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Background: Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations. Methods: This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years. Results: We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change. Conclusion: This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity. [ABSTRACT FROM AUTHOR]

Summary: Background: The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. Aims: To investigate the effects of the NAFLD risk alleles on the all‐cause and cause‐specific mortality in 5581 Chinese adults. Methods: The genome‐wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. Results: Genome‐wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P = 8.6 × 10−7). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29 425.1 person‐years of follow‐up, the overall mortality was 816 per 100 000 person‐years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver‐specific mortality (P for trend = 0.034) but reduced cardiovascular mortality (P for trend = 0.047). A composite genetic‐predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver‐specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver‐specific mortality were found (Pinteraction < 0.05). The reduced serum VLDL1 concentration was responsible for the increased liver‐specific mortality related to NAFLD risk alleles. Conclusion: The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver‐specific mortality but reduce cardiovascular mortality in overweight/obese Chinese. [ABSTRACT FROM AUTHOR]

Background and Purpose: Berberine, a compound from rhizome coptidis, is traditionally used to treat gastrointestinal infections, such as bacterial diarrhoea. Recently, berberine was shown to have hypoglycaemic and hypolipidaemic effects. We investigated the mechanisms by which berberine regulates hepatic lipid metabolism and energy expenditure in mice.Experimental Approach: Liver-specific SIRT1 knockout mice and their wild-type littermates were fed a high-fat, high-sucrose (HFHS) diet and treated with berberine by i.p. injection for five weeks. Mouse primary hepatocytes and human HepG2 cells were treated with berberine and then subjected to immunoblotting analysis and Oil Red O staining.Key Results: Berberine attenuated hepatic steatosis and controlled energy balance in mice by inducing autophagy and FGF21. These beneficial effects of berberine on autophagy and hepatic steatosis were abolished by a deficiency of the nutrient sensor SIRT1 in the liver of HFHS diet-fed obese mice and in mouse primary hepatocytes. SIRT1 is essential for berberine to potentiate autophagy and inhibit lipid storage in mouse livers in response to fasting. Mechanistically, the berberine stimulates SIRT1 deacetylation activity and induces autophagy in an autophagy protein 5-dependent manner. Moreover, the administration of berberine was shown to promote hepatic gene expression and circulating levels of FGF21 and ketone bodies in mice in a SIRT1-dependent manner.Conclusions and Implications: Berberine acts in the liver to regulate lipid utilization and maintain whole-body energy metabolism by mediating autophagy and FGF21 activation. Hence, it has therapeutic potential for treating metabolic defects under nutritional overload, such as fatty liver diseases, type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Xia et al papers. To view these articles, visit https://doi.org/10.1111/apt.16772 and https://doi.org/10.1111/apt.16818 [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus. We investigated whether the deposition of fat in the liver is associated with glycemic abnormalities and evaluated the contribution of the liver fat content (LFC) to the impaired glucose regulation. We conducted a community-based study among 2836 residents (1018 males and 1818 females) without prior known diabetes mellitus from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The standardised ultrasound hepatic-renal echo-intensity and hepatic echo-intensity attenuation rate were used to assess the LFC. The cohort was stratified according to the quintiles for LFC. Two-hour glucose and fasting blood glucose increased across the LFC quintiles after adjustment for age and gender. LFC increased continuously among glucose categories after adjustment for age and gender (NGT: 7.7±0.3%, IFG: 10.0±0.8%, IGT: 11.8±0.5%, IFG+IGT: 11.7±0.9%, new- DM: 12.4±0.6%, P<0.001). By logistic regression analysis, 1% LFC increment independently predicted prediabetes and diabetes (OR 1.032, 1.019–1.045, P<0.001; 1.021, 1.005–1.037, P = 0.012, respectively) after adjustment for all potential confounders. Furthermore, participants with LFC higher than 10% had higher odds ratios of impaired glucose regulation as compared with those with LFC below 10% in fully adjusted logistic models. These results suggest that the LFC is strongly associated with impaired glucose regulation in the Chinese population, and that an even slightly elevated LFC is associated with increased glucose dysregulation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Nonalcoholic fatty liver disease is closely associated with metabolic syndrome and cardiovascular disease (CVD). We investigated whether the liver fat content (LFC) is independently associated with carotid artery intima-media thickness (CIMT) and evaluated the contribution of the LFC to the increased CIMT. Methods: We conducted a community-based study among 1809 participants (682 males and 1127 females) from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The CIMT was determined by ultrasonography. A large CIMT value was defined as 75th percentile of the maximum CIMT. A standardised ultrasonographic hepatic-renal ratio was used to assess the LFC. Results: The median LFC value was 6% (interquartile range, 3–14%), and 34% of the subjects had hepatic steatosis based on the criteria for diagnosis of steatosis by quantitative ultrasound. The maximum CIMT, average CIMT and plaque score were strongly associated with the LFC (β = 0.319, 0.324 and 1.361, respectively; all P < 0.05) after adjustment for age, gender, smoking history, low-density lipoprotein cholesterol and metabolic syndrome. The multiple logistic regression analysis showed that a 1 SD increase in the LFC, the OR for having a large CIMT was 1.350 (95% CI 1.180–1.545; P < 0.001) after adjustment for all potential confounders. Conclusions: These results suggest that the LFC is independently associated with carotid atherosclerosis in the Chinese population, and that the risk of atherosclerosis is proportional to the degree of hepatic steatosis. [Copyright &y& Elsevier]

Nanocellulose has lately emerged as one of the most promising "green" materials due to its unique properties. Nanocellulose can be mainly divided into three types, i.e., cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial cellulose (BC). With the rapid development of technology, nanocellulose has been designed into multidimensional structures, including 1D (nanofibers, microparticles), 2D (films), and 3D (hydrogels, aerogels) materials. Due to its adaptable surface chemistry, high surface area, biocompatibility, and biodegradability, nanocellulose-based composite materials can be further transformed as drug delivery carriers. Herein, nanocellulose-based composite material used for drug delivery was reviewed. The typical drug release behaviors and the drug release mechanisms of nanocellulose-based composite materials were further summarized, and the potential application of nanocellulose-based composite materials was prospected as well. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease that affects over 30% of the world's population. For decades, the heterogeneity of non-alcoholic fatty liver disease (NAFLD) has impeded our understanding of the disease mechanism and the development of effective medications. However, a recent change in the nomenclature from NAFLD to MASLD emphasizes the critical role of systemic metabolic dysfunction in the pathophysiology of this disease and therefore promotes the progress in the pharmaceutical treatment of MASLD. In this review, we focus on the mechanism underlying the abnormality of hepatic lipid metabolism in patients with MASLD, and summarize the latest progress in the therapeutic medications of MASLD that target metabolic disorders. [ABSTRACT FROM AUTHOR]

A series of different contents of glycidyl methacrylate (GMA)-grafted natural rubber (GNR) copolymers were fabricated via green bulk melt-grafting reactions, and super-tough bio-based poly (lactic acid) (PLA)/GNR thermoplastic vulcanizates (TPVs) were achieved by in-situ dynamic vulcanization. Increasing the graft yield, gel fraction, and crosslinking density of GNR vulcanizates effectively improved the ductility of the PLA/GNR TPVs, while prolonging the dynamic vulcanization time and increasing the GMA graft yield led to a notable enhancement in the impact toughness of the PLA/GNR TPVs. PLA/30 wt % GNR TPVs exhibited a significantly increased elongation (410%) and notched impact strength (73.2 kJ/m2), which were 40 and 15 times higher than those of the PLA/30 wt % NR TPVs, respectively. The new bio-based PLA/GNR TPVs offer promise as replacements for petroleum-based polymers in the automotive, 3D printing, and packaging fields. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (P)/alginate (A)/MMT (M) (PAM) composite aerogels was modified through interpenetrating cross-linking of methyltriethoxysilane (Ms) or γ-aminopropyltriethoxysilane (K) and calcium ion (Ca2+) as a cross-linking agent, respectively. The compressive moduli of the cross-linked PAM/MsCa and PAM/KCa aerogels greatly increased to 17.4 and 22.1 MPa, approximately 10.5- and 8.2-fold of that of PAM aerogel, respectively. The limited oxygen index (LOI) values for PAM/MsCa and PAM/KCa composite aerogels increased from 27.0% of PAM aerogel to 40.5% and 56.8%. Compared with non-cross-linked PAM aerogel, the peak heat release rate (PHRR) of PAM/MsCa and PAM/KCa composite aerogels dramatically decreased by 34% and 74%, respectively, whereas the PAM/KCa aerogel presented better flame retardancy and lower smoke toxicity than the PAM/MsCa aerogel because of the release of more inert gases and the barrier action of more compact char layer during the combustion. The highly efficient flame-retardant PAM-based composite aerogels with excellent mechanical properties are promising as a sustainable alternative to traditional petroleum-based foams. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Elevation of Liver Enzymes Within the Normal Limits and Metabolic Syndrome," by M. F. Xia, H. M. Yan and H. D. Lin.

Background: Circulating levels of amino acids were associated with blood pressure (BP) in observational studies. However, the causation of such associations has been hypothesized but is difficult to prove in human studies. Here, we aimed to use two-sample Mendelian randomization analyses to evaluate the potential causal associations of circulating levels of amino acids with BP and risk of hypertension.Methods: We generated genetic instruments for circulating levels of nine amino acids by conducting meta-analyses of genome-wide association study (GWAS) in UK Biobank participants with metabolomic data (n = 98,317) and another published metabolomics GWAS (n = 24,925). Data on the associations of the genetic variants with BP and hypertension were obtained in the UK Biobank participants without metabolomic data (n = 286,390). The causal effects were estimated using inverse-variance weighted method.Results: Significant evidence consistently supported the causal effects of increased branched-chain amino acids (BCAAs, i.e., leucine, isoleucine, and valine) levels on higher BP and risk of hypertension (all P < 0.006 after Bonferroni correction except for Pleucine-on-diastolicBP = 0.008). For example, per standard deviation higher of genetically predicted isoleucine levels were associated with 2.71 ± 0.78 mmHg higher systolic BP and 1.24 ± 0.34 mmHg higher diastolic BP, as well as with 7% higher risk of hypertension (odds ratio: 1.07, [95% CI: 1.04-1.10]). In addition, per standard deviation higher of genetically predicted glycine level was associated with lower systolic BP (- 0.70 ± 0.17 mmHg, P = 4.04 × 10-5) and a lower risk of hypertension (0.99 [0.98-0.99], P = 6.46 × 10-5). In the reverse direction, genetically predicted higher systolic BP was associated with lower circulating levels of glycine (- 0.025±0.008, P = 0.001).Conclusions: This study provides evidence for causal impacts of genetically predicted circulating BCAAs and glycine levels on BP. Meanwhile, genetically predicted higher BP was associated with lower glycine levels. Further investigations are warranted to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vitamin D exerts metabolic activities. We investigated whether the 25-hydroxy vitamin D [25(OH)D] is associated with liver fat content (LFC) and non-alcoholic fatty liver disease (NAFLD) in a middle-aged, elderly Chinese population. Subject/Methods: A total of 2,960 participants (954 men and 2,006 women) aged over 45 years old were enrolled. Each participant underwent a standard interview, anthropometric measurements and laboratory examinations. Vitamin D deficiency and insufficiency was diagnosed when serum 25(OH) D level was < 50 and 50–75nmol/L. An ultrasound quantitative method was used to assess the LFC. Results: Among the 2,960 participants, 1,982 (67.0%) subjects had vitamin D deficiency, 769 (26.0%) had vitamin D insufficiency, and 209 (7%) had normal vitamin D. Male subjects with vitamin D deficiency and insufficiency had significantly higher LFC than those with normal 25(OH)D (P = 0.034), while the LFC values showed no significant difference among the female subjects with vitamin D sufficiency, insufficiency and deficiency (P = 0.396). Univariate correlation analysis showed that 25(OH)D had a significantly negative association with LFC in men (r = -0.085, P = 0.009), but not in women. After adjusting for age, cigarette smoking, examination season, serum calcium, PTH and all possible confounders that displayed significant associations with LFC in univariate correlation analysis, serum 25(OH)D remained associated with LFC in middle-aged and elderly Chinese men. Conclusion: Serum 25(OH)D level was inversely associated with LFC in middle-aged and elderly Chinese men. [ABSTRACT FROM AUTHOR]

Background and Purpose: Salvianolic acid B (SalB) is effective for treating cardiovascular diseases. However, the molecular mechanisms underlying its therapeutic effects remain unclear. Mechanosensitive Piezo1 channels play important roles in vascular biology, although their pharmacological properties are poorly defined. Here, we aimed to identify novel Piezo1 inhibitors and gain insights into their mechanisms of action. Experimental Approach Intracellular Ca2+ ions were measured in HUVECs, murine liver endothelial cells (MLECs), THP‐1 and RAW264.7 cell lines and bone marrow‐derived macrophages (BMDMs). Isometric tensions in mouse thoracic aorta were recorded. Shear‐stress assays with HUVECs were conducted. Patch‐clamp recordings with mechanical stimulation were performed with HUVECs in whole‐cell mode. Foam cell formation was induced by treating BMDMs with oxidised LDL (oxLDL). Atherosclerotic plaque assays were performed with Ldlr−/− and Piezo1 genetically depleted mice on a high‐fat diet. Key Results: Salvianolic acid B inhibited Yoda1‐induced Ca2+ influx in HUVECs and MLECs. Similar results were observed in macrophage cell lines and BMDMs. Furthermore, we demonstrated that salvianolic acid B inhibited Yoda1‐ and mechanically activated currents. Salvianolic acid B suppressed Yoda1‐induced aortic ring relaxation and inhibited HUVECs alignment in the direction of shear stress. Additionally, Yoda1 enhanced the formation of foam cells, which was reversed by salvianolic acid B. Salvianolic acid B also inhibited formation of atherosclerotic plaques and was insensitive to Piezo1 genetic depletion. Conclusion and Implications: Our study provides novel mechanistic insights into the inhibitory role of salvianolic acid B against Piezo1 channels and improves our understanding of salvianolic acid B in preventing atherosclerotic lesions. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19. Highlights: • MAFLD was associated with increased risk and severity of COVID-19. • 31% of COVID-19 patients had MAFLD. • COVID-19 promoted liver injury and progression of MAFLD, especially in the youth. • The mechanism of liver injury in patients with COVID-19 was multifactorial. •Early screen and active treatment of MAFLD is recommended for patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators. Methods: The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators. Results: The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695–0.871), 0.764 (95% CI: 0.663–0.846), 0.837 (95% CI: 0.744–0.906) and 0.902 (95% CI: 0.822–0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.205, P = 0.026) and alanine aminotransferase (ALT, β = 0.192, P = 0.047) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c < 7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI < 30 kg/m2. Conclusions: FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values. [ABSTRACT FROM AUTHOR]

Background: Although thyroid function has been demonstrated to be associated with non-alcoholic fatty liver disease (NAFLD) in different population, the prevalence and features of NAFLD in hyperthyroidism have not been reported. The present study aims to investigate the prevalence of NAFLD and association of thyroid function and NAFLD in hyperthyroidism patients. Methods: This cross-sectional study was performed in Zhongshan Hospital, Fudan University, China. A total 117 patients with hyperthyroidism were consecutively recruited from 2014 to 2015. Thyroid function and other clinical features were measured, liver fat content was measured by color Doppler ultrasonically, NAFLD was defined in patients with liver fat content more than 9.15%. Statistical analyses were performed with SPSS software package version 13.0. Results: The prevalence of NAFLD was 11.97% in hyperthyroidism. Patient with NAFLD had lower free triiodothyronine (FT3) and free thyroxine (FT4) levels than patients without NAFLD (P < 0.05). After adjusting for age, gender, metabolic parameters and inflammation factors, higher FT3 were associated with lower liver fat content (β = − 0.072, P = 0.009) and decreased odds ratio of NAFLD (OR = 0.267, 95%CI 0.087–0.817, P = 0.021). Conclusions: FT3 level was negatively associated with the liver fat content in this population. These results may provide new evidence in the role of thyroid hormone on the regulation of liver fat content and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism. Methods: This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT) with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n = 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15 mg qd, and LSI + berberine (BBR) 0.5 g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H-MRS) to assess liver fat content. Results: As compared with LSI, PGZ + LSI treatment further decreased liver fat content in women (− 15.24% ± 14.54% vs. − 8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (− 9.95% ± 15.18% vs. − 12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism. Conclusion: The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism. Trial registration: Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282. Registered on 3 March 2008, https://register.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Screening for prediabetes and asymptomatic diabetes is important for preventing development to an irreversible stage. The current diagnosis of prediabetes and diabetes is based on blood glucose or HbA1c (an invasive method). The aim of this study was to assess the efficacy and safety of DS21, a new noninvasive technology, for noninvasive screening for prediabetes and diabetes.Methods: A total of 939 subjects were divided into a normal control group (NC, n = 308), impaired glucose regulation group (IGR, n = 312), and diabetes (DM) group (n = 319). All subjects underwent the DS21 test, and mean hands-feet, hand, and feet conductance values were analyzed. The diagnostic accuracy of the conductance value was analyzed by receiver-operating characteristic (ROC) curve.Results: The conductance values for hands-feet, hands, and feet in the DM and IGR groups were significantly lower than those in the NC group (all P < 0.01). The area under the ROC curve  (AUCROC) for distinguishing NC/IGR was highest when using hands-feet conductance values (0.766 [95% confidence interval, CI 0.730, 0.803]). However, the AUCROCs of distinguishing NC/abnormal glucose metabolism (AGM, including IGR+DM), non-diabetes (NDM)/DM, and IGR/DM were highest when using conductance values for hands at 0.782 [95% CI 0.752, 0.812], 0.688 [95% CI 0.653, 0.723] and 0.573 [95% CI 0.528, 0.617], respectively (all P < 0.01). Hand conductance of values 75.0 (sensitivity 0.769, specificity 0.660), 77.1 (sensitivity 0.718, specificity 0.695), 68.4 (sensitivity 0.726, specificity 0.555), and 58.1 (sensitivity 0.384, specificity 0.744) were recommended as the screening thresholds for NC/AGM, NC/IGR, NDM/DM, and IGR/DM, respectively. A hand conductance value 66.0 was also recommended to distinguish NC/AGM due to its high sensitivity and high PPV. No adverse events occurred in the test.Conclusions: DS21 is fast, noninvasive, low cost, reliable and safe, which makes it a feasible device for screening for prediabetes and diabetes, especially in a large population. [ABSTRACT FROM AUTHOR]

Objective: We investigated the relationship between fasting serum fructose levels and the risk of incident type 2 diabetes in a prospective Chinese cohort.Research Design and Methods: Among 949 community-based participants aged ≥40 years without diabetes at baseline, fasting serum fructose levels were measured using liquid chromatography-tandem mass spectrometry. The participants were followed up for the occurrence of diabetes. Cox regression models were performed to analyze the effect of fasting serum fructose levels on risk of incident diabetes.Results: During a median of 3.5 years' follow-up, 179 of 949 (18.9%) participants developed type 2 diabetes. Elevated fasting serum fructose levels were associated with an increased risk of incident diabetes in a dose-response manner. After adjustment for age, sex, BMI, lipid profiles, blood pressure, liver function, smoking and drinking status, baseline glucose level, and sugar-sweetened beverage consumption, a 1-SD increased fasting fructose level was associated with a 35% (95% CI 1.08-1.67) increased risk of developing diabetes. After further adjustment for serum uric acid and estimated glomerular filtration rate, the association was partially attenuated (hazard ratio 1.33 [95% CI 1.07-1.65]). The association was similar by age, prediabetes status, BMI, and family history of diabetes but attenuated in women (P for heterogeneity = 0.037).Conclusions: Elevated fasting serum fructose levels were independently associated with increased risk of incident type 2 diabetes in a middle-aged and older Chinese population. Our data suggest that higher fasting serum fructose levels might serve as a biomarker and/or a contributor to incident diabetes. [ABSTRACT FROM AUTHOR]

Background: Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism. Methods: Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid. Results: FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter. Conclusions: FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation. [ABSTRACT FROM AUTHOR]

• A new two-step crosslinked PVA/alginate/MMT aerogel shows high flame retardancy. • The crosslinked PVA/alginate/MMT aerogel exhibits ultra-low-smoke-toxicity. • The compression property of the crosslinked PVA/alginate/MMT aerogel enhanced. A highly efficient flame-retardant and ultra-low-smoke-toxicity biodegradable material, poly(vinyl alcohol) (PVA)/alginate/montmorillonite (MMT) composite aerogel, was fabricated by a new environment-friendly two-step crosslinking strategy using borate and calcium ions. Compressive and specific moduli of the crosslinked PVA/alginate/MMT (P4A4M4/BA/Ca) aerogel increased to 7.2- and 1.9-folds those of the non-crosslinked aerogel, respectively, and the limited oxygen index value increased to 40.0%. Cone calorimeter tests revealed that the total heat release and peak heat release rate values of the P4A4M4/BA/Ca composite aerogel distinctly decreased. Remarkably, the total smoke release value of the P4A4M4/BA/Ca aerogel was considerably lower than those of non-crosslinked PVA composite aerogels, indicating its superior smoke suppression ability and high fire hazardous safety. The flame-retardancy mechanism of the crosslinked P4A4M4/BA/Ca composite aerogels involved a combination of the gaseous phase and condensed phase flame retardancy. The high-performance PVA/alginate/MMT biodegradable composite aerogels with good sustainability is a promising alternative to conventional flame-retardant foams. [ABSTRACT FROM AUTHOR]

Berberine (BBR), a natural compound extracted from Chinese herb, has been shown to effectively attenuate nonalcoholic fatty liver disease (NAFLD) in clinic. However, the mechanism underlying the effect of BBR is not fully understood. Stearyl-coenzyme A desaturase 1 (SCD1) mediates lipid metabolism in liver. Therefore, we hypothesized that SCD1 mediated the beneficial effect of BBR on NAFLD. The expression of SCD1 was measured in the liver of NAFLD patients and ob/ob mice. The effect of BBR on NAFLD was evaluated in C57BL/6 J mice on high fat diet (HFD). The effect of BBR was also investigated in HepG2 and AML12 cells exposed to high glucose and palmitic acid. Oil red O staining was performed to detect triglyceride (TG) level. Quantitative real-time polymerase chain reaction and Western blot were used to detect the messenger ribonucleic acid (mRNA) and protein expression of target genes. The activity of SCD1 promoter was measured by dual-luciferase reporter assay. The expression of SCD1 was increased in the liver of NAFLD patients and ob/ob mice. BBR reduced hepatic TG accumulation and decreased the expressions of hepatic SCD1 and other TG synthesis related genes both in vivo and in vitro. Knockdown of SCD1 expression mimicked the effect of BBR decreasing TG level in steatotic hepatocytes, whereas overexpression of SCD1 attenuated the effect of BBR. Mechanistically, BBR promoted the phosphorylation of AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein-1c (SREBP-1c) in HepG2 cells and the liver of HFD-fed mice. Activation of the AMPK-SREBP-1c pathway and sterol regulatory element (SRE) motif in SCD1 promoter (−920/-550) was responsible for the BBR-induced suppression of SCD1. BBR reduces liver TG synthesis and attenuates hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway. Image 1 • The expression of SCD1 is increased in the liver of NAFLD patients and mice with fatty liver compared with control group. • Berberine reduces the expression of SCD1 in the liver and attenuates hepatic steatosis. • AMPK-SREBP-1c-SCD1 pathway mediates the effect of berberine on hepatic steatosis. • This study identifies a novel mechanism for berberine in the treatment of steatosis, which may promote its application. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acute sleeve gastrectomy (SG) improves postprandial chylomicron, not VLDL triglycerides (TGs). • Type 2 diabetes (DM) patients after SG show less improvement in postprandial chylomicron TGs than patients without DM. • Postprandial chylomicron metabolites in DM patients after SG increase intestinal cell fatty acid synthesis. • The timing for SG to improve postprandial chylomicron TGs and the potential risk of cardiovascular disease is before DM. It remains unclear whether early sleeve gastrectomy (SG) improves postprandial very-low-density lipoprotein (VLDL) as well as chylomicron triglycerides (TGs) in a weight-independent manner in patients with or without type 2 diabetes (DM). Herein we investigated the early effects of SG on postprandial VLDL and chylomicron kinetics. A liquid meal test was performed before and after 1 week of SG. The plasma was collected for postprandial triglyceride-rich lipoprotein kinetics analyses, including VLDLs and chylomicrons, isolated by high-speed ultracentrifugation. Lipidomics and metabolomics were used to profile lipid and metabolite compositions of plasma and postprandial chylomicrons. De novo fatty acid synthesis in intestinal epithelial cells treated with chylomicron metabolites was examined using RT-PCR, immunoblotting, and free fatty acid measurement. We found that patients with DM had markedly higher VLDL TGs than patients without DM, and such an increase was still retained after SG. In contrast, SG significantly decreased postprandial chylomicron TGs, but surprisingly, the degree of the reduction in patients with DM was less prominent than in patients without DM, confirmed by untargeted lipidomics analysis. Moreover, 5 unique metabolites potentially linked to de novo fatty acid synthesis from the pathway analysis were discovered by further metabolomic analysis of postprandial chylomicrons from patients with DM who underwent SG and verified by In vitro intestinal epithelial cell culture experiments. SG in 1 week did not impact postprandial VLDL but decreased chylomicron TGs. Patients with DM keep higher postprandial chylomicron TG concentrations than patients without it after SG, potentially through some unique metabolites that increase intestinal fatty acid synthesis. These results implicate the timing for SG to reach lower intestinal fatty acid synthesis and postprandial chylomicron TG production is prior to the diagnosis of DM to potentially reduce cardiovascular risks. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A highly-efficient flame retardant PPDA in PLA shows good melt-dripping resistance. • The flame retarded PLA material with only 3 wt% PPDA passes UL-94 V-0 rating. • A small amount of PPDA has little influence on the mechanical properties of PLA. Abstract Flame-retarded poly(lactic acid) (PLA) biodegradable materials are viewed as promising as sustainable alternatives to petroleum-based commodity polymers. A new highly efficient flame retardant, poly(phenylphosphoryl phenylenediamine) (PPDA), was synthesized by the condensation of phenylphosphoryl dichloride with p -phenylenediamine and its structure was confirmed by 1H nulear magnetic resonance and Fourier-transform infrared spectroscopy. When 3 wt% PPDA was incorporated into PLA, the limited oxygen index increased from 20.0% of neat PLA to 25.5% and its UL-94 vertical burning testing achieved V-0 rating. Moreover, the total heat release and peak heat release rate values of PLA/3 wt% PPDA material were decreased from 109.1 MJ/m2 and 643.7 kW/m2 of PLA to 98.3 MJ/m2 and 570.0 kW/m2, respectively, and the fire performance index increased from 0.081 of PLA to 0.132 m2 s/kW. The high fire safety of PPDA in PLA is mainly attributed to the combined effects of the phosphorous-containing radical inhibition and inert gases and the barrier action of the formed char layer. The addition of less than 3 wt% PPDA has little influence on the tensile and impact properties of PLA. The flame retardant PLA blends have great application potential in electrical casing, automobile interiors and three-dimensional printing materials. [ABSTRACT FROM AUTHOR]

Vascular inflammation is a common pathological basis underlying many cardiovascular diseases. As such, the treatment of vascular inflammation has attracted increasing attention. The Piezo1 pathway has long been shown to play an important role in the development of vascular inflammation. Jatrorrhizine (Jat) is an effective component of Rhizoma Coptidis. It is commonly used in the treatment of inflammatory diseases and is a potential drug for the treatment of vascular inflammation. However, its mechanism of action on vascular inflammation remains unclear, as is the effect of Jat on Piezo1. Therefore, we conducted a series of studies on the effect of jatrorrhizine on vascular inflammation in vivo and in vitro. In this study, the effect of Jat treatment on H 2 O 2 -induced endothelial cell inflammation was investigated in vitro, and the potential mechanism of Jat was explored. In in vivo experiments, we investigated the effect of jatrorrhizine on vascular inflammation induced by carotid artery ligation and its effect on the Piezo1 signaling pathway. We found that Jat could reduce the severity of carotid intimal hyperplasia and local vascular inflammation in mice. In the H 2 O 2 -induced inflammation model, cell proliferation and migration were significantly inhibited, and the expression of pro-inflammatory factors was reduced. Importantly, the addition of Jat to endothelial Piezo1 knockout did not produce further significant inhibition. We believe that the role of Jat in the treatment of vascular inflammation may be related to Piezo1. And we believe that Jat has great potential in the treatment of vascular inflammation and cardiovascular diseases. [Display omitted] • Chinese medicine monomer jatrorrhizine has the effect of treating vascular inflammation. • The absence of mechanically sensitive ion channel Piezo1 protein can inhibit the development of vascular inflammation. • Jatrorrhizine can inhibit the opening of piezo1 channel induced by Yoda1. • Jatrorrhizine exerts anti-vascular inflammation by regulating the opening of piezo1 ion channel. [ABSTRACT FROM AUTHOR]

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Stearyl-coenzyme A desaturase 1 (SCD1) knockout mice also show decreased liver TG accumulation; however, whether SCD1 plays a role in the effect of metformin on TG accumulation is unknown. Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation. Methods: HepG2 and AML12 cells were exposed to high glucose and high insulin with or without metformin. An adenovirus was used for the SCD1 knockdown and overexpression. The triglyceride level in cells was detected. The expression of related genes was detected by Western blot and quantitative real-time PCR. A dual-luciferase reporter assay was used to determine the effect of metformin on the transcriptional activity of the SCD1 promoter. Results: Metformin decreased TG accumulation to normal level in HepG2 cells exposed to high glucose and high insulin. The expression of SCD1 and fatty acid synthetase (FAS) was also decreased to normal level by metformin. Knockdown of SCD1 mimicked the effect of metformin on decreasing TG levels in AML12 cells, and the overexpression of SCD1 attenuated the effect of metformin on decreasing TG accumulation in HepG2 cells. The dual-luciferase reporter assay showed that the transcriptional activity of the SCD1 promoter (− 550/+ 199) after metformin treatment was 2-fold lower compared to control group in HepG2 cells. Additionally, the phosphorylation of AMPK after metformin treatment was 2-fold higher, and the expression of sterol regulatory element-binding protein-1c (SREBP-1c) after metformin treatment was about 2-fold lower compared to high glucose and high insulin group in HepG2 cells. Conclusions: Together, these results reveal that metformin reduces TG accumulation in HepG2 cells via inhibiting the expression of SCD1. [ABSTRACT FROM AUTHOR]

Background and aims: Glycated hemoglobin A1c (HbA1c) ≥6.5% (or 48mmol/mol) has been recommended as a new diagnostic criterion for diabetes; however, limited literature is available regarding the effect of age on the HbA1c for diagnosing diabetes and the causes for this age effect remain unknown. In this study, we investigated whether and why age affects the diagnostic efficiency of HbA1c for diabetes in a community-based Chinese population. Methods: In total, 4325 participants without previously known diabetes were enrolled in this study. Participants were stratified by age. Receiver operating characteristic curve (ROC) was plotted for each age group and the area under the curve (AUC) represented the diagnostic efficiency of HbA1c for diabetes defined by the plasma glucose criteria. The area under the ROC curve in each one-year age group was defined as AUCage. Multiple regression analyses were performed to identify factors inducing the association between age and AUCage based on the changes in the β and P values of age. Results: The current threshold of HbA1c (≥6.5% or 48mmol/mol) showed low sensitivity (35.6%) and high specificity (98.9%) in diagnosing diabetes. ROC curve analyses showed that the diagnostic efficiency of HbA1c in the ≥75 years age group was significantly lower than that in the 45–54 years age group (AUC: 0.755 vs. 0.878; P<0.001). Pearson correlation analysis showed that the AUCage of HbA1c was negatively correlated with age (r = -0.557, P = 0.001). When adjusting the red blood cell (RBC) count in the multiple regression model, the negative association between age and AUCage disappeared, with the regression coefficient of age reversed to 0.001 and the P value increased to 0.856. Conclusions: The diagnostic efficiency of HbA1c for diabetes decreased with aging, and this age effect was induced by the decreasing RBC count with age. HbA1c is unsuitable for diagnosing diabetes in elderly individuals because of their physiologically decreased RBC count. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the association of serum betatrophin with the status and progression of nonalcoholic fatty liver disease (NAFLD). Methods: A total of 249 subjects who received ultrasonic examination of liver fat content (LFC) were recruited. Anthropometric and biochemical examinations were performed. Serum betatrophin was measured by ELISA. Results: Compared with control group, serum betatrophin significantly increased in NAFLD group (P < 0.05). There was significant difference in serum betatrophin among control, low liver fat content (LLFC), and high liver fat content (HLFC) groups (P < 0.01). After adjustment for gender, age, BMI, FPG and HbA1c, the betatrophin positively correlated with LFC (r = 0.185, P < 0.01) and TG (r = 0.195, P < 0.01). Stepwise multiple regression analysis indicated serum betatrophin was independently related to LFC (P < 0.05). Multivariate logistic regression analysis revealed subjects in the highest tertile of serum betatrophin had higher odds of having NAFLD after adjustment for traditional NAFLD risk factors (OR = 2.88, 95%CI: 1.15–7.19) (P<0.05). Conclusion: Serum betatrophin is an independent risk factor for NAFLD and potential non-invasive marker for its progression. Serum betatrophin may be helpful for the early diagnosis of NAFLD and improvement of its prognosis. [ABSTRACT FROM AUTHOR]

Background: We recently demonstrated a positive effect of berberine on nonalcoholic fatty liver disease patients after 16 weeks of treatment by comparing mere lifestyle intervention in type 2 diabetes patients with berberine treatment, which decreased the content of hepatic fat. However, the potential mechanisms of the clinical effects are unclear. We used a lipidomic approach to characterize the state of lipid metabolism as reflected in the circulation of subjects with nonalcoholic fatty liver disease (NAFLD) before and after berberine treatment.Methods: Liquid chromatography-mass spectrometry evaluated the various lipid metabolites in serum samples obtained from the participants (41 patients in the berberine group and 39 patients in the mere lifestyle intervention group) before and after treatment.Results: A total of 256 serum lipid molecular species were identified and quantified. Both treatments regulated various types of lipids in metabolic pathways, such as free fatty acids, phosphoglycerides and glycerides, in metabolic pathways, but berberine induced a substantially greater change in serum lipid species compared with mere lifestyle intervention after treatment. Berberine also caused obvious differences on ceramides. Berberine treatment markedly decreased serum levels of ceramide and ceramide-1-phosphate.Conclusions: Berberine altered circulating ceramides, which may underlie the improvement in fatty liver disease. ClinicalTrials.gov NCT00633282, Registered March 3, 2008. [ABSTRACT FROM AUTHOR]

Background and Aims: Although many studies have indicated a relationship between nonalcoholic fatty liver disease (NAFLD) and hyperuricemia, a few studies specifically examining the effects of the severity of liver fat content (LFC) on serum uric acid (SUA) and the presence of hyperuricemia because of the limitation of the examination methods for NAFLD. In this study, we investigate the relationship between the NAFLD and SUA levels in the Chinese population using standardized quantitative ultrasound. Methods: A community-based study was conducted from May 2010 to December 2012. A total of 4,305 people aged 45 years and above without excessive drinking were enrolled. A standard interview and anthropometric and laboratory blood parameters were collected for each person. The standardized ultrasound hepatic/renal ratio and hepatic attenuation rate was used to quantify LFC. Results: The prevalence of NAFLD and hyperuricemia was 33.1% and 17.1%, respectively. A total of 23.5% of the NAFLD subjects had hyperuricemia, and their SUA was higher than that of non-NAFLD subjects (327.2±76.8 vs 301.9±77.4 μmol/L, P<0.001). The LFC was positively correlated with SUA (r = 0.130, P<0.001) and an independent factor for SUA (standardized β = 0.054, P<0.001). The OR for the presence of hypreuricemia was 1.175 (95% CI 1.048–1.318; P<0.001) with a 1 SD increase in the log LFC. LFC greater than 10% was related to elevated SUA and an increased presence of hyperuricemia. Conclusions: LFC accumulation was associated with an increase in the prevalence of hyperuricemia and elevated SUA in our community-based population. LFC greater than 10% is related to the risk for hyperuricemia. [ABSTRACT FROM AUTHOR]

We sequenced a complete mitochondrial genome sequencing of a chronic hepatitis-associated liver cancer disease LEC rat strain for the first time. The total length of the mitogenome was 16,316 bp with 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into liver cancer disease. [ABSTRACT FROM PUBLISHER]