentional mechanism modules in a skip connection, enabling the fusion of spatial and channel information. The TSEF block implements enhanced multi-scale fusion of image spatial and sequence temporal features. In this study, comprehensive experiments were conducted using the PTB-XL large publicly available ECG dataset and the China Physiological Signal Challenge 2018 (CPSC2018) database. The results indicate that STFAC-ECGNet surpasses other cutting-edge techniques in multiple tasks, showcasing robustness and generalization.

Abstract To improve students’ ability to recognize and appreciate artworks, and further enhance their academic performance and classroom satisfaction, this study explores the application of the Convolutional Neural Network (CNN) model based on optimization in art teaching. Firstly, the importance and challenges of art teaching are analyzed. Secondly, the principle and structure of CNN and its application in the classification field are expounded, and then the CNN classification model is optimized. Finally, the effectiveness of the optimized model is verified by experiments. Experimental results show that the optimized model’s accuracy is up to 95.2% in the performance evaluation. The training time of the optimized model is much lower than that of the traditional model, and this model still maintains 95.2% accuracy under the noise of 14.7%. In addition, the accuracy of the optimized model on the unseen test data is 92%. In comparing teaching experiment results, by introducing the CNN classification model, Class B students’ average score of art homework has increased by 4.3 points. The score for class satisfaction is 8.1 points. This indicates that the optimized CNN model has significant advantages in art teaching and can effectively improve students’ classroom satisfaction and academic performance. Therefore, this study has specific reference significance for the innovation of the art teaching model.

Abstract Alkaline hydrogen evolution reaction (HER) for scalable hydrogen production largely hinges on addressing the sluggish bubble‐involved kinetics on the traditional Ni‐based electrode, especially for ampere‐level current densities and beyond. Herein, 3D‐printed Ni‐based sulfide (3DPNS) electrodes with varying scaffolds are designed and fabricated. In situ observations at microscopic levels demonstrate that the bubble escape velocity increases with the number of hole sides (HS) in the scaffolds. Subsequently, we conduct multiphysics field simulations to illustrate that as the hole shapes transition from square, pentagon, and hexagon to circle, where a noticeable reduction in the bubble‐attached HS length and the pressure balance time around the bubbles results in a decrease in bubble size and an acceleration in the rate of bubble escape. Ultimately, the 3DPNS electrode with circular hole configurations exhibits the most favorable HER performance with an overpotential of 297 mV at the current density of up to 1000 mA cm−2 for 120 h. The present study highlights a scalable and effective electrode scaffold design that promotes low‐cost and low‐energy green hydrogen production through the ampere‐level alkaline HER.

Abstract Conducting polymer hydrogel can address the challenges of stricken biocompatibility and durability. Nevertheless, conventional conducting polymer hydrogels are often brittle and weak due to the intrinsic quality of the material, which exhibits viscoelasticity. This property may cause a delay in sensor response time due to hysteresis. To overcome these limitations, we have designed a wrinkle morphology three‐dimensional (3D) substrate using digital light processing technology and then followed by in situ polymerization to form interpenetrating polymer network hydrogels. This novel design results in a wrinkle morphology conducting polymer hydrogel elastomer with high precision and geometric freedom, as the size of the wrinkles can be controlled by adjusting the treating time. The wrinkle morphology on the conducting polymer hydrogel effectively reduces its viscoelasticity, leading to samples with quick response time, low hysteresis, stable cyclic performance, and remarkable resistance change. Simultaneously, the 3D gradient structure augmented the sensor's sensitivity under minimal stress while exhibiting consistent sensing performance. These properties indicate the potential of the conducting polymer hydrogel as a flexible sensor.

Peripheral nerve injury is a major challenge in clinical treatment due to the limited intrinsic capacity for nerve regeneration. Tissue engineering approaches offer promising solutions by providing biomimetic scaffolds and cell sources to promote nerve regeneration. In the present work, we investigated the potential role of skin-derived progenitors (SKPs), which are induced into neurons and Schwann cells (SCs), and their extracellular matrix in tissue-engineered nerve grafts (TENGs) to enhance peripheral neuroregeneration. SKPs were induced to differentiate into neurons and SCs in vitro and incorporated into nerve grafts composed of a biocompatible scaffold including chitosan neural conduit and silk fibroin filaments. In vivo experiments using a rat model of peripheral nerve injury showed that TENGs significantly enhanced nerve regeneration compared to the scaffold control group, catching up with the autograft group. Histological analysis showed improved axonal regrowth, myelination and functional recovery in animals treated with these TENGs. In addition, immunohistochemical staining confirmed the presence of induced neurons and SCs within the regenerated nerve tissue. Our results suggest that SKP-induced neurons and SCs in tissue-engineered nerve grafts have great potential for promoting peripheral nerve regeneration and represent a promising approach for clinical translation in the treatment of peripheral nerve injury. Further optimization and characterization of these engineered constructs is warranted to improve their clinical applicability and efficacy.

BackgroundPrevious studies have reported an association between obesity and risk of sepsis. However, the results have been inconsistent, and no causal inference can be drawn from them. Therefore, we conducted a Mendelian-randomization (MR) study to investigate causal relationships between available obesity-related anthropometric indicators and sepsis risk.MethodsWe performed MR analyses using genome-wide association study (GWAS) summary statistics on 14 anthropometric indicators [namely body mass index (BMI), waist and hip circumferences (WC, HC), basal metabolic rate (BMR), whole-body fat mass (WBFM), trunk fat mass (TFM), leg fat mass (LFM), arm fat mass (AFM), body fat percentage (BFP), whole-body fat-free mass (WBFFM), trunk fat-free mass (TFFM), leg fat-free mass (LFFM), arm fat-free mass (AFFM), and whole-body water mass (WBWM)], sepsis, critical care sepsis, and 28-day death due to sepsis from the UK Biobank and FinnGen cohort. The primary method of MR analysis was inverse variance-weighted average method. Sensitivity analyses, including heterogeneity and horizontal-pleiotropy tests, were conducted to assess the stability of the MR results. Additionally, we applied multiple-variable MR (MVMR) to evaluate the effect of BMI on the relationship between each anthropometric indicator and sepsis risk.ResultsOur MR analysis demonstrated causal relationships between 14 anthropometric indicators and sepsis of different severities. After we adjusted for BMI, MVMR analyses indicated that WC, BMR, LFM, WBFFM, TFFM, AFFM, and WBWM remained significantly associated with the presence of sepsis (all p

BackgroundThe relationship between epilepsy and risk of acute myocardial infarction (AMI) is not fully understood. Evidence from the Stockholm Heart Study indicates that the risk of AMI is increased in people with epilepsy. This study aims to analyze the temporal trends in prevalence, adverse clinical outcomes, and risk factors of AMI in patients with epilepsy (PWE).MethodsPatients aged 18 years or older, diagnosed with epilepsy with or without AMI and hospitalized from January 1, 2008, to December 31, 2017, were identified from the National Inpatient Sample (NIS) database. The Cochran–Armitage trend test and logistic regressions were conducted using SAS 9.4. Odds ratios (ORs) were generated for multiple variables.ResultsA total of 8,456,098 inpatients were eligible for our analysis, including 181,826 comorbid with AMI (2.15%). The prevalence of AMI diagnosis in PWE significantly increased from 1,911.7 per 100,000 hospitalizations in 2008 to 2,529.5 per 100,000 hospitalizations in 2017 (Ptrend

IntroductionGrape is of high economic value. Colletotrichum viniferum, a pathogen causing grape ripe rot and leaf spot, threatens grape production and quality.MethodsThis study investigates the interplay between C. viniferum by Cytological study and transcriptome sequencing.ResultsDifferent grapevine germplasms, V. vinifera cv. Thompson Seedless (TS), V. labrusca accession Beaumont (B) and V. piasezkii Liuba-8 (LB-8) were classified as highly sensitive, moderate resistant and resistant to C. viniferum, respectively. Cytological study analysis reveals distinct differences between susceptible and resistant grapes post-inoculation, including faster pathogen development, longer germination tubes, normal appressoria of C. viniferum and absence of white secretions in the susceptible host grapevine. To understand the pathogenic mechanisms of C. viniferum, transcriptome sequencing was performed on the susceptible grapevine “TS” identifying 236 differentially expressed C. viniferum genes. These included 56 effectors, 36 carbohydrate genes, 5 P450 genes, and 10 genes involved in secondary metabolism. Fungal effectors are known as pivotal pathogenic factors that modulate plant immunity and affect disease development. Agrobacterium-mediated transient transformation in Nicotiana benthamiana screened 10 effectors (CvA13877, CvA01508, CvA05621, CvA00229, CvA07043, CvA05569, CvA12648, CvA02698, CvA14071 and CvA10999) that inhibited INF1 (infestans 1, P. infestans PAMP elicitor) induced cell death and 2 effectors (CvA02641 and CvA11478) that induced cell death. Additionally, transcriptome analysis of “TS” in response to C. viniferum identified differentially expressed grape genes related to plant hormone signaling (TGA, PR1, ETR, and ERF1/2), resveratrol biosynthesis genes (STS), phenylpropanoid biosynthesis genes (PAL and COMT), photosynthetic antenna proteins (Lhca and Lhcb), transcription factors (WRKY, NAC, MYB, ERF, GATA, bHLH and SBP), ROS (reactive oxygen species) clearance genes (CAT, GSH, POD and SOD), and disease-related genes (LRR, RPS2 and GST).DiscussionThis study highlights the potential functional diversity of C. viniferum effectors. Our findings lay a foundation for further research of infection mechanisms in Colletotrichum and identification of disease response targets in grape.

Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual’s quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis.

Abstract Background Melanoma is the most lethal skin cancer characterized by its high metastatic potential. In the past decade, targeted and immunotherapy have brought revolutionary survival benefits to patients with advanced and metastatic melanoma, but these treatment responses are also heterogeneous and/or do not achieve durable responses. Therefore, novel therapeutic strategies for improving outcomes remain an unmet clinical need. The aim of this study was to evaluate the therapeutic potential and underlying molecular mechanisms of RC48, a novel HER2-target antibody drug conjugate, either alone or in combination with dabrafenib, a V600-mutant BRAF inhibitor, for the treatment of advanced BRAF-mutant cutaneous melanoma. Methods We evaluated the therapeutic efficacy of RC48, alone or in combination with dabrafenib, in BRAF-mutant cutaneous melanoma cell lines and cell-derived xenograft (CDX) models. We also conducted signaling pathways analysis and global mRNA sequencing to explore mechanisms underlying the synergistic effect of the combination therapy. Results Our results revealed the expression of membrane-localized HER2 in melanoma cells. RC48 effectively targeted and inhibited the growth of HER2-positive human melanoma cell lines and corresponding CDX models. When used RC48 and dabrafenib synergically induced tumor regression together in human BRAF-mutant melanoma cell lines and CDX models. Mechanically, our results demonstrated that the combination therapy induced apoptosis and cell cycle arrest while suppressing cell motility in vitro. Furthermore, global RNA sequencing analysis demonstrated that the combination treatment led to the downregulation of several key signaling pathways, including the PI3K-AKT pathway, MAPK pathway, AMPK pathway, and FOXO pathway. Conclusion These findings establish a preclinical foundation for the combined use of an anti-HER2 drug conjugate and a BRAF inhibitor in the treatment of BRAF-mutant cutaneous melanoma.

Abstract Colorectal cancer (CRC) is the third most common cancer associated with a poor prognosis. Effective targeted therapy alone or in combination for treating advanced CRC remains to be a major clinical challenge. Here, we propose the therapeutic efficacy and molecular mechanism underlying RC48, a FDA-approved anti-HER2 antibody conjugate via a cleavable linker to the microtubule inhibitor monomethyl auristatin E (MMAE), either alone or in combination with gemcitabine (GEM) in various models of HER2-positive advanced CRC. Our findings demonstrated that HER2 was widely expressed and located on the plasma membrane of CRC patient specimens, PDX xenograft tumors and cell lines. It confirmed that RC48 alone significantly targeted and eradicated HER2 positive CRC tumor in these models. Moreover, we screened a panel of FDA-approved first-line chemotherapy drugs in vitro. We found that GEM exhibited stronger antiproliferative activity compared to the other first-line anti-cancer agents. Furthermore, combination therapy of RC48 and GEM significantly showed synergetic antitumor activity in vitro and in vivo. To gain further mechanistic insights into the combination therapy, we performed RNA-seq analysis. The results revealed that combination treatment of RC48 and GEM regulated multiple signaling pathways, such as PI3K-AKT, MAPK, p53, Foxo, apoptosis, cell cycle and cell senescence, etc., to exert its antitumor activity in CRC cells. Collectively, these preclinical findings demonstrated that RC48 alone or combinational therapy exerted promising antitumor activity, and meriting the preclinical framework for combinational therapy of anti-HER2 drug conjugate drug and chemotherapy drugs for HER2-positive patients with advanced CRC.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP–SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM). To overcome the limitation of traditional tissue-engineered nerve grafts, jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration. To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration, we performed a cDNA microarray analysis of gene expression profiling, a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues. A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration. Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.

Abstract Background Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. Methods The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. Results The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P

Blockchain is gaining popularity as a technology that provides secure data sharing and management for the Internet of vehicles (IoV). The current research on cross-chaining between blockchains is still inefficient, and how to perform efficient cross-chain data communication has not been well studied. This paper studies the cross-chain protocol in the IoV environment, and designs a lightning-c cross-chain protocol based on the lightning network. The protocol consists of three steps. The user opens the cross-chain channel through election of nodes, and conducts transactions in the cross-chain channel, then the cross-chain channel is closed and the transaction is broadcasted to the blockchain. Our proposed approach enables efficient interoperability between heterogeneous blockchains. Compared with the traditional cross-chain protocol BTCRelay, it is proved that the lightning-c cross-chain mechanism can greatly improve the throughput of cross-chain transactions. The experimental results show that the method proposed in this paper is more efficient.

Abstract Parathyroid carcinoma (PC) is a rare malignant endocrine tumor. It can be divided into functional and non-functional types according to the tumor’s ability to secrete parathyroid hormone. Herein, we present a case each of functional and nonfunctional PC. Case 1: Functional PC. The main clinical symptoms were high parathyroid hormone and hypercalcemia with bone injury and other complications. The mass was large, capsulated, and showed vascular invasion. The tumor was surgically removed, along with a part of the tracheal wall and recurrent laryngeal nerve that were invaded by the tumor. The ipsilateral and isthmus thyroid lobe and central lymph nodes were also removed. Medicines were given to lower blood calcium. The patient died 18 months after surgery because of severe pulmonary infection and tracheal stenosis. Case 2: Non-functional PC. The patient showed no obvious clinical symptoms, but physical examination revealed a thyroid nodule. Despite the small diameter, the mass still invaded the surrounding thyroid lobe, fat, and muscle tissue. Surgery was performed to remove the tumor and ipsilateral thyroid lobe and central lymph nodes. The patient survived without recurrence or metastasis. Thus, we believe that the prognosis of PC negatively correlates with the scope of surgery. Early surgery can improve patient prognosis, and physical examination is conducive to early detection of PC. Herein, we provide a description of the diagnostic workup and the treatment approach and review relevant studies. We summarize the clinicopathological characteristics of PC cases to provide evidence for early diagnosis and therapy, to improve patient prognosis.

Federated learning, as a novel distributed machine learning mode, enables the training of machine learning models on multiple devices while ensuring data privacy. However, the existence of single-point-of-failure bottlenecks, malicious threats, scalability of federated learning implementation, and lack of incentive mechanisms have seriously hindered the development of federated learning technology. In recent years, as a distributed ledger, blockchain has the characteristics of decentralization, tamper-proof, transparency, security, etc., which can solve the issues encountered in the above-mentioned federated learning. Particularly, the integration of federated learning and blockchain leads to a new paradigm, called blockchain-based federated learning (BFL), which has been successfully applied in many application scenarios. This paper aims to provide a comprehensive review of recent efforts on blockchain-based federated learning. More concretely, we propose and design a taxonomy of blockchain-based federated learning models, along with providing a comprehensive summary of the state of the art. Various applications of federated learning based on blockchain are introduced. Finally, we expand on current trends and provide new perspectives pertaining to this new and exciting development in the field.

Sleep position recognition plays a crucial role in enhancing individual sleep quality and addressing sleep-related disorders. However, the conventional non-invasive technology for recognizing sleep positions tends to be limited in its widespread application due to high production and computing costs. To address this issue, an enhanced stacking model is proposed based on a specific air bag mattress. Firstly, the hyperparameters of the candidate base model are optimized using the Bayesian optimization algorithm. Subsequently, the entropy weight method is employed to select extreme gradient boosting (XGBoost), support vector machine (SVM), and deep neural decision tree (DNDT) as the first layer of the enhanced stacking model, with logistic regression serving as the meta-learner in the second layer. Comparative analysis with existing machine learning techniques demonstrates that the proposed enhanced stacking model achieves higher classification accuracy and applicability.

PurposeAlthough the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer (PC) remains inconclusive. This study aimed to explore the prevalence of AF and evaluate the relationship between AF and clinical outcomes in PC patients.MethodsPatients diagnosed with PC between 2008 and 2017 were identified from the National Inpatient Sample database. The trends in AF prevalence were compared among PC patients and their subgroups. Multivariable regression models were used to assess the associations between AF and in-hospital mortality, length of hospital stay, total cost, and other clinical outcomes.Results256,239 PC hospitalizations were identified; 41,356 (83.8%) had no AF and 214,883 (16.2%) had AF. AF prevalence increased from 14.0% in 2008 to 20.1% in 2017 (P

Abstract Background A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. Methods A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. Results Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. Conclusion PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future.

Abstract Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with limited therapeutic options readily available. Immunotherapy such as immune checkpoint inhibition has been investigated in TNBC but still encounters low overall response. Neutrophils, the most abundant leukocytes in the body, are increasingly recognized as an active cancer-modulating entity. In the bloodstream, neutrophils escort circulating tumor cells to promote their survival and stimulate their proliferation and metastasis. In the tumor microenvironment, neutrophils modulate the immune milieu through polarization between the anti-tumor and the pro-tumor phenotypes. Through a comprehensive review of recently published literature, it is evident that neutrophils are an important player in TNBC immunobiology and can be used as an important prognostic marker of TNBC. Particularly, in their pro-tumor form, neutrophils facilitate TNBC metastasis through formation of neutrophil extracellular traps and the pre-metastatic niche. These findings will help advance the potential utilization of neutrophils as a therapeutic target in TNBC.

ObjectiveTo examine the effect of brisk walking intervention in occupational populations with normal high blood pressure, and to provide quantified evidence for health improvement of occupational population with normal high blood pressure. MethodsThe information on demographics, physical examination and walking of 4 855 workers with normal high blood pressure were extracted from a brisk walking incentive intervention program for occupation populations conducted during 2016 in China. The substitution effects of low intensity physical activity (LPA), moderate intensity physical activity (MPA) and high intensity physical activity (HPA) instead of sedentary behavior (SB) on health outcomes were analyzed with isochronal substitution model. Results The results of isochronous substitution model analysis showed that the body mass index (BMI), body fat rate (BFP) and visceral fat index (VAI) of occupational people with normal high blood pressure decreased by 0.102 (β = – 0.102), 0.150% (β = – 0.150) and 0.071 (β = – 0.071), respectively when the SB was replaced by MPA time of 30 min/d during the same period. The results of subgroup analysis showed that MPA time of 30 min/d instead of SB during the same period could decrease BMI by an additional 0.120 (β = – 0.120) in male occupational population with normal high blood pressure, and an additional 0.287% (β = – 0.287) and 0.119 (β = – 0.119) in BFP and VAI in female occupational group with normal high blood pressure, respectively. BMI, BFP and VAI decreased by 0.127 (β = – 0.127), 0.192% (β = – 0.192), and 0.098 (β = – 0.098) in normal high blood pressure occupational group aged 49 years old; while BMI and VAI decreased by 0.160 (β = 0.160) and 0.080 (β = – 0.080) in overweight and obese occupational group. BMI, BFP and VAI decreased by an additional 0.206 (β = – 0.206), 0.216% (β = – 0.216) and 0.127 (β = – 0.127), respectively, and BMI and BFP decreased by an additional 0.063 (β = – 0.063) and 0.143% (β = – 0.143) in normal high blood pressure occupation group with normal BFP. The BMI could be decreased by 0.189 (β = – 0.189) in the normal high blood pressure occupational group with BFP-indicated obesity, while the BMI, BFP and VAI could be decreased by 0.144 (β = 0.144), 0.200% (β = – 0.200) and 0.104 (β = – 0.104) in the normal high blood pressure occupational group with VAI-indicated obesity. A 30 min/d HPA time instead of SB during the same period resulted in an additional decrease of 0.641% (β = – 0.641) and 0.295 (β = – 0.295) in BFP and VAI in men with normal high blood pressure, and an additional 1.020% (β = – 1.020) and 0.520 (β = – 0.520) in BFP and VAI in those ≥ 50 years old; BFP could be decreased by an additional 0.748% (β = – 0.748) in normal high blood pressure occupational population with BFP-indicated obesity. Conclusion A 30 min/d MPA time instead of SB during the same period can improve the BMI, BFP and VAI at different degrees in the occupational populations with normal high blood pressure; however there may be no isochronous substitution for health improvement effect of LPA and HPA instead of SB in the whole population; the moderate intensity walking exercise of 100 – 130 steps/min can be promoted in this population.

Abstract Background Inattention has been given to the pathogenesis of adolescent and young adult (AYA) hepatocellular carcinoma (HCC). Due to the more advanced tumor progression and poorer prognosis of AYA-HCC, together with a better tolerance ability, noncirrhotic background, and a stronger willingness to treat AYA-HCC, clinical and molecular biology studies are urgent and necessary, especially for those with hepatitis B infection. Methods For clinical aspects, the overall survival, the recurrence-free survival, and the Cox analyses were performed. Then, functional analysis, gene clustering, metabolic-related analysis, immune infiltration and competing endogenous RNA (ceRNA) construction were carried out using whole transcriptome sequencing technique. Results Based on the clinical information of our HCC cohort, the overall survival and recurrence-free survival rates were worse in the AYA group than in the elderly group as previously described. According to our whole transcriptome sequencing results, functional analysis revealed that metabolism-related pathways as well as protein translation and endoplasmic reticulum processing were enriched. Then the hub metabolism-related genes were screened by metabolite–protein interactions (MPIs) and protein–protein interactions (PPIs). Fatty acid metabolism is a crucial component of metabolic pathways, abnormalities of which may be the reason for the worse prognosis of HBV-AYA HCC. Finally, the relationship of disrupted expression of metabolism-related genes with immune infiltration was also analyzed, and the lncRNA‒miRNA‒mRNA-related ceRNA network for HBV-AYA HCC was constructed, which may provide new cues for HBV-AHA HCC prevention. Conclusion The worse prognosis and recurrence rate of HBV-AYA HCC may be related to abnormalities in metabolism-related pathways, especially disorders of fatty acid metabolism.

In this study, we successfully developed a low RE containing Mg-3Y-2Gd-1Nd-0.5Zr (wt%) alloy with high strength-ductility synergy by combined processes of hot extrusion, hot rolling and ageing. This alloy exhibits an excellent strength-ductility balance (UTS of 345 ± 2.0 MPa, TYS of 301 ± 5.0 MPa and EL of 9.2 ± 1.9%), which is better than that of many Mg-RE wrought alloys with higher RE concentration and even comparable to that of 6061 Al wrought alloy. A long-range chain-like structure consisting of β′ phase, βH phase, βM phase and zig-zag atomic columns is observed for the first time in the studied alloy. The combined process of hot extrusion and hot rolling boosts the formation of deformed grains and low angle grain boundaries, and makes the deformed grains dominate in the alloy strengthening. Under this circumstance, the following ageing generates a novel heterogeneous structure comprising the long-range chain-like structure with broad interparticle spacing and the spacious precipitate-free zones in the deformed grains, which plays a key role in the concurrent strengthening and toughening of the alloy. The present study demonstrates that the deformed grains with long-range chain-like structures and precipitate-free zones is desirable microstructure for the low RE containing Mg alloys to achieve high strength-ductility synergy.

This paper presents an eye image segmentation-based computer-aided system for automatic diagnosis of ocular myasthenia gravis (OMG), called OMGMed. It provides great potential to effectively liberate the diagnostic efficiency of expert doctors (the scarce resources) and reduces the cost of healthcare treatment for diagnosed patients, making it possible to disseminate high-quality myasthenia gravis healthcare to under-developed areas. The system is composed of data pre-processing, indicator calculation, and automatic OMG scoring. Building upon this framework, an empirical study on the eye segmentation algorithm is conducted. It further optimizes the algorithm from the perspectives of “network structure” and “loss function”, and experimentally verifies the effectiveness of the hybrid loss function. The results show that the combination of “nnUNet” network structure and “Cross-Entropy + Iou + Boundary” hybrid loss function can achieve the best segmentation performance, and its MIOU on the public and private myasthenia gravis datasets reaches 82.1% and 83.7%, respectively. The research has been used in expert centers. The pilot study demonstrates that our research on eye image segmentation for OMG diagnosis is very helpful in improving the healthcare quality of expert doctors. We believe that this work can serve as an important reference for the development of a similar auxiliary diagnosis system and contribute to the healthy development of proactive healthcare services.

Abstract The Cenozoic sediments are very thick in the southwest Tarim Basin and very thin in the northwest, but what controls these variations is unclear. Here, we use two‐dimensional thermo‐mechanical models to investigate how the lateral variations in rheological strength and depletion density of cratonic lithosphere mantle affect the cratonic basin deformation. Model results show that the basin basement uplift occurs above either the region with crustal thickening or high depletion in the mantle. A model with a stronger and density‐depleted northern half of cratonic lithosphere mantle in the context of compression matches the differential Cenozoic subsidence and deformation observed in the Tarim Basin well. We propose that a Permian plume led to the lateral heterogeneity of the lithosphere mantle under the Tarim craton, and the modified lithosphere mantle characteristics caused the differential Cenozoic sediment thickness in the Tarim Basin.

Background. Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause–effect relation between plasma MPO levels and RTIs. Materials and Methods. Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane’s Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072–1.251; P0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions. Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

The catalytic performance and the stability of the water electrolysis system have perplexed the practical splitting water. Herein, 3D‐printed metallic electrodes with Janus porosity are reported, which can achieve the efficient bubble emission and provide high surface area. After a further one‐step treatment, the catalysts of Ru–Ni(OH)2 and Fe–Ni(OH)2 nanoarrays are in situ grown on the electrodes. Theoretical calculations and systematical experiments confirm the synergistic effect of the gradient morphology and the in situ grown catalysts. The electrolyzer shows unprecedented activity with an overpotential of 98 mV for hydrogen evolution reaction and 343 mV for oxygen evolution reaction at the current density of 500 mA cm−2 and outperformed stability, which can deliver 500 mA cm−2 at the voltage of 1.638 V for 2100 h with no significant decay, far exceedingly most state‐of‐the‐art electrolyzers. This 3D electrode with controllable bubble motions offers a viable solution for future industrial sustainable hydrogen production technology.

As a typical representative of Chinese sex symbol art, Chun Gong Tu has unique expressive power and artistic value in terms of spatial layout, compositional elements and symbolic presentation. It embodies the visual aesthetic value, psychological aesthetic value and social value of sex symbol art through the portrayal of characters and environmental backgrounds, and is worthy of in-depth exploration. Based on the introduction of Chun Gong Tu, this paper conducts a quantitative study with the aim of providing a feasible path for the development of contemporary Chinese sex symbol art. The study concludes that Chinese sex art education can significantly and positively influence the interest and cultural identity of the audience, and that interest can further stimulate the cultural identity of the Chinese audience, thus promoting the dissemination and creation of sex symbol art in China.

Abstract Purpose To evaluate the effect of postoperative utilization of somatostatin after definitive surgery for duodenal fistula (DF) in preventing a recurrence. Methods Patients with definitive surgery for DF between January 2010 and December 2021 were categorized based on the utilization of somatostatin or not after the surgery. Patients in the Somatostatin group were matched to those in the Non-somatostatin group using propensity scores matching (PSM), so as to evaluate the effect of postoperative use of somatostatin by comparing the two groups. Results A total of 154 patients were divided into the in the Somatostatin group (84) and the Non-somatostatin group (70). Forty-three patients (27.9%) exhibited a recurrent fistula, with which the postoperative use of somatostatin was not associated (19 [22.6%] in the Somatostatin group and 24 (34.3%) in the Non-somatostatin group; unadjusted OR 0.56; 95% CI 0.28–1.14; P = 0.11). However, the postoperative usage of somatostatin served as a protective factor for developing into high-output recurrent fistula (eight (13.3%) in the Somatostatin group and 15 (25%) in the Non-somatostatin group; adjusted OR 0.39; 95% CI 0.15–0.93; P = 0.04). After PSM, the recurrent fistula occurred in 29.2% subjects (35/120). The postoperative usage of somatostatin was not associated with recurrent fistula (13 in PSM Somatostatin group vs. 22 in PSM Non-somatostatin group; unadjusted OR 0.48; 95% CI 0.21–1.07; P = 0.07), while its postoperative usage decreased the incidence of recurrent high-output fistula (5/60 in the PSM Somatostatin group, compared with 13/60 in the PSM Non-somatostatin group; adjusted OR 0.30; 95% CI 0.09–0.95). Conclusion Postoperative use of somatostatin could effectively reduce the incidence of recurrent high-output fistula, without association with overall incidence of postoperative recurrent fistula.

Abstract Background Homologous recombination deficiency (HRD) is a well‐known biomarker which could predict poly‐ADP ribose polymerase 1 (PARP) inhibitor and platinum drug response. As an aggressive cancer, small‐cell lung cancer (SCLC) is sensitive to platinum drugs, but relapse occurs rapidly. Herein, we aim to illustrate the genomic alteration patterns of homologous recombination repair (HRR)‐related genes in a Chinese SCLC cohort and further analyze the relationship among HRR gene mutations and known biomarkers of immune checkpoint inhibitor (ICI) response, including tumor mutation burden (TMB) and programmed cell death‐ligand 1 (PD‐L1) expression. Methods Next‐generation sequencing (NGS)‐based target capture sequencing of 543 cancer‐related genes was performed to analyze the genomic profiles of 133 Chinese SCLC patients, and TMB was calculated. PD‐L1 expression was evaluated in 90 out of 133 patients using the SP142 PD‐L1 immunohistochemistry assay. Results Among the 133 patients with SCLC, 47 (35.3%) had HRR gene mutations. ATM (8.3%) was the most frequently mutated HRR gene in the cohort, followed by NBN (4.5%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (23.4%) and 4 (8.5%) patients, respectively. HRR gene mutations cooccurred with KMT2D gene mutations. There were several differences in genomic alterations between patients with HRR gene mutations (HRR‐Mut) and without HRR mutations (HRR‐WT). The results revealed that TP53 and RB1 were commonly mutated genes in both groups. Mutations in the KMT2D gene and genes in the RTK‐RAS pathway occurred more frequently in the HRR‐Mut group. Furthermore, we found that mutations in HRR genes were associated with high TMB (Wilcoxon, p = 0.048), but there was no correlation of HRR gene mutation status with PD‐L1 expression. Conclusions We exhaustively describe the genomic alteration profile of Chinese SCLC patients and provide further evidence that HRR gene mutations are prevalent in SCLC patients.

Abstract Background The aim was to compare the diffusion tensor imaging (DTI) indices derived from human hearts between 1.5 T and 3.0 T scanners. Additionally, the reproducibility of DTI indices was assessed between 1.5 T and 3.0 T scanners. Methods A total of 18 ex-vivo hearts were derived from patients who underwent heart transplantation. The DTI schemes were performed at 1.5 T and 3.0 T, respectively. Then, the same slices from each ex-vivo heart were selected for image analysis. The student’s t-test or Wilcoxon-rank test was used to compare the statistical differences. The agreement of DTI indices was mainly reported as the interclass correlation coefficient (ICC). Results No significant differences (all P > 0.05) were found in the DTI indices between 1.5 T and 3.0 T scanners. Interestingly, the ICC of all DTI indices was relatively lower with a low b-value. The reproducibility of the helix angle (HA) was relatively lower when compared to the other DTI indices. Conclusion The DTI indices of ex-vivo human hearts between 1.5 T and 3.0 T scanners had no significant differences. The consistency of DTI indices needed caution using a low b-value with different field strengths, and the relatively low reproducibility of HA should be considered.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood–brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Abstract Background Ventilator-associated pneumonia (VAP) is one of the most common intensive care unit (ICU)-acquired infections, which can cause multiple adverse events. Due to bacterial mutation and overuse of antimicrobial drugs, multidrug-resistant organisms (MDRO) has become one of the major causes of postoperative VAP infections in cardiac patients. Therefore, this study aims to explore the risk factors for VAP with MDRO following cardiac surgery in adults. Methods The clinical data of adult VAP patients following cardiac surgery in the hospital from Jan 2017 to May 2021 were analyzed retrospectively, and the patients were divided into the MDRO VAP group and the non-MDRO VAP group. Univariable and multivariable logistic regression analyses were performed on risk factors in patients with MDRO VAP. The species and drug sensitivity of pathogens isolated from the VAP patients were also analyzed. Results A total of 61 VAP cases were involved in this study, with 34 cases in the MDRO VAP group (55.7%) and 27 cases in the non-MDRO VAP group (44.3%). Multivariable logistic regression analysis showed that independent risk factors for MDRO VAP included preoperative creatinine clearance rate (CCR) ≥ 86.6ml, intraoperative cardiopulmonary bypass (CPB) time ≥ 151 min, postoperative acute kidney injury (AKI) and nasal feeding. Gram-negative bacilli were the main pathogens in VAP patients (n = 54, 90.0%), with the highest rate of Acinetobacter baumannii (n = 24, 40.0%). Additionally, patients with MDRO VAP had a significantly longer postoperative intensive care unit (ICU) duration and higher hospitalization costs than non-MDRO VAP patients, but there was no notable difference in the 28-day mortality rate between the two groups. Conclusion Based on implementing measures to prevent VAP, clinicians should pay more attention to patients with kidney disease, longer intraoperative CPB time, and postoperative nasal feeding to avoid MDRO infections.

Neural tissue engineering techniques typically face a significant challenge, simulating complex natural vascular systems that hinder the clinical application of tissue-engineered nerve grafts (TENGs). Here, we report a subcutaneously pre-vascularized TENG consisting of a vascular endothelial growth factor-induced host vascular network, chitosan nerve conduit, and inserted silk fibroin fibers. Contrast agent perfusion, tissue clearing, microCT scan, and blood vessel 3D reconstruction were carried out continuously to prove whether the regenerated blood vessels were functional. Moreover, histological and electrophysiological evaluations were also applied to investigate the efficacy of repairing peripheral nerve defects with pre-vascularized TENG. Rapid vascular inosculation of TENG pre-vascularized blood vessels with the host vascular system was observed at 4 ​d bridging the 10 ​mm sciatic nerve defect in rats. Transplantation of pre-vascularized TENG in vivo suppressed proliferation of vascular endothelial cells (VECs) while promoting their migration within 14 ​d post bridging surgery. More importantly, the early vascularization of TENG drives axonal regrowth by facilitating bidirectional migration of Schwann cells (SCs) and the bands of Büngner formation. This pre-vascularized TENG increased remyelination, promoted recovery of electrophysiological function, and prevented atrophy of the target muscles when observed 12 weeks post neural transplantation. The neural tissue-engineered pre-vascularization technique provides a potential approach to discover an individualized TENG and explore the innovative neural regenerative process.

Disease diagnosis represents a critical and arduous endeavor within the medical field. Artificial intelligence (AI) techniques, spanning from machine learning and deep learning to large model paradigms, stand poised to significantly augment physicians in rendering more evidence-based decisions, thus presenting a pioneering solution for clinical practice. Traditionally, the amalgamation of diverse medical data modalities (e.g., image, text, speech, genetic data, physiological signals) is imperative to facilitate a comprehensive disease analysis, a topic of burgeoning interest among both researchers and clinicians in recent times. Hence, there exists a pressing need to synthesize the latest strides in multi-modal data and AI technologies in the realm of medical diagnosis. In this paper, we narrow our focus to five specific disorders (Alzheimer’s disease, breast cancer, depression, heart disease, epilepsy), elucidating advanced endeavors in their diagnosis and treatment through the lens of artificial intelligence. Our survey not only delineates detailed diagnostic methodologies across varying modalities but also underscores commonly utilized public datasets, the intricacies of feature engineering, prevalent classification models, and envisaged challenges for future endeavors. In essence, our research endeavors to contribute to the advancement of diagnostic methodologies, furnishing invaluable insights for clinical decision making.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-β levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Sensors are crucial in the understanding of machines working under high temperatures and high-pressure conditions. Current devices utilize polymeric materials as electrical insulators which pose a challenge in the device's lifespan. Ceramics, on the other hand, is robust and able to withstand high temperature and pressure. For such applications, a co-fired ceramic device which can provide both electrical conductivity and insulation is beneficial and acts as a superior candidate for sensor devices. In this paper, we propose a novel fabrication technique of complex multi-ceramics structures via 3D printing. This fabrication methodology increases both the geometrical complexity and the device's shape precision. Structural ceramics (alumina) was employed as the electrical insulator whilst providing mechanical rigidity while a functional ceramic (alumina-doped zinc oxide) was employed as the electrically conductive material. The addition of sintering additives, tailoring the printing pastes' solid loadings and heat treatment profile resolves multi-materials printing challenges such as shrinkage disparity and densification matching. Through high-temperature co-firing of ceramics (HTCC) technology, dense high quality functional multi-ceramics structures are achieved. The proposed fabrication methodology paves the way for multi-ceramics sensors to be utilized in high temperature and pressure systems in the near future.

Federated learning is a distributed learning method that seeks to train a shared global model by aggregating contributions from multiple clients. This method ensures that each client’s local data are not shared with others. However, research has revealed that federated learning is vulnerable to poisoning attacks launched by compromised or malicious clients. Many defense mechanisms have been proposed to mitigate the impact of poisoning attacks, but there are still some limitations and challenges. The defense methods are either performing malicious model removal from the geometric perspective to measure the geometric direction of the model or adding an additional dataset to the server for verifying local models. The former is prone to failure when facing advanced poisoning attacks, while the latter goes against the original intention of federated learning as it requires an independent dataset; thus, both of these defense methods have some limitations. To solve the above problems, we propose a robust federated learning method based on geometric and qualitative metrics (FLGQM). Specifically, FLGQM aims to metricize local models in both geometric and qualitative aspects for comprehensive defense. Firstly, FLGQM evaluates all local models from both direction and size aspects based on similarity calculated by cosine and the Euclidean distance, which we refer to as geometric metrics. Next, we introduce a union client set to assess the quality of all local models by utilizing the union client’s local dataset, referred to as quality metrics. By combining the results of these two metrics, FLGQM is able to use information from multiple views for accurate poisoning attack identification. We conducted experimental evaluations of FLGQM using the MNIST and CIFAR-10 datasets. The experimental results demonstrate that, under different kinds of poisoning attacks, FLGQM can achieve similar performance to FedAvg in non-adversarial environments. Therefore, FLGQM has better robustness and poisoning attack defense performance.

Abstract A high-entropy ceramic oxide is used as the cathode for the first time for proton-conducting solid oxide fuel cells (H-SOFCs). The Fe0.6Mn0.6Co0. 6Ni0.6Cr0.6O4 (FMCNC) high-entropy spinel oxide has been successfully prepared, and the in situ chemical stability test demonstrates that the FMCNC material has good stability against CO2. The first-principles calculation indicates that the high-entropy structure enhances the properties of the FMCNC material that surpasses their individual components, leading to lower O2 adsorption energy for FMCNC than that for the individual components. The H-SOFC using the FMCNC cathode reaches an encouraging peak power density (PPD) of 1052 mW·cm−2 at 700 °C, which is higher than those of the H-SOFCs reported recently. Additional comparison was made between the high-entropy FMCNC cathode and the traditional Mn1. 6Cu1.4O4 (MCO) spinel cathode without the high-entropy structure, revealing that the formation of the high-entropy material allows the enhanced protonation ability as well as the movement of the O p-band center closer to the Fermi level, thus improving the cathode catalytic activity. As a result, the high-entropy FMCNC has a much-decreased polarization resistance of 0.057 Ω·cm2 at 700 °C, which is half of that for the traditional MCO spinel cathode without the high-entropy design. The excellent performance of the FMCNC cell indicates that the high-entropy design makes a new life for the spinel oxide as the cathode for H-SOFCs, offering a novel and promising route for the development of high-performance materials for H-SOFCs.

Abstract Background Ulcerative colitis (UC) is a common inflammatory bowel disease, during which cell necroptosis plays key roles in driving inflammation initiation and aggravation. Previous studies reported Receptor Interacting Protein Kinase 3 (RIP3)-mediated necroptosis in multiple diseases, and RIP3 protein in Paneth cells significantly enriched in the intestines of both humans and mice. Therefore, we hypothesized targeting RIP3 to inhibit necroptosis may depress UC. Methods We classified clinical UC samples according to the modified Truelove & Witts criterion. The expression of RIP3 was measured by western blot and immunohistochemistry. Cell proliferation and apoptosis were analyzed by MTT assay and flow cytometry. ROS production and the secretion of inflammatory cytokines were measured by DCFH-DA probe and ELISA assay. TLR4/MyD88/NF-κB signaling pathway was analyzed by western blot. We established experimental colitis model in RIP3 knockout and wild-type mice and disease activity index (DAI) score was calculated. The expression and distribution of tight junction protein were analyzed by immunofluorescence. The ratio of CD4+Foxp3+ T cells in the spleen was detected by flow cytometry. Oxidative damage of mouse colon was assessed by detecting the levels of SOD, MDA and MPO. Data were analyzed by one-way ANOVA or student’s t test. Results The expression of RIP3 in human colon is positively associated with the severity of UC. RIP3 inhibitor GSK872 or RIP3 knockdown reverses the inhibitory effect of TNF-α on proliferation and the promoting effect of TNF-α on apoptosis and necrosis in human intestinal epithelial cells. In addition, RIP3 deficiency inhibits the secretion of inflammatory cytokines (IL-16, IL-17 and IFN-γ) and ROS production induced by TNF-α. In vivo, RIP3 inhibitor Nec-1 effectively improves DSS-induced colitis in mice. In mechanism, RIP3 depression could upregulate the proportion of CD4+Foxp3+ immunosuppressive Treg cells in the spleen while suppressed TLR4/MyD88/NF-κB signaling pathway and ROS generation, and all these anti-inflammation factors together suppress the secretion of inflammatory cytokines and necroptosis of intestinal epithelial cells. Conclusions This study preliminarily explored the regulating mechanism of RIP3 on UC, and Nec-1 may be a promising drug to alleviate the inflammation and necroptosis of the colon in UC patients.

Wallerian degeneration is a complex biological process that occurs after nerve injury, and involves nerve degeneration and regeneration. Schwann cells play a crucial role in the cellular and molecular events of Wallerian degeneration of the peripheral nervous system. However, Wallerian degeneration regulating nerve injury and repair remains largely unknown, especially the early response. We have previously reported some key regulators of Wallerian degeneration after sciatic nerve injury. Baculoviral inhibitor of apoptosis protein repeat-containing protein 3 (BIRC3) is an important factor that regulates apoptosis-inhibiting protein. In this study, we established rat models of right sciatic nerve injury. In vitro Schwann cell models were also established and subjected to gene transfection to inhibit and overexpress BIRC3. The data indicated that BIRC3 expression was significantly up-regulated after sciatic nerve injury. Both BIRC3 upregulation and downregulation affected the migration, proliferation and apoptosis of Schwan cells and affected the expression of related factors through activating c-fos and ERK signal pathway. Inhibition of BIRC3 delayed early Wallerian degeneration through inhibiting the apoptosis of Schwann cells after sciatic nerve injury. These findings suggest that BIRC3 plays an important role in peripheral nerve injury repair and regeneration. The study was approved by the Institutional Animal Care and Use Committee of Nantong University, China (approval No. 2019-nsfc004) on March 1, 2019.

Abstract Purpose The present study aimed to identify the predictive value of duration of postoperative hyperlactatemia in screening patients at high risk of recurrent fistula after major definitive surgery (DS) for intestinal fistula. Methods If the initial postoperative lactate (IPL) > 2 mmol/L, DS was defined as major definitive surgery. The 315 enrolled patients with major DS were divided into group A (2 mmol/L 6 mmol/L). The characteristics of patients were collected, and the duration of postoperative hyperlactatemia was analyzed. According to the occurrence of recurrent fistula (RF), patients were further divided into RF group A, and Non-RF group A; RF group B, and Non-RF group B; and RF group C, and Non-RF group C. Results The duration of postoperative hyperlactatemia was comparable between the RF group A and the Non-RF group A [12 (IQR: 12–24) vs 24 (IQR: 12–24), p = 0.387]. However, the duration of hyperlactatemia was associated with RF in group B (adjusted OR = 1.061; 95% CI: 1.029–1.094; p

The extent to which neurodevelopment is affected by prenatal lead exposure has not been conclusive. In addition, studies on the effects of sex on these relationships are inconsistent. The aim of this study was to investigate the impact of cord blood lead on neurodevelopment in children within sex subgroups. A total of 275 mother-child pairs from the Shanghai mother-child cohort were included. Umbilical cord blood lead was measured using graphite furnace atomic absorption spectrophotometry. The Bayley Scales for Infant Development-III (BSID-III) was used to measure the neurodevelopment of infants at the age of 18 ± 1.5 months. The median and interquartile range of cord blood lead levels in the total participants, male, and female children were 44.0 (24.5) μg/L, 44.0 (24.3) μg/L, and 46.0 (24.0) μg/L, respectively. According to multiple linear regression, cord blood lead concentrations showed a negative association with fine motor scores in all models associated with female children (β = −1.5; 95%confidence interval: −2.6, −0.4). However, prenatal lead levels were not associated with any of the BSID-III scores in male children. In addition, cord serum DHA was found positively related to fine motor scores in male children. Our findings suggest that prenatal lead exposure could lead to decreased motor function, although this phenomenon was only observed in female children. And DHA may be a protective factor against lead exposure in boys. Thus, further studies are needed to investigate the associations between prenatal lead exposure and neurobehavioral development, as well as the mechanism of sex differences.

Lead (Pb), as a deleterious heavy metal, ubiquitously exists in environment and industry, which engenders multi-organ disfunction, especially the brain of infants who are vulnerable to attack from lead-induced neurotoxicity. Although cholesterol sulfate (CS) is crucial constituent of cell membranes and precursor of neurosteroids, which maintains the function and survival of neurons, the role of CS in lead-induced neurological damage still remains incomplete. In this work, Rat Brain Astrocytes cell line (CTX cells) was applied into exploration that protective effects of CS on CTX cell apoptosis induced by lead via the regulation of BDNF/TrkB signaling pathway mediated cholesterol metabolism. We found that CTX cells exposed to lead manifested apparent cytotoxicity, where the viability of CTX cells was significantly suppressed, accompanied with the elevation of apoptosis, in response to a trend towards increases in reactive oxygen species (ROS) production and pro-apoptotic protein Cleaved-caspase3, synchronized with the decline in anti-apoptotic protein Bcl-2. Moreover, accumulation of lead in CTX cells showed a dose-dependent increase, and meanwhile, decrements in cholesterol content occurred along with increase in lead exposure, in which expressions of cholesterol metabolism related proteins and transcriptions of its genes (SREBP2, LDLR, and HMGCR) were diminished. Furthermore, BDNF signaling pathway was obviously blocked after lead exposure, down-regulating expressions of proteins BDNF and TrkB. However, pretreatment with CS detoxified the negative impacts of lead-invoked CTX cell damage, acting as an effective remedy for apoptosis, imbalance of cholesterol metabolism and inhibition of BDNF signaling pathway. In addition, the relationship between BDNF signaling pathway and cholesterol metabolism was further verified, in which cholesterol metabolism related proteins and genes were promoted significantly after the activation of BDNF/TrkB signaling pathway using 7,8-Dihydroxyflavone (7,8-DHF), thereby detoxifying lead-induced CTX cell injury. However, the pretreatment of TrkB inhibitor ANA-12 offset the promotion of 7,8-DHF and ultimately inhibit cholesterol metabolism. Overall, our study demonstrated that CS could initiate the BDNF/TrkB signaling pathway, regulating the cholesterol metabolism against CTX cell apoptosis invoked by lead.

BackgroundAlthough asthma and chronic obstructive pulmonary disease (COPD) are two well-defined and distinct diseases, some patients present combined clinical features of both asthma and COPD, particularly in smokers and the elderly, a condition termed as asthma-COPD overlap (ACO). However, the definition of ACO is yet to be established and clinical guidelines to identify and manage ACO remain controversial. Therefore, in this study, inflammatory biomarkers were established to distinguish asthma, ACO, and COPD, and their relationship with the severity of patients’ symptoms and pulmonary function were explored.Materials and methodsA total of 178 patients, diagnosed with asthma (n = 38), ACO (n = 44), and COPD (n = 96) between January 2021 to June 2022, were enrolled in this study. The patients’ pulmonary function was examined and routine blood samples were taken for the analysis of inflammatory indexes. Logistic regression analysis was used to establish inflammatory biomarkers for distinguishing asthma, ACO, and COPD; linear regression analysis was used to analyze the relationship between inflammatory indexes and symptom severity and pulmonary function.ResultThe results showed that, compared with ACO, the higher the indexes of platelet, neutrophil-lymphocyte ratio (NLR) and eosinophil-basophil ratio (EBR), the more likely the possibility of asthma and COPD in patients, while the higher the eosinophils, the less likely the possibility of asthma and COPD. Hemoglobin and lymphocyte-monocyte ratio (LMR) were negatively correlated with the severity of patients’ symptoms, while platelet-lymphocyte ratio (PLR) was negatively correlated with forced expiratory volume in the 1 s/forced vital capacity (FEV1/FVC) and FEV1 percent predicted (% pred), and EBR was positively correlated with FEV1% pred.ConclusionInflammatory indexes are biomarkers for distinguishing asthma, ACO, and COPD, which are of clinical significance in therapeutic strategies and prognosis evaluation.

Sorafenib, a kinase inhibitor, has shown promising therapeutic efficacy in a subset of patients with acute myeloid leukemia (AML). However, despite its clinical effectiveness, sorafenib resistance is frequently observed in clinical settings, and the mechanisms underlying this resistance as well as effective strategies to overcome it remain unclear. We examined both single-cell and bulk transcription data in sorafenib-resistant and control AML patients and integrated a sorafenib resistance gene signature to predict the sensitivity of AML cells and the clinical outcomes of AML patients undergoing sorafenib therapy. In addition, our drug sensitivity analysis of scRNA-seq data using deconvolution methods showed that venetoclax was effective in targeting sorafenib-resistant AML cells. Mechanistically, sorafenib was found to activate the JAK-STAT3 pathway and upregulate BCL2 expression in sorafenib-resistant AML cells. This upregulation of BCL2 expression rendered the cells vulnerable to the BCL2 inhibitor venetoclax. In conclusion, we developed a platform to predict sorafenib resistance and clinical outcomes in AML patients after therapy. Our findings suggest that the combination of sorafenib and venetoclax could be an effective therapeutic strategy for AML treatment.

Chaolong Wang and colleagues report a large genome-wide association study for COVID-19 severity in Chinese individuals. By meta-analysis with European data, they identify 3 loci associated with severe disease that suggest key roles for the adaptive immune system and the ABO blood group system in development of severe COVID-19.

Eco-friendly farms play an instrumental role in biodiversity conservation worldwide, but there are no applicable assessment and monitoring tools available. Based on the protocol of the Singapore City Biodiversity Index, we proposed a simplified, rapid assessment method, the Agri-Environment Biodiversity Index (ABI, including 3 aspects, 5 indicators, and 10 secondary indicators), to score the biodiversity performance of 9 best-practice farms from a total of >300 eco-friendly farms in China. Using the Delphi method and correlation analysis, we confirmed the suitability of the ABI scoring system and found that the scores were significantly correlated with most of the landscape factors and the majority of the farming methods measured, suggesting that the scoring system could be used as a strategic biodiversity evaluation tool. The results showed that the farm area and the proportion and diversity of natural/seminatural habitats were significantly correlated with ABI scores; this suggests that eco-friendly farms are positive contributors to the whole landscape mosaic, and establishing more of them might benefit biodiversity conservation. This study may guide the landscape and farming management of ecological farms and inform the process of on-farm biodiversity monitoring and assessment.

Cross-cultural studies suggest that people typically prefer to eat familiar foods from their own culture rather than foreign foods from other cultures. On this basis, it is plausible that neural responsiveness elicited by palatable food images from one’s own culture differ from those elicited by food depictions from other cultures. Toward clarifying this issue, we examined neural activation and self-report responses to indigenous (Chinese) versus Western food images among young Chinese adults. Participants (33 women, 33 men) viewed Chinese food, Western food and furniture control images during a functional magnetic resonance imaging (fMRI) scan and then rated the images on “liking,” “wanting,” and “difficult resisting.” Analyses indicated there were no significant differences in self-report ratings of Chinese versus Western food images. However, Chinese food images elicited stronger activation in regions linked to cravings, taste perception, attention, reward, and visual processing (i.e., cerebellum crus, superior temporal gyrus, supramarginal gyrus, middle temporal gyrus, inferior parietal lobule, posterior insula, middle occipital gyrus; inferior occipital gyrus). Conversely, Western food images elicited stronger activation in areas involved in visual object recognition and visual processing (inferior temporal gyrus, middle occipital gyrus, calcarine). These findings underscored culture as a potentially important influence on neural responses to visual food cues and raised concerns about the ecological validity of using “standard” Western food images in neuroimaging studies of non-Western samples. Results also provide foundations for designing culturally informed research and intervention approaches in non-Westerns contexts guided by the use of external food cues that are most salient to the cultural group under study.

Abstract Background We combined anatomy with imaging, transformed the 2D information of various imaging techniques into 3D information, and form the assessment system of real medical imaging cases in order to make up for the deficiencies in the current teaching of the medical imaging technology students. Methods A total of 460 medical imaging students were selected and randomly divided into two groups. The research group received the teaching of the fusion of the original CT and MR data 3D model and the original image combined with 3D anatomical image. CT and MRI data are imported through load DICOM of 3D slicer. Different tissues and organs are segmented by threshold and watershed algorithm of segment editor module. Models are exported through export / import models and label maps in segmentation. Save the NHDR file of the original data and Obj file of the corresponding model through save the NHDR and corresponding Obj files are loaded into probe 1.0 software. The software can give different colors to the three-dimensional models of different organs or tissues to display the stereo models and related data, and display the hook edges of organ models on coronal, sagittal and axial images. At the same time, annotation can be established in the corresponding anatomical position. Finally, it can be saved as a single file of Hwl, and the teaching can be opened at any time through the program of probe 1.0. Statistical analysis Academic self-efficacy scale and Self-directed learning ability scale was adopted by self-directed learning evaluation scale between two groups. Results Compare the theoretical scores and case analysis scores of the two groups. The scores of the study and control groups were significantly higher than those of the control group. Before the experiment, no significant difference was detected in the self-efficacy of learning ability and learning behavior between the two groups, while after the experiment, these differences between the two groups were statistically significan. Moreover, the learning ability self-efficacy and learning behavior of the two groups of students after the experiment was significantly higher than that before the experiment. The self-efficacy of the learning behavior of the control group was higher after the experiment than that before the experiment, albeit the difference was not statistically significant. Conclusions The modern, information-based and humanized experimental teaching mode will be constantly improved under the support of PACS system in order to optimize the medical imaging teaching activities for the development of modern medical education.