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ObjectiveDetecting fractures along roadway sections of coal mines allows for the characterization of the geologic conditions of roadways, thus providing guidance for roadway tunneling and support engineering. However, conventional image processing methods for fractures along roadway sections are susceptible to complex environments in underground coal mines, exhibiting a low fracture detection efficiency. MethodsThis study proposed a novel image processing method for detecting fractures along roadway sections based on a DC-UNet model. This method can be deployed on a mobile terminal and an embedded device, thereby allowing for real-time and effective detection of fractures along roadway sections and enhancing detection efficiency. First, an image dataset of fractures along roadway sections was established. The dataset was then enhanced using image data augmentation techniques, and the images in it were labeled. Subsequently, a framework for the detection and parameter computation of fractures was established based on the DC-UNet architecture. The improved DC-UNet model featured significantly elevated lightweight nature and detection accuracy by improving depthwise separable convolution (DwConv) and incorporating the convolutional block attention module (CBAM)—a dual attention module. Specifically, DwConv was employed to replace conventional convolution operations, reducing the model's parameters and computational load. The CBAM, integrating channel attention with spatial attention, enhanced the model's ability to capture semantic information related to fractures in low-light, dusty, and complex underground environments. Finally, the proposed method was compared with existing image processing algorithms, and the results were validated by importing the DC-UNet model into mobile terminal devices. Results and Conclusions The results indicate that the improved model achieves a fracture detection accuracy of 92%, higher than that of conventional image processing methods. The improved model, after being deployed on mobile devices, shows a data size of 7.52 MB, which is reduced by 68.9% compared to the original model, suggesting a decreased computational load. This model occupies a space of 19.43 MB, representing a reduction of 80.2% compared to the original model, suggesting an enhanced lightweight nature. This model exhibits a detection duration of 0.075 s, satisfying the requirements for field real-time inspection and accelerating the detection speed. Overall, the proposed improved method can be applied to detect fractures along the roadway sections in underground coal mines, laying a foundation for the fracture detection and tunneling engineering of roadways in coal mines.

Abstract Glycosylation, a key mode of protein modification in living organisms, is critical in regulating various biological functions by influencing protein folding, transportation, and localization. Changes in glycosylation patterns are a significant feature of cancer, are associated with a range of pathological activities in cancer‐related processes, and serve as critical biomarkers providing new targets for cancer diagnosis and treatment. Glycoproteins like human epidermal growth factor receptor 2 (HER2) for breast cancer, alpha‐fetoprotein (AFP) for liver cancer, carcinoembryonic antigen (CEA) for colon cancer, and prostate‐specific antigen (PSA) for prostate cancer are all tumor biomarkers approved for clinical use. Here, we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA (glycoRNA). This article focuses primarily on tumor metastasis, immune evasion, metabolic reprogramming, aberrant ferroptosis responses, and cellular senescence to illustrate the role of glycosylation in cancer. Additionally, we summarize the clinical applications of protein glycosylation in cancer diagnostics, treatment, and multidrug resistance. We envision a promising future for the clinical applications of protein glycosylation.

Abstract Background The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics. Methods We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production. Results hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, we found that hUC-MSCs cultured in different media exhibit variations in paracrine capacity and in their support of hematopoietic stem cell (HSC) self-renewal. Conclusion Considering the substantial funding and time required for cell-based drug development, our results underscore the importances of comprehensively optimizing the composition of medium for the specific disease prior to conducting clinical trials of cell-based therapies. The criteria for selecting culture medium should be based on the requirements of the target disease for cellular function. In addition, we provide a way to formulate different customized SFM, which is beneficial for the development of cell therapy industry.

BackgroundObesity, through mechanisms such as insulin resistance and systemic low-grade inflammation, can damage the central nervous system and impair cognitive function. Weight-adjusted waist index (WWI) is a novel measure of obesity that may offer more precise assessments of muscle and fat mass. This study aims to investigate the association between WWI and cognitive function in older Chinese men.MethodsData from the 2011–2018 China Longitudinal Health and Longevity Survey (CLHLS) were used in this study. WWI and cognitive function were examined in both linear and non-linear situations using Kaplan–Meier survival curves, multivariate Cox regression models, and restricted cubic spline (RCS) regression.ResultsThis study included 1,392 older Chinese men aged 65 years and over for whom complete data were available. After controlling for all potential confounding variables, our analysis showed a statistically significant positive association between WWI and cognitive decline. Specifically, for every 1 cm/√kg increase in WWI, the risk of cognitive impairment increased by 17% (HR = 1.17, 95% CI: 1.02–1.35). Using 11.52 cm/√kg as the cutoff point for WWI, we found that High WWI was associated with a 44% increased risk of cognitive impairment compared with Low WWI (HR = 1.44, 95% CI: 1.07–1.96). RCS regression analysis confirmed a linear positive correlation between WWI and cognitive impairment.ConclusionHigher WWI is linked to worse cognitive performance in older Chinese men.

Abstract Chloroplasts are key players in photosynthesis and immunity against microbial pathogens. However, the precise and timely regulatory mechanisms governing the control of photosynthesis-associated nuclear genes (PhANGs) expression in plant immunity remain largely unknown. Here we report that TaPIR1, a Pst-induced RING-finger E3 ubiquitin ligase, negatively regulates Pst resistance by specifically interacting with TaHRP1, an atypical transcription factor histidine-rich protein. TaPIR1 ubiquitinates the lysine residues K131 and K136 in TaHRP1 to regulate its stability. TaHRP1 directly binds to the TaHRP1-binding site elements within the PhANGs promoter to activate their transcription via the histidine-rich domain of TaHRP1. PhANGs expression induces the production of chloroplast-derived ROS. Although knocking out TaHRP1 reduces Pst resistance, TaHRP1 overexpression contributes to photosynthesis, and chloroplast-derived ROS production, and improves disease resistance. TaPIR1 expression inhibits the downstream activation of TaHRP1 and TaHRP1-induced ROS accumulation in chloroplasts. Overall, we show that the TaPIR1-mediated ubiquitination and degradation of TaHRP1 alters PhANGs expression to disrupt chloroplast function, thereby increasing plant susceptibility to Pst.

Abstract Background Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. Case presentation A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. Conclusions In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Abstract Hydrogen sulfide (H2S) has emerged as a novel endogenous gas signaling molecule, joining the ranks of nitric oxide (NO) and carbon monoxide (CO). Recent research has highlighted its involvement in various physiological processes, such as promoting root organogenesis, regulating stomatal movement and photosynthesis, and enhancing plant growth, development, and stress resistance. Tobacco, a significant cash crop crucial for farmers’ economic income, relies heavily on root development to affect leaf growth, disease resistance, chemical composition, and yield. Despite its importance, there remains a scarcity of studies investigating the role of H2S in promoting tobacco growth. This study exposed tobacco seedlings to different concentrations of NaHS (an exogenous H2S donor) − 0, 200, 400, 600, and 800 mg/L. Results indicated a positive correlation between NaHS concentration and root length, wet weight, root activity, and antioxidant enzymatic activities (CAT, SOD, and POD) in tobacco roots. Transcriptomic and metabolomic analyses revealed that treatment with 600 mg/L NaHS significantly effected 162 key genes, 44 key enzymes, and two metabolic pathways (brassinosteroid synthesis and aspartate biosynthesis) in tobacco seedlings. The addition of exogenous NaHS not only promoted tobacco root development but also potentially reduced pesticide usage, contributing to a more sustainable ecological environment. Overall, this study sheds light on the primary metabolic pathways involved in tobacco root response to NaHS, offering new genetic insights for future investigations into plant root development.

Abstract As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.

Accurate determination of the inverse kinematics for the drilling arm of a drilling and anchoring robot is crucial in achieving automatic support in coal mine roadways. Addressing issues such as poor accuracy, limited real-time performance, and susceptibility to local optima, this study presents a novel approach for solving the inverse kinematics problem of an unconventional mechanical arm by combining Monte Carlo random sampling method and Newton iteration method. Initially, a kinematics model is established based on the structure of the drilling arm, and individual coordinate systems are defined for each joint to enable forward kinematics solutions. The Monte Carlo method is employed to determine the motion space of the drill boom. By subdividing the motion space into smaller cubes with a defined step size, a mapping relationship is established between the spatial coordinates of these cubes and the corresponding joint variable values. Using the transformation matrix associated with a given target space point, an index function is employed to identify the relevant small cubes. The points within these cubes, which are closest to the target space point, are calculated, and their corresponding joint variable values are used as initial values. The Newton iteration method is then introduced, utilizing the iterative formula for multivariate functions to determine the variation of each joint variable. The inverse kinematics solution for the unconventional manipulator is obtained through iterative cycles. The simulation results show that, compared with Newton-Raphson iterative method based on random initial values and the particle swarm optimization algorithm, the corresponding average angle error of the calculation results of this method is reduced by 64.98% and 57.34%, and the average time consumption is reduced by 35.90% and 22.33%, respectively, thereby enhancing solution accuracy and real-time performance. The feasibility and effectiveness of the proposed Monte Carlo and Newton iteration method for solving the inverse kinematics problem in unconventional manipulators are verified. Overall, this research provides evidence supporting the practicality and efficiency of the proposed Monte Carlo random sampling method and Newton iteration method for accurate inverse kinematics solutions in unconventional manipulators.

Fusarium is a soil-borne pathogen that poses a serious threat to the quality and yield of hundreds of crops worldwide, particularly tobacco production. Using metabolomics technology, we investigated natural metabolites from disease-conducting soil (DCS) and disease-suppressing soil (DSS) of tobacco rhizosphere as fungicides to control tobacco Fusarium wilt (TFW), which is mainly caused by Fusarium oxysporum. Furthermore, the antifungal mechanisms of these natural metabolites were preliminarily elucidated through various assessments, including antifungal activity determination, chemotaxis effect tests, PI staining experiments, and measurements of extracellular conductivity and protein content. Metabolomics results showed that the DCS with three different disease grades (G1, G5 and G9 groups) had significantly higher levels of 15, 14 and 233 differential rhizosphere metabolites (DRMs) and significantly lower levels of 72, 152 and 170 DRMs compared to the DSS (G0 group). According to KEGG pathway analysis, these DRMs were found to be enriched in the caffeine metabolism, biosynthesis of phenylpropanoids, galactose metabolism and tyrosine metabolism, etc. Linustatin, scopoletin and phenylpropiolic acid were picked out from these DRMs and found to have suppressive activity against F. oxysporum through correlation analysis and antifungal experiments. The three DRMs showed strong inhibitory effects on the growth and spore germination of F. oxysporum at concentrations of 0.5 mM or higher in each test period. Furthermore, F. oxysporum showed a phobotaxis effect against these three DRMs at concentrations as low as 0.25 mM. Finally, we found that the three DRMs had an inhibitory effect on F. oxysporum by destroying the integrity of the cell membrane and increasing the membrane permeability of F. oxysporum. This study firstly reports the inhibition activity of phenylpropiolic acid and linustatin on F. oxysporum, providing a practical and environmentally friendly method for biocontrol of TFW by using natural fungicides.

For the difficulty of pinpointing of tunneling machines in the complex environment of coal mine tunnels,a precise positioning method of roadheader based on inertial navigation and visual fusion is proposed, which uses a positioning scheme of inertial navigation plus "vision+laser target". With the designed four feature point large-sized laser target fixed on the roof of the tunnel and the camera on the tunneling machine to collect laser target images, the scheme uses the circular fitting method to locate the center of the light spot and the EPnP algorithm based on four feature points to calculate the position of the tunneling machine. A “vision+laser target” position detection experiment was conducted in simulated condition of heading face to verify the effectiveness of the method in detecting the position of tunneling machines. The results are as follows: within 30 meters tunnel, the maximum error in the width, position, and height are no more than 28.549, 78.868, and 44.459 mm, which shows accurate detection of the position of the tunneling machine. For the inaccurate pose detection of tunneling machines in inertial navigation measurement, induced by the accumulation of pose errors over time and the machine vibration on the combined positioning system, an improved Sage-Husa adaptive filtering method for inertial navigation and visual information fusion is proposed, which could correct measurement errors by detecting new variance values to improve positioning accuracy. A combined positioning experiment of inertial navigation plus “vision+laser target” was conducted in a simulated heading face environment, using improved Sage-Husa adaptive filtering algorithm to fuse inertial navigation and visual information for comparative analysis, which show that the improved Sage-Husa adaptive filtering algorithm fusion results in smaller positioning errors. The maximum errors of pitch angle, roll angle, and heading angle are 0.029°, 0.051°, and 0.0113°, respectively. Within 30 meters, the position error of tunnel width is within the range of 0.033 m, and the position error of tunnel excavation direction is within the range of 0.062 m. Overall, the proposed inertial navigation plus visual fusion positioning method can meet the accuracy requirements of tunnel excavation positioning.

Objective To study the changes in related parameters after secondary preparation of blood components, in order to further improve the quality of blood components. Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced, and the quality was tested. Then, using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation, and the red blood cells were washed through the Haemonetics ACP 215 device, and the quality was tested. The preparation parameters of blood components were observed, compared and optimized. Results Under comparable centrifugation effects of different centrifugation conditions, the quality control items, which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation, such as volume, hemoglobin, hematocrit and residual white blood cells met the relevant national standards. And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards, while volume exceeded the standard by 7-14 mL, which can be operated to the standard range. In addition, the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75% and 99% respectively. Conclusion There is a certain correlation between primary and secondary preparation of blood components, but the relevant parameters of secondary preparation of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards, thus ensuring clinical treatment effect and safety.

Background: Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation. Summary: As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed. Key Messages: Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R , and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

ObjectiveVitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection.MethodsGenetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids.ResultsVD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription.ConclusionVD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Abstract Caroli’s syndrome is a congenital disease characterized by dilation of intrahepatic bile ducts and congenital hepatic fibrosis. It is a rare condition in clinical work. Typically, the diagnosis of this disease is confirmed through medical imaging. Here, we report a case of atypical Caroli’s syndrome in a patient who presented with recurrent upper gastrointestinal tract bleeding. The patient underwent imaging examinations, liver biopsy and whole exome sequencing. The results of the imaging examination were non-specific. However, with the aid of pathological examination, the patient was diagnosed with Caroli’s syndrome. In conclusion, for cases where the imaging presentation of Caroli’s syndrome is inconclusive, an accurate diagnosis should rely on pathology. By discussing this specific case, our aim is to enhance readers' understanding of this disease, provide valuable information that can aid in the early detection and appropriate management of Caroli’s syndrome, ultimately improving patient outcomes.

Intelligent digging and anchoring equipment in underground coal mines is the key to improve the mining imbalance problem in the industry, and the precise positioning of digging and anchoring equipment is the prerequisite to realize its intelligence. Compared with other traditional positioning methods, the vision-based pose measurement method has been initially applied in underground coal mines for its advantages of no contact and no cumulative error. Aiming at the problems of complex structure of cooperative target and cumbersome calibration of the current visual positioning method of the digging anchor equipment in the face of the underground coal mine, combining with the characteristics of the original laser pointers in the face of the digging, a visual positioning method of the digging and anchoring equipment based on the information of a single laser beam is proposed. By analyzing the laser pointer spot and beam image features, the method proposes a laser spot center extraction method based on two-dimensional inverse tangent function fitting and a laser beam centerline extraction method based on Hough straight line detection, and constructs a binocular visual position solving model based on the point and line features, which results in the real-time position of the anchor digging equipment in the roadway. Finally, in order to verify the feasibility and accuracy of the proposed feature extraction method and visual positioning method, experiments were conducted in the laboratory by building a platform to simulate the working condition environment of the digging face. The results show that the visual localization method of digging and anchoring equipment based on the information of mining laser pointers has high accuracy of position measurement. Within the test range of 50 m, the average measurement errors of the body position along the X-axis, Y-axis and Z-axis under the roadway coordinate system are 25.44, 58.64 and 31.08 mm, respectively, and the maximum errors are 55.16, 127.39 and 63.57 mm, respectively; and the average measurement errors of the pitch angle, yaw angle and roll angle of the body attitude under the roadway coordinate system are 0.22°, 0.22°, 0.41°, and their maximum errors are 0.29°, 0.37°, 0.58°, respectively. The maximum errors are 0.29°, 0.37° and 0.58°, respectively. It meets the requirement of positioning accuracy for the construction of underground roadway in coal mine.

Abstract Objective Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is a common clinical emergency. Transcatheter arterial embolization (TAE) is usually used to locate the bleeding site and provide interventional embolization. During TAE, there is a low positive rate of angiography, and localization of the culprit vessel is difficult. The purpose of this study was to demonstrate the role of preplaced metal clips in TAE for ANVUGIB patients. Materials and methods Patients with ANVUGIB in whom bleeding sites were identified endoscopically and treated with TAE from January 1st, 2005 to July 1st, 2021 were retrospectively included. According to the presence or absence of preplaced metal clips, they were divided into two groups. The main outcome measurements included the clinical success rate and rebleeding rate. Secondary outcome measurements included the mortality rate and the need for surgery. Predictors of the clinical success rate were assessed with univariate analysis and multivariate analysis. Results A total of 102 patients were included in this study, and all of them had undergone arterial embolization. There were 73 cases in the group with metal clips and 29 cases in the group without metal clips with consistent baseline information. The group with metal clips had a higher clinical success rate (82.2% vs. 45.0%, P

Objective To investigate the preparation quality and clinical application effect of pooled platelets with leukocytes reduced. Methods The quality and clinical effect of the buffy-coated method prepared pooled platelets leukocytes reduced (experimental group, n=40) and apheresis platelets leukocytes reduced (control group, n=40) were compared. Results The platelet volume (mL), platelet count (×1011), red blood cell contamination (×108) and residual white blood cell (×106) of the experimental group and control group were 278.90±7.92 vs 276.52±8.01, 2.66±0.09 vs 2.66±0.83, 0.54±0.42 vs 0.83±0.84, 0.29±0.54 vs 0.27±0.51, respectively, with no significant difference. The results of bacterial culture were negative, all met the requirements of relevant national standards. In addition, the CCI (×103, 24 h) and PPR (%) were 15.11±9.86 vs 14.61±12.55 and 54.23±18.70 vs 61.41±19.09 respectively, with no significant difference, indicating a certain degree of therapeutic effect. Conclusion The quality and clinical therapeutic effect of pooled platelets leukocytes reduced were consistent with that of apheresis platelets leukocytes reduced.

Aiming at the problems of low intelligence of current tunneling equipment, difficulty in describing over-excavation, under-excavation and abnormal collision in tunneling process, and difficulty in adapting traditional automatic cutting and memory cutting technology to complex geological conditions, a digital twin-driven virtual teaching memory cutting control method for cantilever roadheader is proposed. By analyzing the research situation of digital twin technology in the field of intelligent coal mining, the overall scheme of memory cutting control system of cantilever roadheader driven by digital twin is designed, and the key technology of memory cutting of cantilever roadheader under complex working conditions is studied. Firstly, the characteristics of digital twin and virtual reality technology are fully utilized to study the virtual teaching strategy under complex working conditions. Based on the Unity3D platform, the virtual twin model of the working face and equipment with the same size of the corresponding entity, the kinematics model of the cutting unit and the virtual collision detection model are established. The virtual model movement is controlled through the intelligent interactive interface at the virtual end, and the teaching trajectory is designed and optimized according to the worker’s experience, so that it can be used as the target expected trajectory of trajectory tracking to make up for the excessive dependence on the worker’s experience caused by the traditional underground manual teaching due to the harsh working conditions. Secondly, in order to improve the quality of section forming, the control method of teaching trajectory tracking and reproduction in memory automatic cutting stage is studied. The dynamic model of cutting part is established by Lagrange method, and the tracking control accuracy of end effector to teaching trajectory is improved by combining iterative learning with sliding mode control. Finally, the simulation control platform of the memory cutting of the cantilever roadheader is built. Through the real-time data transmission and interaction between the virtual space and the physical space and between the modules, the three-dimensional visual simulation of the memory cutting virtual teaching and trajectory tracking control process is completed in the virtual space, and then the memory automatic cutting trajectory tracking control command is generated and sent to the end effector of the physical entity of the cantilever roadheader to drive it to carry out the section forming cutting according to the teaching trajectory. At the same time, the physical sensor collects the pose data of the cantilever roadheader fuselage and the cutting arm, and reversely drives the virtual model to move synchronously. The closed-loop control of robot virtual model and physical entity is realized. On this basis, the virtual and real synchronization of the system, the motion consistency between the virtual prototype and the physical prototype, and the trajectory tracking and reproduction control accuracy are verified. The experimental results show that the system data transmission delay is low, which can ensure the virtual and real consistency and synchronization, and the trajectory tracking control accuracy meets the actual use requirements. This method provides a new idea for memory cutting and intelligent control of tunneling equipment.

Abstract Background With growing cases of breast cancer, WeChat public account, an important information publishing platform of WeChat, has become a breast cancer treatment health information provider to a huge audience. It is essential for health information to possess high-level accuracy and reliability. This work evaluates the quality of health information on breast cancer treatment in WeChat public accounts (WPAs), to benefit the patients while making treatment decisions and provide WPA authors with suggestions on publishing high-quality treatment health information. Methods With “breast cancer” as keywords, searches were implemented on weixin.sogou.com and the WeChat app. The WPAs oriented to patients with breast cancer were selected, and the four latest articles of each WPA were included in a set to be evaluated with DISCERN. Results A total of 37 WPAs and 136 articles published by them were included. The accounts operated by individual users were 54%. The median of overall quality of 136 articles was 44 (interquartile range = 10.75) and ranked as “fair”, of which only 28 (21%) were of “good” or higher quality. Among these articles, 74 (54%) were related to medical treatments, and 13 of them mentioned clinical trials; 36 (27%) dealt with surgery. 101 (74.26%) omitted additional sources of information; 102 (75%) did not explicitly suggest shared decision-making. A significant difference was not found in the dimensions “reliability of the articles” and “specific details of information on treatment choices” between the distinct categories of account subjects and various treatment options (P > 0.05). Conclusions The quality of the articles on breast cancer treatment health information in WPAs was moderate. WPA producers should focus on improving the reliability of information and providing more details on treatment options, to assist patients in making optimal decisions during treatment.

Background: Lung cancer ranks first in both cancer incidence and mortality in China. The emergence of novel treatments for ALK-positive NSCLC led to an improvement in survival and quality of life for patients with advanced ALK mutation-positive non-small cell lung cancer (NSCLC). This study sought to assess the cost-effectiveness of 6 tyrosine kinase inhibitors (TKIs)—crizotinib, alectinib, ceritinib, brigatinib, ensartinib, and lorlatinib—as first-line treatments for ALK-positive NSCLC from the perspective of the Chinese health care system. Methods: A Markov model was developed to estimate the cost-effectiveness of these 6 TKIs. In this model, ALK-positive NSCLC patients were initially simulated to receive 1 of the 6 TKIs as first-line therapy, followed by different TKIs as subsequent treatment and salvage chemotherapy as last-line treatment. Survival data were sourced from the latest published clinical trials. Costs were derived from recent national health insurance negotiations and hospital information systems of selected health care facilities. Utilities for healthy states and adverse events were obtained from the literature. One-way and probabilistic sensitivity analysis as well as scenario analysis was conducted to assess the robustness of the results. Results: Compared to ensartinib, crizotinib, alectinib, ceritinib, brigatinib, and lorlatinib demonstrated incremental quality-adjusted life years (QALYs) of −1.13, 0.39, −0.58, −0.09, and 0.35, respectively. The corresponding incremental costs were $10 677, $33 501, −$6426, $2672, and $24 358. This resulted in ICERs of –$9449/QALY, $85 900/QALY, $11 079/QALY, $29 689/QALY and $69 594/QALY, respectively. Conclusion: Crizotinib was considered to be absolutely dominated by ensartinib. Under a willingness-to-pay threshold of $38 223/QALY, ceritinib and brigatinib were cost-effective compared with ensartinib, while lorlatinib and alectinib were not cost-effective when compared with ensartinib. Overall, brigatinib emerged as the most cost-effective treatment among all the options considered.

Background Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated.Methods We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells’ infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate.Results In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G–Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.Conclusions Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Abstract Objective To date, no direct comparisons have compared the effectiveness of all ALK inhibitors (ALKis) against ALK‐positive non‐small cell lung cancer (NSCLC). The aim of the present study was to investigate the efficacy and safety of ALKis in ALK‐positive NSCLC. Methods The effectiveness of ALKis was evaluated by assessing progression‐free survival (PFS), overall survival (OS), overall response rate (ORR), and PFS with baseline brain metastasis (BM). The serious adverse events (SAEs: Grade ≥ 3) and adverse events (AEs) leading to discontinuation were pooled to evaluate safety. We conducted an indirect treatment comparison between all ALKis by using a Bayesian model. Results Twelve eligible trials including seven treatments were identified. All of the ALKis improved PFS and ORR relative to chemotherapy. Consistent with alectinib, brigatinib, lorlatinib, and ensartinib showed significant differences versus crizotinib and ceritinib. Lorlatinib seemed to prolong PFS compared with alectinib (0.64, 0.37 to 1.07), brigatinib (0.56, 0.3 to 1.05), and ensartinib (0.53, 0.28 to 1.02). No significant difference was found among them in OS except for alectinib versus crizotinib. Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR. Subgroup analyses based on BM indicated that PFS was dramatically lengthened by lorlatinib. Compared with other ALKis, alectinib notably reduced the rate of SAEs. There was no striking difference between discontinuation for AEs, except for ceritinib versus crizotinib. The ranking of validity showed that lorlatinib had the longest PFS (98.32%) and PFS with BM (85.84%) and the highest ORR (77.01%). The rank of probabilities showed that alectinib had the potentially best safety in terms of SAEs (97.85%), and ceritinib had less discontinuation (95.45%). Conclusion Alectinib was the first choice for patients with ALK‐positive NSCLC and even for those with BM, whereas lorlatinib was the second choice. Long‐term follow‐up and prospective studies are warranted to compare ALKis and to verify our conclusions directly.

Abstract Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Abstract Background The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. Methods This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. Results GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P

Abstract The underground coal mine production of the fully mechanized mining face exists many problems, such as poor operating environment, high accident rate and so on. Recently, the intelligent autonomous coal mining is gradually replacing the traditional mining process. The artificial intelligence technology is an active research area and is expect to identify and warn the underground abnormal conditions for intelligent longwall mining. It is inseparable from the construction of datasets, but the downhole dataset is still blank at present. This work develops an image dataset of underground longwall mining face (DsLMF+), which consists of 138004 images with annotation 6 categories of mine personnel, hydraulic support guard plate, large coal, towline, miners’ behaviour and mine safety helmet. All the labels of dataset are publicly available in YOLO format and COCO format. The availability and accuracy of the datasets were reviewed by experts in coal mine field. The dataset is open access and aims to support further research and advancement of the intelligent identification and classification of abnormal conditions for underground mining.

Wide-bandgap (WBG) perovskite has demonstrated great potential in perovskite-based tandem solar cells. The power conversion efficiency (PCE) of such devices has surpassed 34%, signifying a new era for renewable energy development. However, the ion migration reduces the stability and hinders the commercialization, which is yet to be resolved despite many attempts. A big step forward has now been achieved by the simulation method. The detailed thermodynamics and kinetics of the migration process have been revealed for the first time. The stability has been enhanced by more than 100% via the heterojunction layer on top of the WBG perovskite film, which provided extra bonding for kinetic protection. Hopefully, these discoveries will open a new gate for WBG perovskite research and accelerate the application of perovskite-based tandem solar cells.

Rock bolting is a commonly used method for stabilizing the surrounding rock in coal-mine roadways. It involves installing rock bolts after drilling, which penetrate unstable rock layers, binding loose rocks together, enhancing the stability of the surrounding rock, and controlling its deformation. Although recent progress in drilling and anchoring equipment has significantly enhanced the efficiency of roof support in coal mines and improved safety measures, how to deal with drilling rigs’ misalignment with the through-hole center remains a big issue, which may potentially compromise the quality of drilling and consequently affect the effectiveness of bolt support or even result in failure. To address this challenge, this article presents a robotic teleoperation system alongside a hybrid visual servo control strategy. Addressing the demand for high precision and efficiency in aligning the drilling rigs with the center of the drilling hole, a hybrid control strategy is introduced combining position-based and image-based visual servo control. The former facilitates an effective approach to the target area, while the latter ensures high-precision alignment with the center of the drilling hole. The robot teleoperation system employs the binocular vision measurement system to accurately determine the position and orientation of the drilling-hole center, which serves as the designated target position for the drilling rig. Leveraging the displacement and angle sensor information installed on each joint of the manipulator, the system utilizes the kinematic model of the manipulator to compute the spatial position of the end-effector. It dynamically adjusts the spatial pose of the end-effector in real time, aligning it with the target position relative to its current location. Additionally, it utilizes monocular vision information to fine-tune the movement speed and direction of the end-effector, ensuring rapid and precise alignment with the target drilling-hole center. Experimental results demonstrate that this method can control the maximum alignment error within 7 mm, significantly enhancing the alignment accuracy compared to manual control. Compared with the manual control method, the average error of this method is reduced by 41.2%, and the average duration is reduced by 4.3 s. This study paves a new path for high-precision drilling and anchoring of tunnel roofs, thereby improving the quality and efficiency of roof support while mitigating the challenges associated with significant errors and compromised safety during manual control processes.

Abstract Background To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). Methods In this 16‐week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. Results Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high‐density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00–0.16), and diminished low‐density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05–0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to −1.57 mmol/L [95% CI, −2.60 to −0.54]), this difference was abolished in patients whose fasting C‐peptide was ≥0.9 ng/mL. Conclusion Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C‐peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C‐peptide levels be evaluated when using or switching to the novel glucagon‐like peptide‐1 receptor agonists beinaglutide. Trial Registration ClinicalTrials.gov: NCT03829891.

Abstract Objectives Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods We employed an RNA‐sequencing cohort (n = 50) from Sun Yat‐Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA‐BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results In our study, chitinase 3‐like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P

Abstract Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

Abstract Background Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. Methods Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. Results Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. Conclusion Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.

Summary: Endometriosis (EMS) is a prevalent disease and the etiologies has not uniform. Microbiota is associated with human diseases. To delve into the relationship between EMS and microbiota, Ectopic (EM) and eutopic (EU) endometrial tissues, pharyngeal swabs, and stools were collected from EMS patients. The microbiota composition of EM and EU partially overlapped, with similar taxon numbers and diversity, but the richness levels were significantly different. A comparison of intestinal microbes in healthy individuals (FN) and EMS patients (FE) revealed that the richness of Enterococcus, Pseudomonas, Haemophilus, and Neisseria was enhanced in FE. In addition, Enterococcus-induced mice (EFA) presented with a higher degree of lesion infiltration and a wider distribution of lesions. Proteomic analysis revealed the expression of plant homeodomain finger 11 (PHF11) was notably downregulated in EFA. And the downregulated expression of PHF11 was accompanied by the upregulated expression of interleukin 8 (IL-8). Our findings suggest a potential regulatory mechanism for PHF11 in EMS development.

IntroductionThe coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes.MethodsWe retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit).ResultsThere was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes.ConclusionWomen who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections.

Antibacterial hydrogels have attracted significant attention due to their diverse applications, efficient antimicrobial properties, and adaptability to various environments and requirements. However, their relatively fragile structure, coupled with the potential for environmental toxicity when exposed to their surroundings for extended periods, may significantly limit their practical application potential. In this work, a composite hydrogel was synthesized with outstanding mechanical features and antibacterial capability. The hydrogel was developed through the combination of the eco-friendly and enduring antibacterial agent, lignin silver nanoparticles (Lig-Ag NPs), with polyvinyl alcohol (PVA) and sodium alginate (SA), in varying proportions. The successful synthesis of the hydrogel and the dispersed distribution of Lig-Ag NPs within the hydrogel were confirmed by various analytical techniques, including field emission scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), mercury intrusion porosimetry (MIP), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The formation of multiple hydrogen bonds between Lig-Ag NPs and the composites contributed to a more stable and dense network structure of the hydrogel, consequently enhancing its mechanical properties. Rheological tests revealed that the hydrogel exhibited an elastic response and demonstrated outstanding self-recovery properties. Significantly, the antibacterial hydrogel demonstrated effectiveness against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), achieving a

Accurate and reliable pose estimation of boom-type roadheaders is the key to the forming quality of the tunneling face in coal mines, which is of great importance to improve tunneling efficiency and ensure the safety of coal mine production. The multi-laser-beam target-based visual localization method is an effective way to realize accurate and reliable pose estimation of a roadheader body. However, the complex background interference in coal mines brings great challenges to the stable and accurate segmentation and extraction of laser beam features, which has become the main problem faced by the long-distance visual positioning method of underground equipment. In this paper, a semantic segmentation network for underground laser beams in coal mines, RCEAU-Net, is proposed based on U-Net. The network introduces residual connections in the convolution of the encoder and decoder parts, which effectively fuses the underlying feature information and improves the gradient circulation performance of the network. At the same time, by introducing cascade multi-scale convolution in the skipping connection section, which compensates for the lack of contextual semantic information in U-Net and improves the segmentation effect of the network model on tiny laser beams at long distance. Finally, the introduction of an efficient multi-scale attention module with cross-spatial learning in the encoder enhances the feature extraction capability of the network. Furthermore, the laser beam target dataset (LBTD) is constructed based on laser beam target images collected from several coal mines, and the proposed RCEAU-Net model is then tested and verified. The experimental results show that, compared with the original U-Net, RCEAU-Net can ensure the real-time performance of laser beam segmentation while increasing the Accuracy by 0.19%, Precision by 2.53%, Recall by 22.01%, and Intersection and Union Ratio by 8.48%, which can meet the requirements of multi-laser-beam feature segmentation and extraction under complex backgrounds in coal mines, so as to further ensure the accuracy and stability of long-distance visual positioning for boom-type roadheaders and ensure the safe production in the working face.

Introduction: Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and its mechanism is complex involving multiple factors, while delayed ischemic preconditioning (DIPC) has a protective effect on the above process. In our previous study, we found that DIPC can exert its protection on renal IRI by inhibiting the maturation of dendritic cells (DCs), but the mechanism has not been clarified. This study aimed to investigate the protective mechanism of DIPC on renal IRI in mice through Treg mediated by immature DCs (imDCs). Methods: The IRI mice model, DIPC treatment, and conditional CD11c+ DCs (CD11c-DTR) knockout mice were used to perform our study. The maturation and differentiation of DCs and Treg cells in the kidney and spleen were analyzed by flow cytometry. HE staining was used to evaluate the pathology of the kidney tissue. The level of creatinine (Cr), oxidative stress factors (SOD, MDA), and inflammatory factors (TNF-α, IL-10, IL-4) were also measured. Then, imDCs were co-cultured with HK-2 cells, and apoptosis was analyzed with flow cytometry and PI-Hoechst 33,342 fluorescence staining to assess the apoptosis rate of HK-2 cells under hypoxic-reoxygenated (H/R) conditions. Results: DIPC could decrease renal Cr levels, alleviate pathological renal damage, and reduce oxidative stress and inflammation caused by IRI. Moreover, DIPC could decrease the number of mature DCs (mDCs) and increase Treg lymphocyte infiltration in the kidney tissue, while the reduction of DCs reversed this process. In addition, our in vitro experiment found that in the H/R model, the apoptosis of HK-2 cells decreased which were co-cultured with imDCs. Conclusion: DIPC can regulate the differentiation of DCs into imDCs, thus affecting the differentiation level and distribution of Treg cells to exert its protective effect on renal IRI.

Abstract The perivascular epithelioid cell tumor (PEComa) is a rare tumor of interstitial origin characterized by several immunological and muscle cell markers. The clear cell sugar tumor (CCST) of the lung is a type of PEComa defined by thin cell walls and high levels of glycogen in the cytoplasm. We herein reported the case of a 48‐year‐old male with a recurrence of lung CCST. The preoperative diagnosis of the lung mass was performed by percutaneous needle biopsy. During the thoracoscopic resection, multiple adhesions in the thoracic cavity were described. The tumor invaded the chest wall, and the boundaries between the tumor and surrounding normal tissues were unclear. The mediastinal lymph nodes were significantly enlarged. No relevant gene mutations were detected. After concomitant chemoradiotherapy, the patient's condition was stable. We also conducted a literature review and discussed the overall findings.

ObjectivesThe study aimed to investigate the effects of sleep and exercise, individually and jointly, on depressive symptoms in Chinese adolescents.MethodsCluster sampling was used to conduct a cross-sectional, electronic survey among 11,563 students from five primary and high schools in Sichuan Province in Western China. The questionnaire contained custom-designed items concerning sleep and exercise, while it used the Center for Epidemiologic Studies Depression Scale to assess depressive symptoms and the Core Self-Evaluations Scale to assess core self-evaluation. Data were analyzed using descriptive statistics and multivariate linear regression.ResultsA total of 10,185 valid questionnaires were collected, corresponding to an effective response rate of 88.1%. Among the respondents in the final analysis, 5,555 (54.5%) were boys and 4,630 (45.5%) were girls, and the average age was 15.20 ± 1.72 years (range, 11–18 years). Only less than half of the respondents (4,914, 48.2%) reported insufficient sleep, while the remainder (5,271, 51.8%) had adequate sleep. Nearly one-quarter (2,250, 22.1%) reported insufficient exercise, while the remainder (7,935, 77.9%) reported adequate exercise. More than half of the respondents (5,681, 55.7%) were from vocational high school, 3,368 (33.1%) were from junior high school, 945 (9.3%) were from senior high school, and 191 (1.9%) were from primary school. The prevalence of depressive symptoms among all respondents was 29.5% (95% CI 28.7%−30.4%). When other variables were controlled, the depression score did not vary significantly with gender (B = −0.244, SE = 0.127, P = 0.054), but it decreased by 0.194 points per 1-year increase in age (B = −0.194, SE = 0.037, P < 0.001). Students getting adequate sleep had depression scores 2.614 points lower than those getting insufficient sleep (B = −2.614, SE = 0.577, P < 0.001), while students who engaged in adequate exercise had depression scores 1.779 points lower than those not exercising enough (B = −1.779, SE = 0.461, P < 0.001). The depression score decreased by 0.919 points per 1-point increase in the core self-evaluation score (B = −0.919, SE = 0.008, P < 0.001). In regression controlling for gender, age, and core self-evaluation, sleep and exercise were found to be related significantly to influence depressive symptoms (B = 0.821, SE = 0.315, P = 0.009).ConclusionAdequate sleep and adequate exercise are individually associated with milder depressive symptoms in Chinese adolescents. Our results further highlight the need for researchers and clinicians to take into account not only the individual but also the joint effects of sleep and exercise on depression in adolescents when conducting research and designing interventions. If sleep or physical exercise has substantially reduced the risk of depressive symptoms, further reductions by improving sleep and exercise become difficult and may even have opposite effects.

Organoids are a class of multicellular structures with the capability of self-organizing and the characteristic of original tissues, they are generated from stem cells in 3D culture in vitro. Organoids can mimic the occurrence and progression of original tissues and widely used in disease models in recent years. The ability of tumor organoids to retain characteristic of original tumors make them unique for tumorigenesis and cancer therapy. However, the history of organoid development and the application of organoid technology in cancer therapy are not well understood. In this paper, we reviewed the history of organoids development, the culture methods of tumor organoids establishing and the applications of organoids in cancer research for better understanding the process of tumor development and providing better strategies for cancer therapy. The standardization of organoids cultivation facilitated the large-scale production of tumor organoids. Moreover, it was found that combination of tumor organoids and other cells such as immune cells, fibroblasts and nervous cells would better mimic the microenvironment of tumor progression. This might be important developing directions for tumor organoids in the future.

Abstract Background Drug-resistant bacteria are important carriers of antibiotic-resistant genes (ARGs). This fact is crucial for the development of precise clinical drug treatment strategies. Long-read sequencing platforms such as the Oxford Nanopore sequencer can improve genome assembly efficiency particularly when they are combined with short-read sequencing data. Results Alcaligenes faecalis PGB1 was isolated and identified with resistance to penicillin and three other antibiotics. After being sequenced by Nanopore MinION and Illumina sequencer, its entire genome was hybrid-assembled. One chromosome and one plasmid was assembled and annotated with 4,433 genes (including 91 RNA genes). Function annotation and comparison between strains were performed. A phylogenetic analysis revealed that it was closest to A. faecalis ZD02. Resistome related sequences was explored, including ARGs, Insert sequence, phage. Two plasmid aminoglycoside genes were determined to be acquired ARGs. The main ARG category was antibiotic efflux resistance and β-lactamase (EC 3.5.2.6) of PGB1 was assigned to Class A, Subclass A1b, and Cluster LSBL3. Conclusions The present study identified the newly isolated bacterium A. faecalis PGB1 and systematically annotated its genome sequence and ARGs.

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

Food-derived advanced glycation end products (AGEs) are irreversible covalent compounds formed by Maillard reactions of reducing sugars with proteins, nucleic acids and lipids under non-enzymatic conditions. It demonstrated that AGEs areclosely related to human health and involved in the occurrence and development of diabetes and its complications, Alzheimer's disease, intestinal diseases and other diseases. This paper briefly summarizes the harm of AGEs to human health in recent years, starting to foodborn AGEs, foucse on its hazards and prevention, in order to help in-depth research Ages. At the same time, ages inhibitors and blocks its functional channels and other means to prevent potential diseases are worthy of attention, may provide new directions for clinical treatment.

Abstract. Objective:. Diverse antithrombotic strategies were applied to patients undergoing aortic valve replacement. However, the optimal therapeutic regimen for patients undergoing transcatheter aortic valve implantation/replacement (TAVI/TAVR) remains unclear. The purpose of this study was to compare the efficacy and safety of various antithrombotic therapies following TAVI/TAVR. Methods:. Relevant clinical trials evaluating the effect of anticoagulation or antiplatelet regimens on patients after TAVI/TAVR from inception to September 2020 were identified using the PubMed, EMBASE, and the Cochrane Library databases. The inclusion criteria including (1) all patients underwent TAVI/TAVR; (2) the interventions were antithrombotic strategies that prevent the occurrence of thrombotic events in patients; (3) randomized controlled trials or prospective observational studies; and (4) investigation of at least 1 outcome with a follow-up period of ≥3 months. The exclusion criteria including (1) research content was identical or irrelevant to the purpose of the present study; (2) lack of the required outcome index or availability of fragmentary original information; and (3) the full text is not available. The major outcomes were all-cause mortality, thromboembolic complications, and bleeding events. The Cochrane Collaboration's tool and the Newcastle-Ottawa Scale were used for assessing the risk of bias in included studies. Results:. Thirteen studies (3 randomized controlled trials and 10 non-randomized studies) were identified, with a total of 23,497 patients. Four studies compared direct oral anticoagulants (DOACs) with warfarin, 1 study compared aspirin with warfarin, 6 studies compared aspirin plus clopidogrel (dual antiplatelet therapy (DAPT)) with aspirin monotherapy, and 2 studies compared DAPT and aspirin monotherapy with warfarin concurrently. There were no significant differences found between the DOAC and warfarin groups regarding all-cause mortality (risk ratio (RR): 1.03; 95% confidence interval (CI): 0.65–1.64; P = 0.909; Phet = 0.105), clinical adverse events (RR: 1.59; 95% CI: 0.99–2.58; P = 0.057; Phet = 0.738), or bleeding events (RR: 0.93; 95% CI: 0.78–1.11; P = 0.437; Phet = 0.338). The rates of all-cause mortality (RR: 0.71; 95% CI: 0.54–0.93; P = 0.012; Phet = 0.845) and bleeding events (RR: 0.43; 95% CI: 0.22–0.83; P = 0.012; Phet = 0.569) were lower in the aspirin group versus the warfarin group; however, there was no difference in the rate of clinical adverse events (RR: 0.38; 95% CI: 0.14–1.07; P = 0.068; Phet = 0.593). The DAPT group had an advantage versus the aspirin group in all-cause mortality (RR: 0.89; 95% CI: 0.82–0.98; P = 0.013; Phet = 0.299); however, the incidence of bleeding events (RR: 2.06; 95% CI: 1.39–3.07; P

Objective: The study revealed the material basis and potential mechanism of Gynostemma pentaphyllum for preventing obesity through network pharmacology and molecular docking technology. Methods: Using TCMSP database combined with literatures to supplement the screening of active ingredients. Using Pubchem and Swiss target prediction databases to collect the targets of active ingredients of Gynostemma pentaphyllum. Using GeneCards, OMIM and DurgBank databases to obtain obesity targets. Taking the intersection of Gynostemma pentaphyllum action targets and disease targets as Gynostemma pentaphyllum prevention and treatment targets for obesity, and using Cytoscape 3.7.2 software to construct a drug-compound-target network. The STRING database was used to construct a target protein interaction PPI network to screen core targets, Discovery Studio 3.5 was used to docks the selected core targets with the active ingredient molecules, DAVID database performs GO enrichment and KEGG pathway annotation analysised on intersection targets, and built a component-target-pathway interaction network model based on the above results. Results: A total of 16 compounds including quercetin, 3'-methyleriodictyol, ginsenoside f2, and gypenoside XXVIII were selected as the material basis for the prevention and treatment of obesity in Gynostemma pentaphyllum, and 107 targets for the treatment of obesity, including STAT3, AKT1, VEGFA , SRC, EGFR, MAPK3 and other 38 key targets. The results of molecular docking showed that the top 6 core targets of PPI had good binding activities with the corresponding compounds 3'-methyleriodictyol, Rhamnazin, Ruvoside, Spinasterol, ginsenoside f2, CLR, quercetin, Gypenoside XXVIII, speculate on these components may be the main pharmacodynamic components. GO analysis showed that the prevention and treatment of obesity by Gynostemma pentaphyllum mainly involved biological processes such as cell growth, proliferation and metabolic processes, molecular functions such as enzyme binding, protein binding, cellular components such as nucleus and cytoplasm. KEGG pathway enrichment results showed that pathway involving cancer signaling pathways, proteoglycan pathways in cancer, PI3K-Akt signaling pathways, and HIF-1 signaling pathways. Conclusion: This study initially revealed that Gynostemma pentaphyllum could affect the proliferation and differentiation of adipocytes, glucose and lipid metabolism, and maintain body homeostasis through multiple components, multiple targets, and multiple pathways to achieve obesity prevention and treatment, would provide a basis for further research on the effective ingredients and molecular mechanisms.

Introduction: Colorectal cancer (CRC) is the fourth most common cancer worldwide, with high morbidity and mortality rates. In recent years, high-fat diet has been shown to increase CRC morbidity, highlighting the possibility of the application of hypolipidemic drugs for CRC treatment. In this study, we preliminarily evaluated the effects and mechnisms of ezetimibe against CRC through the blockage of lipid absorption in small intesine.Methods: In this study, CRC cell proliferation, invasion, apoptosis, and autophagy were evaluated using cellular and molecular assays. Fluorescent microscopy, and a flow cytometric assay were used to assess mitochondrial activity in vitro. A subcutaneous xenograft mouse model was used to evaluate the effects of ezetimibe in vivo.Results: We found that ezetimibe inhibited CRC cell proliferation, and migration, and facilitated autophage-associated apoptosis in HCT116 and Caco2 cells. Ezetimibe-induced mitochondrial dysfunction in CRC cells was found to be correlated with mTOR signaling activity.Discussion: Ezetimibe exhibits effects against CRC through the promotion of cancer cell death via mTOR signaling-dependent mitochondrial dysfunction, highlighting its potential value in CRC therapy.

Acrylamide exposure through environment pollution and diet is very common in daily life. With the deepening of the study on the toxicity of acrylamide, it has attracted widespread attention for the effects of acrylamide on multiple organs through affecting a variety of programmed cell death. Multiple studies have shown that acrylamide could exert its toxic effect by inducing programmed cell death, but its specific molecular mechanism is still unclear. In this review, the research on the main forms of programmed cell death (apoptosis, autophagy, and programmed necrosis) induced by acrylamide and their possible mechanisms are reviewed. This review may provide basic data for further research of acrylamide and prevention of its toxicity.