Microbial cell wall sorption and Fe-Mn binding in rhizosphere contribute to the obstruction of cadmium from soil to rice.

Screening high-tolerant microorganisms to cadmium (Cd) and revealing their bio-obstruction mechanism could be significant for Cd regulation from farmland to the food chain. We examined the tolerance and bio-removal efficiency of Cd ions of two bacterial strains, Pseudomonas putida 23483 and Bacillus sp. GY16, and measured the accumulation of Cd ions in rice tissues and its different chemical forms in soil. The results showed that the two strains had high tolerance to Cd, but the removal efficiency was decreased successively with increasing Cd concentrations (0.05 to 5 mg kg-1). Cell-sorption accounted for the major proportion of Cd removal compared with excreta binding in both strains, which was conformed to the pseudo-second-order kinetics. At the subcellular level, Cd was mostly taken up by the cell mantle and cell wall, and only a small amount entered into the cytomembrane and cytoplasmic with time progressed (0 to 24 h) in each concentration. The cell mantle and cell wall sorption decreased with increasing Cd concentration, especially in the cytomembrane and cytoplasmic. The scanning electron microscope (SEM) and energy dispersive X-ray (EDS) analysis verified that Cd ions were attached to the cell surface, and the functional groups of C-H, C-N, C=O, N-H, and O-H in the cell surface may participate in cell-sorption process tested by the FTIR analysis. Furthermore, inoculation of the two strains significantly decreased Cd accumulation in rice straw and grain but increased in the root, increased Cd enrichment ratio in root from soil, decreased Cd translocation ratio from root to straw and grain, and increased the Cd concentrations of Fe-Mn binding form and residual form in rhizosphere soil. This study highlights that the two strains mainly removed Cd ions in solution through biosorption and passivated soil Cd as Fe-Mn combined form ascribe to its characteristics of manganese-oxidizing, eventually achieving bio-obstruction of Cd from soil to rice grain.

Pharmacological suppression of glycogen synthase kinase-3 reactivates HIV-1 from latency via activating Wnt/ß-catenin/TCF1 axis in CD4+ T cells.

ABSTRACTHIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) have been implicated in the "Shock and Kill" strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps to develop efficient LRAs. In this study, we demonstrate that the Wnt downstream ß-catenin/TCF1 pathway is a crucial modulator for HIV-1 latency. The pharmacological activation of the ß-catenin/TCF1 pathway with glycogen synthase kinase-3 (GSK3) inhibitors promoted transcription of HIV-1 proviral DNA and reactivated latency in CD4+ T cells; the GSK3 kinase inhibitor 6-bromoindirubin-3'-oxime (6-BIO)-induced HIV-1 reactivation was subsequently confirmed in resting CD4+ T cells from cART-suppressed patients and SIV-infected rhesus macaques. These findings advance our understanding of the mechanisms responsible for viral latency, and provide the potent LRA that can be further used in conjunction of immunotherapies to eradicate viral reservoirs.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery.

BACKGROUND: The aim of this study was to assess the efficacy of naproxen in preventing heterotopic ossification (HO) after hip surgery (total hip arthroplasty [THA] and hip arthroscopy). METHODS: Using databases (PubMed, EMBASE, and Web of Science), we conducted an electronic, systematic search of randomized controlled trials (RCTs) comparing naproxen versus placebo on HO after hip surgery. The risk ratio (RR) of the dichotomous data, weighted mean difference (WMD) of continuous data, and 95% confidence intervals (CIs) were calculated to assess the effects of naproxen in patients with hip surgery. RESULTS: A total of 4 studies including 269 patients were analyzed. Risk of bias was relatively high in allocation concealment and blinding. Compared with control group, administration naproxen was associated with a significantly reduction of the occurrence of HO at final follow-up after hip surgery (P < .05). What's more, naproxen was associated with a reduction of the Brooker I and II HO (P < .05). However, there was no significant difference between the Brooker III HO between naproxen and control groups (P > .05). Furthermore, there was no significant difference between the complications (P > .05) between naproxen and control groups. CONCLUSION: Naproxen has a beneficial role in reducing the total occurrence of HO, Brooker I and II HO after hip surgery. However, conclusions are limited due to the lack of high-quality studies. More high quality studies may help in a more reliable therapy for HO.

[Study on environmental and psychological risk factors for female infertility].

OBJECTIVE: To investigate the environmental and psychological risk factors for female infertility and to provide a scientific basis for the prevention and control of female infertility. METHODS: In a hospital-based case-control study, a self-designed questionnaire was used to survey the cases and controls (1:1) with nation and age (± 2 years) as matching variables. Univariate and multivariate conditional logistic regression models were employed to analyze the datasets. RESULTS: The univariate analysis showed that female infertility was related to the following factors: eating fried foods, alcohol consumption, smoking, staying up late, perm, housing decoration, contact with heavy metals, exposure to radiation, contact with pesticides, working in hot environment, mental stress, uneasiness, helplessness, and despair. The multivariate analysis showed that staying up late (OR = 2.937), housing decoration (OR = 2.963), exposure to radiation (OR = 2.506), contact with pesticides (OR = 2.908), and mental stress (OR = 4.101) were the main risk factors for female infertility. Furthermore, there was an interaction between staying up late and mental stress. CONCLUSION: Female infertility is caused by multiple factors including staying up late, housing decoration, exposure to radiation, contact with pesticides, and mental stress, and there is an interaction between staying up late and mental stress.

Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways.

In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP, Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.

Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis.

BACKGROUND: Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis. This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis. METHODS: Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group, the model group, the magnesium sulfate group and the anisodamine group. The rabbit model of infusion phlebitis, induced by intravenous administration, was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline. We evaluated expression by histopathology, immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blotting assay. RESULTS: Pathohistological changes of the model group were observed, such as loss of venous endothelial cells, inflammatory cell infiltration, edema and thrombus. The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion, inflammatory cell infiltration, proliferation, swelling of endothelium and perivascular hemorrhage. The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P < 0.01). On the contrary, anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group (P < 0.01). There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group (P > 0.05). CONCLUSION: Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1, and shows significant protective effects in an animal model of infusion phlebitis.