Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy.

Tofacitinib (Tof), a commercially available pan-Janus kinases inhibitor, is approved for the treatment of moderate to severe ulcerative colitis. However, its clinical application is limited due to dose-dependent systemic side effects. The present study aims to develop an efficient oral colon-targeted drug delivery systems using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a shell, with Tof loaded into a Bovine Serum Albumin (BSA) core, and improving it with chondroitin sulfate (Chs), thus constructing Tof@BSA-Chs-CP nanoparticles (NPs).

Significance of radiation therapy in frontal glioblastoma patients and exploration of optimal treatment modality: a real-world multiple-center study based on propensity score matching.

Background: Glioblastoma (GBM) exhibits diffuse and invasive growth patterns, with a 5-year overall survival (OS) rate of 5-10%. In addition, approximately 40 percent of GBMs are localized in the frontal lobe, a region closely linked to essential life functions including cognition, so that it cannot be completely eradicated through surgical intervention, leading to very poor prognosis. Postoperative therapy is an essential treatment modality.

The therapeutic effect and possible mechanisms of alginate oligosaccharide on metabolic syndrome by regulating gut microbiota.

Metabolic syndrome (MetS) is a disease condition incorporating the abnormal accumulation of various metabolic components, including overweight or abdominal obesity, insulin resistance and abnormal glucose tolerance, hypertension, atherosclerosis, or dyslipidemia. It has been proved that the gut microbiota and microbial-derived products play an important role in regulating lipid metabolism and thus the onset and development of MetS. Previous studies have demonstrated that oligosaccharides with prebiotic effects, such as chitosan oligosaccharides, can regulate the structure of the microbial community and its derived products to control weight and reduce MetS associated with obesity.

Biportal Endoscopic Paraspinal Decompression for Epidural Cement Leakage Removal: A Technical Note.

Objective: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression.

Methods: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy.

High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation.

Capturing Protein-Protein Interactions with Acidic Amino Acids Reactive Cross-Linkers.

Acidic residues (Asp and Glu) have a high prevalence on protein surfaces, but cross-linking reactions targeting these residues are limited. Existing methods either require high-concentration coupling reagents or have low structural compatibility. Here a previously reported "plant-and-cast" strategy is extended to develop heterobifunctional cross-linkers.

MAVS deSUMOylation by SENP1 inhibits its aggregation and antagonizes IRF3 activation.

Mitochondrial antiviral signaling protein (MAVS) is an adapter that recruits and activates IRF3. However, the mechanisms underpinning the interplay between MAVS and IRF3 are largely unknown. Here we show that small ubiquitin-like modifier (SUMO)-specific protease 1 negatively regulates antiviral immunity by deSUMOylating MAVS.

LPA maintains innate antiviral immunity in a pro-active state via STK38L-mediated IRF3 Ser303 phosphorylation.

Innate immunity is critical for the early detection and elimination of viral invasion. Extracellular signals are crucial for host resistance; however, how extracellular factors prepare the innate immunity for rapid antiviral response remains elusive. Here, we find that serum deprivation largely restricts the innate antiviral responses to RNA and DNA viruses.

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC.

Background: CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC.

Methods: Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design.

Deactylation by SIRT1 enables liquid-liquid phase separation of IRF3/IRF7 in innate antiviral immunity.

Innate antiviral immunity deteriorates with aging but how this occurs is not entirely clear. Here we identified SIRT1-mediated DNA-binding domain (DBD) deacetylation as a critical step for IRF3/7 activation that is inhibited during aging. Viral-stimulated IRF3 underwent liquid-liquid phase separation (LLPS) with interferon (IFN)-stimulated response element DNA and compartmentalized IRF7 in the nucleus, thereby stimulating type I IFN (IFN-I) expression.

Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions.

The global coronavirus disease 2019 (COVID-19) pandemic is currently ongoing. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high proportion of COVID-19 patients exhibit gastrointestinal manifestations such as diarrhea, nausea, or vomiting.

The way of SARS-CoV-2 vaccine development: success and challenges.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). To halt the pandemic, multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide. With novel SARS-CoV-2 variants emerging and circulating widely, whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.

Liquid-liquid phase separation in human health and diseases.

Emerging evidence suggests that liquid-liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions.

Targeting liquid-liquid phase separation of SARS-CoV-2 nucleocapsid protein promotes innate antiviral immunity by elevating MAVS activity.

Patients with Coronavirus disease 2019 exhibit low expression of interferon-stimulated genes, contributing to a limited antiviral response. Uncovering the underlying mechanism of innate immune suppression and rescuing the innate antiviral response remain urgent issues in the current pandemic. Here we identified that the dimerization domain of the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is required for SARS2-NP to undergo liquid-liquid phase separation with RNA, which inhibits Lys63-linked poly-ubiquitination and aggregation of MAVS and thereby suppresses the innate antiviral immune response.

Protein N-myristoylation: functions and mechanisms in control of innate immunity.

Protein N-myristoylation is an important fatty acylation catalyzed by N-myristoyltransferases (NMTs), which are ubiquitous enzymes in eukaryotes. Specifically, attachment of a myristoyl group is vital for proteins participating in various biological functions, including signal transduction, cellular localization, and oncogenesis. Recent studies have revealed unexpected mechanisms indicating that protein N-myristoylation is involved in host defense against microbial and viral infections.

A Dual Role of Type I Interferons in Antitumor Immunity.

Type I interferons (IFN-Is) are a family of cytokines that exert direct antiviral effects and regulate innate and adaptive immune responses through direct and indirect mechanisms. It is generally believed that IFN-Is repress tumor development via restricting tumor proliferation and inducing antitumor immune responses. However, recent emerging evidence suggests that IFN-Is play a dual role in antitumor immunity.

A systematic review of SARS-CoV-2 vaccine candidates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials.

Coronavirus in Continuous Flux: From SARS-CoV to SARS-CoV-2.

The world is currently experiencing a global pandemic caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory disease similar to SARS. Previous studies have suggested that SARS-CoV-2 shares 79% and 96% sequence identity to SARS-CoV and to bat coronavirus RaTG13, respectively, at the whole-genome level. Furthermore, a series of studies have shown that SARS-CoV-2 induces clusters of severe respiratory illnesses (i.

The interactions between cGAS-STING pathway and pathogens.

Cytosolic DNA is an indicator of pathogen invasion or DNA damage. The cytosolic DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) detects DNA and then mediates downstream immune responses through the molecule stimulator of interferon genes (STING, also known as MITA, MPYS, ERIS and TMEM173). Recent studies focusing on the roles of the cGAS-STING pathway in evolutionary distant species have partly sketched how the mammalian cGAS-STING pathways are shaped and have revealed its evolutionarily conserved mechanism in combating pathogens.

Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164.

Purpose: KEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC).

Methods: This phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti-vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B).

Effects of copper treatment on mineral nutrient absorption and cell ultrastructure of spinach seedlings.

The accumulation of heavy metals in soil has serious influence on plant growth and ecosystem balance. It is of great importance to explore the mechanism of plant tolerance to heavy me-tals. Although spinach is supposed to have strong Cu tolerance, the effects of Cu on mineral element absorption and cell ultrastructure are still unclear.

FAF1 Regulates Antiviral Immunity by Inhibiting MAVS but Is Antagonized by Phosphorylation upon Viral Infection.

Mitochondrial antiviral signaling protein (MAVS) is an adaptor of the innate immune receptor retinoic acid-inducible gene 1 (RIG-I) that links recognition of viral RNA to antiviral signaling. Upon interacting with RIG-I, MAVS undergoes lysine 63-linked poly-ubiquitination by the E3 ligase TRIM31 and subsequently aggregates to activate downstream signaling effectors. We find that the scaffold protein FAF1 forms aggregates that negatively regulate MAVS.

Low molecular weight heparin versus rivaroxaban in the treatment of venous thromboembolism in gastrointestinal malignancies.

: Due to their ease of use, the direct oral anticoagulants (DOACs) are an attractive treatment option for cancer-associated venous thromboembolism (VTE) and have been readily adopted by many clinicians. A recent published study comparing a DOAC (edoxaban) to the current standard-of-care low molecular weight heparin dalteparin for the treatment of cancer-associated thrombosis showed that edoxaban was noninferior to dalteparin for recurrent VTE, but the risk of major bleeding was higher. We present three patients with high-risk gastrointestinal malignancies complicated by cancer-associated VTE with progression of thrombosis while treated with the oral direct Xa inhibitor rivaroxaban.

Tumor-derived exosomes antagonize innate antiviral immunity.

Malignancies can compromise innate immunity, but the mechanisms of this are largely unknown. Here we found that, via tumor-derived exosomes (TEXs), cancers were able to transfer activated epidermal growth factor receptor (EGFR) to host macrophages and thereby suppress innate antiviral immunity. Screening of the human kinome identified the kinase MEKK2 in macrophages as an effector of TEX-delivered EGFR that negatively regulated the antiviral immune response.