Lignin bioconversion based on genome mining for ligninolytic genes in Erwinia billingiae QL-Z3.

BACKGROUND: Bioconversion of plant biomass into biofuels and bio-products produces large amounts of lignin. The aromatic biopolymers need to be degraded before being converted into value-added bio-products. Microbes can be environment-friendly and efficiently degrade lignin. Compared to fungi, bacteria have some advantages in lignin degradation, including broad tolerance to pH, temperature, and oxygen and the toolkit for genetic manipulation. RESULTS: Our previous study isolated a novel ligninolytic bacterial strain Erwinia billingiae QL-Z3. Under optimized conditions, its rate of lignin degradation was 25.24% at 1.5 g/L lignin as the sole carbon source. Whole genome sequencing revealed 4556 genes in the genome of QL-Z3. Among 4428 protein-coding genes are 139 CAZyme genes, including 54 glycoside hydrolase (GH) and 16 auxiliary activity (AA) genes. In addition, 74 genes encoding extracellular enzymes are potentially involved in lignin degradation. Real-time PCR quantification demonstrated that the expression of potential ligninolytic genes were significantly induced by lignin. 8 knock-out mutants and complementary strains were constructed. Disruption of the gene for ELAC_205 (laccase) as well as EDYP_48 (Dyp-type peroxidase), ESOD_1236 (superoxide dismutase), EDIO_858 (dioxygenase), EMON_3330 (monooxygenase), or EMCAT_3587 (manganese catalase) significantly reduced the lignin-degrading activity of QL-Z3 by 47-69%. Heterologously expressed and purified enzymes further confirmed their role in lignin degradation. Fourier transform infrared spectroscopy (FTIR) results indicated that the lignin structure was damaged, the benzene ring structure and groups of macromolecules were opened, and the chemical bond was broken under the action of six enzymes encoded by genes. The abundant enzymatic metabolic products by EDYP_48, ELAC_205 and ESOD_1236 were systematically analyzed via liquid chromatography-mass spectrometry (LC-MS) analysis, and then provide a speculative pathway for lignin biodegradation. Finally, The activities of ligninolytic enzymes from fermentation supernatant, namely, LiP, MnP and Lac were 367.50 U/L, 839.50 U/L, and 219.00 U/L by orthogonal optimization. CONCLUSIONS: Our findings provide that QL-Z3 and its enzymes have the potential for industrial application and hold great promise for the bioconversion of lignin into bioproducts in lignin valorization.

Curcumin induces mitophagy by promoting mitochondrial succinate dehydrogenase activity and sensitizes human papillary thyroid carcinoma BCPAP cells to radioiodine treatment.

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.

Total saponins from Panax japonicus attenuate acute alcoholic liver oxidative stress and hepatosteatosis by p62-related Nrf2 pathway and AMPK-ACC/PPARα axis in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax japonicus (T. Nees) C.A. Mey. (PJ) has been used as a tonic traditional Chinese medicine (TCM) for years. Based on its meridian tropism in liver, spleen, and lung, PJ was popularly used to enhance the function of these organs. It is originally recorded with detoxicant effect on binge drink in Ben Cao Gang Mu Shi Yi, a persuasive Chinese materia medica. And binge dink has a close relationship with alcoholic liver disease (ALD). Hence, it's meaningful to investigate whether PJ exerts liver protection against binge drink toxicity. AIM OF THE STUDY: This investigation was carried out not only to emphasize the right recognition of total saponins from PJ (SPJ), but also to study on its sober-up effectiveness and defensive mechanism against acute alcoholic liver injury in vivo and in vitro. MATERIALS AND METHODS: SPJ constituents were verified by HPLC-UV analysis. In vivo, acute alcoholic liver oxidative stress and hepatosteatosis were established by continuous ethanol gavage to C57BL/6 mice for 3 days. SPJ was pre-administered for 7 days to investigate its protective efficacy. Loss of righting reflex (LORR) assay was employed to assess anti-inebriation effect of SPJ. Transaminases levels and hematoxylin and eosin (H&E) staining were measured to indicate the alcoholic liver injury. Antioxidant enzymes were measured to evaluate the oxidative stress degree in liver. Measurement of hepatic lipid accumulation was based on Oil Red O staining. Levels of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). In vitro, HepG2 cells were treated with ethanol for 24 h, and SPJ was pre-administered for 2 h. 2,7-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to indicate reactive oxygen species (ROS) generation. Nrf2 activation was verified by the favor of specific inhibitor, ML385. The nuclear translocation of Nrf2 was indicated with immunofluorescence analysis. Proteins expressions of related pathways were determined by Western blotting. RESULTS: Oleanane-type saponins are the most abundant constituents of SPJ. In this acute model, SPJ released inebriation of mice in a dose dependent manner. It decreased levels of serum ALT and AST, and hepatic TG. Besides, SPJ inhibited CYP2E1 expression and reduced MDA level in liver, with upregulations of antioxidant enzymes GSH, SOD and CAT. p62-related Nrf2 pathway was activated by SPJ with downstream upregulations of GCLC and NQO1 in liver. AMPK-ACC/PPARα axis was upregulated by SPJ to alleviate hepatic lipidosis. Hepatic IL-6 and TNF-α levels were downregulated by SPJ, which indicated a regressive lipid peroxidation in liver. In HepG2 cells, SPJ reduced ethanol-exposed ROS generation. Activated p62-related Nrf2 pathway was verified to contribute to the alleviation of alcohol-induced oxidative stress in hepatic cells. CONCLUSION: This attenuation of hepatic oxidative stress and steatosis suggested the therapeutic value of SPJ for ALD.

[An anti-scald device for warm needling].

Warm needling, i.e. acupuncture with the needle warmed by burning moxa stick or cone, is frequently employed in the treatment of cold and dampness type disorders. During treatment, accidental skin scald may occur if the burning moxa drops on the skin due to slight changes in patient's body position. Thus, we designed and developed an anti-scald device for warm needling which is suitable for any part of the body. This device is made up of two parts, a stainless steel-grid moxa cartridge (including half cylinder, hinge shaft, lug, limit bar, clamping arm, connecting arm, torsion spring, heat insulation pad, through holes) and a clamp holder which is in an integrated structure. The grid moxa cartridge can be used to wrap the burning mugwort cone in all directions to prevent the ignited moxa-cone from falling and skin scalding, and effectively collect the burned moxa ash. At the same time, the clamp holder can be used to help fix the moxa-cone to increase the stability of warm needling operation. The device is convenient to operate and novel in design, can effectively reduce the occurrence of scald accidents in clinical treatment, save time and manpower, and has both economic and ecological benefits, being helpful to the promotion and use of warm needling.

Characterization and Comparative Analysis of Chloroplast Genomes in Five Uncaria Species Endemic to China.

Uncaria, a perennial vine from the Rubiaceae family, is a typical Chinese traditional medicine. Currently, uncertainty exists over the Uncaria genus' evolutionary relationships and germplasm identification. The complete chloroplast genomes of four Uncaria species mentioned in the Chinese Pharmacopoeia and Uncaria scandens (an easily confused counterfeit) were sequenced and annotated. The findings demonstrated that the whole chloroplast genome of Uncaria genus is 153,780-155,138 bp in full length, encoding a total of 128-131 genes, containing 83-86 protein-coding genes, eight rRNAs and 37 tRNAs. These regions, which include eleven highly variable loci and 31-49 SSRs, can be used to create significant molecular markers for the Uncaria genus. The phylogenetic tree was constructed according to protein-coding genes and the whole chloroplast genome sequences of five Uncaria species using four methods. The topology of the two phylogenetic trees showed no difference. The sequences of U. rhynchophylla and U. scandens are clustered in one group, while the U. hirsuta and U. macrophylla are clustered in another group. U. sessilifructus is clustered together with the above two small clades. New insights on the relationship were revealed via phylogenetic research in five Uncaria species. This study will provide a theoretical basis for identifying U. rhynchophylla and its counterfeits, as well as the species of the Uncaria genus. This research provides the initial chloroplast genome report of Uncaria, contributes to elucidating the chloroplast genome evolution of Uncaria in China.

Rhodiola activates macrophage migration inhibitory factor to alleviate non-alcoholic fatty liver disease.

AIMS: Rhodiola was found to be a potential treatment for nonalcoholic fatty liver disease (NAFLD). The macrophage migration inhibitory factor (MIF)-regulated lipophagy and lipid metabolism might be the therapeutic targets of Rhodiola. MAIN METHODS: A 16-week high-fat diet (HFD) was used to simulate a NAFLD mouse model. Rhodiola extract or normal saline were administrated to mice. Blood was collected to assess blood glucose and insulin, and livers were harvested to assess lipid accumulation and metabolism. In cell experiments, the active ingredient of Rhodiola, salidroside, and recombinant MIF protein (rMIF) were used to treat palmitate (PA)-incubated HepG2 cells, with MIF-siRNA or NC-siRNA transfection. Then, the level of lipophagy and lipid metabolism was examined. KEY FINDINGS: Rhodiola improved lipid accumulation and metabolism disorder of HFD mice. The oil red O staining of the liver showed that increased lipid droplets in the NAFLD liver could be relieved by Rhodiola; Rhodiola also alleviated the increasing body weight, liver weight, and HOMA-IR index of HFD mice. Results in cell experiments were consistent: salidroside relieved the lipid droplet accumulation and triglyceride release in PA cells, as well as reduced lipophagosome and lipid metabolism disorder in PA cells. However, all these effects of salidroside were partially blocked by MIF-siRNA transfection. SIGNIFICANCE: Rhodiola reduces lipid accumulation in the liver of NAFLD by facilitating the MIF pathway and the downstream lipophagy and lipid metabolism. MIF may be an endogenous regulator of liver lipophagy and lipid metabolism and a potential therapeutic target for NAFLD.

Exercise inhibits JNK pathway activation and lipotoxicity via macrophage migration inhibitory factor in nonalcoholic fatty liver disease.

The macrophage migration inhibitory factor (MIF) expressed in hepatocytes can limit steatosis during obesity. Lipotoxicity in nonalcoholic fatty liver disease is mediated in part by the activation of the stress kinase JNK, but whether MIF modulates JNK in lipotoxicity is unknown. In this study, we investigated the role of MIF in regulating JNK activation and high-fat fostered liver lipotoxicity during simultaneous exercise treatment. Fifteen mice were equally divided into three groups: normal diet, high-fat diet, and high-fat and exercise groups. High-fat feeding for extended periods elicited evident hyperlipemia, liver steatosis, and cell apoptosis in mice, with inhibited MIF and activated downstream MAPK kinase 4 phosphorylation and JNK. These effects were then reversed following prescribed swimming exercise, indicating that the advent of exercise could prevent liver lipotoxicity induced by lipid overload and might correlate to the action of modulating MIF and its downstream JNK pathway. Similar detrimental effects of lipotoxicity were observed in in vitro HepG2 cells palmitic acid treatment. Suppressed JNK reduced the hepatocyte lipotoxicity by regulating the BCL family, and the excess JNK activation could also be attenuated through MIF supplementation or exacerbated by MIF siRNA administration. The results found suggest that exercise reduces lipotoxicity and inhibits JNK activation by modulating endogenous hepatic MIF in NAFLD. These findings have clinical implications for the prevention and intervention of patients with immoderate diet evoked NAFLD.

[Prevention from PICC-related venous thrombosis in the upper limbs of malignant tumor patients with moxibustion combined with plucking at Jiquan (HT 1): a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of moxibustion combined with plucking technique at Jiquan (HT 1) for preventing peripherally inserted central catheter (PICC)-related venous thrombosis in the upper limbs of malignant tumor patients. METHODS: A total of 80 malignant tumor patients undergoing PICC were randomized into an observation group and a control group, 40 cases in each one. In the control group, the routine care for PICC was exerted. In the observation group, besides the routine care, moxibustion combined with plucking technique at Jiquan (HT 1) was added. Mild moxibustion was exerted along the venous distribution of PICC (avoiding the entry site) for 10 to 15 min, and then, the circling moxibustion was applied to Quchi (LI 11), Xuehai (SP 10) and Tianfu (LU 3), 3 to 5 min at each acupoint. Finally, plucking technique was given at Jiquan (HT 1) for 5 to 10 min. This combined therapy was intervened since the 2nd day of PICC placement, once daily, 5 times a week, for 3 weeks totally. The incidence of the PICC-related venous thrombosis in the upper limbs was compared between the two groups on day 42 of placement. On day 2, 7, 14, 21, 28, 35 and 42 of PICC placement, the peak systolic velocity (PSV) and the end-diastolic velocity (EDV) of the subclavicular vein on the placement side were observed separately in the two groups. RESULTS: The incidence of the PICC-related venous thrombosis in the upper limbs in the observation group was lower than that in the control group (2.5% [1/40] vs 17.5% [7/40], P<0.05). From day 7 to 35 of PICC placement, PSV of the subclavicular vein on the placement side was higher than that on the day 2 of PICC placement in the observation group (P<0.05). On day 28 and 42 of PICC placement, PSV of the subclavicular vein on the placement side was lower than that on the day 2 of PICC placement in the control group (P<0.05). In the observation group, EDV of the subclavicular vein on the placement side was higher than that on the day 2 of PICC placement from day 7 to 28 of PICC placement (P<0.05). In the control group, EDV of the subclavicular vein on the placement side from day 28 to 42 of PICC placement was lower than that on the day 2 of PICC placement (P<0.05). From day 7 to 42 of PICC placement, PSV and EDV of the subclavicular vein on the placement side in the observation group were all higher than those in the control group (P<0.01, P<0.05). CONCLUSION: The combined treatment of moxibustion with plucking technique at Jiquan (HT 1) can effectively prevent PICC-related venous thrombosis in the upper limbs and improve venous blood flow velocity in malignant tumor patients.

Association Between Exposure to Outdoor Artificial Light at Night and Sleep Disorders Among Children in China.

Importance: Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children. Objective: To explore the associations between outdoor ALAN exposure and sleep disorders in children. Design, Setting, and Participants: This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022. Exposures: Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m. Main Outcomes and Measures: Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders. Results: The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm2/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years. Conclusions and Relevance: The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.

[Analysis and suggestions on harvest period standards of plant medicinal materials in 2020 edition of Chinese Pharmacopoeia].

The improvement of the harvest period standards is critical in the quality control of Chinese medicinal materials. The present study statistically analyzed the harvest period standards of plant medicinal materials in the 2020 edition of Chinese Pharmacopoeia(Vol.Ⅰ) and put forward the existing problems and suggestions based on herbal records and modern research to provide references for the improvement of the standards. According to the statistical analysis, in 499 types of plant medicinal materials, harvest period standards are recorded under 486 types, accounting for 97.4%, and are lacking in the remaining. Only one medicinal material(Stellariae Radix) is recorded with the standard of the harvest year. The standards of the harvest season and phenological period are recorded under 233 types, accounting for 46.7%. For 237 types, only harvest season is specified, accounting for 47.5%, and for 15 types, only harvest phenological period is specified, accounting for 3.0%. Among 222 types mainly derived from cultivation and 51 types from wild resources and cultivation, only 11 types are recorded with harvest period of cultivated products. Only Stellariae Radix is recorded with the harvest period standards for the wild and cultivated products separately. The harvest period standards of plant medicinal materials with different medicinal parts have certain rules to follow. The main problems about the harvest period standards are discovered. Specifically, no harvest period standards are recorded under 13 types of plant medicinal materials. Almost all perennial cultivated medicinal materials are not recorded with harvest year standard. No phenological period standard is found under 250 types of plant medicinal materials. There is no clear distinction between the harvest period standards of cultivated and wild products. The evidence for harvest period standards of 26 types of plant medicinal materials that can be harvested all year round is insufficient. As a result, it is proposed to strengthen basic research in response to the above-mentioned problems and improve the harvest period standards as soon as possible to ensure the quality of Chinese medicinal materials.

Dietary supplementation Eucommia ulmoides extract at high content served as a feed additive in the hens industry.

Since numerous natural components in Eucommia ulmoides belong to phytoestrogen, its effect on hens production deserve more attention. To investigate the potential of E. ulmoides extract used as a feed additive, laying performance, egg quality, yolk cholesterol, yolk fatty acids, yolk fatty, yolk volatile components, albumen amino acids, plasma biochemical parameters, intestinal histology, and gut microbiota of hens (n = 120) were determined between basal diet (A) and dietary supplementation low (B), middle (C), and high (D) level E. ulmoides extract for 11 wk. When compared to A group, 2 percentage points elevation in laying rate was observed of D group. Significant up-regulation of immunoglobulin indexes and down-regulation of lipid related indexes in D group were also found if comparison with A group, suggesting that supplementation E. ulmoides extract at a relative high content benefited in immunity enhancing and blood-fat depressing. Meanwhile, obvious variation in albumen amino acids and yolk volatile compounds were inspected as dietary supplementation E. ulmoides extract, especially in D group, implied that the flavor of egg would change under high-level E. ulmoides extract treatment. Besides, villus height and villus height to crypt depth ratio of duodenum, jejunum, and ileum in D group were also significantly higher than that of in A group, indicating high-level E. ulmoides extract contributed to nutrient adsorption via intestinal histology changing. Moreover, the richness, diversity, and composition of gut microbiota in D group also significantly altered with a comparison of A group. These variation caused gut microbiota in D group major enriched in the KEGG pathway of insulin signing pathway, systemic lupus erythematosus, and bacterial invasion of epithelial cells, which were conducive to egg production elevation via facilitating nutrient adsorption, inflammation relieving, blood lipid amelioration, and insulin resistance alleviation. These results indicated that dietary supplementation E. ulmoides extract at high content could serve as a feed additive in the hens industry.

The complete chloroplast genome sequence of Spiraea japonica var. acuminata Franch. (Rosaceae).

Spirea japonica var. acuminata Franch. (Rosaceae) is a Chinese herbal medicine distributed in southwest and east China. The first complete chloroplast genome of Spirea japonica var. acuminata Franch. was assembled and reported in this study. The genome is 153,822 bp in length and contained 125 encoded genes in total, including 80 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The phylogenomic analysis showed that Spirea japonica var. acuminata Franch. was closely related to Spirea blumei, Spirea trilobata, Spirea mongolica and Spirea insularis according to the current sampling extent.

Analysis and suggestions on harvest period standards of plant medicinal materials in 2020 edition of Chinese Pharmacopoeia / 中国中药杂志

The improvement of the harvest period standards is critical in the quality control of Chinese medicinal materials. The present study statistically analyzed the harvest period standards of plant medicinal materials in the 2020 edition of Chinese Pharmacopoeia(Vol.Ⅰ) and put forward the existing problems and suggestions based on herbal records and modern research to provide references for the improvement of the standards. According to the statistical analysis, in 499 types of plant medicinal materials, harvest period standards are recorded under 486 types, accounting for 97.4%, and are lacking in the remaining. Only one medicinal material(Stellariae Radix) is recorded with the standard of the harvest year. The standards of the harvest season and phenological period are recorded under 233 types, accounting for 46.7%. For 237 types, only harvest season is specified, accounting for 47.5%, and for 15 types, only harvest phenological period is specified, accounting for 3.0%. Among 222 types mainly derived from cultivation and 51 types from wild resources and cultivation, only 11 types are recorded with harvest period of cultivated products. Only Stellariae Radix is recorded with the harvest period standards for the wild and cultivated products separately. The harvest period standards of plant medicinal materials with different medicinal parts have certain rules to follow. The main problems about the harvest period standards are discovered. Specifically, no harvest period standards are recorded under 13 types of plant medicinal materials. Almost all perennial cultivated medicinal materials are not recorded with harvest year standard. No phenological period standard is found under 250 types of plant medicinal materials. There is no clear distinction between the harvest period standards of cultivated and wild products. The evidence for harvest period standards of 26 types of plant medicinal materials that can be harvested all year round is insufficient. As a result, it is proposed to strengthen basic research in response to the above-mentioned problems and improve the harvest period standards as soon as possible to ensure the quality of Chinese medicinal materials.

Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis.

Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004).

Metabolic profiling in early pregnancy and associated factors of folate supplementation: A cross-sectional study.

BACKGROUND: Pregnancy generally alters the balance of maternal metabolism, but the molecular profiles in early pregnancy and associated factors of folate supplementation in pregnant women remains incompletely understood. METHODS: Untargeted metabonomics based on high-performance liquid chromatography-high-resolution mass spectrometry integrated with multivariate metabolic pathway analysis were applied to characterize metabolite profiles and associated factors of folate supplements in early pregnancy. The metabolic baseline of early pregnancy was determined by metabolic analysis of 510 serum samples from 131 non-pregnant and 379 pregnant healthy Chinese women. The pathophysiology of adaptive reactions and metabolic challenges induced by folate supplementation in early pregnancy was further compared between pregnant women with (n = 168) and without (n = 184) folate supplements. RESULTS: Compared with non-pregnant participants, 106 metabolites, majority of which are related to amino acids and lysophosphatidylcholine/phosphatidylcholine, and 13 metabolic pathways were significantly changed in early pregnancy. The supplementation of folate in early pregnancy induced marked changes in N-acyl ethanolamine 22:0, N-acyl taurine 18:2, glycerophosphoserine 44:1 and 8,11,14-eicosatrienoate, proline, and aminoimidazole ribotide levels. CONCLUSIONS: During early pregnancy, the metabolism of amino acids significantly changes to meet the physiological requirements of pregnant women. Folate intake may change glucose and lipid metabolism. These findings provide a comprehensive landscape for understanding the basic characteristics and gestational metabolic networks of early pregnancy and folate supplementation. This study provides a basis for further research into the relationship between metabolic markers and pregnancy diseases. TRIAL REGISTRATION: This study protocol was registered on www.ClinicalTrials.gov, NCT03651934, on August 29, 2018 (prior to recruitment).

Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

The Treatment of Rhodiola Mimics Exercise to Resist High-Fat Diet-Induced Muscle Dysfunction via Sirtuin1-Dependent Mechanisms.

Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons. To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit. Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.

Current advances in environmental stimuli regulating the glycyrrhizic acid biosynthesis pathway.

Glycyrrhizic acid, the main active ingredient of licorice, has good antibacterial, anti-tumor, anti-viral, anti-inflammatory, and immunostimulatory activities. However, the content of glycyrrhizic acid fluctuates greatly in different licorice cultivars, and production depends on plant sources, which greatly limits its development and applications. Therefore, increasing glycyrrhizic acid content has become a research priority. In recent years, regulation of the glycyrrhizic acid biosynthesis pathway has been analyzed, the downstream synthesis pathway in licorice has been fully investigated, some key genes have been cloned, polymorphisms have been studied, and the content of glycyrrhizic acid was shown to be regulated by environmental stimuli. This work has provided a basis for studying the regulation mechanism of the glycyrrhizic acid synthesis pathway. This review summarizes and discusses relevant research to provide a current understanding of the glycyrrhizic acid synthesis pathway and its regulation in licorice.

Improving anaerobic digestion of chicken manure under optimized biochar supplementation strategies.

Anaerobic digestion of chicken manure was carried out in this study basing on central composite design to identify the most optimal strategy for biochar supplementation. Model of cumulative methane production (CMP) was established by using response surface methodology. The optimal conditions predicted accordingly, including manure loading of 51.8 g VS/L, biochar dosage of 3.3% VSmanure, and cellulose loading of 98.0 g VS/L, were expected to maximize CMP, i.e., 294 mL/g VSmanure. The results also demonstrated that biochar dosage and its interaction with manure loading were key factors with significant impact on CMP. Biochar dosage higher than 3.5% VSmanure was observed to weaken the transformation of organic substances to methane. Higher dosage of biochar could considerably reduce concentration of organic acids, total ammonia nitrogen, as well as soluble salts. Verification experiment supported validity of the optimal strategy and provided data for cost assessment, which showed positive cost balances from biochar supplementation.

Comparison of anti-inflammatory effects of Lonicerae Japonicae Flos and Lonicerae Flos based on network pharmacology.

Objective: In Chinese herbal medicine (CHM) history, Lonicerae Japonicae Flos and Lonicerae Flos were used clinically as one drug, but now they are admitted as two herbal medicines in Chinese Pharmacopoeia (2010 edition). This study used network pharmacology to investigate whether the two can be used interchangeably for the treatment of inflammatory diseases in TCM clinical practice. Methods: Lonicerae Japonicae Flos and Lonicerae Flos were compared in the inflammation mechanism including core targets, Gene Ontology (GO), pathway and principle chemical components by the method of network pharmacology. Results: Lonicerae Japonicae Flos and Lonicerae Flos shared in six targets accounting for 66.7% of the entire core targets and more than half of the GO terms and pathways are similar. Organic acids are dominent compounds responsible for anti-inflammatory effects. Three of the compounds that bind to core targets including luteolin, quercetin and kaempferol, are shared in both herbs. Conclusion: Due to high similarity between Lonicerae Japonicae Flos and Lonicerae Flos, we believe that they can be used interchangeably for the inflammation in clinical treatment.