Gastric cancer liver metastasis will reduce the efficacy of immunotherapy.

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells, leading to notable efficacy in patients with non-small cell lung cancer, melanoma, and other malignancies through immunotherapy utilization. However, secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression, resulting in reduced overall effectiveness of immune therapy. Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates, progression-free survival, and overall survival when secondary malignant tumors develop in the liver. Through Liu's retrospective analysis, valuable insights are provided for the future clinical management of these patients. Therefore, in patients with gastric cancer (GC), the occurrence of liver metastasis might be indicative of reduced efficacy of immunotherapy. Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.

Identification of Gene Signatures Associated with COVID-19 across Children, Adolescents, and Adults in the Nasopharynx and Peripheral Blood by Using a Machine Learning Approach.

BACKGROUND: Significant variations in immune profiles across different age groups manifest distinct clinical symptoms and prognoses in Coronavirus Disease 2019 (COVID-19) patients. Predominantly, severe COVID-19 cases that require hospitalization occur in the elderly, with the risk of severe illness escalating with age among young adults, children, and adolescents. OBJECTIVE: This study aimed to delineate the unique immune characteristics of COVID-19 across various age groups and evaluate the feasibility of detecting COVID-19-induced immune alterations through peripheral blood analysis. METHODS: By employing a machine learning approach, we analyzed gene expression data from nasopharyngeal and peripheral blood samples of COVID-19 patients across different age brackets. Nasopharyngeal data reflected the immune response to COVID-19 in the upper respiratory tract, while peripheral blood samples provided insights into the overall immune system status. Both datasets encompassed COVID-19 patients and healthy controls, with patients divided into children, adolescents, and adult age groups. The analysis included the expression levels of 62,703 genes per patient. Then, 9 feature-sequencing methods (least absolute shrinkage and selection operator, light gradient boosting machine, Monte Carlo feature selection, random forest, ridge regression, adaptive boosting, categorical boosting, extremely randomized trees, and extreme gradient boosting) were employed to evaluate the association of the genes with COVID-19. Key genes were then utilized to develop efficient classification models. RESULTS: The findings identified specific markers: insulin-like growth factor binding protein 3 (downregulated in the peripheral blood of COVID-19 patients), interferon alpha-inducible protein 27 (upregulated), and SERPING1 (upregulated in nasopharyngeal tissues). In addition, fibulin-2 was downregulated in adolescent patients, but upregulated in the other groups, while epoxide hydrolase 3 was upregulated in healthy controls, but downregulated in children and adolescents. CONCLUSION: This study offers valuable insights into the local and systemic immune responses of COVID-19 patients across age groups, aiding in identifying potential therapeutic targets and formulating personalized treatment strategies.

Aberrant CD45 Immunoreactivity in Neuroendocrine Neoplasms: A Diagnostic Pitfall-Report of 10 Specimens and Clinical Recommendations.

Leukocyte common antigen (LCA), or CD45, is classically thought of as a leukocyte-exclusive protein, and as such, CD45 immunohistochemistry (IHC) is often used as a key differentiator between non-Hodgkin lymphomas (NHLs) and morphologically similar neuroendocrine neoplasms (NENs). Herein, we report our experience regarding aberrant CD45 immunoreactivity in a series of NENs. A natural language search was used to retrieve desired archival patient files. All prior NENs which had a positive neuroendocrine diagnosis or IHC results (synaptophysin, chromogranin, CD56, and/or neuron-specific enolase), as well as CD45 staining performed, were reviewed for possible CD45 positivity (n = 686). Among these 686 NENs, 10 were aberrantly positive for CD45 staining. CD45 showed nuclear, cytoplasmic, and/or membranous staining in tumor cells. The significance of such staining is unclear. Albeit for a minority of patients, pathologists should be aware that NENs may aberrantly stain with CD45 and thereby pose a diagnostic pitfall. Therefore, broadening routine IHC panels is recommended to differentiate NENs more clearly from NHLs.

Salidroside treatment decreases the susceptibility of atrial fibrillation in diabetic mice by reducing mTOR-STAT3-MCP-1 signaling and atrial inflammation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinic, and type 2 diabetes mellitus (T2DM) is an independent risk factor for AF. Salidroside (Sal), the active ingredient of the Rhodiola rosea, has hypoglycemic, anti-inflammatory, anti-fibrotic and anti-arrhythmic effects. The aim of this study is to investigate the effects and underlying molecular mechanisms of Sal on T2DM associated atrial inflammation and the pathogenesis of AF. In the in vivo study, T2DM mice model was established by high-fat diet and intraperitoneal injection of streptozotocin (STZ). Sal (25 mg/kg/d, 50 mg/kg/d, and 100 mg/kg/d) was administered orally for 4 weeks. T2DM caused atrial electrical and structural remodeling and significantly increased the susceptibility of AF. Meanwhile, mTOR-STAT3-MCP-1 signaling and inflammatory markers were also significantly enhanced in diabetic atria. However, Sal dose-dependently ameliorated cardiac dysfunction, mitigated atrial structural and electrical remodeling, and reduced atrial inflammation. Moreover, Sal-treated group exhibited remarkably down-regulated activity of mTOR-STAT3-MCP-1 pathway, and decreased atrial monocyte/macrophage infiltration. In palmitic acid (PA)-challenged HL-1 cells, Sal attenuated cytotoxicity, downregulated the expressions of TNF-α, IL-6, MCP-1, and inhibited the activation of mTOR-STAT3 signaling. However, co-treatment with MHY1485 (a mTOR agonist) reversed these effects. Taken together, the present study demonstrates that Sal treatment decreases the susceptibility of AF in diabetic mice by reducing mTOR-STAT3-MCP-1 signaling and atrial monocyte/macrophage infiltration. Sal treatment may represent a novel preventive therapy for cardiac arrhythmia and atrial fibrillation in diabetic patients.

In Situ Fabrication of Highly Efficient and Stable Cs2NaInCl6: Sb3+@PVDF Composite Films for Optoelectronic Devices.

Lead-free double perovskites (DPs) have superior phase stability and optical properties, which make them competitive for future applications in illumination and displays. However, the preparation of DPs was mainly based on high-temperature heating and hydrochloric acid as a solvent to form powders, which increased the risk and cost of the preparation process and limited its further application. In this study, the growth of Cs2NaInCl6: Sb3+ DPs in polyvinylidene difluoride (PVDF) films was achieved using an in situ fabrication strategy with DMSO as the solvent. The prepared Cs2NaInCl6: Sb3+@PVDF composite films (CFs) can achieve a bright blue emission under 302 nm irradiation. To achieve the optimal luminescent performance of CFs, the photoluminescence (PL) intensity of Cs2NaInCl6: Sb3+@PVDF CFs under various in situ preparation conditions was compared. In addition, the photoluminescence quantum yield (PLQY) of CFs was increased from 0.72% to 83.77% by adjusting the doping amount of Sb3+, and the fluorescence lifetimes t1 and t2 were 131.08 and 1048.52 ns, respectively. Temperature-dependent PL spectroscopy and density functional theory (DFT) calculations indicate that these excellent optical properties are derived from the self-trapped excitons (STEs) at the [SbCl6]3- octahedron and [InCl6]3- octahedron connected via Cl-Na-Cl. The CFs also demonstrated excellent environmental stability, maintaining a relatively stable PL intensity even under conditions of water immersion, high temperatures, and ultraviolet (UV) radiation. Finally, we used the CFs to assemble a blue light-emitting device (LED), which showed good and stable blue emission performance at different currents. This work can provide a new idea for preparing DPs, which is conducive to promoting their commercial application in high-performance optoelectronic devices.

Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study.

BACKGROUND: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. METHODS: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. RESULTS: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). CONCLUSIONS: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

Research progress and application prospect of adipose-derived stem cell secretome in diabetes foot ulcers healing.

Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

Effect of whole-body cryotherapy on recovery after high-intensity training in elite rowers.

The purpose of this study was to investigate the effect of whole-body cryotherapy (WBC) on acute recovery after a single high-intensity training day. Twelve elite professional male rowers from the national aquatic training base. They were randomly divided into a WBC group (n = 6) and a control group (CON group, n = 6). They performed a high-intensity training program, with a single session immediately followed by WBC (-110°C, 3 min) or recovered naturally for 3 min (CON group). Rowing performance, skin temperature, heart rate, blood pressure, and blood lactate concentrations were recorded before training, immediately, 5 min, and 15 min after the intervention. Blood samples were collected early in the morning of the day of intervention and that of the following day. The results indicated that 1) the blood lactate concentrations after WBC were significantly lower than pre-training (p < 0.05); 2) the maximum power significantly decreased immediately after WBC compared to pre-training (p < 0.05); 3) a significant main effect of time was observed for average speed, which significantly decreased after WBC (p < 0.05); 4) a significant main effect of time for blood parameters was observed. Specifically, hematocrit, cortisol, and hemoglobin were significantly lower after WBC than pre-intervention, whereas testosterone/cortisol was significantly higher than pre-intervention (p < 0.05). The results of this study showed that a single session of WBC had a positive effect on accelerating the elimination of blood lactate after HIT, but did not significantly change rowing performance and physiological parameters. A single session of WBC was not an effective strategy for elite rowers for acute recovery after HIT.

Phenotypic age mediates effects of Life's Essential 8 on reduced mortality risk in US adults.

Objective: This study aimed to find out whether phenotypic age could mediate the protective effects of a healthy lifestyle on mortality. Methods: We included adult participants with available data for individual phenotypic age (PhenoAge) and Life's Essential 8 (LE8) scores from the National Health and Nutrition Examination Survey 2005-2010 (three cycles) and linked mortality records until 31 December 2019. Adjusted hazard ratios (HR) were estimated to evaluate the associations of PhenoAge and LE8 scores with all-cause and cardiovascular mortality risk. Mediation analyses were performed to estimate the proportional contribution of PhenoAge to the effect of LE8 on mortality risks. Results: A 1-year increment in PhenoAge was associated with a higher risk of all-cause (HR = 1.04 [95% confidence interval, 1.04-1.05]) and cardiovascular (HR = 1.04 [95% confidence interval, 1.04-1.05]) mortality, independent of chronological age, demographic characteristics, and disease history. High level of LE8 (score: 80-100) was associated with a 3.30-year younger PhenoAge. PhenoAge was estimated to mediate 36 and 22% of the effect of LE8 on all-cause and cardiovascular mortality, respectively (all P < 0.001). As for single-metric scores of LE8, PhenoAge mediated 30%, 11%, 9%, and 7% of the effects of the healthy diet, smoking status, blood pressure, and physical activity on all-cause mortality risk, respectively (all P < 0.05). Conclusion: Adherence to LE8 recommendations slows phenotypic aging. PhenoAge could mediate the effect of LE8 on mortality risk.

Harnessing the power of bioprinting for the development of next-generation models of thrombosis.

Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.

Identification of endoplasmic reticulum stress-associated genes and subtypes for predicting risk signature and depicting immune features in inflammatory bowel disease.

Endoplasmic reticulum stress (ERS) becomes a significant factor in inflammatory bowel disease (IBD), like Crohn's disease (CD) and ulcerative colitis (UC). Our research was aimed at identifying molecular markers to enhance our understanding of ERS and inflammation in IBD, recognizing risk factors and high-risk groups at the molecular level, and developing a predictive model on the grounds of based on ERS-associated genes. This research adopted the least absolute shrinkage and selection operator (LASSO) regression and logistic regression to build a predictive model, and categorized IBD patients into high- and low-risk groups, and then identified four gene clusters. Our key findings included a significant increase in drug target gene expression in high-risk groups, notable discrepancies in immune levels, and functions between high-risk and low-risk groups. Notably, the TAP1 gene emerged as a strong predictor with the highest diagnostic value (area under the curve [AUC] = 0.941). TAP1 encodes proteins required for antigenic peptide transfer across the endoplasmic reticulum (ER) membrane, and its potential as a diagnostic marker and therapeutic target is reflected by its overexpression in IBD tissues. Our study established a new ERS-associated gene model which could forecast the risk, immunological status, and treatment efficacy of patients with IBD. These findings suggest potential targets for personalized therapy and highlight the significance of ERS in the etiology and therapy of IBD. Future studies should explore the therapeutic potential of targeting TAP1 and other ERS-related genes for IBD management.

Structural Regulation Enables High Interfacial Functionality for Ni-Rich Single-Crystalline Cathodes.

Ni-rich single-crystalline layered cathodes have garnered significant attention due to their high energy density and thermal stability. However, they experience severe capacity degradation caused by lattice strain and interfacial side reactions during practical applications. In this study, an effective yttrium modification method is employed to stabilize the structure of Ni-rich single-crystalline LiNi0.83Mn0.05Co0.12O2 (SC-NMC83) to solve these issues. This innovative approach successfully immobilizes oxygen within the material, preventing crack formation while simultaneously broadening the diffusion path of Li+. The yttrium-modified sample (SC-NMC83-Y) exhibits a superior capacity retention compared to the SC-NMC83 sample, with values of 90% and 76.1% after 100 cycles, respectively. This work demonstrates the promising potential of a doping strategy for Ni-rich single-crystalline cathodes and paves a pathway for its practical implementation, such as all-solid-state batteries.

Therapeutic effects of Lianhua Qingke on COPD and influenza virus-induced exacerbation of COPD are associated with the inhibition of NF-κB signaling and NLRP3 inflammasome responses.

Lianhua Qingke (LHQK), a traditional Chinese medicine (TCM) used clinically for the treatment of respiratory diseases with acute tracheobronchitis, and cough, has demonstrated promising efficacy in suppressing inflammation, inhibitingmucin secretion, reducing goblet cell hyperplasia andmaintainingairway epithelial integrity. However, its efficacy in managing chronic obstructive pulmonary disease (COPD) progression, particularly virus-induced acute exacerbations of COPD (AECOPD),remains unclear. Here, cigarette smoke (CS)-induced COPD and CS+virus (influenza H1N1)-triggered AECOPD mouse models were employed to evaluated the therapeutic potential of LHQK. The findings demonstrated that LHQK treatment led to significant improved pulmonary function, suppressed pulmonary inflammation, alleviated lung histopathological changes, and preserved airway epithelial integrity in COPD mice. Additionally, LHQK treatment effectively inhibited viral replication in the lungs of AECOPD mice and decreased recruitment of immune cells (M1 macrophages, progenitor-exhausted T cells and CD8 + T cells) to the lungs. Western blot analysis indicated that the therapeutic effects of LHQK are associated with the inhibition ofNF-κB signaling and NLRP3 inflammasome activation. Collectively, these findings elucidate the underlying mechanisms by which LHQK mitigates COPD and AECOPD, thereby supporting its potential as a therapeutic option for individuals afflicted with these conditions.

Association between different stages of cardiovascular-kidney-metabolic syndrome and the risk of all-cause mortality.

BACKGROUND AND AIMS: Poor cardiovascular-kidney-metabolic (CKM) health is a major determinant of all-cause mortality, which poses a significant burden on global public health systems and socio-economics. However, the association between different stages of CKM syndrome and the risk of all-cause mortality remains unclear. This study aimed to evaluate the association between different stages of CKM syndrome and risk of all-cause mortality. METHODS: A total of 97,777 adults from the Kailuan Study were included. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause mortality according to different stages of CKM syndrome. RESULTS: Over a median follow-up of 15.0 (14.7-15.2) years, we identified 14,805 all-cause mortality cases. The stage of CKM syndrome was positively associated with the risk of all-cause mortality (p-trend <0.001). Compared with Stage 0, the multivariable-adjusted HRs (95 % CIs) of all-cause mortality were 1.24 (1.06-1.45) for Stage 1, 1.72 (1.48-2.00) for Stage 2, 2.58 (2.22-3.01) for Stage 3 and 3.73 (3.19-4.37) for Stage 4. Moreover, the observed associations were more pronounced in younger adults (aged <60 years) compared with older adults (p for interaction <0.001). CONCLUSIONS: Our data showed that a higher stage of CKM syndrome was associated with a higher risk of all-cause mortality, with a particularly pronounced association observed in younger adults. The study emphasized the need for targeted public health strategies and clinical management tailored to the stages of CKM syndrome, aiming to alleviate its burden on individuals and healthcare systems.

Effects of Different Photoperiods on the Transcriptome of the Ovary and Small White Follicles in Zhedong White Geese.

Photoperiod can regulate the broodiness of geese and thus increase their egg-laying rate. The laying performance of geese is mainly determined by ovary and follicle development. To understand the effect of photoperiod on the ovary and small white follicles, sixteen 220-day-old healthy female Zhedong white geese were randomly divided into two groups for long photoperiods (15L:9D) and short photoperiods (9L:15D). The geese were euthanized after two months of feeding, and their ovaries and follicles were collected for transcriptome sequencing. RNA-seq analysis identified 187 and 448 differentially expressed genes in ovaries and small white follicles of different photoperiod groups, respectively. A long photoperiod promotes high expression of SPP1, C6, MZB1, GP1BA, and FCGBP genes in the ovaries, and increases the expression of SPP1, ANGPTL5, ALPL, ZP1, and CHRNA4 genes in small white follicles. Functional enrichment analysis showed that photoperiod could affect respiratory system development, smooth muscle cell proliferation in ovaries, and extracellular matrix-related function in small white follicles. WGCNA revealed 31 gene modules, of which 2 were significantly associated with ovarian weight and 17 with the number of small white follicles. Our results provide a better understanding of the molecular regulation in the photoperiod affecting goose reproduction.

The metabolic signature of blood lipids: a causal inference study using twins.

Dyslipidemia is one of the cardiometabolic risk factors that influences mortality globally. Unraveling the causality between blood lipids and metabolites and the complex networks connecting lipids, metabolites, and other cardiometabolic traits can help to more accurately reflect the body's metabolic disorders and even cardiometabolic diseases. We conducted targeted metabolomics of 248 metabolites in 437 twins from the Chinese National Twin Registry. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) analysis was used for causal inference between metabolites and lipid parameters. Bidirectional mediation analysis was performed to explore the linkages between blood lipids, metabolites, and other seven cardiometabolic traits. We identified 44, 1, and 31 metabolites associated with triglyceride (TG), total cholesterol (TC), and high-density lipoprotein-cholesterol (HDL-C), most of which were gut microbiota-derived metabolites. There were 9, 1, and 14 metabolites that showed novel associations with TG, TC, and HDL-C, respectively. ICE FALCON analysis found that TG and HDL-C may have a predicted causal effect on 23 and six metabolites, respectively, and one metabolite may have a predicted causal effect on TG. Mediation analysis discovered 14 linkages connecting blood lipids, metabolites, and other cardiometabolic traits. Our study highlights the significance of gut microbiota-derived metabolites in lipid metabolism. Most of the identified cross-sectional associations may be due to the lipids having a predicted causal effect on metabolites, but not vice versa, nor are they due to family confounding. These findings shed new light on lipid metabolism and personalized management of cardiometabolic diseases.

Prediction of Solubility of Proteins in Escherichia coli Based on Functional and Structural Features Using Machine Learning Methods.

Protein solubility is a critical parameter that determines the stability, activity, and functionality of proteins, with broad and far-reaching implications in biotechnology and biochemistry. Accurate prediction and control of protein solubility are essential for successful protein expression and purification in research and industrial settings. This study gathered information on soluble and insoluble proteins. In characterizing the proteins, they were mapped to STRING and characterized by functional and structural features. All functional/structural features were integrated to create a 5768-dimensional binary vector to encode proteins. Seven feature-ranking algorithms were employed to analyze the functional/structural features, yielding seven feature lists. These lists were subjected to the incremental feature selection, incorporating four classification algorithms, one by one to build effective classification models and identify functional/structural features with classification-related importance. Some essential functional/structural features used to differentiate between soluble and insoluble proteins were identified, including GO:0009987 (intercellular communication) and GO:0022613 (ribonucleoprotein complex biogenesis). The best classification model using support vector machine as the classification algorithm and 295 optimized functional/structural features generated the F1 score of 0.825, which can be a powerful tool to differentiate soluble proteins from insoluble proteins.

Global Gridded Emission Inventory of Organophosphate Flame Retardants from 2010 to 2020.

As a substitute for brominated flame retardants, organophosphate flame retardants (OPFRs) have become a global concern due to their high toxicity and bioaccumulation. To paint an overall picture of OPFRs in the global environment, the present study develops a gridded global emission inventory of OPFRs on a spatial resolution of 1 × 1° from 2010 to 2020. Revealing a 3.31% average annual increase in emissions, totaling 21,324.42 tons. The production process is the primary source, accounting for 55.43% of emissions, with consumption processes making up the rest. Major sources are in Asia, North America, and Europe. The inventory is verified by implementing emission data into a global atmospheric transport model to predict OPFR concentrations in the global environment and comparing modeled concentrations with field sampled data. The results indicate that the inventory is reliable except for the pristine polar region, where the emission inventory and modeled concentrations underestimate OPFR levels in the atmosphere, likely resulting from ignorance of chemical reactions and the secondary derivative of parent OPFRs during their global long-distance atmospheric transport in the model. This comprehensive data set aids in formulating OPFR emission control policies and assessing health risks.

Cpt1a Drives primed-to-naïve pluripotency transition through lipid remodeling.

Metabolism has been implicated in cell fate determination, particularly through epigenetic modifications. Similarly, lipid remodeling also plays a role in regulating cell fate. Here, we present comprehensive lipidomics analysis during BMP4-driven primed to naive pluripotency transition or BiPNT and demonstrate that lipid remodeling plays an essential role. We further identify Cpt1a as a rate-limiting factor in BiPNT, driving lipid remodeling and metabolic reprogramming while simultaneously increasing intracellular acetyl-CoA levels and enhancing H3K27ac at chromatin open sites. Perturbation of BiPNT by histone acetylation inhibitors suppresses lipid remodeling and pluripotency transition. Together, our study suggests that lipid remodeling promotes pluripotency transitions and further regulates cell fate decisions, implicating Cpt1a as a critical regulator between primed-naive cell fate control.

Relationship Between Control of Cardiovascular Risk Factors and Chronic Kidney Disease Progression, Cardiovascular Disease Events, and Mortality in Chinese Adults.

BACKGROUND: Patients with chronic kidney disease (CKD) are at an elevated risk of cardiovascular disease (CVD) and premature mortality compared to the general population. OBJECTIVES: This study aimed to investigate whether the excess risk of CVD events and death among patients with CKD could be reduced or eliminated through strict control of blood pressure (systolic blood pressure: <130 mm Hg), lipids (low-density lipoprotein cholesterol: <2.6 mmol/L), and glucose (fasting blood glucose: <6.1 mmol/L). METHODS: The authors included 20,254 patients with CKD who were free of CVD or end-stage renal disease and matched them with 35,236 control individuals based on age (±2 years) and sex from the Kailuan study. RESULTS: During a median follow-up period of 12.2 to 12.8 years, 3,875 deaths, 1,888 cases of stroke, 513 cases of myocardial infarction, and 4,825 cases of CKD progression were documented. Among patients with CKD, risk factor controls showed an association with a reduction in myocardial infarction, stroke, CKD progression, and all-cause mortality risk in a dose-dependent manner. Moreover, compared to the non-CKD control individuals, having all 3 risk factors within the target ranges could theoretically eliminate the excess risk of CVD and mortality associated with CKD. Among patients with CKD who had all 3 risk factors controlled, the HRs were 0.80 (95% CI: 0.56-1.14) for myocardial infarction, 0.93 (95% CI: 0.78-1.12) for stroke, and 1.10 (95% CI: 0.98-1.24) for all-cause mortality compared to the non-CKD control individuals. CONCLUSIONS: Patients with CKD who had controlled blood pressure, lipids, and glucose showed no excess risk of death, myocardial infarction, or stroke compared to the general population.