Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

Association of dietary inflammatory index with risk of gestational diabetes mellitus and preeclampsia: a systematic review and meta-analysis.

Findings from observational studies have suggested a possible association between dietary inflammatory index (DII) and risk of gestational diabetes mellitus (GDM) and preeclampsia (PE). However, the results of these studies were inconclusive. A systematic review and meta-analysis was carried out to illuminate this association. Systematic literature search was conducted in PubMed, Web of Science, Cochrane Library, EMBASE, Scopus and other databases from inception until January 2023. The qualities of included studies were assessed using the Newcastle-Ottawa scale. Nine studies (seven cohort, two case-control) were included in the meta-analysis, including 11 423 participants from five different countries. The meta-analysis indicated that a 1-unit increase in the DII score, representing pro-inflammatory diet, was associated with 13 % higher risk of GDM (OR = 1·13; 95 % CI 1·02, 1·25, I2 = 68·4 %, P = 0·004) and 24 % higher risk of PE (OR = 1·24; 95 % CI 1·14, 1·35, I2 = 52·0 %, P = 0·125). Subgroup analysis found that this association was evident among studies with Chinese populations (OR = 1·16; 95 % CI 1·06, 1·28) and studies with mid pregnancy (OR = 1·20; 95 % CI 1·07, 1·34). The findings indicate that pro-inflammatory diet can increase the risk of GDM and PE. Considering some limitations in this study, more studies are needed to verify this association.

Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study.

BACKGROUND AND AIM: Evidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. METHODS AND RESULTS: We employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59-0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37-0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44-0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56-0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58-0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52-0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49-0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63-0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43-0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56-0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. CONCLUSION: This two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases.

Postprandial Triglyceride-Rich Lipoproteins-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Inflammation in White Adipocytes.

BACKGROUND: Obesity and postprandial hypertriglyceridemia, characterized by an increase in triglyceride-rich lipoproteins (TRLs), cause chronic low-grade inflammation. It is unclear how postprandial TRLs affect inflammation in white adipocytes. OBJECTIVES: The objectives of the study were to explore the inflammatory response of postprandial TRLs in white adipocytes and investigate the possible mechanism. METHODS: We measured postprandial triglyceride (TG) and high-sensitivity C-reactive protein (hsCRP) concentrations in 204 recruited subjects and treated white adipocytes from mice with postprandial TRLs from above patients with hypertriglyceridemia. RESULTS: Serum hsCRP concentrations and BMI were positively related to TG concentrations in the postprandial state. Postprandial TRLs increased mRNA and protein expression of inflammatory factors, including interleukin-1ß, via the NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway, and impaired autophagy flux in white adipocytes of mice. TRLs also induced lysosomal damage as evidenced by the reduced protein expression of lysosome-associated membrane proteins-1 and Cathepsin L. Inhibition of Cathepsin B, NLRP3, and mTOR signaling improved autophagy/lysosome dysfunction and inhibited the activation of the NLRP3/Caspase-1 pathway and inflammatory factors induced by TRLs in white adipocytes. CONCLUSIONS: Our results suggest that postprandial hypertriglyceridemia causes chronic inflammation in adipocytes through TRL-induced lysosomal dysfunction and impaired autophagic flux in an mTOR-dependent manner.

RNautophagic regulation of DNMT3a-dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer.

BACKGROUND: Energy balance has long been known to extend lifespans and inhibit carcinogenesis in multiple species by slowing age-related epigenetic changes while the underlying mechanisms remain largely unknown. Herein, we found that starvation activated autophagy to remodel the DNA methylation profile by inhibiting DNMT3a expression. METHODS: Illumina Infinium MethylationEPIC BeadChip and dot blot assay were performed to quantify the global DNA methylation level. Protein-RNA interactions were validated through RNA immunoprecipitation and RNA pull-down assay. In vitro and in vivo experiments were carried out to testify the effect of DNMT3a on chemoresistance. RESULTS: Autophagy is impaired in chemoresistance which was associated with differential DNA methylation and could be reversed by DNMT3a inhibition. Autophagy activation decreases the expression of DNMT3a mRNA, accompanied with the downregulation of chemoresistance-related Linc00942. Knockdown of Linc00942 reduces DNMT3a expression and genome-wide DNA methylation while Linc00942 overexpression increased DNMT3a expression and correlated hypermethylation in cancer cells and primary tumour tissues. Mechanistically, Linc00942 recruits RNA methyltransferase METTL3 to stimulate N6-methyladenosine (m6A) deposit on DNMT3a transcripts, triggering IGF2BP3/HuR to recognize modified mRNA for reinforced stability. SQSTM1/p62 recruits Linc00942 for autophagic degradation which can be abrogated after autophagy inhibition by p62 knockdown or chloroquine treatment. CONCLUSIONS: Inhibition of autophagy increases Linc00942 expression to promote chemoresistance and autophagy activation or hypomethylating agent decitabine restores chemosensitivity by reducing global DNA methylation. Overall, this study identifies a novel methylation cascade linking impaired RNautophagy to global hypermethylation in chemoresistance, and provides a rationale for repurposing decitabine to overcome chemoresistance in cancer treatment.

Blood Service in a Region of China's Qinghai-Tibetan Plateau.

Objectives: The purpose of this paper is to describe blood services in the Aba Tibetan and Qiang Regions, (hereinafter referred to as Aba Prefecture), a region of China's Qinghai-Tibetan Plateau, the third largest area of Tibet and the main inhabited area of the Qiang people. Design: We present a comprehensive investigation into blood donations, donors, screening and supply in the 13 counties of Aba Prefecture based on data from 2013 to 2018. Geography and population were also used to analyze the differences in blood services among different regions. Participants: The number of blood donors totaled 19,047. Results: Over the past 6 years, blood donations have increased by 29 and clinical blood usage by 45%. The blood donation rate was 3.4‱ and per capita blood use was 1.04 mL, both of which were significantly lower than the national average, and blood donation decreased with altitude. It should be noted that the donation rate of the Tibetan and Qiang peoples is much lower than that of the Han population. Moreover, the rejection rate of blood in laboratory testing was found to be higher than the national average, especially in counties located at higher altitudes. Conclusions: Blood donations and usage increased every year in Aba Prefecture, but blood shortage is still an important issue. In addition, the prevalence of transfusion-transmitted diseases is relatively high, which may be linked to lower-education and unfavorable geographical and medical conditions.

Light-switchable transcription factors obtained by direct screening in mammalian cells.

Optogenetic tools can provide fine spatial and temporal control over many biological processes. Yet the development of new light-switchable protein variants remains challenging, and the field still lacks general approaches to engineering or discovering protein variants with light-switchable biological functions. Here, we adapt strategies for protein domain insertion and mammalian-cell expression to generate and screen a library of candidate optogenetic tools directly in mammalian cells. The approach is based on insertion of the AsLOV2 photoswitchable domain at all possible positions in a candidate protein of interest, introduction of the library into mammalian cells, and light/dark selection for variants with photoswitchable activity. We demonstrate the approach's utility using the Gal4-VP64 transcription factor as a model system. Our resulting LightsOut transcription factor exhibits a > 150-fold change in transcriptional activity between dark and blue light conditions. We show that light-switchable function generalizes to analogous insertion sites in two additional Cys6Zn2 and C2H2 zinc finger domains, providing a starting point for optogenetic regulation of a broad class of transcription factors. Our approach can streamline the identification of single-protein optogenetic switches, particularly in cases where structural or biochemical knowledge is limited.

Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer.

INTRODUCTION: Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, the crosstalk between cuproptosis and ferroptosis is obscure. MATERIALS AND METHODS: We analyzed the effect of ferroptosis inducers on copper ionophores-induced cell death through CCK-8 assay. Cuproptosis was studied using immunofluorescence and protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR and western blot were adopted to explore the machinery of ferroptosis inducers enhanced cuproptosis. And mouse xenograft model was built to detect the synergy effect of elesclomol-Cu and sorafenib in vivo. RESULTS: Herein we found that ferroptosis inducers sorafenib and erastin could enhance cuproptosis in primary liver cancer cells by increasing copper dependent lipoylated protein aggregation. Mechanically, sorafenib and erastin upregulated protein lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) protein degradation, and reduced intracellular copper chelator glutathione (GSH) synthesis through inhibiting cystine importing. DISCUSSION/CONCLUSION: Our findings proposed that combination of ferroptosis inducers and copper ionophores to co-targeting ferroptosis and cuproptosis could be a novel therapeutic strategy for primary liver cancer.

HSF1 promotes CD69+ Treg differentiation to inhibit colitis progression.

Regulatory T cells (Tregs) are critical for generating and maintaining peripheral tolerance. Treg-based immunotherapy is valuable for the clinical management of diseases resulting from dysregulation of immune tolerance. However, the lack of potency is a potential limitation of Treg therapy. In addition, CD69 positive-Treg (CD69+ Treg) represent a newly identified subset of Tregs with potent immune suppressive capability. Methods: Foxp3 YFP-Cre CD69 fl/fl and CD4 Cre CD69 fl/fl mice were generated to determine the relevance of CD69 to Treg. Chromatin Immunoprecipitation Assay (ChIP) and luciferase Assay were performed to detect the regulation of CD69 transcription by heat shock transcription factor 1(HSF1). Gene expression was measured by western blotting and qRT-PCR. The differentiation of naive T cells to CD69+Foxp3+ iTregs was determined by flow cytometry. The immunosuppressive ability of Tregs was analyzed by ELISA and flow cytometry. Colon inflammation in mice was reflected by changes in body weight and colon length, the disease activity index (DAI), and H&E staining of colon tissues. Results: Induced Tregs (iTregs) from CD4 Cre CD69 fl/fl mice failed to alleviate colitis. The transcription factor HSF1 interacted with the promoter of the CD69 gene to prompt its transcription during Treg differentiation. Genetic and chemical inhibition of HSF1 impaired CD69+ Treg differentiation and promoted the pathogenesis of colitis in mice. In contrast, HSF1 protein stabilized by inhibiting its proteasomal degradation promoted CD69+ Treg differentiation and alleviated colitis in mice. Moreover, adoptive transfer of iTregs with HSF1 stabilization by proteasome inhibitor (PSI) dramatically prevented the development of colitis in mice and was accompanied by decreased production of pro-inflammatory cytokines and reduced accumulation of pro-inflammatory lymphocytes in colitis tissue, whereas Tregs induced in the absence of PSI were less stable and ineffective in suppressing colitis. Conclusions: HSF1 promotes CD69+ Tregs differentiation by activating the CD69 transcription, which is critical for the immunosuppressive function of Tregs. Stabilization of HSF1 by PSIs results in the efficient generation of Tregs with high potency to treat colitis and probably other autoimmune diseases involving Tregs deficiency.

Comparison between Fasting and Non-Fasting Cut-Off Values of Triglyceride in Diagnosing High Triglyceride in Chinese Hypertensive Outpatients.

Background: Hypertension (HBP) often occurs together with hypertriglyceridemia which indicates elevated triglyceride (TG) and remnant cholesterol (RC) levels. Non-fasting (i.e., postprandial) blood lipid test after a daily meal has been recommended by the European Atherosclerosis Society (EAS). However, little is known about the difference between fasting and non-fasting cut-off values in assessing high TG (HTG) and high RC (HRC) in HBP outpatients. Methods: 225 Chinese outpatients with HBP, including 119 fasting patients (i.e., fasting group) and 106 non-fasting patients (i.e., non-fasting group) were enrolled in this study. Non-fasting levels of blood lipids at 2 h after a daily breakfast were also tested in 33 patients among the fasting group. Venous blood samples were collected. Results: The non-fasting group had significantly higher levels of TG and RC while lower levels of total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol than the fasting group (p < 0.05). According to the TG and RC cut-off values of the EAS, the percentages of HTG and HRC in the non-fasting group were 72.6% and 70.8%, respectively, whereas those in the fasting group were 57.1% and 52.9%, respectively. According to the cut-off value of marked HTG commonly used in the Chinese population in clinical practice, the percentage of marked HTG in the non-fasting group was 57.5%, whereas that in the fasting group was 34.5%. However, the percentages of HTG (57.6% vs. 51.5%) and HRC (51.5% vs. 51.5%) marked HTG (30.3% vs. 33.3%) in the fasting state and at 2 h after a daily breakfast in 33 outpatients did not reach statistical significance. Conclusion: Non-fasting blood lipid tests could find more individuals with HTG as well as those with marked HTG among Chinese outpatients with HBP. It indicates that non-fasting blood lipid tests are worth being recommended in patients with HBP.

Advances in Noble Metal-Decorated Metal Oxide Nanomaterials for Chemiresistive Gas Sensors: Overview.

Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring, exhaled breath diagnosis, and food freshness analysis. Among various chemiresistive sensing materials, noble metal-decorated semiconducting metal oxides (SMOs) have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals. This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures (e.g., nanoparticles, nanowires, nanorods, nanosheets, nanoflowers, and microspheres) for high-performance gas sensors with higher response, faster response/recovery speed, lower operating temperature, and ultra-low detection limits. The key topics include Pt, Pd, Au, other noble metals (e.g., Ag, Ru, and Rh.), and bimetals-decorated SMOs containing ZnO, SnO2, WO3, other SMOs (e.g., In2O3, Fe2O3, and CuO), and heterostructured SMOs. In addition to conventional devices, the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed. Moreover, the relevant mechanisms for the sensing performance improvement caused by noble metal decoration, including the electronic sensitization effect and the chemical sensitization effect, have also been summarized in detail. Finally, major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.

Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study.

Periconceptional folate supplementation is prevalent, raising concerns about possible side effects. The aim of this study was to investigate the associations of folic acid supplementation, dietary folate, serum folate with gestational diabetes mellitus (GDM) risk. In this matched case-control study, 81 pregnant women with GDM (cases) and 81 pregnant women with non-GDM (controls) were identified through age difference (≤3 y) and parity (Both primipara or multipara women) matching, and serum folate levels were measured during the GDM screening (24-28 gestational wk). Folic acid supplementation and dietary folate intake from three months prepregnancy through midpregnancy were assessed using a self-reported questionnaire and food frequency questionnaire. Multivariate binary logistic regression models were used to evaluate the association between folate and GDM. After adjusting for confounding factors, we observed that compared with folic acid supplementation dose ≤400 µg/d, pregnancies without folic acid supplementation and supplemental dose >800 µg/d were associated with GDM risk (adjusted odds ratio=7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratio=4.20, 95% confidence interval: 1.03-17.22), while no significant association with a 400-800 µg/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose ≤24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratio=6.70, 95% confidence interval: 1.22-36.77), while no significant association with folic acid supplementation dose >24 wk and GDM. No significant association of dietary folate and serum folate with GDM was found. No or a higher dose of folic acid supplementation would increase GDM risk and a dose of <800 µg/d is the safe dose.

Determination of the postprandial cut-off value of triglyceride after a daily meal corresponding to fasting optimal triglyceride level in Chinese subjects.

Background: According to the 2021 consensus statement about triglyceride (TG)-rich lipoproteins and their remnants from the European Atherosclerosis Society (EAS), fasting TG level < 1.2 mmol/L is regarded as optimal, otherwise considered as non-optimal TG (NoTG). However, the postprandial cut-off value after a daily meal corresponding to a fasting TG level of 1.2 mmol/L has not been explored. Materials and methods: Six hundred and eighteen inpatients aged 18 to 70 were recruited in this study. Among them, 219 subjects had fasting TG levels < 1.2 mmol/L (i.e., OTG group), and 399 subjects had fasting TG levels ≥ 1.2 mmol/L (i.e., NoTG group). Serum levels of blood lipids, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were monitored at 0, 2, and 4 h after a daily Chinese breakfast according to their dietary habits. Receiver operating characteristic (ROC) curve analysis was used to determine the postprandial cut-off value corresponding to the fasting TG level of 1.2 mmol/L. Kappa statistics were performed to determine the consistency between fasting and postprandial cut-off values in determining whether TG was optimal. Univariate and multivariate logistic regression analyses were conducted to evaluate the associations between NoTG and potential confounders. Subgroup analyses were performed to explore the association between postprandial TG levels at 4h (pTG4h) and NoTG in greater detail. Results: Postprandial levels of TG and RC significantly elevated and peaked at 4h after a daily breakfast in two groups (P < 0.05). The optimal cut-off value at 4h corresponding to fasting TG of 1.2 mmol/L was 1.56 mmol/L. According to the fasting cut-off value, the percentage of patients with NoTG was 64.6% in the fasting state while increasing obviously to 73.3-78.4% at 2 and 4h, respectively, after a daily Chinese breakfast. According to the postprandial cut-off value, the percentage of patients with NoTG at 4h after a daily Chinese breakfast was 62.6% which was close to 64.6% in the fasting state. The Kappa coefficient was 0.551, indicating a moderate consistency between the fasting and postprandial cut-off values in the diagnosis of NoTG. Moreover, the subjects with NoTG determined by the postprandial TG cut-off value had an obviously higher postprandial level of RC (1.2 vs. 0.8 mmol/L) and percentage of HRC (37.1 vs. 32.1%) than those determined by the fasting TG cut-off value. Multivariate logistic regression analyses demonstrated that except for BMI, pTG4h emerged as an independent predictor of not. Subgroup analyses revealed that the association between pTG4h and NoTG was consistent across subgroups. Conclusion: Taken together, we for the first time determined TG 1.56 mmol/L as the postprandial cut-off value corresponding to fasting TG 1.2 mmol/L in Chinese subjects. This could make it more convenient to determine whether TG is optimal or not in the fasting or postprandial state.

Effects of Xuezhikang versus Pravastatin on Triglyceride Level in Patients with T2DM and Dyslipidemia: Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Hypertriglyceridemia, is commonly found in patients with diabetes. Xuezhikang, an extract of red yeast rice, is effective in reducing cardiovascular events in Chinese patients with diabetes and coronary heart disease (CHD). Xuezhikang has been reported to significantly decrease the level of triglycerides (TG), a potential causal risk factor for myocardial infarction. On the basis of a similar reduction in low-density lipoprotein cholesterol, this study will evaluate the effect of xuezhikang on TG levels compared with pravastatin in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia. METHODS: This is an open-label, multicenter, randomized controlled study to assess the effects of xuezhikang (1.2 g/day) and pravastatin (20 mg/day) on TG and other blood lipid parameters in patients with T2DM and dyslipidemia. A total of 114 patients will be enrolled and randomly assigned 1:1 to receive xuezhikang or pravastatin treatment for 6 weeks. RESULT: The primary outcome measure is the change from baseline in fasting TG levels after 6 weeks. The change from baseline in other fasting and postprandial lipid parameters, and glucose profiles at 1, 2, and 4 h after a nutritious breakfast will also be explored. CONCLUSION: This study will evaluate the effect of a 6-week treatment with xuezhikang compared with pravastatin on fasting and postprandial TG levels and other blood lipid parameters in patients with T2DM and dyslipidemia without atherosclerotic cardiovascular disease (ASCVD). The results will provide more information on optimizing the lipid control of patients with diabetes in the primary prevention of ASCVD.

Microsomal prostaglandin E synthase-1 inhibition prevents adverse cardiac remodelling after myocardial infarction in mice.

BACKGROUND AND PURPOSE: Heart failure with reduced ejection fraction (HFrEF) is a major consequence of myocardial infarction (MI). The microsomal prostaglandin E synthase-1 (mPGES-1)/PGE2 pathway has been shown to constrain reperfusion injury after acute myocardial ischaemia. However, it is unknown whether pharmacological inhibition of mPGES-1, a target with lower risk of thrombosis compared with selective inhibition of cyclooxygenase-2, affects chronic cardiac remodelling after MI. EXPERIMENTAL APPROACH: Mice were subjected to left anterior descending coronary artery ligation, followed by intraperitoneal treatment with the mPGES-1 inhibitor compound III (CIII) or 118, celecoxib (cyclooxygenase-2 inhibitor) or vehicle, once daily for 28 days. Urinary prostanoid metabolites were measured by liquid chromatography-tandem mass spectrometry. KEY RESULTS: Chronic administration of CIII improved cardiac function in mice after MI compared with vehicle or celecoxib. CIII did not affect thrombogenesis or blood pressure. In addition, CIII reduced infarct area, augmented scar thickness, decreased collagen I/III ratio, decreased the expression of fibrosis-related genes and increased capillary density in the ischaemic area. Shunting to urinary metabolites of PGI2 , not thromboxane B2 or PGD2 , after inhibition of mPGES-1 was positively correlated with cardiac function after MI. CIII administration significantly increased urinary PGI2 /PGE2 metabolite ratio compared to vehicle or celecoxib. The PGI2 /PGE2 metabolite ratio correlated positively with ejection fraction, fractional shortening and scar thickness. Treatment with 118 also improved cardiac function. CONCLUSION AND IMPLICATIONS: Inhibition of mPGES-1 prevented chronic adverse cardiac remodelling via an augmented PGI2 /PGE2 metabolite ratio and therefore represents a potential therapeutic strategy for development of HFrEF after MI.

Postprandial triglyceride-rich lipoproteins promote the adipogenic differentiation of adipose-derived mesenchymal stem cells via the LRP1/caveolin-1/AKT1 pathway.

Diet-induced obesity (OB) is usually accompanied by hypertriglyceridemia, which is characterized by the accumulation of triglyceride (TG)-rich lipoprotein (TRL) particles in the circulation. We previously found that postprandial TRL combined with insulin induced the adipogenic differentiation of 3T3-L1 preadipocytes, which may represent a key mechanism underlying obesity. However, the specific mechanism and signaling pathway involved in this process remain to be fully elucidated. In this study, we found that, in the postprandial state, patients with obesity had significantly higher levels of TG and remnant cholesterol (RC) than normal-weight controls. In vitro, we found that postprandial TRL, together with insulin, promoted the adipogenic differentiation of adipose-derived mesenchymal stem cells (AMSCs), as evidenced by the increased expression of lipogenesis-related genes and their protein products, including low-density lipoprotein related protein 1 (LRP1). Besides, caveolin-1 (Cav-1) expression was also significantly upregulated under this condition. Cav-1 and LRP1 were observed to interact, and then led to the activation of the PI3K/AKT1 signaling pathway. Meanwhile, the inhibition of LRP1 or Cav-1 significantly attenuated the adipogenic differentiation of AMSCs and downregulated AKT1 phosphorylation levels. Moreover, treatment with a selective AKT1 inhibitor significantly suppressed postprandial TRL and insulin-induced adipogenesis in AMSCs. Combined, our results demonstrated that, in association with insulin, postprandial TRL can promote the adipogenic differentiation of AMSCs in a manner that is dependent on the LRP1/Cav-1-mediated activation of the PI3K/AKT1 signaling pathway. Our findings indicated that a postprandial increase in TRL content is a critical factor in the pathogenesis of hypertriglyceridemia and diet-induced obesity.

Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance.

Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ERα limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ERα increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel. Notably, CAV1 expression inversely correlates with ERα and relates to improved clinical outcomes from nab-paclitaxel treatment. Importantly, ERα stimulates m6A dependent maturation of miR199a-5p, which is elevated in ER+ breast cancer, to inhibit CAV1 translation by antagonizing m6A modification of CAV1 mRNA. Together, our findings reveal a novel role of ERα in promoting m6A modification and subsequent maturation of miR199a-5p, which is upregulated in ER+ breast cancer, leading to the suppression of m6A modification of CAV1 and its mRNA translation, thereby contributing to nab-paclitaxel resistance. Thus, combining an ER antagonist with nab-paclitaxel could offer a promising strategy for treating ER+ breast cancer patients.

Recent Progress on Flexible Room-Temperature Gas Sensors Based on Metal Oxide Semiconductor.

With the rapid development of the Internet of Things, there is a great demand for portable gas sensors. Metal oxide semiconductors (MOS) are one of the most traditional and well-studied gas sensing materials and have been widely used to prepare various commercial gas sensors. However, it is limited by high operating temperature. The current research works are directed towards fabricating high-performance flexible room-temperature (FRT) gas sensors, which are effective in simplifying the structure of MOS-based sensors, reducing power consumption, and expanding the application of portable devices. This article presents the recent research progress of MOS-based FRT gas sensors in terms of sensing mechanism, performance, flexibility characteristics, and applications. This review comprehensively summarizes and discusses five types of MOS-based FRT gas sensors, including pristine MOS, noble metal nanoparticles modified MOS, organic polymers modified MOS, carbon-based materials (carbon nanotubes and graphene derivatives) modified MOS, and two-dimensional transition metal dichalcogenides materials modified MOS. The effect of light-illuminated to improve gas sensing performance is further discussed. Furthermore, the applications and future perspectives of FRT gas sensors are also discussed.

Heterostructured α-Fe2 O3 @ZnO@ZIF-8 Core-Shell Nanowires for a Highly Selective MEMS-Based ppb-Level H2 S Gas Sensor System.

Highly selective and sensitive H2 S sensors are in high demand in various fields closely related to human life. However, metal oxide semiconductors (MOSs) suffer from poor selectivity and single MOS@metal organic framework (MOF) core-shell nanocomposites are greatly limited due to the intrinsic low sensitivity of MOF shells. To simultaneously improve both selectivity and sensitivity, heterostructured α-Fe2 O3 @ZnO@ZIF-8 core-shell nanowires (NWs) are meticulously synthesized with the assistance of atomic layer deposition. The ZIF-8 shell with regular pores and special surface functional groups is attractive for excellent selectivity and the heterostructured α-Fe2 O3 @ZnO core with an additional electron depletion layer is promising with enhanced sensitivity compared to a single MOS core. As a result, the heterostructured α-Fe2 O3 @ZnO@ZIF-8 core-shell NWs achieve remarkable H2 S sensing performance with a high response (Rair /Rgas  = 32.2 to 10 ppm H2 S), superior selectivity, fast response/recovery speed (18.0/31.8 s), excellent long-term stability (at least over 3 months), and relatively low limit of detection (down to 200 ppb) at low operating temperature of 200 °C, far beyond α-Fe2 O3 @ZIF-8 or α-Fe2 O3 @ZnO core-shell NWs. Furthermore, a micro-electromechanical system-based H2 S gas sensor system with low power consumption is developed, holding great application potential in smart cities.

The accuracy of four formulas for LDL-C calculation at the fasting and postprandial states.

Background: Elevated level of low-density lipoprotein cholesterol (LDL-C) is concerned as one of the main risk factors for cardiovascular disease, in both the fasting and postprandial states. This study aimed to compare the measured LDL-C with LDL-C calculated by the Friedewald, Martin-Hopkins, Vujovic, and Sampson formulas, and establish which formula could provide the most reliable LDL-C results for Chinese subjects, especially at the postprandial state. Methods: Twenty-six subjects were enrolled in this study. The blood samples were collected from all the subjects before and after taking a daily breakfast. The calculated LDL-C results were compared with LDL-C measured by the vertical auto profile method, at both the fasting and postprandial states. The percentage difference between calculated and measured LDL-C (total error) and the number of results exceeding the total error goal of 12% were established. Results: The calculated LDL-CF levels showed no significant difference from LDL-CVAP levels at the fasting state. The calculated LDL-CS were significantly higher than LDL-CVAP at the fasting state (P < 0.05), while the calculated LDL-Cs were very close to LDL-CVAP levels after a daily meal. At the fasting state, the median total error of calculated LDL-CF was 0 (quartile: -3.8 to 6.0), followed by LDL-CS, LDL-CMH, and LDL-CV. At the postprandial states, the median total errors of LDL-CS were the smallest, 1.0 (-7.5, 8.5) and -0.3 (-10.1, 10.9) at 2 and 4 h, respectively. The calculated LDL-CF levels showed the highest correlation to LDL-CVAP and accuracy in evaluating fasting LDL-C levels, while the Sampson formula showed the highest accuracy at the postprandial state. Conclusion: The Friedewald formula was recommended to calculate fasting LDL-C, while the Sampson formula seemed to be a better choice to calculate postprandial LDL-C levels in Chinese subjects.