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The ductility and toughness of peak-aged (PA) Mg-RE alloys are significantly influenced by their grain structure characteristics. To investigate this issue, we examined PA Mg-8.24Gd-2.68Y (wt.%) alloys with two distinct grain structures: an extruded-PA sample with dynamic recrystallized (DRXed) fine grains and coarse hot-worked grains, and an extrusion-solution treated and PA sample with grown large equiaxed grains. The results showed that the extruded-PA sample demonstrated a favorable combination of tensile strength (426 MPa) and ductility (7.0 %). Although intergranular microcracks nucleated in the DRXed region due to strain incompatibility, crack propagation was impeded by the DRXed fine grains, inducing intrinsic and extrinsic toughening mechanisms. On the other hand, the hot-worked grains in the extruded-PA sample initiated transgranular cracks after a relatively high strain, attributed to the strain partitioning effect, ultimately leading to failure. In comparison, the solution-treated-PA sample exhibited lower tensile strength and ductility (338 MPa and 3.7 %, respectively). Intergranular cracks nucleated in the CG sample before necking, and the readily formed critical crack, facilitated by the large grain size, exhibited unstable crack growth, resulting in premature failure. This work offers valuable insights for designing high-performance PA Mg-RE alloys and preventing premature failure in practical applications.

Abstract The combination of fingerprint positioning and 5G (the 5th Generation Mobile Communication Technology) offers broader application prospects for indoor positioning technology, but also brings challenges in real-time performance. In this paper, we propose a fingerprint positioning method based on a deep convolutional neural network (DCNN) using a classification approach in a single-base station scenario for massive multiple input multiple output-orthogonal frequency division multiplexing (MIMO-OFDM) systems. We introduce an angle-delay domain fingerprint matrix that simplifies the computation process and increases the location differentiation. The cosine distance is chosen as the fingerprint similarity criterion due to its sensitivity to angular differences. First, the DCNN model is used to determine the sub-area to which the mobile terminal belongs, and then the weighted K-nearest neighbor (WKNN) matching algorithm is used to estimate the position within the sub-area. The positioning performance is simulated in a DeepMIMO indoor environment, showing that the classification DCNN method reduces the positioning time by 77.05% compared to the non-classification method, with only a 1.08% increase in average positioning error.

Abstract Substance Use Disorders (SUDs) present a significant challenge to global public health, with prolonged drug use not only impairing individual health but also hindering social development. Despite various interventions aimed at addressing drug abuse and dependence, a high relapse rate remains a prominent issue. In light of this, this study aims to explore the impact of perceived stress on the relapse of individuals with SUDs, as well as the mediating role of self-control and the moderating role of social support, in hopes of providing new perspectives for interventions to reduce the risk of relapse among individuals with SUDs. By utilizing a convenience sampling method, 420 male individuals with SUDs were recruited from detoxification centers in Guangxi, China. They completed questionnaires on perceived stress, self-control, social support, and tendencies towards relapse. A total of 401 valid datasets were obtained and analyzed using the SPSS Process plugin to conduct a moderated mediation model analysis. Results: (1) Perceived stress had a positive impact on the relapse of individuals with SUDs, (2) Self-control played a partial mediating role between perceived stress and the relapse, (3) The direct effect of perceived stress on the relapse and its first half of the indirect effect were moderated by social support. The research emphasize the critical importance of learning stress management strategies, enhancing self-control, and receiving comprehensive social support in the prevention and treatment of substance dependence. By strengthening self-control and social support as both internal and external resources, the likelihood of relapse among individuals with SUDs can be reduced, contributing to more effective and comprehensive drug rehabilitation strategies.

Abstract Approximately 75% of stroke survivors have movement dysfunction. Rehabilitation exercises are capable of improving physical coordination. They are mostly conducted in the home environment without guidance from therapists. It is impossible to provide timely feedback on exercises without suitable devices or therapists. Human action quality assessment in the home setting is a challenging topic for current research. In this paper, a low-cost HREA system in which wearable sensors are used to collect upper limb exercise data and a multichannel 1D-CNN framework is used to automatically assess action quality. The proposed 1D-CNN model is first pretrained on the UCI-HAR dataset, and it achieves a performance of 91.96%. Then, five typical actions were selected from the Fugl-Meyer Assessment Scale for the experiment, wearable sensors were used to collect the participants’ exercise data, and experienced therapists were employed to assess participants’ exercise at the same time. Following the above process, a dataset was built based on the Fugl-Meyer scale. Based on the 1D-CNN model, a multichannel 1D-CNN model was built, and the model using the Naive Bayes fusion had the best performance (precision: 97.26%, recall: 97.22%, F1-score: 97.23%) on the dataset. This shows that the HREA system provides accurate and timely assessment, which can provide real-time feedback for stroke survivors’ home rehabilitation.

Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Abstract Background Diabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear. Methods Firstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5’s effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated. Results NDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5. Conclusion METTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.

Abstract Background In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. Main body Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. Conclusion ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach. Graphical Abstract

Single B cells-based antibody platforms offer an effective approach for the discovery of useful antibodies for therapeutic or research purposes. Here we present a method for screening equine immunoglobins F(ab)2, which offers the potential advantage of reacting with multiple epitopes on the virus. Using equine influenza virus (EIV) as model, a hemagglutinin (HA) trimer was constructed to bait B cells in vaccinated horses. We screened 370 HA-specific B cells from 1 × 106 PBMCs and identified a diverse set of equine variable region gene sequences of heavy and light chains and then recombined with humanized Ig Fc. Recombinant equine Ig was then self-assembled in co-transfected 293 T cells, and subsequently optimized to obtain HA binding B-cell receptor (s). The recombinant antibodies exhibited a high binding affinity to the HA protein. Antibody H81 exhibited the highest cross neutralizing activities against EIV strains in vitro. Furthermore, it effectively protected EIV-challenged mice, resulting in significantly improved survival, reduced pulmonary inflammation and decreased viral titers. In silico predication identified a functional region of H81 comprising 27 key amino acids cross the main circulating EIV strains. The 12 amino acid residues in this region with the highest binding affinities were screened. Notably, the predicted epitopes of H81 encompassed the documented equine HA receptor binding site, validating its cross-neutralization. In summary, a rapid platform was successfully established to investigate the profiling of equine antigen-recognizing receptors (BCRs) following infection. This platform has the potential to optimize the screening of virus-neutralizing antibodies and aid in vaccine design.

Aerosol emissions from the CO2-capture process have a significant impact on both solvent depletion and environmental contamination. This work comprehensively investigated the emissions of AMP (2-amino-2-methyl-1propanol)/PZ (piperazine) from a bench-scale platform and a CO2-capture pilot plant. The concentration of nuclei in flue gas is a key factor affecting aerosol emissions, and a high nuclei concentration leads to more serious aerosol emission problems. The amine emissions after the absorber in the three different scenarios (no added nuclei, nuclei added, and pilot plant) were 273, 1051, and 1347 mg/Nm3, respectively. Increasing the lean-solvent temperature promoted aerosol emissions, and increasing the liquid/gas ratio and CO2 loading in the lean solvent suppressed aerosol emissions. In the pilot plant, the effects of four mitigation measures were evaluated, and it was found that dry bed and acid washing had better mitigation effects than did conventional water washing; amine emissions could be reduced to as low as 21 mg/Nm3 PZ and 25 mg/Nm3 AMP. This study provides a reference for the design and optimization of carbon-dioxide-capture systems, which can help to reduce the impact on the environment.

ObjectiveSubstance use disorders (SUDs) pose a significant challenge to public health systems worldwide, with persistent high relapse rates underscoring the urgency for innovative intervention strategies. This study embarked on a systematic exploration of the factors influencing relapse among individuals with SUDs, alongside the implementation of targeted Health Qigong intervention to mitigate these effects based on the embodied cognition.MethodsIn the cross-sectional survey, a total of 398 male substance users were recruited to complete the questionnaires assessing depression, self-esteem, resilience, and relapse inclination. Subsequently, 60 participants diagnosed with depression were selected for a Pilot RCT, randomly divided into an intervention group, which underwent a 12-week Health Qigong program designed to combat depression through embodied cognition principles, and a control group, which maintained their daily routines.ResultsStructural equation modeling demonstrated that depression not only had a direct effect on substance users’ relapse, but also exerted an indirect effect through three paths: firstly, via the mediating role of self-esteem; secondly, via the mediating role of resilience; and thirdly, via the chain-mediated role of self-esteem and resilience. Two-factor mixed-design ANOVA showed that the 12-week targeted Health Qigong training not only mitigated depression in individuals with SUDs, but also enhanced self-esteem and mental resilience, and reducing the propensity for relapse.ConclusionThis research identifies critical factors influencing relapse in individuals with SUDs and introduces a novel, non-pharmacological intervention that significantly diminishes relapse rates and enhances recovery outcomes. It highlights the importance of physical activity in promoting mental health improvement and integrates traditional Chinese exercises with contemporary psychological insights, offering a comprehensive approach to drug rehabilitation and the integration of cultural practices in holistic health interventions.

The cornea is a vital tissue of the human body. The health status of the cornea has a great impact on the quality life of person. There has been a great deal of research on the human cornea biomechancis. However, the difficulty in obtaining the human cornea has greatly limited the research of cornea biomechancis. Using finite element modelling has become a very effective and economical means for studying mechanical properties of human cornea. In this review, the geometrical and constitutive models of the cornea are summarised and analysed, respectively. Some factors affecting of the finite element calculation are discussed. In addition, prospects and challenges for the finite element model of the human cornea are presented. This review will be helpful to researchers performing studies in the relevant fields of human cornea finite element analysis.

Background and aimDiagnosing high-risk varices (HRV) is crucial for determining the prognosis and treatment strategy in patients with hepatocellular carcinoma (HCC). Although the Baveno VI consensus guidelines have been validated for assessing HRV in patients with liver cirrhosis, their applicability to those with HCC remains uncertain. This study aims to evaluate the effectiveness of the Baveno VI criteria in screening for HRV in patients with HCC.MethodsWe searched for English-language articles related to Baveno criteria and HCC across PubMed, Embase, Web of Science, and Cochrane databases, covering publications from their inception until April 19, 2024. Our meta-analysis was conducted using STATA 14.0 and Meta-Disc 1.4 software. We assessed the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We analyzed pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) using a random-effects model and constructed a summary receiver operating characteristic (SROC) curve. Based on established consensus, the favorable Baveno VI criteria were defined as a liver stiffness measurement (LSM) < 20 kPa and a platelet count (PLT) > 150×109/L to exclude HRV. This study is registered with PROSPERO under the registration number CRD42024533946.ResultsWe finally brought four studies, including 1277 patients with HCC, into this meta-analysis. The SEN, SPE, DOR, and AUC of favorable Baveno VI criteria in screening HRV in patients with HCC were 0.90 (95% CI: 0.81–0.95), 0.33 (95% CI: 0.25–0.41), 4.44 (95% CI: 2.14–9.22), and 0.59 (95% CI: 0.55–0.64), respectively. The LR+ and LR- of the favorable Baveno VI criteria were 1.34 (95% CI: 1.19–1.50) and 0.30 (95% CI: 0.16–0.58), respectively. Subgroup and meta-regression analyses indicated that BCLC and Child-Pugh stages likely contribute to the heterogeneity in the SPE.ConclusionsThe favorable Baveno VI criteria may not effectively screen HRV in patients with HCC. However, the current evidence is insufficient, and further studies with larger sample sizes and detailed patient subgroups are needed.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024533946.

Background: Keloids are benign skin tumors characterized by fibroblast proliferation, tumor-like biological behavior, and excessive deposition of extracellular matrix in wounded skin. Ferroptosis, a type of programmed cell death, is critical in tumor pathogenesis. We aimed to investigate the role of ferroptosis in keloid formation. Methods: We downloaded public high-throughput sequencing raw count data (GSE92566), containing three normal skin and four keloid samples, from the Gene Expression Omnibus database. Ferroptosis-related genes were obtained from the Ferroptosis database website. The ferroptosis-related differentially expressed genes (FRDEGs) were obtained by merging differentially expressed genes with ferroptosis-related genes. The FRDEGs were then used for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, protein-protein interaction (PPI) network, and microRNA (miRNA)-mRNA network analysis. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate our findings. Results: We found 25 FRDEGs, including 8 up-regulated and 17 down-regulated genes. Pathway enrichment analysis revealed that the Hippo and transforming growth factor β signaling pathways were significantly up-regulated in keloids. In contrast, regulation of the peroxisome proliferator-activated receptor signaling pathway, glutathione metabolism, and unsaturated fatty acid metabolic process were down-regulated. PPI and FRDEGs hub networks were constructed using the STRING database and Cytoscape software. Ten hub genes were identified, including PLA2G6, RARRES2, SNCA, CYP4F8, CDKN2A, ALOX12, FABP4, ALOX12B, NEDD4, and NEDD4L. We constructed a miRNA-mRNA network, which predicted hsa-mir-155-5p, hsa-let-7b-5p, hsa-mir-124-3p, hsa-mir-145-5p, hsa-mir-328-3p, hsa-mir-24-3p, and hsa-mir-10b-5p as the most connected miRNAs regulating ferroptosis in keloids. Finally, we verified the expression levels of the hub genes by RT-qPCR, which confirmed that ALOX12, ALOX12B, and CYP4F8 expression were reduced in keloids. Conclusions: This study provides novel information on ferroptosis-mediated keloid pathogenesis, underscoring the importance of further research in this area to unlock new therapeutic avenues for keloid treatment.

Abstract Image‐based machine learning tools are an ascendant ‘big data’ research avenue. Citizen science platforms, like iNaturalist, and museum‐led initiatives provide researchers with an abundance of data and knowledge to extract. These include extraction of metadata, species identification, and phenomic data. Ecological and evolutionary biologists are increasingly using complex, multi‐step processes on data. These processes often include machine learning techniques, often built by others, that are difficult to reuse by other members in a collaboration. We present a conceptual workflow model for machine learning applications using image data to extract biological knowledge in the emerging field of imageomics. We derive an implementation of this conceptual workflow for a specific imageomics application that adheres to FAIR principles as a formal workflow definition that allows fully automated and reproducible execution, and consists of reusable workflow components. We outline technologies and best practices for creating an automated, reusable and modular workflow, and we show how they promote the reuse of machine learning models and their adaptation for new research questions. This conceptual workflow can be adapted: it can be semi‐automated, contain different components than those presented here, or have parallel components for comparative studies. We encourage researchers—both computer scientists and biologists—to build upon this conceptual workflow that combines machine learning tools on image data to answer novel scientific questions in their respective fields.

Abstract Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5′ end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses’ broad-infectivity range.

Abstract Hepatocellular carcinoma (HCC) is still a public health disease with its high prevalence and morbidity. Short of early diagnosis biomarkers and effective therapy, the treatment of HCC patients hasn’t achieved ideal effect. Hypoxia is a hallmark of HCC, which is mainly induced by imbalance of tumor cell proliferation and insufficient supply of oxygen. Recently, amounting evidence suggested lncRNAs, especially hypoxia-related lncRNAs play a pivotal role in regulating HCC. Hypoxia-related lncRNAs are involved in altering glucose metabolism, maintaining of cancer stem cell-like properties (CSCs), cell apotosis, proliferation and immune escape, which all contribute to the poor prognosis of HCC patients. The novel identified hypoxia-related lncRNAs could be the potential target or biomarkers of HCC, which are beneficial to the clinical treatment. Herein, we summarized currently reported hypoxia-related lncRNAs and their related mechanisms, providing potential application and future perspective of hypoxia-related lncRNAs as a potential therapeutic target.

Pandemics like COVID-19 have highlighted the potential of Photoacoustic imaging (PAI) for Brain-Computer Interface (BCI) communication and lung diagnostics. However, PAI struggles with the clear imaging of blood vessels in areas like the lungs and brain due to their cavity structures. This paper presents a simulation model to analyze the generation and propagation mechanism within phantom tissues of PAI artifacts, focusing on the evaluation of both Anisotropic diffusion filtering (ADF) and Non-local mean (NLM) filtering, which significantly reduce noise and eliminate artifacts and signify a pivotal point for selecting artifact-removal algorithms under varying conditions of light distribution. Experimental validation demonstrated the efficacy of our technique, elucidating the effect of light source uniformity on artifact-removal performance. The NLM filtering simulation and ADF experimental validation increased the peak signal-to-noise ratio by 11.33% and 18.1%, respectively. The proposed technique adds a promising dimension for BCI and is an accurate imaging solution for diagnosing lung diseases.

Aim: To discover novel methylation-related differentially expressed genes (MRDEGs) for cervical cancer, with a focus on their potential for early diagnosis and prognostic assessment. Materials & methods: We integrated data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. TCGA-MRDEGs were identified by analyzing differentially methylated genes (DMGs) and their correlation with gene expression. We examined GEO datasets GSE39001, GSE9750, and GSE46306 for GEO-MRDEGs. Overlapping MRDEGs were subjected to overall survival (OS) analysis to identify prognostic markers. The expression and methylation levels of these genes were validated in a total of 30 tissue samples, comprising 20 from cervical cancer patients and 10 from normal cervical tissues, using qRT-PCR and MassARRAY EpiTYPER Assay. Results: A total of 314 TCGA-MRDEGs and 40 GEO-MRDEGs were identified. Intersection analysis yielded 10 overlapping MRDEGs. Notably, NOVA1, GSTM5, TRHDE, and CXCL12 were found to have reduced expression and increased methylation in cervical cancer, which correlated with poor prognosis. The methylation status and expression levels of these genes were confirmed in tissue specimens. Conclusion: We identified four MRDEGs as potential prognostic biomarkers for cervical cancer. Their clinical utility is highlighted, but further validation in larger cohorts is required to establish their clinical significance.

Cancer stem cells (CSCs) play a crucial role in tumor initiation, recurrence, metastasis, and drug resistance. However, the current understanding of CSCs in hepatocellular carcinoma (HCC) remains incomplete. Through a comprehensive analysis of the database, it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a critical enzyme involved in cholesterol synthesis, is up-regulated in HCC tissues and liver CSCs. Moreover, high expression of HMGCR is associated with a poor prognosis in patients with HCC. Functionally, HMGCR promotes the stemness and metastasis of HCC both in vitro and in vivo. By screening various signaling pathway inhibitors, we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in HCC. Mechanistically, HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger 1. Inhibition of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in HCC. Notably, simvastatin, an FDA-approved cholesterol-lowering drug, has been shown to inhibit stemness and metastasis of HCC by targeting HMGCR. Taken together, our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling, and simvastatin holds the potential for clinical suppression of HCC metastasis.

Effectively utilizing large-scale Private Electric Vehicles (PREVs) in load restoration can enhance the capability of Distribution System Operators (DSOs) to respond to accidental power outages. However, the challenge remains in incentivizing and guiding PREVs to participate in load restoration. This paper proposes a Stackelberg game-based incentive mechanism, with a V2G Station Operator (VSO) discharge guidance model based on the Huff attraction model embedded to address this challenge. The VSO is introduced to manage the issue of PREVs having small individual capacities, and not meeting the criteria for direct participation in electricity markets. Firstly, a framework for involving PREVs in load restoration is introduced, clarifying the responsibilities of PREVs, VSO, DSO, and Distribution Market Operator (DMO), as well as the interrelation of incentive mechanism and discharge guidance strategy. Secondly, models for each game participant are established. The VSO encapsulates the discharge guidance strategy into an optimization model using the Huff attraction-based model that captures the destination choice probabilities of PREVs, and the DSO develops a load restoration model. Thirdly, a Stackelberg game model is established with the DMO as the leader and VSO and DSO as followers. The existence and uniqueness of the proposed Stackelberg game’s equilibrium solution are proven, and a distributed iterative algorithm is employed for the solution. Finally, numerical simulations are performed with the IEEE 33-bus distribution system and a simplified road network to validate the proposed strategy’s effectiveness in guiding PREVs’ participation in load restoration, enhancing the restoration capability of the DSO, and improving the economic efficiency of each participant.

Deep Reinforcement Learning (DRL) is effective in solving complex, non-linear optimization problems, which is particularly relevant in energy management within Integrated Energy Systems (IESs). However, DRL approaches conventionally focus on single-objective policy learning, which is inadequate for the multi-objective optimization tasks commonly encountered in IESs energy management. To improve this, these approaches typically combine multi-objectives, such as operating cost objective and safety objective into a single reward function using scalarization techniques. This reduces the fidelity and interpretability of the objective space and limits its applicability to a wide range of IESs energy management. To address these challenges, this paper presents a novel framework called Multi-Agent and Multi-Objective DRL (MAMODRL). This framework combines value function decomposition and policy gradient methods to achieve a Pareto-optimal solution. The IESs energy management is initially formulated as a multi-objective Markov decision process. Then, an advanced MAMODRL architecture is developed, which includes objective value function networks to facilitate policy optimization. Finally, based on the definition of dominance, Pareto frontier is approximated of IESs energy management. A case study suggests that the proposed approach is effective in solving the Pareto frontier for IESs energy management. To ensure the safe operation of the system, safety threshold is set at the Pareto frontier forming a Pareto optimization with safety conditions. Compared to traditional DRL approaches, the proposed approach is more flexible, interpretable, and capable of making multi-dimensional decisions.

Background: The predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. Methods: This study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. Results: A total of 134 patients, with an average age of 59.78 ± 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661–3.779, P

Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) are members of a group of genetically highly homologous lentiviruses collectively referred to as small ruminant lentiviruses (SRLVs). SRLVs can infect sheep, goats and other small ruminants, causing multisystemic disease with progressive and persistent inflammatory changes, severely reducing animal productivity and impeding animal trade. The capsid protein of SRLVs, p28, is highly conserved among strains and is a commonly used marker for the detection of SRLVs. In this study, two monoclonal antibodies (mAbs), designated G8F7 and A10C12, against p28 were generated using a recombinant p28 protein expressed in Escherichia coli as an immunogen. Functional analysis showed that these two monoclonal antibodies could be used in iELISA, immunofluorescence assays (IFA) and western blot assays to detect p28 or Gag precursor proteins of SRLVs. Two linear epitopes, 61GNRAQKELIQGKLNEEA77 (E61-77) and 187CQKQMDRVLGTRVQQATVEEKMQACR212 (E187-212), which are recognized by G8F7 and A10C12, respectively, were identified through truncation of the GST-fused p28. Amino acid sequence alignment showed that the epitope E61-77 is conserved among SRLVs, with a dominant mutation site (K72R) that does not disrupt recognition by G8F7. E187-212 was found to exhibit variability among SRLVs, but the majority of mutant epitopes are recognized by A10C12, with the exception of a mutant epitope from an isolate with undefined subtypes from Ovis aries, which was not recognized. These findings may facilitate future study of SRLVs and promote the development of methods for the detection of these viruses.

Background: Aged sarcopenia is characterized by loss of skeletal muscle mass and strength, and mitochondrial dysregulation in skeletal myocyte is considered as a major factor. Here, we aimed to analyze the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on mitochondrial reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in aged skeletal muscles. Methods: C2C12 cells were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of cellular ROS, mitochondrial ROS, and expression of PGC-1α and Nrf2. Different PGC-1α expression in cells was established by transfection with small interfering RNA (siRNA) or plasmids overexpressing PGC-1α (pEX-3-PGC-1α). The effects of different PGC-1α expression on cellular ROS, mitochondrial ROS and Nrf2 expression were measured in cells. Wild type (WT) mice and PGC-1α conditional knockout (CKO) mice were used to analyze the effects of PGC-1α on aged sarcopenia and expression of Nrf2 and CD38 in gastrocnemius muscles. Diethylmaleate, a Nrf2 activator, was used to analyze the connection between PGC-1α and Nrf2 in cells and in mice. Results: In C2C12 cells, the expressions of PGC-1α and Nrf2 were declined by the 7β-OHC treatment or PGC-1α silence. Moreover, PGC-1α silence increased the harmful ROS and decreased the Nrf2 protein expression in the 7β-OHC-treated cells. PGC-1α overexpression decreased the harmful ROS and increased the Nrf2 protein expression in the 7β-OHC-treated cells. Diethylmaleate treatment decreased the harmful ROS in the 7β-OHC-treated or PGC-1α siRNA-transfected cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia, decreased Nrf2 expression and increased CD38 expression in gastrocnemius muscles compared with the WT mice. Diethylmaleate treatment improved the muscle function and decreased the CD38 expression in the old two genotypes. Conclusions: Our study demonstrated that PGC-1α modulated mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2.

Introduction Keloids, benign fibroproliferative tumours characterised by excessive fibroblast proliferation and over-deposition of extracellular matrix, pose a therapeutic challenge with high recurrence rates. Betamethasone (diprospan) injection (BI) is one of the most common non-invasive therapies for keloids. Pulsed dye laser (PDL) has the function of closing microvessels, which may become one of the auxiliary treatment methods of BI and may enhance its curative effect. Some studies suggest that the combination of a dual-wavelength dye laser (DWL) and BI may offer superior efficacy. This randomised controlled trial aims to evaluate whether the combined therapy of DWL+BI outperforms BI alone in treating keloids.Methods and analysis This single-centre, parallel positive control, randomised trial evaluates the efficacy and safety of DWL (585 nm PDL+1064 nm neodymium-doped yttrium aluminium garnet) combined with BI for keloid treatment. Enrolling 66 adult patients, participants are randomised into DWL+BI or BI groups in a 1:1 ratio. Over 12 weeks, each group undergoes four treatment sessions, ensuring blinding for outcome assessors. Data collection occurs at multiple time points (4, 12, 24 and 52 weeks), with primary outcomes assessing the Vancouver Scar Scale (VSS) improvement rate 24 weeks after the last intervention. Secondary outcomes include VSS improvement rates, changes in keloid volume, changes in relative perfusion index measured by laser speckle contrast imaging, Patient and Observer Scar Assessment Scale results and patient satisfaction. Safety assessments include vital signs, laboratory tests, pregnancy tests and self-reports of adverse reactions.Ethics and dissemination The results will be presented in peer-reviewed journals and at international conferences. This study is approved by the Ethics Committee of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.Trial registration number Chinese Clinical Trial Register (ChiCTR2400080148).

The Tibetan Plateau (TP) is the headwater of the Yangtze, Yellow, and the transboundary Yarlung Zangbo, Lancang, and Nujiang Rivers, providing essential and pristine freshwater to around 1.6 billion people in Southeast and South Asia. However, the temperature rise TP has experienced is almost three times that of the global warming rate. The rising temperature has resulted in glacier retreat, snow cover reduction, permafrost layer thawing, and so forth. Here we show, based on the longest observed streamflow data available for the region so far, that changing climatic conditions in the TP already had significant impacts on the streamflow in the headwater basins in the area. Our analysis indicated that the annual average temperature in the headwater basins of these five major rivers has been rising on a trend averaging 0.38 °C·decade−1 since 1998, almost triple the rate before 1998, and the change of streamflow has been predominantly impacted by precipitation in these headwater basins. As a result, streamflow in the Yangtze, Yarlung Zangbo, Lancang, and Nujiang River headwater areas is on a decreasing trend with a reduction of flow ranging from 3.0 ×109–5.9 ×109 m3·decade−1 (−9.12% to −16.89% per decade) since 1998. The increased precipitation in the Tangnahai (TNH) and Lanzhou (LZ) Basins contributed to the increase of their streamflows at 8.04% and 14.29% per decade, respectively. Although the increased streamflow in the headwater basins of the Yellow River may ease some of the water resources concerns, the decreasing trend of streamflow in the headwater areas of the southeastern TP region since 1998 could lead to a water crisis in transboundary river basins for billions of people in Southeast and South Asia.

Purposes The corneal shape and mechanical properties of cornea and contact lens material have a certain impact on the correction effect of contact lens. Methods In this paper, a finite element model of corneal wearing orthokeratology lens was established by using hyperelasticity materials, and the biomechanical response of cornea after wearing lens was analyzed by changing the shape of cornea (different curvature and thickness) and the material parameters of cornea and orthokeratology lens. Findings The results showed that when the corneal curvature changed 4 m−1, the displacement difference at apex of the cornea central area changed by 15.7 μm, and when the corneal thickness changed by 75 μm, the displacement difference at apex of the central area changed by 12.3 μm; when the corneal material parameter k1 increased by 3 times, the change of displacement difference at apex of the cornea central area was 39.2 μm, when the C10 value increased by 4 times, the change of displacement difference was 55.5 μm, while when the orthokeratology lens material parameter E increased by 3 times, the change of displacement difference was only 0.2 μm. Conclusions When using orthokeratology lens to correct myopia, it is necessary to fully consider the influence of corneal morphology and the mechanical properties of the cornea on the correction effect.

Abstract Background Equine piroplasmosis is caused by two tick-borne protozoan parasites, Theileria equi and Babesia caballi,, which are clinically relevant in susceptible horses, donkeys, and mules. Moreover, equine piroplasmosis significantly constrains international trading and equestrian events. Rapidly diagnosing both parasites in carrier animals is essential for implementing effective control measures. Here, a rapid immunochromatographic test for the simultaneous detection of antibodies to T. equi and B. caballi was evaluated using samples from horses and donkeys collected in Greece, Israel, and Italy. The results were compared with an improved competitive enzyme-linked immunosorbent assay (cELISA) for detecting antibodies to both parasites using the same panel of samples. Methods Blood samples were collected from 255 horses and donkeys. The panel consisted of 129 horses sampled at four locations in northern Greece, 105 donkeys sampled at four locations in Sicily, and 21 horses sampled at two locations in Israel. The rapid test and the cELISA were performed according to the manufacturer’s instructions, and the results were subjected to a statistical analysis to determine the sensitivity and specificity of both tests and their association. Results The immunochromatographic test provided a result within 15 min and can be performed in the field, detecting both pathogens simultaneously. The overall coincidence rate between the rapid test and the cELISA for detecting antibodies against T. equi was 93% and 92.9% for B. caballi. The rapid test’s sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for T. equi were above 91.5%. Sixteen samples were positive for both parasites in the rapid test and eight in the cELISA. Either test had no significant association between T. equi and B. caballi detection. The detection rates of both parasites were significantly higher in Italy than in Greece or Israel and in donkeys than in horses. The agreement for T. equi between the results of both tests was high in Greece (93.8%) and Italy (95.2%) and moderate in Israel (76.2%). For B. caballi, the specificity and NPV of the rapid test were high (94.2% and 98.3%, respectively), although the sensitivity and PPV were moderate (69.2% and 39.1%, respectively) due to the small sample size. However, for B. caballi, the sensitivity was higher with the rapid test. Conclusions The rapid test detected T. equi and B. caballi simultaneously in the field, potentially replacing laborious cELISA testing and is recommended for import/export purposes. The test can also be helpful for the differential diagnosis of clinical cases, since seropositivity may rule out equine piroplasmosis since it does not indicate current or active infection. Graphical Abstract

Abstract The development of stable and efficient ligands is of vital significance to enhance the catalytic performance of carbonylation reactions of alkenes. Herein, an aryldiphosphine ligand (L11) bearing the [Ph2P(ortho-C6H4)]2CH2 skeleton is reported for palladium-catalyzed regioselective carbonylation of alkenes. Compared with the industrially successful Pd/1,2-bis(di-tert-butylphosphinomethyl)benzene catalyst, catalytic efficiency catalyzed by Pd/L11 on methoxycarbonylation of ethylene is obtained, exhibiting better catalytic performance (TON: >2,390,000; TOF: 100,000 h−1; selectivity: >99%) and stronger oxygen-resistance stability. Moreover, a substrate compatibility (122 examples) including chiral and bioactive alkenes or alcohols is achieved with up to 99% yield and 99% regioselectivity. Experimental and computational investigations show that the appropriate bite angle of aryldiphosphine ligand and the favorable interaction of 1,4-dioxane with Pd/L11 synergistically contribute to high activity and selectivity while the electron deficient phosphines originated from electron delocalization endow L11 with excellent oxygen-resistance stability.

Abstract Background Totally preperitoneal hernioplasty (TPP) is a concept which was introduced for distinguishing with totally extraperitoneal (TEP). There is few evidence reflecting the single incision laparoscopic totally preperitoneal (SIL-TPP) characteristic. The aim of study is to demonstrate the feasibility of single incision laparoscopic totally preperitoneal hernioplasty (SIL-TPP) and compare the outcomes with the single incision laparoscopic totally extraperitoneal hernioplasty (SIL-TEP) technique. Methods During August 2018 and July 2022, 200 inguinal hernia patients received SIL-TPP and 56 patients received SIL-TEP in the First hospital of Ningbo university. The demographics, clinical characteristics, intraoperative and postoperative parameters were retrospectively analysed. Results SIL-TPP and SIL-TEP hernia repair were successfully conducted in all patients. There was no conversation happened in two group. Patients’ demographics were comparable when compared between the two groups adding the comparison initial 52 cases analysis (P > 0.05). The mean unilateral hernia operative time was significant shorter in the SIL-TPP group than SIL-TEP group (unilateral: 81.38 ± 25.32 vs. 95.96 ± 28.54, P: 0.001). Further study of unilateral hernia operative time revealed the mean indirect hernia operative time was significant shorter in the SIL-TPP group than SIL-TEP group (indirect: 81.38 ± 25.33 vs. 95.87 ± 28.54, P: 0.001). The unilateral hernia operation time trend of initial 52 cases of two group analysis revealed the operation time of SIL-TPP reduced faster than SIL-TEP along with treating number increasing (Figs. 2 and 3). The comparison of initial equal quantity unilateral hernia patient mean operative time revealed the SIL-TPP group was significant shorter than SIL-TEP group (85.77 ± 22.76 vs. 95.87 ± 28.54, P: 0.049). The rate of peritoneum tearing of SIL-TPP group was significant high than SIL-TEP (P = 0.005). Conclusion SIL-TPP hernia repair is a superior procedure and possess its own distinguished advantages. We recommend it rather than SIL-TEP for treating inguinal hernia, especially for indirect hernia. However, large-scale randomized controlled trials comparing SIL-TPP and SIL-TEP are needed to confirm these results.

Abstract Background Vulvar migration is a rare complication of filler injection for breast augmentation, generally presenting as repeated pain and fever. We will report a case of woman with polyacrylamide hydrogel breast injection develops vulvar abscess. Case presentation A woman with a history of polyacrylamide hydrogel breast injection was noted to have vulvar abscess due to migration of filler materials. Filler removal surgery and vacuum sealing drainage was performed for this patient. The patient was discharged from the hospital with no further complications. After a review of pertinent literature, only four previous case reports are found. Local inflammatory response, infection, large volume injections, inframammary fold destruction, hematogenous or lymphatic migrate, trauma, gravity and external pressure could play essential parts in the migration of injected filler. Conclusion Polyacrylamide hydrogel migration poses a worldwide challenge, necessitating personalized solutions. Our case study underscores the importance of comprehensive examinations for individuals with a history of filler breast injection when suspecting vulvar filler migration.

Quantitative description of the complex relationship between rolling process and microstructure is crucial for improving the performance of 2205 duplex stainless steel products. In this work, four distinct rolling processes were used for three passes of hot rolling of 2205 duplex stainless steel. The study delved into the macroscopic morphology, microstructural gradients, and texture evolution of 2205 duplex stainless steel sheets in various rolling states. In addition, a data expansion method was used to expand the original experimental data, and the support vector machine model optimized by genetic algorithm was used to accurately describe the complex relationship between different rolling processes and microstructures. The results indicate that the proposed variable thickness cross-rolling method renders a more uniform microstructure in the rolled piece, with significantly refined grains and the formation of a distinct structural gradient. Among them, when using process 3 rolling, the grain size in the edge area of the plate after three passes of rolling is finer and the degree of recrystallization is higher, which is conducive to improving the problem of poor thermal plasticity at the edges and providing a basis for studying the suppression of edge crack damage in 2205 duplex stainless steel. In addition, the proposed machine learning model accurately predicted the grain size of plates in different rolling states, aligning closely with experimental findings.

Abstract Background Bloodstream infection of Klebsiella pneumoniae (BSI-KP) were associated with increased mortality. Klebsiella pneumoniae was tested to susceptible to colistin by E-test and broth microdilution method in clinical laboratory. This study aimed to assess the efficacy of colistin versus tigecycline, carbapenem monotherapy and combination in the treatment of BSI-KP. Methods Electronic databases such as PubMed, Web of Science and Embase were searched. The last search was in November 24th, 2022, addressing the colistin, carbapenems and tigecycline monotherapy and combination treatments in patients with BSI-KP. The primary outcomes were 30-day or 28-day mortality. OR where available with 95% CI were pooled in random-effects meta-analysis. Results Following the outlined search strategy, a total of 658 articles were identified from the initial database searching. Six studies, 17 comparisons were included. However, they all were observational design, lacking high-quality randomized controlled trials (RCTs). Moderate or low-quality evidences suggested that colistin monotherapy was associated with an OR = 1.35 (95% CI = 0.62–2.97, P = 0.45, Tau 2 = 0.00, I 2 = 0%) compared with tigecycline monotherapy, OR = 0.81 (95% CI = 0.27–2.45, P = 0.71, Tau 2 = 0.00, I 2 = 0%) compared with carbapenem monotherapy. Compared with combination with tigecycline or carbapenem, Colistin monotherapy resulted in OR of 3.07 (95% CI = 1.34–7.04, P = 0.008, Tau 2 = 0.00, I 2 = 0%) and 0.98 (95%CI = 0.29–3.31, P = 0.98, Tau 2 = 0.00, I 2 = 0% ), respectively. Conclusions Colistin, carbapenem and tigecycline monotherapy showed similar treatment effects in patients who suffered from BSI-KP. Compared with colistin monotherapy, colistin combined tigecycline therapy might play the synergism effects. Trial registration retrospectively registered.

In the process of ion-adsorption rare earth ore leaching, the migration characteristics of the wetting front in multi-hole injection holes and the influence of wetting front intersection effect on the migration distance of wetting fronts are still unclear. Besides, wetting front migration distance and leaching time are usually required to optimize the leaching process. In this study, wetting front migration tests of ion-adsorption rare earth ores during the multi-hole fluid injection (the spacing between injection holes was 10 cm, 12 cm and 14 cm) and single-hole fluid injection were completed under the constant water head height. At the pre-intersection stage, the wetting front migration laws of ion-adsorption rare earth ores during the multi-hole fluid injection and single-hole fluid injection were identical. At the post-intersection stage, the intersection accelerated the wetting front migration. By using the Darcy's law, the intersection effect of wetting fronts during the multi-hole liquid injection was transformed into the water head height directly above the intersection. Finally, based on the Green-Ampt model, a wetting front migration model of ion-adsorption rare earth ores during the multi-hole unsaturated liquid injection was established. Error analysis results showed that the proposed model can accurately simulate the infiltration process under experimental conditions. The research results enrich the infiltration law and theory of ion-adsorption rare earth ores during the multi-hole liquid injection, and this study provides a scientific basis for optimizing the liquid injection well pattern parameters of ion-adsorption rare earth in situ leaching in the future.

Three-dimensional (3D) roughness of discontinuity affects the quality of the rock mass, but 3D roughness is hard to be measured due to that the discontinuity is invisible in the engineering. Two-dimensional (2D) roughness can be calculated from the visible traces, but it is difficult to obtain enough quantity of the traces to directly derive 3D roughness during the tunnel excavation. In this study, a new method using Bayesian theory is proposed to derive 3D roughness from the low quantity of 2D roughness samples. For more accurately calculating 3D roughness, a new regression formula of 2D roughness is established firstly based on wavelet analysis. The new JRC3D prediction model based on Bayesian theory is then developed, and Markov chain Monte Carlo (MCMC) sampling is adopted to process JRC3D prediction model. The discontinuity sample collected from the literature is used to verify the proposed method. Twenty groups with the sampling size of 2, 3, 4, and 5 of each group are randomly sampled from JRC2D values of 170 profiles of the discontinuity, respectively. The research results indicate that 100%, 90%, 85%, and 60% predicting JRC3D of the sample groups corresponding to the sampling size of 5, 4, 3, and 2 fall into the tolerance interval [JRCtrue–1, JRCtrue + 1]. It is validated that the sampling size of 5 is enough for predicting JRC3D. The sensitivities of sampling results are then analyzed on the influencing factors, which are the correlation function, the prior distribution, and the prior information. The discontinuity across the excavation face at ZK78 + 67.5 of Daxiagu tunnel is taken as the tunnel engineering application, and the results further verify that the predicting JRC3D with the sampling size of 5 is generally in good agreement with JRC3D true values.

With the rapid development of digital media and entertainment industry, the importance of 3D mesh animation has become increasingly prominent. However, the traditional production methods are faced with problems such as high computational complexity and unnatural effects when dealing with complex motion. To improve the production efficiency and quality of 3D mesh animation, this study innovatively integrates integer programming, nonlinear constraint optimization, and machine learning algorithms to construct a new 3D mesh animation optimization algorithm. Comparative analysis of the improved machine learning algorithm shows that the mean absolute error of the algorithm is 0.00048 and the fit degree is 98.8%, which is better than the comparison algorithm. Then, the performance of the proposed 3D mesh animation optimization algorithm is analyzed. The results show that the rendering speed and average frame rate of the proposed algorithm are 29.5 FPS and 28.7 FPS, respectively, which is superior to the comparison algorithm. The algorithm can effectively improve the efficiency and quality of animation production, and inject new vitality into the development of digital media and entertainment industry. This study not only provides new ideas and methods for optimizing 3D mesh animation, but also provides useful references for research and applications in related fields.

Detection of high impedance faults (HIFs) has been traditionally a main challenge in the protection of distribution systems, since they do not generate enough current to be reliably detected by conventional over-current relays. Data-based methods are alternative HIF detection methods which avoid threshold settings by training a classification or regression model. However, most of them lack interpretability and are not compatible with various distribution networks. This paper proposes an object detection-based HIF detection method, which has higher visualization and can be easily applied to different scenarios. First, based on the analysis of HIFs, a Butterworth band-pass filter is designed for HIF harmonic feature extraction. Subsequently, based on the synchronized data provided by distribution-level phasor measurement units, global HIF feature gray-scale images are formed through combining the topology information of the distribution network. To further enhance the feature information, a locally excitatory globally inhibitory oscillator region attention mechanism (LEGIO-RAM) is proposed to highlight the critical feature regions and inhibit useless and fake information. Finally, an object detection network based You Only Look Once (YOLO) v2 is established to achieve fast HIF detection and section location. The obtained results from the simulation of the proposed approach on three different distribution networks and one realistic distribution network verify that the proposed method is highly effective in terms of reliability and generalization.

Abstract The AE and damage characteristics of three types of pore-structured rock under the same working conditions are studied by means of uniaxial cyclic loading and unloading tests. The results suggest that with repeated loading and unloading, AE ringing increases as a “jump”, and the denser the structure, the earlier the “jump” occurs. The AE cumulative energy shows a “step” upward trend, but there is a significant difference in the “step” spacing. By comparing the energy distribution of rocks with different pore structures, it can be seen that the smaller the porosity and the smaller the pore size, the greater the energy input and storage, and the earlier the internal failure. Compared with the other two energy-based damage calculation methods, the damage calculation method defined in this paper is closer to the true internal damage level of the rock loading cycle. The NSE value of the modified damage variable calculation method was significantly improved and it was shown that the dissipated energy before pore compaction is the main energy causing damage, after pore compaction the combined effects of dissipated energy and plastic deformation energy result in rock damage.

African horse sickness (AHS) is an acute, fatal, contagious disease of animals of the family Equidae and is caused by infection with the African horse sickness virus (AHSV). Based on the outer capsid protein VP2, AHSV is classified into nine serotypes (AHSV−1 to −9) with little or no serological cross-reactivity between them. In 2020, AHS outbreaks caused by AHSV−1 were reported in Thailand and Malaysia, marking the first occurrences of AHS in Southeast Asia. However, little is known about the antigenic profile of AHSV−1 VP2. In this study, a recombinant VP2 protein was expressed in Escherichia coli and used as an immunogen, and three monoclonal antibodies (mAbs), designated 7D11, 10A9, and 9E7, against AHSV−1 VP2, were generated. These three mAbs were then successfully used in IFA, WB, and ELISA for the detection of AHSV−1 VP2. Two overlapping linear epitopes, 670NEFDFE675 (E670–675) recognized by 9E7 and 670NEFDF674 (E670–674) recognized by 7D11 and 10A9, were identified through truncation of GST-fused VP2. Amino acid sequence alignment shows that the 670NEFDFE675 motif is completely conserved within AHSV−1 but is highly divergent in other AHSV serotypes. Our studies provide an important tool for basic research into AHSV−1 and for the diagnosis of AHSV−1.

In the Junggar Basin plague focus, Rhombomys opimus and Meriones meridianus live together, and their parasitic fleas have a similar community structure. However, R. opimus has significantly higher positive rates of Yersinia pestis and anti-F1 antibody compared with M. meridianus. In this study, Y. pestis- and antiF1 antibody-negative R. opimus and M. penicilliger were collected in Qitai county, Fukang city and Mulei county of the eastern part of the Junggar Basin. The genomic DNA was extracted from their spleen tissues, and RT1-Db1*exon1 was amplified through PCR procedure and then sequenced. Sequence analysis was performed and molecular diversity parameters were calculated and compared. The results showed that there were significant differences in nucleotide composition, amino acid composition, number and distribution of single nucleotide polymorphism (SNP) sites and number of haplotypes between R. opimus and M. penicilliger. The nucleotide diversity (π) for R. opimus was 0.00420 ± 0.00139, the haplotype diversity (h) was 0.833 ± 0.086, and the average number of nucleotide differences (K) was 2.02564. The π for M. penicilliger was 0.06569 ± 0.02524, and the h was 1.000 ± 0.045, and the K was 10.4444. The fixation index (FST) value between R. opimus and M. penicilliger was 0.9207. Furthermore, the FST value within R. opimus (0.0275) was significantly lower than that within M. penicilliger (0.2106), indicating a greater genetic variation of M. penicilliger compared with R. opimus. In conclusion, the genetic diversity analysis based on RT1-Db1*exon1 showed that M. penicilliger had higher gene polymorphism and greater genetic differentiation compared with R. opimus in the Junggar Basin plague focus, which might be associated with the low infection rate of Y. pestis.

Abstract Background According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long‐term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. Methods From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. Results The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13–14 years and 262 cases (95.3%) aged 15–19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p

Marine biological fouling is a widespread phenomenon encountered by various oceanic ships and naval vessels, resulting in enormous economic losses. Herein, novel 4,5-dichloro-2-octyl-isothiazolone@sodium alginate/chitosan microcapsules (DCOIT@ALG/CS) were prepared through composite gel method using DCOIT as core materials, ALG and CS as shells, and CaCl2 as the cross-linking agent. The formed microcapsules (MCs) with Ag nanoparticles (AgNPs) were then filled in UV-curable polysiloxane (UV-PDMS), followed by UV irradiation to yield UV-PDMS/microcapsules/AgNPs (UV-PDMS/MCs/Ag) composite coatings. The constructed micro–nano dual-scale surface using the MCs and AgNPs improved the antifouling and antibacterial properties of UV-PDMS/MCs/Ag coatings. The as-obtained UV-PDMS/MCs/Ag coatings exhibited a static contact angle of about 160°, shear strength of 2.24 MPa, tensile strength of 3.32 MPa and elongation at break of 212%. The synergistic bacteriostatic effects of DCOIT and AgNPs in UV-PDMS/MCs/Ag coatings resulted in a bactericidal rate of 200 μg ml−1 towards Escherichia coli and Staphylococcus aureus with saturation at 100% within 10 min. In sum, the proposed composite coatings look promising for future marine transportation, pipeline networks and undersea facilities.

BackgroundWuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic.ObjectiveThis study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017–2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools.MethodsThis study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis.ResultsFrom 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools.ConclusionWe successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

Background: Mitochondrial dysregulation in skeletal myocytes is considered a major factor in aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target of rapamycin complex 1 (mTORC1) in aged skeletal muscles. Methods: C2C12 myoblasts were stimulated by 50 μM 7β-hydroxycholesterol (7β-OHC) to observe the changes of DNA damage, mitochondrial membrane potential (Δψm), mitochondrial ROS and PGC-1α protein. The PGC-1α silence in the C2C12 cells was established by siRNA transfection. The levels of DNA damage, Δψm, mitochondrial ROS, Sestrin2 and p-S6K1/S6K1 proteins were observed after the PGC-1α silence in the C2C12 cells. Recombinant Sestrin2 treatment was used to observe the changes of DNA damage, Δψm, mitochondrial ROS and p-S6K1/S6K1 protein in the 7β-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. Wild-type (WT) mice and muscle-specific PGC-1α conditional knockout (MKO) mice, including young and old, were used to analyse the effects of PGC-1α on muscle function and the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles. Recombinant Sestrin2 was administrated to analyse its effects on muscle function in the old WT mice and old MKO mice. Results: 7β-OHC treatment induced DNA damage, mitochondrial dysfunction and decrease of PGC-1α protein in the C2C12 cells. PGC-1α silence also induced DNA damage and mitochondrial dysfunction in the C2C12 cells. Additionally, PGC-1α silence or 7β-OHC treatment decreased the levels of Sestrin2 and p-S6K1/S6K1 protein in the C2C12 cells. Recombinant Sestrin2 treatment significantly improved the DNA damage and mitochondrial dysfunction in the 7β-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia and decreased the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles when compared to the WT mice. Recombinant Sestrin2 treatment improved muscle function and increased p-S6K1 levels in the old two genotypes. Conclusion: This research demonstrates that PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway.

Habitat fragmentation has become a serious threat to amphibian populations worldwide. Concrete anti-seepage, widely applied in waterway construction, has posed a threat by causing amphibians to easily fall into concrete irrigation channels and struggle to escape. However, our understanding of the impact of irrigation channels on frog movement and survival remains limited. In this study, we evaluated the effects of concrete-lined irrigation channels on the escape ability of a common Chinese frog (Pelophylax nigromaculatus). We also analyzed the correlation between the morphology and locomotion ability of the frogs, tested the impact of irrigation channel slope gradient and substrate material on their escape ability, and proposed an optimized design for frog ramps to assist trapped frogs in escaping. The results showed that the frogs have easily fallen into these channels and encountered difficulties in escaping during field activities. As body size was positively related to the frogs’ ability to climb the slope of irrigation channels, the design parameters of the frog ramps should focus on the movement ability of the frogs. The maximum climbing gradients for most frogs on concrete, reverse slope (the protruding structure is placed in the opposite direction of the channel slope), grass and crushed stone are 40°, 50°, 60° and 65°, respectively. Based on experimental tests of the ability of the frogs to climb on various slopes and substrates, we suggest that the slope gradient of concrete irrigation channels should be less than 40°. The findings offer references for scholars and engineers to improve ecological engineering designs of irrigation channels throughout the world.

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Abstract Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF’s roles in neurodevelopmental disorders. Here, a 6 years and 3 months‐old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease‐related family history. Whole exome sequencing identified a novel heterozygous in‐frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP‐binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild‐type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live‐cell imaging of the cargo‐trafficking assay revealed that mutant KIF5C lost the peroxisome‐transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo‐transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.