Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes.

Obesity-prone (OP) individuals have a significant predisposition to obesity and diabetes. Previously, we have found that OP individuals, despite being normal in weight and BMI, have already exhibited diabetes-related DNA methylation signatures. However, the underlying mechanisms remain obscure. Here we determined the effects of gut microbiota on DNA methylation and investigated the underlying mechanism from microbial-derived short-chain fatty acids (SCFAs). Diabetes-related DNA methylation loci were screened and validated in a new OP cohort. Moreover, the OP group was revealed to have distinct gut microbiota compositions, and fecal microbiota transplantation (FMT) demonstrated the role of gut microbiota in inducing diabetes-related DNA methylations and glucolipid disorders. UPLC-ESI-MS/MS analysis indicated a significantly lower level of total fecal SCFAs in the OP group. The gut microbiota from OP subjects yielded markedly decreased total SCFAs, while notably enriched propionate. Additionally, propionate was also identified by variable importance in projection (VIP) score as the most symbolic SCFAs of the OP group. Further cellular experiments verified that propionate could induce hypermethylation at locus cg26345888 and subsequently inhibit the expression of the target gene DAB1, which was crucially associated with clinical vitamin D deficiency and thus may affect the development and progression of diabetes. In conclusion, our study revealed that gut microbiota-derived propionate induces specific DNA methylation, thus predisposing OP individuals to diabetes. The findings partially illuminate the mechanisms of diabetes susceptibility in OP populations, implying gut microbiota and SCFAs may serve as promising targets both for clinical treatment and medication development of diabetes.

Influence of Various Heat Treatments on Microstructures and Mechanical Properties of GH4099 Superalloy Produced by Laser Powder Bed Fusion.

The microstructures and mechanical properties of a γ'-strengthened nickel-based superalloy, GH4099, produced by laser powder bed fusion, at room temperature and 900 °C are investigated, followed by three various heat treatments. The as-built (AB) alloy consists of cellular/dendrite substructures within columnar grains aligning in <100> crystal orientation. No γ' phase is observed in the AB sample due to the relatively low content of Al +Ti. Following the standard solid solution treatment, the molten pool boundaries and cellular/dendrite substructures disappear, whilst the columnar grains remain. The transformation of columnar grains to equiaxed grains occurs through the primary solid solution treatment due to the recovery and recrystallization process. After aging at 850 °C for 480 min, the carbides in the three samples distributed at grain boundaries and within grains and the spherical γ' phase whose size is about 43 nm ± 16 nm develop in the standard solid solution + aging and primary solid solution + aging samples (SA and PA samples) while the bimodal size of cubic (181 nm ± 85 nm) and spherical (43 nm ± 16 nm) γ' precipitates is presented in the primary solid solution + secondary solid solution + aging sample (PSA samples). The uniaxial tensile tests are carried out at room temperature (RT) and 900 °C. The AB sample has the best RT ductility (~51% of elongation and ~67% of area reduction). Following the three heat treatments, the samples all acquire excellent RT tensile properties (>750 MPa of yield strengths and >32% of elongations). However, clear ductility dips and intergranular fracture modes occur during the 900 °C tensile tests, which could be related to carbide distribution and a change in the deformation mechanism.

Microplastics in marine-derived traditional Chinese medicine, potential threat to patients.

Microplastics (MPs) contamination is widely found in marine organisms. Marine traditional Chinese medicines (MTCM) are derived from marine organisms, but there are no relevant reports on detecting MPs in MTCM. This study selected samples of MTCM from two representative pharmaceutical companies, Brand F and Brand Z, including mother-of-pearl, stone cassia, seaweed, pumice, oyster, kombu, calcined Concha Arcae, cuttlebone, and clam shell to detect and analyze the presence of MPs. The abundance, type, color, size, and composition of MPs were investigated. Varying degrees of MPs contamination was present in all MTCM. The abundance of MPs in different MTCM ranged from 0.07 to 9.53 items/g. Their type, color, and size are similar, mainly fiber, transparent and size <2 mm. The composition of MPs is primarily made of cotton, cellulose and rayon. This study contributes to the first record of MPs in MTCM. Our results show that microplastic pollution is common in MTCM, which may cause potential risk to patients consuming MTCM.

Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.

Epigenetic Studies of Chinese Herbal Medicine: Pleiotropic Role of DNA Methylation.

Accumulating knowledge has been achieved on DNA methylation participating in numerous cellular processes and multiple human diseases; however, few studies have addressed the pleiotropic role of DNA methylation in Chinese herbal medicine (CHM). CHM has been used worldwide for the prevention and treatment of multiple diseases. Newly developed epigenetic techniques have brought great opportunities for the development of CHM. In this review, we summarize the DNA methylation studies and portray the pleiotropic role of DNA methylation in CHM. DNA methylation serves as a mediator participating in plant responses to environmental factors, and thus affecting CHM medicinal plants growth and bioactive compound biosynthesis which are vital for therapeutic effects. Furthermore, DNA methylation helps to uncover the pharmaceutical mechanisms of CHM formulae, herbs, and herbal-derived compounds. It also provides scientific validation for constitution theory and other essential issues of CHM. This newly developed field of DNA methylation is up-and-coming to address many complicated scientific questions of CHM; it thus not only promotes disease treatment but also facilitates health maintenance.

Chemical profiling of root bark extract from Oplopanax elatus and its in vitro biotransformation by human intestinal microbiota.

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus. A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus, whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus.

Effect of Knowledge/Practice of COVID-19 Prevention Measures on Return-to-Work Concerns; Attitudes About the Efficacy of Traditional Chinese Medicine: Survey on Supermarket Staff in Huanggang, China.

Objective: The objective of this study was to investigate how knowledge and practice of coronavirus disease 2019 (COVID-19) prevention measures affected concerns about returning to work among supermarket staff. Attitudes about the ability of traditional Chinese medicine (TCM) to prevent COVID-19 were also assessed. Methods: A cross-sectional study was conducted in Huanggang, Hubei Province, China from April 23 to 25, 2020. Participants were invited to fill out an electronic questionnaire on their cell phones. Results: The results showed that from 2,309 valid questionnaires, 61.5% of participants were concerned about resuming work. Major concerns included asymptomatic infection (85.01%) and employees gathering in the workplace (78.96%). Multivariate logistic regression indicated that the female gender, having school-aged children and pregnancy were risk factors for being concerned about resuming work, while good knowledge and practice of preventive measures were protective factors. Knowledge and practice of preventive measures were positively correlated. Among preventive measures, the highest percentage of participants knew about wearing masks and washing hands. Meanwhile, 65.8% of participants expressed confidence in the ability of TCM to prevent COVID-19, where 74 and 51.3% thought there was a need and a strong need, respectively, for preventive TCM-based products. Among them, 71.5% preferred oral granules. Regarding TCM as a COVID-19 preventative, most were interested in information about safety and efficacy. Conclusion: These findings suggested that promoting knowledge and practices regarding COVID-19 prevention can help alleviate concerns about returning to work. Meanwhile, TCM can feasibly be accepted to diversify COVID-19 prevention methods. Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2000031955.

Comparison of ultrasonic-assisted and regular leaching of germanium from by-product of zinc metallurgy.

A major source of germanium recovery and also the source of this research is the by-product of lead and zinc metallurgical process. The primary purpose of the research is to investigate the effects of ultrasonic assisted and regular methods on the leaching yield of germanium from roasted slag containing germanium. In the study, the HCl-CaCl2 mixed solution is adopted as the reacting system and the Ca(ClO)2 used as the oxidant. Through six single factor (leaching time, temperature, amount of Ca(ClO)2, acid concentration, concentration of CaCl2 solution, ultrasonic power) experiments and the comparison of the two methods, it is found the optimum collective of germanium for ultrasonic-assisted method is obtained at temperature 80 °C for a leaching duration of 40 min. The optimum concentration for hydrochloric acid, CaCl2 and oxidizing agent are identified to be 3.5 mol/L, 150 g/L and 58.33 g/L, respectively. In addition, 700 W is the best ultrasonic power and an over-high power is adverse in the leaching process. Under the optimum condition, the recovery of germanium could reach up to 92.7%. While, the optimum leaching condition for regular leaching method is same to ultrasonic-assisted method, except regular method consume 100 min and the leaching rate of Ge 88.35% is lower about 4.35%. All in all, the experiment manifests that the leaching time can be reduced by as much as 60% and the leaching rate of Ge can be increased by 3-5% with the application of ultrasonic tool, which is mainly thanks to the mechanical action of ultrasonic.