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As SARS-CoV-2 and influenza viruses co-circulate, co-infections with these viruses generate an increasing concern to public health. To evaluate the prevalence and clinical impacts of SARS-CoV-2 and influenza A virus co-infections during the 2021-2022 influenza season, SARS-CoV-2-positive samples from 462 individuals were collected from October 2021 to January 2022. Of these individuals, 152 tested positive for influenza, and the monthly co-infection rate ranged from 7.1% to 48%. Compared to the Delta variant, individuals infected with Omicron were less likely to be co-infected and hospitalized, and individuals who received influenza vaccines were less likely to become co-infected. Three individuals had two samples collected on different dates, and all three developed a co-infection after their initial SARS-CoV-2 infection. This study demonstrates high prevalence of co-infections in central Missouri during the 2021-2022 influenza season, differences in co-infection prevalence between the Delta and the Omicron waves, and the importance of influenza vaccinations against co-infections.

Renal injury is an important factor in the development of chronic kidney diseases that pathologically manifested as renal fibrosis and podocyte damage. In the disease state, renal fibroblasts lead to high expression levels of α-smooth muscle actin (α-SMA), while podocytes undergo epithelial–mesenchymal transition, leading to proteinuria. Celastrol, a bioactive compound in the medicinal plant Tripterygium wilfordii, was found to delay the progression of early diabetic nephropathy and attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, its effect on the renal system in 5/6 nephrectomized (Nx) rats remains unknown. The aim of this study was to explore the protective effects of celastrol and its underlying mechanisms in 5/6 Nx rats. We found that 24 h proteinuria and levels of blood urea nitrogen, serum creatinine, triglycerides, serum P, renal index and cholesterol significantly increased ( P

In this study, we compute the correlation functions of Wilson(-'t Hooft) loops with chiral primary operators in the $ \mathcal{N}=4 $ supersymmetric Yang-Mills theory with $ \mathcal{N}=4 $ gauge symmetry, which has a holographic dual description of the Type IIB superstring theory on the $ \mathcal{N}=4 $ background. Specifically, we compute the coefficients of the chiral primary operators in the operator product expansion of Wilson loops in the fundamental representation, Wilson-'t Hooft loops in the symmetric representation, Wilson loops in the anti-fundamental representation, and Wilson loops in the spinor representation. We also compare these results to those of the $ \mathcal{N}=4 $ super Yang-Mills theory.

Accumulating evidence have demonstrated that circular RNAs (circRNAs) exert important roles in tumor initiation and progression. Nevertheless, the role and mechanism of circRNA ceramide synthase 6 (circCERS6) in epithelial ovarian cancer (EOC) remain to be clarified. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay, we measured RNA and protein expression. We analyzed the effects of circCERS6/microRNA-630 (miR-630)/Ras-association domain family member 8 (RASSF8) axis in cell proliferation, migration, and invasion by 5-Ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, scratch test, and transwell assay. Using RNA-pull down assay and dual-luciferase reporter assay, the interaction between miR-630 and circCERS6 or RASSF8 was verified. The in vivo role of circCERS6 in tumor growth was analyzed using xenograft mice model. CircCERS6 expression was markedly reduced in EOC tissues and cell lines. CircCERS6 overexpression hampered the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of EOC cells. CircCERS6 directly interacted with miR-630. miR-630 expression was up-regulated in EOC tissues and cell lines. CircCERS6 overexpression-induced anti-tumor effects in EOC were largely reversed by the overexpression of miR-630. RASSF8 was a direct target of miR-630. RASSF8 level was decreased in EOC tissues and cell lines. CircCERS6 up-regulated RASSF8 expression by acting as a molecular sponge for miR-630 in EOC cells. CircCERS6 overexpression-mediated suppressive effects in EOC cells were largely overturned by the silence of RASSF8. CircCERS6 overexpression blocked tumor growth in vivo. CircCERS6 overexpression hampered the proliferation, migration, invasion, and EMT of EOC cells by up-regulating RASSF8 via sponging miR-630.

A user-friendly steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) prefers no calibration for its target recognition algorithm, however, the existing calibration-free schemes perform still far behind their calibration-based counterparts. To tackle this issue, learning online from the subject's unlabeled data is investigated as a potential approach to boost the performance of the calibration-free SSVEP-based BCIs.An online adaptation scheme is developed to tune the spatial filters using the online unlabeled data from previous trials, and then developing the online adaptive canonical correlation analysis (OACCA) method.A simulation study on two public SSVEP datasets (Dataset I and II) with a total of 105 subjects demonstrated that the proposed online adaptation scheme can boost the CCA's averaged information transfer rate (ITR) from 94.60 to 158.87 bits/min in Dataset I and from 85.80 to 123.91 bits/min in Dataset II. Furthermore, in our online experiment it boosted the CCA's ITR from 55.81 bits/min to 95.73 bits/min. More importantly, this online adaptation scheme can be easily combined with any spatial filtering-based algorithms to achieve online learning.By online adaptation, the proposed OACCA performed much better than the calibration-free CCA, and comparable to the calibration-based algorithms.This work provides a general way for the SSVEP-based BCIs to learn online from unlabeled data and thus avoid calibration.

Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. In this study, whole-exome sequencing and co-segregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro functional assays were used to analyze the pathogenicity of a novel CFTR mutation. We identified a novel compound heterozygous mutation of CFTR comprising the known disease-causing variant c.1210-11T > G (also known as IVS9‐5T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. Our study revealed that this novel compound heterozygous mutation is involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

Millions of Norway rats (Rattus norvegicus)inhabit New York City (NYC), presenting the potential for transmission of SARS-CoV-2 from humans to rats and other wildlife. We evaluated SARS-CoV-2 exposure among 79 rats captured from NYC during the fall of 2021. Results showed that 13 of 79 rats (16.5%) tested IgG or IgM positive, and partial genomes of SARS-CoV-2 were recovered from four rats that were qRT-PCR positive. Using a virus challenge study, we also showed that Alpha, Delta, and Omicron variants can cause robust infections in wild-type Sprague Dawley (SD) rats, including high level replications in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Additionally, the Delta variant resulted in the highest infectivity. In summary, our results indicated that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the potential risk of secondary zoonotic transmission from urban rats and the need for further monitoring of SARS-CoV-2 in those populations.ImportanceSince its emergence causing the COVID-19 pandemic, the host tropism expansion of SARS-CoV-2 raises a potential risk for reverse-zoonotic transmission of emerging variants into rodent species, including wild rat species. In this study, we presented both genetic and serological evidence for SARS-CoV-2 exposure in wild rat population from New York City, and these viruses are potentially linked to the viruses during the early stages of the pandemic. We also demonstrated that rats are susceptible to additional variants (i.e., Alpha, Delta, and Omicron) predominant in humans and that the susceptibility to different variants vary. Our findings highlight the potential risk of secondary zoonotic transmission from urban rats and the need for further monitoring of SARS-CoV-2 in those populations.

Background Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs. Methods Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and cancer datasets. Overexpression and knockdown of FAM129A in glioma stem cells were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms. Results FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation. Conclusion FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.

Supplementary Data from Differentiation Therapy Exerts Antitumor Effects on Stem-like Glioma Cells

Purpose: Stem-like tumor cells comprise a highly tumorigenic and therapy-resistant tumor subpopulation, which is believed to substantially influence tumor initiation and therapy resistance in glioma. Currently, therapeutic, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population; retinoic acid is well known as a potent modulator of differentiation and proliferation in normal stem cells. In glioma, knowledge about the efficacy of retinoic acid–induced differentiation to target the stem-like tumor cell pool could have therapeutic implications.Experimental Design: Stem-like glioma cells (SLGC) were differentiated with all-trans retinoic acid–containing medium to study the effect of differentiation on angiogenesis, invasive growth, as well as radioresistance and chemoresistance of SLGCs. In vivo effects were studied using live microscopy in a cranial window model.Results: Our data suggest that in vitro differentiation of SLGCs induces therapy-sensitizing effects, impairs the secretion of angiogenic cytokines, and disrupts SLGCs motility. Further, ex vivo differentiation reduces tumorigenicity of SLGCs. Finally, we show that all-trans retinoic acid treatment alone can induce antitumor effects in vivo.Conclusions: Altogether, these results highlight the potential of differentiation treatment to target the stem-like cell population in glioblastoma. Clin Cancer Res; 16(10); 2715–28. ©2010 AACR.

Although intended to control pests, pesticides affect a phylogenetically diverse range of non-target species contributing to global biodiversity declines1–7. However, the magnitude of this risk is only partly understood. Here, we show that pesticides negatively affect non-target organisms across the tree of life. We analyzed 26,096 effect sizes from 1,705 studies reporting effects of insecticides, fungicides and herbicides on growth, reproduction, behaviour, and other biomarkers of non-target terrestrial and aquatic taxa. Pesticides negatively affected invertebrate and vertebrate animals, seed and spore-producing plants, as well as bacteria and fungi. Pesticides formulated to target a particular taxon negatively affected phylogenetically distant groups, e.g. insecticidal neonicotinoids impacted amphibians, fish, mammals and monocotyledonous plants. The effects were evident for field-realistic exposures, were more pronounced in temperate than tropical regions, and were consistent in magnitude for exposure in aquatic and terrestrial environments. The detection of strong detrimental effects of pesticides across a wide range of non-target organisms questions current regulatory practices. Adoption of sustainable management practices (e.g. agricultural ecological intensification, integrated pest management, and non-pesticide control) may help balance food security alongside reducing dependencies on pesticide with their associated risks to nature.

Promoting neurogenesis and proliferation of endogenous neural stem/progenitor cells (NSPCs) is considered a promising strategy for neurorehabilitation after stroke. Our previous study revealed that a moderate dose of artesunate (ART, 150mg/kg) could enhance functional recovery in middle cerebral artery occlusion (MCAO) mice. This study aimed to investigate the effects of ART treatment on neurogenesis and proliferation of NSPCs using a rodent MCAO model. MRI results indicated that the ischemic brain volume of MCAO mice was reduced by ART treatment. The results of diffusion tensor imaging, electron microscopic, and immunofluorescence of Tuj-1 also revealed that ischemia-induced white matter lesion was alleviated by ART treatment. After ischemia/reperfusion, endogenous NSPCs were activated by ART, which was displayed by comparing the proportion of Brdu+ neuronal precursor cells in the ipsilateral subventricular zone and peri-infarct cortex. Furthermore, the neuro-restorative effects of ART were abolished by the overexpression of FOXO3a. These findings suggested that ART could rescue penumbra damage and alleviate white matter injury, subsequently contributing to post-stroke functional recovery by promoting neurogenesis and proliferation of endogenous NSPCs via the FOXO3a/p27Kip1 pathway.

As a new type of waste heat conversion machine, the roots power machine can convert low-quality waste heat resources that are difficult to use into mechanical energy. In order to study the influence of tip clearance and radial clearance on the roots power machine, experimental studies were conducted with the roots power machine having different combination of tip and radial clearances and their influence on the performance of the roots power machine was examined. A parametric study was undertaken using CFD to find the sensitivity of these clearances in influencing the performance of roots power machine in the range of 0.2-0.5 mm. From the analysis, it was inferred that radial clearance was sensitive for clearance range of 0.25-0.5 mm and tip clearance in the range of 0.2-0.25 mm. Reduction in clearance from 0.5 mm to 0.2 mm caused an increase of 10.368 and 11.423 % in mechanical and volumetric efficiency respectively.

Mucosal immune regulation is considered a key aspect of immunopathogenesis of IgA nephropathy (IgAN). Direct experimental evidence clarifying the role of intestinal mucosa attributes in IgAN is lacking. In this study, a mouse model was established via multiple low-dose intraperitoneal injections of Lactobacillus casei cell wall extract (LCWE) emulsified with Complete Freund's Adjuvant (CFA). We found continuous and stable deposition of IgA in glomerular mesangial areas, accompanying high circulating levels of IgA and IgA-IgG complexes. Expression of the key extracellular matrix components collagen IV and fibronectin also increased in the mesangial areas of LCWE-induced mice. IgA

The excited-state double proton transfer (ES-DPT) properties of 1,5-dihydroxyanthraquinone (1,5-DHAQ) in various solvents were investigated using femtosecond transient absorption spectroscopy and the DFT/TDDFT method. The steady-state fluorescence spectra in toluene, tetrahydrofuran (THF) and acetonitrile (ACN) solvents presented that the solvent polarity has an effect on the position of the ESDPT fluorescence emission peak for the 1,5-DHAQ system. Transient absorption spectra show that the increasing polarity of the solvent accelerates the rate of excited state dynamics. Calculated potential energy curves analysis further verified the experimental results. The ESDPT barrier decreases gradually with the increase of solvent polarity from toluene, THF to ACN solvent. It is convinced that the increase of solvent polarity can promote the occurrence of the ESDPT dynamic processes for the 1,5-DHAQ system. This work clarifies the mechanism of the influence of solvent polarity on the ESDPT process of 1,5-DHAQ, which provides novel ideas for design and synthesis of new hydroxyanthraquinone derivatives.