Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

Performance evaluation and clinical application of the UA-5600 automatic dry chemistry urine analyzer in renal diseases.

Background: Urine testing as a routine screening programme, abnormal test results can be suggestive to clinicians but can sometimes be overlooked, and the establishment of a diagnostic model can better assist clinicians in identifying potential problems. BLD (blood), LEU (leukocyte), PRO (protein) and GLU (glucose) are the four most important parameters in urine testing, and the accuracy of their results is a key concern for clinicians, so it is essential to verify the accuracy of their results. In this study, we evaluated the analytical and clinical performance of Mindray's automatic urine dry chemistry analyzer, the UA-5600 (Hereinafter referred to as the (UA-5600), and the test strips configured with the instrument, and developed a machine-learning (ML) model for kidney disease screening from the results of 11 parameters output from the UA-5600 with the aim of detecting abnormal urine test results. Methods: Urine samples from outpatients and inpatients at The First Affiliated Hospital of Sun Yat-sen University were collected from August to September 2022 to evaluate the performance of the Mindray UA-5600 dry chemistry analyzer and test strips. The evaluation of the UA-5600 and its test strips focused on the agreement of the urine BLD and LEU readings with the RBC (red blood cell) and WBC (white blood cell) counts obtained by the Mindray EH-2090 urine formed element analyzer. We also compared the PRO and GLU readings with the results of the Mindray BS-2800M biochemistry analyzer. Urine samples from outpatients and inpatients were retrospectively analysed and grouped according to LIS diagnosis. Additionally, eight ML models for kidney disease screening were developed using 11 parameters measured by the UA-5600. And the model was validated by the validation set. Results: The UA-5600 had an 89.55% concordance rate for BLD and a 91.04% concordance rate for LEU compared to the EH-2090 analyzer. When benchmarked against the BS-2800M, the concordance rates for PRO and GLU were 94.14% and 95.20%, respectively. A total of 1,691 samples were used for the construction of the ML models, of which 346 patients (135 males and 211 females, age range: 18 to 98 years) diagnosed with renal disease, and 1,345 patients (397 males and 948 females, age range: 18 to 92 years) with non-renal disease diagnosed with other conditions. Notably, the Naïve Bayes (NB) model, which was built from the UA-5600 parameters, demonstrated superior predictive capabilities for renal disease, with an area under the receiver operating characteristic curve of 0.9470, a sensitivity of 0.7767, and a specificity of 0.9457. Conclusions: The Mindray UA-5600 demonstrates robust detection abilities for both BLD and LEU, and its results for PRO and GLU align closely with those obtained from the chemistry analyzer. The NB model has a good screening ability and shows promise as an effective screening tool.

Effect of Meal-Timing on the Association of Unsaturated Fatty Acids with All-Cause and Cardiovascular Mortality among Adults: A Prospective Cohort Study with 10-Year Follow-Up.

BACKGROUND: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. METHODS: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. RESULTS: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. CONCLUSIONS: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.

Epigallocatechin-3-gallate inhibits osteogenic differentiation of vascular smooth muscle cells through the transcription factor JunB.

Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.

Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

Prevalence rate of primary osteoporosis in China: a meta-analysis.

BACKGROUND: Primary osteoporosis (POP) is recognized as a "silent disease" and often ignored. This meta-analysis aimed to determine the prevalence of POP in the Chinese population over the past 20 years to raise awareness of the disease's epidemiology, which is hoped to help prevent and treat the condition better. METHODS: Eight English and three Chinese language databases were searched systematically from January 2002 to December 2023. Relevant data were analysed using Stata 16.0. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. A funnel plot was further drawn in combination with Egger and Begg tests to determine publication bias. RESULTS: A total of 45 studies (241,813 participants) were included. The meta-analysis revealed that the overall prevalence of POP in the Chinese population was 18.2% (95% CI: 14.7-21.7%), showing a positive correlation with age. Specifically, prevalence rates were 23.4% (18.3-28.5%) in women and 11.5% (9.1-13.9%) in men. A notable increase was observed within the span of 20 years (16.9% before 2010 and 20.3% in 2011-2020). Notably, regional variations were observed, with southern China reporting a lower prevalence of 16.4% compared to 20.2% in northern China. Meta-regression suggested that sample size significantly influenced the estimation of point prevalence (P = 0.037). CONCLUSIONS: Over the past two decades, there has been an increase in the prevalence of POP within the Chinese population. The growing prevalence of older individuals and women further highlights the urgency for tailored disease prevention and control measures.

Clinical and pathologic characterization of a mouse model of graded limbal stem cell deficiency.

Limbal stem cell deficiency (LSCD) is a clinically challenging eye disease caused by damage to limbal stem cells (LSCs). Currently, the international consensus classifies LSCD into three clinical stages based on the disease severity. However, no existing animal models attempt to replicate the varying degrees of LSCD observed in clinical cases. The present study demonstrates an easy-to-create, reproducible, and reliable mouse model of graded LSCD. To achieve mild, moderate, or severe LSCD, filter paper rings with a variety of central angles (90°, 180°, or 270°) are utilized to deliver alkali burns to different sizes of the limbal area (1, 2, or 3 quarters). The animal model has successfully resulted in the development of clinical signs and pathological manifestations in escalating severity that are similarly observed in the three clinical stages of LSCD. Our study thus provides new insights into distinct pathological features underlying different grades of LSCD and serves as a new tool for further exploring the disease mechanisms and developing new effective therapeutics for repairing damaged LSCs.

Quantitative proteomics reveals the dynamic proteome landscape of zebrafish embryos during the maternal-to-zygotic transition.

Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

Extraordinary Structural Reconstruction of Nanolaminated Ta2FeC MAX Phase for Enhanced Oxygen Evolution Performance.

Renewable energy technologies, such as water splitting, heavily depend on the oxygen evolution reaction (OER). Nanolaminated ternary compounds, referred to as MAX phases, show great promise for creating efficient electrocatalysts for OER. However, their limited intrinsic oxidative resistance hinders the utilization of conductivity in Mn+1Xn layers, leading to reduced activity. In this study, a method is proposed to improve the poor inoxidizability of MAX phases by carefully adjusting the elemental composition between Mn+1Xn layers and single-atom-thick A layers. The resulting Ta2FeC catalyst demonstrates superior performance compared to conventional Fe/C-based catalysts with a remarkable record-low overpotential of 247 mV (@10 mA cm-2) and sustained activity for over 240 h. Notably, during OER processing, the single-atom-thick Fe layer undergoes self-reconstruction and enrichment from the interior of the Ta2FeC MAX phase toward its surface, forming a Ta2FeC@Ta2C@FeOOH heterostructure. Through density functional theory (DFT) calculations, this study has found that the incorporation of Ta2FeC@Ta2C not only enhances the conductivity of FeOOH but also reduces the covalency of Fe─O bonds, thus alleviating the oxidation of Fe3+ and O2-. This implies that the Ta2FeC@Ta2C@FeOOH heterostructure experiences less lattice oxygen loss during the OER process compared to pure FeOOH, leading to significantly improved stability. These results highlight promising avenues for further exploration of MAX phases by strategically engineering M- and A-site engineering through multi-metal substitution, to develop M2AX@M2X@AOOH-based catalysts for oxygen evolution.

Clinical Implications of Estimating Glomerular Filtration Rate with Different Equations in Heart Failure Patients with Preserved Ejection Fraction.

INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and  < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or  < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Prevalence and influencing factors of kinesiophobia in older patients with primary osteoporosis: A cross-sectional survey.

AIM: To explore the prevalence of kinesiophobia in older patients with primary osteoporosis and analyze its influencing factors. METHODS: A cross-sectional survey was conducted among 221 older patients with primary osteoporosis in a general hospital in Kunming, China. Data were collected through a sociodemographic-clinical questionnaire, Tampa Scale for Kinesiophobia-11 (TSK-11), Global Pain Scale (GPS), Five Facets Mindfulness Questionnaire-Short Form (FFMQ-SF), and Hospital Anxiety and Depression Scale (HADS). SPSS 27.0 software was utilized for univariate and binary logistic regression analyses. RESULTS: The findings revealed that the prevalence of kinesiophobia in this study was 57.01 %. Age, history of fractures, chronic obstructive pulmonary disease (COPD), lumbar disc herniation, chronic pain, mindfulness, anxiety, and depression were identified as significant influencing factors of kinesiophobia in the binary logistic regression analyses. CONCLUSION: Healthcare professionals should be attentive to occurrence of kinesiophobia. Timely measures should be implemented to improve pain, anxiety and depression, and employ mindfulness interventions to mitigate kinesiophobia.

Regulating the Electronic Structure of MAX Phases Based on Rare Earth Element Sc to Enhance Electromagnetic Wave Absorption.

MAX phases are highly promising materials for electromagnetic (EM) wave absorption because of their specific combination of metal and ceramic properties, making them particularly suitable for harsh environments. However, their higher matching thickness and impedance mismatching can limit their ability to attenuate EM waves. To address this issue, researchers have focused on regulating the electronic structure of MAX phases through structural engineering. In this study, we successfully synthesized a ternary MAX phase known as Sc2GaC MAX with the rare earth element Sc incorporated into the M-site sublayer, resulting in exceptional conductivity and impressive stability at high temperatures. The Sc2GaC demonstrates a strong reflection loss (RL) of -47.7 dB (1.3 mm) and an effective absorption bandwidth (EAB) of 5.28 GHz. It also achieves effective absorption of EM wave energy across a wide frequency range, encompassing the X and Ku bands. This exceptional performance is observed within a thickness range of 1.3 to 2.1 mm, making it significantly superior to other Ga-MAX phases. Furthermore, Sc2GaC exhibited excellent absorption performance even at elevated temperatures. After undergoing oxidation at 800 °C, it achieves a minimum RL of -28.3 dB. Conversely, when treated at 1400 °C under an argon atmosphere, Sc2GaC demonstrates even higher performance, with a minimum RL of -46.1 dB. This study highlights the potential of structural engineering to modify the EM wave absorption performance of the MAX phase by controlling its intrinsic electronic structure.

Facile Preparation of ß-Cyclodextrin-Modified Polysulfone Membrane for Low-Density Lipoprotein Adsorption via Dopamine Self-Assembly and Schiff Base Reaction.

A facile method for the immobilization of ß-cyclodextrin on polysulfone membranes with the aim of selectively adsorbing low-density lipoprotein (LDL) was established, which is based on the self-assembly of dopamine on the membrane followed by the Schiff base reaction with mono-(6-ethanediamine-6-deoxy)-ß-cyclodextrin. The surface modification processes were validated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transform infrared spectroscopy. Surface wettability and surface charge of the membranes were investigated through the water contact angle and zeta potential analysis. The cyclodextrin-modified polysulfone membrane (PSF-CD) showed good resistance to protein solutions, as shown by the measurement of BSA adsorption. The assessment of BSA adsorption revealed that the cyclodextrin-modified polysulfone membrane (PSF-CD) exhibited excellent resistance to protein solutions. To investigate the adsorption and desorption behaviors of the membranes in single-protein or binary-protein solutions, an enzyme-linked immunosorbent assay was employed. The results revealed that the PSF-CD possessed remarkable adsorption capacity and higher affinity for LDL in both single-protein and binary-protein solutions, rendering it a suitable material for LDL apheresis.

Optical Information Transmission and Multimode Fluorescence Anticounterfeiting of Ca2-xMgxGe7O16:Mn2.

Multimode emission of Mn2+ for multimode fluorescence anticounterfeiting is achieved by cation site and interstitial occupancy in Ca2-xMgxGe7O16. The rings in Ca2-xMgxGe7O16 have a significant distortion for Mn2+ ions to enter the ring interstitials with a luminescence center at 665 nm, which is supported by XRD refinement results and first-principles calculations. The interstitial Mn2+ ion has good thermal stability with an activation energy of 0.36 eV. Surprisingly, these two luminescence centers, the cation site Mn and the interstitial Mn, have an obvious afterglow, and the disappearing afterglow will reappear by heating or irradiating with the 980 nm laser. The afterglow is significantly enhanced, as MnO2 is used as the manganese source, which is explained in detail by the thermal luminescence spectrum. Finally, Ca2-xMgxGe7O16:Mn2+ fully demonstrates its excellent prospects in fluorescent anticounterfeiting, information encryption, and optical information storage.

The response of structure and nitrogen removal function of the biofilm on submerged macrophytes to high ammonium in constructed wetlands.

The ammonium exceedance discharge from sewage treatment plants has a great risk to the stable operation of subsequent constructed wetlands (CWs). The effects of high ammonium shocks on submerged macrophytes and epiphytic biofilms on the leaves of submerged macrophytes in CWs were rarely mentioned in previous studies. In this paper, the 16S rRNA sequencing method was used to investigate the variation of the microbial communities in biofilms on the leaves of Vallisneria natans plants while the growth characteristics of V. natans plants were measured at different initial ammonium concentrations. The results demonstrated that the total chlorophyll and soluble sugar synthesis of V. natans plants decreased by 51.45% and 57.16%, respectively, and malondialdehyde content increased threefold after 8 days if the initial NH4+-N concentration was more than 5 mg/L. Algal density, bacterial quantity, dissolved oxygen, and pH increased with high ammonium shocks. The average removal efficiencies of total nitrogen and NH4+-N reached 73.26% and 83.94%, respectively. The heat map and relative abundance analysis represented that the relative abundances of phyla Proteobacteria, Cyanobacteria, and Bacteroidetes increased. The numbers of autotrophic nitrifiers and heterotrophic nitrification aerobic denitrification (HNAD) bacteria expanded in biofilms. In particular, HNAD bacteria of Flavobacterium, Hydrogenophaga, Acidovorax, Acinetobacter, Pseudomonas, Aeromonas, and Azospira had higher abundances than autotrophic nitrifiers because there were organic matters secreted from declining leaves of V. natans plants. The analysis of the nitrogen metabolic pathway showed aerobic denitrification was the main nitrogen removal pathway. Thus, the nitrification and denitrification bacterial communities increased in epiphytic biofilms on submerged macrophytes in constructed wetlands while submerged macrophytes declined under ammonium shock loading.

Water Radiocatalysis for Selective Aqueous-Phase Methane Carboxylation with Carbon Dioxide into Acetic Acid at Room Temperature.

Methane (CH4) carboxylation with carbon dioxide (CO2) into acetic acid (CH3COOH) is an ideal chemical reaction to utilize both greenhouse gases with 100% atom efficiency but remains a great challenge under mild conditions. Herein, we introduce a concept of water (H2O) radiocatalysis for efficient and selective aqueous-phase CH4 carboxylation with CO2 into CH3COOH at room temperature. H2O radiolysis occurs under γ-ray radiation to produce ·OH radicals and hydrated electrons that efficiently react with CH4 and CO2, respectively, to produce ·CH3 radicals and ·CO2- species facilely coupling to produce CH3COOH. CH3COOH selectivity as high as 96.9 and 96.6% calculated respectively from CH4 and CO2 and a CH3COOH production rate of as high as 121.9 µmol·h-1 are acquired. The water radiocatalysis driven by γ-rays is also applicable to selectively produce organic acids from other hydrocarbons and CO2.

Plant-based diets, mediating biomarkers, and mortality risk among adults with diabetes or prediabetes.

Background: A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods: This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results: Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P-trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P-trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P-trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P-trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions: For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA. Here we investigated the clinical impact and underlying molecular characteristics of C. sinensis infection-related iCCA. METHODS: We performed single-cell RNA sequencing, whole-exome sequencing, RNA sequencing, metabolomics and spatial transcriptomics in 251 patients with iCCA from three medical centers. Alterations in metabolism and the immune microenvironment of C. sinensis-related iCCAs were validated through an in vitro co-culture system and in a mouse model of iCCA. RESULTS: We revealed that C. sinensis infection was significantly associated with iCCA patients' overall survival and response to immunotherapy. Fatty acid biosynthesis and the expression of fatty acid synthase (FASN), a key enzyme catalyzing long-chain fatty acid synthesis, were significantly enriched in C. sinensis-related iCCAs. iCCA cell lines treated with excretory/secretory products of C. sinensis displayed elevated FASN and free fatty acids. The metabolic alteration of tumor cells was closely correlated with the enrichment of tumor-associated macrophage (TAM)-like macrophages and the impaired function of T cells, which led to formation of an immunosuppressive microenvironment and tumor progression. Spatial transcriptomics analysis revealed that malignant cells were in closer juxtaposition with TAM-like macrophages in C. sinensis-related iCCAs than non-C. sinensis-related iCCAs. Importantly, treatment with a FASN inhibitor significantly reversed the immunosuppressive microenvironment and enhanced anti-PD-1 efficacy in iCCA mouse models treated with excretory/secretory products from C. sinensis. CONCLUSIONS: We provide novel insights into metabolic alterations and the immune microenvironment in C. sinensis infection-related iCCAs. We also demonstrate that the combination of a FASN inhibitor with immunotherapy could be a promising strategy for the treatment of C. sinensis-related iCCAs. IMPACT AND IMPLICATIONS: Clonorchis sinensis (C. sinensis)-infected patients with intrahepatic cholangiocarcinoma (iCCA) have a worse prognosis and response to immunotherapy than non-C. sinensis-infected patients with iCCA. The underlying molecular characteristics of C. sinensis infection-related iCCAs remain unclear. Herein, we demonstrate that upregulation of FASN (fatty acid synthase) and free fatty acids in C. sinensis-related iCCAs leads to formation of an immunosuppressive microenvironment and tumor progression. Thus, administration of FASN inhibitors could significantly reverse the immunosuppressive microenvironment and further enhance the efficacy of anti-PD-1 against C. sinensis-related iCCAs.