Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Identification of novel targets associated with cholesterol metabolism in nonalcoholic fatty liver disease: a comprehensive study using Mendelian randomization combined with transcriptome analysis.

Background: There is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear. Methods: The differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes. Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed. Results: We identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD. Conclusion: Our study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.

Correlation between organizational support, self-efficacy, and core competencies among long-term care assistants: a structural equation model.

Introduction: Long-term care assistants are taking on more important roles in the healthcare system. The purpose of this study was to investigate what demographic factors influence the core competencies of nursing assistants, as well as to investigate the levels of organizational support, self-efficacy, and core competencies among nursing assistants in China, to explore the relationship between them. Methods: This is a cross-sectional study with prospective data collection based on a self-report questionnaire. A total of 320 long-term care assistants from two healthcare institutions. We collected socio-demographic characteristics and measured their perceived organizational support, self-efficacy, and core competency levels of the participants. Pearson correlation tests were conducted to examine the relationships among three variables, and a structural equation model was developed to test the interrelationships among these variables. Results: The results indicated that age, employment type, licensing status, monthly income, pre-job training, and training methods were associated with core competency, with nursing knowledge identified as a weak area in core competencies. There were significant associations among each dimension of perceived organizational support, self-efficacy, and core competencies (p < 0.01). The structural equation model demonstrated good fit: X 2/df = 2.486, GFI = 0.974, CFI = 0.988, IFI = 0.988, TLI = 0.977, RMSEA = 0.068, SRMR = 0.013. The direct effect of organizational support on core competencies was 0.37, with self-efficacy mediating the relationship between organizational support and core competencies, yielding an indirect effect of 0.122 and a total effect coefficient of 0.492 (all p < 0.001). Conclusion: Training in core competencies should prioritize nursing knowledge. Enhanced perceived organizational support and self-efficacy among nursing assistants were associated with higher core competencies.

Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing.

BACKGROUND: The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage-related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established. OBJECTIVE: This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. METHODS AND RESULTS: Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage-specific knockout of Trem2 (T2-cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)-4 binds directly to Trem2, inactivating MAPK/AP-1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co-culture of fibroblasts and macrophages showed that macrophages from T2-cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing. CONCLUSIONS: These analyses offer novel insight into the role of IL-4/Trem2 signalling as a mediator of myeloid cell-fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.

Rutaecarpine alleviates inflammation and fibrosis by targeting CK2α in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus. During the progression of DN, the proliferation of glomerular mesangial cells (GMCs) leads to the deposition of excessive extracellular matrix (ECM) in the mesangial region, eventually resulting in glomerulosclerosis. Rutaecarpine (Rut), an alkaloid found in the traditional Chinese medicinal herb Fructus Evodiae (Euodia rutaecarpa (Juss.) Benth.), has many biological activities. However, its mechanism of action in DN remains unknown. This study used db/db mice and high glucose (HG)-treated mouse mesangial cells (SV40 MES-13) to evaluate the protective effects of Rut and underlying mechanisms on GMCs in DN. We found that Rut alleviated urinary albumin and renal function and significantly relieved renal pathological damage. In addition, Rut decreased the ECM production, and renal inflammation and suppressed the activation of TGF-ß1/Smad3 and NF-κB signaling pathways in vitro and in vivo. Protein kinase CK2α (CK2α) was identified as the target of Rut by target prediction, molecular docking, and cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR). Furthermore, Rut could not continue to play a protective role in HG-treated SV40 cells after silencing CK2α. In summary, this study is the first to find that Rut can suppress ECM production and inflammation in HG-treated SV40 cells by inhibiting the activation of TGF-ß1/Smad3 and NF-κB signaling pathways and targeting CK2α. Thus, Rut can potentially become a novel treatment option for DN.

Ambient Air Pollution and Hospitalizations for Schizophrenia in China.

Importance: Schizophrenia episodes may be triggered by short-term environmental stimuli. Short-term increases in ambient air pollution levels may elevate the risk of schizophrenia episodes, yet few epidemiologic studies have examined this association. Objective: To investigate whether short-term increases in air pollution levels are associated with an additional risk of schizophrenia episodes, independent of absolute air pollution concentrations, and whether sustained increases in air pollution levels for several days are associated with more pronounced risks of schizophrenia episodes. Design, Setting, and Participants: This nationwide, population-based, time-stratified case-crossover study was performed based on hospitalization records for schizophrenia across 295 administrative divisions of prefecture-level or above cities in China. Records were extracted from 2 major health insurance systems from January 1, 2013, to December 31, 2017. Thirty-six cities with a small number of schizophrenia hospitalizations (n < 50) were excluded. Data analysis for this study was performed from January to March 2024. Exposure: Daily absolute concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were collected. Air pollution increases between neighboring days (APINs) were generated as the differences in absolute air pollution concentrations on the current day minus that on the previous day. Sustained increases (APIN ≥5 µg/m3 for PM2.5 and PM10, APIN ≥1 µg/m3 for nitrogen dioxide and sulfur dioxide, and APIN ≥0.05 mg/m3 for carbon monoxide) lasting for 1 or more to 4 or more days were defined for different air pollutants. Main Outcome and Measure: Patients with schizophrenia episodes were identified by principal discharge diagnoses of schizophrenia. A conditional logistic regression model was used to capture the associations of absolute concentrations, APINs, and sustained increase events for different air pollutants with risks of schizophrenia hospitalizations. Results: The study included 817 296 hospitalization records for schizophrenia across 259 Chinese cities (30.6% aged 0-39 years, 56.4% aged 40-64 years, and 13.0% aged ≥65 years; 55.04% male). After adjusting for the absolute concentrations of respective air pollutants, per-IQR increases in 6-day moving average (lag0-5) APINs of PM2.5, PM10, nitrogen dioxide, sulfur dioxide, and carbon monoxide were associated with increases of 2.37% (95% CI, 0.88%-3.88%), 2.95% (95% CI, 1.46%-4.47%), 4.61% (95% CI, 2.93%-6.32%), 2.16% (95% CI, 0.59%-3.76%), and 2.02% (95% CI, 0.39%-3.68%) in schizophrenia hospitalizations, respectively. Greater risks of schizophrenia hospitalizations were associated with sustained increases in air pollutants lasting for longer durations up to 4 or more days. Conclusions and Relevance: This case-crossover study of the association between ambient air pollution increases and schizophrenia hospitalizations provides novel evidence that short-term increases in ambient air pollution levels were positively associated with an elevated risk of schizophrenia episodes. Future schizophrenia prevention practices should pay additional attention to APINs, especially sustained increases in air pollution levels for longer durations, besides the absolute air pollution concentrations.

Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review.

BACKGROUND: Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60-65%), CALR (20-25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations. CASE PRESENTATION: A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved. CONCLUSIONS: The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

Inflammatory factors and risk of lung adenocarcinoma: a Mendelian randomization study mediated by blood metabolites.

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear. Methods: This study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses. Results: The MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.). Conclusion: This study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidence-based medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications.

Long-term contamination of decabromodiphenyl ether reduces sediment multifunctionality: Insights from nutrient cycling, microbial ecological clusters, and microbial co-occurrence patterns.

Despite the widespread detection of polybrominated diphenyl ethers in aquatic ecosystems, their long-term effects on sediment multifunctionality remain unclear. Herein, a 360-day microcosm experiment was conducted to investigate how decabromodiphenyl ether (BDE-209) contamination at different levels (0.2, 2, and 20 mg/kg dry weight) affects sediment multifunctionality, focusing on carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling. Results showed that BDE-209 significantly increased sediment total organic carbon, nitrate, ammonium, available phosphorus, and sulfide concentrations, but decreased sulfate. Additionally, BDE-209 significantly altered key enzyme activities related to nutrient cycling. Bacterial community dissimilarity was positively correlated with nutrient variability. Long-term BDE-209 exposure inhibited C degradation, P transport and regulation, and most N metabolic pathways, but enhanced C fixation, methanogenesis, organic P mineralization, inorganic P solubilization, and dissimilatory sulfate reduction pathways. These changes were mainly regulated by microbial ecological clusters and keystone taxa. Overall, sediment multifunctionality declined under BDE-209 stress, primarily related to microbial co-occurrence network complexity and ecological cluster diversity. Interestingly, sediment C and N cycling had greater impacts on multifunctionality than P and S cycling. This study provides crucial insights into the key factors altering multifunctionality in contaminated sediments, which will aid pollution control and mitigation in aquatic ecosystems.

PARN Maintains RNA Stability to Regulate Insulin Maturation and GSIS in Pancreatic ß Cells.

Diabetes, a metabolic disorder characterized by hyperglycemia, underscores the importance of normal pancreatic ß-cell development and function in maintaining glucose homeostasis. Poly(A)-specific ribonuclease (PARN) serves as the principal regulator of messenger RNA (mRNA) stability, yet its specific role in pancreatic ß cells remains unclear. This study utilizes mice with targeted PARN deficiency in ß cells to elucidate this role. Notably, Parn conditional knockout mice present unaltered ß-cell development and insulin sensitivity but reduced glucose-stimulated insulin secretion (GSIS). The observed outcomes are corroborated in NIT-1 cells. Furthermore, transcriptomic analyses reveal aberrant mRNA expression of genes crucial for insulin secretion in PARN-deficient ß cells. Insights from linear amplification of complementary DNA ends and sequencing and coimmunoprecipitation experiments reveal an interaction between PARN and polypyrimidine tract-binding protein 1 (PTBP1), regulating the RNA stability of solute carrier family 30, member 8 (Slc30a8) and carbohydrate sulfotransferase 3 (Chst3). Interference with either PARN or PTBP1 disrupts this stability. These data indicate that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs. These findings provide compelling evidence indicating that PARN is a potential therapeutic target for enhancing insulin maturation and secretion.

Water limitation drives species loss in grassland communities after nitrogen addition and warming.

Nutrient addition, particularly nitrogen, often increases plant aboveground biomass but causes species loss. Asymmetric competition for light is frequently assumed to explain the biomass-driven species loss. However, it remains unclear whether other factors such as water can also play a role. Increased aboveground leaf area following nitrogen addition and warming may increase transpiration and cause water limitation, leading to a decline in diversity. To test this, we conducted field measurements in a grassland community exposed to nitrogen and water addition, and warming. We found that warming and/or nitrogen addition significantly increased aboveground biomass but reduced species richness. Water addition prevented species loss in either nitrogen-enriched or warmed treatments, while it partially mitigated species loss in the treatment exposed to increases in both temperature and nitrogen. These findings thus strongly suggest that water limitation can be an important driver of species loss as biomass increases after nitrogen addition and warming when soil moisture is limiting. This result is further supported by a meta-analysis of published studies across grasslands worldwide. Our study indicates that loss of grassland species richness in the future may be greatest under a scenario of increasing temperature and nitrogen deposition, but decreasing precipitation.

Similarity-based metric analysis approach for predicting osteogenic differentiation correlation coefficients and discovering the novel osteogenic-related gene FOXA1 in BMSCs.

Background: As a powerful tool, bioinformatics analysis is playing an increasingly important role in many fields. Osteogenic differentiation is a complex biological process involving the fine regulation of numerous genes and signaling pathways. Method: Osteogenic differentiation-related genes are collected from the online databases. Then, we proposed two indexes Jaccard similarity and Sorensen-Dice similarity to measure the topological relevance of genes in the human PPI network. Furthermore, we selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation. Subsequently, we performed functional a enrichment analysis of these top-ranked genes to check whether these candidate genes identified by similarity-based metrics are enriched in some specific biological functions and states. we performed a permutation test to investigate the similarity score with four well-known osteogenic differentiation-related pathways including hedgehog signaling pathway, BMP signaling, ERK pathway, and Wnt signaling pathway to check whether these osteogenic differentiation-related pathways can be regulated by FOXA1. Lentiviral transfection was used to knockdown and overexpress gene FOXA1 in human bone mesenchymal stem cells (hBMSCs). Alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS) were employed to investigate osteogenic differentiation of hBMSCs. Result: After data collection, human PPI network involving 19,344 genes is included in our analysis. After simplifying, we used Jaccard and Sorensen-Dice similarity to identify osteogenic differentiation-related genes and integrated into a final similarity matrix. Furthermore, we calculated the sum of similarity scores with these osteogenic differentiation-related genes for each gene and found 337 osteogenic differentiation-related genes are involved in our analysis. We selected three pathways involving osteoblast-related transcription factors, osteoblast differentiation, and RUNX2 regulation of osteoblast differentiation for investigation and performed functional enrichment analysis of these top-ranked 50 genes. The results collectively demonstrate that these candidate genes can indeed capture osteogenic differentiation-related features of hBSMCs. According to the novel analyzing method, we found that these four pathways have significantly higher similarity with FOXA1 than random noise. Moreover, knockdown FOXA1 significantly increased the ALP activity and mineral deposits. Furthermore, overexpression of FOXA1 dramatically decreased the ALP activity and mineral deposits. Conclusion: In summary, this study showed that FOXA1 is a novel significant osteogenic differentiation-related transcription factor. Moreover, our study has tightly integrated bioinformatics analysis with biological knowledge, and developed a novel method for analyzing the osteogenic differentiation regulatory network.

Involvement of the AMPK Pathways in Muscle Development Disparities across Genders in Muscovy Ducks.

The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits (p < 0.05). Compared to male ducks, the level of serum testosterone in female ducks was decreased, and the estradiol levels were increased (p < 0.05). The RNA-seq analysis identified 102 upregulated and 49 downregulated differentially expressed genes. KEGG analysis revealed that among the top 10 differentially enriched pathways, the AMPK signaling pathway is closely related to muscle growth and development. Additionally, the mRNA and protein levels of CD36, CPT1A, LPL, and SREBP1 were increased and the P-AMPK protein level decreased in the female ducks compared to the male ducks (p < 0.05). In conclusion, muscle development potential difference between male and female ducks is regulated by sex hormones. This process is likely mediated through the activation of the AMPK pathway.

Characterization of a marine endolysin LysVPB against Vibrio parahaemolyticus.

Currently, there is an urgent to develop safe and environmentally friendly alternatives to antibiotics for combating Vibrio parahaemolyticus. Endolysins are considered promising antibacterial agents due to their desirable range of action and ability to deal with antibiotic-resistant bacteria. While numerous Vibrio phages have been identified, the research on their endolysins is still in its infancy. In this study, a novel endolysin called LysVPB was cloned and expressed in Pichia pastoris. Phylogenetic analysis revealed that LysVPB bears little resemblance to other known endolysins, highlighting its unique nature. Homology modeling identified a putative calcium-binding site in LysVPB. The recombinant LysVPB achieved a lytic activity of 64.8 U/mL and had a molecular weight of approximately 17 kDa. LysVPB exhibited enhanced efficacy at pH 9.0, with 60% of its maximum activity observed within the broad pH range of 6.0-10.0. The catalytic efficiency of LysVPB peaked at 30 °C but significantly declined beyond 50 °C. Ba2+, Co2+, and Cu2+ showed inhibitory effects on the activity of LysVPB, while Ca2+ can boost it to 126.8%. Furthermore, LysVPB exhibited satisfactory efficacy against strains of V. parahaemolyticus. LysVPB is an innovative phage lysin with good characteristics that are specific to certain hosts. The modular nature of LysVPB allows for efficient domain exchange with alternative lysins as antimicrobial components and fusion with antimicrobial peptides. This opens up possibilities for engineering chimeric lysins in a broader range of target hosts with high antimicrobial effectiveness and strong activity under physiological conditions.

Dynamic change of lymphocytes associated with short-term prognosis in anti-MDA5-positive dermatomyositis with interstitial lung disease: a multicenter retrospective study.

Lymphopenia is a unique manifestation of anti-MDA5 positive dermatomyositis with interstitial lung disease (MDA5 + DM-ILD). This study aimed to investigate the relationship between dynamic changes in peripheral lymphocytes and short-term prognosis in patients of MDA5 + DM-ILD. Two hundred sixty-three MDA5 + DM-ILD patients were divided into different groups according to lymphocyte count and death or survival within 1 month, then the differences in clinical features and outcomes were compared. Associations between lymphocytes and risk of death within 1 month were also investigated in different lymphocyte groups using Cox proportional hazard models. A generalized additive mixed model (GAMM) was established to analyze the dynamic changes of lymphocytes in the death 1-month group. Lymphocytes of the patients who died within 1 month were significantly lower than survivors by different lymphocyte grouping methods, and the total lymphocytes showed a gradually decreasing trend in non-survivors. And the difference between survivors and non-survivors was more obvious over time. The lowest tertile of baseline lymphocytes as a reference, the hazard ratios for death within 1 month in the highest tertile were 0.497 (95% CI 0.26-0.949, P for trend = 0.033) after adjustment for potential confounders. GAMM analysis found a mean daily decrease of lymphocytes (0.034 × 10^9/L) after admission in death 1-month patients. Low baseline lymphocytes and gradually declined lymphocytes are both associated with a high risk of death within 1 month. However dynamic changes in lymphocytes can better reflect the disease status and better predict the short-term prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. Key points •Low baseline lymphocytes and gradually decreased trend along time correlated with poor short-term prognosis in MDA5 + DM-ILD patients. •Dynamic changes of lymphocytes can better reflect the disease status and better predict the 1-month prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. •Generalized additive mixed model (GAMM) analysis found that in 1-month non-survivors, peripheral blood lymphocytes decreased by 0.034 × 10^9/L per day, while the lymphocytes in survivors gradually increased.

Causal effects between personality and psychiatric traits and lung cancer: a bidirectional two-sample Mendelian randomization and bibliometric study.

Introduction: The causality between personality and psychiatric traits and lung cancer (LC) remains unclear. Therefore, we aimed to elucidate the causality between these traits and LC. Methods: Bidirectional two-sample Mendelian randomization (MR) and bibliometric approaches were conducted to estimate the causality between personality (neuroticism, extraversion, agreeableness, conscientiousness, and openness) and psychiatric (schizophrenia, attention-deficit/hyperactivity disorder [ADHD], major depressive disorder, autism spectrum disorder, bipolar disorder, insomnia, and anxiety) traits and LC and its subtypes (lung squamous cell carcinoma, lung adenocarcinoma, and small cell LC). Summary data of these traits were extracted from large datasets (17,375-462,341 participants). Inverse variance weighting was used as the primary MR analysis, with supplementary models, including MR-Egger and weighted medians. Sensitivity analyses were conducted to detect pleiotropy. Bibliometric data were retrieved from the Web of Science Core Collection, Scopus, and PubMed. The main mapping techniques adopted were co-word, collaboration, and citation analyses. Results: Schizophrenia was associated with an increased risk of LC (odds ratio [OR] = 1.077, 95% confidence interval [CI] = 1.030-1.126, P = 0.001). Moreover, LC increased the risk of ADHD (OR = 1.221, 95% CI = 1.096-1.362, P < 0.001). No significant bidirectional associations were observed between other mental traits and LC and its subtypes. Causality, psychiatry, and psychiatric comorbidity are emerging keywords. Research dynamics and landscapes were revealed. Conclusion: This study suggests that schizophrenia is a risk factor for LC and that LC is a risk factor for ADHD. Furthermore, causality, psychiatry, and psychiatric comorbidity have become emerging research trends in related fields.

Vertical variation of antibiotic resistance genes and their interaction with environmental nutrients in sediments of Taihu lake.

Antibiotic resistance is a growing environmental issue. As a sink for antibiotic resistance genes (ARGs), lake surface sediments are well known for the spread of ARGs. However, the distribution pattern of ARGs and their relationship with environmental factors in vertical sediment layers are unclear. In this study, we investigated the resistome distribution in sediment cores from Taihu Lake using metagenomic analysis. The results showed that the abundance of total ARGs increased by 153% as the sediment depth rose from 0 to 50 cm, and the ARG Shannon index significantly increased. Among all the ARG types, efflux pump genes (e.g., mexT and mexW) were dominant, especially in 40-50 cm sediment. The variation in ARG with depth described above was related to the changes in bacterial adaptation to environmental gradients. Specifically, sulfate and nitrate concentrations decreased with depth, and random forest analysis showed that they were the main factors affecting the changes in ARG abundance. Environmental factors were also found to indirectly impact the distribution of ARGs by affecting the bacterial community. Potential sulfate-reducing gene/nitrate-reducing gene-ARG co-hosts were annotated through metagenomic assembly. The dominant co-hosts, Curvibacter, and Comamonas, which were enriched in deeper sediments, may have contributed to the enrichment of ARGs in deep sediments. Overall, our findings demonstrated that bacterial-mediated sulfate and nitrate reduction was closely related to sediment resistance, which provided new insights into the control of antibiotic resistance.

The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC.

Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field.

Actein ameliorates diet-induced obesity through the activation of AMPK-mediated white fat browning.

BACKGROUND: Targeting white adipose tissue (WAT) browning to increase systemic energy expenditure is a promising therapeutic strategy to combat obesity. Actein from Actaea cimicifuga L. has recently been reported to ameliorate high fat-induced hepatic steatosis. However, the effect of actein on diet-induced obesity merits more and further investigation. PURPOSE: We aimed to examine the anti-obesity potential of actein and unravel its actions on WAT browning. METHODS: The effect of actein on diet-induced obesity was evaluated using a high-fat diet model in C57BL/6 mice. Systemic energy expenditure of mice was measured with a combined indirect calorimetry system. Quantitative real-time PCR analyses were performed to investigate the mRNA levels of genes involved in thermogenesis, browning, and lipolysis. The protein levels were assessed by Western blot. Moreover, WAT explants and a transwell co-culture system consisting of SVFs and adipocytes were constructed to study the mechanisms of actein on promoting WAT browning and lipolysis. RESULTS: At a dosage of 5 mg/kg/d, actein not only protected mice against diet-induced obesity and insulin resistance, but also reversed pre-established obesity and glucose intolerance in mice. Meanwhile, actein facilitated systemic energy expenditure by activating WAT lipolysis and browning. Further, mechanistic studies revealed that actein indirectly induced epididymal adipocyte lipolysis and directly promoted a white-to-beige conversion of subcutaneous adipocytes by activating the AMPK signaling. CONCLUSION: Actein ameliorated diet-induced obesity and was discovered as a natural lead compound directly targeting white-to-beige conversion of subcutaneous adipocytes, suggesting the potential of developing new therapies for obesity and associated metabolic disorders.