Reasons, Efficacy and Safety of Switching to Dolutegravir-Based Regimens Among Virologically Suppressed PLWH: A Retrospective Cohort Study of 96 Weeks.

Purpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG. Methods: PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96. Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/µL (IQR 420.5-758) to 642 cells/µL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen. Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.

Enrichment Culture but Not Metagenomic Sequencing Identified a Highly Prevalent Phage Infecting Lactiplantibacillus plantarum in Human Feces.

Lactiplantibacillus plantarum (previously known as Lactobacillus plantarum) is increasingly used as a probiotic to treat human diseases, but its phages in the human gut remain unexplored. Here, we report its first gut phage, Gut-P1, which we systematically screened using metagenomic sequencing, virus-like particle (VLP) sequencing, and enrichment culture from 35 fecal samples. Gut-P1 is virulent, belongs to the Douglaswolinvirus genus, and is highly prevalent in the gut (~11% prevalence); it has a genome of 79,928 bp consisting of 125 protein coding genes and displaying low sequence similarities to public L. plantarum phages. Physiochemical characterization shows that it has a short latent period and adapts to broad ranges of temperatures and pHs. Furthermore, Gut-P1 strongly inhibits the growth of L. plantarum strains at a multiplicity of infection (MOI) of 1e-6. Together, these results indicate that Gut-P1 can greatly impede the application of L. plantarum in humans. Strikingly, Gut-P1 was identified only in the enrichment culture, not in our metagenomic or VLP sequencing data nor in any public human phage databases, indicating the inefficiency of bulk sequencing in recovering low-abundance but highly prevalent phages and pointing to the unexplored hidden diversity of the human gut virome despite recent large-scale sequencing and bioinformatics efforts. IMPORTANCE As Lactiplantibacillus plantarum (previously known as Lactobacillus plantarum) is increasingly used as a probiotic to treat human gut-related diseases, its bacteriophages may pose a certain threat to their further application and should be identified and characterized more often from the human intestine. Here, we isolated and identified the first gut L. plantarum phage that is prevalent in a Chinese population. This phage, Gut-P1, is virulent and can strongly inhibit the growth of multiple L. plantarum strains at low MOIs. Our results also show that bulk sequencing is inefficient at recovering low-abundance but highly prevalent phages such as Gut-P1, suggesting that the hidden diversity of human enteroviruses has not yet been explored. Our results call for innovative approaches to isolate and identify intestinal phages from the human gut and to rethink our current understanding of the enterovirus, particularly its underestimated diversity and overestimated individual specificity.

Insight into the generation and consumption mechanism of tightly bound and loosely bound extracellular polymeric substances by mathematical modeling.

The quantity of tightly bound extracellular polymeric substances (TB-EPS) and loosely bound extracellular polymeric substances (LB-EPS) are recognized to be crucial for activated sludge flocculability and settleability. However, the generation and consumption mechanisms of TB-EPS and LB-EPS are vague, and there is no effective model to quantitatively predict LB-EPS and TB-EPS. In this work, a decrease in LB-EPS and TB-EPS was verified to increase the absolute value of the zeta potential and decrease the sludge settling volume, which affects the flocculation and settling performance of sludge. Hence, we comparatively developed, calibrated and validated two different mathematical model structure (named expanded unified model-TL1 and expanded unified model-TL2), aiming to systematically reveal the generation and consumption mechanism of TB-EPS and LB-EPS and quantitatively predict changes of TB-EPS and LB-EPS. On the basis of microbial physiology and the existing literature, two different mechanisms of the generation and consumption of TB-EPS and LB-EPS are described. According to the validation performed, expanded unified model-TL2 fit better with experimental TB-EPS and LB-EPS, which described with the hypotheses: (i) TB-EPS and LB-EPS are simultaneously generated while activate biomass growth on external substrate, (ii) LB-EPS can also be hydrolyzed by TB-EPS, and (iii) Biomass-associated products (BAP) are hydrolyzed by LB-EPS, and it was further proven to be more realistic from the perspective of microbial physiology. This study systematically revealed the generation and consumption mechanism of TB-EPS and LB-EPS by mathematical modeling, and provides a basis for regulating the concentrations of them to improve sludge settling capacity and system stability.

Model-based evaluation of the impacts of aeration on tightly bound and loosely bound extracellular polymeric substance production under non-steady-state conditions.

Tightly bound extracellular polymeric substances (TB-EPS) and loosely bound extracellular polymeric substances (LB-EPS) affect the flocculability and settleability of sludge and the transfer of oxygen, which are highly related to aeration. In this study, we systemically evaluated the expanded unified model-TL2.1 for its long-term simulation of TB-EPS and LB-EPS. Two different aeration conditions and three different influent carbon sources were used to evaluate the model, and the simulation results fit well with the experimental data. TB-EPS and LB-EPS production increased with aeration intensity. The influence of aeration parameters on TB-EPS and LB-EPS production in a short-term batch system and long-term sequencing batch reactor (SBR) system was compared. The aeration parameters included the total transfer coefficient (kLa) and the concentration of dissolved oxygen at the interface (CS). To ensure a high removal rate of substrates and ammonia nitrogen and achieve a stable active biomass concentration, the following aeration parameters can be adopted to reduce energy wastage during aeration: when CS is 2 mg/L, kLa can be set above 30 h-1 and below 50 h-1; when kLa is 50 h-1, CS can be set above 1 mg/L and below 1.5 mg/L. This study systematically revealed the influence of aeration on TB-EPS and LB-EPS formation in an SBR system through a mathematical model, and it provides a theoretical basis for better understanding aeration.

Biological stimulation with Fe(III) promotes the growth and aerobic denitrification of Pseudomonas stutzeri T13.

Certain metal ions can contribute to the functional microorganisms becoming dominant by stimulating their metabolism and activity. Therefore, Pseudomonas stutzeri T13 was used to investigate the impacts of biological stimulation with certain metal ions on aerobic denitrifying bacteria. Results showed that with the addition of 0.036 mmol/L Fe3+ ions, the nitrogen-assimilation capacity of P. stutzeri T13 significantly increased by 43.99% when utilizing ammonium as the sole nitrogen source. Kinetic models were applied to analyze the role of Fe3+ ions in the growth, and results indicated that increasing Fe3+ ion concentrations decreased the decay rate. The maximum nitrate reduction rate increased from 9.55 mg-N L-1 h-1 to 19.65 mg-N L-1 h-1 with Fe3+ ion concentrations increasing from 0.004 to 0.036 mmol/L, which was due to the increased level of napA gene transcription and activity of nitrate reductase. This study provides a theoretical foundation for further understanding of the mechanism of Fe3+ ion stimulation of aerobic denitrification, benefiting the practicable application of aerobic denitrifiers.

Characterisation of Pseudomonas stutzeri T13 for aerobic denitrification: Stoichiometry and reaction kinetics.

The mechanism of total nitrogen (TN) removal at aerobic condition in wastewater treatment plants (WWTPs) has been one of the most popular research fields. However, the role of aerobic denitrification in TN removal was unclear because of the lack of stoichiometric coefficients and kinetic constants of aerobic denitrification bacterium. Thus, this study aimed to investigate the stoichiometry and kinetics of aerobic denitrification by using Pseudomonas stutzeri T13 as a model aerobic denitrification bacterium. Results indicated that strain T13 obtained the maximum yield coefficient (0.1098 mol biomass-N/mol COD) when using NH4+-N as the sole nitrogen source. This value decreased slightly (0.1077 mol biomass-N/mol COD) during aerobic denitrification, but was still higher than that of conventional denitrification. The half-saturation constants for ammonium, nitrate and nitrite ( [Formula: see text] , [Formula: see text] and [Formula: see text] ) of strain T13 were fitted based on the experimental data and were 2.72, 18.33 and 209.07 mg/L, respectively. The validity of the stoichiometric coefficients and kinetic constants was tested at two extra conditions and perfect fitting results were obtained. To our knowledge, this is the first time to report the stoichiometric coefficients and kinetic constants of aerobic denitrification. These parameters will be useful in modelling nitrogen removal performance in systems inoculated with aerobic denitrification bacterium. Moreover, this study could provide an experimental basis for further clarifying the mechanism of aerobic denitrification from a quantitative perspective.

Adsorption-desorption behavior of magnetic amine/Fe3O4 functionalized biopolymer resin towards anionic dyes from wastewater.

In this work, a new kind of magnetic amine/Fe3O4 functionalized biopolymer resin (amine/Fe3O4-resin) was prepared and applied to remove various anionic dyes from water. Methyl Orange (MO), Reactive Brilliant Red K-2BP (RBR) and Acid Red 18 (AR) were selected as the typical anionic dye for this research. Meanwhile, amine/Fe3O4-resin was characterized by VSM, XRD, FT-IR, SEM, TEM and XPS. Three anionic dyes removed by amine/Fe3O4-resin were investigated using batch adsorption technique, and the parameters including adsorbent dosage, pH, contact time and temperature were considered. Due to a large number of amine groups and high surface areas, amine/Fe3O4-resin exhibited a remarkably high adsorption capacity for all three dyes, reaching 101.0mg/g, 222.2mg/g and 99.4mg/g for RBR, MO and AR at 25°C, respectively. The pseudo second order model and Langmuir model agreed well with the experimental data, and regeneration experiments indicated its merit of separability and reusability.