Routes to molecular glue degrader discovery.

Molecular glue degraders (MGDs) represent a unique class of targeted protein degradation (TPD) modalities. By facilitating protein-protein interactions between E3 ubiquitin ligases and neo-substrates, MGDs offer a novel approach to target previously undruggable or insufficiently drugged disease-causing proteins. Here, we present an overview of recently reported MGDs, highlighting their diverse mechanisms, and we discuss mechanism-based strategies to discover new MGDs and neo-substrates.

The Bidirectional Association Between Metabolic Syndrome and Long-COVID-19.

Background: The rapid global spread of a new coronavirus disease known as COVID-19 has led to a significant increase in mortality rates, resulting in an unprecedented worldwide pandemic.

Methods: The impact of COVID-19, particularly its long-term effects, has also had a profound effect on the health and well-being of individuals.Metabolic syndrome increases the risk of heart and brain diseases, presenting a significant danger to human well-being.

The Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists as Novel Diabetes Drugs Are Mediated via the Suppression of miR-203a-3p and miR-429 Expression.

Coronary artery disease (CAD) is associated with a high fatality rate and a heavy global health care burden. Glucagon-like peptide-1 (GLP-1) exerts positive cardiovascular effects, although the molecular mechanisms are unclear. Therefore, this study aimed to verify whether the cardioprotective effects of GLP-1 are mediated through the regulation of micro-RNA (miRNA) expression.

mtROS-mediated mitophagy is involved in aflatoxin-B induced liver injury in ducks.

Aflatoxin B (AFB) is highly toxic to the liver and can cause excessive production of mitochondrial reactive oxygen species (mtROS) in hepatocytes, leading to oxidative stress, inflammation, fibrosis, cirrhosis, and even liver cancer. The overproduction of mtROS can induce mitophagy, but whether mtROS and mitophagy are involved in the liver injury induced by AFB in ducks remains unclear. In this study, we first demonstrated that overproduction of mtROS and mitophagy occurred during liver injury induced by AFB exposure in ducks.

PD-1-CD28-enhanced receptor and CD19 CAR-modified tumor-infiltrating T lymphocytes produce potential anti-tumor ability in solid tumors.

The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter "PD-1-CD28-TCR-T" or "CD19 CAR-TCR-T" cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model.

USP20 deubiquitinates and stabilizes the reticulophagy receptor RETREG1/FAM134B to drive reticulophagy.

The endoplasmic reticulum (ER) serves as a hub for various cellular processes, and maintaining ER homeostasis is essential for cell function. Reticulophagy is a selective process that removes impaired ER subdomains through autophagy-mediatedlysosomal degradation. While the involvement of ubiquitination in autophagy regulation is well-established, its role in reticulophagy remains unclear.

Peste des petits ruminants virus infection induces endoplasmic reticulum stress and apoptosis via IRE1-XBP1 and IRE1-JNK signaling pathways.

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial.

Correlation Between Thyroid-Related Hormones and Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients with Normal Thyroid Function: A Retrospective Study.

Purpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).

Patients And Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred.

Single [0001]-oriented zinc metal anode enables sustainable zinc batteries.

The optimization of crystalline orientation of a Zn metal substrate to expose more Zn(0002) planes has been recognized as an effective strategy in pursuit of highly reversible Zn metal anodes. However, the lattice mismatch between substrate and overgrowth crystals has hampered the epitaxial sustainability of Zn metal. Herein, we discover that the presence of crystal grains deviating from [0001] orientation within a Zn(0002) metal anode leads to the failure of epitaxial mechanism.

Ribavirin inhibits peste des petits ruminants virus proliferation .

Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates.

Zinc Transporters Serve as Prognostic Predictors and their Expression Correlates with Immune Cell Infiltration in Specific Cancer: A Pan-cancer Analysis.

The disruption of zinc (Zn) homeostasis has been implicated in cancer development and progression through various signaling pathways. Maintaining intracellular zinc balance is crucial in the context of cancer. Human cells rely on two families of transmembrane transporters, SLC30A/ZNT and SLC39A/ZIP, to coordinate zinc homeostasis.

Diosbulbin C, a novel active ingredient in Dioscorea bulbifera L. extract, inhibits lung cancer cell proliferation by inducing G0/G1 phase cell cycle arrest.

Background: Despite the critical progress of non-small cell lung cancer (NSCLC) therapeutic approaches, the clinical outcomes remain considerably poor. The requirement of developing novel therapeutic interventions is still urgent. In this study, we showed for the first time that diosbulbin C, a natural diterpene lactone component extracted from traditional Chinese medicine Dioscorea bulbifera L.

Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle.

Stress granules (SGs) are dynamic, membrane-less organelles. With their formation and disassembly processes characterized, it remains elusive how compositional transitions are coordinated during prolonged stress to meet changing functional needs. Here, using time-resolved proteomic profiling of the acute to prolonged heat-shock SG life cycle, we identify dynamic SG proteins, further segregated into early and late proteins.

Mini PROTACs: N-end rule-mediated degradation on the horizon.

Heterobifunctional proteolysis-targeting chimeras (PROTACs) offer a promising cancer treatment avenue by efficiently degrading unwanted cellular proteins. A recent study from Zhang et al. demonstrated the successful utilization of the N-end rule in PROTAC design, allowing for a modular degradation rate tailored to the oncogenic driver BCR-ABL.

Assessment of degradability and endothelialization of modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluders over time in vivo.

Objective: To evaluate the fiber-degradation and endothelialization of a modified poly L-lactic acid (PLLA) atrial septal defect (ASD) occluder for a long time in vivo.

Methods: A total of 57 New Zealand rabbits were selected to establish the vasculature implantation model, which would be used to characterize the mechanical properties and pathological reaction of PLLA filaments (a raw polymer of ASD occluder). In total, 27 Experimental piglets were used to create the ASD model for the catheter implantation of PLLA ASD occluders.

Post-translational modifications in stress granule and their implications in neurodegenerative diseases.

Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics.

Metagenomic next-generation sequencing for rapid detection of pulmonary infection in patients with acquired immunodeficiency syndrome.

Background: Acquired immunodeficiency syndrome (AIDS) is associated with a high rate of pulmonary infections (bacteria, fungi, and viruses). To overcome the low sensitivity and long turnaround time of traditional laboratory-based diagnostic strategies, we adopted metagenomic next-generation sequencing (mNGS) technology to identify and classify pathogens.

Results: This study enrolled 75 patients with AIDS and suspected pulmonary infections who were admitted to Nanning Fourth People's Hospital.

Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.

Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet.

The interconnection of endoplasmic reticulum and microtubule and its implication in Hereditary Spastic Paraplegia.

The endoplasmic reticulum (ER) and microtubule (MT) network form extensive contact with each other and their interconnection plays a pivotal role in ER maintenance and distribution as well as MT stability. The ER participates in a variety of biological processes including protein folding and processing, lipid biosynthesis, and Ca storage. MTs specifically regulate cellular architecture, provide routes for transport of molecules or organelles, and mediate signaling events.

Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules.

Eukaryotic stress granules (SGs) are highly dynamic assemblies of untranslated mRNAs and proteins that form through liquid-liquid phase separation (LLPS) under cellular stress. SG formation and elimination process is a conserved cellular strategy to promote cell survival, although the precise regulation of this process is poorly understood. Here, we screened six E3 ubiquitin ligases present in SGs and identified TRIM21 (tripartite motif containing 21) as a central regulator of SG homeostasis that is highly enriched in SGs of cells under arsenite-induced oxidative stress.

What Ratio of Warmth to Competence Is Ideal for Likable Friends?

The current study aimed to test the perceivers' ratings of likability and their willingness to become friends with targets who have different ratios of warmth to competence. In Study 1, we recruited 106 females and 61 males. The results of Study 1 showed that perceivers were reluctant to become friends with targets that had extreme ratios of warmth to competence (0:5 or 5:0).

The Role and Therapeutic Potential of Macropinocytosis in Cancer.

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis.

Intelligent fault diagnosis of helical gearboxes with compressive sensing based non-contact measurements.

Helical gearboxes play a critical role in power transmission of industrial applications. They are vulnerable to various faults due to long-term and heavy-duty operating conditions. To improve the safety and reliability of helical gearboxes, it is necessary to monitor their health conditions and diagnose various types of faults.

Enhanced removal of diclofenac via coupling Pd catalytic and microbial processes in a H-based membrane biofilm reactor: Performance, mechanism and biofilm microbial ecology.

Diclofenac (DCF) is a most widely used anti-inflammatory drug, which has attracted worldwide attention given its low biodegradability and ecological damage, especially toxic effects on mammals including humans. In this study, a H-based membrane biofilm reactor (H-MBfR) was constructed with well-dispersed Pd nanoparticles generated in situ. The Pd-MBfR was applied for catalytic reductive dechlorination of DCF.