The role of macrophage polarization and related key molecules in pulmonary inflammation and fibrosis induced by coal dust dynamic inhalation exposure in Sprague-Dawley rats.

Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-ß. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation.

Application of apical myocardial perfusion quantitative analysis by contrast-enhanced ultrasound utilizing high-frequency linear probe.

BACKGROUND: Due to insufficient near-field resolution and artifacts, it is challenging to evaluate the left ventricular apical perfusion with phased-array probes. By combining high-frequency linear probe and contrast-enhanced ultrasound (CEUS), imaging of apical myocardial perfusion could be improved. The study aims to evaluate the preliminary application of CEUS by high-frequency linear probes to assess the apical perfusion. METHODS: The study enrolled retrospectively 91 patients to test the feasibility of the novel method. In protocol 1, patients were stratified into a group with left anterior descending artery (LAD) stenosis (N = 40) and a group without LAD stenosis or coronary artery disease (N = 41) based on the degree of coronary artery narrowing, quantified by >50% stenosis in coronary angiography. Receiver operating characteristics (ROC) analysis was performed to test the diagnostic value of perfusion parameters. In protocol 2, the reproducibility of high-frequency linear probe in apical perfusion analysis was compared with the conventional phased-array probe in 30 patients. RESULTS: (1) The novel method is feasible in 81(89.01%) patients. (2) In protocol 1, to detect LAD stenosis, the best cut-off of ß, T, A, and MBF were 10.32, 3.28, 9.39, and 4.99, respectively. Area under the curve of ß, T, A, and MBF were .880, .881, .761, and .880, respectively. (3) In protocol 2, compared with phased-array probe, the quantitative analysis of high-frequency linear probe is of high reproducibility and could get good curve fitting (R2 = .29 vs. R2 = .71, P < .01). CONCLUSION: Observation of apical perfusion using this method is feasible and quantitative analysis allows an accurate and convenient identification of LAD stenosis. This method provides an alternative for patients who have difficulties in visualizing the apical region with a phased-array probe.

Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway.

We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.

The Safety of Injections in the Infraorbital Region.

BACKGROUND:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications. OBJECTIVE:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection. METHODS:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution. RESULTS:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%). CONCLUSION:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Study on the Aesthetic Parameters and Proportions of the External Contour for Minimally Invasive Facial Injection.

OBJECTIVE: The aim of this study was to further guide the diagnosis and treatment programs for clinical facial contouring with injectable fillers by studying the facial contour parameters and proportion preferences consistent with Asian aesthetics. METHODS: A total of 89 subjects (42 males and 47 females aged 20-60 years) who met the inclusion criteria were enrolled in this study. The subjects were grouped by age, sex, and external contour attractiveness score, and the external contour aesthetic parameters and proportions of the subjects in different groups were measured and analysed. RESULTS: The upper facial breadth and lower facial breadth decreased with age, with significant differences between the 50-60-year age group and other age groups (P < 0.01). The nasomental angle showed a decreasing trend with age, with significant differences between the 40-49-year age group and the 20-29-year and 30-39-year age groups (P < 0.05). Males and females were significantly different in calva height, total head height, lower facial height, and calva height to total head height ratio (P < 0.05). With increasing age, the external contour attractiveness scores of males and females both showed decreasing trends, with significant differences between the 50-60-year age group and other age groups (P < 0.05). CONCLUSION: The calva height and the cranioauricular angle have a significant impact on external contour attractiveness. In general, temporal depression, cheek sagging, lateral cheek depression, and an ill-defined mandibular border will occur due to ageing, collagen loss, ligament laxity and sagging, and soft tissue atrophy and sagging, reducing the attractiveness of the external contour. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Performance Pressure and Employee Presenteeism: The Joint Effects of Authoritarian Leadership and Independent Self-Construal.

Due to the increasing competition in the market and the limited availability of high-quality employment opportunities, an increasing number of employees struggle to maintain a balance between their physical conditions and performance demands, resulting in a more widespread occurrence of "working while ill". However, little is known about the controlled motivation behind the phenomenon under pressure. Drawing on self-determination theory, this study utilized 281 questionnaire data to examine the positive effect of performance pressure on employee presenteeism, and to explore the moderating role of authoritarian leadership and its joint moderation function effect with independent self-construal. The results indicated that performance pressure had a significant positive effect on employee presenteeism. Authoritarian leadership imposed an enhanced moderating effect between performance pressure and employee presenteeism, while independent self-construal diminished the augmentative moderating role played by authoritarian leadership in the relationship between performance pressure and employee presenteeism. This study reveals the controlled motivation of employee presenteeism under performance pressure, taking into account the cultural background and organizational context of China. Moreover, it also offers novel perspectives for effectively managing this phenomenon.

Controllable synthesis of TiO2/graphene composites for human voice recognition in strain sensor.

Low-dimensional materials have demonstrated strong potential for use in diverse flexible strain sensors for wearable electronic device applications. However, the limited contact area in the sensing layer, caused by the low specific surface area of typical nanomaterials, hinders the pursuit of high-performance strain-sensor applications. Herein, we report an efficient method for synthesizing TiO2-based nanocomposite materials by directly using industrial raw materials with ultrahigh specific surface areas that can be used for strain sensors. A kinetic study of the self-seeded thermal hydrolysis sulfate process was conducted for the controllable synthesis of pure TiO2 and related TiO2/graphene composites. The hydrolysis readily modified the crystal form and morphology of the prepared TiO2 nanoparticles, and the prepared composite samples possessed a uniform nanoporous structure. Experiments demonstrated that the TiO2/graphene composite can be used in strain sensors with a maximum Gauge factor of 252. In addition, the TiO2/graphene composite-based strain sensor showed high stability by continuously operating over 1,000 loading cycles and aging tests over three months. It also shows that the fabricated strain sensors have the potential for human voice recognition by characterizing letters, words, and musical tones.

Response strategies of stem/leaves endophyte communities to nano-plastics regulate growth performance of submerged macrophytes.

Research on the toxicity effects of nano-plastics on submerged macrophytes has been increasing over the past several years. However, how the endophytic bacteria of submerged macrophytes respond to nano-plastics remains unknown, although they have been widely shown to help terrestrial plants cope with various environmental stressors. Here, a microcosm experiment was performed to unravel the effects of high concentration of nano-plastics (20 mg/L) on three submerged macrophyte (Vallisneria natans, Potamogeton maackianus, Myriophyllum spicatum) and their endophytic bacterial communities. Results indicated that nano-plastics induced antioxidative stress in plants, but significantly reduction in relative growth rate (RGR) only occurred in V. natans (from 0.0034 to -0.0029 day-1), accompanied by change in the stem/leaves endophyte community composition. Further analysis suggested nano-plastics caused a reduction in environmental nutrient availability and the proportion of positive interactions between endophyte communities (43%), resulting in the lowest RGR of V. natans. In contrast, endophytes may help P. maackianus and M. spicatum cope with nano-plastic stress by increasing the proportion of positive correlations among communities (70% and 75%), leaving their RGR unaffected. Collectively, our study elucidates the species-specific response strategies of submerged macrophyte-endophyte to nano-plastics, which helps to reveal the different phytoremediation potential of submerged macrophytes against nano-plastic pollution.

SLC38A3 Promotes the Proliferation and Migration of Tumor Cells and Predicts Poor Prognosis in Colorectal Cancer.

Previous studies have revealed that abnormal expressions of membrane transporters were associated with colorectal cancer (CRC). We herein performed a comprehensive bioinformatics analysis to identify the key transporter protein-related genes involved in CRC and potential mechanisms. Differentially expressed transporter protein-related genes (DE-TPRGs) were identified from CRC and normal samples using The Cancer Genome Atlas database. SLC38A3 expression was validated by immunohistochemistry and RT-qPCR, and the potential mechanism was explored. A total of 63 DE-TPRGs (29 up-regulated and 34 down-regulated) were screened. Inside, ABCC2, ABCG2, SLC4A4, SLC9A3, SLC15A1, and SLC38A3 were identified as hub genes. SLC38A3 is indeed upregulated in colorectal cancer patients. Furthermore, we found that knockdown of SLC38A3 inhibited the proliferation and migration of HCT116 cells, and Hsp70 ATPase activator could rescue it. Overall, SLC38A3 is a novel potential biomarker involved in CRC progression and promotes the proliferation and migration of tumor cells by positively regulating the function of Hsp70.

Synthesis, magnetic properties, biotoxicity and potential mechanism of modified nano zero-valent iron for decolorization of dye wastewater.

SiO2-coated nano zero-valent iron (nZVI) has emerged as a fine material for the treatment of dye wastewater due to its large specific surface area, high surface activity, and strong reducibility. However, the magnetic properties based on which SiO2-coated nZVI (SiO2-nZVI) could effectively separate and recover from treated wastewater, and the biotoxicity analysis of degradation products of the dye wastewater treated by SiO2-nZVI remain unclear. In this study, SiO2-nZVI was synthesized using a modified one-step synthesis method. The SiO2-nZVI nanoparticles were characterized using Transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, Fully automatic specific surface and porosity analyzer, Vibrating sample magnetometer, and Zeta potential analyzer. The removal rate of methyl orange (MO) by SiO2-nZVI composite reached 98.35% when the degradation performance of SiO2-nZVI treating MO was optimized. Since SiO2-nZVI analysed by magnetic hysteresis loops had large saturation magnetization and strong magnetic properties, SiO2-nZVI exhibited excellent ferromagnetic behaviour. The analysis of the degradation products showed that the MO treated by SiO2-nZVI was converted into a series of intermediates, resulting in reducing the toxicity of MO. The potential mechanism of MO degradated by SiO2-nZVI was speculated through degradation process and degradation kinetics analysis. Overall, the SiO2-nZVI composite may be regarded as a promising catalyst for decolorization of dye wastewater.

Application of an echocardiographic index to characterize right ventricular-pulmonary arterial coupling in heart failure.

Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV-pulmonary arterial (RV-PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end-systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV-PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non-invasive surrogate of RV-PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV-PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature.

Identification of key mitochondria-related genes and their potential crosstalk role with immune pattern in Idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) stands out as a life-threatening and one of the most severe interstitial lung diseases. The pathogenesis of IPF is not fully understood, while recent studies have highlighted the association of mitochondrial dysfunction with IPF. This study is dedicated to pinpointing crucial genes related to mitochondria that potentially impact the advancement of IPF, thereby offering new perspectives on the pathogenesis of this condition. METHODS: The Gene Expression Omnibus (GEO) database was utilized to download three datasets (GSE32537, GSE92592, and GSE150910), following which a comprehensive analysis was conducted to identify differentially expressed mitochondria-related genes (DEMTRGs) in the IPF lung tissues. Subsequently, GO and KEGG enrichment analysis of the DEMTRGs was performed. Next, external datasets and in vivo experiments were performed to validate their expression. Additionally, a Logistic regression model based on key DEMTRGs was constructed, and the model's ability to distinguish between IPF and controls was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Finally, gene set enrichment analysis (GSEA) and CIBERSORT algorithm were conducted. RESULTS: We identified five key DEMTRGs (ALDH18A1, ALDH1B1, MCCC1, ACAT1, and PDHA1), ALDH18A1 and ALDH1B1 exhibited upregulated expression levels, whereas MCCC1, ACAT1, and PDHA1 showed downregulation in the lung tissue of individuals with IPF. The expression levels of these key DEMTRGs were validated by an independent external dataset (GSE53845) and the bleomycin-induced pulmonary fibrosis mice. In addition, the ROCs indicated that the diagnostic model constructed based on key DEMTRGs could effectively distinguish between IPF and controls (AUC>0.8). GSEA analysis and immune-related analysis shed light on the potential mechanisms through which these key DEMTRGs influence IPF. CONCLUSION: Our research has pinpointed key genes associated with mitochondria that may ultimately contribute to the progression of IPF by exerting regulatory effects on mitochondrial function, thereby influencing multiple cellular processes.

Solute transport characteristics at the lakebed sediment-water interface due to multiple influences of dual seasonal lakes.

Multiple coexisting seasonal lakes are observed in the Poyang Lake basin. The interaction between surface water and groundwater, along with solute transport at the sediment-water interface (SWI), plays a crucial role in material cycling within the Poyang Lake ecosystem. However, the mechanisms governing how the relative positions of these lakes influence solute transport at the SWI remain unclear. This study employs indoor experiments and simulations based on real topography to investigate how the separation distance and elevation differences between two seasonal lakes, termed "lake A" (situated farther from the main lake) and "lake B" (closer to the main lake), affect solute transport. Findings highlight a distinct recharge pattern from lake A to lake B and the main lake during periodic water level fluctuations. A reduced distance between dual seasonal lakes results in a diminished water level drop in lake B during dry seasons. Proximity allows lake A to contribute more solutes to the main lake while promoting solute transport from lake B to the main lake, increasing the pore water recharge flux to overlying water in lake B. In cases where the separation distance has insufficient impact on water levels, the speed of pore water flow in this area inversely correlates with the distance between dual lakes. Reducing the distance intensifies solute transport into the bottom of lake A. Lower the elevation of lake B increases the water level difference between dual seasonal lakes, curtailing pollution within the lakebed. Elevating lake B forms hydrological isolation and more severe pollution of the lakebed. Solutes predominantly transport between lake B and the main lake, with pollution spreading to the lakebed of lake A and transitioning to downward diffusion over time. This research provides valuable insights for the hydraulic regulation of seasonal lakes and holds significance for the ecological restoration of Poyang Lake.

Nitrogen removal performance and mechanisms of three aquatic plants for farmland tail water purification.

Constructed wetlands (CWs) are commonly used to control excessive nitrogen from farmlands; however, the interactions between vegetation and microorganisms, nitrogen removal performance, and the mechanisms involved remain unclear in subtropical areas. This study aimed to investigate the nitrogen removal performance and mechanism of CWs containing Canna indica, Acorus calamus, and Thalia dealbata. The results show that CWs with plants had significantly higher nitrogen removal efficiencies than those without, with those planted with T. dealbata having the highest efficiency. T. dealbata performed better than the other two plants due to its high biomass and excellent nitrogen uptake capacity; more importantly, CWs with it had the highest abundance of nitrogen functional genes. Microbial nitrification-denitrification, the primary process of nitrogen removal in CWs, contributed to 88 %, 91 %, and 84 % of the TN removal in the CWs with C. indica, A. calamus, and T. dealbata, respectively, 29 %-158 % higher than that in CWs without plants. Microorganisms played a crucial role in nitrogen removal in the CWs, while plants significantly stimulated microbial activity by enhancing microbial abundance and creating a suitable environment for growth and metabolism. These results can help in understanding the contribution of plants in cleaning farmland tailwater and further optimization of plant configuration and management strategies in wetland ecosystems to improve nitrogen removal efficiency.

High-expressed ACAT2 predicted the poor prognosis of platinum-resistant epithelial ovarian cancer.

BACKGROUND: Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC). METHODS: ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ2 test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models. RESULTS: ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15-4.11, P = 0.017) affected OS independently, rather than PFI and PFS. CONCLUSION: The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.

The Association of High Lipoprotein(a) Concentration and Risk of Ischaemic Stroke in Atrial Fibrillation Patients.

Background: Lipoprotein(a) [Lp(a)] is a well-established risk factor for ischaemic stroke (IS). It is unclear whether Lp(a) is associated with IS in patients with atrial fibrillation (AF). The aim of this study is to explore the association between the concentration of Lp(a) and the risk of IS in AF patients, hope to find the potential risk factor for the IS in AF patients. Methods: This study is a retrospective cohort study. The screened AF patients between January 2017 and July 2021 were matched at 1:1 by the propensity score matching (PSM) method in the Second Affiliated Hospital of Nanchang University. Associations between Lp(a) and ischaemic stroke were analysed using logistic regression models, stratified analysis and sensitivity analysis. Statistical analyses were conducted using IBM SPSS software. Results: The number of enrolled participates is 2258, which contains 1129 non-AF patients and 1129 AF patients. Among IS patients, the median Lp(a) concentration was higher than that of controls (17.03 vs. 15.36 mg/dL, P = 0.032). The Spearman rank-order correlation coefficients revealed significant positive relationships between IS and Lp(a) (P = 0.032). In addition, a significant increase in IS risk was associated with Lp(a) levels >30.00 mg/dL in unadjusted model [OR:1.263, 95% CI(1.046-1.523), P = 0.015], model 1 [OR:1.284, 95% CI(1.062,1.552), P = 0.010], model 2 [OR: 1.297, 95% CI(1.07,1.573). P = 0.008], and model 3 [OR: 1.290, 95% CI (1.064, 1.562). P = 0.009]. The stratified analysis indicated that this correlation was not affected by female sex [1.484 (1.117, 1.972), P = 0.006], age ≤ 60 [1.864 (1.067-3.254), P=0.029], hypertension [1.359 (1.074, 1.721), P = 0.011], or non-coronary heart disease (CHD) [1.388 (1.108, 1.738), P = 0.004]. Conclusion: High levels of Lp(a) were significantly related to IS in AF patients and may be a potential risk factor in the onset of an IS in AF patients.

Integrated ATAC-seq and RNA-seq Analysis of In Vitro Cultured Skeletal Muscle Satellite Cells to Understand Changes in Cell Proliferation.

Skeletal muscle satellite cells, the resident stem cells in pig skeletal muscle, undergo proliferation and differentiation to enable muscle tissue repair. The proliferative and differentiative abilities of these cells gradually decrease during in vitro cultivation as the cell passage number increases. Despite extensive research, the precise molecular mechanisms that regulate this process are not fully understood. To bridge this knowledge gap, we conducted transcriptomic analysis of skeletal muscle satellite cells during in vitro cultivation to quantify passage number-dependent changes in the expression of genes associated with proliferation. Additionally, we explored the relationships between gene transcriptional activity and chromatin accessibility using transposase-accessible chromatin sequencing. This revealed the closure of numerous open chromatin regions, which were primarily located in intergenic regions, as the cell passage number increased. Integrated analysis of the transcriptomic and epigenomic data demonstrated a weak correlation between gene transcriptional activity and chromatin openness in expressed genic regions; although some genes (e.g., GNB4 and FGD5) showed consistent relationships between gene expression and chromatin openness, a substantial number of differentially expressed genes had no clear association with chromatin openness in expressed genic regions. The p53-p21-RB signaling pathway may play a critical regulatory role in cell proliferation processes. The combined transcriptomic and epigenomic approach taken here provided key insights into changes in gene expression and chromatin openness during in vitro cultivation of skeletal muscle satellite cells. These findings enhance our understanding of the intricate mechanisms underlying the decline in cellular proliferation capacity in cultured cells.

Effectiveness of musculoskeletal manipulations in patients with neck pain: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Neck pain is a common problem that severely affects physical and mental health. While musculoskeletal manipulations are recommended as the first-line treatment for adults with neck pain, the comparative effectiveness of different musculoskeletal manipulations remains unclear. This systematic review and network meta-analysis of randomised controlled trials (RCTs) will compare the effectiveness of different types of musculoskeletal manipulations, with the overarching aim of guiding clinical practice. METHODS AND ANALYSIS: Two independent reviewers will search four English electronic databases (Web of Science, Cochrane Library, EMBASE, PubMed) and three Chinese electronic databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang) for relevant RCTs published from 1 January 2013 to 30 April 2023. The Clinical Trials Registry (ClinicalTrials.gov) will be searched for completed but unpublished RCTs. English and Chinese will be used to search English databases and Chinese databases, respectively. RCTs of musculoskeletal manipulations for adults (aged ≥18 years) with neck pain will be considered eligible for inclusion. A pairwise meta-analysis and network meta-analysis will be performed, and pooled risk ratios, standardised mean differences and 95% CIs will be determined. ETHICS AND DISSEMINATION: Ethics approval is not required as this study is a literature review. The results of this review will be published in peer-reviewed journals or disseminated at conferences. PROSPERO REGISTRATION NUMBER: CRD42023420775.

Structure-activity relationship study of 1,6-naphthyridinone derivatives as selective type II AXL inhibitors with potent antitumor efficacy.

The role of AXL in various oncogenic processes has made it an attractive target for cancer therapy. Currently, kinase selectivity profiles, especially circumventing MET inhibition, remain a scientific issue of great interest in the discovery of selective type II AXL inhibitors. Starting from a dual MET/AXL-targeted lead structure from our previous work, we optimized a 1,6-naphthyridinone series using molecular modeling-assisted compound design to improve AXL potency and selectivity over MET, resulting in the potent and selective type II AXL-targeted compound 25c. This showed excellent AXL inhibitory activity (IC50 = 1.1 nM) and 343-fold selectivity over the highly homologous kinase MET in biochemical assays. Moreover, compound 25c significantly inhibited AXL-driven cell proliferation, dose-dependently suppressed 4T1 cell migration and invasion, and induced apoptosis. Compound 25c also showed noticeable antitumor efficacy in a BaF3/TEL-AXL xenograft model at well-tolerated doses. Overall, this study presented a potent and selective type II AXL-targeted lead compound for further drug discovery.

Gene polymorphisms of METTL5 and METTL16 are related to epithelial ovarian cancer risk in South China: A three-center case-control study.

Background: The potential relation of methyltransferase-like gene polymorphisms and epithelial ovarian cancer (EOC) remains unclear. Methods: Five SNPs (METTL5 rs3769767 A>G, METTL16 rs1056321 T>C, METTL5 rs10190853 G>A, METTL5 rs3769768 G>A and METTL16 rs11869256 A>G) of methyltransferase-like genes was selected trough NCBI dbSNP database. Two hundred and eighty-eight cases and 361 controls were enrolled from three hospitals in South China to conduct the case-control study. Genomic DNA was abstracted from peripheral blood and genotyped through a TapMan assay. Stratified analysis was conducted to explore the association of rs10190853, rs3769768, rs11869256 genotype and EOC susceptibility. The combination analysis was adopted to evaluate the relation between inferred haplotypes of the METTL5, METTL16 genes and EOC risk. Multifactor dimensionality reduction (MDR) analysis was performed to verify the interaction of SNPs. Results: Among the five analyzed SNPs, METTL5 rs3769768 AA exhibited a significant association with increased EOC risk, while METTL5 rs10190853 GA, METTL16 rs11869256 GA was certified to decrease the susceptibility of EOC. The stratified analysis further revealed the harmful effect of METTL5 rs3769768 AA in EOC patients. On the contrary, METTL16 rs11869256 AG/GG and METTL5 rs10190853 AA showed the reduced risk of EOC in patients of specific subgroups. Combination analysis identified that haplotypes AAA highly connected with reduced risk of EOC. MDR analysis revealed that these SNPs existed no specific interactions. Conclusion: METTL5 rs3769768 was related to increased risk of EOC. METTL5 rs10190853 and METTL16 rs11869256 decreased the susceptibility in EOC. METTL5 and METTL16 could be potential target of molecular therapy and prognosis markers.