Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial.

AIMS/HYPOTHESIS: In sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA. METHODS: Adults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat. RESULTS: In total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin-placebo) was -0.08 mmol/l (95% CI -0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI -0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was -1.47 kg (95% CI -2.58, -0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs. CONCLUSIONS/INTERPRETATION: Blood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV. TRIAL REGISTRATION: The trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry ( www.isrctn.com/ ), registration number: ISCRTN76157257. FUNDING: This research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.

Micro-dynamic process of cadmium removal by microbial induced carbonate precipitation.

Microbially induced carbonate precipitation (MICP) is a technique used extensively to address heavy metal pollution but its micro-dynamic process remains rarely explored. In this study, A novel Cd-tolerant ureolytic bacterium DL-1 (Pseudochrobactrum sp.) was used to study the micro-dynamic process. With conditions optimized by response surface methodology, the removal efficiency of Cd2+ could achieve 99.89%. Three components were separated and characterized in the reaction mixture of Cd2+ removal by MICP. The quantitative-dynamic distribution of Cd2+ in different components was revealed. Five synergistic effects for Cd2+ removal were found, including co-precipitation, adsorption by precipitation, crystal precipitation on the cell surface, intracellular accumulation and extracellular chemisorption. Importantly, during Cd2+ removal by MICP, the phenomenon that crystalline nanoparticles adhere to the cell surface, but without any micrometer-sized precipitation encapsulated bacterial cells was observed. This indicated that the previously studied model of bacterial cells as nucleation sites for metal cation precipitation and crystal growth is oversimplified. Our findings provided valuable insights into the mechanism of heavy metals removal by MICP, and a more straightforward method for studying biomineralization-related dynamic process.

Effects of environmental factors on soil bacterial community structure and diversity in different contaminated districts of Southwest China mine tailings.

A mass of tailings left by mineral exploitation have caused serious environmental pollution. Although many studies have shown that soil microorganisms have the potential to remediate environmental pollution, the interaction mechanism between microorganisms and the surrounding environment of tailings is still unclear. In this study, 15 samples around pyrite mine tailing were collected to explore the ecological effects of environmental factors on bacterial community. The results showed that most of the samples were acidic and contaminated by multiple metals. Cadmium (Cd), copper (Cu), nickel (Ni) migrated and accumulated to into downstream farmlands while chromium (Cr) was the opposite. Proteobacteria, Chloroflex and Actinobacteria were the dominant phyla. Soil pH, total phosphorus (TP), total nitrogen (TN), available potassium (AK), available phosphorus (AP), the bacteria abundance and diversity all gradually increased with the increase of the distance from the tailing. Invertase, acid phosphatase, total organic carbon (TOC), pH, TP and Cr were the main influencing factors to cause the variation of bacterial community. This work could help us to further understand the changes in soil microbial communities around pollution sources.

Coprinus comatus endophytic bacteria characteristics and mechanisms for the cadmium resistance.

Characteristics and resistant mechanisms of macro-fungus endophytic bacteria to cadmium (Cd) have not been well defined. Strains L1 and L3 with Cd-resistant capacity were isolated from the fruiting body of Coprinus comatus, which were identified as Bacillus sp. Under the stress of Cd, the morphologies of both L1 and L3 changed to reduce the threat of Cd. The results of Fourier Transform Infrared Spectrometry indicated that functional groups such as -OH, -COOH, and -NH2 participated in the Cd adsorption process. The contents of Cd adsorbed on the cell wall of L1 were 83.46-174.51% higher than that of L3. On the contrary, the contents of Cd accumulated in L1 cytoplasm were 38.77-74.77% lower than that of L3. As the level of Cd increased from 10 to 30 mg/L, the percentages of Cd distributed on the cell walls of L1 and L3 increased by 42.43% and 26.78%, respectively. The results also revealed that the contents of Cd absorbed by the sterilized strains L1 and L3 were 47.67-64.94% and 8.65-78.63% higher than that of living ones, respectively. In addition, the proline production of L1 was 23.75-109.68% higher than that of L3, while the malondialdehyde (MDA) production of L1 was 0.96-15.60% lower than that of L3. Thus, through the comparison of endophytic bacterial physiological responses, the possible characteristics and resistant mechanisms of macro-fungus endophytic bacteria under Cd stress were firstly reported.

Improved phytoremediation of heavy metal contaminated soils by Miscanthus floridulus under a varied rhizosphere ecological characteristic.

Miscanthus floridulus is a plant with high biomass and heavy metal tolerance, which is a good candidate for phytoremediation. It is essential to explore how to improve its remediation ability, especially the rhizosphere ecological characteristics which are significant for phytoremediation efficiency. Therefore, the heavy metals accumulation of M. floridulus, rhizosphere soil physicochemical properties, enzyme activities, and bacterial community of different distances from the tailing were measured, focusing on the relationship between phytoremediation ability and rhizosphere ecological characteristics. The results show that the stronger the phytoremediation ability is, the better is the soil environment, and the higher the coverage with plants. Soil rhizosphere environment and the phytoremediation ability are shaped by heavy metals. Rhizosphere microecology may regulate phytoremediation by improving soil nutrients and enzyme activities, alleviating heavy metal toxicity, changing rhizosphere microbial community structure, increasing beneficial microbial abundance, promoting heavy metals accumulation by plants. This study not only clarified the relationship between rhizosphere ecological factors, but also elucidated the phytoremediation regulatory mechanism. Some of microbial taxa might developed as biological bioinoculants, providing the possibility to promote the growth of plants with ecological restoration ability and improve the phytoremediation efficiency.

Evaluation of phytoremediation potential of native dominant plants and spatial distribution of heavy metals in abandoned mining area in Southwest China.

A field investigation on the content of heavy metals in soils and dominant plants was conducted in three sites (A<0.5 km, B<1.0 km, C<1.5 km) with different distances of mine tailings. The spatial distribution of heavy metals and the accumulation in plants were compared, and the candidate species for ecosystem restoration were selected. The results indicated that the soil was polluted by chromium (Cr), Cadmium (Cd), copper (Cu), nickel (Ni) in varying degrees, which is 2.07, 2.60, 1.79, and 4.49 times higher than the Class-Ⅱ standard in China. The concentrate of Ni, Cd, and Zinc (Zn) increased, while Cr, Lead (Pb), and Cu decreased with the distance from the mine tailings. 73 species (34 families) were found and mainly herbaceous plants. The concentrate of Cd, Cu, Cr, and Ni in 29 dominant plants were measured and 66.67%, 21.43%, 100%, 47.62% plants exceeded the normal concentration range. Based on the comparative analysis of heavy metal content, bioconcentration factor, and translocation factor in plants, Polygonum capitatum has good phytoextraction ability, Boehmeria nivea, Chrysanthemum indicum, Miscanthus floridulus, Conyza canadensis, Rubus setchuenensis, Senecio scandens, and Arthraxon hispidus showed remarkable phytostabilization abilities of Cr, Cd, Ni, and Cu, which can be used as potential phytoremediation candidate.

A Bacillus and Lysinibacillus sp. bio-augmented Festuca arundinacea phytoremediation system for the rapid decontamination of chromium influenced soil.

Phytoremediation as an efficient and eco-friendly soil detoxification method has received widespread attention. In this study, two newly screened Chromium (Cr) reducing strains (Bacillus sp. AK-1 and Lysinibacillus sp. AK-5) were used to remediate Cr contaminated soil in conjunction with the application of hyperaccumulator tall fescue (Festuca arundinacea), thus establishing a soil Cr decontamination system. In this system, soil urease and dehydrogenase activities were increased, the malondialdehyde (MDA) contents in leaves of tall fescue were significantly decreased, while glutathione (GSH) contents increased. In terms of Cr fractions, the proportion of acetic acid extractable Cr decreased by 12.82-20.00% in treatment groups, respectively, compared with CK, while residual Cr increased by 9.41-22.37%. Moreover, biomass, root length and shoot length of tall fescue in treatment groups increased by 80.77-139.74%, 60.85-68.04%, 7.06-27.10%, respectively. In addition, the root system of tall fescue accumulated 303.887-372.167 mg kg-1 of Cr, and the aboveground part accumulated 16.289-19.289 mg kg-1 of Cr. Therefore, the application of strains AK-1 and AK-5 reduced the toxicity of Cr to plants and greatly increased plant accumulation potential, which indicated that AK-1 and AK-5 could improve removal efficiency of phytoremediation in Cr contaminated soil by reducing its bio-toxicity and promoting growth of tall fescue growth.