Conditional Activation of Protein Therapeutics by Templated Removal of Peptide Nucleic Acid Masking Groups.

Interleukin-2 (IL-2)-based therapeutics are emerging as treatments for immunotherapy; however, systemic activation of immune cells hampers their success. Chemically controlling the activity of potent cytokines could mitigate unwanted T cell stimulation and widen their therapeutic window. In this study, we developed a strategy for the conditional activation of proteins utilizing removable peptide nucleic acid (PNA) masking groups.

A recombinant protein vaccine induces protective immunity against SARS-CoV-2 JN.1 and XBB-lineage subvariants.

The emergence of XBB- and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations. In addition, the unfavorable impacts of immune imprinting, stemming from continuous exposure to antigens from circulated viruses, have been observed to incline immune response against earlier lineages, thereby declining the neutralization to newly emerged Omicron subvariants.

Clinical and omics biomarkers in osteoarthritis diagnosis and treatment.

Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts the quality of life for hundreds of millions, and is a major cause of disability. Despite this, diagnostic and therapeutic options for OA are still limited. With advances in molecular biology, an increasing number of OA biomarkers have been identified, which not only enhances our understanding of OA pathogenesis, but also offers new approaches for OA diagnosis and treatment.

Prevalence and Prognostic Significance of Sarcopenia in Gynecologic Oncology: A Systematic Review and Meta-Analysis.

Background: Sarcopenia in gynaecologic oncology patients has garnered increasing attention, but its prevalence has not been comprehensively summarized. This study aims to integrate the prevalence of sarcopenia in this population through systematic evaluation and meta-analysis, providing a reference for future clinical research.

Methods: A computerized search of PubMed, Embase, The Cochrane Library, Web of Science and other databases was conducted to collect relevant literature on the prevalence of sarcopenia in gynaecologic oncology patients and its impact on prognosis, with a timeframe from the inception of the databases to July 2024.

mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice.

The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In this study, we designed new mRNA vaccines, BSCoV05 and BSCoV06, and generated point mutations in the receptor-binding domain (RBD) of the original Wuhan strain to increase their broad-spectrum antiviral activity.

Multiorgan proteomic analysis of infected animal models predict potential host factors for chikungunya virus.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is primarily known for causing severe joint and muscle symptoms, but its pathological effects have extended beyond these tissues. In this study, we conducted a comprehensive proteomic analysis across various organs in rodent and nonhuman primate models to investigate CHIKV's impact on organs beyond joints and muscles and to identify key host factors involved in its pathogenesis. Our findings reveal significant species-specific similarities and differences in immune responses and metabolic regulation, with proteins like Interferon-Stimulated Gene 15 (ISG15) and Retinoic Acid-Inducible Gene I (RIG-I) playing crucial roles in the anti-CHIKV defense.

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials.

The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.

A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2.

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants.

Surfactant-modified zein nanoparticles adsorbents for ultrafast and efficient removal of Cr(VI).

The adsorption and removal of heavy metal ions Cr(VI) is of great significance for human health and ecological environment. Here, an ultrafast and high efficient adsorbent for Cr(VI) was developed based on cetyltrimethylammonium bromide (CTAB)-modified zein nanoparticles (C-ZNPs). In comparison to pristine zein nanoparticles (ZNPs) (11.

Combination therapy of dexamethasone, rituximab, and cyclosporine for adults with primary immune thrombocytopenia: a prospective observational study.

Background: To assess the effectiveness of the combination of dexamethasone, rituximab, and cyclosporine in treating adults with primary immune thrombocytopenia (ITP).

Research Design And Methods: This prospective study enrolled consecutive adult patients diagnosed with ITP at the 967th Hospital of the Chinese People's Liberation Army Joint Service Support Force Hospital between November 2019 and February 2023.

Results: Twenty-eight patients (13 males, median age 43.

Liquid biopsy for early cancer detection: technological revolutions and clinical dilemma.

Introduction: Liquid biopsy is an innovative advancement in oncology, offering a noninvasive method for early cancer detection and monitoring by analyzing circulating tumor cells, DNA, RNA, and other biomarkers in bodily fluids. This technique has the potential to revolutionize precision oncology by providing real-time analysis of tumor dynamics, enabling early detection, monitoring treatment responses, and tailoring personalized therapies based on the molecular profiles of individual patients.

Areas Covered: In this review, the authors discuss current methodologies, technological challenges, and clinical applications of liquid biopsy.

Designed endocytosis-inducing proteins degrade targets and amplify signals.

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras (LYTACs) and cytokine receptor-targeting chimeras (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor.

CHIKV infection drives shifts in the gastrointestinal microbiome and metabolites in rhesus monkeys.

Background: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis.

Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis.

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis.

Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes.

The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection.

An efficient ratiometric fluorescence and colorimetric dual-mode probe for convenient determination of nitrite in real samples and .

Developing an effective and convenient nitrite detection method is indispensable in food safety, environmental monitoring, clinical diagnosis of diseases, and many other areas. Herein, a dicyanoisophorone derivative, TMN-NH2 with large Stokes shift and near-infrared (NIR) emission, was proposed as a ratiometric fluorescence and colorimetric dual-mode probe for the rapid determination of NO in acidic media, showing excellent selectivity and high sensitivity. The sensing mechanism is based on the diazotization of TMN-NH2 with NO and subsequent diazonium salt hydrolysis to form a hydroxyl-substituted product (TMN-OH).

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time.

Zona Glomerulosa-Derived Klotho Modulates Aldosterone Synthase Expression in Young Female Mice.

Klotho plays a critical role in the regulation of ion and fluid homeostasis. A previous study reported that haplo-insufficiency of Klotho in mice results in increased aldosterone synthase (CYP11B2) expression, elevated plasma aldosterone, and high blood pressure. This phenotype was presumed to be the result of diminished Klotho expression in zona glomerulosa (zG) cells of the adrenal cortex; however, systemic effects on adrenal aldosterone production could not be ruled out.

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys.

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants.

Multifunctional nanoparticles for enhanced sonodynamic-chemodynamic immunotherapy with glutathione depletion.

This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling.