m6A epitranscriptomic modification of inflammation in cardiovascular disease.

Cardiovascular disease is currently the number one cause of death endangering human health. There is currently a large body of research showing that the development of cardiovascular disease and its complications is often accompanied by inflammatory processes. In recent years, epitranscriptional modifications have been shown to be involved in regulating the pathophysiological development of inflammation in cardiovascular diseases, with 6-methyladenine being one of the most common RNA transcriptional modifications. In this review, we link different cardiovascular diseases, including atherosclerosis, heart failure, myocardial infarction, and myocardial ischemia-reperfusion, with inflammation and describe the regulatory processes involved in RNA methylation. Advances in RNA methylation research have revealed the close relationship between the regulation of transcriptome modifications and inflammation in cardiovascular diseases and brought potential therapeutic targets for disease diagnosis and treatment. At the same time, we also discussed different cell aspects. In addition, in the article we also describe the different application aspects and clinical pathways of RNA methylation therapy. In summary, this article reviews the mechanism, regulation and disease treatment effects of m6A modification on inflammation and inflammatory cells in cardiovascular diseases in recent years. We will discuss issues facing the field and new opportunities that may be the focus of future research.

Characterization and potential lipid-lowering effects of lactic acid bacteria isolated from cats.

Introduction: This study aimed to study the characterization and the potential lipid-lowering effects of new isolated lactic acid bacteria from the feces of healthy adult cats. Methods: We collected 85 cat fecal samples, isolated, screening lactic acid bacteria strains from samples, and investigated their in vitro and in vivo biological properties. Results: A total of 221 lactic acid bacteria strains were isolated from 85 cat fecal samples. Sixteen strains with calcium dissolution rings greater than 1 mm were identified and selected for further characterization. Three lactic acid bacteria strains, Lactobacillus plantarum L-27-2, Pediococcus lactis L-14-1, and Enterococcus faecium, were identified as showing the most promising rates of cholesterol degradation (greater than 20%) and bacteriostatic radius (over 15 mm). These three strains exhibited robust growth and adherence to epithelial cells, along with adaptability to low pH (greater than 70%) and high bile salt conditions (greater than 60%), and remarkable cholesterol degradation and anti-pathogen activity. Sixteen mice were fed a high-fat diet (HFD) from 4 to 8 weeks of age, while a control group of the same size received a normal diet (ND). At 8 weeks of age, serum, feces and adipose tissue were collected. The results showed that, compared with mice fed an HFD diet alone, all mice fed an HFD diet plus lactic acid bacteria could decrease weight gain. P < 0.05 and the pathological changes of adipose tissue were alleviated. In addition, mice fed L-14-1 and F203 showed abdominal fat accumulation decreased (P < 0.05). Mice fed L-27-2 showed serum and liver triglyceride (TG) decreased (P < 0.05) and mice fed F203 showed serum high density lipoprotein cholesterol (HDL-C) increased (P < 0.01). mice fed L-27-2 and L-14-1 showed inflammatory cytokines (IL-6) was decreased (P < 0.01) Analysis of the fecal microbiota of mice fed these three lactic acid bacteria strains revealed alterations in the gut microbial community. There were common changes in intestinal microbes in mice fed these three lactic acid bacteria: (1) Bacteroides decreased; (2) Myxococcus increased; (3) Lachnoclostridium decreased. The microbes mentioned are all part of the core intestinal flora. Discussion: This study provided three potential lactic acid bacteria for alleviating animal obesity and inflammation.

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases.

Terpenoids are one of the largest class of natural products with diverse structures and activities. This enormous diversity is embedded in enzymes called terpene synthases (TSs), which generate diverse terpene skeletons via sophisticated cyclization cascades. In addition to the many highly selective TSs, there are many promiscuous TSs that accept multiple prenyl substrates, or even noncanonical ones, with 6, 7, 8, 11, and 16 carbon atoms, synthesized via chemical approaches, C-methyltransferases, or engineered lepidopteran mevalonate pathways. The substrate promiscuity of TSs not only expands the structural diversity of terpenes but also highlights their potential for the discovery of novel terpenoids via combinatorial biosynthesis. In this review, we focus on the current knowledge on multisubstrate terpene synthases (MSTSs) and highlight their potential applications.

Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan-Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan-Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

An Online Digital Imaging Excitation Sensor for Wind Turbine Gearbox Wear Condition Monitoring Based on Adaptive Deep Learning Method.

This paper designed and developed an online digital imaging excitation sensor for wind power gearbox wear condition monitoring based on an adaptive deep learning method. A digital imaging excitation sensing image information collection architecture for magnetic particles in lubricating oil was established to characterize the wear condition of mechanical equipment, achieving the real-time online collection of wear particles in lubricating oil. On this basis, a mechanical equipment wear condition diagnosis method based on online wear particle images is proposed, obtaining data from an engineering test platform based on a wind power gearbox. Firstly, a foreground segmentation preprocessing method based on the U-Net network can effectively eliminate the interference of bubbles and dark fields in online wear particle images, providing high-quality segmentation results for subsequent image processing, A total of 1960 wear particle images were collected in the experiment, the average intersection union ratio of the validation set is 0.9299, and the accuracy of the validation set is 0.9799. Secondly, based on the foreground segmentation preprocessing of wear particle images, by using the watered algorithm to obtain the number of particles in each size segment, we obtained the number of magnetic particle grades in three different ranges: 4-38 µm, 39-70 µm, and >70 µm. Thirdly, we proposed a method named multidimensional transformer (MTF) network. Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE) are used to obtain the error, and the maintenance strategy is formulated according to the predicted trend. The experimental results show that the predictive performance of our proposed model is better than that of LSTM and TCN. Finally, the online real-time monitoring system triggered three alarms, and at the same time, our offline sampling data analysis was conducted, the accuracy of online real-time monitoring alarms was verified, and the gearbox of the wind turbine was shut down for maintenance and repair.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

Pentraxin-3 and Outcomes in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Long pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. In addition, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of patients with CKD. Study Design: A systematic review and meta-analysis. Setting & Participants: Patients with CKD treated with or without dialysis. Selection Criteria for Studies: A cohort study with a minimum 1-year follow-up. Data Extraction: Risk measurements, adjusted hazard risk with 95% CI, and modified variables. Analytical Approach: To aggregate the adjusted effect estimates, a fixed-effects or random-effects model was employed. Results: Nine studies covering 1,825 patients with CKD were selected in the present review. Six of the 9 studies exclusively included patients receiving hemodialysis. The collected findings indicated that patients with CKD in the highest tertile of PTX-3 demonstrated significantly higher risks of all-cause mortality (HR, 1.92; 95% CI, 1.44-2.56), cardiovascular death (HR, 1.98; 95% CI, 1.28-3.05), infectious death (HR, 5.26; 95% CI, 1.60-17.31), and fatal and nonfatal cardiovascular events (HR, 1.81; 95% CI, 1.35-2.42), as compared with those in the lowest tertile. These significant associations with risk were also observed when effect estimates were presented as per unit change in the PTX-3. Moreover, when comparing the prognostic value of PTX-3 and CRP in the same individuals (5 studies covering 904 patients), PTX-3 proved to be a satisfactory predictor of adverse events in these patients, whereas CRP failed to exhibit such predictive capability, regardless of the type of effect estimate used. Limitations: A relatively small sample size and some heterogeneity. Conclusions: Pentraxin 3 is associated with adverse events in individuals with CKD and may be a more reliable predictor of adverse clinical events than CRP in this population.

Systemic inflammatory markers are useful in predicting the prognosis of patients with CKD. Pentraxin-3 (PTX-3) is an emerging biomarker of inflammation compared with other members of the pentraxin family, such as C-reactive protein (CRP). This meta-analysis evaluated the prognostic value of PTX-3 in predicting adverse outcomes in patients with CKD. Also, we compared the prognostic values between PTX-3 and CRP in the subset of studies with data on CRP. We found that patients with CKD with higher circulating PTX-3 levels had a significantly heightened risk of adverse outcomes compared with those with lower PTX-3 levels. By contrast, CRP did not appear to be a good predictor of adverse events. Pentraxin-3 might be a more reliable prognostic marker than CRP in patients with CKD.

Exosomes for neurodegenerative diseases: diagnosis and targeted therapy.

PURPOSE OF REVIEW: Neurodegenerative diseases are still challenging clinical issues, with no curative interventions available and early, accurate diagnosis remaining difficult. Finding solutions to them is of great importance. In this review, we discuss possible exosomal diagnostic biomarkers and explore current explorations in exosome-targeted therapy for some common neurodegenerative diseases, offering insights into the clinical transformation of exosomes in this field. RECENT FINDINGS: The burgeoning research on exosomes has shed light on their potential applications in disease diagnosis and treatment. As a type of extracellular vesicles, exosomes are capable of crossing the blood - brain barrier and exist in various body fluids, whose components can reflect pathophysiological changes in the brain. In addition, they can deliver specific drugs to brain tissue, and even possess certain therapeutic effects themselves. And the recent advancements in engineering modification technology have further enabled exosomes to selectively target specific sites, facilitating the possibility of targeted therapy for neurodegenerative diseases. The unique properties of exosomes give them great potential in the diagnosis and treatment of neurodegenerative diseases, and provide novel ideas for dealing with such diseases.

Monoaxial Screws Versus Polyaxial Screws Osteosynthesis for Unstable Atlas Fractures: A Retrospective, Comparative Study With a Minimum Follow-Up of 3 years.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The study aimed to compare the radiological parameters, clinical outcomes, and long-term effects of the posterior osteosynthesis with polyaxial screw-rod system and the monoaxial screw-rod system in the treatment of unstable atlas fractures. METHODS: We retrospectively analyzed the clinical data of 33 patients with posterior ORIF for unstable atlas fractures in our hospital from August 2013 to June 2020, with a minimum of 3 years of follow-up. Polyaxial screws (group A) were used in 12 patients and monoaxial screws (group B) in 21 patients. Perioperative data, radiological parameters, and clinical outcomes were collected and compared between the 2 surgical approaches. RESULTS: The operative time, blood loss, time of screw-rod system placement, and hospital stay were significantly lower in group A than in group B. At the last follow-up, the visual analog scale (VAS) score and anterior arch reduction rate of the atlas in group A were lower than those in group B, while the lateral mass displacement (LMD) in group A was higher than that in group B. There was no significant difference between Group A and Group B in terms of the anterior atlantodental interval (AADI), posterior arch reduction rate of the atlas, range of motion (ROM), and neck disability index (NDI). CONCLUSIONS: Monoaxial screws can achieve better reduction results for unstable atlas fractures, especially for the anterior arch of atlas. However, the surgical operation of monoaxial screws is more complicated than that of polyaxial screws and has more complications. Appropriate implants should be selected for the treatment of unstable atlas fractures based on the type of atlas fracture, the experience of surgeons, and the demands of patients.

TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation.

BACKGROUND: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated. METHODS: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl4) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte. RESULTS: Herein, we report that the expression level of ENPP1 are increased in patients with NAFLD liver tissue and in mouse model of NAFLD. Hypomethylation of ENPP1, is associated with the perpetuation of hepatocyte autophagy and liver fibrosis in the NAFLD. ENPP1 hypomethylation is mediated by the DNA demethylase TET3 in NAFLD liver fibrosis and hepatocyte autophagy. Additionally, knockdown of TET3 methylated ENPP1 promoter, reduced the ENPP1 expression, ameliorated the experimental NAFLD. Mechanistically, TET3 epigenetically promoted ENPP1 expression via hypomethylation of the promoter. Knocking down TET3 can inhibit the hepatocyte autophagy but an overexpression of ENPP1 showing rescue effect. CONCLUSIONS: We describe a novel epigenetic mechanism wherein TET3 promoted ENPP1 expression through promoter hypomethylation is a critical mediator of NAFLD. Our findings provide new insight into the development of preventative measures for NAFLD.

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs).

With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.

Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

Structure-guided discovery of protein and glycan components in native mastigonemes.

Mastigonemes, the hair-like lateral appendages lining cilia or flagella, participate in mechanosensation and cellular motion, but their constituents and structure have remained unclear. Here, we report the cryo-EM structure of native mastigonemes isolated from Chlamydomonas at 3.0 Å resolution. The long stem assembles as a super spiral, with each helical turn comprising four pairs of anti-parallel mastigoneme-like protein 1 (Mst1). A large array of arabinoglycans, which represents a common class of glycosylation in plants and algae, is resolved surrounding the type II poly-hydroxyproline (Hyp) helix in Mst1. The EM map unveils a mastigoneme axial protein (Mstax) that is rich in heavily glycosylated Hyp and contains a PKD2-like transmembrane domain (TMD). Mstax, with nearly 8,000 residues spanning from the intracellular region to the distal end of the mastigoneme, provides the framework for Mst1 assembly. Our study provides insights into the complexity of protein and glycan interactions in native bio-architectures.

Effects of polystyrene microplastics on the metabolic level of Pseudomonas aeruginosa.

Given the widespread presence of Pseudomonas aeruginosa in water and its threat to human health, the metabolic changes in Pseudomonas aeruginosa when exposed to polystyrene microplastics (PS-MPs) exposure were studied, focusing on molecular level. Through non-targeted metabolomics, a total of 64 differential metabolites were screened out under positive ion mode and 44 under negative ion mode. The content of bacterial metabolites changed significantly, primarily involving lipids, nucleotides, amino acids, and organic acids. Heightened intracellular oxidative damage led to a decrease in lipid molecules and nucleotide-related metabolites. The down-regulation of amino acid metabolites, such as L-Glutamic and L-Proline, highlighted disruptions in cellular energy metabolism and the impaired ability to synthesize proteins as a defense against oxidation. The impact of PS-MPs on organic acid metabolism was evident in the inhibition of pyruvate and citrate, thereby disrupting the cells' normal participation in energy cycles. The integration of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that PS-MPs mainly caused changes in metabolic pathways, including ABC transporters, Aminoacyl-tRNA biosynthesis, Purine metabolism, Glycerophospholipid metabolism and TCA cycle in Pseudomonas aeruginosa. Most of the differential metabolites enriched in these pathways were down-regulated, demonstrating that PS-MPs hindered the expression of metabolic pathways, ultimately impairing the ability of cells to synthesize proteins, DNA, and RNA. This disruption affected cell proliferation and information transduction, thus hampering energy circulation and inhibiting cell growth. Findings of this study supplemented the toxic effects of microplastics and the defense mechanisms of microorganisms, in turn safeguarding drinking water safety and human health.

Spatial variations of DOM in a diverse range of lakes across various frozen ground zones in China: Insights into molecular composition.

Dissolved organic matter (DOM) plays a significant role in aquatic biogeochemical processes and the carbon cycle. As global climate warming continues, it is anticipated that the composition of DOM in lakes will be altered. This could have significant ecological and environmental implications, particularly in frozen ground zones. However, there is limited knowledge regarding the spatial variations and molecular composition of DOM in lakes within various frozen ground zones. In this study, we examined the spatial variations of in-lake DOM both quantitatively, focusing on dissolved organic carbon (DOC), and qualitatively, by evaluating optical properties and conducting molecular characterization using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Lakes in cold regions retained more organic carbon compared to those in warmer regions, the comparison of the mean value of DOC concentration of all sampling sites in the same frozen ground zone showed that the highest mean lake DOC concentration found in the permafrost zone at 21.4 ± 19.3 mg/L. We observed decreasing trends in E2:E3 and MLBL, along with increasing trends in SUVA254 and AImod, along the gradually warming ground. These trends suggest lower molecular weight, reduced aromaticity, and increased molecular lability of in-lake DOM in the permafrost zone compared to other frozen ground zones. Further FT-ICR MS characterization revealed significant molecular-level heterogeneity of DOM, with the lowest abundance of assigned DOM molecular formulas found in lakes within permafrost zones. In all studied zones, the predominant molecular formulas in-lake DOM were compounds consisted by CHO elements, accounting for 40.1 % to 63.1 % of the total. Interestingly, the percentage of CHO exhibited a gradual decline along the warming ground, while there was an increasing trend in nitrogen-containing compounds (CHON%). Meanwhile, a substantial number of polyphenols were identified, likely due to the higher rates of DOM mineralization and the transport of terrestrial DOM derived from vascular plants under the elevated temperature and precipitation conditions in the warming region. In addition, sulfur-containing compounds (CHOS and CHNOS) associated with synthetic surfactants and agal derivatives were consistently detected, and their relative abundances exhibited higher values in seasonal and short-frozen ground zones. This aligns with the increased anthropogenic disturbances to the lake's ecological environment in these two zones. This study reported the first description of in-lake DOM at the molecular level in different frozen ground zones. These findings underline that lakes in the permafrost zone serve as significant hubs for carbon processing. Investigating them may expand our understanding of carbon cycling in inland waters.

Deciphering the relationship between the ordered pore structure and solid-phase microextraction behavior of covalent organic frameworks for phenols.

The extraction performance of materials is highly related to their physical structure. However, the precise impact of ordered pore structure in covalent organic frameworks (COFs) on extraction performance are still puzzling. To look insight into this, a series of COFs with varying degrees of ordered pore structures were prepared at room temperature by adjusting reaction time and their extraction efficiencies toward phenolic compounds were investigated. The experimental results revealed that the COF with a short range ordered pore structure exhibited a higher affinity for phenolic compounds along with a larger enrichment factor, while the COF with a long range ordered pore structure demonstrated faster extraction kinetics. The investigation into interaction mechanism revealed that the density of available sites is responsible for these differences. Taking COF-OMe-0.5 h as solid-phase microextraction fiber coating, a highly efficient and sensitive quantitative analysis method for phenolic compounds was established by combining it with gas chromatograph-mass spectrometer. The established method boasts high enrichment factors (7192-29440), wide linear ranges (2.0-10000 ng L-1), and low detection limits (0.24-0.54 ng L-1). This study provides a conceptual guide for constructing desirable COFs with controlled pore structures for specific applications.

Projected population exposure to heatwaves in Xinjiang Uygur autonomous region, China.

The intensification of heatwaves dues to climate change is a significant concern, with substantial impacts on ecosystems and human health, particularly in developing countries. This study utilizes NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP-CMIP6) and projected population data accounting for China's population policies to project changes in various grades of heatwaves (light, moderate, and severe) and the population exposure to heatwaves (PEH) in Xinjiang under three shared socioeconomic pathways (SSP1-2.6, SSP2-4.5, and SSP5-8.5). The results show that the number of days and intensity of heatwaves in Xinjiang are projected to increase. Heatwaves occurring in Xinjiang will predominantly be severe heatwaves (SHW) in the long-term under the SSP5-8.5 scenario, and the number of SHW days projected to increase by 62 ± 18.4 days compared to the reference period. Changes in heatwaves are anticipated to influence PEH, estimating population exposure to light, moderate, and severe heatwaves (LPEH, MPEH, and SPEH) at 534.6 ± 64 million, 496.2 ± 43.5 million, and 1602.4 ± 562.5 million person-days, respectively, in the long-term under the SSP5-8.5 scenario. The spatial distribution of PEH is projected to be consistent with that of the reference period, with high values persisting in Urumqi, Kashgar and Hotan. Changes in PEH are primarily driven by climate effects, followed by interactive effects, while population effects contribute the least. Therefore, mitigating climate change is crucial to reduce the PEH in Xinjiang.

m6A epitranscriptomic and epigenetic crosstalk in cardiac fibrosis.

Cardiac fibrosis, a crucial pathological characteristic of various cardiac diseases, presents a significant treatment challenge. It involves the deposition of the extracellular matrix (ECM) and is influenced by genetic and epigenetic factors. Prior investigations have predominantly centered on delineating the substantial influence of epigenetic and epitranscriptomic mechanisms in driving the progression of fibrosis. Recent studies have illuminated additional avenues for modulating the progression of fibrosis, offering potential solutions to the challenging issues surrounding fibrosis treatment. In the context of cardiac fibrosis, an intricate interplay exists between m6A epitranscriptomic and epigenetics. This interplay governs various pathophysiological processes: mitochondrial dysfunction, mitochondrial fission, oxidative stress, autophagy, apoptosis, pyroptosis, ferroptosis, cell fate switching, and cell differentiation, all of which affect the advancement of cardiac fibrosis. In this comprehensive review, we meticulously analyze pertinent studies, emphasizing the interplay between m6A epitranscriptomics and partial epigenetics (including histone modifications and noncoding RNA), aiming to provide novel insights for cardiac fibrosis treatment.

Investigating Oxidative Stress Associated with Myocardial Fibrosis by High-Fidelity Visualization and Accurate Evaluation of Mitochondrial GSH Levels.

Myocardial fibrosis is frequently accompanied by elevated levels of oxidative stress. Mitochondrial glutathione (mGSH), an essential biomolecule for maintaining redox homeostasis in mitochondria, could serve as an effective indicator for investigating the oxidative stress associated with myocardial fibrosis. In this study, a ratiometric fluorescent probe named Mito-NS6, capable of being anchored in mitochondria and reversibly responding to GSH with an appropriate dissociation equilibrium constant, was rationally designed and utilized to visualize and evaluate the changes of mGSH levels caused by oxidative stress in myocardial fibrosis. Benefiting from the good performance of Mito-NS6, we successfully achieved the quantification of mGSH in cardiac fibroblasts using a confocal laser-scanning microscope, revealing that salvianolic acid B (SalB) can act as an effective drug to alleviate myocardial fibrosis through depressing oxidative stress. Moreover, we employed ratio fluorescence imaging to track the fluctuation in GSH levels within a mice model of myocardial fibrosis induced by isoproterenol and found that myocardial fibrosis caused a higher oxidative stress level in myocardial tissue as well as heart organs. These results provide a novel point of view for the diagnosis and treatment of myocardial fibrosis.