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"Yan, Xiang"
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Metabolomics Signatures in Type 2 Diabetes: A Systematic Review and Integrative Analysis
Abstract
Objective
Metabolic signatures have emerged as valuable signaling molecules in the biochemical process of type 2 diabetes (T2D). To summarize and identify metabolic biomarkers in T2D, we performed a systematic review and meta-analysis of the associations between metabolites and T2D using high-throughput metabolomics techniques.
Methods
We searched relevant studies from MEDLINE (PubMed), Embase, Web of Science, and Cochrane Library as well as Chinese databases (Wanfang, Vip, and CNKI) inception through 31 December 2018. Meta-analysis was conducted using STATA 14.0 under random effect. Besides, bioinformatic analysis was performed to explore molecule mechanism by MetaboAnalyst and R 3.5.2.
Results
Finally, 46 articles were included in this review on metabolites involved amino acids, acylcarnitines, lipids, carbohydrates, organic acids, and others. Results of meta-analysis in prospective studies indicated that isoleucine, leucine, valine, tyrosine, phenylalanine, glutamate, alanine, valerylcarnitine (C5), palmitoylcarnitine (C16), palmitic acid, and linoleic acid were associated with higher T2D risk. Conversely, serine, glutamine, and lysophosphatidylcholine C18:2 decreased risk of T2D. Arginine and glycine increased risk of T2D in the Western countries subgroup, and betaine was negatively correlated with T2D in nested case-control subgroup. In addition, slight improvements in T2D prediction beyond traditional risk factors were observed when adding these metabolites in predictive analysis. Pathway analysis identified 17 metabolic pathways may alter in the process of T2D and metabolite-related genes were also enriched in functions and pathways associated with T2D.
Conclusions
Several metabolites and metabolic pathways associated with T2D have been identified, which provide valuable biomarkers and novel targets for prevention and drug therapy.
Journal Article
Roles and mechanisms of exosomal non-coding RNAs in human health and diseases
Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are closely related to a variety of biological and functional aspects of human health. When the exosomal ncRNAs undergo tissue-specific changes due to diverse internal or external disorders, they can cause tissue dysfunction, aging, and diseases. In this review, we comprehensively discuss the underlying regulatory mechanisms of exosomes in human diseases. In addition, we explore the current knowledge on the roles of exosomal miRNAs, lncRNAs, and circRNAs in human health and diseases, including cancers, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, and infectious diseases, to determine their potential implication in biomarker identification and therapeutic exploration.
Journal Article
Research on Graphic Design Image Processing Technology Based on Reference Relation
At present, with the rapid economic progress, some emerging technologies have emerged. Processing and designing various images with the help of computer software has been widely used in the field of graphic design. With the wide popularization and in-depth application of computers, the application of computer graphics and images in print advertisement design is deepening day by day. Graphic is one of the basic elements of graphic design. As a visual symbol, graphics play a role in carrying and disseminating information and expressing thoughts and emotions. Using computer system for graphic design and production has become the international and domestic development trend, which is the requirement of the times, modernization and the development of the industry itself. Based on the reference relationship, this paper expounds the choice of graphics in graphic design, the role of graphics in graphic design and the relationship between graphics and layout in graphic design. The exploration of graphic elements in graphic design is conducive to the understanding and application of graphic elements in graphic design and the effective transmission of information.
Journal Article
Combination of probiotics with different functions alleviate DSS-induced colitis by regulating intestinal microbiota, IL-10, and barrier function
The potential of probiotics for treating ulcerative colitis (UC) has attracted increasing attention. However, more studies are still needed to guide physicians on the proper selection and use of probiotics. Here, we propose that combination of multiple probiotics with different functions can reduce intestinal inflammation. In this study, the effects of probiotics (Lactobacillus reuteri, Bacillus coagulans, Bifidobacterium longum, and Clostridium butyricum) on the physiology and histopathology of colon were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. The combined species, as well as the species individually, were tested and compared with sulfasalazine (SASP) and two Chinese herbal therapies. Results show that the functions of the four probiotic strains were different in regulating intestinal immunity and barrier function. The four-species probiotic cocktail was more effective than the species individually and anti-inflammatory drugs in repairing the dysbiosis of mucosal microbial ecology and reducing intestinal inflammation. The multi-strain probiotic mixture increased the proportion of beneficial bacteria and decreased the proportion of pro-inflammatory bacteria in the colonic mucosa. In addition, probiotic mixture significantly enhanced the expression of IL-10 and intestinal barrier function. These results suggest that a combination of multiple probiotics with different functions has synergistic effects and can restore the balance of interactions between microorganisms and immunological niches.
Journal Article
Biological nitrogen removal from wastewater using sulphur-driven autotrophic denitrification
Biological denitrification process in mainstream wastewater treatment often needs dosing supplemental electrons, consequently adding a remarkable operating cost. Organic carbon compounds are nowadays the most intensively used electron sources in full-scale wastewater treatment, corresponding with the well-understood carbon-nitrogen biogeochemistry for heterotrophic denitrification process. In the twenty-first century, the low-carbon technology is on calling to reduce the carbon footprint and relieve climate changing threatens. Autotrophic denitrification is highly recommended for mainstream wastewater treatment. The reduced-sulphur compounds (such as sulphide, elemental sulphur, and thiosulphate) could be utilised as electron donors, to drive sulphur cycle reactions to reduce nitrate and nitrite to dinitrogen gas. Based on the literature review and our own research experiences, this paper presents our perspectives on sulphur-driven autotrophic denitrification. It particularly focuses on the functional enzymes, sulphur bioreactors, and influential operating factors. Overall, this paper provides new insights on sulphur-nitrogen biogeochemistry and application as a low-carbon technology for nitrogen removal during municipal wastewater treatment.
Journal Article
The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor
Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that lacks effective therapeutic interventions. SARS-CoV-2 infects ACE2-expressing cells and gains cell entry through either direct plasma membrane fusion or endocytosis. Recent studies have shown that in addition to ACE2, heparan sulfate proteoglycans (HSPGs) also play an important role in SARS-CoV-2 cell attachment by serving as an attachment factor. Binding of viral spike protein to HSPGs leads to the enrichment of local concentration for the subsequent specific binding with ACE2. We therefore hypothesize that blocking the interactions between viral spike protein and the HSPGs will lead to inhibition of viral replication. In this study, we report our findings of the broad-spectrum antiviral activity and the mechanism of action of lactoferrin (LF) against multiple common human coronaviruses as well as SARS-CoV-2. Our study has shown that LF has broad-spectrum antiviral activity against SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E in cell culture, and bovine lactoferrin (BLF) is more potent than human lactoferrin. Mechanistic studies revealed that BLF binds to HSPGs, thereby blocking viral attachment to the host cell. The antiviral activity of BLF can be antagonized by the HSPG mimetic heparin. Combination therapy experiment showed that the antiviral activity of LF is synergistic with remdesivir in cell culture. Molecular modelling suggests that the N-terminal positively charged region in BLF (residues 17-41) confers the binding to HSPGs. Overall, LF appears to be a promising drug candidate for COVID-19 that warrants further investigation.
Journal Article
The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study
Background
The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes.
Methods
In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001–2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines.
Results
Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284–1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes.
Conclusions
There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.
Journal Article
An Enhanced Mapping Function with Ionospheric Varying Height
Mapping function (MF) converts the line-of-sight slant total electron content (STEC) into the vertical total electron content (VTEC), and vice versa. In an MF, an essential parameter is the ionospheric effective height. However, the inhomogeneous ionosphere makes this height vary spatially and temporally, meaning it is not a global constant. In the paper, we review several mapping functions and propose a mapping function that utilizes the ionospheric varying height (IVH). We investigate impacts of the IVH on mapping errors and on the ionospheric modeling, as well as on the satellite and receiver differential code biases (DCBs). Our analysis results indicate that the mapping errors using IVH are smaller than those from the fixed height of 450 km. The integral height achieves smaller mapping errors than using a fixed height of 450 km, an improvement of about 8% when compared with the fixed height of 450 km. And 35% smaller mapping errors were found using HmF2 at the lower latitude. Also, the effects of IVH on the satellite DCBs are about 0.1 ns, and larger impacts on the receiver DCBs at 1.0 ns.
Journal Article
Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial
Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (
n
= 99) or undergo active surveillance (
n
= 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360–0.792;
P
= 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier:
ChiCTR2000037655
.
Results from a multicenter, randomized phase 2 trial in China show that adjuvant anti-PD-1 therapy in patients with resected hepatocellular carcinoma with microvascular invasion leads to prolonged recurrence-free survival compared to active surveillance.
Journal Article