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Subjective visual vertical test is considered as an effective technique to evaluate otolith organ function and central pathway of gravity perception. This test is non-invasive, easy to operate and has little stimulation. At present, there are few such studies in China. This paper reviews the concept, measurement principle and method, influencing factors, application, advantages and disadvantages of subjective visual vertical test.

This study aimed to evaluate the effects of dietary egg yolk phosphatidylcholine (EPC) and soybean phosphatidylcholine (SPC) on obesity mice fed a high-fat diet (HFD). After 60 days of dietary intervention, the effects were evaluated by biochemical indices and serum lipidomic analysis. EPC and SPC markedly reduced serum total cholesterol, serum triacylglycerol (TAG) and low-density lipoprotein cholesterol, while increased high-density lipoprotein cholesterol. EPC was more effective in reducing malondialdehyde and superoxide dismutase in liver than SPC. Main lipids including glycerophospholipids, TAG, sphingolipids and fatty acyls were significantly modified by EPC. Compared with HFD, EPC increased 10 main differential lipids such as phosphatidyl ethanolamine (22:6_20:0). The expressions of related protein including sterol-regulatory element binding proteins sterol-regulatory element binding proteins (SREBP-1c) and peroxisome proliferator-activated receptor α (PPAR-α) were significantly down-regulated with EPC treatment. Therefore, EPC was more effective than SPC in improving obesity by regulating glycerophospholipid metabolism.

The domestic emission control area (DECA) policy has been implemented in China since 2017. However, its impact on ship emissions and in turn urban air quality is still unclear. In this study, real-time single particle measurements were carried out at a site in urban Guangzhou, about 1 km downwind of Huangpu Port, the largest maritime transport hub in southern China, in the summer of 2020 using a single particle aerosol mass spectrometer (SPAMS). During the campaign, the hourly averaged number fraction of ship emitted particles, using vanadium as a chemical indicator, varied from 0 to 14% with an average of 2 ± 1%. Ship emitted single particles contain organic carbon (OC), elemental carbon (EC), metals, sulfate and nitrate. More than 95% of ship emitted particles were sulfate-containing particles and the relative peak areas (RPAs) of sulfate and vanadium in the hourly average mass spectra of ship emitted particles were highly correlated (R

The objective of this study was to investigate the suitability of incorporating pitaya fruit fermented by antifungal LAB strains Lactiplantibacillus plantarum and Pediococcus pentosaceus at 1: 30 °C for 24h or 2: 31 °C for 19.5h as an ingredient with respect to bread making performance and bio-preservation effect. Underlying mechanisms related to gluten protein hydrolysis, starch hydrolysis, and yeast activity in dough were explored. The antioxidant activity, antifungal activity and bread making performance of the resulted breads were analyzed. Also, the antifungal phenolic acids in the breads were identified and quantified. Incorporation of fermented substrates in dough increased yeast activity and gas production capacity, but decreased gas retention capacity. This was attributed to increased dough acidity after incorporating fruit substrates. As a result, reducing sugar and free sulfhydryl (SH) groups increased in these doughs which indicated higher starch and gluten protein hydrolysis, respectively. However, SH groups increased at lower rate in presence of substrates fermented by L. plantarum and P. pentosaceus at condition 2 than 1. This could be due to improvement of gluten network as revealed by decreased α-helix (%) and increased β-turn (%) in secondary gluten structures in these doughs which subsequently resulted in more homogeneous microstructural properties than in presence of unfermented substrate compared to wheat dough. Subsequently, bread specific volume increased (6.6–20.0%) in presence of fermented substrates, especially fermented by L. plantarum at (2). Moreover, bread incorporated with fermented substrates (P. pentosaceus than L. plantarum at 1 than 2) had enhanced antioxidant activities, lower fungal growth rates based on challenge tests and mold free shelf life. Antifungal phenolic acids such as gallic acids, caffeic acid, protocatechuic acid were only detected in bread incorporated with fruit substrates, and their total content higher in fermented substrates., Lactic acid bacteria fermentation; Pitaya fruit substrate; Bread making quality; Bio-preservation; Antioxidant activity.

Precision livestock management requires animal traceability and disease trajectory, for which discriminating between or re-identifying individual animals is of significant importance. Existing re-identification (re-ID) methods are mostly proposed for persons and vehicles, compared with which animals are extraordinarily more challenging to be re-identified because of subtle visual differences between individuals. In this paper, we focus on image-based re-ID of yaks (Bos grunniens), which are indispensable livestock in local animal husbandry economy in Qinghai-Tibet Plateau. We establish the first yak re-ID dataset (called YakReID-103) which contains 2, 247 images of 103 different yaks with bounding box, direction-based pose, and identity annotations. Moreover, according to the characteristics of yaks, we modifiy several person re-ID and animal re-ID methods as baselines for yak re-ID. Experimental results of the baselines on YakReID-103 demonstrate the challenges in yak re-ID. We expect that the proposed benchmark will promote the research of animal biometrics and extend the application scope of re-ID techniques.

Physiologic adaptations to fasting ensure health when food intake is limited; engaging these regulatory mechanisms is a potential tool for T2D and obesity. One approach utilizes SGLT2 inhibitors (SGLT2i), which reduce glucose, weight and cardiovascular/renal complications. In preclinical studies, we demonstrated SGLT2i induce a fasting-like transcriptional program in liver, and identified Ctcfl (CCTC-binding factor (CTCF)-like, also known as Boris, or Brother Of Regulator of Imprinting sites), as a top-ranking upregulated transcript in SGLT2i-treated C57BL/6J mice (↑1.5-fold, p=0.017). Ctcfl was also upregulated 2.5-fold with fasting as compared to ad lib-fed littermates. Thus, we hypothesize Ctcfl mediates fasting-related transcription via dynamic epigenetic regulation of chromatin accessibility.To identify drivers of increased Ctcfl expression in the fasting state, we performed in vitro studies in cultured AML12 hepatocytes revealing a key role for AMPK activation and mTOR inhibition as upstream regulators of Ctcfl. Transcriptomic analysis in siRNA-mediated Ctcfl knockdown (KD) vs. wild type (WT) cells indicates Ctcfl regulates critical pathways of lipid/carbohydrate metabolism, mitochondrial biogenesis, and transcriptional mediators of fasting (e.g., Hnf4, Srebf, Chrebp, Pgc1α). Single-cell RNAseq revealed distinct populations in Ctcfl-KD vs. WT cells, with the two largest sub-clusters of Ctcfl-KD cells enriched in genes associated with mTOR and insulin signaling and Tfeb target genes. Conversely, gain-of-function studies via overexpression of human CTCFL resulted in significant repression of key transcription factors and enzymes regulating lipid/cholesterol metabolism and gluconeogenesis (Pgc1α). In conclusion, we demonstrate that AMPK and mTor-mediated pathways regulate Ctcfl, a mediator of fasting-associated lipid and glucose transcriptional programs in the liver, potentially via alterations in chromatin accessibility. Disclosure V. Efthymiou: None. J. I. Chimene-weiss: None. L. Zhou: None. S. Osataphan: None. L. Su: None. M. Patti: Consultant; Self; Cello Health, Fractyl Laboratories, Inc., MBX, Poxel SA, WGBH, Other Relationship; Self; Xeris Pharmaceuticals, Inc., Research Support; Self; Dexcom, Inc.

Purpose This study investigated the characteristics of tumor-associated immune cells (TAICs) in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathological variables. Methods The immune cell infiltrates of 71 specimens of stages I-IV LSCC were examined. The density of TAICs expressing CD3, CD4, CD8, CD68, and CD163 was assessed using immunohistochemical staining and image analysis in peritumoral and intratumoral regions. Results Higher densities of CD3+ and CD8+ cell and lower densities of CD68+ and CD163+ cell infiltrations were found in early tumor stages than in late tumor stages. A higher percentage of patients with strong CD3+ and CD8+ immune cell infiltration and weak CD68+ cell infiltration in both tumor regions presented with T1 stage tumors compared with T4 stage tumors. Further, strong CD68+ cells infiltration in both regions was observed in a greater number of patients who had a relapse, while a weak CD3+ cells infiltration in both regions was found in a greater number of patients with nodal lymphatic metastasis. The univariate analysis showed that a high density of peritumoral CD3+ and CD8+ immune cells in both regions was significantly associated with a favorable overall survival (OS) (P = 0.004; P = 0.006; P = 0.042). In contrast, a high density of intratumoral CD68+ cells and peritumoral CD163+ cells was significantly associated with poor OS durations (P = 0.026; P = 0.030). The multivariate analysis demonstrated that a high density of peritumoral CD163+ cells correlated with poor OS after adjusting for tumor stage, recurrence, and nodal lymphatic metastasis (P = 0.034). This study found different patterns of TAIC infiltration in LSCC. The density and location of TAICs infiltration correlated with the clinicopathological characteristics of LSCC. Conclusion A combined analysis of the density of TAICs and their location may help predict patient survival and response to checkpoint inhibitors.

Adverse early-life exposures program an increased risk of chronic metabolic diseases in adulthood. However, the effects of genistein consumption in early life on metabolic health are unclear. Our objective was to investigate whether perinatal genistein intake could mitigate the deleterious effects of a high-fat diet (HF) on metabolism in dams and female offspring and to explore the role of the gut microbiota in mediating the transgenerational effects. C57BL/6 female mice were fed a HF, HF with genistein (0.6 g kg-1 diet) or normal control diet for 3 weeks before mating and throughout pregnancy and lactation. The offspring had free access to normal diet from weaning to 24 weeks of age. A glucose tolerance test was performed and the levels of serum insulin and lipid were measured. The cecal contents were collected for 16s rDNA sequencing. The results showed that perinatal genistein intake could not only significantly reduce blood glucose levels, insulin and free fatty acids (FFA) in dams, but also improve glucose tolerance, insulin sensitivity and serum lipid profiles in adult female offspring. Significant enrichment of short-chain fatty acid (mainly butyrate)-producing bacteria might play crucial roles in deciphering the metabolic benefits of perinatal genistein intake in dams. The obvious decrease in harmful microorganisms and increase in Erysipelotrichaceae_incertae_sedis were associated with the protective effects of maternal genistein intake on female offspring. In addition, Bifidobacterium might be an important factor for deciphering the metabolic improvement in both dams and female offspring by dietary genistein. Overall, perinatal genistein intake attenuated the harmful effects of HF on metabolism in both dams and female offspring, and the protective effects were associated with the alterations in the gut microbiota, which provides new evidence and targets for mitigating the poor effects of adverse early-life exposures on metabolic health in later life.

Integration of human papillomavirus (HPV) DNA into the human genome is considered as a key event in cervical carcinogenesis. Here, we perform comprehensive characterization of large-range virus-human integration events in 16 HPV16-positive cervical tumors using the Nanopore long-read sequencing technology. Four distinct integration types characterized by the integrated HPV DNA segments are identified with Type B being particularly notable as lacking E6/E7 genes. We further demonstrate that multiple clonal integration events are involved in the use of shared breakpoints, the induction of inter-chromosomal translocations and the formation of extrachromosomal circular virus-human hybrid structures. Combined with the corresponding RNA-seq data, we highlight LINC00290, LINC02500 and LENG9 as potential driver genes in cervical cancer. Finally, we reveal the spatial relationship of HPV integration and its various structural variations as well as their functional consequences in cervical cancer. These findings provide insight into HPV integration and its oncogenic progression in cervical cancer.

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2020Q3 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 1,754 reports of drug-induced liver injury in patients with COVID-19. The ROR for drug-induced liver injury was 1.4 (95% CI, 1.1–1.7), 3.6 (95% CI, 2.7–4.7), and 0.8 (95% CI, 0.7-1.0) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (ROR, 4.9; 95% CI, 3.7–6.5), compared with hydroxychloroquine/chloroquine only (ROR, 4.3; 95% CI, 3.0-6.2), and compared with remdesivir (ROR, 10.4; 95% CI, 7.2–15.0). Conclusions In the FAERS, we observed a disproportional signal for severe drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.

Epidermal growth factor (EGF) plays an important role in nutrients absorption. However, whether it can be an effective additive to improve the growth performance and nutrients absorption in lipopolysaccharide (LPS) challenged early weaning piglets is still unknown. A 14-days trial was conducted to investigate how EGF attenuates the effect of LPS on the growth performance, nutrient digestibility, microelement absorption of early-weaned pigs, and study the underlying mechanism. A total of 48 early weaned piglets, aged 25 days, were randomly distributed to four groups (control, EGF, LPS and EGF + LPS groups) consisting of a 2 × 2 factorial design. The main factors were the level of LPS (HLPS = high LPS: 100 μg/kg body weight, ZLPS = low LPS: 0 μg/kg body weight) and EGF (HEGF = high EGF: 2 mg/kg diet, ZEGF = low EGF: 0 mg/kg diet). Each group had four replicates and each replicate consisted of three piglets. The results showed that piglets injected with HLPS level significantly decreased the average daily gain (ADG), and significantly increased the feed conversion ratio (FCR) compared with the piglets injected with ZLPS level, while piglets fed HEGF level significantly increased the average daily feed intake (ADFI) compared with the piglets fed ZEGF level (p &lt, 0.05). Piglets injected with HLPS level significantly decreased the apparent digestibility of crude fat compared with the piglets injected with ZLPS level (p &lt, 0.05). Piglets injected with HLPS level significantly increased the concentration of most microelements in the gastrointestinal tract chyme and feces, and significantly decreased the expression levels of most microelement transport-relative genes in the mucosa of gastrointestinal tissues compared with the piglets injected with ZLPS level (p &lt, 0.05). Piglets fed HEGF level significantly decreased the concentration of microelement in the gastrointestinal tract chyme and feces, and significantly increased the expression levels of the microelement transport-relative genes in the mucosa of gastrointestinal tissues compared with the piglets fed ZEGF level (p &lt, 0.05). In conclusion, dietary EGF could attenuate the negative effect of LPS exposure on the apparent digestibility of crude fat and microelement absorption of early-weaning piglets. EGF and LPS influenced the absorption of essential trace element through changing the expression levels of microelement transport-relative genes in the mucosa of gastrointestinal tissues. In the early weaning piglets, EGF can be used as an additive to increase the essential trace elements absorption.

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59–3.46), 3.16 (2.68–3.73), and 5.39 (4.63–6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15–5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09–6.94), and compared with remdesivir (3.85; 3.03–4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19.

This study was conducted to investigate the effects of different patterns and sources of Zn, Fe, Cu, Mn, and Se on performance, mineral deposition (liver, kidney, pancreas, spleen, pectorals muscle, and tibia), and excretion of laying hens, then to find an optimal dietary supplemental pattern of trace elements in laying hens. A total of 864 healthy laying hens with similar laying rate (Roman, 26-week-old) were randomly divided into nine treatments, with six replications of 16 birds per replication, including a control treatment and four patterns with different element sources (inorganic or organic): (1) Control treatment (basic diet without added extra trace minerals, CT), pattern 1, NRC (1994) recommended level (NRC-L): (2) inorganic minerals of NRC-L pattern (IN), (3) organic minerals of NRC-L pattern (ON), pattern 2, NY/T 33-2004 recommended level (NY/T-L): (4) inorganic minerals of NY/T-L pattern (IY), (5) organic minerals of NY/T-L pattern (OY), pattern 3, 50% NRC (1994) recommended level (50% NRC-L): (6) inorganic minerals of 50% NRC-L pattern (IHN), (7) organic minerals of 50% NRC-L pattern (OHN), pattern 4, the ratio of minerals in blood of laying hens was taken as the supplement proportion of trace elements, and Zn was supplemented depended on NRC recommended level (TLB): (8) inorganic minerals of TLB pattern (IB), (9) organic minerals of TLB pattern (OB). Two weeks were allowed for adjustment to the conditions and then measurements were made over eight weeks. Supplementation of trace elements led to increased daily egg weight (p &lt, 0.05). Patterns of minerals in diets affected the content of liver Mn, pancreas Mn, tibia Mn, and the tissues Se (p &lt, 0.05). Sources of minerals had positive effects on daily egg weight (p &lt, 0.05), the concentrations of liver Fe, kidney Cu, tissues Se (except spleen), and fecal Se (p &lt, 0.05). In conclusion, diet supplemented with the organic trace minerals of 50% NRC-L pattern (OHN) in laying hens promoted optimum laying performance, mineral deposition, and reduced mineral excretion.

Colon cancer is a common malignancy of the digestive tract with high morbidity and mortality. There is an urgent need to identify effective biomarkers for the early diagnosis of colon cancer and to prolong patient survival. Cyclins are a family of proteins that directly participate in the cell cycle and are associated with many types of tumors, but the role and regulatory mechanism of most cyclin family members in colon cancer remain unclear. Here, we provide a systematic and comprehensive study of cyclin family gene expression and their potential roles in colon cancer. Pan-cancer analysis revealed that cyclin genes were most differentially expressed in colon adenocarcinoma. Among the four datasets of colon cancer from The Cancer Genome Atlas and the Gene Expression Omnibus, six cyclin genes (CCNA2, CCNB1, CCND1, CCNE1, CCNF, and CCNJL) were differentially expressed between normal and tumor tissues. Four of them (CCNA2, CCNB1, CCNE1, and CCNF) were notably elevated in the early TNM stages and significantly correlated with overall survival. Meanwhile, the expression of CCNA2 and CCNB1 was positively correlated with tumor-killing immune cells, such as CD8+ T cells.The copy numbers of CCNA2, CCNB1, CCND1, CCNE1, and CCNF was positively related to gene expression. The methylation levels of CCNB1 were lower in tumor tissues than in normal tissues and were negatively correlated with gene expression. The receiver operating characteristic curves indicated that the gene expression of 24 cyclins had higher predictive accuracy than the TNM stage. Pathway analysis showed that cyclin genes were tightly associated with apoptosis, the cell cycle, hormone ER, the RAS/MAPK pathway, mismatch repair, mTORC1 signaling, KRAS signaling, Akt, and TGFB in colon cancer. Weighted gene co-expression network analysis suggested that cyclin genes were closely linked to CDK1, BIRC5, PLK1, and BCL2L12. At the protein level, Cyclin A2 and Cyclin B1 were also expressed higher in colon adenocarcinoma tissues. In addition, cyclin genes were highly related to the drug sensitivity of some FDA-approved drugs, such as MEK and EGFR inhibitors, which might provide guidance for clinical treatment. In conclusion, cyclin genes are promising biomarkers for the diagnosis and prognosis of colon cancer.

Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01352-4.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Glucokinase-maturity onset diabetes of the young (GCK-MODY) represents a rare genetic disorder due to mutation in the glucokinase (GCK) gene. The low incidence of vascular complications in GCK-MODY makes it a natural paradigm for interrogating molecular mechanisms promoting vascular health under prolonged hyperglycemia. Clinical rate of misdiagnosis has remained high, and a reliable serum lipid biomarker that precedes genetic screening can facilitate correct diagnosis and treatment. Herein, we comprehensively quantitated 565 serum lipids from 25 classes in 105 subjects (42 nondiabetic controls, 30 GC K-MODY patients, 33 drug-naïve, and newly-onset T2D patients). At false-discovery rate (FDR)

Additional file 1.

Introduction Type 1 diabetes mellitus (T1DM) is characterized by an absolute deficiency of insulin and dependence on insulin therapy. Therefore, glycemic control and management are important for T1DM patients, particularly glycemic variability, which is associated with the development of diabetic complications. However, insufficient attention has been paid to the glycemic variability in T1DM patients so far. Our objective was to identify the effects of food intake on glycemic variability in T1DM patients. Methods This was a single-center study that took place in the outpatient clinics of Peking Union Medical College Hospital. A total of 68 Chinese T1DM patients between June 2018 and June 2019 were enrolled. After the baseline demographic and clinical characteristics were evaluated, each participant underwent 14-day flash glucose monitoring (FGM). They recorded caloric intake of breakfast, lunch, and dinner at least 3 days/week using a “Menthol Health” app. After 2 weeks, we obtained the FGM data and did further data analysis. Baseline characteristics and glycemic variability index generated by FGM were compared among groups. A general linear model was used to compare data among groups after adjusting for potential confounding factors. The quantitative relationship between two continuous variables was explored by constructing a linear regression equation. Results The results showed that the C-peptide level was independently correlated with the mean of daily differences (MODD) after adjusting for the possible confounders (β = − 0.239, p = 0.046). The dietary nutrition intake had no effect on glycemic variability. However, the nutritional composition of carbohydrate, fat, and protein was an independent risk factor for time spent in hypoglycemia (TBR) post adjustment (β = − 0.213, p = 0.054). However, there was no impact of daily total energy intake on glycemic variability index. Conclusion In our study, dietary nutrition intake had no effect on glycemic variability, but residual β-cell function was identified as an influencing factor for glycemic variability in T1DM adults. However, nutritional macronutrient composition played some roles in the occurrence of hypoglycemia. This might provide new evidence for the clinical glycemic control and management of T1DM in the Chinese population.

Background: Epidermal growth factor (EGF) plays an important role in nutrient utilization. A 14-days trial was conducted to investigate how EGF attenuates the effect of lipopolysaccharide (LPS) on the growth performance and the nutrient utilization of early-weaned pigs.Methods: A total of 48 early weaned piglets were randomly distributed among 4 groups, which included the control, EGF, LPS and EGF + LPS groups. Each group had 6 replicates and each replicate consisted of 2 piglets. The experiment lasted for 14 d.Results: The results showed that LPS exposure significantly decreased the average daily gain (ADG) and significantly increased the feed conversion ratio (FCR) of the weaned pigs compared with the groups without LPS treatment (PConclusion: Dietary EGF could attenuate the effect of LPS exposure on the essential trace element absorption by changing the expression levels of microelement transport-relative genes of early-weaned pigs.

Nod-like receptor pyrin containing (NLRP)3 inflammasome-mediated neuroinflammation is involved in the pathology of Parkinson's disease (PD), but the roles of other inflammasomes in PD remain unclear. The NLRP3 inhibitor MCC950 exerts neuroprotective effects in several neurological diseases. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-induced mouse model with or without intraperitoneal MCC950 administration, we assessed whether specifically the NLRP3 inflammasome is activated in the nigrostriatal system and whether MCC950 has therapeutic potential in this PD model. Western blots were used to determine the nigrostriatal expression of inflammasome-specific proteins, including NLRP1, NLRP2, NLRP3, nod-like receptor CARD containing 4 (NLRC4), and absent in melanoma 2 (AIM2). The pole, hanging, and swimming tests were used to assess functional deficits, western blots and immunostainings were used to analyze dopaminergic neuronal degeneration, as well as activation of glial cells and the NLRP3 inflammasome. NLRP3 expression in the nigrostriatal system of MPTP-induced mice was significantly increased compared to control, whereas NLRP1, NLRP2, NLRC4, and AIM2 expression in the nigrostriatal system, as well as NLRP3 expression in the cerebral cortex and hippocampus, were similar in the two groups. Furthermore, MPTP-induced mice exhibited behavioral dysfunctions, dopaminergic neuronal degeneration, and activation of glial cells and the NLRP3 inflammasome. MCC950 treatment of MPTP-induced mice improved behavioral dysfunctions, reduced dopaminergic neuronal degeneration, and inhibited the activation of glial cells and the NLRP3 inflammasome. In conclusion, these findings indicated that NLRP3, not NLRP1, NLRP2, NLRC4, and AIM2, may be the key inflammasome that promotes MPTP-induced pathogenesis. MCC950 protects against MPTP-induced nigrostriatal damage and may be a novel promising therapeutic approach in treating MPTP-induced PD.

The aim of this meta-analysis was to assess the risks of endocrine adverse events in patients with malignancies treated with different types and different doses of immune checkpoint inhibitors (ICIs). PubMed and Embase were searched for randomized controlled trials on ICIs and endocrine adverse events since 2000, and meta-analysis was carried out. Twenty-six randomized controlled trials comprising 13 824 patients with malignancies were included. Compared with the other tumor therapies (used as a control group), patients treated with programmed death-1 inhibitors appeared to be at higher risks of hypothyroidism, hyperthyroidism, thyroiditis, hypophysitis or hypopituitarism, and type 1 diabetes mellitus, while there was no difference in the risk of primary adrenal insufficiency. It was also found that patients treated with cytotoxic T-lymphocyte-associated protein-4 inhibitors were at higher risk of hypophysitis or hypopituitarism, primary adrenal insufficiency, and hypothyroidism. In comparison, patients treated with programmed death-ligand 1 inhibitors were at higher risk of hyperthyroidism and hypothyroidism. Compared with the control group, both low-dose and high-dose ICI groups were at higher risk of hypothyroidism and hyperthyroidism, and the low-dose group had increased risk of thyroiditis and primary adrenal insufficiency. There was no significant difference in the risk of type 1 diabetes between the low-dose group and the high-dose group. The risk of hypophysitis or hypopituitarism in the high-dose group (relative risk, 20.12; 95% confidence interval, 8.02-50.46) was significantly higher than that in the low-dose group (relative risk, 4.92; 95% confidence interval, 2.11-11.47). The risk of endocrine adverse events was increased in patients treated with ICIs. Different types and doses of ICIs have varying characteristics of endocrine adverse events.

DNA methylation plays a vital role in transcription regulation. Reduced representation bisulfite sequencing (RRBS) is becoming common for analyzing genome-wide methylation profiles at the single nucleotide level. A major goal of RRBS studies is to detect differentially methylated regions (DMRs) between different biological conditions. The previous tools to predict DMRs lack consistency. Here, we simulated RRBS datasets with significant attributes of real sequencing data under a wide range of scenarios, and systematically evaluated seven DMR detection tools in terms of type I error rate, precision/recall (PR), and area under ROC curve (AUC) using different methylation levels, sequencing coverage depth, length of DMRs, read length, and sample sizes. DMRfinder, methylSig, and methylKit were our preferred tools for RRBS data analysis, in terms of their AUC and PR curves. Our comparison highlights the different applicability of DMR detection tools and provides information to guide researchers towards the advancement of sequence-based DMR analysis.

Transfer RNA-derived RNA fragments (tRFs) are a class of small non-coding RNAs that are abundant in many organisms, but their role in cancer has not been fully explored. Here, we report a functional genomic landscape of tRFs in 8118 specimens across 15 cancer types from The Cancer Genome Atlas. These tRFs exhibited characteristics of widespread expression, high sequence conservation, cytoplasmic localization, specific patterns of tRNA cleavage and conserved cleavage in tissues. A cross-tumor analysis revealed significant commonality among tRF expression subtypes from distinct tissues of origins, characterized by upregulation of a group of tRFs with similar size and activation of cancer-associated signaling. One of the largest superclusters was composed of 22 nt 3′-tRFs upregulated in 13 cancer types, all of which share the activation of Ras/MAPK, RTK and TSC/mTOR signaling. tRF-based subgrouping provided clinically relevant stratifications and significantly improved outcome prediction by incorporating clinical variables. Additionally, we discovered 11 cancer driver tRFs using an effective approach for accurately exploring cross-tumor and platform trends. As a proof of concept, we performed comprehensive functional assays on a non-microRNA driver tRF, 5′-IleAAT-8-1-L20, and validated its oncogenic roles in lung cancer in vitro and in vivo. Our study also provides a valuable tRF resource for identifying diagnostic and prognostic biomarkers, developing cancer therapy and studying cancer pathogenesis.

Background: Early-life overnutrition programs increased risks of metabolic disorders in adulthood. Regular exercise is widely accepted to be an effective measure to maintain metabolic health. However, the transgenerational effects of maternal exercise and the specific mechanism are largely unclear. Aims: Our objective was to investigate whether maternal exercise could alleviate the metabolic disturbances induced by early-life overnutrition in both dams and offspring and to explore the role of gut microbiota-liver axis in mediating the transgenerational metabolic reprogramming. Methods: C57BL/6 females were randomly divided into three groups 3 weeks before mating and during pregnancy: the control group, high-fat group, and high-fat with exercise group (voluntary wheel running training). They received their original diets during lactation. The male offspring had ad libitum access to chow diet from weaning to 24 weeks of age. Glucose tolerance test and serum biochemical parameters were detected. The cecal contents from dams at weaning and 8-week and 24 week of offspring were collected for 16s rDNA sequencing. Hepatic HE staining and transcriptome were performed in adult offspring. Results: The results showed that perinatal high-fat diet resulted in significant glucose intolerance, insulin resistance and lipid profiles disorders in both dams and offspring. Maternal exercise markedly improved insulin sensitivity in dams and metabolic disorders in offspring from young into adulthood, especially the hepatic steatosis. The decrease in harmful bacteria and the persistent enrichment of short chain fatty acid producers from mothers to adult offspring, particularly the genus Odoribacter, were all associated with improvement in metabolism by maternal exercise. In addition, maternal exercise significant upregulated FGF21 and genes involved in the fatty acid oxidation and TCA cycle in adult offspring, which were down-regulated by perinatal high-fat diet and were significantly correlated with the altered microbial species. Conclusion: Overall, maternal exercise could significantly mitigate the detrimental effects of perinatal high-fat diet on metabolism in both dams and male offspring. The continuous alterations in gut microbiota and reprogramming hepatic metabolism might be critical factors in deciphering the transgenerational metabolic benefits of maternal exercise, which provides some novel evidence and targets for combating the metabolic diseases.

This decision analytical model describes several key epidemiological features of imported coronavirus disease 2019 (COVID-19) cases in Wenzhou, China.

The transition, in extent and characteristics, of atmospheric emissions caused by the modernization of the heavy-duty on-road fleet was studied utilizing roadside measurements. Emissions of particle number (PN), particle mass (PM), black carbon (BC), nitrogen oxides (NOx), carbon monoxide (CO), hydrocarbon (HC), particle size distributions, and particle volatility were measured from 556 individual heavy-duty trucks (HDTs). Substantial reductions in PM, BC, NOx, CO, and to a lesser extent PN were observed from Euro III to Euro VI HDTs by 99 %, 98 %, 93 %, and 57 % for the average emission factors of PM, BC, NOx, and CO, respectively. Despite significant total reductions in NOx emissions, the fraction of NO2 in the NOx emissions increased continuously from Euro IV to Euro VI HDTs. Larger data scattering was evident for PN emissions in comparison to solid particle number (SPN) for Euro VI HDTs, indicating a highly variable fraction of volatile particle components. Particle size distributions of Euro III to enhanced environmentally friendly vehicle (EEV) HDTs were bimodal, whereas those of Euro VI HDTs were nucleation mode dominated. High emitters disproportionately contributed to a large fraction of the total emissions with the highest-emitting 10 % of HDTs in each pollutant category being responsible for 65 % of total PM, 70 % of total PN, and 44 % of total NOx emissions. Euro VI HDTs, which accounted for 53 % of total kilometres driven by Swedish HDTs, were estimated to only contribute to 2 %, 6 %, 12 %, and 47 % of PM, BC, NOx, and PN emissions, respectively. A shift to a fleet dominated by Euro VI HDTs would promote a transition of atmospheric emissions towards low PM, BC, NOx, and CO levels. Nonetheless, reducing PN, SPN, and NO2 emissions from Euro VI HDTs is still important to improve air quality in urban environments.

Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs whose biological roles in cancers are not well understood. Emerging evidence suggests that tRFs are involved in gene regulation at multiple levels. In this study, we constructed an integrative database, OncotRF (http://bioinformatics.zju.edu.cn/OncotRF), for in silico exploration of tRF functions, and identification of diagnostic and prognostic biomarkers in cancers. The database contains an analysis pipeline for tRF identification and characterization, analysis results of 11,211 small RNA sequencing samples and 8,776 RNA sequencing samples, and clinicopathologic annotation data from The Cancer Genome Atlas (TCGA). The results include: tRF identification and quantification across 33 cancers, abnormally expressed tRFs and genes, tRF-gene correlations, tRF-gene networks, survival analyses, and tRF-related functional enrichment analyses. Users are also able to identify differentially expressed tRFs, predict their functions, and assess the relevance of the tRF expression levels to the clinical outcome according to user-defined groups. Additionally, an online Kaplan-Meier plotter is available in OncotRF for plotting survival curves according to user-defined groups. OncotRF will be a valuable online database and functional annotation tool for researchers studying the roles, functions, and mechanisms of tRFs in human cancers.

Rare diseases are usually chronically debilitating or even life-threatening with diagnostic and therapeutic challenges in current clinical practice. It has been estimated that 80% of rare diseases are genetic in origin, and thus genome sequencing-based diagnosis offers a promising alternative for rare-disease management. In this study, 79 individuals from 16 independent families were performed for whole-genome sequencing (WGS) in an effort to identify the causative mutations for 16 distinct rare diseases that are largely clinically intractable. Comprehensive analysis of variations, including simple nucleotide variants (SNVs), copy-number variations (CNVs), and structural variations (SVs), was implemented using the WGS data. A flexible analysis pipeline that allowed a certain degree of misclassification of disease status was developed to facilitate the identification of causative variants. As a result, disease-causing variants were identified in 10 of the 16 investigated diseases, yielding a diagnostic rate of 62.5%. Additionally, new potentially pathogenic variants were discovered for two disorders, including IGF2/INS-IGF2 in mitochondrial disease and FBN3 in Klippel–Trenaunay–Weber syndrome. Our WGS analysis not only detected a CNV associated with 3p deletion syndrome but also captured a simple sequence repeat (SSR) variation associated with Machado–Joseph disease. To our knowledge, this is the first time the clinical WGS analysis of short-read sequences has been used successfully to identify a causative SSR variation that perfectly segregates with a repeat expansion disorder. After the WGS analysis, we confirmed the initial diagnosis for three of 10 established disorders and modified or corrected the initial diagnosis for the remaining seven disorders. In summary, clinical WGS is a powerful tool for the diagnosis of rare diseases, and its diagnostic clarity at molecular levels offers important benefits for the participating families.

An improved fruit fly optimization algorithm based on knowledge memory (KM-FOA) is proposed for solving continuous functions problems. It is featured with mechanisms devised for solving the concern...

Motivation The rapid development of next-generation sequencing technology provides an opportunity to study genome-wide DNA methylation at single-base resolution. However, depletion of unmethylated cytosines brings challenges for aligning bisulfite-converted sequencing reads to a large reference. Software tools for aligning methylation reads have not yet been comprehensively evaluated, especially for the widely used reduced representation bisulfite sequencing (RRBS) that involves enrichment for CpG islands (CGIs). Results We specially developed a simulator, RRBSsim, for benchmarking analysis of RRBS data. We performed extensive comparison of seven mapping algorithms for methylation analysis in both real and simulated RRBS data. Eighteen lung tumors and matched adjacent tissues were sequenced by the RRBS protocols. Our empirical evaluation found that methylation results were less consistent between software tools for CpG sites with low sequencing depth, medium methylation level, on CGI shores or gene body. These observations were further confirmed by simulations that indicated software tools generally had lower recall of detecting these vulnerable CpG sites and lower precision of estimating methylation levels in these CpG sites. Among the software tools tested, bwa-meth and BS-Seeker2 (bowtie2) are currently our preferred aligners for RRBS data in terms of recall, precision and speed. Existing aligners cannot efficiently handle moderately methylated CpG sites and those CpG sites on CGI shores or gene body. Interpretation of methylation results from these vulnerable CpG sites should be treated with caution. Our study reveals several important features inherent in methylation data, and RRBSsim provides guidance to advance sequence-based methylation data analysis and methodological development. Availability and implementation RRBSsim is a simulator for benchmarking analysis of RRBS data and its source code is available at https://github.com/xwBio/RRBSsim or https://github.com/xwBio/Docker-RRBSsim. Supplementary information Supplementary data are available at Bioinformatics online.

We previously demonstrated that paternal obesity is associated with offspring metabolic risk during later life, and that paternal SGLT2i treatment improves offspring metabolic phenotypes. Since the placenta is a key determinant of prenatal growth and development, we hypothesized the placenta could mediate the impact of paternal obesity and paternal SGLT2i treatment. Male C57BL/6J mice were fed standard chow (Purina 9F) or 60% high-fat diet (HFD, D12492, Research Diet), or 60% HFD plus the SGLT2 inhibitor canagliflozin (CANA, 25 mg/kg/d) for 4 weeks before mating with chow-fed females. Placenta were collected on E16.5, and RNA-seq was performed on placenta from male offspring (paternal chow, pChow, n=4, pHFD, n=5, and pHFD+CANA, n=4), and differentially expressed genes were identified using Limma. Placenta weight was significantly lower in pHFD (0.089±0.004 g, 7 litters from 6 fathers) vs. both pChow (0.108±0.011 g, 4 litters, 4 fathers) and pHFD+CANA (0.107±0.013 g, 5 litters, 5 fathers)(p1.8) for gene sets in steroid metabolic, drug catabolic, and protein-containing complex remodeling processes. Genes responsible for enrichment included cholesterol biosynthesis (Hmgcs1), transport (Apob, Apoa1/2/4, Apom, Apoc1, Vldlr, Pcsk9) and steroid hormone biosynthesis genes (Hsd3b1, Cyp11b1), all upregulated in pHFD by 1.5-3-fold. These results suggest pHFD could potentially affect maternal and fetal cholesterol homeostasis. pHFD+CANA altered expression of 154 genes vs. pHFD (7 up-, 147 down, FDR |1.5|); 18 gene sets were downregulated by pHFD+CANA (GSEA NES

Quality loss of frozen dough products were mainly attributed to ice recrystallisation on gluten and yeast activity during frozen storage. Little was reported on role of sourdough metabolites and acidification on gluten protein behavior during frozen storage of dough. Here, the effects of in situ formed exopolysaccharide (EPS) in red bean sourdough fermented by Weissella confusa QS813 and sourdough acidification on gluten protein matrix and quality of frozen gluten-red bean dough was investigated during 0, 1, and 5 freeze-thaw cycles (FTC). Underlying mechanisms were explored to compare changes in gluten, water distribution, rheological and microstructural properties of frozen gluten-red bean dough during FTC. Gluten protein conformation analysis showed that EPS in sourdough and sourdough acidification reduced rate of increase of glutenin macropolymer (GMP) depolymerization (3.07%), GMP content (0.88%), and free sulfhydryl content in frozen gluten-red bean doughs during FTC. Secondary structure analysis showed that β-turns increased while α-helix and β-sheet structures decreased in frozen gluten-red bean doughs with sourdough during FTC. EPS in red bean sourdough reduced water distribution by enhancing water binding capacity. This suggested that EPS probably formed bonds with gluten and red bean components like proteins, resulting in a dough structurally tolerant to distortions caused by ice recrystallisation during FTC. Furthermore, synergistic interactions between EPS and acidification improved viscoelastic properties and stabilized microstructural integrity of frozen gluten-red bean doughs. These findings gave new insights and suggested potential clean label application of sourdough fermentation to enhance legume ingredient functionality in frozen dough products in bakery food industry.

Preeclampsia is a pregnancy-specific disorder, which is a leading cause of maternal and perinatal mortality and morbidity. A lower increase of estrogen, compared with the increase in progesterone, is associated with pathogenesis of the disease during pregnancy. G-protein-coupled receptor 30 (GPR30) mediates the action of estrogen, however remains to be investigated in preeclampsia. The levels of GPR30 were measured in placentae from uncomplicated pregnancies and pregnancies complicated by preeclampsia using immunohistochemistry and western blotting. GPR30 expression was additionally measured in placental HTR8/SVneo cells following 17β-estrogen (E2) treatment in normal or hypoxia-reoxygenation conditions by western blotting. In addition, the outgrowth of HTR8/SVneo cells following E2 treatment in hypoxia-reoxygenation conditions was measured. Levels of GPR30 were significantly reduced in placentae from women with preeclampsia as compared with uncomplicated pregnancies. Treatment with E2 significantly increased the expression of GPR30 in HTR8/SVneo cells, in normal and hypoxia-reoxygenation conditions. Furthermore, treatment with E2 increased the outgrowth of HTR8/SVneo cells in hypoxia-reoxygenation conditions. The present study demonstrated lowered placental expression of GPR30 in preeclampsia. Estrogen treatment increases GPR30 expression in extravillous trophoblast and GPR30 may be involved in extravillous trophoblast invasion.

Nowadays, location based services (LBS) has become one of the most popular applications with the rapid development of mobile Internet technology. More and more research is focused on discovering the required services among massive information according to the personalized behavior. In this paper, a collaborative filtering (CF) recommendation algorithm is presented based on the Location-aware Hidden Markov Model (LHMM). This approach includes three main stages. First, it clusters users by making a pattern similarity calculation of their historical check-in data. Then, it establishes the location-aware transfer matrix so as to get the next most similar service. Furthermore, it integrates the generated LHMM, user's score and interest migration into the traditional CF algorithm so as to generate a final recommendation list. The LHMM-based CF algorithm mixes the geographic factors and personalized behavior and experimental results show that it outperforms the state-of-the-art algorithms on both precision and recall.

The placenta is the exchange organ between the mother and the fetus. The inadequate function of this organ is associated with a number of pregnancy disorders. Hypoxia and oxidative stress during placental development may induce endothelial dysfunction, resulting in the reduction in the perfusion of the placenta. During pregnancy, the levels of estrogen are increased. Decreased estrogen levels have been reported in women with preeclampsia. However, whether estrogen is involved in placental angiogenesis remains unclear. In this study, we aimed to investigate the effects of estrogen on endothelial cell tube formation and to elucidate the underlying mechanisms. For this purpose, human umbilical vein endothelial cells (HUVECs) were cultured with 17-β-estradiol under conditions of hypoxia/reoxygenation (H/R). The total pipe length of the tube-like structure on endothelial cells was measured. The expression levels of G-protein-coupled receptor 30 (GPR30) and endothelial nitric oxide synthase (eNOS) and Akt were also measured in the endothelial cells following treatment with 17-β-estradiol under H/R conditions by western blot analysis and immunostaining. We found that the total pipe length of the tube-like structure on endothelial cells was significantly reduced. This reduction was reversed by treatment with 17-β-estradiol. The expression of GPR30 in endothelial cells was significantly increased following treatment with 17-β-estradiol under H/R conditions. Furthermore, the levels of eNOS and Akt in endothelial cells were also significantly increased following treatment with 17-β-estradiol under H/R conditions. The activation of eNOS was inhibited by wortmannin, an inhibitor of PI3K/Akt. Our data thus demonstrate that estrogen prevents the failure of endothelial cell tube formation induced by H/R. GPR30 plays an important role in these protective effects through the activation of eNOS and Akt in endothelial cells. Our data suggest that increased levels of estrogen are important for placental angiogenesis.

With the development and application of super rice breeding, elite rice hybrids with super high-yielding potential have been widely developed in last decades in China. Xieyou9308 is one of the most famous super hybrid rice varieties. To uncover the genetic mechanism of Xieyou9308’s high yield potential, a recombinant inbred line (RIL) population derived from cross of XieqingzaoB and Zhonghui9308 was re-sequenced and investigated on the grain yield (GYD) and its three component traits, number of panicles per plant (NP), number of filled grains per panicle (NFGP), and grain weight (GW). Unconditional and conditional genome-wide association analysis, based on a linear mixed model with epistasis and gene-environment interaction effects, were conducted, using ~0.7 million identified SNPs. There were six, four, seven, and seven QTSs identified for GYD, NP, NFGP, and GW, respectively, with accumulated explanatory heritability varying from 43.06% to 48.36%; additive by environment interactions were detected for GYD, some minor epistases were detected for NP and NFGP. Further, conditional genetic mapping analysis for GYD given its three components revealed several novel QTSs associated with yield than that were suppressed in our unconditional mapping analysis.

SummaryInsulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.

The transition in extent and characteristics of atmospheric emissions caused by the modernisation of the heavy-duty on-road fleet were studied utilising roadside measurements. Emissions of particle number (PN), particle mass (PM), black carbon (BC), nitrogen oxides (NOx), carbon monoxide (CO), hydrocarbon (HC), particle size distributions and particle volatility were measured from 556 individual heavy-duty trucks (HDTs). Substantial reductions in PM, BC, NOx, CO and to a lesser extent PN were observed from Euro III to Euro VI HDTs by 99 %, 98 %, 93 % and 57 % for the average emissions factors of PM, BC, NOx, and CO respectively. Despite significant total reductions in NOx emissions, the fraction of NO2 in the NOx emissions increased continuously from Euro IV to Euro VI HDTs. Larger data scattering was evident for PN emissions in comparison to solid particle number (SPN) for Euro VI HDTs, indicating a highly variable fraction of volatile particle components. Particle size distributions of Euro III to EEV HDTs were bimodal, whereas those of Euro VI HDTs were nucleation mode dominated. High emitters disproportionately contributed to a large fraction of the total emissions with the highest-emitting 10 % of HDTs in each pollutant category being responsible for 65 % of total PM, 70 % of total PN and 44 % of total NOx emissions, respectively. Euro VI HDTs, which accounted for 53 % of total kilometres driven by Swedish HDTs, were estimated to only contribute to 2 %, 6 %, 12 % and 47 % of PM, BC, NOx, and PN emissions. A shift to a Euro VI HDTs dominant fleet would promote a transition of atmospheric emissions towards low PM, BC, NOx, and CO levels. Nonetheless, reducing PN, SPN, and NO2 emissions from Euro VI HDTs is still important to improve air quality in urban environments.

Background Lean body mass has been identified as a key determinant of left ventricular mass and wall thickness. However, the importance of lean body mass or other body‐size measures as normative determinants of carotid intima‐media thickness ( cIMT ), a widely used early indicator of atherosclerosis, has not been well established. Methods and Results Carotid artery ultrasound measurements of cIMT and carotid artery plaque burden (derived from plaque number and maximum size) and measurements of body size, including height, body mass index, weight, body fat proportion, and lean body mass ([1−body fat proportion]×weight), were recorded in 25 020 participants from 10 regions of China. Analyses were restricted to a healthy younger subset (n=6617) defined as never or long‐term ex‐regular smokers aged cIMT , but was not associated with plaque burden: overall, each 10 kg higher lean body mass was associated with a 0.03 (95% CI , 0.03–0.04) mm higher cIMT ( P =5×10 −33 ). Fat mass, height, and other body‐size measures were more weakly associated with cIMT . Conclusions The strong association of lean body mass with cIMT, but not with plaque burden, in healthy adults suggests a normative relationship rather than reflecting atherosclerotic pathology. Common mechanisms may underlie the associations of lean body mass with cIMT and with nonatherosclerotic vascular traits.

ObjectiveTo comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age.MethodsThis study included 92 284 participants aged 39–51 years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics.ResultsDuring a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction ConclusionOur findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle.

Adverse early-life exposures program increased risk of chronic metabolic diseases in adulthood. However, the effects of genistein supplementation in early life on metabolic health in later life are largely unclear. Our objective was to investigate whether maternal genistein intake could mitigate the deleterious influence of a maternal high-fat diet on glucose and lipid metabolism in offspring and to explore the role of gut microbiota in mediating the transgenerational effects. C57BL/6 female mice were fed either a high-fat diet (HF), high-fat diet with genistein (0.6 g/kg diet) (HFG) or normal control diet (C) for 3 weeks before pregnancy and throughout pregnancy and lactation. The male offspring had ad libitum access to normal chow diet from weaning to 24 weeks of age. Then the content of inguinal subcutaneous adipose tissue (SAT) and epididymal visceral adipose tissue (VAT) were weighed. Glucose tolerance test (GTT), the level of serum insulin and lipid profiles were analyzed. The caecal contents were collected for 16S rDNA sequencing. The results showed that maternal genistein intake could significantly reduce blood glucose levels during GTT, fasting insulin levels, VAT mass and serum triglyceride levels as well as increase high-density lipoprotein cholesterol in adult male offspring. Significant decrease of germs from the Tenericutes phylum and enrichment of Rikenella as well as SCFA (short-chain fatty acid)-producing bacteria, including Alloprevotella, Odoribacter, and Clostridium XlVa, in offspring of genistein fed dams might play crucial roles in the improvement of glucose and lipid metabolism. Overall, early-life genistein intake attenuated the harmful effects of maternal HF on metabolism in adult offspring and the protective effects were associated with the alterations in gut microbiota, which provides new evidence and targets for mitigate the poor effects of adverse early-life exposures on metabolic health in later life.

This paper studies the finite-time synchronization and parameter identification of fractional-order Lorenz chaotic systems with uncertain parameters. Based on the Lyapunov stability theory, a finite-time controller and parameter correction laws are designed. The finite-time synchronization of fractional-order Lorenz chaotic systems is achieved. Moreover, all uncertain parameters of the fractional-order Lorenz system are also identified. Finally, numerical simulation results are provided to demonstrate the effectiveness of the proposed control scheme.