Gemcitabine Inhibits Poliovirus Replication and Interferes with Viral RNA Elongation

While we are approaching the end game of global eradication of circulating wild-type polioviruses(PV), vaccination with oral poliovirus vaccine (OPV) has led to emergence of circulating vaccine-derived poliovirus (cVDPV) and vaccine-associated paralytic poliomyelitis (VAPP). Complete cessation of all poliovirus infections may require stopping use of OPV and formulating improved vaccines and new antiviral drugs. Currently, no licensed drugs are available to treat chronically infected poliovirus excreters. Here, we created a modified PV expressing Gaussia Luciferase (PV-GLuc) and developed a cell-based high-throughput screening (HTS) antiviral assay. Using the validated HTS assay, we screened the FDA-approved drug library of compounds and identified candidate agents capable of inhibiting PV replication. We then characterized anti-poliovirus activity for the best hit, Gemcitabine, a nucleoside analogue used in tumor chemotherapy. We found that Gemcitabine inhibited PV Mahoney replication with IC50 of 0.3μM. It completely protected HeLa cells from PV-induced cytopathic effects at 5μM, without detectable toxicity for cell viability. Furthermore, Gemcitabine metabolite directly inhibited the ability of PV RNA polymerase to synthesize or elongate PV RNA. Since PV RNA polymerase is somehow conserved among species in Picornaviridae family, Gemcitabine may be further developed as an attractive broad-spectrum antiviral for PV and others

Data_Sheet_5_Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies.PDF

BackgroundBacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.Materials and methodsWe searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.ResultsA total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P ConclusionThis meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.</p

Data_Sheet_2_Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies.PDF

BackgroundBacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.Materials and methodsWe searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.ResultsA total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P ConclusionThis meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.</p

Data_Sheet_3_Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies.PDF

BackgroundBacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.Materials and methodsWe searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.ResultsA total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P ConclusionThis meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.</p

Data_Sheet_4_Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies.PDF

BackgroundBacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.Materials and methodsWe searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.ResultsA total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P ConclusionThis meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.</p

Table_1_Vitamin D deficiency increases the risk of bacterial vaginosis during pregnancy: Evidence from a meta-analysis based on observational studies.DOCX

BackgroundBacterial vaginosis (BV) is the most common microbiological syndrome in women of childbearing age, causing numerous adverse health issues in pregnant women. Several observational studies have discussed the association between vitamin D deficiency and the risk of BV during pregnancy, but the results were inconclusive. Therefore, this meta-analysis aimed to explore the association between vitamin D deficiency and BV risk in pregnant women.Materials and methodsWe searched four databases, including PubMed, Embase, Cochrane Library, and Web of Science, from their inception to July 2022. Pooled odds ratios (OR) with corresponding 95% confidence intervals (CI) were estimated using random effects models. Additionally, we conducted subgroup analyses to identify the potential sources of between-study heterogeneity. Sensitivity analysis was performed using the method of exclusion, one study at a time. Publication bias was examined using Egger’s test and funnel plot.ResultsA total of 14 studies from 13 articles including 4,793 participants were eligible for this meta-analysis. The outcome showed that vitamin D deficiency may increase the risk of BV during pregnancy by 54% (OR, 1.54; 95% CI, 1.25–1.91; P ConclusionThis meta-analysis showed that vitamin D deficiency is positively associated with the risk of BV during pregnancy. Further high-quality prospective cohort studies are needed to determine whether vitamin D intake reduces the prevalence of BV in pregnant women.</p

Synthesis and Characterization of Electron-Deficient Asymmetrically Substituted Diarylindenotetracenes

Electron-deficient asymmetrically substituted diarylindenotetracenes were prepared via a series of Friedel–Crafts acylations, aryl–aryl cross-couplings, and an intramolecular oxidative cyclization to form the indene ring. Single-crystal X-ray experiments showed good π–π overlap with π–π distances ranging from 3.26 to 3.76 Å. Both thermogravimetric analysis and differential scanning calorimetry indicated that asymmetrically substituted indenotetracenes (ASIs) are stable at elevated temperatures. From cyclic voltammetry experiments, HOMO/LUMO energy levels of ASI derivatives were determined to be near −5.4/–4.0 eV. UV/visible absorption spectra showed strong absorption of light between 400 and 650 nm with molar attenuation coefficients from 10⁴ to 10⁵ M^–1 cm^–1. ASIs were also found to have very low fluorescence quantum yields, less than 4%. Using the solid-state packing determined from the single-crystal X-ray experiments, computational modeling indicated that ASI molecules should favor electron transport

Free-Standing Mn₃O₄@CNF/S Paper Cathodes with High Sulfur Loading for Lithium–Sulfur Batteries

Free-standing paper cathodes with layer-by-layer structure are synthesized for high-loading lithium–sulfur (Li–S) battery. Sulfur is loaded in a three-dimensional (3D) interconnected nitrogen-doped carbon nanofiber (CNF) framework impregnated with Mn₃O₄ nanoparticles. The 3D interconnected CNF framework creates an architecture with outstanding mechanical properties. Synergetic effects generated from physical and chemical entrapment could effectively suppress the dissolution and diffusion of the polysulfides. Electrochemical measurements suggest that the rationally designed structure endows the electrode with high utilization of sulfur and good cycle performance. Specifically, the cathode with a high areal sulfur loading of 11 mg cm^–2 exhibits a reversible areal capacity over 8 mAh cm^–2. The fabrication procedure is of low cost and readily scalable. We believe that this work will provide a promising choice for potential practical applications

Cell-Based High-Throughput Screening Assay Identifies 2′,2′-Difluoro-2′-deoxycytidine Gemcitabine as a Potential Antipoliovirus Agent

As we approach the global eradication of circulating wild-type polioviruses (PV), vaccination with oral poliovirus vaccine (OPV) has led to the emergence of circulating vaccine-derived poliovirus (cVDPV) and vaccine-associated paralytic poliomyelitis (VAPP). Complete cessation of all poliovirus infections may require stopping use of OPV and formulating improved vaccines and new antiviral drugs. Currently, no licensed drugs are available to treat chronically infected poliovirus excretors. Here, we created a modified PV expressing Gaussia Luciferase (Sb-Gluc) and developed a cell-based high-throughput screening (HTS) antiviral assay. Using the validated HTS assay, we screened the FDA-approved drug library of compounds and identified candidate agents capable of inhibiting PV replication. We then characterized antipoliovirus activity for the best hit, gemcitabine, a nucleoside analogue used in tumor chemotherapy. We found that gemcitabine inhibited PV Mahoney replication with an IC₅₀ of 0.3 μM. It completely protected HeLa cells from PV-induced cytopathic effects at 25 μM, without detectable toxicity for cell viability. Furthermore, a gemcitabine metabolite directly inhibited the ability of PV RNA polymerase to synthesize or elongate PV RNA. Because PV RNA polymerase is somehow conserved among species in the <i>Picornaviridae</i> family, gemcitabine may be further developed as an attractive broad-spectrum antiviral for PV and others

Partial Fluorination as a Strategy for Crystal Engineering of Rubrene Derivatives

Through a close examination of the intermolecular interactions of rubrene (<b>1a</b>) and select derivatives (<b>1b</b>–<b>1p</b>), a clearer understanding of why certain fluorinated rubrene derivatives pack with planar tetracene backbones has been achieved. In this study we synthesized, crystallized, and determined the packing structure of new rubrene derivatives (<b>1h</b>–<b>p</b>). Previously, we proposed that introducing electron-withdrawing CF₃ substituents induced planarity by reducing intramolecular repulsion between the peripheral aryl groups (<b>1e</b>–<b>g</b>). However, we found that in most cases, further increasing the fluorine content of rubrene lead to twisted tetracene backbones in the solid state. To understand how rubrene (<b>1a</b>) and its derivatives (<b>1b</b>–<b>p</b>) pack in the solid state, we (re)­examined the crystal structures through a systematic study of the close contacts. We found that planar tetracene cores occur when close contacts organize to produce an <i>S</i> symmetry element about a given rubrene molecule. We report the first instance of rubrene derivatives (<b>1l</b> and <b>1n</b>) that pack in a two-dimensional brick motif. The prospects for new rubrene derivatives in semiconductors were estimated by calculating the reorganization energies of the monomers and transfer integrals of the dimers we observed. Our work allows for the rational design and improved crystal engineering of new rubrene derivatives