Research on Fault Prediction Method of Elevator Door System Based on Transfer Learning.

The elevator door system plays a crucial role in ensuring elevator safety. Fault prediction is an invaluable tool for accident prevention. By analyzing the sound signals generated during operation, such as component wear and tear, the fault of the system can be accurately determined. This study proposes a GNN-LSTM-BDANN deep learning model to account for variations in elevator operating environments and sound signal acquisition methods. The proposed model utilizes the historical sound data from other elevators to predict the remaining useful life (RUL) of the target elevator door system. Firstly, the opening and closing sounds of other elevators is collected, followed by the extraction of relevant sound signal characteristics including A-weighted sound pressure level, loudness, sharpness, and roughness. These features are then transformed into graph data with geometric structure representation. Subsequently, the Graph Neural Networks (GNN) and long short-term memory networks (LSTM) are employed to extract deeper features from the data. Finally, transfer learning based on the improved Bhattacharyya Distance domain adversarial neural network (BDANN) is utilized to transfer knowledge learned from historical sound data of other elevators to predict RUL for the target elevator door system effectively. Experimental results demonstrate that the proposed method can successfully predict potential failure timeframes for different elevator door systems.

Stress reduction through cortical bone thickening improves bone mechanical behavior in adult female Beclin-1+/- mice.

Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/- mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/- mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/- female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/- murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/- mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/- mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/- mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.

Effect of fasting plasma glucose level in severe fever and thrombocytopenia syndrome patients without diabetes.

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0-11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS.

Expression of Caudal-Type Homologous Transcription Factor-2 (CDX2) in Duodenal Carcinoma and its Relationship with Prognosis.

Objective: Caudal-type homologous transcription factor 2 (CDX2) has been shown to be associated with prognosis in colorectal cancer, with those with high expression having a good prognosis and those with low expression having a poor prognosis. As duodenal and colorectal cancers are similar in histological origin, we suspect that CDX2 expression in duodenal cancer may also be related to prognosis. Therefore, the aim of this study was to investigate the expression of CDX2 in duodenal cancer and its relationship with prognosis. Methods: We collected the clinical data and pathological sections of 61 patients diagnosed with duodenal cancer by histopathology or cytology at Shanghai Changhai Hospital, Naval Medical University, from November 2011 to December 2022. CDX2 expressionin in duodenal cancer was detected by immunohistochemical analysis (streptavidin-peroxidasemethod, SP). Survival analysis was conducted using the Kaplan-Meier method and the Log-rank test. Multivariate analysis was performed using the Cox regression analysis. Results: The positive rate of CDX2 in duodenal carcinoma was 78.7% (48/61). The positive rate of CDX2 expression in patients with stage I/II was higher than that in patients with stage III/IV (P < .05), and there was no correlation between CDX2 expression and gender, age, degree of differentiation, CEA and anemia (P > .05). Univariate analysis by Kaplan-Meier and Log-rank test showed that the expression of CDX2, degree of differentiation, TNM staging and CEA were associated with the prognosis of CDX2 in the negative and positive for the OS 21.6 months and 49.8 months, respectively (P = .015). The median OS of poorly differentiated patients and moderately/well-differentiated patients were 13 months and 82.5 months, respectively (P < .001). The median OS for Stage I/II and Stage III/IV patients was 72.3 and 13 months, respectively (P < .001). The median OS of CEA < 5 ug/L and ≥5 ug/L were 49.8 months and 9.4 months, respectively (P = .002). Age, gender and whether anemia were not associated with prognosis (P > .05). Multivariate analysis by Cox regression analysis showed that the expression of CDX2 (RR=2.697, 95%CI: 1.191-6.106, P = .017) was an independent prognostic factor of duodenal carcinoma. The results suggest that the expression of CDX2 in duodenal cancer is closely related to the prognosis. Those with positive expression have a better prognosis and those with negative expression have a worse prognosis. Conclusion: CDX2 serves as an autonomous prognostic determinant in individuals diagnosed with duodenal cancer. Notably, patients exhibiting positive CDX2 expression demonstrate a considerably improved prognosis compared to those with negative CDX2 expression. CDX2 may play an important role as an tumor suppressor gene in the development of duodenal cancer. CDX2 can be used as an important factor for evaluating the prognosis of patients with duodenal cancer, and it has the potential to be a target for duodenal cancer therapy.

Prediction of bilateral thyroid carcinoma and lateral cervical lymph node metastasis in PTC patients with suspicious thyroid nodules.

PURPOSE: This study aimed to evaluate the factors associated with bilateral papillary thyroid carcinoma (PTC) and lateral cervical lymph node metastasis (LLNM) in patients with suspicious unilateral PTC. METHODS: This study analyzed patients with suspicious unilateral PTC who were enrolled in a university hospital between 2016 and 2019 in Zhejiang, China. Using logistic regression, the study examined the factors associated with bilateral PTC and LLNM in demographic data, anthropometric measurements, lifestyle factors, medical history, preoperative diagnostic tests, and histopathological factors. RESULTS: A total of 256 patients, with a mean age of 49 years, were enrolled. Bilateral PTC was associated with multifocality (aOR: 5.069, 95% CI: 2.440-10.529, P < 0.001), and contralateral nodule in the upper (aOR: 9.073, 95% CI: 2.111-38.985, P = 0.003) and middle (aOR: 9.926, 95% CI: 2.683-36.717, P < 0.001). LLNM was positively associated with bilateral PTC (aOR, 4.283, 95% CI: 1.378-13.308, p = 0.012), male (aOR, 3.377, 95% CI: 1.205-9.461, P = 0.021), upper location of carcinoma (aOR, 3.311, 95% CI: 1.091-10.053, p = 0.035), and punctate echogenic foci (aOR, 3.309, 95% CI: 1.165-9.394, P = 0.025). Contralateral maximal nodule in the upper (aOR: 0.098, 95% CI: 0.015-0.628, p = 0.014), middle (aOR: 0.114, 95% CI: 0.033-0.522, p < 0.001), and lower (aOR, 0.028, 95% CI: 0.003-0.276, P = 0.002) location were inversely associated with LLNM. CONCLUSION: Upper and middle location of contralateral nodule and tumor multifocality predicted the risk bilateral PTC. Bilateral PTC, male, upper tumor location, punctate echogenic foci and contralateral nodule location in the entire lobes were independent predictors for LLNM.

Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3.

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Moracin D suppresses cell growth and induces apoptosis via targeting the XIAP/PARP1 axis in pancreatic cancer.

BACKGROUND: Pancreatic cancer, a tumor with a high metastasis rate and poor prognosis, is among the deadliest human malignancies. Investigating effective drugs for their treatment is imperative. Moracin D, a natural benzofuran compound isolated from Morus alba L., shows anti-inflammation and anti-breast cancer properties and is effective against Alzheimer's disease. However, the effect and mechanism of Moracin D action in pancreatic cancer remain obscure. PURPOSE: To investigate the function and molecular mechanism of Moracin D action in repressing the malignant progression of pancreatic cancer. METHODS: Pancreatic cancer cells were treated with Moracin D, and cell proliferation was evaluated by cell counting kit-8 (CCK-8) and immunofluorescence assays. The clonogenicity of pancreatic cancer cells was assessed based on plate colony formation and soft agar assay. Flow cytometry was used to detect cell apoptosis. The expression of proteins related to the apoptosis pathway was determined by Western blot analysis. Moracin D and XIAP were subjected to docking by auto-dock molecular docking analysis. Ubiquitination levels of XIAP and the interaction of XIAP and PARP1 were assessed by co-immunoprecipitation analysis. Moracin D's effects on tumorigenicity were assessed by a tumor xenograft assay. RESULTS: Moracin D inhibited cell proliferation, induced cell apoptosis, and regulated the protein expression of molecules involved in caspase-dependent apoptosis pathways. Moracin D suppressed clonogenicity and tumorigenesis of pancreatic cancer cells. Mechanistically, XIAP could interact with PARP1 and stabilize PARP1 by controlling its ubiquitination levels. Moracin D diminished the stability of XIAP and decreased the expression of XIAP by promoting proteasome-dependent XIAP degradation, further blocking the XIAP/PARP1 axis and repressing the progression of pancreatic cancer. Moracin D could dramatically improve the chemosensitivity of gemcitabine in pancreatic cancer cells. CONCLUSION: Moracin D repressed cell growth and tumorigenesis, induced cell apoptosis, and enhanced the chemosensitivity of gemcitabine through the XIAP/PARP1 axis in pancreatic cancer. Moracin D is a potential therapeutic agent or adjuvant for pancreatic cancer.

Liraglutide attenuates angiotensin II-induced aortic dissection and aortic aneurysm via inhibiting M1 macrophage polarization in APOE -/- mice.

BACKGROUND: Aortic Aneurysm and Dissection (AAD) are severe cardiovascular conditions with potentially lethal consequences such as aortic rupture. Existing studies suggest that liraglutide, a long-acting glucagon-like peptide receptor (GLP-1R) agonist, offers protective benefits across various cardiovascular diseases. However, the efficacy of liraglutide in mitigating AAD development is yet to be definitively elucidated. METHODS: Ang II (Angiotension II) infusion of APOE-/- mouse model with intraperitoneal injection of liraglutide (200 µg/kg) to study the role of GLP-1R in AAD formation. Bone Marrow Derived Macrophages (BMDM) and Raw264.7 were incubated with LPS, liraglutide, exendin 9-39 or LY294002 alone or in combination. SMC phenotype switching was examined in a macrophage and vascular smooth muscle cell (VSMC) co-culture system. An array of analytical methods, including Western Blot, Immunofluorescence Staining, Enzyme-LinkedImmunosorbent Assay, Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, and so on were employed. RESULTS: Our investigation revealed a significant increase in M1 macrophage polarization and GLP-1R expression in aortas of AD patients and Ang II-induced AAD APOE-/- mice. Administering liraglutide in APOE-/- mice notably reduced Ang II-induced AAD incidence and mortality. It was found that liraglutide inhibits M1 macrophage polarization primarily via GLP-1R activation, and subsequently modulates vascular smooth muscle cell phenotypic switching was the primary mechanism. RNA-Seq and subsequent KEGG enrichment analysis identified CXCL3, regulated by the PI3K/AKT signaling pathway, as a key element in liraglutide's modulation of M1 macrophage polarization. CONCLUSION: Our study found liraglutide exhibits protective effects against AAD by modulating M1 macrophage polarization, suppressing CXCL3 expression through the PI3K/AKT signaling pathway. This makes it a promising therapeutic target for AAD, offering a new avenue in AAD management.

Dual modal improved enzyme-linked immunosorbent assay for aflatoxin B1 detection inspired by the interaction of amines with Prussian blue nanoparticles.

This work reports an improved enzyme-linked immunosorbent assay (ELISA) via the interaction between prussian blue nanoparticles (PBNPs) and amines for aflatoxin B1 (AFB1) detection. The effect of different amines on the structure and properties of PBNPs was systematically investigated. Amines with pKb < 7, like ethylenediamine (EDA), can decompose structure of PBNPs, leading to the reduction of extinction coefficient and photothermal effect. Whereas, amines with large pKb > 7, such as o-phenylenediamine (OPD), could undergo catalytic oxidation by PBNPs, resulting in the production of fluorescent and colored oxidation products. Accordingly, EDA and OPD were used to construct improved ELISA. Specifically, silica nanoparticles, on which AFB1 aptamer and amino binding agent (ethylenediaminetetraacetic acid disodium salt, EDTA•2Na) were previously assembled via carboxyl-amino linkage, are anchored to microplates by AFB1 and antibody. EDA concentration can be regulated by EDTA•2Na to affect extinction coefficient and photothermal effect of PBNPs, thereby achieving visual colorimetric and portable photothermal signal readout (Model 1). OPD concentration can also be controlled by EDTA•2Na, thus generating colorimetric and ultrasensitive fluorescent signals through PBNPs catalysis (Model 2). The proposed strategy not only opens new avenue for signal readout mode of biosensing, but also provides universal technique for hazards.

Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system.

JOURNAL/nrgr/04.03/01300535-202410000-00026/figure1/v/2024-02-06T055622Z/r/image-tiff Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Comparison of laparoscopic hepatectomy and percutaneous radiofrequency ablation for the treatment of small hepatocellular carcinoma: a meta-analysis.

AIM: The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. METHODS: We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. RESULTS: A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). CONCLUSION: There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.

Characteristics of Resting-State Electroencephalogram Network in α-Band of Table Tennis Athletes.

BACKGROUND: Table tennis athletes have been extensively studied for their cognitive processing advantages and brain plasticity. However, limited research has focused on the resting-state function of their brains. This study aims to investigate the network characteristics of the resting-state electroencephalogram in table tennis athletes and identify specific brain network biomarkers. METHODS: A total of 48 healthy right-handed college students participated in this study, including 24 table tennis athletes and 24 controls with no exercise experience. Electroencephalogram data were collected using a 64-conductive active electrode system during eyes-closed resting conditions. The analysis involved examining the average power spectral density and constructing brain functional networks using the weighted phase-lag index. Network topological characteristics were then calculated. RESULTS: The results revealed that table tennis athletes exhibited significantly higher average power spectral density in the α band compared to the control group. Moreover, athletes not only demonstrated stronger functional connections, but they also exhibited enhanced transmission efficiency in the brain network, particularly at the local level. Additionally, a lateralization effect was observed, with more potent interconnected hubs identified in the left hemisphere of the athletes' brain. CONCLUSIONS: Our findings imply that the α band may be uniquely associated with table tennis athletes and their motor skills. The brain network characteristics of athletes during the resting state are worth further attention to gain a better understanding of adaptability of and changes in their brains during training and competition.

Facile Tailoring of Metal-Organic Frameworks for Förster Resonance Energy Transfer-Driven Enhancement in Perovskite Photovoltaics.

Förster resonance energy transfer (FRET) has demonstrated its potential to enhance the light energy utilization ratio of perovskite solar cells by interacting with metal-organic frameworks (MOFs) and perovskite layers. However, comprehensive investigations into how MOF design and synthesis impact FRET in perovskite systems are scarce. In this work, nanoscale HIAM-type Zr-MOF (HIAM-4023, HIAM-4024, and HIAM-4025) is meticulously tailored to evaluate FRET's existence and its influence on the perovskite photoactive layer. Through precise adjustments of amino groups and acceptor units in the organic linker, HIAM-MOFs are synthesized with the same topology, but distinct photoluminescence (PL) emission properties. Significant FRET is observed between HIAM-4023/HIAM-4024 and the perovskite, confirmed by spectral overlap, fluorescence lifetime decay, and calculated distances between HIAM-4023/HIAM-4024 and the perovskite. Conversely, the spectral overlap between the PL emission of HIAM-4025 and the perovskite's absorption spectrum is relatively minimal, impeding the energy transfer from HIAM-4025 to the perovskite. Therefore, the HIAM-4023/HIAM-4024-assisted perovskite devices exhibit enhanced EQE via FRET processes, whereas the HIAM-4025 demonstrates comparable EQE to the pristine. Ultimately, the HIAM-4023-assisted perovskite device achieves an enhanced power conversion efficiency (PCE) of 24.22% compared with pristine devices (PCE of 22.06%) and remarkable long-term stability under ambient conditions and continuous light illumination.

The potential mechanism of ursolic acid in the treatment of bladder cancer based on network pharmacology and molecular docking.

OBJECTIVE: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking. METHODS: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, in vitro experiments were performed to further validate the predicted results. RESULTS: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes (STAT3, VEGFA, CASP3, TP53, IL1B, and CCND1). The in vitro experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway. CONCLUSIONS: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment.

[Potential Ecological Risk Characteristics and Source Apportionment of Heavy Metals in Farmland Soils around Typical Factories in Hunan Province Based on Monte-Carlo Simulation].

In order to explore the pollution characteristics， ecological risks， and pollution sources of heavy metals in farmland soils around typical factories in Hunan Province， the content characteristics of eight heavy metals in farmland soils around fluoride factories， leather factories， and plating plants were analyzed. The geo-accumulation index and potential ecological risk index were used to evaluate the pollution and environmental risk of heavy metals. The correlation analysis， hierarchical cluster analysis， and principal component analysis were used to analyze the sources of heavy metals. The Monte-Carlo model was used to evaluate the probability risk of regional ecological risk. The results showed that the main pollution elements in the soil were Cd and Zn， and their mean values were 4.46 and 2.73 times the background values， respectively. Zn was at a mild pollution level in the soil of the three typical factories， and Cd was at a moderate pollution level in the whole fluoride factory. The pollution sources of heavy metals in the typical factories were mainly natural sources， industrial activity sources （industrial waste discharge， mineral mining， and smelting activities）， traffic sources， etc. The results of potential ecological risk assessment showed that the ecological risk of the fluoride factory was at a high risk level， and the ecological risk of the leather factory and plating plants was at a high risk level. Cd was the main contributing element. The results of Monte-Carlo probabilistic ecological risk assessment reduced the uncertainty of deterministic assessment， which could provide scientific basis for accurate risk management and control in the regions.

OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway.

Glioblastoma, IDH-Wild type (GBM, CNS WHO Grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor with high morbidity, high mortality, and poor patient prognosis. The global burden of GBM is increasing notably due to limited treatment options, drug delivery problems, and the lack of characteristic molecular targets. OTU deubiquitinase 4 (OTUD4) is a potential predictive factor for several cancers such as breast cancer, liver cancer, and lung cancer. However, its function in GBM remains unknown. In this study, we found that high expression of OTUD4 is positively associated with poor prognosis in GBM patients. Moreover, we provided in vitro and in vivo evidence that OTUD4 promotes the proliferation and invasion of GBM cells. Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination. On the other hand, OTUD4 binds to fibroblast growth factor receptor 1 (FGFR1) and reduces FGFR1's K6 and K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing the activation of the downstream MAPK signaling pathway. Collectively, our results revealed that OTUD4 promotes GBM progression via OTUD4-CDK1-MAPK axis, and may be a prospective therapeutic target for GBM treatment.

lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis.

Introduction: In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment. Material and methods: We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC was quantified by qPCR in different times and concentrations of ox-LDL treatment conditions. Cell apoptosis rate and cell cycle profiles were assessed by flow cytometry and TUNEL assay. The target association was confirmed using a luciferase reporter assay and Western blot. Results: We found that GAPLINC expression was induced by ox-LDL treatment, but cell proliferation ability was significantly inhibited. We further confirmed that overexpressing of lncRNA GAPLINC in ox-LDL-exposed HAECs decreased cell proliferation by increasing cell apoptosis and arresting cell cycle in G2/M and S phase. Importantly, the detailed mechanistic analysis elucidated that LncRNA GAPLINC acts as a decoy to sequester miR-183-5p to prevent it from binding to target PDCD4. MiR-183-5p targets GAPLINC, and PDCD4 is a downstream target of miR-183-5p, and the cellular effects of this direct interaction were confirmed by a rescue assay experiment. Conclusions: The present study demonstrates that upregulation of lncRNA GAPLINC represses the binding of miR-183-5p to the PDCD4 promoter region and then promotes PDCD4 expression, thereby inducing cell apoptosis and suppressing endothelial cell proliferation.

Bio-catalyzed oxidation self-charging zinc-polymer batteries.

Oxidation self-charging batteries have emerged with the demand for powering electronic devices around the clock. The low efficiency of self-charging has been the key challenge at present. Here, a more efficient autoxidation self-charging mechanism is realized by introducing hemoglobin (Hb) as a positive electrode additive in the polyaniline (PANI)-zinc battery system. The heme acts as a catalyst that reduces the energy barrier of the autoxidation reaction by regulating the charge and spin state of O2. To realize self-charging, the adsorbed O2 molecules capture electrons of the reduced (discharged state) PANI, leading to the desorption of zinc ions and the oxidation of PANI to complete self-charging. The battery can discharge for 12 min (0.5 C) after 50 self-charging/discharge cycles, while there is nearly no discharge capacity in the absence of Hb. This biology-inspired electronic regulation strategy may inspire new ideas to boost the performance of self-charging batteries.

Chlorothalonil exposure compromised mouse oocyte in vitro maturation through inducing oxidative stress and activating MAPK pathway.

Chlorothalonil (CTL) is widely used in agricultural production and antifoulant additive globally due to its broad spectrum and non-systemic properties, resulting in its widespread existence in foods, soil and water. Extensive evidence demonstrated that exposure to CTL induced adverse effects on organisms and in particular its reproductive toxicity has been attracted public concern. However, the influences of CTL on oocyte maturation is mysterious so far. In this study, we documented the toxic effects of CTL on oocyte in vitro maturation and the related underlying mechanisms. Exposure to CTL caused continuous activation of spindle assembly checkpoints (SAC) which in turn compromised meiotic maturation in mouse oocyte, featured by the attenuation of polar body extrusion (PBE). Detection of cytoskeletal dynamics demonstrated that CTL exposure weakened the acetylation level of α-tubulin and impaired meiotic spindle apparatus, which was responsible for the aberrant state of SAC. Meanwhile, exposure to CTL damaged the function of mitochondria, inducing the decline of ATP content and the elevation of reactive oxygen species (ROS), which thereby induced early apoptosis and DNA damage in mouse oocytes. In addition, exposure to CTL caused the alteration of the level of histone H3 methylation, indicative of the harmful effects of CTL on epigenetic modifications in oocytes. Further, the CTL-induced oxidative stress activated mitogen-activated protein kinase (MAPK) pathway and injured the maturation of oocytes. In summary, exposure to CTL damaged mouse oocyte in vitro maturation via destroying spindle assembly, inducing oxidative stress and triggering MAPK pathway activation.