Rhizobacterial communities of five co-occurring desert halophytes

Background Recently, researches have begun to investigate the microbial communities associated with halophytes. Both rhizobacterial community composition and the environmental drivers of community assembly have been addressed. However, few studies have explored the structure of rhizobacterial communities associated with halophytic plants that are co-occurring in arid, salinized areas. Methods Five halophytes were selected for study: these co-occurred in saline soils in the Ebinur Lake Nature Reserve, located at the western margin of the Gurbantunggut Desert of Northwestern China. Halophyte-associated bacterial communities were sampled, and the bacterial 16S rDNA V3–V4 region amplified and sequenced using the Illumina Miseq platform. The bacterial community diversity and structure were compared between the rhizosphere and bulk soils, as well as among the rhizosphere samples. The effects of plant species identity and soil properties on the bacterial communities were also analyzed. Results Significant differences were observed between the rhizosphere and bulk soil bacterial communities. Diversity was higher in the rhizosphere than in the bulk soils. Abundant taxonomic groups (from phylum to genus) in the rhizosphere were much more diverse than in bulk soils. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and Planctomycetes were the most abundant phyla in the rhizosphere, while Proteobacteria and Firmicutes were common in bulk soils. Overall, the bacterial community composition were not significantly differentiated between the bulk soils of the five plants, but community diversity and structure differed significantly in the rhizosphere. The diversity of Halostachys caspica, Halocnemum strobilaceum and Kalidium foliatum associated bacterial communities was lower than that of Limonium gmelinii and Lycium ruthenicum communities. Furthermore, the composition of the bacterial communities of Halostachys caspica and Halocnemum strobilaceum was very different from those of Limonium gmelinii and Lycium ruthenicum. The diversity and community structure were influenced by soil EC, pH and nutrient content (TOC, SOM, TON and AP); of these, the effects of EC on bacterial community composition were less important than those of soil nutrients. Discussion Halophytic plant species played an important role in shaping associated rhizosphere bacterial communities. When salinity levels were constant, soil nutrients emerged as key factors structuring bacterial communities, while EC played only a minor role. Pairwise differences among the rhizobacterial communities associated with different plant species were not significant, despite some evidence of differentiation. Further studies involving more halophyte species, and individuals per species, are necessary to elucidate plant species identity effects on the rhizosphere for co-occurring halophytes

Metagenomic Insights into Microbial Community Structure, Function, and Salt Adaptation in Saline Soils of Arid Land, China

Soil salinization is spread in the dryland of NW China due to the dry or extreme dry climate. Increased salinization damages the health and function of soil systems and influences the microbial community structure and function. Some studies have been conducted to reveal the microbial community structure and isolate the microorganisms of saline soil or salt-lake sediments in this region. However, the functions of microorganisms and their response to salinization, i.e., their adaptation strategy to a wide salinization range in arid environments, are less understood. Here, we applied metagenomics technology to investigate the microbial community structure, function, and their relationship with salinization, and discussed the adaptative strategy of microorganisms to different saline environments. A total of 42 samples were sequenced on the Illumina PE500 platform. The archaea and bacteria constituted the dominant kingdoms; Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes were the dominant bacterial phyla; and Euryarchaeota were the dominant archaeal phylum. The microbial communities showed significant structure divergence according to the salt concentration (saline (mean EC 22 mS/cm) and hypersaline (mean EC 70 mS/cm)), wherein the communities were dominated by bacteria in saline soils and archaea in hypersaline soils. Most of the dominant bacterial representation decreased with salinity, while the archaea increased with salinity. KEGG functional annotation showed that at level 2, the cell motility, environmental adaptation, signal transduction, signaling molecules and interaction, glycan biosynthesis and metabolism, and metabolism of other amino acids were reduced from saline to hypersaline, whereas the metabolism of cofactors and vitamins, folding sorting and degradation, replication and repair, transcription and translation, amino acid biosynthesis, glycolysis/gluconeogenesis, and carbon fixation increased with salinity. The increased salt content decreased the carbohydrate activities of microorganisms. The osmolyte regulation substance synthesis and absorption-related genes were more abundant in saline soils than in hypersaline soils, whereas the Na+/H+ antiporter genes (mnhB-E) and H+/Na+-transporting ATPase genes (atpA-F, I, K) were significantly higher in hypersaline soils. This indicated that in saline soils, microorganisms primarily synthesize and/or uptake compatible solutes to cope with osmotic stress, whereas in the hypersaline habitat, the high-salt-in strategy was predicated to be adopted by the halophilic/extremely halophilic microorganisms, coupled with a high abundance of replication and repair, cofactors and vitamin metabolism, nucleotide metabolism, and carbon fixation to provide energy and ensure cell regeneration. In conclusion, increases in salinity influence the microbial communities’ structure and function, as well as the adaptation of microorganisms

Long Noncoding RNA PVT1 as a Novel Diagnostic Biomarker and Therapeutic Target for Melanoma

Accumulating evidences indicated that plasmacytoma variant translocation 1 (PVT1) plays vital roles in several cancers. However, the expression, functions, and clinical values of PVT1 in melanoma are still unknown. In this study we measured the expression of PVT1 in clinical tissues and serum samples and explored the diagnostic value of PVT1 for melanoma and the effects of PVT1 on melanoma cell proliferation, cell cycle, and migration. Our results, combined with publicly available PVT1 expression data, revealed that PVT1 is upregulated in melanoma tissues compared with nonneoplastic nevi tissues. Serum PVT1 level is significantly increased in melanoma patients compared with age and gender-matched nonmelanoma controls with melanocytic nevus. Receiver operating characteristic curve analyses revealed that serum PVT1 level could sensitively discriminate melanoma patients from controls. Furthermore, serum PVT1 level indicted melanoma dynamics. Functional experiments showed that overexpression of PVT1 promotes melanoma cells proliferation, cell cycle progression, and migration, while depletion of PVT1 significantly inhibits melanoma cells proliferation, cell cycle progression, and migration. Collectively, our results indicate that PVT1 functions as an oncogene in melanoma and could be a potential diagnostic biomarker and therapeutic target for melanoma

Eremophilane sesquiterpenes from the endophytic fungus <i>Xylaria</i> sp. GDG-102

<p>A new eremophilane sesquiterpene, xylareremophil (<b>1</b>), together with five known eremophilanes, 1α,10α-epoxy-3α-hydroxyeremophil-7(11)-en-12,8β-olide (<b>2</b>), 1,10α,13-trihydroxyeremophil-7(11)-en-12,8-olide (<b>3</b>), 1α,10α-epoxy-13-hydroxyeremophil-7(11)-en-12,8β-olide (<b>4</b>), mairetolides B (<b>5</b>) and G (<b>6</b>) were isolated from the endophytic fungus <i>Xylaria</i> sp. GDG-102 cultured from <i>Sophora tonkinensis.</i> Their structures were elucidated on the basis of spectroscopic data analysis. The absolute configurations of <b>1</b> was determined by comparing computed electronic circular dichroism (ECD) and optical rotation (OR) with experimental results. Compounds <b>1</b>, <b>5</b> and <b>6</b> showed antibacterial activities against <i>Proteus vulgaris</i>, <i>Micrococcus luteus</i>, <i>Micrococcus lysodeikticus</i> and <i>Bacillus subtilis</i> with MIC values of 25–100 μg/mL.</p

Two new coumarins from the bark of <i>Streblus indicus</i> (Bur.) Corner

<p>Two new coumarins 7-<i>O</i>-(6-<i>O</i>-(5-<i>O</i>-3,4,5-tri-methoxycinnamate-<i>β</i>-d-apiofuranosyl-<i>β</i>-d-glucopyranosyl)-6-methoxy coumarin (<b>1</b>) and 7-<i>O</i>-(6-<i>O</i>-(4-(2-hydroxy-1-hydroxymethyl-ethoxy)-3-methoxy-cinnamyl)-<i>β</i>-d-glucopyranosyl)-6-methoxy coumarin (<b>2</b>), along with 10 known metabolites, were isolated from the bark of <i>Streblus indicus</i>, their structures were identified by comparison of experimental and published spectroscopic data. (<i>S</i>)-marmesinin (<b>6</b>) and scoparone (<b>7</b>) exhibited moderate antimicrobial activity <i>in vitro</i> against <i>Staphylococcus aureus</i> strain with the MIC values of 62.5 and 125.0 μg/mL, respectively. Betulinic acid showed inhibitory activity <i>in vitro</i> against MCF-7 cell with IC₅₀ value of 9.5 ± 0.1 μM.</p

Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trialResearch in context

Summary: Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95–428.68 h]) than that of Placebo (271.33 h [IQR 219.00–529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07–1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory