Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Two {CuI[P4Mo6]2}-Based Coordination Polymers Incorporating In Situ Converted Tetrapyridyl Ligands for Trace Analysis of Nitrofuran Antibiotics.

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4″,4‴-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

Five glycosylation-related gene signatures predict the prognostic risks of lung adenocarcinoma.

This study aimed to identify glycosylation-related genes associated with lung adenocarcinoma (LUAD) prognosis through comprehensive bioinformatic analysis. Glycosylation-related genes were identified from the Human Gene Nomenclature Committee, and LUAD prognostic genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)-GSE68465 datasets. Glycosylation risk score (GLRS) was calculated to predict LUAD prognostic risk. Samples were grouped into GLRS-high and GLRS-low and compared. The Tumor Immune Dysfunction and Exclusion (TIDE) score was computed to assess the antitumor immune escape possibility after immunotherapy. From 213 glycosylation-related genes, five gene signatures served as prognostic LUAD predictors using univariate and stepwise Cox regression analyses. GLRS-based models were constructed using TCGA and GSE68465 samples; their sensitivity and specificity in predicting LUAD prognosis were confirmed. GLRS was an independent LUAD prognostic factor and contributed to the nomogram to predict patient survival. High GLRS was associated with advanced tumor stage and higher mutation frequencies, estimate scores, and TIDE scores. GLRS-high and GLRS-low patients differed in immune cell infiltration and epithelial-mesenchymal transition (EMT)-related gene expression. Thus, we propose five glycosylation-related gene signatures to predict overall survival and prognostic risks of LUAD. Their regulatory roles may be related to immune invasion, immunotherapy response, mutation, and EMT.

Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth.

BACKGROUND: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. METHODS: The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin. RESULTS: Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death. CONCLUSIONS: Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate.

Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: a network meta-analysis.

BACKGROUND: Long-term antiviral treatments are associated with a significantly lower hepatocellular carcinoma (HCC) incidence in chronic hepatitis B (CHB) patients by reducing HBV DNA concentrations. However, it is still controversial whether antiviral strategies affect HCC development in antiviral treatment-naïve CHB patients. This study aimed to estimate the incidence of HCC in antiviral treatment-naïve CHB patients who were treated with Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF) and compare the efficacy of two treatment regimens in HCC reduction. METHODS: The PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were systematically searched until June 24, 2021. The pooled incidence and 95% confidence interval of HCC were calculated by the Freeman-Tukey double arcsine transformation method. The efficacies of ETV and TDF treatments in HCC reduction were compared through a network meta-analysis. RESULTS: A total of 27 studies were identified as eligible for this systematic review. The incidence densities in the ETV and TDF treatment groups were 2.78 (95% CI: 2.21-3.40) and 2.59 (95% CI: 1.51-3.96) per 100 persons-year among patients with preexisting cirrhosis and 0.49 (95% CI: 0.32-0.68) and 0.30 (95% CI: 0.06-0.70) per 100 persons-year among patients without preexisting cirrhosis. As the proportion of CHB patients with preexisting cirrhosis increased, the incidence density of HCC also increased gradually. Compared with other Nucleos(t)ide analogs (NAs) treatments, ETV and TDF treatments significantly lowered the risk of HCC, with hazard ratios (HRs) of 0.60 (95% CI: 0.40-0.90) and 0.56 (95% CI: 0.35-0.89), respectively. However, there was no difference in the incidence density of HCC between ETV and TDF treatments (HR = 0.92, 95% CI: 0.71-1.20) regardless of preexisting cirrhosis. CONCLUSION: ETV and TDF treatments were associated with significantly lower risks of HCC than other NAs treatments. However, no difference was observed between ETV and TDF treatments in the risk of HCC development regardless of preexisting cirrhosis among treatment-naïve CHB patients.

Screening of central obesity among normal-weight children and adolescents in Shandong, China.

The prevalence of central obesity in the total population has been reported in numerous studies. However, information on the prevalence of central obesity within normal-category BMI is scant. In the present study, we examined the profiles of central obesity among normal-weight children and adolescents. A total of 29 516 (14 226 boys and 15 290 girls) normal-weight children and adolescents (excluding underweight, overweight and obesity) aged 7-18 years were included in the final analysis. Central obesity was defined by the international age- and sex-specific cut-offs of waist circumference (WC) and threshold of waist:height ratio (WHtR ≥ 0·5). All subjects were classified into four groups (Q1-Q4) according to the age- and sex-specific quartiles of BMI, those in the upper fourth (Q4) were defined as 'high-normal BMI' and those in the lower fourth (Q1) were defined as 'low-normal BMI'. The prevalence of central obesity as measured by WC was 9·90 (95 % CI 9·41, 10·39) % for boys and 8·11 (95 % CI 7·68, 8·54) % for girls; by WHtR was 2·97 (95 % CI 2·69, 3·25) % for boys and 2·44 (95 % CI 2·20, 2·68) % for girls. Subjects in the Q4 group had a much higher prevalence of central obesity than their counterparts in the Q1 group (P < 0·01). Our findings suggest that the health risks of children with normal-weight central obesity may be missed when BMI is used alone as a measure; it is meaningful to include WC in clinical practice and to include the simple message 'Keep your waist to less than half your height'.

Metabolomics and Lipidomics Profiling in Asymptomatic Severe Intracranial Arterial Stenosis: Results from a Population-Based Study.

No data are available on the serum metabolomics and lipidomics profiles of people with asymptomatic intracranial arterial stenosis. We explored the characteristic metabolites of individuals with asymptomatic severe intracranial arterial stenosis (asICAS) using untargeted serum metabolomics and lipidomics analyses based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). This case-control study included 25 participants with asICAS and 25 age- and sex-matched controls free of asICAS, who were all diagnosed by using magnetic resonance angiography and derived from the same population-based study. Serum metabolomics and lipidomics profiles were determined using UPLC-HRMS, and possible biomarker metabolites were identified. Compared with the control group, the asICAS group showed higher levels of free choline, glycerophosphocholine, uracil, taurine, and four peptide molecules and lower levels of free fatty acids, hydroxydodecanedioic acid, hydroxy valeryl carnitine, hydroxytetradecanedioic acid, and two sphingomyelin molecules. The serum metabolomics and lipidomics profiles for people with asICAS are characterized by abnormal metabolism of sphingomyelin, taurine/hypotaurine, pyrimidine, and protein (peptide). The biological changes in asICAS may mainly involve taurine/hypotaurine, glycerophospholipid, and sphingolipid metabolism pathways. Biofunctional analysis indicated that these differential metabolites were correlated with metabolic diseases such as early myocardial injury, heart failure, and diabetes.

Out of Southern East Asia of the Brown Rat Revealed by Large-Scale Genome Sequencing.

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.

Regulation and related mechanism of GSN mRNA level by hnRNPK in lung adenocarcinoma cells.

Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression. Furthermore, hnRNPK knockdown affected the migration ability of H1299 and A549 cells which could be rescued by ectopic expression of GSN in those cells. Conversely, GSN knockdown in hnRNPK-overexpressing cells could abort the stimulatory effect of hnRNPK on the cell migration. These results suggest that hnRNPK function in the regulation of cell migration is GSN-dependent. Taken together, these data unveiled a new mechanism of regulation of the GSN expression by hnRNPK and provides new clues for the discovery of new anti-metastatic therapy.

Dynamic expressions of hypothalamic genes regulate seasonal breeding in a natural rodent population.

Seasonal breeding is a universal reproductive strategy in many animals. Hypothalamic genes, especially type 2 and 3 iodothyronine deiodinases (Dio2/3), RFamide-related peptide 3 (Rfrp-3), kisspeptin (Kiss-1) and gonadotropin-releasing hormone (GnRH), are involved in a photoperiodic pathway that encodes seasonal signals from day length in many vertebrate species. However, the seasonal expression patterns of these genes in wild mammals are less studied. Here, we present a four-year field investigation to reveal seasonal rhythm and age-dependent reproductive activity in male Brandt's voles (Lasiopodomys brandtii) and to detect relationships among seasonal expression profiles of hypothalamic genes, testicular activity, age and annual day length. From breeding season (April) to nonbreeding season (October), adult male voles displayed a synchronous peak in gonadal activity with annual day length around summer solstice, which was jointly caused by age structure shifts and age-dependent gonadal development patterns. Overwintered males maintained reproductive activity until late in the breeding season, whereas most newborn males terminated gonadal development completely, except for a minority of males born early in spring. Consistently, the synchronous and opposite expression profiles of Dio2/3 suggest their central function to decode photoperiodic signals and to predict the onset of the nonbreeding season. Moreover, changes in Dio2/3 signals may guide the actions of Kiss-1 and Rfrp-3 to regulate the age-dependent divergence of reproductive strategy in wild Brandt's vole. Our results provide evidence on how hypothalamic photoperiod genes regulate seasonal breeding in a natural rodent population.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

PURPOSE: To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. METHODS: Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. RESULTS: During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. CONCLUSIONS: Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

The intestinal absorption properties of flavonoids in Hippophaë rhamnoides extracts by an in situ single-pass intestinal perfusion model.

The purpose of this study was to investigate the absorption properties of isorhamnetin (IS), quercetin (QU), and kaempferol (KA) in total flavones of Hippophaë rhamnoides L. (TFH) by an in situ single-pass intestinal perfusion model. The results indicated that IS, QU, and KA in TFH were absorbed site-dependently, and both enterohepatic circulation and intestinal flora could participate in their absorption processes. The absorption mechanisms of IS, QU, and KA in TFH were involved in both passive diffusion and active transport, and the mediation of efflux transporter multidrug resistance-associated proteins (MRPs) should not be neglected.

Design and Implementation of Autonomous and Non-Autonomous Time-Delay Chaotic System Based on Field Programmable Analog Array.

Time-delay chaotic systems can have hyperchaotic attractors with large numbers of positive Lyapunov exponents, and can generate highly stochastic and unpredictable time series with simple structures, which is very suitable as a secured chaotic source in chaotic secure communications. But time-delay chaotic systems are generally designed and implemented by using analog circuit design techniques. Analog implementations require a variety of electronic components and can be difficult and time consuming. At this stage, we can now solve this question by using FPAA (Field-Programmable Analog Array). FPAA is a programmable device for implementing multiple analog functions via dynamic reconfiguration. In this paper, we will introduce two FPAA-based design examples: An autonomous Ikeda system and a non-autonomous Duffing system, to show how a FPAA device is used to design programmable analog time-delay chaotic systems and analyze Shannon entropy and Lyapunov exponents of time series output by circuit and simulation systems.

[Assisted reproductive technology for male patients with end-stage renal disease: A case-based discussion on strategies and ethical issues].

OBJECTIVE: To explore normalized and reasonable strategies of assisted reproductive technology (ART) for patients with end-stage renal disease (ESRD) under ethical supervision based on the experience with a case of ART for an ESRD male. METHODS: A male patient with ESRD successfully fathered a child through in vitro intracytoplasmic sperm injection (ICSI) in our center. We performed an epidemiological analysis, reviewed the relevant literature and explored the feasibility, ethical issues and strategies of ART for male patients with ESRD. RESULTS: ESRD affected the reproductive hormone levels, sperm quality and erectile function of the patient. Considering the contradictions between the reproductive right and the uncertainty of disease prognosis of the patient and the health of the offspring and his wife, we comprehensively evaluated the physical and mental conditions of the patient, obtained the informed consent, submitted the case to the Ethics Committee of Reproductive Medicine. CONCLUSIONS: With respect to ART for ESRD patients, importance should be attached to their rights of reproduction and choice of reproductive technology. In the process of ART, the physical conditions of the patient ought to be evaluated comprehensively and rigorously, and the related ethical principles followed strictly.

Long-term efficacy of a hepatitis E vaccine.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. METHODS: In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. RESULTS: During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups. CONCLUSIONS: Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

Porous Metal-Organic Frameworks with Chelating Multiamine Sites for Selective Adsorption and Chemical Conversion of Carbon Dioxide.

A combination of carbon dioxide (CO2) capture and chemical fixation in a one-step process is attractive for chemists and environmentalists. In this work, by incorporating chelating multiamine sites to enhance the binding affinity toward CO2, two novel metal-organic frameworks (MOFs) [Zn2(L)(2,6-NDC)2(H2O)]·1.5DMF·2H2O (1) and [Cd2(L)(2,6-NDC)2]·1.5DMF·2H2O (2) (L = N1-(4-(1 H-1,2,4-triazole-1-yl)benzyl)- N1-(2-aminoethyl)ethane-1,2-diamine, 2,6-H2NDC = 2,6-naphthalenedicarboxylic acid, DMF = N, N-dimethylformamide) were achieved under solvothermal conditions. Both 1 and 2 possess high selectivity for adsorption of CO2 over CH4 at room temperature under atmospheric pressure. Moreover, 1 has one-dimensional tubular channels decorated with multiactive sites including NH2 groups and coordination unsaturated Lewis acid metal sites, leading to efficient catalytic activity for chemical fixation of CO2 by reaction with epoxides to give cyclic carbonates under mild conditions.

Proteomics analysis reveals a potential new target protein for the lipid-lowering effect of Berberine8998.

Berberine8998 is a newly synthesized berberine derivative with better lipid-lowering activity and improved absorption. The objective of this study was to investigate the effects of berberine8998 on serum cholesterol and lipid levels in vivo and to examine the mechanisms involved. Hamsters on high-fat diet (HFD) were administered berberine or berberine8998 (50 mg·kg-1·d-1, ig) for 3 weeks. Berberine8998 administration significantly lowered the total cholesterol, triglycerides and LDL-C levels in HFD hamsters. Bioinformatics revealed that berberine and berberine8998 shared similar metabolic pathways and fatty acid metabolism was the predominant pathway. Western blot validation results showed that peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) and long-chain fatty acid-CoA ligase 1 (ACSL1), two proteins involved in fatty acid metabolism, were expressed differently in the berberine8998 group than in the untreated group and the berberine treatment group. Biochemistry results showed that berberine8998 significantly lowered the non-esterified fatty acid (NEFA) levels, which may lead to a reduction in TG levels in the berberine8998 treatment group and the differences observed in proteomics analyses. Pharmacokinetic analysis conducted in rats. After administration of berberine or berberine8998 (50 mg/kg, ig), berberine8998 exhibited a remarkably improved absorption with increasing bioavailability by 6.7 times compared with berberine. These findings suggest that berberine8998 lowers cholesterol and lipid levels via different mechanisms than berberine, and its improved absorption makes it a promising therapeutic candidate for the treatment of hypercholesterolemia and obesity.

YWHAZ Binds to TRIM21 but Is Not Involved in TRIM21-stimulated Osteosarcoma Cell Proliferation.

OBJECTIVE: Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation. METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ. RESULTS: TRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21. CONCLUSION: Our results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.