RNAscope 2.5 HD Red assay

S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters

In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity, but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2 infection in vitro, few have proven to be effective in vivo.

Natural reservoir Rousettus aegyptiacus bat host model of orthonairovirus infection identifies potential zoonotic spillover mechanisms

The human-pathogenic Kasokero virus (KASV; genus Orthonairovirus) has been isolated from the sera of Egyptian rousette bats (ERBs; Rousettus aegyptiacus) captured in Uganda and unengorged Ornithodoros (Reticulinasus) faini ticks collected from the rock crevices of ERB colonies in South Africa and Uganda. Although evidence suggests that KASV is maintained in an enzootic transmission cycle between O.

Increased expression of miR-194-5p through the circPVRL3/miR-194-5p/SOCS2 axis promotes proliferation and metastasis in pancreatic ductal adenocarcinoma by activating the PI3K/AKT signaling pathway

MicroRNAs (miRNAs), as an indispensable type of non-coding RNA (ncRNA), participate in diverse biological processes. However, the specific regulatory mechanism of certain miRNAs in pancreatic ductal adenocarcinoma (PDAC) remains unclear.The expression of miR-194-5p in PDAC tissue microarray and cell lines were detected by RNA-scope and real-time quantitative PCR (RT-qPCR). The function of proliferation and migration carried by miR-194-5p in vitro and vivo was observed by several functional experiments.

ADAMTSL3 knock-out mice develop cardiac dysfunction and dilatation with increased TGFβ signalling after pressure overload

Heart failure is a major cause of morbidity and mortality worldwide, and can result from pressure overload, where cardiac remodelling is characterized by cardiomyocyte hypertrophy and death, fibrosis, and inflammation. In failing hearts, transforming growth factor (TGF)β drives cardiac fibroblast (CFB) to myofibroblast differentiation causing excessive extracellular matrix production and cardiac remodelling. New strategies to target pathological TGFβ signalling in heart failure are needed. Here we show that the secreted glycoprotein ADAMTSL3 regulates TGFβ in the heart.

Liver alterations and detection of SARS-CoV-2 RNA and proteins in COVID-19 autopsies

The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung. However, other organs also are affected. Here, we report histopathologic findings in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed at the Semmelweis University (Budapest, Hungary). Between March 2020 through March 2022, 150 autopsies on patients who died of COVID-19 were analyzed.

Non-neuronal TRPA1 encodes mechanical allodynia associated with neurogenic inflammation and partial nerve injury in rats

The proalgesic transient receptor potential ankyrin 1 (TRPA1) channel, expressed by a subpopulation of primary sensory neurons, has been implicated in various pain models in mice. However, evidence in rats indicates that TRPA1 conveys nociceptive signals elicited by channel activators, but not those associated with tissue inflammation or nerve injury.

Interleukin-10 induces expression of CD39 on CD8+T cells to potentiate anti-PD1 efficacy in EGFR-mutated non-small cell lung cancer

Anti-PD-1(L1) therapies are less efficacious in patients with EGFR-mutated non-small-cell lung cancer. However, the underlying mechanism is poorly understood.The characteristics of T cells in EGFR-mutated and wild-type tumors were analyzed based on The Cancer Genome Atlas database and clinical samples. Plasma levels of 8 T-cell-related cytokines were evaluated and its association with immunotherapy efficacy were explored. Association between EGFR signaling pathway and IL-10 was examined through tumor cell lines and clinical tumor samples.

SOX17-positive rete testis epithelium is required for Sertoli valve formation and normal spermiogenesis in the male mouse

Seminiferous tubules (STs) in the mammalian testes are connected to the rete testis (RT) via a Sertoli valve (SV). Spermatozoa produced in the STs are released into the tubular luminal fluid and passively transported through the SV into the RT. However, the physiological functions of the RT and SV remain unclear. Here, we identified the expression of Sox17 in RT epithelia. The SV valve was disrupted before puberty in RT-specific Sox17 conditional knockout (Sox17-cKO) male mice. This induced a backflow of RT fluid into the STs, which caused aberrant detachment of immature spermatids.

Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection

Mice reconstituted with human immune systems are instrumental in the investigation of HIV-1 pathogenesis and therapeutics. Natural killer (NK) cells have long been recognized as a key mediator of innate anti-HIV responses. However, established humanized mouse models do not support robust human NK cell development from engrafted human hematopoietic stem cells (HSCs). A major obstacle to human NK cell reconstitution is the lack of human interleukin-15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor.

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