Reactive oxygen species-responsive virus-mimicking nanodrug for the treatment of influenza A virus infection.

Drug therapy is an important measure to reduce the morbidity and mortality of influenza. However, small molecule drugs have inherent limitations, such as poor water solubility, non-specific biological distribution, and susceptibility to degradation during blood circulation, which impose a great burden on patients, both physically and mentally. Inspired by the high levels of reactive oxygen species (ROS) at the site of influenza A virus (IAV) infection, we have developed an intelligent responsive virus-mimicking nanodrug (Zana@HA-Lip) based on a biomimetic approach, reduces the damage of the drug to normal tissues or organs while achieving the purpose of antiviral therapy by precisely releasing the drug at the lesion site.

sp. BI87 from human gut: potent anticancer activities and divergence from known lineages.

Cancer is among the deadliest diseases with few truly curative therapies. Recent studies have shown that the human intestinal microbiota contains bacteria that exhibit potent suppressive effects on cancer or coordinate anticancer functions with the immune system. However, whether the peculiar anticancer trait was acquired stochastically by a strain of a non-anticancer bacterial species or an intrinsic property of a phylogenetic lineage of bacteria remained unclear.

Machine Learning-Enhanced Single-Particle Tracking for Rapid Screening of Tumor Immunomodulatory Drugs.

The tumor microenvironment plays a critical role in tumor progression and immune response, with the extracellular matrix (ECM) regulating immune cell infiltration. However, the interplay between ECM dynamics and tumor immunity remains poorly understood, and current methods for evaluating immunomodulatory drugs are limited by scalability and cost. Here, we present a robust approach combining single-particle tracking (SPT) of quantum dots (QDs) with machine learning to characterize the extracellular space (ECS) in live tumor tissues and assess drug efficacy.

Revealing the Correlation between Structural Evolution and Reversible Phase Transition of Single-Crystalline Ni-Rich Cathode.

Single-crystal nickel-rich cathodes are widely used in electric vehicles. However, the irreversible phase transition of H2-H3 during cycling leads to severe lattice distortion and disruption of the crystal structure, which seriously hinders their practical application. Herein, we formed an atomic rearrangement structure with a superlattice phenomenon on the surface of the material by lattice engineering to achieve the reversible phase transition of H2-H3 and obtained structurally stable cathode materials.

Multi-level inhibition of SARS-CoV-2 invasion by cannabidiol and epigallocatechin gallate.

The global pandemic coronavirus disease 2019 (COVID-19) attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study aimed at combination therapies with natural polyphenolic compounds, such as cannabidiol (CBD), green tea polyphenols (Tea-poly), epigallocatechin gallate (EGCG) and theaflavin (TF), to investigate in vitro their inhibitory effects on virus invasion and viral spike (S) protein expression. Among the compounds tested, CBD and Tea-poly exhibited the most significant inhibitory effects on virus entry, comparable to the positive control chloroquine (CQ).

Efficient Artificial T Cell Therapy for Bacterial-Colonized Tumors.

Tumor-colonizing bacteria can impede the efficacy of cancer treatments and elevate the risk of metastatic spread. While cytotoxic T lymphocytes (CTLs) are essential for destroying tumor cells, they lack the ability to eliminate bacteria. Here, the artificial T cells (ATC) are presented for tumors, particularly those colonized with intracellular bacteria.

Genetic detection of a novel pathogenic variant in patients with early-onset severe retinal dystrophy.

Purpose: Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are genetic disorders affecting the retina, causing significant visual impairment from early childhood. Although over 26 genes have been implicated in EOSRD, the genetic basis remains incompletely characterized in a subset of cases. Our study aims to understand the mutational spectrum of LRAT-related EOSRD in an autosomal recessive family.

An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters.

Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subunit immunogens with a human IgG Fc backbone can be used as a mucosal vaccine but its effectiveness in delivery in animal models, and its immunogenicity and the vaccine-induced protection against viral infections requires further studies. Here we investigate a bivalent RBD-Fc vaccine that includes the spike receptor-binding domains (RBDs) of the ancestral and BQ.

Apoptotic Cell-Mimicking Nanocarriers Enhance Splenic Red Pulp Delivery through Lipid Pool Modulation.

Spleen-targeted nanovaccines hold promise for enhancing immune responses and protective effect, yet their effectiveness is hindered by challenges such as inevitable liver retention, limited speed of immune activation, and poor biocompatibility. Natural lipids typically possess excellent biocompatibility, allowing for favorable interactions with cells and tissues in the body, thereby reducing immune responses and toxicity. In this study, we proposed a selective spleen-targeting strategy for custom designing the nanocarriers utilizing the biomimetic concept of apoptotic cell membranes and natural lipid pool modulation.

Ratiometric Dual-Response Quantum Dot Spherical Nucleic Acid for Monitoring Viral Secondary Bacterial Infections.

Viral-bacterial coinfections present intricate pathologies that exacerbate disease progression and elevate mortality rates. Understanding the dynamic interplay between viruses and bacteria during coinfection is critical for developing effective therapeutic interventions. However, current diagnostic tools primarily rely on static detection methods, limiting their ability to monitor real-time infection dynamics.

The combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity.

Background: Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed to investigate the inhibitory effects of flaxseed lignans (FL) on the biological behaviors of BC and evaluate the roles of FL in enhancing the anticancer effects of PDi.

Methods: HPLC was used to detect the content of enterolactone (ENL), the bacterial transformation product of FL.

Scalable production and purification of engineered ARRDC1-mediated microvesicles in a HEK293 suspension cell system.

Engineering of human ARRDC1-mediated microvesicles (ARMMs) as non-viral vehicles for delivery of gene therapies bears the potential to enable novel therapeutic paradigms. We evaluated two scalable strategies to generate ARMMs loaded with protein cargo, by transient transfection or stable cell line-based production. The upstream ARMMs production processes utilized a suspension-adapted HEK293-derived line, termed 5B8.

Targeted Degradation of ZBP1 with Covalent PROTACs for Anti-Inflammatory Treatment of Infections.

Z-DNA binding protein 1 (ZBP1) has emerged as a critical pathogen-sensing protein that upon activation, triggers necroptotic signaling cascades, leading to a potent inflammatory response and potentially causing significant tissue damage. However, available drugs specifically developed for the effective inhibition or degradation of ZBP1 is still lacking so far. In this study, we developed a potent covalent recognition-based PROTAC (C-PROTAC) molecule for the degradation of ZBP1.

Dual Pathways of Photorelease Carbon Monoxide via Photosensitization for Tumor Treatment.

Carbon monoxide (CO) gas therapy, as an emerging therapeutic strategy, is promising in tumor treatment. However, the development of a red or near-infrared light-driven efficient CO release strategy is still challenging due to the limited physicochemical characteristics of the photoactivated carbon monoxide-releasing molecules (photoCORMs). Here, we discovered a novel photorelease CO mechanism that involved dual pathways of CO release via photosensitization.

Enterolactone combined with m6A Reader IGF2BP3 inhibits malignant angiogenesis and disease progression in ovarian cancer.

Background: Among all gynecological cancers, ovarian cancer is the leading cause of death. Epithelial ovarian cancer (EOC) accounts for over 85 % of ovarian cancer cases and is characterized by insidious onset, early metastasis, and a high recurrence rate. Alterations in gut microbiota, often as a consequence of chemotherapy, can promote cancer development and exacerbate the disease.

Rapid Deployment of Antiviral Drugs Using Single-Virus Tracking and Machine Learning.

The outbreak of emerging acute viral diseases urgently requires the acceleration of specialized antiviral drug development, thus widely adopting phenotypic screening as a strategy for drug repurposing in antiviral research. However, traditional phenotypic screening methods typically require several days of experimental cycles and lack visual confirmation of a drug's ability to inhibit viral infection. Here, we report a robust method that utilizes quantum-dot-based single-virus tracking and machine learning to generate unique single-virus infection fingerprint data from viral trajectories and detect the dynamic changes in viral movement following drug administration.

Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion.

Aim: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment.

Methods: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT).

An Inhalable Nanoshield for Effective Prevention of Influenza Virus Infections.

Influenza virus (IV) infection currently poses a serious and continuing threat to the global public health. Developing effective prevention strategies is important to defend against infection and spread of IV. Here, we developed a triple-protective nanoshield against IV infection in the lungs, formed by self-assembling DSPE-PEG amphiphilic polymers encapsulating the flu-preventive antiviral drug Arbidol internally.

Quantitatively Dissecting Triple Roles of Dynactin in Dynein-Driven Transport of Influenza Virus by Quantum Dot-Based Single-Virus Tracking.

After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected using quantum dot-based single-virus tracking.

Revealing Different Pathways for Influenza A Virus To Reach Microtubules after Endocytosis by Quantum Dot-Based Single-Virus Tracking.

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous.