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Aiming at the difficulties of mobile robots in the underground tunnel of a coal mine, such as difficult position sensing and low positioning accuracy due to the influence of the environment, a precise positioning method for mobile robots using laser targets as the positioning reference is proposed. According to the characteristics of the roadway environment and the laser tracking detection principle, establish the distributed deployment strategy of the laser target network, construct the body positioning detection platform based on the laser target network and laser tracker; based on the known spatial information of the roadway and the laser target position information, construct the roadway coordinate system and the position information database and build it into the laser target, and utilize the positioning detection platform to decipher the actual position information of the laser target under the laser transmitter coordinate system, and establish the laser target positioning accuracy. The actual position information of the laser target in the coordinate system of the laser transmitter is solved using the positioning detection platform, and the correlation relationship between the coordinate system of the laser target in the roadway and the coordinate system of the fuselage is established; the coordinate information of the four characteristic points of the laser tracker stored in the database is used as the input of the positioning model of the laser transmitter, and the laser target, and the position information of the fuselage is solved by the EPnP (Efficient Perspective-n-Point) algorithm, and the roadway of the laser target is used to solve the position information of the fuselage. The body position information is solved by EPnP (Efficient Perspective-n-Point) algorithm, and the minimum residual sum of squares of the laser target lane coordinates and the measured coordinates is used to characterize the body position error, construct the body position error model, and minimize the body position error by Levenberg-Marquardt algorithm, and obtain the accurate position information of the mobile robot in the lane coordinate system through the spatial coordinate conversion. After experimental verification, the maximum error of mobile robot distance measurement along the direction of the roadway, the width direction, and the height direction is less than 11.33, 8.12, 8.57 mm; the maximum errors of the actual and theoretical positions of the dynamic trajectory measurement in the roadway direction, width direction and height direction are 2.74%, 3.14% and 2.36 %, and the stable measurement of body positioning is guaranteed in the complex roadway with turns. The stable measurement of body positioning meets the requirements of positioning accuracy of mobile robots in underground coal mines.

Abstract Background Neoadjuvant chemotherapy (NAC) with anthracycline sequential paclitaxel is the standard regimen for triple negative breast cancer (TNBC), while TNBC with residual positive axillary lymph node after standard NAC indicates poor prognosis. There is no evidence that vinorelbine alone can be used as an adjuvant intensive therapy for such patients at present. Methods We recruited TNBC patients with clinical stage of T1-4/N1-3/M0, who received NAC with 8 cycles of anthracycline sequential paclitaxel and had residual tumor in axillary lymph node after surgery. The patients were randomly divided into adjuvant intensive treatment group (Group A) and control group (Group B). The patients in group A received vinorelbine at a dose of 25 mg/m2 on days 1/8 of a 21-day cycle with four planned cycles, while the control group received no therapy. Stratified according to the Miller-Payne system of the primary lesion (G1-2/G3-5). The endpoints included distant disease-free survival (DDFS), recurrence-free survival (RFS), overall survival (OS), and safety. Results A total of 22 eligible patients were enrolled in this study, the 3-year DDFS and RFS rates in the group A were significantly higher than those in group B (90.0% vs. 42.4%, p = 0.022, both) at a median follow-up of 36 months. All patients in the group A completed the scheme in full dose, and no grade 3/4 adverse event occurred. Conclusions TNBC patients with residual positive axillary lymph nodes after NAC of anthracycline sequential paclitaxel could benefit from adjuvant intensive therapy of vinorelbine with a good safety. Trail registration The study was registered on the Clinical Trial registry website ( https://register.clinicaltrials.gov , NCT03270007) (Registration Date: 08/30/2017).

Abstract The generation of a substantial amount of construction waste (CW) poses significant challenges to the green transition of highway construction projects. However, the construction industry lacks integration of construction waste management (CWM) practices into the construction process. This paper aims to develop a calculation for assessing the performance of CWM to monitor its effectiveness in highway construction. Initially, this study utilizes the Site waste management plan (SWMP) as a foundation and develops a Construction Waste Management Performed Assessment Method (CWMPAM). The extension of CWM is incorporated into earned value management (EVM) to manage costs, schedules, and the performance of CWM within a unified framework. The functionality and sensitivity of CWMPAM and CWM-embedded EVM are validated through pilot testing and scenario analysis. The research results are computerized into a calculator to facilitate the practical application of CWM, and its validity is tested using random cases. CWMPAM and CWM-embedded EVM prove satisfactory in assessing and monitoring the execution and performance of CWM. The developed calculator simplifies the practical application of the outcomes. Essentially, the developed calculator represents a groundbreaking integration of CWM and construction management, enabling project managers to monitor and compare the CWM performance across different segments of highway construction. Not only does this contribute to the green transformation of highway projects, it also promotes high quality and sustainable development in the construction industry.

Abstract Background Aerobic glycolysis is a tumor cell phenotype and a hallmark in cancer research. The alternative splicing of the pyruvate kinase M (PKM) gene regulates the expressions of PKM1/2 isoforms and the aerobic glycolysis of tumors. Polypyrimidine tract binding protein (PTBP1) is critical in this process; however, its impact and underlying mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to investigate the role of PTBP1 crotonylation in CRC progression. Methods The crotonylation levels of PTBP1 in human CRC tissues and cell lines were analyzed using crotonylation proteomics and immunoprecipitation. The main crotonylation sites were identified by immunoprecipitation and immunofluorescent staining. The glycolytic capacities of CRC cells were evaluated by measuring the glucose uptake, lactate production, extracellular acidification rate, and glycolytic proton efflux rate. The role and mechanism of PTBP1 crotonylation in PKM alternative splicing were determined by Western blot, quantitative real-time PCR (RT-qPCR), RNA immunoprecipitation, and immunoprecipitation. The effects of PTBP1 crotonylation on the behaviors of CRC cells and CRC progression were assessed using CCK-8, colony formation, cell invasion, wound healing assays, xenograft model construction, and immunohistochemistry. Results The crotonylation level of PTBP1 was elevated in human CRC tissues compared to peritumor tissues. In CRC tissues and cells, PTBP1 was mainly crotonylated at K266 (PTBP1 K266-Cr), and lysine acetyltransferase 2B (KAT2B) acted as the crotonyltranferase. PTBP1 K266-Cr promoted glycolysis and lactic acid production, increasing the PKM2/PKM1 ratio in CRC tissues and cells. Mechanistically, PTBP1 K266-Cr enhanced the interaction of PTBP1 with heterogeneous nuclear ribonucleoprotein A1 and A2 (hnRNPA1/2), thus affecting the PKM alternative splicing. PTBP1 K266-Cr facilitated CRC cell proliferation, migration, and metastasis in vitro and in vivo. Pathologically, a high level of PTBP1 K266-Cr was associated with poor prognosis in CRC patients. Conclusions Crotonylation of PTBP1 coordinates tumor cell glycolysis and promotes CRC progression by regulating PKM alternative splicing and increasing PKM2 expression.

Objective Osteoporosis is a severe bone disease with a complex pathogenesis involving various immune processes. With the in‐depth understanding of bone immune mechanisms, discovering new therapeutic targets is crucial for the prevention and treatment of osteoporosis. This study aims to explore novel bone immune markers related to osteoporosis based on single‐cell and transcriptome data, utilizing bioinformatics and machine learning methods, in order to provide novel strategies for the diagnosis and treatment of the disease. Methods Single cell and transcriptome data sets were acquired from Gene Expression Omnibus (GEO). The data was then subjected to cell communication analysis, pseudotime analysis, and high dimensional WGCNA (hdWGCNA) analysis to identify key immune cell subpopulations and module genes. Subsequently, ConsensusClusterPlus analysis was performed on the key module genes to identify different diseased subgroups in the osteoporosis (OP) training set samples. The immune characteristics between subgroups were evaluated using Cibersort, EPIC, and MCP counter algorithms. OP's hub genes were screened using 10 machine learning algorithms and 113 algorithm combinations. The relationship between hub genes and immunity and pathways was established by evaluating the immune and pathway scores of the training set samples through the ESTIMATE, MCP‐counter, and ssGSEA algorithms. Real‐time fluorescence quantitative PCR (RT‐qPCR) testing was conducted on serum samples collected from osteoporosis patients and healthy adults. Results In OP samples, the proportions of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and neutrophils increased significantly by 6.73% (from 24.01% to 30.74%) and 6.36% (from 26.82% to 33.18%), respectively. We found 16 intersection genes and four hub genes (DND1, HIRA, SH3GLB2, and F7). RT‐qPCR results showed reduced expression levels of DND1, HIRA, and SH3GLB2 in clinical blood samples of OP patients. Moreover, the four hub genes showed positive correlations with neutrophils (0.65–0.90), immature B cells (0.76–0.92), and endothelial cells (0.79–0.87), while showing negative correlations with myeloid‐derived suppressor cells (negative 0.54–0.73), T follicular helper cells (negative 0.71–0.86), and natural killer T cells (negative 0.75–0.85). Conclusion Neutrophils play a crucial role in the occurrence and development of osteoporosis. The four hub genes potentially inhibit metabolic activities and trigger inflammation by interacting with other immune cells, thereby significantly contributing to the onset and diagnosis of OP.

Abstract Prostate cancer (PCa) is one of the most important health problems among elderly men in China, with the increasing aging of the population. A cross-sectional survey was conducted in eastern China from 2022 to 2023. Recruitment included a total of 70,342 participants aged 60 or older. Social demographic information, such as individual factors like age, education levels and behavior habits, physical examination and laboratory tests results were collected. Age-standardized prevalence rates were estimated by a direct method with a standard population. T test and chi-square test were used to compare the statistical differences. Multivariate regression models were used to identify the risk factors of PCa. Overall, the crude and age-standardized PCa prevalence is 0.93% and 0.91%, respectively in eastern China. When we adjusted all the co-variables, it showed that high age, smoking, having a higher BMI and higher CA19-9 were associated with a higher risk for a prostate cancer diagnosis. Faced with the demographic transition, innovative strategies are needed to control and prevent PCa. Conducting early screening among male population in community health service centers in eastern of China, especially among a population with associated risk factors such as high age, obesity, and conducting community-based intervention programs might be helpful to address this increasingly significant health problem.

Abstract The LONP1 gene encodes Lon protease, which is responsible for degrading damaged or misfolded proteins and binding mitochondrial DNA. Previously, LONP1 variants have been identified in patients with cerebral, ocular, dental, auricular, and skeletal anomalies (CODAS syndrome) and mitochondrial diseases. Seizures were occasionally observed. However, the association between LONP1 and epilepsy remains elusive. In this study, we performed trio-based whole-exome sequencing in a cohort of 450 patients with unexplained epilepsy and identified four pairs of compound heterozygous LONP1 variants in four unrelated cases. All patients exhibited good responses to anti-seizure medications and demonstrated no developmental delay or intellectual disabilities. The variant allele frequencies observed in this study were absent or low in the general population and were significantly lower than those of benign variants. At least one variant in each biallelic pair affected hydrogen bonding and/or altered protein stability. The CODAS syndrome-associated variants were concentrated in the AAA+ module, especially the α domain. Four of the five mitochondrial disease-associated variants were located in the AAA + domain and the NTD5H and NTD3H subdomains. In contrast, each of the biallelic variants from the patients with pure epilepsy had one variant located in the linker domain, and the other variant located in the mitochondrial targeting sequence or P domain. This study suggested that LONP1 gene is potentially a novel candidate gene for pure epilepsy. The phenotypic variation is associated with the sub-regional effects of variants.

Abstract Objective This study aims to assess the consistency of various CT-FFR software, to determine the reliability of current CT-FFR software, and to measure relevant influence factors. The goal is to build a solid foundation of enhanced workflow and technical principles that will ultimately improve the accuracy of measurements of coronary blood flow reserve fractions. This improvement is critical for assessing the level of ischemia in patients with coronary heart disease. Methods 103 participants were chosen for a prospective research using coronary computed tomography angiography (CCTA) assessment. Heart rate, heart rate variability, subjective picture quality, objective image quality, vascular shifting length, and other factors were assessed. CT-FFR software including K software and S software are used for CT-FFR calculations. The consistency of the two software is assessed using paired-sample t-tests and Bland-Altman plots. The error classification effect is used to construct the receiver operating characteristic curve. Results The CT-FFR measurements differed significantly between the K and S software, with a statistical significance of P

Understanding the response of solid combustibles under high radiant fluxes is critical in predicting the thermal damage from extreme scenarios. Unlike the more moderate radiant fluxes in conventional hydrocarbon fires, extreme events such as strong explosion, concentrated sunlight and directed energy can generate dynamic radiant fluxes at the MW/m2 level, creating a unique threat to materials. This study investigates the pyrolysis and spontaneous ignition behaviors of corrugated cardboard by using both experimental and numerical methods, under 10-cm dynamic high radiant fluxes ranging from 0.2 to 1.25 MW/m2 for 10 s. The spontaneous ignition process at dynamic high radiant fluxes was recorded and quantified. Two ignition modes were found at the critical radiant flux of 0.4 MW/m2, namely hot-gas spontaneous ignition and hot-residue piloted ignition. The latter is not the focus of this paper due to its extremely small probability of occurrence. The research reveals that the increase in flux intensity induces shorter delay times for both pyrolysis and ignition, lower ignition energy density, along with a corresponding rise in the critical mass flux and surface temperature at ignition moment. The simulation results are generally aligned with the experimental findings, despite some divergences may be attributed to model simplifications and parameter assumptions. The work contributes to a deeper insight into material behavior under extreme radiation, with valuable implications for fire safety and hazard assessment.

Abstract PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (

The automation degree of sealing technology in coal mine is insufficient, and the automatic directional drilling rig can improve the automation degree of sealing. A colloidal slip with double friction force for automatic directional drilling machine is designed to solve the problem that the clamping device of automatic directional drilling machine is bad. Two kinds of colloidal structures are proposed to realize the difference of friction between active drill pipe jointing and unjointing, and to ensure the smooth jointing of drill pipe. Using the nonlinear finite element method, Mooney-Rivlin strain energy function was used to describe the mechanical properties of colloid, and the simulation of colloid clamping hole sealer was carried out. The working friction of colloid of different materials was obtained, and the rationality of the two structural colloids was verified. The influence of the compression amount of adhesive strip on the surface of the colloid on the stress of the hole sealer was studied. The effect of the number of adhesive strips on the colloidal surface on the axial friction force was investigated. The results show that natural rubber and polyurethane rubber are reasonable as colloidal materials, the compression of rubber strips is 0.9 mm, and the number of rubber strips is 3.

Abstract In order to obtain the pattern of variation of PM2.5concentrations in the atmosphere in Nanchang City, we build a Support Vector Regression(SVR) with modified Whale Optimization Algorithm(WOA) hybrid model (namely mWOA-SVR model) that can predict the PM2.5concentration. Firstly, according to the Pearson correlation coefficient (PCC) method to examine the dynamic relationship between air pollutants and meteorological factors together with them, PM10, SO2and CO were selected as air pollutant concentration characteristics, while daily maximum and minimum temperatures, and wind power levels were selected as meteorological characteristics; then, using modified WOA algorithm for parameter selection of SVR model, four sets of better parameter combinations were found; finally, the mWOA-SVR model was built by the four sets parameters to predict PM2.5concentration. The results show that the prediction accuracy of mixed mWOA-SVR model with pollutant concentration plus weather factors as the feature was higher than single pollutant concentration.

Abstract Impaired intestinal homeostasis is a major pathological feature of inflammatory bowel diseases (IBD). Mannose and selenium (Se) both demonstrate potential anti-inflammatory and anti-oxidative properties. However, most lectin receptors bind free monosaccharide ligands with relatively low affinity and most Se species induce side effects beyond a very narrow range of dosage. This has contributed to a poorly explored therapies for IBD that combine mannose and Se to target intestinal epithelial cells (IECs) for normalization gut homeostasis. Herein, a facile and safe strategy for ulcerative colitis (UC) treatment was developed using optimized, mannose-functionalized Se nanoparticles (M-SeNPs) encapsulated within a colon-targeted hydrogel delivery system containing alginate (SA) and chitosan (CS). This biocompatible nanosystem was efficiently taken up by IECs and led to increased expression of Se-dependent glutathione peroxidases (GPXs), thereby modulating IECs’ immune response. Using a mouse model of DSS-induced colitis, (CS/SA)-embedding M-SeNPs (C/S-MSe) were found to mitigate oxidative stress and inflammation through the inhibition of the NF-kB pathway in the colon. This stabilized mucosal homeostasis of IECs and ameliorated colitis-related symptoms, thereby providing a potential new approach for treatment of IBD.

Abstract It is well-known that all Feynman integrals within a given family can be expressed as a finite linear combination of master integrals. The master integrals naturally group into sectors. Starting from two loops, there can exist sectors made up of more than one master integral. In this paper we show that such sectors may have additional symmetries. First of all, self-duality, which was first observed in Feynman integrals related to Calabi-Yau geometries, often carries over to non-Calabi-Yau Feynman integrals. Secondly, we show that in addition there can exist Galois symmetries relating integrals. In the simplest case of two master integrals within a sector, whose definition involves a square root r, we may choose a basis (I 1, I 2) such that I 2 is obtained from I 1 by the substitution r → −r. This pattern also persists in sectors, which a priori are not related to any square root with dependence on the kinematic variables. We show in several examples that in such cases a suitable redefinition of the integrals introduces constant square roots like 3 $$ \sqrt{3} $$ . The new master integrals are then again related by a Galois symmetry, for example the substitution 3 $$ \sqrt{3} $$ → − 3 $$ -\sqrt{3} $$ . To handle the case where the argument of a square root would be a perfect square we introduce a limit Galois symmetry. Both self-duality and Galois symmetries constrain the differential equation.

Abstract Background Myelocytomatosis (MYC) transcription factors are crucial mediators of the response of plants to environmental stresses through via binding to DNA regulatory regions. However, few systematic characterizations of MYC genes are available in Cucurbitaceae species. Results In this study, we identified 10, 8, 12, and 10 MYC genes in Cucumis sativus, Cucumis melo, Citrullus lanatus, and Benincasa hispida, respectively. Characterization revealed that all of the MYC proteins contain a highly conserved H4-V5-E6-E8-R9-R11-R12 sequence, which is essential for the binding of DNA regulatory regions. Evolutionary analysis enabled us to categorize 40 predicted MYC proteins from seven species into five distinct groups and revealed that the expansion of the MYC genes occurred before the divergence of monocots and dicots. The upstream promoter regions of the MYC genes contain a variety of developmental, stress, and hormone-responsive regulatory elements. The expression of cucumber MYC genes varies significantly across organs, with particularly high expression of CsaV3_3G001710 observed across all organs. Transcriptomic analysis revealed that certain cucumber MYC genes undergo specific upregulation or downregulation in response to both biotic and abiotic stressors. In particular, under temperature stress, the cucumber genes CsaV3_3G007980 and CsaV3_3G001710 were significantly upregulated. Interestingly, the homologs of these two genes in C. lanatus presented a similar expression pattern to that in C. sativus, whereas in B. hispida, they presented the opposite pattern, i.e., significant downregulation. These findings indicated that these two genes indeed respond to temperature stress but with different expression patterns, highlighting the divergent functions of homologous genes across different species. Conclusions This study analyzed the size and composition of the MYC gene family in four Cucurbitaceae species and investigated stress-responsive expression profiles, especially under temperature stress. All the results showed that MYC genes play important roles in development and stress responses, laying a theoretical foundation for further investigations of these response mechanisms.

Abstract Background Good gastric preparation is indispensable for Magnetic-controlled Capsule Endoscopy (MCE) examination, but there is no consensus yet. We aim to explore the clinical application value of positioning exercises in improving the quality of MCE examination. Methods Clinical data of 326 patients who underwent MCE examination from January 2020 to December 2023 were collected. The included patients were divided into two groups: the conventional medication preparation group (CMP group, accepted mucosal cleansing medication only) and the positioning exercises group (PE group, accepted mucosal cleansing medication plus positioning exercises). A comparison was made between the two groups in terms of gastric cavity cleanliness score, visibility score, and detection rate of positive lesions. Results The examination time was (21.29 ± 5.82) minutes in the PE group and (30.54 ± 6.37) minutes in the CMP group, showing a significant difference between the two groups (P 0.05). Conclusion Positioning exercises before MCE examination can improve the quality of gastric mucosal images and reduce the duration of the examination for patients.

In order to study the influence characteristics of cored heat pipes on the temperature field of coal pile and the feasibility of preventing the spontaneous combustion of coal pile, the heat transfer law of two kinds of heat pipes with core and without core under different heat source temperature conditions was tested by experiments, and the heat transfer effect of different arrangement modes of cored heat pipes on large area coal pile was analyzed by numerical simulation. The results show that under different heat source temperature conditions, the maximum cooling range of cored heat pipe is 130.6 K, and the maximum cooling range of non-cored heat pipe is 118.6 K. The influence of heat pipes on the internal temperature field of coal pile can be divided into three regions according to the distance: high efficiency cooling zone, transition zone and slow cooling zone; the high temperature area inside the coal pile is smaller with triangular tube group arrangement; the best heat transfer effect is obtained when the spacing between tubes is 25 cm; compared with the tube group arrangement, the distance between tubes has more influence on the heat transfer effect of the core heat pipe.

Highlights The NiFeLa catalyst with 3d-5d orbital coupling exhibits remarkable oxygen evolution reaction (OER) activity and stability, enabling an anion-exchange membrane water electrolyzers device to achieve a cell voltage of only 1.58 V at 1 A cm−2 as well as long-term stability over 600 h. The introduction of La disrupts the symmetry of Ni-Fe units and optimize d band center, which affects the d-p orbital hybridization between the metal sites on the surface of the catalyst and oxygen-containing intermediates during the OER process. The 5d-introduced NiFeLa has enhanced adsorption strength of oxygen intermediates, which can reduce the rate-determining step energy barrier and prevent catalyst dissolution.

Abstract Aims The endoscopic treatment of esophagogastric varices is challenging, and the nationwide application of endoscopic therapies for various types of esophagogastric varices and different clinical scenarios remains unclear. This study investigated the use of endoscopic therapy for portal hypertension in China. Methods This study used a questionnaire survey initiated by the Liver Health Consortium in China to investigate the use of endoscopic therapies for portal hypertension. Questionnaires were released online from January 30, 2023 to February 28, 2023 and filled out by chief physicians or senior instructors responsible for endoscopic therapies in participating hospitals across 31 provinces (autonomous regions and municipalities) in China. Comparisons of guideline adherence between primary and referral medical centers were performed using the chi‐square test or Fisher's exact test. Results In total, 836 hospitals participated in the survey. For primary and secondary prophylaxis of esophagogastric variceal bleeding (EGVB), adherence to the national guidelines was 72.5% (606/836) and 39.2% (328/836), respectively. Significant differences were observed in the rate of adherence between the primary and referral centers for primary (79.9% [111/139] vs. 71.0% [495/697], p = 0.033) and secondary prophylaxis (27.3% [38/139] vs. 41.6% [290/697], p = 0.002). Of the hospitals, 78.2% (654/836) preferred endoscopic therapies for acute EGVB, and the timing of endoscopy was usually within 12 h (48.5%, 317/654) and 12–24 h (36.9%, 241/654) after bleeding. Endoscopic therapy was more likely to be the first choice of treatment for acute EGVB in referral centers than in primary centers (82.6% [576/697] vs. 56.1% [78/139], p

Background The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Abstract Background Glucose fluctuations may be involved in the pathophysiological process of cardiomyocyte apoptosis, but the exact mechanism remains elusive. This study focused on exploring the mechanisms related to glucose fluctuation-induced cardiomyocyte apoptosis. Methods Diabetic rats established via an injection of streptozotocin were randomized to five groups: the controlled diabetic (CD) group, the uncontrolled diabetic (UD) group, the glucose fluctuated diabetic (GFD) group, the GFD group rats with the injection of 0.9% sodium chloride (NaCl) (GFD + NaCl) and the GFD group rats with the injection of N-acetyl-L-cysteine (NAC) (GFD + NAC). Twelve weeks later, cardiac function and apoptosis related protein expressions were tested. Proteomic analysis was performed to further analyze the differential protein expression pattern of CD and GFD. Results The left ventricular ejection fraction levels and fractional shortening levels were decreased in the GFD group, compared with those in the CD and UD groups. Positive cells tested by DAB-TUNEL were increased in the GFD group, compared with those in the CD group. The expression of Bcl-2 was decreased, but the expressions of Bax, cleaved caspase-3 and cleaved caspase-9 were increased in response to glucose fluctuations. Compared with CD, there were 527 upregulated and 152 downregulated proteins in GFD group. Txnip was one of the differentially expressed proteins related to oxidative stress response. The Txnip expression was increased in the GFD group, while the Akt phosphorylation level was decreased. The interaction between Txnip and Akt was enhanced when blood glucose fluctuated. Moreover, the application of NAC partially reversed glucose fluctuations-induced cardiomyocyte apoptosis. Conclusions Glucose fluctuations lead to cardiomyocyte apoptosis by up-regulating Txnip expression and enhancing Txnip-Akt interaction.

Abstract Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

In the realm of intelligent sports, the integration of triboelectric nanogenerators (TENGs) marks a transformative approach toward energy sustainability and more advanced athletic monitoring. By leveraging the principle of triboelectricity, TENGs ingeniously convert mechanical energy from athletes’ movements into electrical energy, which offers a green and efficient power solution for wearable technology. This paper presents an innovative study on the application of TENG technology in sports science, with the results illustrating the potential utility of TENGs in revolutionizing the way we monitor, analyze, and enhance athletic performance. Through the development of self-powered wearables and equipment, TENGs facilitate real-time data collection on physiological and biomechanical parameters, ultimately enabling personalized training adjustments and injury prevention strategies. Our findings underscore the dual benefit of TENGs in promoting environmental sustainability by reducing the overall reliance on traditional energy sources and growing the capabilities of intelligent sports systems. This research contributes to the burgeoning field of nano-energy sports applications while setting the stage for future explorations into the optimization of TENG integration in athletic performance enhancement. Finally, the paper concludes by discussing remaining challenges in this area and opportunities for further research.

Abstract Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups;

Abstract Background With the continuous improvement of diagnosis and treatment technology for cervical spine-related diseases in children at home and abroad, the demand for exploring the developmental anatomy and function of children's cervical spine of different ages is increasing. So the aim of this study was to investigate the changes of anatomical indicators in neurocentral synchondrosis (NCS) of C2–C7 with age and the developmental characteristics of different vertebrae in children aged 1–6 years old. Method A retrospective collection of 160 cases of normal cervical spine CT images of children aged 1–6 years old in provincial tertiary hospitals, according to the age group of 1-year-old into 6 groups. The original data of continuously scanned cervical spine tomography images were imported into Mimics16.0 software, under the two-dimensional image window, selected the measurement tool under the Measurements toolbar to measure and statistically analyzed the anatomical indicators such as cross diameter, sagittal diameter, height, perimeter and area of NCS in the C2–C7 segment of the cervical spine on the coronal plane and cross-section. Results There was no significant difference in the anatomical indexes of cervical spine NCS in children compared with the left and right sides of the same vertebrae (P > 0.05). The same cervical spine generally had differences between the age groups of 1–4 years old and 5–6 years old (P

Abstract Background Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear. Methods Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics. Results ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect. Conclusion ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification.

Abstract Bone defects pose significant challenges in healthcare, with over 2 million bone repair surgeries performed globally each year. As a burgeoning force in the field of bone tissue engineering, 3D printing offers novel solutions to traditional bone transplantation procedures. However, current 3D-printed bone scaffolds still face three critical challenges in material selection, printing methods, cellular self-organization and co-culture, significantly impeding their clinical application. In this comprehensive review, we delve into the performance criteria that ideal bone scaffolds should possess, with a particular focus on the three core challenges faced by 3D printing technology during clinical translation. We summarize the latest advancements in non-traditional materials and advanced printing techniques, emphasizing the importance of integrating organ-like technologies with bioprinting. This combined approach enables more precise simulation of natural tissue structure and function. Our aim in writing this review is to propose effective strategies to address these challenges and promote the clinical translation of 3D-printed scaffolds for bone defect treatment. Graphical abstract

Abstract Background Free fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study. Results This study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling. Conclusions The differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Abstract Introduction Early screening and identification are crucial for fall prevention, and developing a new method to predict fall risk in the elderly can address the current lack of objectivity in assessment tools. Methods A total of 132 elderly individuals over 80 years old residing in some nursing homes in Shanghai were selected using a convenient sampling method. Fall history information was collected, and gait data during a 10-meter walk were recorded. Logistic regression was employed to establish the prediction model, and a nomogram was used to assess the importance of the indicators. The Bootstrap method was utilized for internal validation of the model, while the verification set was used for external validation. The predictive performance of the model was evaluated using the area under the ROC curve, calibration curve, and decision curve analysis (DCA) to assess clinical benefits. Results The incidence of falls in the sample population was 36.4%. The Tinetti Gait and Balance Test (TGBT) score (OR = 0.832, 95% CI: 0.734,0.944), stride length (OR = 0.007, 95% CI: 0.000,0.104), difference in standing time (OR = 0.001, 95% CI: 0.000,0.742), and mean stride time (OR = 0.992, 95% CI:0.984,1.000) were identified as significant factors. The area under the ROC curve was 0.878 (95% CI: 0.805, 0.952), with a sensitivity of 0.935 and specificity of 0.726. The Brier score was 0.135, and the Hosmer-Lemeshow test (χ 2 = 10.650, P = 0.222) indicated a good fit and calibration of the model. Conclusion The TGBT score, stride length, difference in standing time, and stride time are all protective factors associated with fall risk among the elderly. The developed risk prediction model demonstrates good discrimination and calibration, providing valuable insights for early screening and intervention in fall risk among older adults.

Abstract Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor’s ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.