Formation and Recombination Dynamics of Polarons in Goethite: A Time-Domain Ab Initio Study.

The temperature and the coordination environment significantly affect polaron dynamics. Using goethite (FeOOH) as a model, our study examines polaron formation and recombination behavior under various conditions, including electron injection, photoexcitation, and heterovalent doping. Ab initio and nonadiabatic molecular dynamics (NAMD) simulations reveal that polaron formation in FeOOH is dependent on temperature via an adiabatic mechanism with higher temperatures leading to shorter formation times. Only electron polarons form in FeOOH, regardless of the formation method. NAMD simulations indicate that photoexcited electron polaron recombination is significantly faster in FeOOH than in Fe2O3. This difference arises from the distinct coordination environments, resulting in higher inelastic charge-phonon scattering and stronger nonadiabatic coupling in FeOOH. Our findings highlight the crucial roles of temperature and coordination environment in polaron dynamics, offering valuable insights for designing materials to optimize carrier dynamics.

Cardiovascular health and cancer mortality: evidence from US NHANES and UK Biobank cohort studies.

BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

Highly Selective Synthesis of Acetic Acid from Hydroxyl-Mediated Oxidation of Methane at Low Temperatures.

Direct methane conversion and, in particular, the aerobic oxidation to acetic acid, remain an eminent challenge. Here, we reported a zeolite-supported Au-Fe catalyst (Au-Fe/ZSM-5) that converted methane to acetic acid with molecular oxygen as an oxidant in the presence of CO. Specifically, Au nanoparticles catalyzed the formation of hydroxyl species from the reaction of CO, O2, and H2O, meanwhile ZSM-5-supported atomically dispersed Fe species were responsible for the hydroxyl-mediated coupling of CH4 and CO to generate acetic acid. The reaction over 50 mg of Au-Fe/ZSM-5 under 62 bar (CH4: CO: O2 = 14: 14: 3) at 120 °C for 3.0 h yielded 5.7 millimoles of acetic acid per gram of the catalyst (mmol gcat-1) with the selectivity of 92%, outperformed most of reported catalysts. Significantly, the catalyst remained active even at 60 °C. We anticipate that this hydroxyl-mediated route may guide the design of optimized catalysts for the direct methane functionalization at low temperatures.

LSPR-susceptible metasurface platform for spectrometer-less and AI-empowered diagnostic biomolecule detection.

In response to the growing demand for biomolecular diagnostics, metasurface (MS) platforms based on high-Q resonators have demonstrated their capability to detect analytes with smart data processing and image analysis technologies. However, high-Q resonator meta-atom arrays are highly sensitive to the fabrication process and chemical surface functionalization. Thus, spectrum scanning systems are required to monitor the resonant wavelength changes at every step, from fabrication to practical sensing. In this study, we propose an innovative dielectric resonator-independent MS platform that enables spectrometer-less biomolecule detection using artificial intelligence (AI) at a visible wavelength. Functionalizing the focused vortex MS to capture gold nanoparticle (AuNP)-based sandwich immunoassays causes the resulting vortex beam profiles to be significantly affected by the localized surface plasmon resonance (LSPR) occurring between AuNPs and meta-atoms. The convolutional neural network algorithm was carefully trained to accurately classify the AuNP concentration-dependent focused vortex beam, facilitating the determination of the concentration of the targeted diagnostic biomolecule. Successful in situ identification of various biomolecule concentrations was achieved with over 99 % accuracy, indicating the potential of combining an LSPR-susceptible MS platform and AI for continuously tracking various chemical and biological compounds.

Clinical characteristics of double negative atypical inflammatory demyelinating disease: A prospective study.

OBJECTIVE: This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue-based assays (TBA) using rat brain indirect immunofluorescence. METHODS: We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow-up. RESULTS: In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti-astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow-up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti-astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti-astrocyte antibodies (66.7%, 20/30) (p = 0.008). The presence of anti-astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087-4.627; p = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224-5.078; p = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150-0.869; p = 0.023) was protective factor. INTERPRETATION: Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti-astrocyte antibodies or ≥4 cerebrum lesions at first attack.

Oxidized paramylon self-assembled nanoparticles loaded with fucoxanthin attenuate insulin resistance in HpeG2 cells.

Fucoxanthin (Fx) has garnered significant interest due to its exceptional biological properties. However, its efficacy in enhancing food quality and human health is contingent upon the solubility of the compound in water and its physicochemical stability. Therefore, nanocarriers must be developed to enhance the stability and biocompatibility of Fx. In this study, oxidized paramylon and Fx self-assembled nanoparticles (Fx-OEP) were prepared via the anti-solvent method, with a loading rate of 82.47 % for Fx. The Fx-OEP exhibited robust storage and photostability. In vitro simulated digestion assays demonstrated that Fx-OEP effectively protected Fx from premature gastric release, while achieving a release efficiency of 72.17 % in the intestinal phase. Fx-OEP has the capacity to scavenge a range of reactive oxygen species (ROS) induced by cellular oxidative stress. Treatment with Fx-OEP resulted in a significant reduction in ROS accumulation in insulin-resistant HepG2 cells, which was attributed to the activation of the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. This, in turn, activated insulin receptor substrate 1/glucose transporter type 4 (IRS1/GLUT4), promoting cellular glucose absorption and utilization. These findings indicate the potential of self-assembled nanoparticles based on oxidized paramylon as a new type of nanocarrier for delivering hydrophobic substances.

Heat-killed Bifidobacterium longum BBMN68 and inulin protect against high-fat diet-induced obesity by modulating gut microbiota.

Introduction: Obesity, a pervasive global epidemic, has heightened susceptibility to chronic ailments and diminished the overall life expectancy on a global scale. Probiotics and inulin (IN) have been documented to mitigate obesity by exerting an influence on the composition of the gut microbiota. Whether heat-killed Bifidobacterium longum BBMN68 (MN68) and IN have an anti-obesity effect remains to be investigated. Methods: In this study, Wistar rats were fed a high-fat diet (HFD), and orally administered heat-killed MN68 (2 × 1011 CFU/kg) and/or inulin (0.25 kg/kg) for 12 weeks. Histological analysis, serology analysis and 16S rRNA gene sequencing were performed. Results: Heat-killed MN68 + IN treatment showed an enhanced effect on preventing weight gain, diminishing fat accumulation, and regulating lipid metabolism, compared to either heat-killed MN68 treatment or inulin treatment. Gut microbiota results showed that heat-killed MN68 + IN treatment significantly increased the relative abundance of Bacteroidota, Oscillospira, Intestinimonas, Christensenella, and Candidatus_Stoquefichus, and reduced the relative abundance of Enterococcus. Furthermore, heat-killed MN68 + IN significantly increased the SCFA levels, which were correlated with changes in the gut microbiota. Discussion: This research provides support for the application of heat-killed MN68 and IN in the treatment of obesity, and highlights the combination of heat-killed BBMN68 and IN as functional food ingredients.

Diversity patterns and ecological assembly mechanisms of bacterial communities in the northeastern Indian Ocean epipelagic waters during the northeast monsoon.

Disentangling microbial community diversity patterns and assembly mechanisms is critical for understanding ecological processes and evaluating biogeochemical cycling in ecosystems. However, the diversity patterns and assembly mechanism of the microbial communities in the epipelagic waters in the northeastern Indian Ocean (NEIO) on the spatial scale are still unclear. In this study, we investigated the spatial dynamics, geographic distribution pattern, and assembly process of the bacterial community using 532 samples collected from the epipelagic waters in the NEIO during the northeast monsoon. The results indicate that the bacterial richness and Bray-Curtis dissimilarity exhibited the strongest correlations with depth compared to the latitudinal and longitudinal scales. The dissolved oxygen was identified as the most important environmental factor affecting the bacterial richness and Bray-Curtis dissimilarity compared to temperature and salinity. The distance-decay relationship (DDR) of the bacterial community strengthened with increasing water depth. Turnover was the predominant ß-diversity component influencing the spatial changes in the whole bacterial community. The dispersal limitation of the stochastic process and homogeneous selection of the deterministic process governed the bacterial ecological assembly process of the whole bacterial community. Abundant and rare subcommunities differed in terms of the niche breath, composition changes. The abundant subcommunities exhibited a much wider niche breath than the rare subcommunities. Regarding the abundant subcommunity species changes, the contributions of the turnover and nestedness varied with the water depth and oceanic region. In contrast, turnover was the major ß-diversity component regarding the changes in the rare species. These data improve our understanding of the ecological processes of bacterial community assemblages in the NEIO.

Carboxymethylation of paramylon derived from Euglena gracilis and its hypoglycemic mechanism in diabetic mice.

Paramylon is a polysaccharide primarily composed of ß-1,3-glucan, characterized by its high crystallinity and insolubility in water. Enhancing its water solubility through structural modifications presents an effective strategy to unlock its biological activity. In this study, carboxymethylation was employed to produce carboxymethylated paramylon (CEP) with varying carboxyl concentrations. The successful introduction of carboxyl groups led to a notable improvement in water solubility. In vivo experiments demonstrated that CEP reduced fasting blood glucose levels by 24.42 %, improved oral glucose tolerance, and enhanced insulin sensitivity in diabetic mice. Additionally, CEP regulated lipid homeostasis and ameliorated liver damage. Through modulation of the adenosine monophosphate-activated protein kinase/phosphoinositide 3-kinase/protein kinase B pathway and the glucose-6-phosphatase/phosphoenolpyruvate carboxykinase pathway, CEP effectively regulated hepatic glucose absorption and production. Furthermore, CEP mitigated diabetes-induced lipid metabolism disorders. These findings suggest that CEP holds significant promise in ameliorating glucose metabolism disorder, indicating its potential as a novel hypoglycemic functional food.

Association between triglyceride-glucose index and gallstones: a cross-sectional study.

This study used data from the National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between the triglyceride-glucose (TyG) index and gallstones. We evaluated the data collected between 2017 to 2020. To evaluate the relationship between TyG index and gallstones, logistic regression analysis, basic characteristics of participants, subgroup analysis, and smooth curve fitting were utilized. The study included 3870 participants over the age of 20 years, 403 of whom reported gallstones, with a prevalence rate of 10.4%. After adjusting for all confounding factors, the risk of gallstones increased by 41% for each unit increase in the TyG index (OR 1.41, 95% CI 1.07, 1.86). The smooth curve fitting also showed a positive correlation between the TyG index and gallstones. Subgroup analysis revealed a significant positive relationship between the TyG index and the risk of gallstones in those aged < 50 years, women, individuals with total cholesterol levels > 200 mg/dL, individuals with body mass index (BMI) > 25, and individuals without diabetes. The risk of gallstones is positively correlated with a higher TyG index. Thus, the TyG index can be used as a predictor of the risk of gallstones.

Oriented Synthesis of Glycine from CO2, N2, and H2O via a Cascade Process.

Air contains carbon, hydrogen, oxygen, and nitrogen elements that are essential for the constitution of amino acids. Converting the air into amino acids, powered with renewable electricity, provides a green and sustainable alternative to petrochemical-based methods that produce waste and pollution. Here, taking glycine as an example, we demonstrated the complete production chain for electrorefining amino acids directly from CO2, N2, and H2O. Such a prospective scheme was composed of three modules, linked by a spontaneous C-N bond formation process. The high-purity bridging intermediates, separated from the stepwise synthesis, boosted both the carbon selectivity from CO2 to glycine of 91.7% and nitrogen selectivity from N2 to glycine of 98.7%. Under the optimum condition, we obtained glycine with a partial current density of 160.8 mA cm-2. The high-purity solid glycine product was acquired with a separation efficiency of 98.4%. This work unveils a green and sustainable method for the abiotic creation of amino acids from the air components.

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and sarcopenia.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

Constituents from leaves of Macaranga hemsleyana.

Objective: To study constituents of the leaves of Macaranga hemsleyana, and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and antiproliferative activity. Methods: The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120, silica gel, Sephadex LH-20, and HPLC. The structures of compounds were determined by 1D, 2D NMR, and HR-ESI-MS data. The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase (LDH) procedure. The antiproliferative activity was evaluated using MTT assay. Results: The study led to the isolation of 23 compounds, including one new compound, identified as (2Z)-3-[4-(ß-D-glucopyranosyloxy)-2'-hydroxy-5'-methoxyphenyl]-2-propenoic acid (1), together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile (2), methyl 4-methoxynicotinate (3), 4-methoxynicotinonitrile (4), 1-(3-O-ß-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone (5), neoisoastilbin (6), isoastilbin (7), aromadendrin (8), neoastilbin (9), astilbin (10), quercitrin (11), neoschaftoside (12), apigenin 6,8-bis-C-α-L-arabinoside (13), vitexin (14), bergenin (15), scopoletin (16), glucopyranoside salicyl (17), koaburside (18), benzyl ß-D-glucoside (19), icariside B5 (20), roseoside (21), loliolide (22), and adenosine (23). The tested compounds did not show LDH inhibition nor antiproliferative activity. Conclusion: Compound 1 was a new glycoside. Compounds 2 and 3 were obtained for the first time from natural source. The 22 known compounds constituted of alkaloids (2-4, 23), phenolics (5, 15, 17, 18), flavonoids (6-14), coumarin (16), benzyl glycoside (19), and norsesquiterpenes (20-22). All the compounds, 1-23, were revealed from M. hemsleyana for the first time. This is the initial uncovering of molecules 1-10, 12, 13, 17-19, and 23 from the genus Macaranga. The isolated compounds, 11, 14-16, and 20-22 established taxonomic classification of M. hemsleyana in Euphorbiaceae family. Flavonoids were outstanding as chemosystematic markers of Macaranga genus.

Facet sensitivity of iron carbides in Fischer-Tropsch synthesis.

Fischer-Tropsch synthesis (FTS) is a structure-sensitive reaction of which performance is strongly related to the active phase, particle size, and exposed facets. Compared with the full-pledged investigation on the active phase and particle size, the facet effect has been limited to theoretical studies or single-crystal surfaces, lacking experimental reports of practical catalysts, especially for Fe-based catalysts. Herein, we demonstrate the facet sensitivity of iron carbides in FTS. As the prerequisite, {202} and {112} facets of χ-Fe5C2 are fabricated as the outer shell through the conformal reconstruction of Fe3O4 nanocubes and octahedra, as the inner cores, respectively. During FTS, the activity and stability are highly sensitive to the exposed facet of iron carbides, whereas the facet sensitivity is not prominent for the chain growth. According to mechanistic studies, {202} χ-Fe5C2 surfaces follow hydrogen-assisted CO dissociation which lowers the activation energy compared with the direct CO dissociation over {112} surfaces, affording the high FTS activity.

Clinical significance of TROAP in endometrial cancer and the antiproliferative and proapoptotic effects of TROAP knockdown in endometrial cancer cells: integrated utilization of bioinformatic analysis and in vitro test verification.

Trophinin-associated protein (TROAP), a cytoplasmic protein essential for spindle assembly and centrosome integrity during mitosis, has been reported to serve as an oncogene in various tumors. However, its role in endometrial cancer (EC) progression is still undefined. TROAP expression in EC was analyzed via GEPIA and HPA databases. The diagnostic and prognostic values of TROAP were examined by ROC curve analysis and Kaplan-Meier plotter, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Apoptosis was assessed using TUNEL and flow cytometry assays. GSEA was performed to explore TROAP-related pathways in EC. Expression of TROAP, proliferating cell nuclear antigen (PCNA), Ki-67, cleaved-caspase-3 (cl-caspase-3), caspase-3, active ß-catenin, and total ß-catenin was detected using western blot analysis. TROAP was upregulated in EC. TROAP served as a potential diagnostic and prognostic marker in EC patients. TROAP silencing suppressed proliferation and enhanced apoptosis in EC cells. GSEA revealed that EC and Wnt signaling pathways were related to the expression of TROAP. We further demonstrated that TROAP knockout repressed the Wnt/ß-catenin pathway in EC cells. Moreover, SKL2001, a Wnt/ß-catenin activator, partially abrogated the effects of TROAP silencing on EC cell proliferation and apoptosis, while the signaling inhibitor XAV-939 had the opposite effect. In conclusion, TROAP knockout retarded proliferation and elicited apoptosis in EC cells by blocking the Wnt/ß-catenin pathway.

Decoupling of high-resolution surface pH and DO reveals temporal algal bloom dynamics on the East China Sea.

The stoichiometric ratio between seawater CO2 and dissolved oxygen (DO) during phytoplankton metabolism holds significant importance in evaluating ecological and biogeochemical processes. We collected high-resolution underway temperature, salinity, DO, and pH data in the East China Sea inner shelf in May 2017. Our results revealed high pH (8.36) and supersaturated DO (171 %) in the outer Changjiang Estuary, indicating the occurrence of an algal bloom event. They were significantly correlated with a regression slope of 0.0029, which roughly followed the Redfield ratio. In contrast, a much higher ratio (0.0088) manifested in a low-salinity patch on north of the Changjiang Estuary, featuring a pH of 8.40 and oxygen saturation of approximately 123 %. The substantially faster air-sea equilibrium rate of O2 than CO2 probably caused such decoupling, offering insight into the temporal evolutions of algal bloom. Theoretically, a steeper regression slope implies an earlier onset of algal bloom. An end-member mixing model was constructed to exclude the physical mixing influences on dissolved inorganic carbon (ΔDIC) and DO (ΔDO). Furthermore, we conducted simulations to explore the temporal variations of ΔDIC-ΔDO regression slope with time. Comparing slopes derived from simulation and mixing model suggested that the biological signal of the decoupled waters likely preceded our observations by 6-10 days. Satellite results captured high-Chl a waters southwest of the low-salinity patch a week before our observation, potentially transported northward by prevailing southwest wind. Given that oxygen and pH are frequently measured in aquatic environments, their combined assessment could be a valuable method for assessing temporal algal bloom dynamics.

Artificial sweeteners and risk of incident cardiovascular disease and mortality: evidence from UK Biobank.

BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.

Historical reconstruction of glacier mass balance and its contribution to water resources in the Sawir Mountains from 2000 to 2020.

Glacial changes are crucial to regional water resources and ecosystems in the Sawir Mountains. However, glacial changes, including the mass balance and glacial meltwater of the Sawir Mountains, have sparsely been reported. Three model calibration strategies were constructed including a regression model based on albedo and in-situ mass balance of Muz Taw Glacier (A-Ms), regression model based on albedo and geodetic mass balance of valley, cirque, and hanging glaciers (A-Mr), and degree-day model (DDM) to obtain a reliable glacier mass balance in the Sawir Mountains and provide the latest understanding in the contribution of glacial meltwater runoff to regional water resources. The results indicated that the glacial albedo reduction was significant from 2000 to 2020 for the entire Sawir Mountains, with a rate of 0.015 (10a)-1, and the spatial pattern was higher in the east compared to the west. Second, the three strategies all indicated that the glacier mass balance has been continuously negative during the past 20 periods, and the average annual glacier mass balance was -1.01 m w.e. Third, the average annual glacial meltwater runoff in the Sawir Mountains from 2000 to 2020 was 22 × 106 m3, and its contribution to streamflow was 25.81 % from 2000 to 2018. The glacier contribution rates in the Ulkun- Ulastu, Lhaster, and Kendall River basins were 31.37 %, 22.51 %, and 19.27 %, respectively.

Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases.

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.