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Abstract The testis serves as the primary site for spermatogenesis in mammals and is a crucial organ for the secretion of male hormones. Heat stress (HS) can have adverse effects on the seminiferous tubules, sperm quality, and sperm fertilization capability within the testis. Despite numerous previous studies describing various time points after heat stress in mice, a systematic and comprehensive dataset on heat stress and recovery in mice has been lacking. This study aimed to explore the gene expression changes in the recovery of multiple seminiferous epithelial cycles and spermatogenic cycles in mouse testicles after heat stress. We obtained high-throughput bulk RNA-seq data from testicular tissue of 4 NC mice and 32 HS mice (divided into 9 groups: NC, 30 min, 2 h, 6 h, 24 h, 3d, 8d, 24d, 47d, and 95d) and illustrated the dynamic changes in differential genes. This data set provides valuable insights into the detailed dynamic changes of one or more spermatogenic cycles after heat stress in mouse testicles, as well as the molecular mechanisms involved.

Abstract Background This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. Methods A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. Results The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. Conclusions Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.

Abstract The time-dependent effects in steel-concrete composite beam bridges can intensify track irregularities, subsequently leading to amplified train-bridge coupling vibrations. This phenomenon may increase the stress amplitudes in the bridge steel, thereby impacting the fatigue performance of the composite structures. This paper employs multiple rigid body dynamics to construct a high-speed train model and utilizes the finite element method to develop a steel-concrete composite beam element model that accounts for time-dependent effects, interfacial slip, and shear hysteresis. This approach enables the computational analysis of the train-bridge coupling system, facilitating an investigation into the influence of concrete’s time-dependent effects on the fatigue performance of railway steel-concrete composite bridges. Focusing on a 40-m simply supported composite bridge, the train-bridge coupling dynamic responses were computed for each operational year within a decade of the completion of construction. Applying the P-M linear fatigue damage accumulation theory, statistical analysis of stress history data across various operational periods was conducted to quantify the fatigue damage induced by a single eight-car high-speed train on the lower flange of the mid-span steel beam and the beam-end studs. The findings reveal that the beam-end studs sustain greater damage than the mid-span steel beam. Moreover, the detrimental impact of time-dependent effects diminishes with the increase of operational years. Notably, compared to the initial year, the fatigue damage to the lower flange of the mid-span steel beam by an eight-car train in the tenth year has surged by 39.3%. Conversely, the damage to the beam-end studs has decreased by 47.5%.

Abstract Background Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. Aims We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. Methods In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data. Results We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288). Conclusions These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Abstract The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Three mole percent yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) ceramics are exemplary materials for dental restoration due to their high mechanical strength, fracture toughness, chemical endurance, and biocompatibility. Nevertheless, 3Y-TZP ceramics are opaque and their CAD/CAM manufacturing process may cause micro-cracks in conventional clinical practice. In this study, 3Y-TZP ceramic samples were prepared using vat photopolymerization, pre-sintering, external staining, and final high-temperature sintering. The microstructures, mechanical properties, optical properties, and cytotoxicity of the 3Y-TZP ceramic samples were investigated. The results indicate that with increasing Fe3+ concentration of staining solution from 0.1 mol/L to 0.3 mol/L and increasing staining time from 5 s to 30 min, the 3Y-TZP ceramic samples showed a tetragonal crystal structure of zirconia with densely packed grains and a slight increase in grain size. The flexural strength, Vickers hardness, and fracture toughness of 3Y-TZP ceramic samples stained in 0.1–0.3 mol/L Fe3+ solution for 5 s to 3 min were all greater than 665 MPa, 11.9 GPa, and 5 MPa m1/2, respectively, meeting the mechanical requirements for clinical application. Colorimetric analysis revealed a decrease in L* (black-white index) from 90.4 to 81.3, an increase in a* (green-red index) from −1.5 to 3.2, and an increase in b* (blue-yellow index) from 11.6 to 20.3, approximating the commercial VITA 3D-Master Shade Guide chromaticity. Furthermore, the 3Y-TZP ceramic samples exhibited a cell viability of 90% or higher toward L929 cells.

Abstract Background This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). Methods This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. Results A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18–41.09; P

Abstract Infertility, a worldwide reproductive health concern, impacts approximately one in five couples. Male infertility, stemming from spermatogenic dysfunction and reduced sperm quality, stands as a primary factor contributing to infertility. Given the global decrease in male fertility linked to environmental factors like the greenhouse effect, it is crucial to develop a comprehensive understanding of how increased temperatures impact both the quantity and quality of sperm. In this study, we utilized Pandora-seq technology to detect the small non-coding RNAs (sncRNAs) expression profile in the testicular tissue of heat-stressed mice. The investigation explores the dynamic shifts in sncRNAs within the mouse testis under heat stress, including miRNAs, tsRNAs, piRNAs, rsRNAs and other sncRNAs. Furthermore, we successfully identified differentially expressed sncRNAs in testicular tissues before and after heat stress. Subsequently, we conducted functional enrichment analysis on the potential predicted target genes of differentially expressed miRNAs and tsRNAs. These datasets will constitute a valuable foundational resource for further investigations into the decline in male reproductive capacity triggered by heat stress.

Abstract Objective To reveal the contributing effects of MTDH gene SNPs in the risk of invasive ductal breast cancer (IDC). Patients and methods A case–control study was conducted, recruiting a total of 300 cases of IDC and 565 cancer-free controls from East China. Genotyping of three single-nucleotide polymorphisms (SNPs) in the MTDH gene was performed. Genomic DNA was extracted from peripheral blood samples of patients. The three SNPs (rs1311 T > C, rs16896059 G > A, rs2449512 A > G) in the MTDH gene were selected for detection using a TaqMan real-time polymerase chain reaction assay. The association between MTDH and the risk of IDC was analyzed employing an epidemiology case–control study and a multinomial logistic regression model. Results Among the three evaluated SNPs, rs1311 T > C, rs16896059 G > A, and rs2449512 A > G demonstrated a significant association with an increased risk of IDC. Furthermore, stratified analysis revealed that individuals carrying the rs1311 CC genotype, rs16896059 GA/AA genotypes, and rs2449512 GG genotype were more susceptible to developing IDC in subgroups of patients younger than 53 years, without family history of IDC, pre-menopause status, clinical stage 2, high grade, with no distant metastasis or invasion, Her2-positive type, ER positive, PR positive, and Ki67 cells less than 10%. However, carriers of the rs16896059 GA/AA genotypes and rs2449512 GG genotype had an elevate the risk of IDC in patients with tumor size larger than 2 cm, post-menopause status, clinical stage 3, with invasion, lymph node infiltration, ER negative, PR negative, Her2 negative, and Ki67 cells exceeding 10%. Compared to the reference haplotype TGA, haplotypes TAA, TAG, and TGG were significantly associated with an increased IDC risk. Conclusion In this study, we demonstrated a significant association between MTDH gene polymorphisms and an increased risk of IDC. Moreover, our findings suggested that MTDH gene polymorphisms could serve as a potential biomarker for IDC subtyping and therapeutic selection.

Abstract Background Previous studies evaluating the association between prediabetes the prognosis of patients with acute myocardial infarction (AMI) showed inconsistent results. The aim of the meta-analysis was to compare the long-term incidence of major adverse cardiovascular events (MACEs) between AMI patients with prediabetes and normoglycemia. Methods Relevant prospective cohort studies were obtained by searching Medline, Web of Science, and Embase databases. Only studies with follow-up duration of at least one year were included. A random-effects model was utilized to pool the results by incorporating the influence of heterogeneity. Results Twelve studies with 6972 patients with AMI were included. Among them, 2998 were with prediabetes and 3974 were with normoglycemia. During a mean follow-up of 52.6 months, 2100 patients developed MACEs. Compared to those with normoglycemia, AMI patients with prediabetes were associated with a higher incidence of MACEs (risk ratio [RR]: 1.30, 95% confidence interval: 1.07 to 1.58, p = 0.008; I2 = 67%). Subgroup analysis showed a stronger association between prediabetes and MACEs in studies of patients with mean age ≥ 60 years compared to

Abstract Background Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are mutual risk factors, with both conditions inducing cognitive impairment and anxiety. However, whether OSA exacerbates cognitive impairment and anxiety in patients with T2DM remains unclear. Moreover, TREM2 upregulation has been suggested to play a protective role in attenuating microglia activation and improving synaptic function in T2DM mice. The aim of this study was to explore the regulatory mechanisms of TREM2 and the cognitive and anxiety-like behavioral changes in mice with OSA combined with T2DM. Methods A T2DM with OSA model was developed by treating mice with a 60% kcal high-fat diet (HFD) combined with intermittent hypoxia (IH). Spatial learning memory capacity and anxiety in mice were investigated. Neuronal damage in the brain was determined by the quantity of synapses density, the number and morphology of brain microglia, and pro-inflammatory factors. For mechanism exploration, an in vitro model of T2DM combined with OSA was generated by co-treating microglia with high glucose (HG) and IH. Regulation of TREM2 on IFNAR1-STAT1 pathway was determined by RNA sequencing and qRT-PCR. Results Our results showed that HFD mice exhibited significant cognitive dysfunction and anxiety-like behavior, accompanied by significant synaptic loss. Furthermore, significant activation of brain microglia and enhanced microglial phagocytosis of synapses were observed. Moreover, IH was found to significantly aggravate anxiety in the HFD mice. The mechanism of HG treatment may potentially involve the promotion of TREM2 upregulation, which in turn attenuates the proinflammatory microglia by inhibiting the IFNAR1-STAT1 pathway. Conversely, a significant reduction in TREM2 in IH-co-treated HFD mice and HG-treated microglia resulted in the further activation of the IFNAR1-STAT1 pathway and consequently increased proinflammatory microglial activation. Conclusions HFD upregulated the IFNAR1-STAT1 pathway and induced proinflammatory microglia, leading to synaptic damage and causing anxiety and cognitive deficits. The upregulated TREM2 inT2DM mice brain exerted a negative regulation of the IFNAR1-STAT1 pathway. Mice with T2DM combined with OSA exacerbated anxiety via the downregulation of TREM2, causing heightened IFNAR1-STAT1 pathway activation and consequently increasing proinflammatory microglia. Graphical Abstract

Abstract Purpose Preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) belong to lung function injury. PRISm is a precursor to COPD. We compared and evaluated the different basic information, imaging findings and survival curves of 108 lung cancer patients with different pulmonary function based on high resolution computed tomography (HRCT). Methods This retrospective study was performed on 108 lung cancer patients who did pulmonary function test (PFT) and thoracic HRCT. The basic information was evaluated: gender, age, body mass index (BMI), smoke, smoking index (SI). The following pulmonary function findings were evaluated: forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio. The following computed tomography (CT) findings were evaluated: appearance (bronchiectasis, pneumonectasis, atelectasis, ground-glass opacities [GGO], interstitial inflammation, thickened bronchial wall), diameter (aortic diameter, pulmonary artery diameter, MPAD/AD ratio, inferior vena cava diameter [IVCD]), tumor (volume, classification, distribution, staging [I, II, III, IV]). Mortality rates were calculated and survival curves were estimated using the Kaplan-Meier method. Results Compared with normal pulmonary function group, PRISm group and COPD group were predominantly male, older, smoked more, poorer lung function and had shorter survival time after diagnosis. There were more abnormal images in PRISm group and COPD group than in normal lung function group (N-C group). In PRISm group and COPD group, lung cancer was found late, and the tumor volume was larger, mainly central squamous carcinoma. But the opposite was true for the N-C group. The PRISm group and COPD group had significant poor survival probability compared with the normal lung function group. Conclusions Considerable differences regarding basic information, pulmonary function, imaging findings and survival curves are found between normal lung function group and lung function injury group. Lung function injury (PRISm and COPD) should be taken into account in future lung cancer screening studies.

Abstract The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.

Abstract Objectives To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) for low to intermediate-risk prostate cancer (PCa), as well as its correlation with the prognostic Gleason score (GS). Materials and methods Retrospective analysis of MRI images and relevant clinical data from patients with prostate disease. The differences in ADC between different GS groups were compared, and the efficacy of ADC in PCa diagnosis were analyzed. Furthermore, the diagnostic performance of the mean ADC (ADCmean) and minimum ADC (ADCmin) values was compared. Results There were 1414 patients with 1631 lesions. In terms of GS, both ADCmin and ADCmean values of the GS 4 + 3 group were significantly lower than those of the GS 3 + 4 group, GS 3 + 3 group, and the benign group, with all differences being statistically significant (p

Abstract Background The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA

Abstract Background Beta-amyloid (Aβ) deposition in the brain parenchyma is a crucial initiating step in the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathology. Furthermore, dysfunction of plaque-associated microglia, also known as disease-associated microglia (DAM) has been reported to accelerate Aβ deposition and cognitive impairment. Our previous research demonstrated that intermittent hypoxia training (IHT) improved AD pathology by upregulating autophagy in DAM, thereby enhancing oligomeric Aβ (oAβ) clearance. Considering that oAβ internalization is the initial stage of oAβ clearance, this study focused on the IHT mechanism involved in upregulating Aβ uptake by DAM. Methods IHT was administered to 8-month-old APP/PS1 mice or 6-month-old microglial vacuolar protein sorting 35 (VPS35) knockout mice in APP/PS1 background (MG VPS35 KO: APP/PS1) for 28 days. After the IHT, the spatial learning-memory capacity of the mice was assessed. Additionally, AD pathology was determined by estimating the nerve fiber and synapse density, Aβ plaque deposition, and Aβ load in the brain. A model of Aβ-exposed microglia was constructed and treated with IHT to explore the related mechanism. Finally, triggering receptor expressed on myeloid cells 2 (TREM2) intracellular recycling and Aβ internalization were measured using a fluorescence tracing technique. Results Our results showed that IHT ameliorated cognitive function and Aβ pathology. In particular, IHT enhanced Aβ endocytosis by augmenting the intracellular transport function of microglial TREM2, thereby contributing to Aβ clearance. Furthermore, IHT specifically upregulated VPS35 in DAM, the primary cause for the enhanced intracellular recycling of TREM2. IHT lost ameliorative effect on Aβ pathology in MG VPS35 KO: APP/PS1 mice brain. Lastly, the IHT mechanism of VPS35 upregulation in DAM was mediated by the transcriptional regulation of VPS35 by transcription factor EB (TFEB). Conclusion IHT enhances Aβ endocytosis in DAM by upregulating VPS35-dependent TREM2 recycling, thereby facilitating oAβ clearance and mitigation of Aβ pathology. Moreover, the transcriptional regulation of VPS35 by TFEB demonstrates a close link between endocytosis and autophagy in microglia. Our study further elucidates the IHT mechanism in improving AD pathology and provides evidence supporting the potential application of IHT as a complementary therapy for AD. Graphical abstract

Abstract Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Abstract The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

Abstract The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

Abstract Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.

Abstract While the role of crystal facets is well known in traditional heterogeneous catalysis, this effect has not yet been thoroughly studied in plasmon-assisted catalysis, where attention has primarily focused on plasmon-derived mechanisms. Here, we investigate plasmon-assisted electrocatalytic CO2 reduction using different shapes of plasmonic Au nanoparticles - nanocube (NC), rhombic dodecahedron (RD), and octahedron (OC) - exposing {100}, {110}, and {111} facets, respectively. Upon plasmon excitation, Au OCs doubled CO Faradaic efficiency (FECO) and tripled CO partial current density (jCO) compared to a dark condition, with NCs also improving under illumination. In contrast, Au RDs maintained consistent performance irrespective of light exposure, suggesting minimal influence of light on the reaction. Temperature experiments ruled out heat as the main factor to explain such differences. Atomistic simulations and electromagnetic modeling revealed higher hot carrier abundance and electric field enhancement on Au OCs and NCs than RDs. These effects now dominate the reaction landscape over the crystal facets, thus shifting the reaction sites when comparing dark and plasmon-activated processes. Plasmon-assisted H2 evolution reaction experiments also support these findings. The dominance of low-coordinated sites over facets in plasmonic catalysis suggests key insights for designing efficient photocatalysts for energy conversion and carbon neutralization.

Abstract Background Obesity is the main risk factor leading to the development of various respiratory diseases, such as asthma and pulmonary hypertension. Pulmonary microvascular endothelial cells (PMVECs) play a significant role in the development of lung diseases. Aconitate decarboxylase 1 (Acod1) mediates the production of itaconate, and Acod1/itaconate axis has been reported to play a protective role in multiple diseases. However, the roles of Acod1/itaconate axis in the PMVECs of obese mice are still unclear. Methods mRNA-seq was performed to identify the differentially expressed genes (DEGs) between high-fat diet (HFD)-induced PMVECs and chow-fed PMVECs in mice (|log2 fold change| ≥ 1, p ≤ 0.05). Free fatty acid (FFA) was used to induce cell injury, inflammation and mitochondrial oxidative stress in mouse PMVECs after transfection with the Acod1 overexpressed plasmid or 4-Octyl Itaconate (4-OI) administration. In addition, we investigated whether the nuclear factor erythroid 2-like 2 (Nrf2) pathway was involved in the effects of Acod1/itaconate in FFA-induced PMVECs. Results Down-regulated Acod1 was identified in HFD mouse PMVECs by mRNA-seq. Acod1 expression was also reduced in FFA-treated PMVECs. Acod1 overexpression inhibited cell injury, inflammation and mitochondrial oxidative stress induced by FFA in mouse PMVECs. 4-OI administration showed the consistent results in FFA-treated mouse PMVECs. Moreover, silencing Nrf2 reversed the effects of Acod1 overexpression and 4-OI administration in FFA-treated PMVECs, indicating that Nrf2 activation was required for the protective effects of Acod1/itaconate. Conclusion Our results demonstrated that Acod1/Itaconate axis might protect mouse PMVECs from FFA-induced injury, inflammation and mitochondrial oxidative stress via activating Nrf2 pathway. It was meaningful for the treatment of obesity-caused pulmonary microvascular endotheliopathy.

In this study, the pyrroloquinoline quinone (PQQ) high-yield mutant J1-1 of Methylobacterium glucophilum MP688 was used to do bioinformatics analysis to extract the two methanol dehydrogenase (MDH) genes from the genome, mpq0771 and mpq2496. The effects of Ca2+ and La3+ on bacterial growth, PQQ synthesis, MDH expression, and enzyme activity were explored, as well as the roles of the two enzymes in methanol metabolism. The results showed that Ca2+ and La3+ both increased J1-1 bacteriophage growth and decreased PQQ synthesis in the context of fast viral development. In the presence of Ca2+, mpq0771 expression increased in strain J1-1. La3+ inhibited mpq0771 expression while promoting mpq2496 expression and increasing total bacterial MDH viability. The knockout bacteria J1-1Δmpq0771 could not grow in methanol, but with the addition of La3+, it could grow in methanol and synthesize PQQ, and MDH activity was identified. The product encoded by mpq0771 was a Ca2+-dependent MDH, and the product encoded by mpq2496 was a La3+-dependent MDH, and La3+ could increase the production of mpq2496 and replace mpq0771 as a methanol dehydrogenase.

Abstract Background Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. Methods This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. Results The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p

Abstract Robot joints are the main structure for controlling the motion of the machine body, where the motion state of them directly affects the performance of the industrial robot. Due to the difficulty of obtaining the joint torque information of industrial robots, it is very hard to monitor the motion state of them. Based on the velocity and force driven by current of motors, we propose a novel Bayesian optimization framework to predict the joint motion state of industrial robot in this paper. Based on the temporal correlation of joint current and the correlation between the current and motion state of joint, we use the LSTM and BiLSTM to regressing prediction of the current and state of joint motor first. Then, the Bayesian optimization method is used to adjust the hyperparameters of our network, which realize the analysis of the joint motor current under different motion states and improve the accuracy of the prediction of joint motion states. Finally, we design the joint current acquisition platform of industrial robot based on Hall current sensors, which can collect joint currents without contact and generate experimental dataset. Comparing with the popular intelligent methods, the results show that our Bayesian optimization framework realizes a more accurate prediction of motion state for the four-axis industrial robot on the basis of contact-less current acquisition.

Abstract Skeletal muscle is the largest metabolic organ of the human body. Maintaining the best quality control and functional integrity of mitochondria is essential for the health of skeletal muscle. However, mitochondrial dysfunction characterized by mitochondrial dynamic imbalance and mitophagy disruption can lead to varying degrees of muscle atrophy, but the underlying mechanism of action is still unclear. Although mitochondrial dynamics and mitophagy are two different mitochondrial quality control mechanisms, a large amount of evidence has indicated that they are interrelated and mutually regulated. The former maintains the balance of the mitochondrial network, eliminates damaged or aged mitochondria, and enables cells to survive normally. The latter degrades damaged or aged mitochondria through the lysosomal pathway, ensuring cellular functional health and metabolic homeostasis. Skeletal muscle atrophy is considered an urgent global health issue. Understanding and gaining knowledge about muscle atrophy caused by mitochondrial dysfunction, particularly focusing on mitochondrial dynamics and mitochondrial autophagy, can greatly contribute to the prevention and treatment of muscle atrophy. In this review, we critically summarize the recent research progress on mitochondrial dynamics and mitophagy in skeletal muscle atrophy, and expound on the intrinsic molecular mechanism of skeletal muscle atrophy caused by mitochondrial dynamics and mitophagy. Importantly, we emphasize the potential of targeting mitochondrial dynamics and mitophagy as therapeutic strategies for the prevention and treatment of muscle atrophy, including pharmacological treatment and exercise therapy, and summarize effective methods for the treatment of skeletal muscle atrophy.

Abstract Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Abstract Background Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. Results The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. Conclusions Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

C-reactive protein (CRP) plays a crucial role in the diagnosis and monitoring of the non-specific acute phase response in humans. In contrast, rat CRP (rCRP) is an atypical acute-phase protein that possesses unique features, such as a possible incapacity to trigger the complement system and markedly elevated baseline plasma concentrations. To facilitate in vitro studies on these unique characteristics, obtaining high-quality pure rCRP is essential. Here we explored various strategies for rCRP purification, including direct isolation from rat plasma and recombinant expression in both prokaryotic and eukaryotic systems. Our study optimized the recombinant expression system to enhance the secretion and purification efficiency of rCRP. Compared to traditional purification methods, we present a streamlined and effective approach for the expression and purification of rCRP in the Pichia pastoris system. This refined methodology offers significant improvements in the efficiency and effectiveness of rCRP purification, thereby facilitating further structural and functional studies on rCRP.

Background and aimsThe role of dietary factors in metabolic dysfunction-associated steatotic liver disease (MASLD)—which represents a new definition of liver steatosis and metabolic dysfunction— remains unclear. This study aimed to explore the relationships between dietary indices and MASLD.MethodsWe analyzed data from the United States National Health and Nutrition Examination Survey (NHANES) 2017–2020 cycle, including 4,690 participants with complete vibration-controlled transient elastography (VCTE) data. Multivariate logistic regression models adjusted for covariates were used to assess the association between dietary indices, MASLD, and MASLD-associated liver fibrosis (MASLD-LF). Restricted cubic spline (RCS) models and subgroup analyses were also performed.ResultsThe Alternative Healthy Eating Index (AHEI), Healthy Eating Index-2020 (HEI-2020), Dietary Approaches to Stop Hypertension Index (DASHI), and Mediterranean Diet Index (MEDI) were found to be negatively associated with MASLD risk, while the Dietary Inflammatory Index (DII) had a positive association. The highest quartile of MEDI was linked to a 44% reduction in MASLD risk [Q1 vs. Q4 odds ratio (OR): 0.56; 95% confidence interval (CI): 0.34–0.94, P for trend: 0.012]. DASHI was uniquely associated with a reduced risk of MASLD-LF (continuous OR: 0.79; 95% CI: 0.64–0.97; p for trend: 0.003). Our RCS curves indicated a nonlinear association with DASHI-MASLD (p-overall: 0.0001, p-nonlinear: 0.0066). Subgroup analyses showed robust associations among the non-Hispanic White and highly educated populations.ConclusionSpecific dietary patterns were associated with reduced risks of MASLD and MASLD-LF. The DASHI, in particular, showed a significant protective effect against MASLD-LF. These findings suggest potential dietary interventions for managing MASLD and MASLD-LF, although large-scale randomized controlled trials are warranted to validate these findings.

In the growing season of 2021, a severe drought occurred in Central Asia impacting various local ecosystems and socio-economic conditions. However, there is limited research on the spatiotemporal characteristics of this drought and its effects on local vegetation. To address this gap, this study utilizes the standardized precipitation evapotranspiration index (SPEI) to quantitatively evaluate the spatiotemporal drought characteristics, and standardized anomalies to assess drought impacts on vegetation greenness and productivity. The drought-induced reduction in vegetation greenness and production was also decomposed into environmental drivers based on a random forest model. Our findings can be summarized as follows: During the 2021 growing season, Central Asia experienced one of the most severe drought events in the past 40 years, with approximately 42.57 % of the region facing record-breaking drought conditions. Abnormally low precipitation (PRE), prolonged high temperatures (TMP) and evapotranspiration also occurred during the drought event. The drought had a significant detrimental effect on vegetation, leading to an approximately 10 % reduction in vegetation greenness and around 13 % in productivity. Soil moisture (SM) was found to be the most critical factor influencing vegetation greenness loss during drought conditions. Leaf Area Index (LAI) and SM emerged as the primary drivers for the reduction of Gross Primary Productivity (GPP) and Solar-Induced Fluorescence (SIF). The antecedent environmental conditions had a significant impact on the decline in vegetation greenness and productivity during the 2021 drought event, accounting for approximately 30 %–35 % and 52–69 % of the respective losses. The findings of this study highlight the importance of taking into account antecedent climate factors when studying the impacts of drought on vegetation.

Background With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them.Methods In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases.Results We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins.Conclusion We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

IntroductionBacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis (E. faecalis) is capable of causing a variety of infectious diseases, but there have been few studies of E. faecalis persisters. Previous studies have shown that the sex pheromone cCF10 secreted by E. faecalis induces conjugative plasmid transfer. However, whether the pheromone cCF10 regulates the persistence of E. faecalis has not been investigated.MethodsAs a result, we investigated the effect and potential molecular mechanism of pheromone cCF10 in regulating the formation of persisters in E. faecalis OG1RF using a persistent bacteria model.Results and discussionThe metabolically active E. faecalis OG1RF reached a persistence state and temporarily tolerated lethal antibiotic concentrations after 8 h of levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting a persistence rate of 0.109 %. During the growth of E. faecalis OG1RF, biofilm formation was a critical factor contributing to antibiotic persistence, whereas 10 ng/mL cCF10 blocked persister cell formation. Notably, cCF10 mediated the antibiotic persistence of E. faecalis OG1RF via regulating metabolic activity rather than suppressing biofilm formation. The addition of cCF10 stimulated the Opp system and entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining the metabolically active state of bacteria and reducing persister cell generation. These findings offer valuable insights into the formation, as well as the control mechanism of E. faecalis persisters.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167–7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922–41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374–12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780–10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771–0.894) and 0.821 (95 % CI 0.720–0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

In light of the limited efficacy of conventional methods for identifying pavement cracks and the absence of comprehensive depth and location data in two-dimensional photographs, this study presents an intelligent strategy for extracting road cracks. This methodology involves the integration of laser point cloud data obtained from a vehicle-mounted system and a panoramic sequence of images. The study employs a vehicle-mounted LiDAR measurement system to acquire laser point cloud and panoramic sequence image data simultaneously. A convolutional neural network is utilized to extract cracks from the panoramic sequence image. The extracted sequence image is then aligned with the laser point cloud, enabling the assignment of RGB information to the vehicle-mounted three dimensional (3D) point cloud and location information to the two dimensional (2D) panoramic image. Additionally, a threshold value is set based on the crack elevation change to extract the aligned roadway point cloud. The three-dimensional data pertaining to the cracks can be acquired. The experimental findings demonstrate that the use of convolutional neural networks has yielded noteworthy outcomes in the extraction of road cracks. The utilization of point cloud and image alignment techniques enables the extraction of precise location data pertaining to road cracks. This approach exhibits superior accuracy when compared to conventional methods. Moreover, it facilitates rapid and accurate identification and localization of road cracks, thereby playing a crucial role in ensuring road maintenance and traffic safety. Consequently, this technique finds extensive application in the domains of intelligent transportation and urbanization development. The technology exhibits significant promise for use in the domains of intelligent transportation and city development.

The biomass raw material magnolol with a biphenyl structure was used to synthesize bio-based epoxy resin, and flexible polyetheramine curing agents(D230, D400, D2000 and T403) were used to cure the bio-based epoxy anti-erosion coating. The effects of polyetheramine molecular weight and functionality on the mechanical properties, corrosion resistance and anti-erosion protection performance of magnolol epoxy resin were explored, and the anti-erosion mechanism of magnolol epoxy coatings was proposed. Results showed that the magnolol epoxy coating cured with D230 maintained a high impedance value(1.25×1011 Ω·cm2) after 15 d of immersion in 3.5%(mass fraction) NaCl solution. The coating cured with T403 possessed a high tensile strength(26.59 MPa), low friction coefficient(0.373) and wear rate [0.018 3 mm3/(N·m)], while the magnolol epoxy coating cured with D2000 exhibited lower mass loss(244.74 mg) and volume loss(157 mm3) in the erosion test. Under the coupled erosion of solid/liquid/gas three-phase flow, the longer flexible segment of D2000 endowed the magnolol epoxy coating with better elasticity and flexibility, and therefore reduced the impact of the erosion medium, thus showing excellent anti-erosion performance.

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA. Objective: This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development. Methods: A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis. Results: IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms. Conclusion: This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA). The Translational Potential of this Article: The study demonstrated that the regulation of SMARCC1 by IRF1 plays a crucial role in the development of OA. Knocking down either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms in rat models. These symptoms included inflammatory infiltration, cartilage degradation, and tissue injury. These findings suggest that targeting the IRF1-SMARCC1 regulatory axis, as well as the associated epigenetic modifications, could potentially be a novel approach in the development of OA therapies, offering new opportunities for disease management and improved patient outcomes.

Abstract Body size has historically been considered the primary source of difference in the pharmacokinetics (PKs) of monoclonal antibodies (mAbs) between children aged greater than or equal to 2 years and adults. The contribution of age‐associated differences (e.g., ontogeny) beyond body‐size differences in the pediatric PKs of mAbs has not been comprehensively evaluated. In this study, the population PK of two mAbs (nivolumab and ipilimumab) in pediatric oncology patients were characterized. The effects of age‐related covariates on nivolumab or ipilimumab PKs were assessed using data from 13 and 10 clinical studies, respectively, across multiple tumor types, including melanoma, lymphoma, central nervous system tumors (CNSTs), and other solid tumors. Clearance was lower in pediatric patients (aged 1–17 years) with solid tumors or CNST than in adults after adjusting for other covariates, including the effect of body size. In contrast, clearance was similar in pediatric patients with lymphoma to that in adults with lymphoma. The pediatric effects characterized have increased the accuracy of the predictions of the model, facilitating its use in subsequent exposure comparisons between pediatric and adult patients, as well as for exposure–response analyses to inform pediatric dosing. This study approach may be applicable to the optimization of pediatric dosing of other mAbs and possibly other biologics.

Weak shear bond strength (SBS) has always been a challenge for clinical bonding of 3mol% yttria-stabilized tetragonal zirconia (3Y-TZP). With the development of additive manufacturing technology, vat photopolymerization (VPP) is an alternative that allows zirconia to form precise complex structures and achieve bionic structure molding based on the natural advantages of different organisms in relation to biological structure, microstructure, and mechanical behavior. As report goes, the toe structure of tree frog can effectively achieve friction enhancement on humid and flooded surfaces. In this paper, we present a new type of 3Y-TZP material loaded with tree-frog bionic structures via VPP additive manufacturing to improve SBS between resin cement and 3Y-TZP for clinical requirements. And flexural strength, finite element analysis and accuracy analysis of bio-inspired 3Y-TZP is carried out to verify its feasibility of clinical application. The SBS of the bio-inspired group with 250 μm width and 250 μm height reached a maximum of 22.7 ± 1.3 MPa before hydrothermal aging, the flexural strength of the bio-inspired group with 250 μm width and 150 μm height decreased the least, reaching 825 ± 30 MPa, and the accuracy analysis of the central-incisor veneer restoration loaded with the bionic structures showed that the average deviation value was 0.033 ± 0.036 mm. This study has found that these bionic structures can effectively improve the SBS of the interface between zirconia and resin cement, while flexural strength and accuracy can also meet requirements of clinical dental application.

Discontinuous perfobond rib shear (PBL) connectors can be applied to fabricated steel-concrete composite beams. In this paper, six push-out specimens were designed to explore the shear performance of PBL under static and repeated loads. Four specimens were used for static push-out test. The remaining two were used for fatigue push-out test. The static load test mainly considers the influence of concrete at steel plate end and post-cast strip on the shear bearing capacity, initial shear stiffness and load-slip curve of discontinuous PBL shear connectors. On the basis of the test results, the calculating formulas of the shear capacity and shear stiffness of discontinuous PBL connectors considering the influence of end bearing, bond group effect and post-cast strip are proposed. The predicted results of the formula are close to the experiment. From the fatigue test results, it is found that the fatigue performance of above specimens with C50 and UHPC is better than that with studs, but the fatigue resistance of discontinuous PBL connectors with UHPC is not increased in proportion to the shear capacity. In addition, the residual slip and shear stiffness of PBL specimens after cyclic loading are related to fatigue load amplitude.

In the global precipitation measurement (GPM) era, the integrated multisatellite retrievals for GPM (IMERG) stands as a pivotal precipitation algorithm. This study aims to evaluate the accuracy of IMERG in capturing precipitation frequency and volume in the Yellow River Basin, China. Four satellite-based precipitation estimates (SPEs) from three algorithmic versions of IMERG were analyzed on an hourly scale using gauge observations. An improved error component procedure was employed to identify error sources. Results showed that all four IMERG products effectively captured the spatial distribution patterns and seasonal changes of precipitation, IMERG_F demonstrated the best overall performance, followed by IMERG_L, while IMERG_E performed the worst. However, they tended to overestimate precipitation. IMERG_F_Cal performed the best for precipitation frequency detection, with the highest probability of detection (POD = 52.7%) and the lowest missed events (MIS = 47.3%). Error component analysis highlights false bias as the main source of error, followed by missed bias. In winter, missed bias was the primary error source. Notably, a significant overestimation of precipitation was observed along the Yellow River. In detail, false bias dominated IMERG_E, IMERG_L, and IMERG_F_UnCal below 800 m in spring, summer, and autumn. However, in winter, missed bias became the primary error source for these three products at elevations above 200m and for IMERG_F_Cal above 500 m. IMERG_F_Cal exhibited false bias as the primary error source in all seasons. Suggested algorithm developers focus on improving IMERG SPEs' identification capabilities for light precipitation events and rainstorms. Findings can provide a reference for improving the IMERG product algorithms and enhancing users’ understanding of the error characteristics and sources of IMERG products.

Abstract Anomaly detection is a highly important task in the field of data analysis. Traditional anomaly detection approaches often strongly depend on data size, structure and features, while introducing the idea of ensemble into anomaly detection can greatly improve the generalization ability. Ensemble-based anomaly detection methods still face some challenges, however, such as data imbalance, time and space demand and the selection of base detectors. To this end, we propose a selective ensemble method for anomaly detection based on parallel learning (SEAD-PL). First, a differentiated stratified sampling method is designed to alleviate the problem of data imbalance. Then, a distributed parallel training frame is built to address the problem of excessive time and space consumption for base detector training. Finally, a clustering-based ensemble selection strategy is introduced to balance the accuracy and diversity of base detectors. Experiments are performed on six datasets, which demonstrate that the proposed method has obvious advantages over four selected methods.

Abstract An exposure–response (E–R) safety analysis was conducted across adult and pediatric (

Abstract Background The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. Methods Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. Results Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. Conclusion This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.

Zinc (Zn)-based alloys are considered the next-generation biodegradable material for promising bone-implant devices due to their good degradability, formability, and functionality. Nevertheless, the as-cast Zn alloys showed a low strength-toughness, making it challenging to meet the mechanical properties requirements for high-load-bearing bone implants due to their hexagonal close-packed structure, coarse grain size, and less sliding system. Herein, we have developed biodegradable Zn–5Ce alloys by cerium (Ce) alloying followed by hot-rolling, hot-extrusion, and high-pressure torsion (HPT), respectively, for potential bone-implant application. Mechanical testing revealed that the HPT sample exhibited the best mechanical performance matching among the Zn–5Ce samples with a high ultimate tensile strength of ∼345 MPa, yield strength of ∼230 MPa, a moderate elongation of ∼11.4%, and macro-hardness of ∼96.6 HB. Electrochemical corrosion and static immersion testing revealed that the HPT sample showed the highest electrochemical corrosion rate of ∼416 μm/y and degradation rate of ∼43.8 μm/y in Hanks' solution among the Zn–5Ce samples, which is suitable for degradation rate requirements for bone-implant application. Bio-tribological testing revealed that the HPT sample showed high bio-tribological properties matching in Hanks’ solution with the lowest friction coefficients of ∼0.530 and moderate wear loss of ∼2.2 mg. Cytocompatibility and osteogenic differentiation assessment revealed that the diluted extract of the HPT sample showed the highest cytocompatibility towards 3T3 and MG-63 cells and osteogenic differentiation performance towards 3T3 cells among the most diluted extracts. Accordingly, the HPT Zn–5Ce sample is expected to be used for high-load-bearing degradable bone-implant devices, including bone fixation and guided bone regeneration systems.

ABSTRACTSerum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of “partial cure” in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg

Cardiopulmonary bypass (CPB) is a common technique in cardiac surgery but is associated with acute kidney injury (AKI), which carries considerable morbidity and mortality. In this review, we explore the range and definition of CPB-associated AKI and discuss the possible impact of different disease recognition methods on research outcomes. Furthermore, we introduce the specialized equipment and procedural intricacies associated with CPB surgeries. Based on recent research, we discuss the potential pathogenesis of AKI that may result from CPB, including compromised perfusion and oxygenation, inflammatory activation, oxidative stress, coagulopathy, hemolysis, and endothelial damage. Finally, we explore current interventions aimed at preventing and attenuating renal impairment related to CPB, and presenting these measures from three perspectives: (1) avoiding CPB to eliminate the fundamental impact on renal function; (2) optimizing CPB by adjusting equipment parameters, optimizing surgical procedures, or using improved materials to mitigate kidney damage; (3) employing pharmacological or interventional measures targeting pathogenic factors.

IntroductionWalking plays a crucial role in promoting physical activity among older adults. Understanding how the built environment influences older adults’ walking behavior is vital for promoting physical activity and healthy aging. Among voluminous literature investigating the environmental correlates of walking behaviors of older adults, few have focused on walking duration across different age groups and life stages, let alone examined the potential nonlinearities and thresholds of the built environment.MethodsThis study employs travel diary from Zhongshan, China and the gradient boosting decision trees (GBDT) approach to disentangle the age and retirement status differences in the nonlinear and threshold effects of the built environment on older adults’ walking duration.ResultsThe results showed built environment attributes collectively contribute 57.37% for predicting older adults’ walking duration, with a higher predicting power for the old-old (70+ years) or the retired. The most influencing built environment attribute for the young-old (60–70 years) is bus stop density, whereas the relative importance of population density, bus stop density, and accessibility to green space or commercial facilities is close for the old-old. The retired tend to walk longer in denser-populated neighborhoods with better bus service, but the non-retired are more active in walking in mixed-developed environments with accessible commercial facilities. The thresholds of bus stop density to encourage walking among the young-old is 7.8 counts/km2, comparing to 6 counts/km2 among the old-old. Regarding the green space accessibility, the effective range for the non-retired (4 to 30%) is smaller than that of the retired (12 to 45%).DiscussionOverall, the findings provide nuanced and diverse interventions for creating walking-friendly neighborhoods to promote walking across different sub-groups of older adults.