GBDT_KgluSite: An improved computational prediction model for lysine glutarylation sites based on feature fusion and GBDT classifier.

BACKGROUND: Lysine glutarylation (Kglu) is one of the most important Post-translational modifications (PTMs), which plays significant roles in various cellular functions, including metabolism, mitochondrial processes, and translation. Therefore, accurate identification of the Kglu site is important for elucidating protein molecular function. Due to the time-consuming and expensive limitations of traditional biological experiments, computational-based Kglu site prediction research is gaining more and more attention. RESULTS: In this paper, we proposed GBDT_KgluSite, a novel Kglu site prediction model based on GBDT and appropriate feature combinations, which achieved satisfactory performance. Specifically, seven features including sequence-based features, physicochemical property-based features, structural-based features, and evolutionary-derived features were used to characterize proteins. NearMiss-3 and Elastic Net were applied to address data imbalance and feature redundancy issues, respectively. The experimental results show that GBDT_KgluSite has good robustness and generalization ability, with accuracy and AUC values of 93.73%, and 98.14% on five-fold cross-validation as well as 90.11%, and 96.75% on the independent test dataset, respectively. CONCLUSION: GBDT_KgluSite is an effective computational method for identifying Kglu sites in protein sequences. It has good stability and generalization ability and could be useful for the identification of new Kglu sites in the future. The relevant code and dataset are available at https://github.com/flyinsky6/GBDT_KgluSite .

Comparative analysis of electronic, magnetic, catalytic properties of clusters (PS4, CrnPS4, AlnPS4, GanPS4, n = 1 ~ 3) based on density functional theory.

CONTEXT: The article presents a comparative study of the electronic, magnetic and catalytic properties of CrPS4, AlPS4, GaPS4 and their expanded structures. It is finally found that: When n = 2, 3, the internal electron mobility of the configurations is stronger than when n = 0,1. When n = 1, the five configurations, except configuration 1Cr(4), are susceptible to both electrophilic and nucleophilic reactions at the same time. The configurations are more prone to nucleophilic reactions when n = 2 and 3, and the reaction sites are mainly located on the metal atoms; the more metal atoms, the more nucleophilic reaction sites. When the M atoms in the configuration are Al and Ga atoms, there is no big difference between the contribution of metal atoms and non-metal atoms to the magnetism in the configuration, while in the configuration containing Cr atoms, the metal atoms contribute more to the magnetism and mainly originate from the d-orbitals, which has better magnetic properties and greater application value. Configuration 2Cr(4) and configuration 1Cr(2) have better catalytic and adsorption activities and are most suitable as catalysts. METHODS: In the article, based on topological principles, density functional theory, B3LYP functional and def2-tzvp basis group and Gaussian16 quantum chemistry software were used to optimise the calculations of the clusters CrPS4, AlPS4, GaPS4 and their expanded configurations, with the most stable structure selected for each cluster, and finally, with the help of Multiwfn program, the required analytical data were obtained by assisting the calculations.

Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults.

BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

Improving the physicochemical and pharmacokinetic properties of olaparib through cocrystallization strategy.

Olaparib (OLA) is the first PARP inhibitor worldwide used for the treatment of ovarian cancer. However, the oral absorption of OLA is extremely limited by its poor solubility. Herein, pharmaceutical cocrystallization strategy was employed to optimize the physicochemical and pharmacokinetic properties. Four cocrystals of OLA with oxalic acid (OLA-OA), malonic acid (OLA-MA), fumaric acid (OLA-FA) and maleic acid (OLA-MLA) were successfully discovered and characterized. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the formation of cocrystals rather than salts, and the possible hydrogen bonding patterns were analyzed through molecular surface electrostatic potential calculations. The in vitro and in vivo evaluations indicate that all of the cocrystals demonstrate significantly improved dissolution performance, oral absorption and tabletability compared to pure OLA. Among them, OLA-FA exhibit sufficient stability and the most increased Cmax and AUC0-24h values that were 11.6 and 6.1 times of free OLA, respectively, which has great potential to be developed into the improved solid preparations of OLA.

Tuning the Pharmacokinetic Performance of Quercetin by Cocrystallization.

Quercetin (QUE) is a widely studied nutraceutical with a number of potential therapeutic properties. Although QUE is abundant in the plant kingdom, its poor solubility (≤20 µg/mL) and poor oral bioavailability have impeded its potential utility and clinical development. In this context, cocrystallization has emerged as a useful method for improving the physicochemical properties of biologically active molecules. We herein report a novel cocrystal of the nutraceutical quercetin (QUE) with the coformer pentoxifylline (PTF) and a solvate of a previously reported structure between QUE and betaine (BET). We also report the outcomes of in vitro and in vivo studies of QUE release and absorption from a panel of QUE cocrystals: betaine (BET), theophylline (THP), l-proline (PRO), and novel QUEPTF. All cocrystals were found to exhibit an improvement in the dissolution rate of QUE. Further, the QUE plasma levels in Sprague-Dawley rats showed a 64-, 27-, 10- and 7-fold increase in oral bioavailability for QUEBET·MeOH, QUEPTF, QUEPRO, and QUETHP, respectively, compared to QUE anhydrate. We rationalize our in vivo and in vitro findings as the result of dissolution-supersaturation-precipitation behavior.

Enhancement of phytoextraction efficiency coupling Pteris vittata with low-dose biochar in arsenic-contaminated soil.

Phytoremediation of arsenic (As) by Pteris vittata (P. vittata) is a cost-effective and environmentally friendly method for restoring As-contaminated sites. However, the phytoextraction efficiency is low in some cases, such as clay soil, thus biochar was applied to enhance the efficiency of As extraction. The paper investigated the effect of biochar on soil characteristic, As mobility, and As uptake in P. vittata with a 90-day greenhouse experiment. Biochar derived from rice straw was added at rates of 0.5, 1.5, and 4% (w/w). The results showed that, under biochar amendment, soil pH raised from 5.24 to 6.03 and 4.91 to 5.85, soil dissolved organic carbon (DOC) increased 11.1-46.1% and 2.8-11.2%, respectively, in rhizosphere and bulk soils. Biochar also increased soil catalase (CAT) activity significantly, especially for the rhizosphere soil. Besides, biochar increased the labile As in the soils and transfer coefficient from roots to aboveground, thereby enhancing As accumulation by P. vittata tissues. The accumulation of As in fronds of P. vittata was up to 350 mg kg-1 in 1.5% biochar, which was more than twice the control and far beyond other biochar treatments. The results indicate that biochar addition is favorable to improve phytoremediation of P. vittata in As-contaminated soil and 1.5% (w/w) biochar may be a reasonable application ratio, thus providing an effective solution to enhance the efficiency of As phytoextraction.

Biochar increased soil catalase activity in the rhizosphere of P. vittata.Biochar increased the labile concentration of arsenic in soil and arsenic accumulation in P. vittata significantly.Combining biochar and P. vittata reduced arsenic in soil.Biochar amendment was favorable for phytoremediation of P. vittata in arsenic-contaminated soil.

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-ß/Smad signaling pathway.

Cardiac fibrosis is a serious public health problem worldwide that is closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process and clinical prognosis. Numerous studies have shown that the TGF-ß/Smad signaling pathway plays a key role in the progression of cardiac fibrosis. Therefore, targeted inhibition of the TGF-ß/Smad signaling pathway may be a therapeutic measure for cardiac fibrosis. Currently, as the investigation on non-coding RNAs (ncRNAs) move forward, a variety of ncRNAs targeting TGF-ß and its downstream Smad proteins have attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used in treating the cardiac fibrosis. As more and more molecular mechanisms of natural products, herbal formulas, and proprietary Chinese medicines are revealed, TCM has been proven to act on cardiac fibrosis by modulating multiple targets and signaling pathways, especially the TGF-ß/Smad. Therefore, this work summarizes the roles of TGF-ß/Smad classical and non-classical signaling pathways in the cardiac fibrosis, and discusses the recent research advances in ncRNAs targeting the TGF-ß/Smad signaling pathway and TCM against cardiac fibrosis. It is hoped, in this way, to give new insights into the prevention and treatment of cardiac fibrosis.

Current Status of Metabolic Compliance and Risk of Cardiovascular Disease in Patients with Type 2 Diabetes in the Zhuang Population in China.

Introduction: This study aimed to investigate the blood glucose, blood pressure, and blood lipid status in Zhuang patients with T2DM and to analyze the correlation between compliance with metabolic monitoring and cardiovascular risk factors. Methods: A total of 1975 Zhuang patients with T2DM were evaluated in four Class III Grade A hospitals in three prefecture-level cities in the Guangxi Zhuang Autonomous Region between January and August 2022. Laboratory indicators, lifestyle, and demographic characteristics were collected. Results: The compliance rates for blood glucose, blood pressure, and blood lipids were 26.08%, 45.77%, and 30.58%, respectively, and only 5.06% of the patients reached the standard in all three indices. The compliance rates for blood glucose, blood pressure, and blood lipids in the CVD group were 32.92%, 21.74%, and 9.94%, respectively. In the CVD group, the usage rates of hypoglycemic, antihypertensive, and lipid-lowering drugs were 77.54%, 3.17%, and 4.11%, respectively. Binary logistic regression analysis showed that older age (OR = 1.033, 95% CI [1.016, 1.050]), female (OR = 0.402, 95% CI [0.260, 0.621]), smoke (OR = 1.994, 95% CI [1.361, 2.922]), blood pressure noncompliance + use of antihypertensive drugs (OR = 0.348, 95% CI [0.230, 0.527]), and blood lipid noncompliance + use of lipid-lowering drugs (OR = 0.244, 95% CI [0.142, 0.417]) were risk factors for CVDs, and moderate-intensity exercise (OR = 0.439, 95% CI [0.300,0.640]) was protective against CVD. Conclusions: Older age, female, smoke, blood lipid levels, and blood pressure noncompliance were risk factors for CVD while moderate-intensity exercise was observed to be protective.

Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

Effects of aerobic training and resistance training in reducing cardiovascular disease risk for patients with prediabetes: A multi-center randomized controlled trial.

AIMS: Aerobic training (AT) and resistance training (RT) can reduce blood glucose and type 2 diabetes risk, and increase muscle mass for prediabetes patients. However, the impact of long-term AT and RT on cardiovascular disease (CVD) risk remains unclear. The purpose of this study was to investigate the impact of AT and RT on CVD risk reduction in prediabetes patients. MATERIALS AND METHODS: 248 prediabetes patients were enrolled in this multi-center randomized controlled trial (RCT). Patients were randomly divided into 3 groups: RT (n = 82), aerobic training (AT (n = 83)), and control group (n = 83). Participants in RT and AT groups had moderate RT or AT 3 times a week (150 min/week) under supervision in 3 research centers for 24 months. Primary outcome was CVD risk measured by Framingham Risk Score (FRS) and The Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool. Secondary outcomes included in HOMA2-IR, HbA1c, blood pressure and serum lipid profile. RESULTS: Both RT and AT groups experienced a significant reduction in HOMA2-IR, HbA1c, LDL-C, TC, SBP, and DBP at the end of 12 and 24 months. Compared to the control group, Both RT and AT groups had significant reduction of the Chinese 10-year ICVD risk (P < 0.05), but FRS CVD risk declined significantly only in the AT group (all P < 0.05). Although FRS CVD risk decreased more in the RT group than in the control group, the difference was not statistically significant. After adjusting for age, gender, statin use, BMI, and WHR, in COX's proportional hazard model, RT (HR = 0.419, P = 0.037) and AT (HR = 0.310, P = 0.026) were protective factors for CVD risk in prediabetes patients. 24-month RT and AT decreased respectively 58.1% and 69.0% of CVD risk (10-year ICVD risk assessment) in prediabetes patients. CONCLUSIONS: This study demonstrated that 24-month moderate AT reduces the Chinese 10-year ICVD risk and FRS CVD risk in prediabetes patients. RT groups had significant reduction of CVD risk (10-year ICVD risk assessment) in prediabetes patients. TRIAL REGISTRATION: Clinical trial registration number: NCT02561377. DATE OF REGISTRATION: 24/09/2015.

The tonoplast-localized transporter OsNRAMP2 is involved in iron homeostasis and affects seed germination in rice.

Vacuolar storage of iron (Fe) is important for Fe homeostasis in plants. When sufficient, excess Fe could be stored in vacuoles for remobilization in the case of Fe deficiency. Although the mechanism of Fe remobilization from vacuoles is critical for crop development under low Fe stress, the transporters that mediate vacuolar Fe translocation into the cytosol in rice remains unknown. Here, we showed that under high Fe2+ concentrations, the Δccc1 yeast mutant transformed with the rice natural resistance-associated macrophage protein 2 gene (OsNRAMP2) became more sensitive to Fe toxicity. In rice protoplasts and transgenic plants expressing Pro35S:OsNRAMP2-GFP, OsNRAMP2 was localized to the tonoplast. Vacuolar Fe content in osnramp2 knockdown lines was higher than in the wild type, while the growth of osnramp2 knockdown plants was significantly influenced by Fe deficiency. Furthermore, the germination of osnramp2 knockdown plants was arrested. Conversely, the vacuolar Fe content of Pro35S:OsNRAMP2-GFP lines was significantly lower than in the wild type, and overexpression of OsNRAMP2 increased shoot biomass under Fe deficiency. Taken together, we propose that OsNRAMP2 transports Fe from the vacuole to the cytosol and plays a pivotal role in seed germination.

IgG Immunocomplexes Drive the Differentiation of a Novel Subset of Osteoclasts Independent of RANKL and Inflammatory Cytokines.

Potentiation of receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis by IgG immunocomplexes (ICs) is generally considered an important pathway leading to cartilage and bone destruction in rheumatoid arthritis (RA). However, whether IgG ICs possess pro-osteoclastogenic potential independent of RANKL and inflammatory cytokines is unclear. Here we demonstrate that by fully cross-linking human FcγRIIa (hFcγRIIa) or co-ligating hFcγRIIa and TLR4, IgG ICs alone could drive the differentiation of human blood monocytes into nuclear factor of activated T cells cytoplasmic 1 (NFATc1-negative nonclassical osteoclasts (NOCs). Surprisingly, IgG ICs could also overrule RANKL-induced classical osteoclast (COC) differentiation in vitro. In mouse model of collagen-induced arthritis, hFcγRIIa-transgenic, but not nontransgenic control, mice suffered from cartilage/bone destruction accompanied by the presence of NFATc1- NOCs lining the eroded cartilage surface in affected joints. Our results not only identify a novel subset of IC-induced NOCs but also provide a possible explanation for the uncoupling of FcγR-mediated cartilage destruction from RANKL-related bone erosion in autoinflammatory arthritis. © 2021 American Society for Bone and Mineral Research (ASBMR)..

Effect of Aerobic and Resistance Training on Endothelial Progenitor Cells in Mice with Type 2 Diabetes.

Since no study has explored whether exercise could improve impaired proliferation, migration, and angiogenesis of endothelial progenitor cells (EPCs) in animal models or humans with type 2 diabetes, we aimed to explore the effect of different models of exercise on EPC function and expression of caveolin-1, PI3K, and AKT in mice with type 2 diabetes. Male db/db mice (age: 8 weeks) with type 2 diabetes were subjected to aerobic training (AT), resistance training (RT), or combined aerobic and resistance training (AT+RT) 3 or 4 days/week. Mice in the control group remained sedentary with no specific training requirement. Bone marrow-derived EPCs were isolated, and the protein concentrations of caveolin-1, Pi3k, and AKT, and EPC function, were identified in the 1st, 4th, 8th, and 12th weeks of the intervention. Greater increases in proliferation, migration, and angiogenesis were observed in the AT, RT, and AT+RT groups than in the control group. AT+RT was more effective than AT or RT in improving the migratory and angiogenesis function of EPCs in mice with type 2 diabetes and achieved maximum improvement after 8 weeks of intervention. Western blot analysis showed that caveolin-1, p-PI3k, and p-Akt levels were obviously increased in the AT, RT, and AT+RT groups compared with the control group. The expression level of these proteins in the AT+RT group was higher than that in the AT and RT groups. AT+RT may be a helpful reference when choosing exercise methods for the prevention of diabetes-related cardiovascular diseases.

Localized Intensification of Arsenic Release within the Emergent Rice Rhizosphere.

Behavior of trace elements in flooded/lowland rice soils is controlled by root-zone iron oxidation. Insoluble iron species bind/capture toxic elements, i.e., arsenic. However, it was recently observed that within this territory of arsenic immobilization lies a zone of prolific iron release, accompanied by a significant flux of arsenic in close proximity to rice root apices. Questions still remain on how common this phenomenon is and whether the chemical imaging approaches or soils/cultivars used influence this event. Here, three types of ultrathin/high-resolution diffusive gradient in thin films (DGT) substrates were integrated with oxygen planar optodes in a multilayer system, providing two-dimensional mapping of solute fluxes. The three DGT approaches revealed a consistent/overlapping spatial distribution with localized flux maxima for arsenic, which occurred in all experiments, concomitant with iron mobilization. Soil/porewater microsampling within the rhizosphere revealed no significant elevation in the solid phase's total iron and arsenic concentrations between aerobic and anaerobic zones. Contrary to arsenic, phosphorus bioavailability was shown to decrease in the arsenic/iron flux maxima. Rice roots, in addition to their role in nutrient acquisition, also perform a key sensory function. Flux maxima represent a significant departure from the chemical conditions of the bulk/field environment, but our observations of a complete rhizosphere reveal a mixed mode of root-soil interactions.

Aerobic and resistance training enhances endothelial progenitor cell function via upregulation of caveolin-1 in mice with type 2 diabetes.

BACKGROUND: To explore the effect of aerobic training (AT), resistance training (RT) or a combination of AT and RT (AT+RT) on the function of endothelial progenitor cells (EPCs) in mice with type 2 diabetes and the potential effective mechanisms METHODS: Eight-week-old db/db male mice were used as type 2 diabetic animal models in this study. Mice were randomly assigned to the control group (n = 5), AT group (n = 5), RT group (n = 5) and AT+RT group (n = 5). Mice in the control group remained sedentary with no specific training requirement. Mice were motivated to perform AT, RT or AT+RT by a gentle pat on their body for 3 or 4 days/week for 14 days. AT was performed by treadmill running, RT was performed by ladder climbing and AT+RT involved both AT and RT. Bone-derived EPCs were isolated after 14 days of the intervention. EPC expression of CD31, CD34, CD133, CD144 and VEGFR2 was detected by immunofluorescence staining. Fluorescence detection was performed on attached mononuclear cells to detect double-positive EPCs. We then explored the effect of caveolin-1 knockdown (lentiviral vector with caveolin-1-siRNA) on the proliferation and adherence of EPCs and the concentration of caveolin-1 and PI3K/AKT via western blot analyses. RESULTS: Compared to the mice in the control group, the mice in the AT, RT and AT+RT groups presented significant increases in proliferation and adherence after 14 days of intervention. AT+RT induced an increase in EPC adherence, which was greater than that of the control, RT and AT groups. Caveolin-1 knockdown inhibited the EPC proliferative and adherent abilities. The AT+RT group showed higher levels of caveolin-1 and p-AKT than the control group, but these changes were decreased by caveolin-1-siRNA transfection. CONCLUSION: Combined AT and RT is an effective way to improve EPC function through upregulation of caveolin-1 in mice with type 2 diabetes.

Comparing the effects of 6 months aerobic exercise and resistance training on metabolic control and ß-cell function in Chinese patients with prediabetes: A multicenter randomized controlled trial.

BACKGROUND: It is clear that aerobic training (AT) can delay pancreatic exhaustion and slow the progression from prediabetes to type 2 diabetes (T2D), but there is little information regarding the effects of resistance training (RT) in people with prediabetes. This study compared the effectiveness of RT and AT in improving metabolic control and protecting ß-cell function in people with prediabetes. METHODS: Chinese subjects (n = 248) with prediabetes were randomized to three groups: AT (n = 83), RT (n = 82) and control (n = 83). Subjects in the RT group performed 13 different resistance exercises per session using an elastic string. Those in the AT group performed aerobic exercises at 60%-70% of maximum heart rate. In both cases, exercises were performed three times per week for a period of 6 months. The primary outcome was improvement in metabolic control. Longitudinal changes between groups were tested using repeated-measures analysis of variance. RESULTS: Of the initial 248 participants, 217 finished the study, but all participants were included in the intention-to-treat analyses. There were no significant differences in demographic characteristics among the RT, AT, and control groups (P > 0.05). Changes in HbA1c were not significantly greater in RT than AT cohort (P = 0.059), but the decrease in HbA1c in both exercise groups was higher than in the control group (P < 0.05). CONCLUSIONS: In subjects with prediabetes, RT appears to improve metabolic control and preserve ß-cell function comparable to AT.

Effect of 12-Month Resistance Training on Changes in Abdominal Adipose Tissue and Metabolic Variables in Patients with Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To examine the effects of resistance training relative to aerobic training on abdominal adipose tissue and metabolic variables in adults with prediabetes. METHODS: 105 participants with prediabetes were randomized into the resistance training group (RT, n = 35), aerobic training group (AT, n = 35), and control group (CG, n = 35). The participants completed supervised 12-month exercise; the control group followed the primary lifestyle without exercise intervention. The primary outcomes were visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by computed tomography (CT). Secondary outcomes were body composition, lipid profile, and metabolic variables. RESULTS: A total of 93 participants completed the study. There were nonsignificant differences between groups before intervention. After training, VAT decreased significantly in AT and RT compared with CG (P = 0.001 and P = 0.014, respectively). Although no significant difference in SAT was found across groups, SAT decreased significantly over time within each exercise group (all P = 0.001). Increase in muscle mass was greater in RT than that in AT and CG (P = 0.031 and P = 0.045, respectively). Compared with CG, fasting plasma glucose (FPG) decreased significantly in RT and AT (P = 0.003 and P = 0.014, respectively). There was a significant difference in the number of prediabetes who converted to diabetes among AT and RT, as compared with the control group (P = 0.031 and P = 0.011, respectively). No significant differences were observed in lipid, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin (FI), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), HOMA-IR, and HOMA-ß across groups. CONCLUSION: Both aerobic training and resistance training are effective in reducing abdominal adipose tissue and fasting plasma glucose in adults with prediabetes. Importantly, resistance training but not aerobic training is effective in augmenting muscle mass. TRIAL REGISTRATION: The trial is registered with NCT02561377 (date of registration: 24/09/2015).

Kaposi's sarcoma manifested as lower gastrointestinal bleeding in a HIV/HBV-co-infected liver cirrhosis patient: A case report.

BACKGROUND: Kaposi's sarcoma (KS) is one of the most common cancers in human immunodeficiency virus (HIV)-positive patients and leads to a high prevalence of morbidity and mortality. It usually appears as cutaneous or mucous lesions. Patients with visceral KS are asymptomatic and clinically silent. As the disease advances, patients may progress from a normal condition to exhibiting severe symptoms. CASE SUMMARY: A 27-year-old man presented with a 2-mo history of fever, bearing-down pain, and rectal bleeding. His hepatitis B virus DNA level was 2.7 ×107 IU/mL. Abdominal computed tomography (CT) indicated liver cirrhosis. Before he was admitted to our hospital, he was diagnosed with HIV infection. His CD4 count was 24 cells/µL. Pelvic cavity CT suggested a thickened rectum wall accompanied by multiple enlarged lymph nodes. The patient was initially treated as having haemorrhoidal varices with bleeding, telbivudine for anti-hepatitis B virus treatment, and antibiotics for anti-infection. After half a month of treatment, the patient felt that his lower lumbus ache and bearing-down pain had not improved, and a colonoscopy was conducted. The result revealed a rectal mass that was histologically confirmed as KS with rectal spindle cells that were positive for cluster of differentiation 117 (CD117), CD34, human herpes virus 8, and CD31. He was administered systemic chemotherapy with 36 mg/d liposomal doxorubicin six times. The patient experienced no sign of lower gastrointestinal bleeding again. CONCLUSION: This case highlights the diagnosis of primary KS with lower gastrointestinal bleeding in HIV-positive patients, which means visceral KS could not be excluded. The gold standard relies on colonoscopy and biopsy findings.

Arsenic-resistance mechanisms in bacterium Leclercia adecarboxylata strain As3-1: Biochemical and genomic analyses.

Microbial arsenic transformation is important in As biogeochemical cycles in the environment. In this study, a new As-resistant bacterial strain Leclercia adecarboxylata As3-1 was isolated and its associated mechanisms in As resistance and detoxification were evaluated based on genome sequencing and gene annotations. After subjecting strain As3-1 to medium containing arsenate (AsV), AsV reduction occurred and an AsV-enhanced bacterial growth was observed. Strain As3-1 lacked arsenite (AsIII) oxidation ability and displayed lower AsIII resistance than AsV, probably due to its higher AsIII accumulation. Polymerase chain reaction and phylogenetic analysis showed that strain As3-1 harbored a typical AsV reductase gene (arsC) on the plasmids. Genome sequencing and gene annotations identified four operons phoUpstBACS, arsHRBC, arsCRDABC and ttrRSBCA, with 8 additional genes outside the operons that might have involved in As resistance and detoxification in strain As3-1. These included 5 arsC genes explaining why strain As3-1 tolerated high AsV concentrations. Besides ArsC, TtrB, TtrC and TtrA proteins could also be involved in AsV reduction and consequent energy acquisition for bacterial growth. Our data provided a new example of diverse As-regulating systems and AsV-enhanced growth without ArrA in bacteria. The information helps to understand the role of As in selecting microbial systems that can transform and utilize As.