DMBT1 promotes SARS-CoV-2 infection and its SRCR-derived peptide inhibits SARS-CoV-2 infection.

DMBT1 is a large scavenger receptor cysteine rich (SRCR) B protein that has been reported as a tumor suppressor gene and a co-receptor for HIV-1 infection. Here we found DMBT1 is a major mucosal protein bound to SARS-CoV-2. Overexpression of DMBT1 in 293T cells may enhanced infection by SARS-CoV-2 in ACE2 dependent manner.

Glycosylphosphatidylinositol biosynthesis functions as a conserved host defense pathway against coronaviruses via regulation of LY6E.

Coronaviruses, including SARS-CoV-2, rely on host factors for their replication and pathogenesis, while hosts deploy defense mechanisms to counteract viral infections. Although numerous host proviral factors have been identified, the landscape of host restriction factors and their underlying mechanisms remain less explored. Here, we conducted genome-wide CRISPR knockout screens using three distinct coronaviruses-SARS-CoV-2, HCoV-OC43 (a common cold human virus from the genus Betacoronavirus) and porcine epidemic diarrhea virus (Alphacoronavirus) to identify conserved host restriction factors.

Multi-Cohort High-Dimensional Proteomics Reveals Early Risk Markers for Lymphoid Cancer Subtypes.

This study aims to investigate the early stages of lymphoid malignancy pathogenesis and identify novel pre-diagnostic proteomic markers for lymphoma. Using the SomaScan-7K platform, we analyzed 6,412 unique plasma proteins in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, comprising 4,565 participants (484 incident lymphoid malignancy cases, median follow-up 9 years). We identified over 500 unique protein-lymphoid malignancy associations.

Soluble MFGE8 mediates cell entry of Crimean-Congo hemorrhagic fever virus.

Unlabelled: Crimean Congo hemorrhagic fever virus (CCHFV) causes fatal tick-borne disease in humans and is a priority pathogen of the World Health Organization. No licensed vaccines or specific antiviral drugs are available. To understand the cell entry of CCHFV and identify potential antiviral targets to combat the disease, here, we perform the CRISPR knockout screen in wild-type cells, followed by a complementary CRISPR activation screen in cells deficient in common attachment factors (heparan sulfate, AXL, TIM-1).

DAZAP2 functions as a pan-coronavirus restriction factor by inhibiting viral entry and genomic replication.

The SARS-CoV-2 pandemic and the emergence of novel variants underscore the need to understand host-virus interactions and identify host factors that restrict viral infection. Here, we perform a genome-wide CRISPR knockout screen to identify host restriction factors for SARS-CoV-2, revealing DAZAP2 as a potent antiviral gene. DAZAP2, previously implicated in SARS-CoV-2 restriction, is found to inhibit viral entry by blocking virion fusion with both endolysosomal and plasma membranes.

Rapid generation of HCoV-229E and HCoV-OC43 reporter viruses and replicons for antiviral research.

Introduction: The large size of coronavirus genome, along with the instability of certain genomic sequences, makes the construction of reverse genetics for coronaviruses particularly challenging. The rapid development and application of reverse genetics systems for coronaviruses require further exploration.

Methods: Using transformation-associated recombination (TAR) cloning in yeast and the CRISPR-Cas9 system, reverse genetics systems of two mild coronaviruses HCoV-OC43 and HCoV-229E were rapidly established.

Protective Role of High-Density Lipoprotein Cholesterol in Stress Urinary Incontinence with Special Emphasis on Overweight/Obese Individuals.

Increasing evidence shows that lipid metabolism is closely related to the pathogenesis of stress urinary incontinence (SUI). This study aimed to investigate the association between high-density lipoprotein cholesterol (HDL-C) levels and female SUI, evaluate dose-response relationships, and determine the causal effect of HDL-C on SUI risk. Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (2001-2020, n = 18,415), we assessed the dose-response relationship between HDL-C and SUI using restricted cubic splines and weighted logistic regression.

Proteomics and the Risk of Incident Embolic and Thrombotic Stroke.

Objective: Personalized approaches to ischemic stroke diagnosis are needed. We determine differences in proteomic signatures of incident embolic (EIS) and thrombotic stroke (TIS) by age and resultant pathways using large-scale proteomics.

Methods: Participants in the Atherosclerosis Risk in Communities Study (ARIC) from visit 2 (V2, 1990-1992) until 2020 without prevalent stroke with available SomaScan data (4,955 protein targets) at V2 (mid-life, n = 10,929), and then again at visit 5 (V5, 2011-2013, n = 4,463) were included.

Phosphorylated Toll-like receptor 3 nuclear translocation in cancer cell promotes metastasis and chemoresistance.

Aberrant expression and subcellular location of innate sensors in cancer cells, such as Toll-like receptors (TLRs), correlates with pro-tumoral inflammation and cancer progression, but the mechanism is still largely unknown. Deciphering the proinflammatory mediators in tumor microenvironment will contribute to the development of cancer therapeutics. By using immunohistochemistry in pancreatic ductal adenocarcinoma (PDAC) and multiple other cancer samples, here we found that cancer cell TLR3, a well-known cytoplasmic dsRNA sensor, translocated to the nucleus especially upon chemotherapy stress.

Discovering plasma proteins associated with breast cancer incidence in post-menopausal women in ARIC.

Background: Plasma proteomic data can be used to discover breast cancer risk biomarkers beyond established risk factors. Discovery using a large-scale platform in a diverse population is needed.

Methods: We investigated 4,712 plasma proteins and breast cancer risk among post-menopausal women in a prospective cohort analysis in the Atherosclerosis Risk in Communities study.

Single-cycle Rift Valley fever virus particles from stable replicon cells enable discovery of antiviral CNX-1351 for multiple RNA viruses.

Rift Valley fever virus (RVFV) is a high-containment pathogen that causes severe diseases in humans, with no approved therapeutics available. Its classification as a biosafety level 3 (BSL-3) agent has limited research and therapeutic development due to safety concerns. In this study, we developed a stable replicon cell line maintaining the replication of L and S genomic segments of RVFV.

Trends in the prevalence of kidney stones among U.S. Adults with obesity from 2007 to 2020.

Background: Kidney stones are a significant health concern in the United States, and their increasing prevalence is linked to increasing obesity rates. This study aimed to assess the trends in kidney stone prevalence among U.S.

The Single Amino Acid Change of R516K Enables Efficient Generation of Vesicular Stomatitis Virus-Based Crimean-Congo Hemorrhagic Fever Reporter Virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a medically important tick-borne virus, causing severe hemorrhagic diseases in humans. There are no approved vaccines and therapeutics for CCHFV infection. The study of CCHFV authentic virus requires biosafety level 3 facilities, hindering the research and development of antivirals.

A Genome-wide Association study of Buccal Mucosa Cancer in India and Multi-ancestry Meta-analysis Identifies Novel Risk Loci and Gene-environment Interactions.

Genome-wide association studies (GWAS) of oral cancers (OC) to date have focused predominantly on European Ancestry (EA) populations. India faces an excess burden of OC, but the most common site of occurrence is the cancer of the buccal mucosa, which is relatively rare in EA populations. We conducted a GWAS of buccal mucosa cancer (BMC) comprising 2,160 BMC cases and 2,325 controls from different geographical locations in India.

Ucenprubart is an agonistic antibody to CD200R with the potential to treat inflammatory skin disease: preclinical development and a phase 1 clinical study.

CD200R is a checkpoint inhibitory receptor central to the pathogenesis of inflammatory skin disease. Here we describe the development and phase 1 clinical study (NCT03750643) of ucenprubart, a CD200R agonist antibody to downregulate immune system inflammation. Preclinical studies find ucenprubart inhibiting Fcγ receptor-induced cytokine secretion from myeloid cells in vitro and demonstrating efficacy in a mouse contact hypersensitivity model.

High-temperature field-free superconducting diode effect in high-T cuprates.

The superconducting diode effect (SDE) is defined by the difference in the magnitude of critical currents applied in opposite directions. It has been observed in various superconducting systems and attracted high research interests. However, the operating temperature of the SDE is typically low and/or the sample structure is rather complex.

Alcohol Consumption Does not Modify the Polygenic Risk Score-Based Genetic Risk of Breast Cancer in Postmenopausal Women: Atherosclerosis Risk in Communities Study.

High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study.

Quantum Griffiths Singularity in a Three-Dimensional Superconductor to Anderson Critical Insulator Transition.

Disorder is ubiquitous in real materials and can have dramatic effects on quantum phase transitions. Originating from the disorder enhanced quantum fluctuation, quantum Griffiths singularity (QGS) has been revealed as a universal phenomenon in quantum criticality of low-dimensional superconductors. However, due to the weak fluctuation effect, QGS is very challenging to detect experimentally in three-dimensional (3D) superconducting systems.

Improved angle measurement model for folded optical paths in multi-degree-of-freedom measurement systems.

Multi-degree-of-freedom (MDOF) measurement systems are crucial in the domain of precision manufacturing, where miniaturization represents a significant developmental trend. Folded optical paths are commonly employed in the angle measurement modules of these systems as a means to reduce equipment size. However, these paths introduce angle coupling, which renders traditional angle measurement models inadequate.

A Novel Protein Sourced from Chinese Medicine Residue for Golden Pompano Feed: Endothelium Corneum Gigeriae Galli Residue (ECGGR).

Fishmeal is an important protein source in aquafeed. However, due to the limited natural resources, fishmeal is in short supply, resulting in a price surge for fishmeal. Here, we reported a kind of Chinese medicine residue, endothelium corneum gigeriae galli residue (ECGGR), as a fishmeal substitute in the diets of .

Single-cell spatiotemporal analysis of the lungs reveals Slamf9 macrophages involved in viral clearance and inflammation resolution.

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages.

Anti-inflammatory effects of resveratrol in treating interstitial cystitis/bladder pain syndrome: a multi-faceted approach integrating network pharmacology, molecular docking, and experimental validation.

This study aims to investigate the anti-inflammatory effects of Resveratrol (RES) in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by integrating network pharmacology, molecular docking, and experimental validation. Potential targets of RES were identified using DrugBank and SwissTargetPrediction, while IC/BPS-related targets were obtained from DisGeNET and Genecards. Molecular docking was performed using UCSF Chimera and SwissDock to validate the binding affinity of RES to key targets.