Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia.

The low analgesic efficiency has limited magnesium used in analgesia. Here, we report boron hydride (BH) with ion current rectification activity can significantly improve the analgesic efficiency of magnesium, even higher than morphine. The synthesized injectable MgB2 composes of hexagonal boron sheets alternating with Mg2+. In pathological environment, while the intercalated Mg2+ will be exchanged by H+, the 2-dimensional borophene-analogue BH sheets will be formed to interact with the charged cations via the cation-pi interaction, synergistically leading to a sort of two-way dynamic modulation of sodium and potassium ion currents in neurons. By coordinating with the released Mg2+ to compete Ca2+, the threshold potential remarkably increases from the normal -35.9 mV to -5.9 mV, which significantly suppresses neuronal excitability, providing a potent analgesic effect. In three typical pain models , including CFA-induced inflammatory pain, PINP- or CCI-induced neuropathic pain, MgB2 demonstrates its analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than the clinical MgSO4, respectively. The development of MgB2 as analgesic drugs addresses the unmet medical need of pain relief without the risks of drug tolerance or addiction to opioids.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Association between drinking water sources and cognitive functioning in Chinese older adults residing in rural areas.

OBJECTIVES: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China. METHODS: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction. RESULTS: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index. CONCLUSIONS: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults.

The Difference between Stress Deformation and Adsorption Deformation of Coal Reservoirs and Its Role in Permeability Prediction.

The key to the variation in permeability within coal reservoirs lies in the stress-induced deformation and desorption-induced deformation during the coalbed methane (CBM) production. The differences in sample scale and measurement methods between stress-induced deformation and desorption-induced deformation significantly affect the accuracy of permeability measurements. Therefore, in order to elucidate the relationship between stress-induced deformation and adsorption-induced deformation, as well as the influencing factors, and to assess the accuracy of permeability evolution prediction, this study conducted a series of parallel experiments, including compression deformation experiments under stress loading (stress-induced deformation), methane adsorption-induced deformation experiments (adsorption-induced deformation), µCT scanning, and overburden permeability measurements.The results of the study indicate that stress-induced deformation and adsorption-induced deformation are negatively correlated but exhibit a relatively weak correlation. Stress-induced deformation encompasses deformation of coal matrix, minerals, and fractures, whereas adsorption-induced deformation primarily reflects coal matrix deformation. While there is some overlap between the two, they are not entirely identical. The main influencing factor of stress-induced deformation is the mechanical strength of coal, with minerals in coal increasing the Young's modulus of coal reservoirs. Among them, minerals that are more dispersed and have smaller particles have a more significant impact on stress-induced deformation. The primary influencing factor of adsorption-induced deformation is the deformation capability of the coal matrix, with minerals and fractures having less significant effects. Permeability changes are controlled by fracture deformation, but stress-induced deformation measurements weakly reflect this aspect, leading to an inability to accurately predict the scale of the impact of effective stress changes on permeability during CBM production and CO2-ECBM processes. In contrast, adsorption-induced deformation relatively accurately reflects the deformation capability of the coal matrix and provides a more accurate prediction of permeability rebound under the condition of almost unchanged effective stress in the late stages of mining. Therefore, deformation parameters under stress loading are challenging to directly apply to the prediction of permeability evolution, while adsorption-induced deformation parameters can be effectively utilized.

Cervical cancer subtype identification and model building based on lipid metabolism and post-infection microenvironment immune landscape.

Background: As the second most common gynecological cancer, cervical cancer (CC) seriously threatens women's health. The poor prognosis of CC is closely related to the post-infection microenvironment (PIM). This study investigated how lipid metabolism-related genes (LMRGs) affect CC PIM and their role in diagnosing CC. Methods: We analyzed lipid metabolism scores in the CC single-cell landscape by AUCell. The differentiation trajectory of epithelial cells to cancer cells was revealed using LMRGs and Monocle2. Consensus clustering was used to identify novel subgroups using the LMRGs. Multiple immune assessment methods were used to evaluate the immune landscape of the subgroups. Prognostic genes were determined by the LASSO and multivariate Cox regression analysis. Finally, we perform molecular docking of prognostic genes to explore potential therapeutic agents. Results: We revealed the differentiation trajectory of epithelial cells to cancer cells in CC by LMRGs. The higher LMRGs expression cluster had higher survival rates and immune infiltration expression. Functional enrichment showed that two clusters were mainly involved in immune response regulation. A novel LMR signature (LMR.sig) was constructed to predict clinical outcomes in CC. The expression of prognostic genes was correlated with the PIM immune landscape. Small molecular compounds with the best binding effect to prognostic genes were obtained by molecular docking, which may be used as new targeted therapeutic drugs. Conclusion: We found that the subtype with better prognosis could regulate the expression of some critical genes through more frequent lipid metabolic reprogramming, thus affecting the maturation and migration of dendritic cells (DCs) and the expression of M1 macrophages, reshaping the immunosuppressive environment of PIM in CC patients. LMRGs are closely related to the PIM immune landscape and can accurately predict tumor prognosis. These results further our understanding of the underlying mechanisms of LMRGs in CC.

Reconfiguring the Hydrogen Networks of Aqueous Electrolyte to Stabilize Iron Hexacyanoferrate for High-Voltage Decoupled Cell.

Prussian blue analogs (PBAs) as insertion-type cathodes have attracted significant attention in various aqueous batteries to accommodate metal or non-metal ions while suffering from serious dissolution and consequent inferior lifespan. Herein, we reveal that the dissolution of PBAs primarily originates from the locally elevated pH of electrolytes that are caused by proton co-insertion during discharge. To address this issue, a water-locking electrolyte (WLE) has been strategically implemented, which interrupts the generation and Grotthuss diffusion of protons by breaking the well-connected hydrogen bonding network in aqueous electrolytes. As a result, the WLE enables the iron hexacyanoferrate to endure over 1000 cycles at a 1C rate and supports a high-voltage decoupled cell with an average voltage of 1.95 V. These findings provide insights for mitigating dissolution problems in electrode materials, thereby enhancing the viability and performance of aqueous batteries.

Psychosocial adjustment changes and related factors in young and middle-aged patients with first-episode acute myocardial infarction: a longitudinal study.

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis.

BACKGROUND: Toxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of Dioscorea bulbifera L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. PURPOSE: To evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. METHOD: The effect of DIOB on NSCLCL in vitro was evaluated through CCK8, colony formation, and flow cytometry. The in vivo efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. RESULTS: DIOB effectively hindered the progression of NSCLC both in vitro and in vivo settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. CONCLUSION: For the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain.

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1ß, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation.

Triglyceride-Glucose Index Predicts Major Adverse Cardiovascular and Cerebrovascular Events in Patients with Atrial Fibrillation.

This study aimed to explore the relationship between the trajectory of the triglyceride-glucose (TyG) index and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).This prospective study included 1979 patients with AF, who were initially selected from the Kailuan study. Patients of AF were split into four groups according to the value of TyG index. The clinical endpoint was MACCE, including myocardial infarction and ischemic stroke. Cox proportional hazard models were employed to examine the hazard ratio (HR) and 95% confidence interval (CI) for MACCE in various trajectory groups.The mean age of all patients with AF was 67.65 ± 11.15 years, and 1752 (88.53%) were male. Over a median follow-up duration of 5.31 years, in total 227 MACCE were recorded. MACCE cumulative incidence in Quartile 4 (26.96%) was significantly higher than those in other quartiles (P = 0.023). Multivariate Cox proportional hazards regression analysis showed that a higher TyG index (Quartile 4) was significantly and positively linked to MACCE in patients with AF (P = 0.023, HR: 2.103; 95% CI: 1.107-3.994).The evaluated TyG index is significantly associated with an increased risk of MACCE in patients with AF.

Deciphering the pathogenic risks of microplastics as emerging particulate organic matter in aquatic ecosystem.

Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities. We found that both microplastics and leaves have comparable impacts on microbial community structures and functions, enriching opportunistic pathogens and ARGs, which may pose potential environmental risks. These effects are likely driven by their influences on water properties, including dissolved organic carbon, nitrate, DO, and pH. However, microplastics uniquely promoted pathogens as keystone species and further amplified their capacity as hosts for ARGs, potentially posing a higher pathogenic risk than natural POM. Our research also emphasized the importance of considering both PA and FL bacteria when assessing microplastic impacts, as they exhibited different responses. Overall, our study elucidates the role and underlying mechanism of microplastics as an emerging POM in intensifying pathogenic risks of aquatic ecosystems in comparison with conventional natural POM.

Diagnostic and Therapeutic Challenges in Lemierre Syndrome: A Case Report Using Metagenomic Next Generation Sequencing.

Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.

Responsive Organic Fluorescent Aggregates Based on Ion-π Interactions Away from Fluorescent Conjugated Groups.

Responsive organic luminescent aggregates have a wide range of application fields, but currently there is still a lack of reasonable molecular design strategies. Introducing ion-π interactions into molecules can effectively alter their luminescent properties. However, current research typically focuses on ion localization at luminescent conjugated groups with the strong interaction forces. In this work, we introduce the flexible alkoxy chain spacers between fluorescent conjugated groups and ion-π interaction sites, and then adjust the fluorescence performance of the molecule by changing the strength of ion-π interactions. Bromine ion-based molecules with strong ion-π interactions exhibit high and stable fluorescence quantum yields in crystals and amorphous powders under the external stimuli. Hexafluorophosphate ion-based molecules with weak ion-π interactions have the high fluorescence quantum yield in crystals and very low fluorescence quantum yield in amorphous powders, showing variable fluorescence intensities under external stimuli. This demonstrates a new class of responsive organic luminescent solid-state materials.

Late-Stage C-H Nitration of Unactivated Arenes by Fe(NO3)3·9H2O in Hexafluoroisopropanol.

Operationally simple and generally applicable arene nitration with cheap and easily accessible chemicals has been a long-sought transformation in the synthetic organic community. In this work, we realized this goal with nontoxic and inexpensive Fe(NO3)3·9H2O as the nitro source and easily recyclable solvent hexafluoroisopropanol as the promotor via a network of hydrogen-bonding interactions. As a result of the relative mildness and high reliability of this protocol, late-stage nitration of various highly functionalized natural products and commercially available drugs was realized.

Exercise promotes brain health: a systematic review of fNIRS studies.

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

Mass spectrometry-based pseudotargeted metabolomics reveals metabolic variations in a2-induced gastric cancer cell.

Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world. Compound a2, a Jiyuan oridonin derivative, exhibited excellent anti-proliferative activity against GC cells. To investigate the gastric cellular response to a2 therapy as a novel drug candidate, we adopted a pseudotargeted metabolomics method to explore metabolic variation in a2-induced MGC-803 gastric cells using liquid chromatography tandem mass spectrometry combined with multivariate statistical analysis. The results showed that a2 treatment induced significant metabolic changes in the levels of aminoacyl-tRNA biosynthesis, alanine, aspartate and glutamate metabolism, pyrimidine metabolism, and tricarboxylic acid cycle, approximately 80% of the metabolites were down-regulated in the low-dose and high-dose groups including aspartate, tryptophan, sedoheptulose 7-phosphate, succinate, 2'-deoxyadenosine, uridine, cytidine, etc. which can provide evidence for a new therapy of GC.

Tailoring the interfacial microenvironment of magnetic metal-organic frameworks using amino-acid-based ionic liquids for lipase immobilization.

Modifying the carrier interface is a promising method to improve the microenvironment of immobilized enzymes and enhance their activity and stability. In this work, using proline as amino acid, magnetic metal-organic frameworks (MOFs) were modified with an amino-acid-based ionic liquid (AAIL) with two hydroxyl groups followed by adsorption of porcine pancreatic lipase (PPL). The activity recovery of the prepared immobilized lipase (MMOF-AAIL/PPL) was up to 162 % higher than that of MMOF-PPL (70.8 %). The Michaelis constant of MMOF-AAIL/PPL was 0.0742 mM lower than that of MMOF-PPL, but the catalytic efficiency was 0.0223 min-1 which was higher than MMOF-PPL. Furthermore, MMOF-AAIL/PPL maintained 85.6 % residual activity after stored for 40 days and its residual activity was 71.9 % while that for MMOF-PPL was 58.8 % after incubated in 6 M urea for 2 h. Particularly, after ten consecutive cycles, the residual activity of MMOF-AAIL/PPL still reached 84.4 %. In addition, the magnetic properties of the support facilitate the separation process which improves the utilization efficiency of immobilized enzymes.

Association of the triglyceride-glucose index with early-onset atherosclerotic cardiovascular disease events and all-cause mortality: a prospective cohort study.

BACKGROUND: The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. METHODS: The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. RESULTS: During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38-1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17-1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear < 0.01), and a linear association between TyG index and all-cause mortality (P for non-linear = 0.476). CONCLUSIONS: A higher TyG index is significantly associated with an increased incidence of early-onset ASCVD events and all-cause mortality in a young and middle-aged population from North China.

Spartina alterniflora invasion altered phosphorus retention and microbial phosphate solubilization of the Minjiang estuary wetland in southeastern China.

Spartina alterniflora invasion is considered a critical event affecting sediment phosphorus (P) availability and stock. However, P retention and microbial phosphate solubilization in the sediments invaded with or without S. alterniflora have not been fully investigated. In this study, a sequential fractionation method and high-throughput sequencing were used to analyze P transformation and the underlying microbial mechanisms in the sediments of no plant (NP) zone, transition (T) zone, and plant (P) zone. Results showed that except for organic phosphate (OP), total phosphate (TP), inorganic phosphate (IP), and available phosphate (AP) all followed a significant decrease trend from the NP site to the T site, and to the P site. The vertical decrease of TP, IP, and AP was also observed with an increase in soil depth. Among the six IP fractions, Fe-P, Oc-P, and Ca10-P were the predominant forms, while the presence of S. alterniflora resulted in an obvious P depletion except for Ca8-P and Al-P. Although S. alterniflora invasion did not significantly alter the alpha diversity of phosphate-solubilizing bacteria (PSB) harboring phoD gene, several PSB belonging to p_Proteobacteria, p_Planctomycetes, and p_Cyanobacteriota showed close correlations with P speciation and IP fractions. Further correlation analysis revealed that the reduced soil pH, soil TN and soil EC, and the increased soil TOC mediated by the invasion of S. alterniflora also significantly correlated to these PSB. Overall, this study elucidates the linkage between PSB and P speciation and provides new insights into understanding P retention and microbial P transformation in the coastal sediment invaded by S. alterniflora.

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.