Advances in gut microbiome in metabonomics perspective: based on bibliometrics methods and visualization analysis

Background and aimsGastrointestinal microbial metabolomics is closely related to the state of the organism and has significant interaction with the pathogenesis of many diseases. Based on the publications in Web of Science Core Collection(WoSCC) from 2004 to 2022, this study conducted a bibliometric analysis of this field, aiming to understand its development trend and frontier, and provide basic information and potential points for in-depth exploration of this field.MethodsAll articles on gastrointestinal flora and metabolism published from 2004 to 2022 were collected and identified in WoCSS. CiteSpace v.6.1 and VOSviewer v.1.6.15.0 were used to calculate bibliometric indicators, including number of publications and citations, study categories, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. A map was drawn to visualize the data based on the analysis results for a more intuitive view.ResultsThere were 3811 articles in WoSCC that met our criteria. Analysis results show that the number of publications and citations in this field are increasing year by year. China is the country with the highest number of publications and USA owns the highest total link strength and citations. Chinese Acad Sci rank first for the number of institutional publications and total link strength. Journal of Proteome Research has the most publications. Nicholson, Jeremy K. is one of the most important scholars in this field. The most cited reference is “Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease”. Burst detection indicates that Urine, spectroscopy, metabonomic and gut microflora are long-standing hot topics in this field, while autism spectrum disorder and omics are likely to be at the forefront of research. The study of related metabolic small molecules and the application of gastrointestinal microbiome metabolomics in various diseases are currently emerging research directions and frontier in this field.ConclusionThis study is the first to make a bibliometric analysis of the studies related to gastrointestinal microbial metabolomics and reveal the development trends and current research hotspots in this field. This can contribute to the development of the field by providing relevant scholars with valuable and effective information about the current state of the field

Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624)

Video-based Smoky Vehicle Detection with A Coarse-to-Fine Framework

Automatic smoky vehicle detection in videos is a superior solution to the traditional expensive remote sensing one with ultraviolet-infrared light devices for environmental protection agencies. However, it is challenging to distinguish vehicle smoke from shadow and wet regions coming from rear vehicle or clutter roads, and could be worse due to limited annotated data. In this paper, we first introduce a real-world large-scale smoky vehicle dataset with 75,000 annotated smoky vehicle images, facilitating the effective training of advanced deep learning models. To enable fair algorithm comparison, we also build a smoky vehicle video dataset including 163 long videos with segment-level annotations. Moreover, we present a new Coarse-to-fine Deep Smoky vehicle detection (CoDeS) framework for efficient smoky vehicle detection. The CoDeS first leverages a light-weight YOLO detector for fast smoke detection with high recall rate, and then applies a smoke-vehicle matching strategy to eliminate non-vehicle smoke, and finally uses a elaborately-designed 3D model to further refine the results in spatial temporal space. Extensive experiments in four metrics demonstrate that our framework is significantly superior to those hand-crafted feature based methods and recent advanced methods. The code and dataset will be released at https://github.com/pengxj/smokyvehicle

Summary

Research article RNF17, a component of the mammalian germ cell nuage, is essential for spermiogenesi

The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate.

NF449, a sulfated compound derived from the antiparasitic drug suramin, was previously reported to inhibit infection by enterovirus A71 (EV-A71). In the current work, we found that NF449 inhibits virus attachment to target cells, and specifically blocks virus interaction with two identified receptors--the P-selectin ligand, PSGL-1, and heparan sulfate glycosaminoglycan--with no effect on virus binding to a third receptor, the scavenger receptor SCARB2. We also examined a number of commercially available suramin analogues, and newly synthesized derivatives of NF449; among these, NF110 and NM16, like NF449, inhibited virus attachment at submicromolar concentrations. PSGL-1 and heparan sulfate, but not SCARB2, are both sulfated molecules, and their interaction with EV-A71 is thought to involve positively charged capsid residues, including a conserved lysine at VP1-244, near the icosahedral 5-fold vertex. We found that mutation of VP1-244 resulted in resistance to NF449, suggesting that this residue is involved in NF449 interaction with the virus capsid. Consistent with this idea, NF449 and NF110 prevented virus interaction with monoclonal antibody MA28-7, which specifically recognizes an epitope overlapping VP1-244 at the 5-fold vertex. Based on these observations we propose that NF449 and related compounds compete with sulfated receptor molecules for a binding site at the 5-fold vertex of the EV-A71 capsid

Comparative AAV-eGFP Transgene Expression Using Vector Serotypes 1–9, 7m8, and 8b in Human Pluripotent Stem Cells, RPEs, and Human and Rat Cortical Neurons

Recombinant adeno-associated virus (rAAV), produced from a nonpathogenic parvovirus, has become an increasing popular vector for gene therapy applications in human clinical trials. However, transduction and transgene expression of rAAVs can differ across in vitro and ex vivo cellular transduction strategies. This study compared 11 rAAV serotypes, carrying one reporter transgene cassette containing a cytomegalovirus immediate-early enhancer (eCMV) and chicken beta actin (CBA) promoter driving the expression of an enhanced green-fluorescent protein (eGFP) gene, which was transduced into four different cell types: human iPSC, iPSC-derived RPE, iPSC-derived cortical, and dissociated embryonic day 18 rat cortical neurons. Each cell type was exposed to three multiplicity of infections (MOI: 1E4, 1E5, and 1E6 vg/cell). After 24, 48, 72, and 96 h posttransduction, GFP-expressing cells were examined and compared across dosage, time, and cell type. Retinal pigmented epithelium showed highest AAV-eGFP expression and iPSC cortical the lowest. At an MOI of 1E6 vg/cell, all serotypes show measurable levels of AAV-eGFP expression; moreover, AAV7m8 and AAV6 perform best across MOI and cell type. We conclude that serotype tropism is not only capsid dependent but also cell type plays a significant role in transgene expression dynamics

NF449, NF110, and NM16 inhibit virus interactions with Jurkat cells.

<p>(A) Infection by EV-A71-1095, in the presence of inhibitors, measured by staining for VP1 expression. (B) Inhibition of virus attachment by NF449, NF110, and NM16. Results are indicated as the mean and S.D. for triplicate samples. Asterisks indicate <i>P</i> < 0.01 compared to the no inhibitor control.</p

Inhibition of EV-A71 attachment by newly-synthesized NF449 analogues.

<p>(A) Attachment of ³⁵S-labeled EV-A71-1095 to RD cells in the presence of compounds at 0.4 or 4 μM. Results from two experiments, one testing NM1-11 and one testing NM12-16, are combined, and are normalized to results for the no inhibitor control in each experiment. (B) Virus attachment to RD monolayers in the presence of NF449, NF110, and NM16. Results are indicated as the mean and S.D. for triplicate samples. Asterisks indicate <i>P</i> < 0.01 compared to the no inhibitor control.</p

NF449 and NF110 specifically prevent attachment of a monoclonal antibody to the viral 5-fold vertex.

<p>(A) An EV-A71 pentamer shown with the 5-fold vertex at the center. VP1-98 (red) was mutated in an NF449 escape mutant. VP1-242K (light blue) is involved in virus interaction with PSGL-1. VP1-244K (dark blue) is implicated both in virus interactions with both PSGL-1 and NF449. The MA28-7 footprint, as determined by cryo-electronmicroscopy, is outlined in black. The VP2 epitope recognized by mAb 10F0 is indicated in green. (B) NF449 inhibits immunoprecipitation of EV-A71-1095 by MA28-7 but not by 10F0. EV-A71-1095 concentrated from supernatants of infected cells was incubated with MA28-7 or 10F0 fixed to Protein G beads, in the presence of NF449 at the indicated concentrations, or 200 μM Pirodavir; beads were washed, and immunoprecipitated proteins were examined on Coomassie-stained gels. Molecular weight markers are shown at the left. Arrows at the right indicate capsid proteins VP0 and VP1, and brackets indicate antibody heavy (HC) and light chains (LC). (C) NF449 and NF110 inhibit attachment of MA28-7 to mature virions. Purified ³⁵S-labeled mature virions were incubated with MA28-7-coated beads, in the presence of inhibitors as indicated. (D) NF110 inhibits attachment of MA28-7, but not 10F0 or MA105, to procapsids. Purified ³⁵S-labeled procapsids were incubated with monoclonal antibodies fixed to Protein G beads, in the presence of 20 μM NF110. Results are indicated as the mean and S.D. for triplicate samples. Asterisks indicate <i>P</i> < 0.01 compared to the no inhibitor control.</p