Explore the vast range of titles available.

While blood gene signatures have shown promise in tuberculosis (TB) diagnosis and treatment monitoring, most signatures derived from a single cohort may be insufficient to capture TB heterogeneity in populations and individuals. Here we report a new generalized approach combining a network-based meta-analysis with machine-learning modeling to leverage the power of heterogeneity among studies. The transcriptome datasets from 57 studies (37 TB and 20 viral infections) across demographics and TB disease states were used for gene signature discovery and model training and validation. The network-based meta-analysis identified a common 45-gene signature specific to active TB disease across studies. Two optimized random forest regression models, using the full or partial 45-gene signature, were then established to model the continuum from Mycobacterium tuberculosis infection to disease and treatment response. In model validation, using pooled multi-cohort datasets to mimic the real-world setting, the model provides robust predictive performance for incipient to active TB risk over a 2.5-year period with an AUROC of 0.85, 74.2% sensitivity, and 78.3% specificity, which approximates the minimum criteria (>75% sensitivity and >75% specificity) within the WHO target product profile for prediction of progression to TB. Moreover, the model strongly discriminates active TB from viral infection (AUROC 0.93, 95% CI 0.91–0.94). For treatment monitoring, the TB scores generated by the model statistically correlate with treatment responses over time and were predictive, even before treatment initiation, of standard treatment clinical outcomes. We demonstrate an end-to-end gene signature model development scheme that considers heterogeneity for TB risk estimation and treatment monitoring.

The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian–human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir. In monkeys infected with an AIDS-like virus, a combination of a broadly neutralizing antibody and an immune stimulator during antiretroviral therapy suppressed viral rebound after antiretroviral drug discontinuation.

Biodiversity plays important roles in ecosystem functions and genetic diversity is a key component of biodiversity. While effects of genetic diversity on ecosystem functions have been extensively documented, no study has tested how genetic diversity of plants influences greenhouse gas fluxes from plant-soil systems. We assembled experimental populations consisting of 1, 4 or 8 genotypes of the clonal plant Hydrocotyle vulgaris in microcosms, and measured fluxes of CO 2 and CH 4 from the microcosms. The fluxes of CO 2 and CO 2 equivalent from the microcosms with the 1-genotype populations of H. vulgaris were significantly lower than those with the 4- and 8-genotype populations, and such an effect increased significantly with increasing the growth period. The cumulative CO 2 flux was significantly negatively related to the growth of the H. vulgaris populations. However, genotypic diversity did not significantly affect the flux of CH 4 . We conclude that genotypic diversity of plant populations can influence CO 2 flux from plant-soil systems. The findings highlight the importance of genetic diversity in regulating greenhouse gas fluxes.

Depression is a common mental disorder in modern society. A traditional Chinese medicine Huanglian-Wendan decoction with potential anti-inflammation is used as a clinical antidepressant. Our previous study showed central and peripheral inflammatory responses in a rat model of depression developed by chronic unpredictable mild stress (CUMS). Here, we investigated the anti-inflammatory activity and mechanism of Huanglian-Wendan decoction in CUMS rats. LC-MS/MS and HPLC were performed to determine the major compounds in water extract of this decoction. This study showed that Huanglian-Wendan decoction significantly increased sucrose consumption and reduced serum levels of interleukin-1 beta (IL-1β), IL-6, and alanine aminotransferase (ALT) in CUMS rats. Moreover, this decoction inhibited nuclear entry of nuclear factor-kappa B (NF-κB) with the reduction of phosphorylated protein of NF-κB (p-NF-κB) and inhibitor of NF-κB alpha (p-IκBα) and downregulated protein of nod-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), and IL-1β in liver and brain regions of CUMS rats. These findings demonstrated that Huanglian-Wendan decoction had antidepressant activity with hepatoprotection in CUMS rats coinciding with its anti-inflammation in both periphery and central. The inhibitory modulation of NF-κB and NLRP3 inflammasome activation by Huanglian-Wendan decoction may mediate its antidepressant action.

Parental effects can influence offspring fitness, which may further impact interspecific competition. However, few studies have tested the role of clonal parental effects in regulating interspecific interactions and examined the underlying mechanisms. We conducted two consecutive experiments with two clonal plants ( Pistia stratiotes and Eichhornia crassipes ). In the first experiment, the mother ramet of P. stratiotes and E. crassipes were grown in two nutrient levels and treated with a DNA demethylation reagent (5-azacytidine) or not. In the second experiment, the offspring ramets from each of the four treatments in the first experiment were grown alone (no competition) or with a heterospecific neighbor (with interspecific competition). We found no parental nutrient effect on the competitive ability of E. crassipes , but a significant parental nutrient effect of both E. crassipes and P. stratiotes on the competitive ability of P. stratiotes . Furthermore, the parental nutrient effect of P. stratiotes on the competitive ability of P. stratiotes varied depending on the DNA methylation status of both P. stratiotes and E. crassipes . These clonal parental effects were related to resource provisioning and/or DNA methylation. We conclude that clonal parental nutrient effects can regulate interspecific competition between P. stratiotes and E. crassipes by altering the competitive ability of P. stratiotes . Both resource provisioning and epigenetic mechanisms can be involved in these clonal parental effects. By regulating interspecific competition, clonal parental effects may further influence species coexistence, community structure, and ecosystem functioning.