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Abstract Objective To evaluate the efficacy of sentinel lymph node biopsy (SLNB) in cT1/2N0 minor salivary gland cancer (mSGC) located within the oral cavity. Methods A retrospective analysis was conducted on patients diagnosed with cT1/2N0 oral mSGC, who were categorized into two groups based on neck management approaches. The impact of SLNB versus observation on regional control and overall survival was assessed using a Cox model. Results A total of 177 patients were included in the study, with 53 cases undergoing SLNB. All patients had at least one sentinel lymph node, with the majority having two sentinel lymph nodes. The sentinel lymph nodes were predominantly situated in level I, followed by level II. Four patients had positive sentinel lymph nodes, all of whom had primary tumors in the tongue or the floor of the mouth, and were classified as cT2 stage. This yielded a sensitivity and specificity of 100%, a false negative rate of 0%, and a negative predictive value of 100% for SLNB in predicting occult metastasis. In terms of regional control, SLNB exhibited a reduced hazard ratio of 0.90 (95% confidence interval: 0.64–0.96) compared to observation. However, SLNB did not confer a superior overall survival benefit compared to observation. Conclusion In patients with cT1/2N0 oral mSGC, SLNB proved to be both technically feasible and oncologically safe. When contrasted with observation, SLNB was associated with enhanced regional control, particularly recommending its use for cases of cT2 mSGC arising from the tongue or the floor of the mouth.

Preservation conditions are key to enriching shallow shale gas. Therefore, the veins of two typical wells in the Shixi syncline in northern Guizhou as research objects. Based on core observation, vein thin-section observation, cathodoluminescence, calcite in situ U-Pb dating, fluid inclusion microthermometry, Raman spectrum shift, single well basin simulation, and C-O isotope geochemical analysis, the researchers clarified the characteristics of the veins and the differences in paleofluid activity, as well as their significance for shale gas preservation. The results showed that: 1) a small number of high-angle fractures had developed mainly in the Shixi syncline in northern Guizhou. The width of viens is small and filled primarily with early calcite-quartz and late calcite. The inclusions were mainly methane and brine. The proportion of brine inclusions in the SD1 well was greater than that in the SX1 well. The SD1 well has experienced more intense second-stage uplift and denudation, and the consequent gas loss is serious. 2) The results of the C-O isotope analysis showed that most of the vein-forming fluids were derived from marine carbonate rocks. The O3b had obvious negative deviations of δ13C and δ18O, which were modified by exogenous or deep hydrothermal fluid. The C-O isotope difference between the vein bodies and the surrounding rock of the SX1 well was small, and the preservation conditions were better. 3) The difference in gas content in the Shixi syncline depends on the degree of damage to gas reservoir preservation conditions caused by burial depth and other factors. Shixi syncline is a wide and gentle syncline with central retention enrichment mode. Therefore, clarifying the development of shale veins, the characteristics of paleofluid activity, and their significance for shale gas preservation can lay a foundation for studying the enrichment mechanism of shallow shale gas and thus guide further exploration and development.

Abstract Objective We aim to estimate the prevalence of baseline clinically significant distress in Chinese patients with head and neck squamous cell carcinoma (HNSCC) before receiving the first radiotherapy and assess factors predictive of distress. Methods One hundred and sixty-eight patients were enrolled to complete a set of questionnaires including Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). Of these, 131 questionnaires were available for the final analysis. The accuracy of DT was validated using HADS as the gold standard, and receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff score of DT. Results Distress was reported in sixty-two patients (47%). Patients who were visited in the last week (p = 0.022) and those with medical-related occupations (p = 0.017) were less likely to suffer from psychological distress. Additionally, religious belief was negatively associated with both the DT and HADS-T scores, indicating that patients with religious beliefs were less likely to report high levels of distress (odds ratio (OR) for DT ≥ 4 = 0.291, p = 0.039; OR for HADS-T ≥ 15 = 0.316, p = 0.047). Factors such as age, gender, marital status, education and residency did not contribute to distress levels. DT was significantly correlated with HADS-T (Correlation coefficient (r) = 0.624, p

Abstract Background Motile Sperm Domain-Containing Protein 1 (MOSPD1) has been implicated in breast cancer (BC) pathophysiology, but its exact role remains unclear. This study aimed to assess MOSPD1 expression levels in BC versus normal tissues and investigate its diagnostic potential. Methods MOSPD1 expression was analyzed in BC and normal tissues, with Receiver Operating Characteristic analysis for diagnostic evaluation. Validation was performed using immunohistochemistry. Functional studies included tumor growth assays, MOSPD1 suppression and overexpression experiments, and testing BC cell responses to anti-PD-L1 therapy. Results MOSPD1 expression was significantly higher in BC samples than normal tissues, correlating with poor clinical outcomes in BC patients. MOSPD1 suppression inhibited tumor growth, while overexpression accelerated it. Silencing MOSPD1 enhanced BC cell sensitivity to anti-PD-L1 therapy and decreased Th2 cell activity. In vivo experiments supported these findings, showing the impact of MOSPD1 on tumor growth and response to therapy. Conclusions Elevated MOSPD1 levels in BC suggest its potential as a biomarker for adverse outcomes. Targeting MOSPD1, particularly with anti-PD-L1 therapy, may effectively inhibit BC tumor growth and modulate immune responses. This study emphasizes the significance of MOSPD1 in BC pathophysiology and highlights its promise as a therapeutic target.

Abstract Background The acute levodopa challenge test (ALCT) is a universal method for evaluating levodopa response (LR). Assessment of Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) is a key step in ALCT, which is some extent subjective and inconvenience. Methods This study developed a machine learning method based on instrumented Timed Up and Go (iTUG) test to evaluate the patients’ response to levodopa and compared it with classic ALCT. Forty-two patients with parkinsonism were recruited and administered with levodopa. MDS-UPDRS III and the iTUG were conducted in both OFF-and ON-medication state. Kinematic parameters, signal time and frequency domain features were extracted from sensor data. Two XGBoost models, levodopa response regression (LRR) model and motor symptom evaluation (MSE) model, were trained to predict the levodopa response (LR) of the patients using leave-one-subject-out cross-validation. Results The LR predicted by the LRR model agreed with that calculated by the classic ALCT (ICC = 0.95). When the LRR model was used to detect patients with a positive LR, the positive predictive value was 0.94. Conclusions Machine learning based on wearable sensor data and the iTUG test may be effective and comprehensive for evaluating LR and predicting the benefit of dopaminergic therapy.

Abstract Background Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. Methods The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA. Results IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. Conclusion Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

Fluorescent cell imaging technology is fundamental in life science research, offering a rich source of image data crucial for understanding cell spatial positioning, differentiation, and decision-making mechanisms. As the volume of this data expands, precise image analysis becomes increasingly critical. Cell segmentation, a key analysis step, significantly influences quantitative analysis outcomes. However, selecting the most effective segmentation method is challenging, hindered by existing evaluation methods' inaccuracies, lack of graded evaluation, and narrow assessment scope. Addressing this, we developed a novel framework with two modules: StyleGAN2-based contour generation and Pix2PixHD-based image rendering, producing diverse, graded-density cell images. Using this dataset, we evaluated three leading cell segmentation methods: DeepCell, CellProfiler, and CellPose. Our comprehensive comparison revealed CellProfiler's superior accuracy in segmenting cytoplasm and nuclei. Our framework diversifies cell image data generation and systematically addresses evaluation challenges in cell segmentation technologies, establishing a solid foundation for advancing research and applications in cell image analysis.

The intricate task of precisely segmenting retinal vessels from images, which is critical for diagnosing various eye diseases, presents significant challenges for models due to factors such as scale variation, complex anatomical patterns, low contrast, and limitations in training data. Building on these challenges, we offer novel contributions spanning model architecture, loss function design, robustness, and real-time efficacy. To comprehensively address these challenges, a new U-Net-like, lightweight Transformer network for retinal vessel segmentation is presented. By integrating MobileViT+ and a novel local representation in the encoder, our design emphasizes lightweight processing while capturing intricate image structures, enhancing vessel edge precision. A novel joint loss is designed, leveraging the characteristics of weighted cross-entropy and Dice loss to effectively guide the model through the task's challenges, such as foreground-background imbalance and intricate vascular structures. Exhaustive experiments were performed on three prominent retinal image databases. The results underscore the robustness and generalizability of the proposed LiViT-Net, which outperforms other methods in complex scenarios, especially in intricate environments with fine vessels or vessel edges. Importantly, optimized for efficiency, LiViT-Net excels on devices with constrained computational power, as evidenced by its fast performance. To demonstrate the model proposed in this study, a freely accessible and interactive website was established (https://hz-t3.matpool.com:28765?token=aQjYR4hqMI), revealing real-time performance with no login requirements.

The shale of the Lower Cambrian Niutitang Formation in the Guizhou region has undergone complex diagenesis and has developed different types of pore textures, which affect the occurrence status of shale. In the present study, we applied scanning electron microscopy (SEM) and an isotherm analysis of low-temperature nitrogen gas adsorption to shale core samples drawn from the Niutitang Formation in the Guizhou region to quantify the shale pore development characteristics. In addition, we conducted a shale geochemical analysis in light of the main controlling factors for pore development. The results indicate that the shale pores and fractures of the Niutitang Formation can be divided into three types: organic pores, inorganic pores, and micro fractures. The organic pores are mainly distributed in the organic matter between inorganic mineral particles, with small pore diameters, which are characterized by inkpot, elliptic, and beaded shapes. The inorganic pores are mainly composed of narrow slit intragranular pores and intergranular pores. The micro fractures develop parallel plates with four-side openings and splint plates. The pores of the shale are mainly mesopores (53%), followed by micropores and macropores, with pore diameter distributions ranging mainly from 1 to 50 nm. The specific surface area is mainly provided by nanoscale pores with average diameters of less than 4 nm. Therefore, the smaller pore makes a greater contribution to the specific surface area, while the specific surface area increases with an increase in the total pore volume. The study further indicates that organic carbon content is the most important internal factor for shale pore development, especially in terms of the control of volume and the specific surface area of micropores. Moreover, quartz content has a certain effect on shale pores; the pore volume and specific surface area increase with increasing quartz content, but the control effect is not obvious. The effect of clay minerals on shale pores is negligible. The type of organic matter is also an important factor in controlling the developmental difference of shale pores, and a high degree of thermal evolution is not conducive to organic pore development. It was therefore concluded that intergranular pores and microfractures, mainly mesopores, are the main reservoir space and migration channels of Niutitang shale in the study area. The organic carbon content, mineral components, organic matter type, and degree of thermal evolution jointly control the development of shale pores, among which the organic carbon content is the most important influencing factor.

Abstract Background tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which are generated from tRNAs and are reported to participate in several biological processes in diseases, especially cancer; however, the mechanism of tsRNA involvement in colorectal cancer (CRC) and 5-fluorouracil (5-FU) is still unclear. Methods RNA sequencing was performed to identify differential expression of tsRNAs in CRC tissues. CCK8, colony formation, transwell assays, and tumor sphere assays were used to investigate the role of tsRNA-GlyGCC in 5-FU resistance in CRC. TargetScan and miRanda were used to identify the target genes of tsRNA-GlyGCC. Biotin pull-down, RNA pull-down, luciferase assay, ChIP, and western blotting were used to explore the underlying molecular mechanisms of action of tsRNA-GlyGCC. The MeRIP assay was used to investigate the N(7)-methylguanosine RNA modification of tsRNA-GlyGCC. Results In this study, we uncovered the feature of tsRNAs in human CRC tissues and confirmed a specific 5’ half tRNA, 5’tiRNA-Gly-GCC (tsRNA-GlyGCC), which is upregulated in CRC tissues and modulated by METTL1-mediated N(7)-methylguanosine tRNA modification. In vitro and in vivo experiments revealed the oncogenic role of tsRNA-GlyGCC in 5-FU drug resistance in CRC. Remarkably, our results showed that tsRNA-GlyGCC modulated the JAK1/STAT6 signaling pathway by targeting SPIB. Poly (β-amino esters) were synthesized to assist the delivery of 5-FU and tsRNA-GlyGCC inhibitor, which effectively inhibited tumor growth and enhanced CRC sensitive to 5-FU without obvious adverse effects in subcutaneous tumor. Conclusions Our study revealed a specific tsRNA-GlyGCC-engaged pathway in CRC progression. Targeting tsRNA-GlyGCC in combination with 5-FU may provide a promising nanotherapeutic strategy for the treatment of 5-FU-resistance CRC. Graphical Abstract

Abstract Background Hematopoiesis in mammal is a complex and highly regulated process in which hematopoietic stem cells (HSCs) give rise to all types of differentiated blood cells. Previous studies have shown that hairy and enhancer of split (HES) repressors are essential regulators of adult HSC development downstream of Notch signaling. Methods In this study, we investigated the role of HES1, a member of HES family, in fetal hematopoiesis using an embryonic hematopoietic specific Hes1 conditional knockout mouse model by using phenotypic flow cytometry, histopathology analysis, and functional in vitro colony forming unit (CFU) assay and in vivo bone marrow transplant (BMT) assay. Results We found that loss of Hes1 in early embryonic stage leads to smaller embryos and fetal livers, decreases hematopoietic stem progenitor cell (HSPC) pool, results in defective multi-lineage differentiation. Functionally, fetal hematopoietic cells deficient for Hes1 exhibit reduced in vitro progenitor activity and compromised in vivo repopulation capacity in the transplanted recipients. Further analysis shows that fetal hematopoiesis defects in Hes1 fl/fl Flt3Cre embryos are resulted from decreased proliferation and elevated apoptosis, associated with de-repressed HES1 targets, p27 and PTEN in Hes1-KO fetal HSPCs. Finally, pharmacological inhibition of p27 or PTEN improves fetal HSPCs function both in vitro and in vivo. Conclusion Together, our findings reveal a previously unappreciated role for HES1 in regulating fetal hematopoiesis, and provide new insight into the differences between fetal and adult HSC maintenance.

Recent years have witnessed significant advancements in methodologies and techniques for the synthesis of energetic materials, which are expected to shape future manufacturing and applications. Techniques including continuous flow chemistry, electrochemical synthesis, microwave-assisted synthesis, and biosynthesis have been extensively employed in the pharmaceutical and fine chemical industries and, gratifyingly, have found broader applications. This review comprehensively introduces recent advancements in the utilization of these emerging techniques, aiming to provide a catalyst for the development of novel green methods and techniques for synthesizing energetic materials.

Abstract Tobacco mosaic virus (TMV) is widely recognized as one of the most important plant viruses, causing significant agricultural losses in terms of both quality and yield worldwide each year. This study demonstrated the biosynthesis of copper oxide nanoparticles (CuONPs) using orange peel extract for effective control of TMV infection both in vitro and in vivo. After treatment with CuONPs (100 mg/L) for 2 h, TMV particles exhibited evident fragmentation in vitro, reducing infectivity on tobacco plants. Similarly, the application of CuONPs on Nicotiana benthamiana (N. benthamiana) positively impeded viral replication and accumulation in vivo. Interestingly, the expression of systemic resistance-related genes (PR1, PR2, ERF1, and JAZ3) in the host plant was up-regulated by CuONPs treatment, supporting that CuONPs activated plant immunity to inhibit TMV. Importantly, the application of CuONPs (100 mg/L) did not exhibit any toxic effects on tobacco and, instead, resulted in the promotion of chlorophyll content, as well as an increase in the fresh weight and dry weight of the plant when compared to the control treatment. Overall, we proposed that the appropriate concentration of CuONPs (100 mg/L) can directly break viral particles by passivating, boost plant immunity by stimulating systemic acquired resistance (SAR), and provide nutritional supplements to promote plant growth.

Abstract Background Adverse drug events (ADEs) represent challenges affecting Africa’s healthcare systems owing to the increased healthcare expenditure and negative health outcomes of ADEs. Objectives We aimed to systematically review published studies on ADEs and synthesize the existing evidence of ADE prevalence in Africa. Methods Studies reporting on ADE occurrence in African settings and published from Jan 1, 2000 to Oct 1, 2023 were identified by searching PubMed, EBSCO, Science Direct, and Web of Science. Studies that either articulately investigated ADEs caused by clinical condition (such as HIV patients) or ADEs caused by exposure to specific drug(s) (such as antibiotics) were considered specific and the remaining were general. Grouped ADE prevalence rates were described using median and interquartile range (IQR). PROSPERO registration (CRD42022374095). Results We included 78 observational studies from 15 African countries that investigated the prevalence of ADEs leading to hospital admissions (17 studies), developed during hospitalizations (30 studies), and captured in the outpatient departments (38 studies) or communities (4 studies). Twelve studies included multiple settings. The median prevalence of ADE during hospitalization was 7.8% (IQR: 4.2–21.4%) and 74.2% (IQR: 54.1–90.7%) in general and specific patients, respectively. The ADE-related fatality rate was 0.1% and 1.3% in general and specific patients. The overall median prevalence of ADEs leading to hospital admissions was 6.0% (IQR: 1.5–9.0%); in general, patients and the median prevalence of ADEs in the outpatient and community settings were 22.9% (IQR: 14.6–56.1%) and 32.6% (IQR: 26.0–41.3%), respectively, with a median of 43.5% (IQR: 16.3–59.0%) and 12.4% (IQR: 7.1–28.1%) of ADEs being preventable in general and specific patients, respectively. Conclusions The prevalence of ADEs was significant in both hospital and community settings in Africa. A high ADE prevalence was observed in specific patients, emphasizing important areas for improvement, particularly in at-risk patient groups (e.g., pediatrics, HIV, and TB patients) in various settings. Due to limited studies conducted in the community setting, future research in this setting is encouraged.

Peach gummosis, a devastating disease caused by Neofusicoccum parvum, significantly shortens peach tree lifespan and reduces the yield of peach trees. Despite its impact, the molecular mechanism underlying this disease remains largely unexplored. In this study, we used RNA-seq, sugar metabolism measurements, and an integrated transcriptional and metabolomic analysis to uncover the molecular events driving peach gummosis. Our results revealed that N. parvum infection drastically altered the transcripts of cell wall degradation-related genes, the log2Fold change in the transcript level of Prupe.1G088900 encoding xyloglucan endotransglycosylase decreased 2.6-fold, while Prupe.6G075100 encoding expansin increased by 2.58-fold at 12 hpi under N. parvum stress. Additionally, sugar content analysis revealed an increase in maltose, sucrose, L-rhamnose, and inositol levels in the early stages of infection, while D-galactose, D-glucose, D-fructose consistently declined as gummosis progressed. Key genes related to cell wall degradation and starch degradation, as well as UDP-sugar biosynthesis, were significantly upregulated in response to N. parvum. These findings suggest that N. parvum manipulates cell wall degradation and UDP-sugar-related genes to invade peach shoot cells, ultimately triggering gum secretion. Furthermore, weighted gene co-expression network analysis (WGCNA) identified two transcription factors, ERF027 and bZIP9, as central regulators in the downregulated and upregulated modules, respectively. Overall, this study enhances our understanding of the physiological and molecular responses of peach trees to N. parvum infection and provide valuable insights into the mechanisms of peach defense against biotic stresses.

With significant advancements in the study of DNA Damage Response (DDR) and Fanconi Anemia (FA) signaling, we previously introduced the term “FA signaling” to encompass “all signaling transductions involving one or more FA proteins.” This network has now evolved into the largest cellular defense network, integrating over 30 key players, including ATM, ATR, BLM, HRR6, RAD18, FANCA, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4, ERCC4, RAD51, BRCA1, UBE2T, XRCC2, MAD2L2, RFWD3, FAAP20, FAAP24, FAAP100, and CENPX. This system responds to both endogenous and exogenous cellular insults. However, the mutational signatures associated with this defense mechanism in non-FA human cancers have not been extensively explored. In this study, we report that different types of human cancers are characterized by distinct somatically mutated genes related to DDR/FA signaling, each accompanied by a unique spectrum of potential driver mutations. For example, in pan-cancer samples, ATM emerges as the most frequently mutated gene (5%) among the 31 genes analyzed, with the highest number of potential driver mutations (1714), followed by BRCA2 (4% with 970 putative driver mutations). However, this pattern is not universal across specific cancer types. For example, FANCT is the most frequently mutated gene in breast (14%) and liver (4%) cancers. In addition, the alteration frequency of DDR/FA signaling due to these mutations exceeds 70% in a subtype of prostate cancer, with each subtype of brain, breast, lung, and prostate cancers displaying distinct patterns of gene alteration frequency. Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies.

This study aims to investigate the effect of the combined method of freeze–thaw and leaching on the removal of cadmium (Cd) in soil and to provide a theoretical basis for the remediation of farmland soil polluted by heavy metals. The removal process and mechanism of Cd were deduced through oscillatory leaching experiments and freeze–thaw leaching simulation experiments, and the influence of the freeze–thaw leaching technology on the soil environment was evaluated. The results of oscillatory leaching showed that a mixture consisting of 0.80 mol/L citric acid and 0.80 mol/L ferric chloride in a 1:19 vol ratio effectively remove 47.75 % of Cd, indicating that the composite leaching agent could effectively remove Cd from the soil. The results of the freeze–thaw leaching simulation experiment showed that although the freeze–thaw leaching treatment increased the total Cd content in the 0–5 cm soil layer, the total Cd content in the 5–10 cm, 10–15 cm, and 15–20 cm soil layers decreased by 5.08 %, 2.39 %, and 5.68 %, respectively. The freeze–thaw leaching increased the content of exchangeable Cd (p

Abstract Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)‐ or natural aging‐induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY‐abundant culture medium of osteocytes (OCY‐CM) from osteoarthritic mice possess pro‐inflammatory, pro‐osteoclastic, and pro‐neurite outgrowth effects, while OCY‐CM from the intermittent fasting‐treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM‐induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

Phytoremediation is a sustainable way to clean contaminated urban soil, but selecting the right plants and designing communities is crucial. This study focuses on the vegetation in a disused steel plant in Chongqing, China, abandoned for nearly two decades. The goal is to reveal the plant community and succession patterns to inform the restoration of brownfield sites. This study combined the sample line and plot to investigate the vegetation and its growth environment in the Steel Plant. Information was recorded, including plant species, quantity, distribution, soil nutrients, humidity, and light. Cluster analysis categorized plant community types, and redundancy analysis examined the link between environmental conditions and plant types. The study found that: 1) There are 65 plant species (including 13 native trees) in the steel plant’s brownfield area, with Broussonetia papyrifera, Pteris vittata, and Debregeasia orientalis being the most abundant. The plants inside the plant were divided into seven groups based on species composition. 2) Soil moisture showed a significant positive correlation (Pearson index of 0.628) with plant survival, followed by a notable correlation with light intensity. 3) Environmental conditions partly influenced plant species composition and abundance variations. 4) 11 hyper-accumulating plant species were identified, focusing on three: the As hyper-accumulator Pteris vittata and the Cd hyper-accumulators Solanum nigrum and Debregeasia orientalis. The findings of this research will offer valuable insights for applying phytoremediation techniques in addressing contamination issues in brownfields within steel plants.

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10–250 ng L−1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L−1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L−1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

Abstract Due to the lack of sufficient labeled data for the prostate and the extensive and complex semantic information in ultrasound images, accurately and quickly segmenting the prostate in transrectal ultrasound (TRUS) images remains a challenging task. In this context, this paper proposes a solution for TRUS image segmentation using an end-to-end bidirectional semantic constraint method, namely the BiSeC model. The experimental results show that compared with classic or popular deep learning methods, this method has better segmentation performance, with the Dice Similarity Coefficient (DSC) of 96.74% and the Intersection over Union (IoU) of 93.71%. Our model achieves a good balance between actual boundaries and noise areas, reducing costs while ensuring the accuracy and speed of segmentation.

Summary: E2F transcription factors (E2Fs) are a group of genes that encode a family of transcription factors. They have been identified as being involved in the tumor progression of various cancer types. However, little is known about the expression level, genetic variation, molecular mechanism, and prognostic value and immune infiltration of different E2Fs in HNSCC.In this study, we utilized multiple databases to investigate the mRNA expression level, genetic alteration, and biological function of E2Fs in HNSCC patients. Then, the relationship between E2Fs expression and its association with the occurrence, progress, prognosis, and immune cell infiltration in patients with HNSCC was evaluated. We found that all eight E2Fs were higher expressed in HNSCC tissues than in normal tissues, and the expression levels of E2F1/2/3/4/5/6/8 were also associated with the stage and grade of HNSCC. The abnormal expression of E2F1/2/4/8 in HNSCC patients is related to the clinical outcome. The expression of E2Fs was statistically correlated with the immune cell infiltration in HNSCC and the infiltration of B cells and CD8+ T cells were positively associated with better OS in HNSCC patients. Furthermore, we verified the E2F2 at the tissue level in the validation experiment. Our study may provide novel insights into the choice of immunotherapy targets and potential prognostic biomarkers in HNSCC patients.

Abstract Objective To evaluate the clinical efficacy and imaging outcomes of percutaneous endoscopic lumbar discectomy (PELD) combined with platelet-rich plasma (PRP) for the treatment of lumbar disc herniation (LDH). Methods A total of 155 patients with LDH between January 2020 and June 2022 were retrospective analyzed, of which 75 underwent PELD with PRP and 80 underwent PELD only. Clinical functional scores and imaging data were compared. Clinical functional scores included visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), Japanese Orthopedic Association score (JOA), Oswestry Disability Index (ODI) and modified MacNab criteria. Imaging data included disc height index (DHI), spinal cross-sectional area (SCSA), disc protrusion size (DPZ), and ratio value of disc grey scales (RVG). Results Both groups showed clinical improvement, and VAS-LP, VAS-BP, JOA and ODI were significantly improved in the PRP group compared with the control group at 3, 6 and 12 months postoperatively (P 0.05). No serious complications occurred during the follow-up period. Conclusion PELD combined with PRP is a safe and effective method for treating patients with LDH. PRP injection was beneficial for delaying disc degeneration and promoting disc remodeling.

Abstract This paper efficiently addresses the high-dimensional robust order scheduling problem. A novel algorithm named dynamic cooperative coevolution based on an implicit decision variable classification approach (DCC/IDVCA) is developed to search for robust order schedules. To significantly reduce the computational resources required for solving the high-dimensional robust order scheduling problem, we propose decomposing the original decision variables through implicit classification methods. First, a novel estimation method is introduced to evaluate the weighted contribution of variables to robustness. This method utilizes historical information, including the variation of the overall mean effective fitness and the frequency of variables being classified into highly robustness-related subcomponents in previous cycles, for evaluating their weighted contribution to robustness. Then, based on the corresponding weighted robustness contributions, the original variables are classified into highly and weakly robustness-related variables. Finally, these two types of variables are decomposed into highly and weakly robustness-related subgroups within a dynamic cooperative coevolution framework and optimized separately. In the experimental section, the proposed algorithm is applied to two practical order scheduling problems in discrete manufacturing industry. The experimental results demonstrate that the proposed algorithm achieves competitive outcomes compared to state-of-the-art high-dimensional robust multi-objective optimization algorithms.

MgH2 is considered one of the most promising hydrogen storage materials because of its safety, high efficiency, high hydrogen storage quantity and low cost characteristics. But some shortcomings are still existed: high operating temperature and poor hydrogen absorption dynamics, which limit its application. Porous Ni3ZnC0.7/Ni loaded carbon nanotubes microspheres (NZC/Ni@CNT) is prepared by facile filtration and calcination method. Then the different amount of NZC/Ni@CNT (2.5, 5.0 and 7.5 wt%) is added to the MgH2 by ball milling. Among the three samples with different amount of NZC/Ni@CNT (2.5, 5.0 and 7.5 wt%), the MgH2-5 wt% NZC/Ni@CNT composite exhibits the best hydrogen storage performances. After testing, the MgH2-5 wt% NZC/Ni@CNT begins to release hydrogen at around 110 °C and hydrogen absorption capacity reaches 2.34 wt% H2 at 80 °C within 60 min. Moreover, the composite can release about 5.36 wt% H2 at 300 °C. In addition, hydrogen absorption and desorption activation energies of the MgH2-5 wt% NZC/Ni@CNT composite are reduced to 37.28 and 84.22 KJ/mol H2, respectively. The in situ generated Mg2NiH4/Mg2Ni can serve as a ''hydrogen pump'' that plays the main role in providing more activation sites and hydrogen diffusion channels which promotes H2 dissociation during hydrogen absorption process. In addition, the evenly dispersed Zn and MgZn2 in Mg and MgH2 could provide sites for Mg/MgH2 nucleation and hydrogen diffusion channel. This attempt clearly proved that the bimetallic carbide Ni3ZnC0.7 is a effective additive for the hydrogen storage performances modification of MgH2, and the facile synthesis of the Ni3ZnC0.7/Ni@CNT can provide directions of better designing high performance carbide catalysts for improving MgH2.

Abstract Objective Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. Methods Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2’s effect on tau phosphorylation. Results Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. Conclusion Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

Aging increases the risks of various diseases and the vulnerability to death. Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases. This study demonstrates that extracellular vesicles from human urine-derived stem cells (USC-EVs) efficiently inhibit cellular senescence in vitro and in vivo. The intravenous injection of USC-EVs improves cognitive function, increases physical fitness and bone quality, and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice. The anti-aging effects of USC-EVs are not obviously affected by the USC donors’ ages, genders, or health status. Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase (PLAU) and tissue inhibitor of metalloproteinases 1 (TIMP1). These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases, cyclin-dependent kinase inhibitor 2A (P16INK4a), and cyclin-dependent kinase inhibitor 1A (P21cip1). These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

Globally, over three billion people rely on traditional solid fuels for cooking and heating, leading to significant household air pollution and critical public health concerns. While transitioning to clean energy carriers faces challenges of accessibility and affordability—especially among low-income, rural populations—alternative strategies like kitchen layout modifications and the use of ventilation fans may effectively reduce exposure to pollutants. Here, we analyze factors influencing the adoption of separated kitchens and mechanical ventilation and evaluate changes in human exposure to PM2.5 under different kitchen renovation scenarios by conducting a nationwide survey of household kitchen characteristics in rural China. We found that although 82% of rural households have kitchens separated from other rooms, only 34% use mechanical ventilation. The adoption of ventilation fans is significantly influenced by income and education levels. We estimate that widespread implementation of ventilation fans and separated kitchen designs could prevent approximately 67400 premature deaths annually, resulting in a health benefit of about USD 19 billion per year—substantially exceeding the costs involved. These findings suggest that cost-effective kitchen renovations offer enormous potential for substantial health benefits and present a practical solution compared to the challenges of clean energy transitions in rural areas.

Immunotherapy has recently attracted considerable attention. However, currently, a thorough analysis of the trends associated with the epithelial-mesenchymal transition (EMT) and immunotherapy is lacking. In this study, we used bibliometric tools to provide a comprehensive overview of the progress in EMT-immunotherapy research. A total of 1,302 articles related to EMT and immunotherapy were retrieved from the Web of Science Core Collection (WOSCC). The analysis indicated that in terms of the volume of research, China was the most productive country (49.07%, 639), followed by the United States (16.89%, 220) and Italy (3.6%, 47). The United States was the most influential country according to the frequency of citations and citation burstiness. The results also suggested that Frontiers in Immunotherapy can be considered as the most influential journal with respect to the number of articles and impact factors. “Immune infiltration,” “bioinformatics analysis,” “traditional Chinese medicine,” “gene signature,” and “ferroptosis” were found to be emerging keywords in EMT-immunotherapy research. These findings point to potential new directions that can deepen our understanding of the mechanisms underlying the combined effects of immunotherapy and EMT and help develop strategies for improving immunotherapy.

Objectives To explore a precise control pathway based on patient clinical variations for haemostatic clip usage in laparoscopic cholecystectomy (LC) through on-site research data from a teaching hospital. Specifically, the study aimed to: (1) to calculate the optimal haemostatic clip consumption in LC based on diagnostic grouping and surgical combinations, and (2) to provide evidence for cost containment of high-value medical consumables used in LC.Design Retrospective observational study.Setting Hospital in southwest China.Participants The inclusion criteria were set as inpatients whose medical records included International Classification of Diseases codes 1–3 with code 51.2300 (corresponding to LC surgery) and who were discharged on medical advice. A dataset containing 1001 patients without any haematological diagnoses was collected.Primary and secondary outcome measures Two ordered multinomial logit models were established to identify factors affecting haemostatic clip use in LC. Two-step clustering was used to form subgroups. The premodel included preoperative variables (acute cholecystitis and scarring/fibrotic atrophy), while the full model added intraoperative variables (anatomical variation and severe adhesions). Both models met application prerequisites.Results Key factors influencing haemostatic clip usage were identified, including acute cholecystitis, scarring/fibrotic atrophy, anatomical variation and severe adhesions. Consumption references for haemostatic clips were established for LC patients with good prognoses on discharge. The ordered multinomial logit model revealed that acute cholecystitis decreased the odds of using four or more clips (p

Shale gas accumulation and leakage histories are significant for evaluating the prospects of hydrocarbon exploration. The Wufeng Formation in northern Guizhou is a potential target for shale gas exploration and development. This work selected a typical Well YH1 to conduct detailed fluid inclusion analyses in the Wufeng Formation. We integrated the inclusion results with systematic core description, thin-section microscopic observation, laser Raman spectroscopy, microscopic temperature measurement, and burial–thermal history to reveal shale gas accumulation and leakage histories in northern Guizhou. The results show that the source rocks of the Wufeng Formation occurred in oil generation since the Permian and entered the stage of natural gas generation at the end of the Late Triassic. During the Early Jurassic and Early Cretaceous, shale gas accumulated in the Wufeng Formation reservoirs, and the stratigraphical pressure coefficient ranged from 1.47 to 1.97. Under the influence of the Yanshan orogeny, northern Guizhou experienced a rapid uplift and exhumation since the end of the Early Cretaceous. Under the influence of this tectonic, the stratigraphical pressure plummeted to the normal level, adversely impacting the accumulated shale gas in reservoirs and resulting in leakage events since the end of the Early Cretaceous. The reservoirs were further destroyed and adjusted, and the gas continued to leak because of a long-term and large-scale uplift and exhumation during the Himalayan orogeny. This work clarified that shale gas accumulation and leakage histories are significant for evaluating petroleum exploration.

Background: Emergency observation unit in China are characterized by a high number of patients, complexity of diseases, and instability of patient conditions, leading to low patient satisfaction. The Kano model is an effective method widely used to identify customer demands and improve service quality to enhance customer satisfaction. However, its application in emergency observation unit has been studied less. This study aims to design a questionnaire based on the Kano model and identify the demands of emergency observation patients to determine priorities for improvements in the emergency observation unit and improve patient satisfaction. Methods: A cross-sectional study was conducted in Guizhou Provincial People's Hospital from March 21st, 2023, to May 20th, 2023. A convenient sampling method was used to recruit 100 patients from the emergency observation unit, who completed a questionnaire designed based on the Kano model to assess their demands for care service. Data were analyzed using IBM SPSS Statistics 28.0 software. The element selection line and sensitivity analysis were used to determine factors for patient service demand improvement. Results: A total of 13 patient service demands for improvement were screened out from 19 service demands, including 1 item of must-be quality (M), 11 item of one-dimensional quality (O), and 1 item of attractive quality (A), These attributes showed significant differences in patients’ sociodemographic characteristics. Conclusion: The Kano model is a valuable tool for identifying the characteristics of patients' service demands, and the element screening method can be employed to establish the hierarchy of these demands. These results offer crucial direction for creating forthcoming nursing management initiatives in emergency observation unit.

ABSTRACT The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

ObjectivesTo explore the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) on lung adenosquamous cell carcinoma (ASC) with EGFR mutation.MethodsEfficacy of EGFR-TKIs in the treatment of advanced or recurrent lung ASC with EGFR mutations was assessed retrospectively in 44 patients. Pooled analysis of 74 patients using EGFR-TKIs, including 30 patients selected from 11 publications, was conducted.ResultsIn our retrospective research, patients treated with EGFR-TKI in ASC with EGFR mutations had objective response rate (ORR) of 54.5%, disease control rate (DCR) of 79.5%, median progression free survival (mPFS) of 8.8 months, and median overall survival (mOS) of 19.43 months, respectively. A pooled analysis reveals ORR, DCR, mPFS, and mOS are, respectively, 63.4%, 85.9%, 10.00 months, and 21.37 months for ASC patients. In patients with deletions in exon 19 and exon 21 L858R mutations, mPFS (11.0 versus 10.0 months, P=0.771) and mOS (23.67 versus 20.33 months, P=0.973) were similar. Erlotinib or gefitinib-treated patients had an overall survival trend that was superior to that of icotinib-treated patients.ConclusionsASC harboring EGFR mutations can be treated with EGFR-TKI in a similar manner to Adenocarcinoma (ADC) harboring EGFR mutations. There is still a need for further investigation to identify the separate roles of ASC’s two components in treating EGFR.

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

Abstract Background Due to the unfavorable prognosis associated with lung adenocarcinoma (LUAD), the development of targeted therapies and immunotherapies is essential. Cuproptosis, an emerging form of regulated cell death, is implicated in mitochondrial metabolism and is induced by copper ions. This study aimed to explore the prognostic value of cuproptosis‐ and immune‐related genes (CIRGs) in LUAD. Methods We used The Cancer Genome Atlas database to develop a prognostic prediction model for LUAD patients based on eight CIRGs. Using Cox regression analysis, we determined that the CIRG signature is a reliable, independent prognostic factor. We further identified PSMD11 as a critical CIRG and performed immunohistochemistry to study the protein expression levels of PSMD11 in LUAD tissues. We also investigated the impact of PSMD11 on the biological behavior of lung cancer cell lines. Results We found that patients with low PSMD11 expression levels displayed an improved prognosis compared with those with high PSMD11 expression levels. Overexpression of PSMD11 enhanced proliferation, migration, invasion, and tumor growth of lung carcinoma cell line A549, while PSMD11 knockdown diminished proliferation, migration, invasion, and tumor growth of lung carcinoma cell line PC9. Additionally, we discovered that PSMD11 expression was positively correlated with the infiltration of myeloid‐derived suppressor cells and the increased expression of immunosuppressive molecules. Conclusion These findings suggest that PSMD11 may serve as a valuable prognostic biomarker and therapeutic target for LUAD.

The performance of model predictive control strategies for hybrid electric vehicles (HEVs) highly depends on the accuracy of future speed predictions. This paper proposes improved prediction models for deterministic model predictive control (DMPC) and stochastic model predictive control (SMPC), respectively. For DMPC, the neural network-based predictor is first introduced and taken as the benchmark predictor. A novel deterministic predictor considering historical prediction errors is proposed, which relies on the assumption that the offset between the prediction and measurement at current instant is a good estimate of the offset in the short future. Based on the proposed deterministic predictor, a stochastic predictor that considers the distribution law of historical data at different locations is further proposed for SMPC. Simulation results show that the controller using the proposed deterministic prediction model improves fuel economy by 2.89%, and the controller using the proposed stochastic prediction model improves fuel economy by 4.5% compared with the benchmark.

Background: This study aimed to identify the risk factors associated with mortality among patients co-infected with human immunodeficiency virus (HIV) and Talaromyces marneffei (TM) in China, and develop a risk prediction model. Methods: In this retrospective cohort analysis conducted from 2013 to 2024, comprehensive clinical data from 160 patients were analyzed using a logistic regression model to identify mortality predictors and construct a predictive model. An additional 36 patients constituted the validation cohort, which was specifically designed to evaluate the predictive value of the model. Model performance was assessed using the area under the curve (AUC). Results: The overall mortality rate for hospitalized patients with HIV/TM co-infection was 17.35 %. The median age was 35.0 years, and 89.30 % were male. Additionally, 89.80 % of the patients reported fever and 87.76 % presented with lymphadenopathy. Key independent risk factors associated with mortality included age (odds ratio (OR): 1.103, 95 % confidence interval (CI) = 1.033–1.178, P = 0.003), procalcitonin (PCT) levels (OR: 1.270, 95 % CI = 1.052–1.534, P = 0.013), and urea to albumin ratio (UAR) (OR: 1.491, 95 % CI = 1.175–1.892, P

Automatic coordinated control of power transformers is essential to stable operation of power systems. However, there still lack mature intelligent solutions for this purpose. As a result, this paper proposes a reinforcement learning-based automatic collaborative control approach for power transformers. Firstly, by establishing the state space and action of the transformer control system, deep reinforcement learning is used to optimize the control strategy. Then, deep Q-network is utilized to automatically learning and adjust the operating parameters of each transformer to achieve coordinated control of power systems. In the algorithm design, we consider multiple factors such as power grid load and voltage stability. And they are incorporated into the reward function of reinforcement learning to facilitate learning appropriate control strategies. The experimental results show that the new method not only improves the response speed of the control system, but also effectively enhances the stability and robustness. In addition, we conducted in-depth analysis on the convergence and learning efficiency of the system, verifying the feasibility and superiority of the proposed method compared with traditional methods.

Abstract Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.

Abstract Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

Abstract Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ADTC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Abstract Background Patients with COVID-19 undergoing pressure support ventilation (PSV) with extracorporeal membrane oxygenation (ECMO) commonly had high respiratory drive, which could cause self-inflicted lung injury. The aim of this study was to evaluate the influence of different levels of partial pressure of carbon dioxide(PaCO2) on respiratory effort in COVID-19 patients undergoing PSV with ECMO. Methods ECMO gas flow was downregulated from baseline (respiratory rate

Abstract Aurora-A kinase interacting protein 1 (AURKAIP1) has been proved to take an intermediary role in cancer by functioning as a negative regulator of Aurora-A kinase. However, it remains unclear whether and how AURKAIP1 itself would directly engage in regulating malignancies. The expression levels of AURKAIP1 were detected in triple negative breast cancer (TNBC) by immunohistochemistry and western blots. The CCK8, colony formation assays and nude mouse model were conducted to determine cell proliferation whereas transwell and wound healing assays were performed to observe cell migration. The interaction of AURKAIP1 and DEAD-box helicase 5 (DDX5) were verified through co-immunoprecipitation and successively western blots. From the results, we found that AURKAIP1 was explicitly upregulated in TNBC, which was positively associated with tumor size, lymph node metastases, pathological stage and unfavorable prognosis. AURKAIP1 silencing markedly inhibited TNBC cell proliferation and migration in vitro and in vivo. AURKAIP1 directly interacted with and stabilized DDX5 protein by preventing ubiquitination and degradation, and DDX5 overexpression successfully reversed proliferation inhibition induced by knockdown of AURKAIP1. Consequently, AURKAIP1 silencing suppressed the activity of Wnt/β-catenin signaling in a DDX5-dependent manner. Our study may primarily disclose the molecular mechanism by which AURKAIP1/DDX5/β-catenin axis modulated TNBC progression, indicating that AURKAIP1 might serve as a therapeutic target as well as a TNBC-specific biomarker for prognosis.

Limestone calcined clay cement (LC3), enhanced through reactions with volcanic ash and the interaction between limestone and clay, significantly improves the performance of cementitious materials. It has the potential to cut CO2 emissions by up to 30% and energy consumption in cement manufacture by 15% to 20%, providing a promising prospect for the large-scale production of low-carbon cement with a lower environmental effect. To effectively manufacture LC3 concrete, this study utilized limestone (15%), calcined clay (30%), and gypsum (5%) as supplementary cementitious materials (SCMs), replacing 50% of ordinary Portland cement (OPC). However, in regions abundant in sulfate, sulfate attack can cause interior cracking of concrete, reducing the longevity of the building. To address this issue, microcapsules containing microcrystalline wax, ceresine wax, and nano-CaCO3 encapsulated in epoxy resin were prepared and successfully incorporated into LC3 concrete. Sulfate resistance tests were conducted through sulfate dry–wet cycles, comparing samples with and without microcapsules. The findings revealed that the initial mechanical and permeability properties of LC3 concrete did not significantly differ from OPC concrete. LC3 concrete with added microcapsules (SP4) exhibited enhanced resistance to sulfate attack, reducing mass loss and compressive strength degradation. SEM images displayed a mesh-like structure of repair products in SP4. After 14 days of self-repair, SP4 exhibited a 44.2% harmful pore ratio, 98.1% compressive strength retention, 88.7% chloride ion diffusion coefficient retention, 91.12 mV maximum amplitude, and 9.14 mV maximum frequency amplitude. The experimental results indicate that the presence of microcapsules enhances the sulfate attack self-healing performance of LC3 concrete.

The cracking of link slabs in jointless bridges presents significant challenges due to the complexity of their stress conditions. This study focused on analyzing the transverse stresses in link slabs of jointless steel–concrete composite bridges. Utilizing linear elasticity theory and partial differential equations of plates, the deflection and stress distribution functions for the link slabs were determined. The validity of these analytical solutions was confirmed through comparisons with finite element models and load tests. Results from both the load tests and the finite element model indicate that the upper face of the girder end link slabs experiences maximum tensile stresses in both transverse and longitudinal directions. The stress values obtained from the analytical method align well with these results, showing that the total stress, when considering transverse stresses, reaches 107% of the longitudinal stresses alone. Furthermore, a 40% reduction in longitudinal girder spacing or a 50% increase in girder end length can lead to link slab stresses of 128% and 145% of the longitudinal stresses, respectively. This finding suggests that even loads lower than those designed based solely on longitudinal stresses can result in cracking. Therefore, it is recommended that transverse stresses be considered in the design of link slabs for jointless bridges. Relying solely on conventional longitudinal stress analyses may underestimate actual stress conditions and contribute to the formation of cracks.

In order to study the effect of the circulation control technology on the electromagnetic scattering characteristics of the wing, a variety of low-scattering carrier models were designed based on the characteristics of the circulation control wing and the mechanical rudder surface. The radar scattering cross sections of the different models were then calculated by using the multilayer fast multipole algorithm. A comparative analysis of different models revealed that the use of the circulation control technique can reduce the front RCS level of the wing. Furthermore, the scaling effect was found to be more significant for the HH-polarised RCS at high frequency and the VV-polarised RCS at low frequency. The air source cavity structure of the jet system will increase the front and back RCS levels of the wing. Conversely, the back RCS level can be reduced by the oblique design of the jet nozzle. In the process of achieving attitude control, the wing applying the circulation control technique can significantly reduce its own front and side RCS levels, as well as the fluctuations of RCS levels throughout manoeuvres, in comparison to the usage of mechanical rudders. The findings of the study elucidate the scattering characteristics of the circulation control wing, which can serve as a reference for the stealth performance of unconventional layout aircraft.

Not available.