Association of adherence to the EAT-Lancet diet with risk of dementia according to social economic status: a prospective cohort in UK Biobank.

The EAT-Lancet Commission has proposed a reference diet aiming to promote human health and environmental sustainability. Socioeconomic disadvantage and poor diet are well-known risk factors for dementia; however, whether the effect of this reference diet on dementia varies by socioeconomic status has not been investigated. The dietary habits of 190,893 participants from UK-Biobank were assessed; the association of EAT-Lancet diet with incident dementia across socioeconomic status was determined by Cox models. One thousand seven hundred twenty-eight dementia cases were identified during a median of 12.24 years follow-up. An inverse association between adherence to EAT-Lancet diet and all-cause dementia (high vs. low; hazard ratio [HR], 95% confidence interval [CI]: 0.82, 0.72-0.94) or late-onset dementia (high vs. low; HR, 95% CI: 0.78, 0.68-0.91) was observed only in individuals with high socioeconomic status. On the contrary, no protective effects of EAT-Lancet diet on early-onset dementia were observed, regardless of the socioeconomic status. Our findings indicated that adherence to an environment-friendly diet helps attenuate risk of dementia only in individuals with high socioeconomic level.

The efficacy of Keverprazan based quadruple therapy for Helicobacter pylori eradication:a phase III, randomized, double-blind, multicenter trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker, whose advantages as a potent acid suppressor in Helicobacter pylori (H. pylori) eradication has not yet been demonstrated. This study aimed to evaluate the efficacy of Keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. METHODS: Adult patients with H. pylori infection were enrolled and randomized to take Keverprazan (KEV group) or Esomeprazole (ESO group)-quadruple therapy (regimen contains Keverprazan 20 mg or Esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, bismuth potassium citrate 240 mg) twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. RESULTS: Full analysis set showed the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for KEV group and ESO group, respectively (difference: 5.29%; 95% CI: -0.55% to 11.18%). Superiority of Keverprazan over Esomeprazole in terms of eradication rate was observed in the per-protocol set (P=0.0382). The eradication rates for patients resistant or not resistant to clarithromycin were both numerically higher in KEV group than ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 96.67 vs. 93.38% for clarithromycin-nonresistance). The incidence of adverse events was similar in KEV and ESO group (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity and leading to no deaths. CONCLUSIONS: Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy provided effective H. pylori eradication and was non-inferior to Esomeprazole-based regimen.

Adoption of region-specific diets in China can help achieve gains in health and environmental sustainability.

The vast heterogeneity in dietary practices across China has led to profound regional disparities in health and environment. To address this issue, we developed a region-specific reference diet (RRD) that is better aligned with Chinese culinary traditions, affordable, sparing of natural and environmental resources, and contributes to health. The adoption of the RRD has proven to be a viable solution to facilitate a rapid transition towards a healthy and environmentally sustainable diet across the country when compared to dietary guidelines from the World Health Organization, the EAT-Lancet Commission and the Chinese Nutrition Society. The RRD improved health in all regions and resulted in reductions of all five environmental impacts measured. Given China's huge population and its major impact on global sustainability, the widespread adoption of the RRD would not only yield substantial health benefits domestically, but also contribute significantly to global food security and sustainability efforts.

UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive human malignancy without effective treatment. Yes-associated protein (YAP) is a critical effector of the Hippo pathway, which is essential in thyroid carcinogenesis. However, the underlying mechanisms of aberrant YAP expression in ATC are not completely understood. Ubiquitylation-related enzyme siRNA screening identified the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) as a stabilizer of YAP in ATC cells. UBR1 deficiency reduced YAP protein levels and its target gene expression. UBR1 directly interacted with YAP and promoted its monoubiquitylation, competitively suppressing its polyubiquitylation and resulting in extended protein half-life. UBR1 depletion reduced ATC cell proliferation and migration in vitro. Xenograft tumor studies also suggested that UBR1 knockdown suppressed ATC cell growth in vivo. Furthermore, exogenous YAP expression partially reversed the inhibitive effects of UBR1 depletion on ATC cell proliferation and migration. Our studies demonstrated that UBR1 directly interacts with YAP and stabilized it in a monoubiquitylation-dependent manner, consequently promoting ATC tumorigenesis, suggesting that UBR1 might be a potentially therapeutic target for ATC treatment.

Sex-specific association of circulating Isthmin-1 with isolated post-challenge hyperglycemia.

Introduction: To explore the distribution of Isthmin-1 (ISM1) level and its association with isolated post-challenge hyperglycemia (IPH). Methods: A total of 522 participants without a history of diabetes were invited to attend a standard 75g 2-h oral glucose tolerance test (OGTT), and 71 subjects were further invited for a 3-h oral minimal model test. Insulin sensitivity and ß-cell function were evaluated using both HOMA and estimated from OGTT. Circulating ISM1 levels were determined by a commercially available ELISA kit. Results: A total of 76 (14.6%) participants were diagnosed as IPH, accounting for 61.3% of the newly diagnosed diabetes. ISM1 levels were significantly higher in men than in women (1.74 ng/mL versus 0.88 ng/mL). The inverse correlation between ISM1 and ß-cell function and IPH was only significant in men. After multivariate adjustment, per unit increment in ISM1 was associated with 0.68-fold (95% CI: 0.49-0.90) reduced odds ratio (OR) of IPH in men. Compared to men with the lowest ISM1 levels, the adjusted OR of IPH with the highest ISM1 levels decreased by 73% (95% CI: 0.11-0.61). Moreover, incorporation of ISM1 into the New Chinese Diabetes Risk Score (NCDRS) model yielded a substantial improvement in net reclassification improvement of 58% (95% CI: 27%-89%) and integrated discrimination improvement of 6.4% (95% CI: 2.7%-10.2%) for IPH. Conclusions: ISM1 was significantly and independently associated with IPH, and serves as a feasible biomarker for the early identification of men with high risk of IPH.

Ultrarobust, Self-Healing Poly(urethane-urea) Elastomer with Superior Tensile Strength and Intrinsic Flame Retardancy Enabled by Coordination Cross-Linking.

Poly(urethane-urea) elastomers (PUUEs) have gained significant attention recently due to their growing demand in electronic skin, wearable electronic devices, and aerospace applications. The practical implementation of these elastomers necessitates many exceptional properties to ensure robust and safe utilization. However, achieving an optimal balance between high mechanical strength, good self-healing at moderate temperatures, and efficient flame retardancy for poly(urethane-urea) elastomers remains a formidable challenge. In this study, we incorporated metal coordination bonds and flame-retarding phosphinate groups into the design of poly(urethane-urea) simultaneously, resulting in a high-strength, self-healing, and flame-retardant elastomer, termed PNPU-2%Zn. Additional supramolecular cross-links and plasticizing effects of phosphinate-endowed PUUEs with relatively remarkable tensile strength (20.9 MPa), high elastic modulus (10.8 MPa), and exceptional self-healing efficiency (above 97%). Besides, PNPU-2%Zn possessed self-extinguishing characteristics with a limiting oxygen index (LOI) of 26.5%. Such an elastomer with superior properties can resist both mechanical fracture and fire hazards, providing insights into the development of robust and high-performance components for applications in wearable electronic devices.

Association between Life's essential 8 and incident cardiovascular disease among individuals with depression: a prospective study.

BACKGROUND: Depression is an increasing illness worldwide that severely diminishes the quality of life. The study sought to elucidate the association of the American Heart Association's Life's Essential 8 (LE8) metrics with the incidence of cardiovascular disease (CVD) among depression participants and further quantify the related theoretical reduction of long-term CVD burden. METHODS: 20,832 participants with depression from UK-Biobank were included. LE8, including diet quality, physical activity, nicotine exposure, sleep duration, body mass index, lipids, glucose, and blood pressure, was calculated at baseline and categorized into low, medium, and high levels. Hazard ratios (HR) and 95% confidence interval (95%CI) for major cardiovascular events (MACE) was calculated using Cox models. We further quantified population attributable fractions (PAF) for CVD. RESULTS: During a median follow-up of 12.0 years, 658 MACE were recorded. After multi-variable adjustment, compared with participants with low LE8, people with high LE8 had a decreased risk of MACE (HR, 95%CI: 0.32, 0.22-0.47), non-fatal MACE (0.39, 0.26-0.61), myocardial infarction (0.23, 0.12-0.44), and ischaemic stroke (0.52, 0.27-0.99). Overall, 50.7% (95%CI: 34.5-66.9%) of MACE and 48.0% (95%CI: 29.5-66.4%) of non-fatal MACE were attributable to the low and medium adherence to LE8 at the 5-year follow-up, respectively. Sub-optimal control of blood pressure ranked as the top contributor to all types of CVD in individuals with depression. CONCLUSIONS: Optimal adherence to LE8 was associated with lower burden of CVD in depression. Adopting a comprehensive lifestyle intervention might help further reduce CVD burden in mental disorders.

Epidemiology, risk factors, and vaccine effectiveness for SARS-CoV-2 infection among healthcare workers during the omicron pandemic in Shanghai, China.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69-8.38) and medical examination area (aOR 2.47, 95% CI 1.10-5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0-0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17-0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21-2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15-0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

How does land consolidation affect nongrain production? Evidence from county-level data in Jiangsu Province, China.

Using county-level panel data for Jiangsu Province from 2008 to 2018, this study adopted a fixed effect model to analyze the impact of land consolidation on crop planting structure, also considering the moderating effect of distance from the city center and the heterogeneous effect of various types of land consolidation. The results revealed that farmland consolidation and land reclamation had a negative impact on the proportion of grain crops (rice, wheat, and corn) cultivated, which declined by 0.0051 % (0.0069 %), 0.0055 % (0.0124 %), and 0.0101 % (0.0123 %) for every 1 % increase in investment, construction area, and newly added arable land from farmland consolidation (land reclamation), respectively, demonstrating that land consolidation has not prevented, or even encouraged nongrain production expansion. The production conditions of reclaimed arable land and land transfer practices following consolidation may be factors affecting these declines. Notably, the negative effect of land consolidation on crop planting structure weakens when the land is further away from the city center. To ensure food security, priority should be given to follow-up management after land consolidation and rational oversight and guidance following land transfer.

Efficient Transformation of Water Vapor into Hydrogen by Dielectric Barrier Discharge Loaded with Bamboo Carbon Bed Structured by Fibrous Material.

A new method of efficiently transforming water vapor into hydrogen was investigated by dielectric barrier discharge (DBD) loaded with bamboo carbon bed structured by fibrous material in an argon medium. Hydrogen productivity was measured in three different reactors: a non-loaded DBD (N-DBD), a bamboo carbon (BC) bed DBD (BC-DBD), and a quartz wool (QW)-loaded BC DBD (QC-DBD). The effects of the quality ratio of BC to QW and relative humidity on hydrogen productivity were also investigated in QC-DBD at various flow rates. The reaction process and mechanism were analyzed by scanning electron microscopy, X-ray photoelectron spectroscopy, N2 physisorption experiments, infrared spectroscopy, and optical emission spectroscopy. A new reaction pathway was developed by loading BC into the fibrous structured material to activate the reaction molecules and capture the O-containing groups in the DBD reactor. A hydrogen productivity of 17.3 g/kWh was achieved at an applied voltage of 5 kV, flow rate of 4 L/min, and 100% relative humidity (RH) in the QC-DBD with a quality ratio of BC to QW of 3.0.

Joint association of sleep quality and physical activity with metabolic dysfunction-associated fatty liver disease: a population-based cross-sectional study in Western China.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing threat leading to substantial disease burden globally. Poor sleep and physical inactivity are common in modern societies and independently associated with MAFLD, however, their joint effects on MAFLD remains unclear. METHODS: This population-based cross-sectional study was conducted in Xinjiang Uygur Autonomous Region, China, between July 2019 and September 2021. Self-reported sleep behaviors and physical activity (PA) were assessed using validated questionnaires. The primary outcome was radiological diagnosis of MAFLD. RESULTS: Of the 10 089 participants aged 47.0 (9.1) years (51.6% men), 3854 (38.2%) individuals had MAFLD. Poor sleep quality and physical inactivity were independently and jointly associated with an increased prevalence of MAFLD, independent of traditional risk factors (P < 0.05). Compared to subjects with guideline-recommended moderate-to-vigorous PA (MVPA) and good sleep quality, individuals with no recommended MVPA and poor sleep had the highest possibility of MAFLD (odds ratio = 2.36, 95% confidence interval: 1.81 - 3.08). Enhancing sleep quality substantially attenuated MAFLD prevalence regardless of the volume of PA, whereas, engaging in PA well above current guidelines did not adequately counteract the adverse impacts of poor sleep on MAFLD. CONCLUSIONS: Public health awareness and strategies concurrently targeting both sleep quality and PA should be encouraged to curb the climbing prevalence of MAFLD.

Anti-resonant hollow core fiber with excellent bending resistance in the visible spectral range.

The development of wideband guided hollow-core anti-resonant fiber (HC-ARF) that covers the sensitive range of the human eye's visible spectrum is progressing rapidly. However, achieving low-loss wideband transmission with a small bending radius remains a challenging issue to be addressed. In light of this, we propose a novel, to our knowledge, HC-ARF with a nested double-semi-elliptical cladding structure in the visible spectral region. By employing finite element method simulations, we investigate the confinement loss, bending loss, and single-mode performance of this fiber design. The result shows that the confinement loss of this new fiber exhibits below 10-5 dB·m-1 across almost the entire visible band range, with a minimum loss of 1.55 × 10-7 dB·m-1 achieved for λ = 650 nm. Furthermore, this fiber demonstrates excellent resistance to bending and can maintain an ultra-low bending loss as low as 3 × 10-7 dB·m-1 even under extreme bending conditions with a radius of only 3 cm. Notably, its 3-dB bending radius reaches just 3.5 cm for λ = 532 nm. Additionally, it exhibits outstanding single-mode conductivity under various bending scenarios and achieves a high extinction ratio of up to 104 for higher-order modes after parameter optimization for specific wavelengths.

Conditions that promote transcellular neutrophil migration in vivo.

Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have previously shown that genetically replacing VE-cadherin with a VE-cadherin-α-catenin (VEC-αC) fusion construct-which binds constitutively to actin-obstructs junctions, and blocks leukocyte extravasation in lung, skin and postcapillary venules of cremaster muscle. However, neutrophil recruitment into the inflamed peritoneal cavity was unimpaired. Investigating reasons for this, here, we visualized neutrophil diapedesis by 3D intravital video microscopy in the cremaster muscle and omentum, the major site of neutrophil recruitment into the peritoneal cavity. We found that 80% of neutrophil-extravasation occurred through HEVs in the omentum, which was unimpaired by VEC-αC. In addition, in larger venules (60-85 µm) of both tissues, less than 15% of neutrophils extravasated transcellularly in WT mice. However, in VEC-α-C mice, transcellular diapedesis increased severalfold in the omentum, but not in the cremaster. In line with this, omental venules expressed higher levels of ICAM-1 and atypical chemokine receptor 1. Furthermore, only in the omentum, VEC-αC expression caused reduced elongation of venular endothelium in flow-direction, suggesting different biomechanical properties. Collectively, VEC-αC does not inhibit paracellular transmigration in all types of venules and can modulate the diapedesis route.

The physicochemical interacting mechanisms and real-time spectral induced polarization monitoring of lead remediation by an aeolian soil.

Compared to traditional lead-remediating materials, natural-occurring paleosol is ubiquitous and could be a promising alternative due to its rich content in calcite, a substance known for its lead-removal ability via carbonate dissolution-PbCO3 precipitation process. Yet, the capability of paleosol to remediate aqueous solutions polluted with heavy metals, lead included, has rarely been assessed. To fill this gap, a series of column permeation experiments with influent Pb2+ concentrations of 2000, 200, and 20 mg/L were conducted and monitored by the spectral induced polarization technique. Meanwhile, the SEM-EDS, XRD, XPS, FTIR and MIP tests were carried out to unveil the underlying remediation mechanisms. The Pb-retention capacity of paleosol was 1.03 mmol/g. The increasing abundance of Pb in the newly-formed crystals was confirmed to be PbCO3 by XRD, SEM-EDS and XPS. Concurrently, after Pb2+ permeation, the decreasing calcite content in paleosol sample from XRD test, and the appearance of Ca2+ in the effluent confirmed that the dissolution of CaCO3 followed by the precipitation of PbCO3 was the major mechanism. The accumulated Pb (i.e., the diminished Ca) in paleosol was inversely proportional (R2 >0.82) to the normalized chargeability (mn), an SIP parameter denoting the quantity of polarizable units (primarily calcite).

Journal requirement for data sharing statements in clinical trials: a cross-sectional study.

OBJECTIVES: Data sharing statements are considered routine in clinical trial reporting and represent a step toward data transparency. The International Committee of Medical Journal Editors (ICMJE) required clinical trials to publish data sharing statements. We aimed to assess the requirement for data sharing statements of individual participant data by biomedical journals and explore associations between journal characteristics and journal requirements for data sharing statements. STUDY DESIGN AND SETTING: In this cross-sectional study, we included all biomedical journals that published clinical trials from January 1, 2019, to December 31, 2022, and that were indexed by the Journal Citation Reports. The study outcome was the journal requirement for data sharing statements. Multivariable logistic regression analysis was used to assess the relationship between journal characteristics and requirement for data sharing statements. RESULTS: Of the 3229 biomedical journals included in the analysis, 2345 (72.6%) required authors to include data sharing statements. Journals published in the UK (OR, 3.19 [95% CI, 2.43-4.22]) and endorsing the Consolidated Standards of Reporting Trials (OR, 3.30 [95% CI, 2.78-3.92]) had greater odds of requiring data sharing statements. Journals that were open access, non-English language, in the Journal Citation Reports group of clinical medicine, and on the ICMJE list had lower odds of requiring data sharing statements, with ORs ranging from 0.18 to 0.81. CONCLUSION: Despite ICMJE recommendations, more than 27% of the biomedical journals that published clinical trials did not require clinical trials to include data sharing statements, highlighting room for improved transparency.

In Vitro Evaluation of Chito-Oligosaccharides on Disappearance Rate of Nutrients, Rumen Fermentation Parameters, and Micro-Flora of Beef Cattle.

The study aimed to investigate the effect of dietary chitosan oligosaccharides (COS) meal levels on the nutrient disappearance rate, rumen fermentation, and microflora of beef cattle in vitro. A total of 24 fermentation tanks were randomly divided into four treatments containing 0% COS (CON), 0.02% COS, 0.04% COS, and 0.08% COS for an 8-day experiment period, with each treatment comprising six replicates. The disappear rates of DM, CP, EE, and total gas production were quadratically increased with increasing COS levels. The disappear rates of DM, CP, EE, and ADF were greatest, whereas the total gas production was lowest in the 0.08% COS group. The pH, NH3-N, MCP, the content of propionate, isobutyrate, butyrate, valerate, and the A/P were quadratically increased with increasing COS levels, while the A/P were linearly decreased. The pH, MCP, and the content of propionate, and butyrate were highest, whereas the NH3-N and the content of acetate, isobutyrate, valerate, and the A/P were lowest in the 0.08% COS group. Microbiomics analysis showed that the rumen microbial diversity was not altered between the CON and the 0.08% COS group. However, the relative abundance of Methanosphaera, Ruminococcus, Endomicrobium, and Eubacterium groups was increased, and the relative abundance of pathogenic bacteria Dorea and Escherichia-Shigella showed a decrease in the 0.08% COS group. Overall, the 0.08% COS was the most effective among the three addition levels, resulting in an increase in the disappearance rate of in vitro fermented nutrients and improvements in rumen fermentation indexes and microbial communities. This, in turn, led to the maintenance of rumen health.

Impact Response Features and Penetration Mechanism of UHMWPE Subjected to Handgun Bullet.

Ensuring military and police personnel protection is vital for urban security. However, the impact response mechanism of the UHMWPE laminate used in ballistic helmets and vests remains unclear, making it hard to effectively protect the head, chest, and abdomen. This study utilized 3D-DIC technology to analyze UHMWPE laminate's response to 9 mm lead-core pistol bullets traveling at 334.93 m/s. Damage mode and response characteristics were revealed, and an effective numerical calculation method was established that could reveal the energy conversion process. The bullet penetrated by 1.03 mm, causing noticeable fiber traction, resulting in cross-shaped failure due to fiber compression and aggregation. Bulge transitioned from circular to square, initially increasing rapidly, then slowing. Maximum in-plane shear strain occurred at ±45°, with values of 0.0904 and -0.0928. Model accuracy was confirmed by comparing strain distributions. The investigation focused on bullet-laminate interaction and energy conversion. Bullet's kinetic energy is converted into laminate's kinetic and internal energy, with the majority of erosion energy occurring in the first four equivalent sublaminates and the primary energy change in the system occurring at 75 µs in the fourth equivalent sublayer. The results show the damage mode and energy conversion of the laminate, providing theoretical support for understanding the impact response mechanism and improving the efficiency of protective energy absorption.

Molecular Dynamics Simulation of the Interaction within the Carboxymethyl Cellulose-Modified Montmorillonite Lamellae at Aggressive CuCl2 Concentrations.

To elucidate the degradation mechanism of the CMC-modified MMT composite at aggressive Cu2+ concentrations, large scale molecular dynamics simulation was conducted for CuCl2 concentrations ranging from 0 to 800 mM. Both CMC and MMT followed the Langmuir isotherm for Cu2+ adsorption, and the adsorption capacity of CMC (8.75 mmol/g) was much higher than that of MMT (0.83 mmol/g). Despite the CMC mass ratio being only 4.1%, it adsorbed up to 34.3% of the total adsorbed Cu2+. The Cu2+ attraction ability hierarchy of oxygen-containing functional groups in the CMC is as follows: carboxylic oxygens > alcoholic oxygens > carbinolic oxygens > bridging oxygens > glucose oxygens. Carboxyls were the most effective in chelating and complexing with Cu2+, and they could be intentionally added in artificially synthesized polymer-MMT composites for Cu2+ containment. Formation of the Cu2+ cation bridge between CMC and MMT at aggressive CuCl2 concentrations contributed to the transition of CMC density distribution from unimodality to bimodality and enhanced resistance of polymer elution. As the CuCl2 concentration increased, the stoichiometric ratio between the chelated Cu2+ and carboxylic oxygens increased from 1:2 to 1:1, suggesting the evolution of the Cu2+ chelation mechanism.

Gut microbial metabolism is linked to variations in circulating non-high density lipoprotein cholesterol.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-c) was a strong risk factor for incident cardiovascular diseases and proved to be a better target of lipid-lowering therapies. Recently, gut microbiota has been implicated in the regulation of host metabolism. However, its causal role in the variation of non-HDL-c remains unclear. METHODS: Microbial species and metabolic capacities were assessed with fecal metagenomics, and their associations with non-HDL-c were evaluated by Spearman correlation, followed by LASSO and linear regression adjusted for established cardiovascular risk factors. Moreover, integrative analysis with plasma metabolomics were performed to determine the key molecules linking microbial metabolism and variation of non-HDL-c. Furthermore, bi-directional mendelian randomization analysis was performed to determine the potential causal associations of selected species and metabolites with non-HDL-c. FINDINGS: Decreased Eubacterium rectale but increased Clostridium sp CAG_299 were causally linked to a higher level of non-HDL-c. A total of 16 microbial capacities were found to be independently associated with non-HDL-c after correcting for age, sex, demographics, lifestyles and comorbidities, with the strongest association observed for tricarboxylic acid (TCA) cycle. Furthermore, decreased 3-indolepropionic acid and N-methyltryptamine, resulting from suppressed capacities for microbial reductive TCA cycle, functioned as major microbial effectors to the elevation of circulating non-HDL-c. INTERPRETATION: Overall, our findings provided insight into the causal effects of gut microbes on non-HDL-c and uncovered a novel link between non-HDL-c and microbial metabolism, highlighting the possibility of regulating non-HDL-c by microbiota-modifying interventions. FUNDING: A full list of funding bodies can be found in the Sources of funding section.