RNA 5-Methylcytosine Facilitates the Maternal-to-Zygotic Transition by Preventing Maternal mRNA Decay.

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.

Causal Effects of Stochastic PrEP Interventions on HIV Incidence Among Men Who Have Sex With Men.

Antiretroviral preexposure prophylaxis (PrEP) is highly effective in preventing human immunodeficiency virus (HIV) infection, but uptake has been limited and inequitable. Although interventions to increase PrEP uptake are being evaluated in clinical trials among men who have sex with men (MSM), those trials cannot evaluate effects on HIV incidence. Estimates from observational studies of the causal effects of PrEP-uptake interventions on HIV incidence can inform decisions about intervention scale-up. We used longitudinal electronic health record data from HIV-negative MSM accessing care at Fenway Health, a community health center in Boston, Massachusetts, from January 2012 through February 2018, with 2 years of follow-up. We considered stochastic interventions that increased the chance of initiating PrEP in several high-priority subgroups. We estimated the effects of these interventions on population-level HIV incidence using a novel inverse-probability weighted estimator of the generalized g-formula, adjusting for baseline and time-varying confounders. Our results suggest that even modest increases in PrEP initiation in high-priority subgroups of MSM could meaningfully reduce HIV incidence in the overall population of MSM. Interventions tailored to Black and Latino MSM should be prioritized to maximize equity and impact.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

INTRODUCTION: The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. OBJECTIVE: We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. METHODS: The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. RESULTS: Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. CONCLUSION: The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

Evaluating Model Specification When Using the Parametric G-Formula in the Presence of Censoring.

The noniterative conditional expectation (NICE) parametric g-formula can be used to estimate the causal effect of sustained treatment strategies. In addition to identifiability conditions, the validity of the NICE parametric g-formula generally requires the correct specification of models for time-varying outcomes, treatments, and confounders at each follow-up time point. An informal approach for evaluating model specification is to compare the observed distributions of the outcome, treatments, and confounders with their parametric g-formula estimates under the "natural course." In the presence of loss to follow-up, however, the observed and natural-course risks can differ even if the identifiability conditions of the parametric g-formula hold and there is no model misspecification. Here, we describe 2 approaches for evaluating model specification when using the parametric g-formula in the presence of censoring: 1) comparing factual risks estimated by the g-formula with nonparametric Kaplan-Meier estimates and 2) comparing natural-course risks estimated by inverse probability weighting with those estimated by the g-formula. We also describe how to correctly compute natural-course estimates of time-varying covariate means when using a computationally efficient g-formula algorithm. We evaluate the proposed methods via simulation and implement them to estimate the effects of dietary interventions in 2 cohort studies.

Recovery of Li2CO3 from Spent LiFePO4 by Using a Novel Impurity Elimination Process.

The large-scale implementations of lithium iron phosphate (LFP) batteries for energy storage systems have been gaining attention around the world due to their quality of high technological maturity and flexible configuration. Unfortunately, the exponential production of LFP batteries is accompanied by an annual accumulation of spent batteries and a premature consumption of the lithium resource. Recycling souring critical battery materials such as Li2CO3 is essential to reduce the supply chain risk and achieve net carbon neutrality goals. During the recovery of Li2CO3, impurity removal is the most crucial step in the hydrometallurgy process of spent LiFePO4, which determines the purity of Li2CO3. By investigating and comparing the results of impurity elimination from the purified Li+-containing liquids with strong and weak alkalis under identical pH conditions, respectively, a strategy based on an alkali mixture has been proposed. The purified Li+-containing liquid was, thereafter, concentrated and sodium carbonate was added in order to precipitate Li2CO3. As a result, a high purity Li2CO3 (99.51%) of battery grade was obtained. LiFePO4 prepared with the recovered Li2CO3 and FePO4 as raw materials also displayed a comparative high capacity and stable cycle performance to the commercial product and further verified the electrochemical activity of the recovered materials.

Effect of abdominal weight training with and without cough machine assistance on lung function in the patients with prolonged mechanical ventilation: a randomized trial.

PURPOSE: The patients with prolonged mechanical ventilation (PMV) have the risk of ineffective coughing and infection due to diaphragm weakness. This study aimed to explore the effect of abdominal weight training (AWT) intervention with/without cough machine (CM) assistance on lung function, respiratory muscle strength and cough ability in these patients. METHODS: Forty patients with PMV were randomly assigned to three groups: AWT group (n = 12), AWT + CM group (n = 14) and control group (n = 14). Change of maximum inspiratory pressure (MIP), Maximum expiratory pressure (MEP) and peak cough flow (PCF) between 1 day before and 2 weeks after the intervention were compared among these three groups. RESULTS: MIP before and after intervention in AWT group (30.50 ± 11.73 vs. 36.00 ± 10.79; p < 0.05) and AWT + CM group (29.8 ± 12.14 vs. 36.14 ± 10.42; p < 0.05) compared with control group (28.43 ± 9.74 vs 26.71 ± 10.77; p > 0.05) was significantly improved. MEP before and after intervention in AWT group (30.58 ± 15.19 vs. 41.50 ± 18.33; p < 0.05) and AWT + CM group (27.29 ± 12.76 vs 42.43 ± 16.96; p < 0.05) compared with control group (28.86 ± 10.25 vs. 29.57 ± 14.21; p > 0.05) was significantly improved. PCF before and after intervention in AWT group in AWT group (105.83 ± 16.21 vs. 114.17 ± 15.20; p < 0.05) and AWT + CM group (108.57 ± 18.85 vs. 131.79 ± 38.96; p < 0.05) compared to control group (108.57 ± 19.96 vs. 109.86 ± 17.44; p > 0.05) showed significant improvements. AWT + CM group had significantly greater improvements than control group in MIP and peak cough flow than control group (13.71 ± 11.28 vs 19.64 ± 29.90, p < 0.05). CONCLUSION: AWT can significantly improve lung function, respiratory muscle strength, and cough ability in the PMV patients. AWT + CM can further improve their expiratory muscle strength and cough ability. Trial registration ClinicalTrials.gov registry (registration number: NCT0529538 retrospectively registered on March 3, 2022).

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs. We found that late passage (P25 or later) UCMSCs (LP-UCMSCs) exhibited impaired proangiogenic abilities. Treatment of P25 UCMSCs with rapamycin (900 nM) reversed the senescent phenotype and notably enhanced the proangiogenic activity of senescent UCMSCs. In a nude mouse model of hindlimb ischemia, intramuscular injection of rapamycin-treated P25 UCMSCs into the ischemic limb significantly promoted neovascularization and ischemic limb salvage. We further analyzed the changes in the expression of angiogenesis-associated genes in rapamycin-primed MSCs and found higher expression of several genes related to angiogenesis, such as VEGFR2 and CTGF/CCN2, in primed cells than in unprimed MSCs. Taken together, our data demonstrate that rapamycin is a potential drug to restore the proangiogenic activity of senescent MSCs, which is of importance in treating ischemic diseases and tissue engineering.

Intrathecal therapy for tuberculous meningitis: propensity-matched cohort study.

OBJECTIVE: The study aimed to determine the safety and efficacy of intrathecally administered isoniazid (INH) and prednisolone in addition to systemic anti-TB therapy and compare it with systemic anti-TB therapy alone in adult patients with tuberculous meningitis (TBM). METHODS: In this retrospective study, patients were categorized into two groups: Group A patients received systematic anti-TB therapy alone, Group B patients received IT INH (50 mg) and prednisolone (25 mg) twice a week together with the same standard systemic anti-TB therapy as Group A, in addition to the standard systemic anti-TB therapy. Functional outcomes were compared between the two groups in a prosperity-matched cohort using propensity score matching (PSM) method. RESULTS: A total of 198 patients with TBM were enrolled. After PSM, 30 patients from each group were analyzed, so that there was no significant difference in the characteristics of the two groups. Mortality at follow-up was significantly lower among patients receiving additional IT therapy (4/30, 13.3%) compared with matched patients receiving systemic anti-TB therapy alone (11/30, 36.7%, P value = 0.037). CONCLUSIONS: In this propensity score-matched cohort, the addition of IT INH and prednisolone to systemic anti-TB therapy could be effective for the better outcome among adult TBM patients. Further large-scale, prospective, and randomized controlled trials are warranted to the best timing and indication of IT therapy.

Association between serum vitamin D levels and visceral adipose tissue among adolescents: a cross-sectional observational study in NHANES 2011-2015.

BACKGROUND: In recent years, obesity and vitamin D deficiency are more prevalent among adolescents. Improving our knowledge of the link between vitamin D and visceral adipose tissue (VAT) is essential for the health of adolescents. This study aimed to examine the connection between serum vitamin D levels and VAT mass among adolescents participating in the United States. METHODS: This is a cross-sectional study that used data from the 2011 to 2015 National Health and Nutrition Examination Survey (NHANES). The connection between serum vitamin D levels and VAT was investigated using weighted multiple linear regression models. Potential nonlinear relationships were explored using smooth curve fitting. RESULTS: The analysis included 3171 adolescents aged 12-19 years. Vitamin D levels were shown to be inversely linked with VAT in the full-adjusted model (ß = - 0.34, 95% CI: - 0.49 to - 0.19). When stratified analyses by gender, this negative relationship persisted in the girls' group (ß = - 0.39, 95% CI: - 0.60 to - 0.19), but not in the boys' group (ß = - 0.06, 95% CI: - 0.25 to 0.13). When stratified analysis by race, this negative relationship persisted in the Mexican American group (ß = - 0.61, 95% CI: - 1.03 to - 0.19), and the non-Hispanic White group (ß = - 0.27, 95% CI: - 0.54 to - 0.01), but not in the other groups. CONCLUSIONS: Our findings confirmed that serum vitamin D levels negatively correlated with VAT among adolescents in the United State, especially in girls, the Mexican American and non-Hispanic White. Further research is needed to determine whether increasing serum vitamin D levels decrease VAT among adolescents.

A new cyclic peptide from Selaginella tamariscina.

A new cyclic peptide selapeptin B (1), together with one known nor-lignan glycoside moellenoside C (2), was isolated from Selaginella tamariscina. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS. Two compounds were evaluated for cytotoxic activities against B16F10, MDA-MB-231, and MDA-MB-468 cell lines by MTT assay. Compound 1 showed the potent activity against B16F10 melanoma cell lines.

Two new flavonol glycosides from Selaginella tamariscina.

Two new flavonol glycosides 3,5,7-trimethoxyflavone-4'-O-[5'''-O-p-coumaroyl-ß-D-apiofuranoyl-(1'''→2'')-ß-D-glucopyranoside] (1) and 3,5,7-trimethoxyflavone -4'-O-ß-D-glucopyranoside (2) were isolated from Selaginella tamariscina. The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS spectrometry. Two compounds were evaluated for cytotoxic activities against A-375, MCF-7, MDA-MB-231 and MDA-MB-468 cell lines by MTT assay. Unfortunately, two compounds displayed no cytotoxic activities.

Synthesis and Biological Evaluation of Dipeptide-Based Stilbene Derivatives Bearing a Biheterocyclic Moiety as Potential Fungicides.

The escalating demand for crop production, environmental protection, and food safety warrants the development of new fungicides with greater efficiency, environmental friendliness, and innocuous metabolites to fight against destructive phytopathogens. Herein, we report on the synthesis and antifungal activity of dipeptide-based stilbene derivatives bearing a thiophene-substituted 1,3,4-oxadiazole fragment for the first time. In vitro bioassay indicated that the target compounds had remarkable antifungal potency superior to previously reported counterparts without a dipeptidyl group, of which compound 3c exhibited the highest activity against Botrytis cinerea with EC50 values of 106.1 µg/mL. Moreover, the in vivo protective effect of compound 3c (59.1%) against tomato gray mold was more potent than that of carboxin (42.0%). Preliminary investigations on the mode of action showed that compound 3c induced marked hyphal malformations and increased the membrane permeability of B. cinerea as well as inhibiting mycelial respiration. These promising results suggest that this novel type of molecular framework has great potential to be further developed as alternative fungicides.

[Mechanism of Bupleurum scorzonerifolium and Paeonia lactiflora herbal pair against liver cancer: an exploration based on UPLC-Q-TOF-MS combined with network pharmacology].

This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.

Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People's Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.

Synergism between the phosphatidylinositol 3-kinase p110ß isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation.

BACKGROUND: Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110ß (PI3Kß) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kß. METHODS: To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient's specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kß inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated. RESULTS: MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients' specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kß and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin. CONCLUSION: Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kß and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.

Parametric g-formula implementations for causal survival analyses.

The g-formula can be used to estimate the survival curve under a sustained treatment strategy. Two available estimators of the g-formula are noniterative conditional expectation and iterative conditional expectation. We propose a version of the iterative conditional expectation estimator and describe its procedures for deterministic and random treatment strategies. Also, because little is known about the comparative performance of noniterative and iterative conditional expectation estimators, we explore their relative efficiency via simulation studies. Our simulations show that, in the absence of model misspecification and unmeasured confounding, our proposed iterative conditional expectation estimator and the noniterative conditional expectation estimator are similarly efficient, and that both are at least as efficient as the classical iterative conditional expectation estimator. We describe an application of both noniterative and iterative conditional expectation to answer "when to start" treatment questions using data from the HIV-CAUSAL Collaboration.

Creating a Scoring System with an Armband Wearable Device for Table Tennis Forehand Loop Training: Combined Use of the Principal Component Analysis and Artificial Neural Network.

BACKGROUND: This study presents an intelligent table tennis e-training system based on a neural network (NN) model that recognizes data from sensors built into an armband device, with the component values (performances scores) estimated through principal component analysis (PCA). METHODS: Six expert male table tennis players on the National Youth Team (mean age 17.8 ± 1.2 years) and seven novice male players (mean age 20.5 ± 1.5 years) with less than 1 year of experience were recruited into the study. Three-axis peak forearm angular velocity, acceleration, and eight-channel integrated electromyographic data were used to classify both player level and stroke phase. Data were preprocessed through PCA extraction from forehand loop signals. The model was trained using 160 datasets from five experts and five novices and validated using 48 new datasets from one expert and two novices. RESULTS: The overall model's recognition accuracy was 89.84%, and its prediction accuracies for testing and new data were 93.75% and 85.42%, respectively. Principal components corresponding to the skills "explosive force of the forearm" and "wrist muscle control" were extracted, and their factor scores were standardized (0-100) to score the skills of the players. Assessment results indicated that expert scores generally fell between 60 and 100, whereas novice scores were less than 70. CONCLUSION: The developed system can provide useful information to quantify expert-novice differences in fore-hand loop skills.

Two new selariscinins from Selaginella tamariscina (Beauv.) Spring.

Two new selariscinins named selariscinin F (1) and selariscinin G (2), along with one known selariscinin D (3) were isolated from Selaginella tamariscina. The structures of 1-3 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS.

Acute Lower Respiratory Infections Associated With Respiratory Syncytial Virus in Children With Underlying Congenital Heart Disease: Systematic Review and Meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common viral pathogen associated with acute lower respiratory infections (ALRIs), with significant childhood morbidity and mortality worldwide. Estimates reporting RSV-associated ALRI (RSV-ALRI) severity in children with congenital heart disease (CHD) are lacking, thus warranting the need to summarize the available data. We identified relevant studies to summarize the findings and conducted a meta-analysis of available data on RSV-associated ALRI hospitalizations in children aged <5 years, comparing those with underlying CHD to those without CHD. METHODS: We conducted a systematic search of existing relevant literature and identified studies reporting hospitalization of children aged <5 years with RSV-ALRI with underlying or no CHD. We summarized the data and conducted (where possible) a random-effects meta-analysis to compare the 2 groups. RESULTS: We included 18 studies that met our strict eligibility criteria. The risk of severe RSV-ALRI (odds ratio, 2.2; 95% confidence interval [CI], 1.6-2.8), the rate of hospitalization (incidence rate ratio, 2.8; 95% CI, 1.9-4.1), and the case-fatality ratio (risk ratio [RR], 16.5; 95% CI, 13.7-19.8) associated with RSV-ALRI was higher among children with underlying CHD as compared to those without no CHD. The risk of admission to the intensive care unit (RR, 3.9; 95% CI, 3.4-4.5), need for supplemental oxygen therapy (RR, 3.4; 95% CI, .5-21.1), and need for mechanical ventilation (RR, 4.1; 95% CI, 2.1-8.0) was also higher among children with underlying CHD. CONCLUSION: This is the most detailed review to show more-severe RSV-ALRI among children aged <5 years with underlying CHD, especially hemodynamically significant underlying CHD, as compared those without CHD, supporting a need for improved RSV prophylactics and treatments that also have efficacy in children older than 1 year.

Gemmobacter caeruleus sp. nov., a novel species originating from lake sediment.

An aerobic, Gram-stain-negative, non-spore-forming and rod-shaped bacterial strain, designated N8T, was isolated from the interfacial sediment of Taihu Lake in PR China. The strain formed white to blue colonies on R2A agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain N8T represented a member of the genus Gemmobacter and was most closely related to Gemmobacter aquaticus A1-9T (97.97 %). The average nucleotide identity and digital DNA-DNAhybridization values between strain N8T and G. aquaticus A1-9T based on their whole genomes were 78.8 and 21.7 %, respectively. Q-10 was the main predominant ubiquinone. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0 and C16 : 0. The G+C content of the genomic DNA was 66.1 mol%. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, two unidentified glycolipids and two unidentified lipids. Based on its physiological, biochemical and chemotaxonomic characteristics, strain N8T represents a novel species of the genus Gemmobacter, for which the name Gemmobacter caeruleus sp. nov. is proposed. The type strain is N8T=(KACC 21307T=MCCC 1K04036T).