Targeting the liquid-liquid phase separation of nucleocapsid broadly inhibits the replication of SARS-CoV-2 strains.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global public health crisis. The nucleocapsid (N) protein plays a pivotal role in a variety of biological processes in the life cycle of SARS-CoV-2, such as viral assembly. In this study, we investigated the liquid-liquid phase separation (LLPS) capacity of the N protein of seven SARS-CoV-2 strains, including the variants of concern (VOC) and interest (VOI), and its impact on viral replication.

High-gradient microstructured hybrid microfluidic chip for rare tumor cell capture.

Cancer remains the leading cause of death worldwide, and early detection can significantly reduce patient mortality. Circulating tumor cells (CTCs), which are tumor cells shed from the primary tumor and transported to distant sites through the bloodstream, are key biomarkers for cancer diagnosis and contain critical information reflecting the primary tumor, making them important for monitoring cancer progression. Microfluidic chips utilizing a purely physical capture technique based on the size and deformability differences between CTCs and other blood cells have proven to be effective in capturing CTCs.

Pistol Ribozyme-Driven Catalytic Spherical Nucleic Acid Integrates Gene and Chemotherapy for Enhanced Cancer Therapy.

Gene-targeted therapies are revolutionizing cancer treatment due to their high specificity and low toxicity. Among these, ribozymes hold promise as independent gene therapy agents capable of directly cleaving target mRNAs. The pistol ribozyme, discovered in 2015, stands out for its compact structure and robust cleavage activity, making it a promising candidate for RNA silencing under physiological conditions.

High-Resolution Proteomics Unveils Salivary Gland Disruption and Saliva-Hemolymph Protein Exchange in -Infected Mosquitoes.

sporozoites, the stage that initiates a malaria infection, must invade the mosquito salivary glands (SGs) before transmitting to a vertebrate host. However, the effects of sporozoite invasion on salivary gland physiology and saliva composition remain largely unexplored. We examined the impact of infection on salivary glands using high-resolution proteomics, gene expression, and morphological analysis.

Fabrication and evaluation of stationary phases with different morphology from two imidazole-based ligands for nonchiral and chiral electrochromatographic separation.

In this work, two metal-organic porous materials from the two imidazole-based ligands (4-methylimidazole-5-carbaldehyde (aImeIm) and histidine (His)) and the same metal source (Zn(CHCOO)·2HO), namely His-ZIF-93 with a crystal zeolite imidazolate framework and His/aImeIm@Zn with an amorphous networks, were first designed and synthesized by the one-pot method. They were used as the stationary phases (SPs) of open-tubular capillary electrochromatography (OT-CEC) to evaluate and compare their separation performance for the nonchiral and chiral compounds. His-ZIF-93-bonded OT-CEC column successfully separated five families of nonchiral analytes due to the synergistic effect of His and the crystal framework.

An Arbitrary-Scale Super-Resolution Network for Multi-Contrast MRI With Permuted Cross-Attention.

In magnetic resonance imaging (MRI), low-resolution (LR) images often hamper clinical diagnosis and research due to constraints in imaging conditions and technology limitations. Recent studies in super-resolution (SR) reconstruction of multi-contrast MRI have shown promise by leveraging the complementary information from different MRI contrasts. However, existing multi-contrast MRI SR techniques face several challenges: 1) a lack of pre-alignment precision can result in distorted reconstructions; 2) prevailing transformer network structures, with their smaller windows (e.

An integrated flavoromics and chemometric analysis of the characteristic flavor, chemical basis and flavor wheel of ancient plant ripened pu-erh tea.

Ripened pu-erh tea derived from sun-dried green tea leaves of ancient tea plants (APRPT) is recognized for its premium quality and unique flavor profile, yet its characteristic flavor chemistry remains insufficiently elucidated. Here, five representative APRPTs were collected and characterized by integrating flavoromics and chemometric approaches. The APRPTs exhibited a thick, reddish infusion color, a mellow taste, and a strong, long-lasting mushroom aroma.

Synergistic Anion-Cation Chemistry Enables Highly Stable Zn Metal Anodes.

Engineering aqueous electrolytes with an ionic liquid (IL) for the zinc (Zn) metal anode has been reported to enhance the electrochemical performances of the Zn metal batteries (ZMBs). Despite these advancements, the effects of IL and the mechanisms involving their anions and cations have been scarcely investigated. Here, we introduce a novel electrolyte design strategy that synergizes anion-cation chemistry using a halogen-based IL and elucidates the underlying mechanism.

Dynamic Fluorescence Imaging of Orally-administered Tumor-targeting A1-R Expressing Green Fluorescent Protein Trafficking Through the Gastrointestinal System to Target Fibrosarcomas in Nude Mice.

Background/aim: A1-R (A1-R) expresses green fluorescent protein (GFP) and has the ability to selectively target and inhibit all major cancer types in murine models without persistently infecting healthy tissue. A1-R is being developed for tumor targeting by oral administration. The aim of the present study was to demonstrate real-time imaging of orally-administered A1-R in a fibrosarcoma nude-mouse model and to visualize its trafficking through the gastrointestinal system to the tumor and normal organs.

Engineered Methioninase-expressing Tumor-targeting A1-R Inhibits Syngeneic-Cancer Mouse Models by Depleting Tumor Methionine.

Background/aim: We previously developed A1-R, which selectively targets and kills tumors. In the present study, we established recombinant methioninase (rMETase)-producing A1-R (A1-R-rMETase), by transfer of the gene, to target methionine addiction of syngeneic-cancer mouse models.

Materials And Methods: A plasmid containing the gene was extracted from METase-producing recombinant and inserted into A1-R using electroporation.

Serum insulin-like growth factor 1 and the prognosis of patients with advanced liver diseases: a meta-analysis.

Introduction: Serum insulin-like growth factor 1 (IGF-1), a hepatocyte-derived cytokine, has been suggested to reflect hepatic function reserve. The aim of this systematic review and meta-analysis was to investigate the association between serum IGF-1 levels upon the admission and prognosis of patients with advanced liver diseases.

Methods: A thorough examination of the literature was conducted across various databases, namely PubMed, Embase, Web of Science, Wanfang, and CNKI, with the aim of identifying relevant cohort studies.

Vitexin enhances mitophagy and improves renal ischemia-reperfusion injury by regulating the p38/MAPK pathway.

Vitexin (VI) is a naturally occurring flavonoid derived from the leaves and seeds of Vitex, recognized for its strong antioxidant properties. This study aims to explore its effects on renal ischemia-reperfusion injury (IRI) and investigate the underlying mechanisms. We utilized hypoxia-reoxygenation (H/R) models with HK-2 cell lines and renal ischemia-reperfusion (I/R) models in mice, applying vitexin preconditioning to assess its influence on renal IRI.

Chinese expert consensus on refined diagnosis, treatment, and management of advanced primary liver cancer (2023 edition).

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients.

Combining immune checkpoint inhibitors and molecular-targeted agents with hepatic arterial infusion chemotherapy for hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus.

Background: Hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus (HCC-IVC/RATT) has a poor prognosis and lacks evidence for standard first-line systemic therapy. This study aims to evaluate the effectiveness and safety of three therapeutic regimens in HCC-IVC/RATT: immune checkpoint inhibitors plus molecular-targeted agents (ICI-MTA), hepatic arterial infusion chemotherapy (HAIC), and their combination (ICI-MTA-HAIC).

Methods: This multicenter retrospective cohort study included consecutive HCC-IVC/RATT who received ICI-MTA-HAIC, ICI-MTA, or HAIC from June 2015 to December 2023.

Single-cell transcriptomics reveals the alteration of immune cell profile in peripheral blood of Henoch-Schonlein purpura.

Henoch-Schönlein purpura (HSP) is an autoimmune vasculitis affecting multiple organs, and the understanding of circulating immune cell types and their states associated with disease subtypes of HSP remains incomplete. Here, we performed a comprehensive assessment of peripheral blood mononuclear cells of healthy donors and HSP patients, using both single-cell RNA sequencing and multiparameter flow cytometry. We revealed that HSP patients exhibited broad immune activation, evidenced by increased proportions of Effector memory CD8+ T, CD14+ monocytes, Tfh, Th2, Th17, Plasma, and B cells and decreased proportions of Naïve CD4+ T, Treg, Th1, and NK cells.

A Long-Life Zinc-Bromine Single-Flow Battery Utilizing Trimethylsulfoxonium Bromide as Complexing Agent.

Aqueous zinc-bromine single-flow batteries (ZBSFBs) are highly promising for distributed energy storage systems due to their safety, low cost, and relatively high energy density. However, the limited operational lifespan of ZBSFBs poses a significant barrier to their large-scale commercial viability. Here, trimethylsulfoxonium bromide (TMSO), a nonquaternary ammonium salt, is introduced as a bromine complexing agent to extend the cycle life of ZBSFBs by reducing the imbalance of active substances.

Excision of HIV-1 Provirus in Human Primary Cells with Nanocapsuled TALEN Proteins.

Despite the tremendous success of combination antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV) infection, the durability and persistence of latent reservoirs of HIV-infected cells in HIV-infected patients remain obstacles to achieving HIV cure. While technically challenging, the most direct means to eradicate latent reservoirs is to destroy the HIV provirus, thus ensuring that HIV virions are not produced while preserving resident cells. Transcription activator-like effector nucleases (TALEN)─a genome editing method with high DNA targeting efficiency─have been investigated as a potential gene therapy by disrupting the HIV-1 coreceptor CCR5 genes in HIV target cells or HIV proviral DNA in infected cells.

Spatiotemporal Correlation Analysis for the Incidence of Esophageal and Gastric Cancer From 2010 to 2019: Ecological Study.

Background: Esophageal and gastric cancer were among the top 10 most common cancers worldwide. In addition, sex-specific differences were observed in the incidence. Due to their anatomic proximity, the 2 cancers have both different but also shared risk factors and epidemiological features.

The clinical frailty scale is associated with an increased risk of postoperative complications and the development of post-traumatic osteoarthritis in elderly patients with trimalleolar ankle fractures - a retrospective study.

Background: The Clinical Frailty Scale (CFS) is a tool to assess the overall health of older adults. There are few reports of CFS and prognosis of ankle fracture. The objective of this study was to determine the predictive power of the CFS for adverse clinical and radiographic outcomes after surgery in elderly patients with trimalleolar fractures.

LPCAT1, the Enzyme Responsible for Converting LPC to PC, Promotes OPC Differentiation In Vitro.

Myelin is the key structure for high-speed information transmission and is formed by oligodendrocytes (OLs) which are differentiated from oligodendrocyte precursor cells (OPCs) in the central nervous system. Lipid is the main component of myelin and the role of lipid metabolism-related molecules in myelination attach increasing attention. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) mediates the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), and its role in myelination draws our interest as LPC is a classical demyelination inducer and PC is a major component of myelin.

Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus.

Background: The small intestine harbors a rich array of intestinal intraepithelial lymphocytes (IELs) that interact with structural cells to collectively sustain gut immune homeostasis. Dysregulation of gut immune homeostasis was implicated in the pathogenesis of multiple autoimmune diseases, however, whether this homeostasis is disrupted in a lupus autoimmune background remains unclear.

Methods: We performed single-cell RNA sequencing (scRNA-seq) analyses to elucidate immune and structural milieu in the intestinal epithelium of MRL/Lpr lupus mice (Lpr mice) and MRL/Mpj control mice (Mpj mice).

AFN-Net: Adaptive Fusion Nucleus Segmentation Network Based on Multi-Level U-Net.

The task of nucleus segmentation plays an important role in medical image analysis. However, due to the challenge of detecting small targets and complex boundaries in datasets, traditional methods often fail to achieve satisfactory results. Therefore, a novel nucleus segmentation method based on the U-Net architecture is proposed to overcome this issue.

Integrated transcriptome and metabolome analysis of liver reveals unsynchronized growth mechanisms in blunt-snout bream (Megalobrama amblycephala).

Background: Megalobrama amblycephala presents unsynchronized growth, which affects its productivity and profitability. The liver is essential for substance exchange and energy metabolism, significantly influencing the growth of fish.

Results: To investigate the differential metabolites and genes governing growth, and understand the mechanism underlying their unsynchronized growth, we conducted comprehensive transcriptomic and metabolomic analyses of liver from fast-growing (FG) and slow-growing (SG) M.

Effects of Polyol Types on Underwater Curing Properties of Polyurethane.

This study aims to develop castable polyurethane suitable for applications on wet substrates or underwater construction. Polyurethanes were synthesized using various polyols with similar hydroxyl values, including poly(tetrahydrofuran) polyol, polyester polyol, castor oil-modified polyol, soybean oil-modified polyol, and cashew nut shell oil-modified polyol. The corresponding polyurethane curing products were evaluated for their underwater curing characteristics by volume expansion ratios and adhesion strength on dry and wet substrates, combined with analyses of reaction exothermic behavior, wetting properties on dry and wet substrates, interfacial tension, and microstructure characterization from the perspectives of reaction activity and water solubility.