Research progress of SHP-1 agonists as a strategy for tumor therapy.

Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP-1) is a member of protein tyrosine phosphatase (PTP) family, and serves as a crucial negative regulator of various oncogenic signaling pathways. The development of SHP-1 agonists has garnered extensive research attention and is considered as a promising strategy for treating tumors. In this review, we comprehensively analyze the advancements of SHP-1 agonists, focusing on their structures and biological activities.

A Self-Healing Transparent Waterborne Polyurethane Film with High Strength and Toughness Based on Cation-π Interactions.

Giving waterborne polyurethane (WPU) coatings self-healing properties not only maintains the coating's environmentally friendly characteristics but also extends the material's service life and enables sustainable development. Therefore, self-healing WPUs have received an increasing amount of attention from researchers. However, it is a serious challenge to overcome the original shortcomings of WPU coatings, such as poor strength, low hardness, and weak adhesion, as well as the introduction of self-healing properties resulting in further degradation of strength-mechanical properties and heat resistance.

Megabenthic Diversity Patterns on a Seamount in the Philippine Sea: Implications for Conservation Planning on the Kyushu-Palau Ridge.

The oligotrophic tropical western Pacific region is characterized by a high density of seamounts, with the Kyushu-Palau Ridge (KPR) being the longest seamount chain here. Effective spatial management plans for seamount ecosystems necessitate an understanding of distribution patterns and key environmental factors influencing benthic communities. However, knowledge regarding deep-sea biodiversity patterns over intricate topography remains limited.

Molecular characterization of a novel fusarivirus infecting the plant-pathogenic fungus Nigrospora sphaerica.

Here, we describe a novel mycovirus, tentatively designated as "Nigrospora sphaerica fusarivirus 2" (NsFV2), which was isolated from the phytopathogenic fungus Nigrospora sphaerica strain HNXX-Ns20. NsFV2 has a single-stranded positive-sense RNA (+ ssRNA) genome of 6,156 nucleotides, excluding the poly(A) tail, and contains two putative open reading frames (ORFs). ORF1 encodes a large polypeptide of 1,509 amino acids (aa) containing a conserved RNA-dependent RNA polymerase (RdRp) domain and a viral helicase domain.

METTL14 downregulates GLUT9 through m6A methylation and attenuates hyperuricemia-induced fibrosis in mouse renal tubular epithelial cells.

Hyperuricemia is a known risk factor for chronic kidney disease (CKD) and subsequent renal fibrosis. N6-methyladenosine (m6A) is the most prevalent chemical modification in eukaryotic mRNAs and has been implicated in various diseases. However, its role in hyperuricemic nephropathy (HN) remains unclear.

ALDH2 alleviates inflammation and facilitates osteogenic differentiation of periodontal ligament stem cells in periodontitis by blocking ferroptosis via activating Nrf2.

This paper elucidated the effects and mechanisms of aldehyde dehydrogenase 2 (ALDH2) on periodontitis. Rat model of periodontitis and periodontal ligament stem cell (PDLSC) model of periodontitis were constructed. PDLSC were transfected by ALDH2 overexpression vectors, and then treated by ML385 (Nrf2 inhibitor), ferrostatin-1 (ferroptosis inhibitor) and FIN56 (ferroptosis inducer), respectively.

Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.

Two-thirds of signaling hormones and one-third of approved drugs exert their effects by binding and modulating the G protein-coupled receptors (GPCRs) activation. While the activation mechanism for monomeric GPCRs has been well-established, little is known about GPCRs in dimeric form. Here, by combining transition pathway generation, extensive atomistic simulation-based Markov state models, and experimental signaling assays, we reveal an asymmetric, stepwise millisecond allosteric activation mechanism for the metabotropic glutamate receptor subtype 5 receptor (mGlu5), an obligate dimeric class C GPCR.

Controllable Design and Synthesis of Polyurethane Elastomers Containing Polar Dangling Chains with High Mechanical Properties and Wide Damping Temperature Range.

Vibration and noise severely affect the operation of mechanical equipment and is also detrimental to human health. Therefore, the development of high performance damping materials is crucial. However, current methods to improve damping properties often come at the expense of mechanical properties, resulting in inferior mechanical performance of materials.

Qigui-Yishen decoction delays renal fibrosis in mice with chronic kidney disease by regulating TM and PAI-1.

Objective: To explore the mechanism of Qigui-Yishen decoction in delaying renal fibrosis in mice by regulating thrombin regulatory protein (Thrombomodulin, TM) and plasminogen activator inhibitor-1 (PAI-1) based on network pharmacology.

Methods: The active ingredients of Qigui Yishen decoction and their target molecules associated with chronic kidney disease (CKD) were retrieved from websites and databases, sorted out, and screened, and the possible targets of Qigui Yishen decoction for reducing CKD renal fibrosis were predicted and analyzed. Forty Institute of Cancer research (ICR) rats were used to establish a unilateral ureteral obstruction (UUO) model, and divided into several groups: sham operation group, model group, high concentration decoction group (1 g/mL), low concentration decoction group (0.

Carbon Dot Nanozyme Ameliorating Ischemia-Reperfusion-Induced Muscle Injury by Antioxidation and Downregulating iNOS/COX-2 Pathway.

Skeletal muscle ischemia-reperfusion (IR) injury is a prevalent type of muscle injury caused by events, such as trauma, arterial embolism, and primary thrombosis. The development of an IR injury is associated with oxidative stress and an excessive inflammatory response. Nanozymes, which have exceptional free radical scavenging activities, have gained significant attention for treating oxidative stress.

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear.

G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.

G protein-coupled receptors (GPCRs), the largest family of human membrane proteins and an important class of drug targets, play a role in maintaining numerous physiological processes. Agonist or antagonist, orthosteric effects or allosteric effects, and biased signaling or balanced signaling, characterize the complexity of GPCR dynamic features. In this study, we first review the structural advancements, activation mechanisms, and functional diversity of GPCRs.

A subset of megakaryocytes regulates development of hematopoietic stem cell precursors.

Understanding the regulatory mechanisms facilitating hematopoietic stem cell (HSC) specification during embryogenesis is important for the generation of HSCs in vitro. Megakaryocyte emerged from the yolk sac and produce platelets, which are involved in multiple biological processes, such as preventing hemorrhage. However, whether megakaryocytes regulate HSC development in the embryonic aorta-gonad-mesonephros (AGM) region is unclear.

Autophagy regulates the maturation of hematopoietic precursors in the embryo.

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage.

A Structure-Based Allosteric Modulator Design Paradigm.

Allosteric drugs bound to topologically distal allosteric sites hold a substantial promise in modulating therapeutic targets deemed undruggable at their orthosteric sites. Traditionally, allosteric modulator discovery has predominantly relied on serendipitous high-throughput screening. Nevertheless, the landscape has undergone a transformative shift due to recent advancements in our understanding of allosteric modulation mechanisms, coupled with a significant increase in the accessibility of allosteric structural data.

Discovery of FLT3-targeting PROTACs with potent antiproliferative activity against acute myeloid leukemia cells harboring FLT3 mutations.

Acute myeloid leukemia (AML) patients harboring Fms-like tyrosine kinase 3 (FLT3) mutations often suffer from poor prognosis and relapse. Targeted protein degradation utilizing proteolysis targeting chimeras (PROTACs) is considered as a novel therapeutic strategy in drug discovery and may be a promising modality to target FLT3 mutations for the development of potent anti-AML drugs. Herein, a kind of FLT3-targeting PROTACs was rationally developed based on a FLT3 inhibitor previously reported by us.

DRD4 alleviates acute kidney injury by suppressing ISG15/NOX4 axis-associated oxidative stress.

Acute kidney injury (AKI) is a life-threatening health condition associated with increasing morbidity and mortality. Despite extensive research on the mechanisms underlying AKI, effective clinical tools for prediction and treatment remain scarce. Oxidative stress and mitochondrial damage play a critical role in AKI and dopamine D4 receptor (DRD4) has been confirmed to be associated with oxidative stress.

Deciphering the comprehensive knowledgebase landscape featuring infertility with IDDB Xtra.

Infertility affects ∼15% of couples globally and half of cases are related to genetic disorders. Despite growing data and unprecedented improvements in high-throughput sequencing technologies, accumulated fertility-related issues concerning genetic diagnosis and potential treatment are urgent to be solved. However, there is a lack of comprehensive platforms that characterise various infertility-related records to provide research applications for exploring infertility in-depth and genetic counselling of infertility couple.

RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1.

This study aimed to explore the role of miR-429 on the progression of oral squamous cell carcinoma (OSCC). OSCC cell lines were transfected with miR-429 mimic, pcDNA3.1-RUNX1, or pcDNA3.

LOX-1 regulation of H-type vascular endothelial cell regeneration in hyperglycemia.

Aims: Diabetic osteoporosis (DOP) is the most common secondary form of osteoporosis. Diabetes mellitus affects bone metabolism; however, the underlying pathophysiological mechanisms remain unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression is upregulated in conditions characterized by vascular injury, such as atherosclerosis, hypertension, and diabetes.

Platelet-derived extracellular vesicles are associated with kidney injury in patients with urosepsis.

Background: There is increasing evidence that platelet-derived extracellular vesicles (PEVs) may be involved in the mechanisms of inflammatory storm and organ damage in sepsis. However, there are no available studies on PEVs and renal injury in patients with urosepsis.

Methods: We analyzed the concentration and ratio of PEVs in plasma by flow cytometry and measured plasma IL-1β/IL-6/TNF-α/NGAL levels by ELISA.

Self-Healing Elastomers with Unprecedented Ultrahigh Strength, Superhigh Fracture Energy, Excellent Puncture Resistance, and Durability Based on Supramolecule Interlocking Networks Formed by Interlaced Hydrogen Bonds.

Due to the multiple different properties in self-healing elastomers that are mutually exclusive based on the different and contradictory molecule chain structures, simultaneously achieving the ultrahigh mechanical performance and high durability of self-healing elastomers is a great challenge and the goal that has always been pursued. Herein, we report a novel strategy to fabricate a self-healing elastomer by introducing interlaced hydrogen bonds with superhigh binding energy. Distinguishing from the quadruple hydrogen bonds reported already, the interlaced hydrogen bond with a lower repulsive secondary interaction and higher binding energy is composed of two molecule units with different lengths and steric hindrance.

Superhydrophilic and Antifriction Thin Hydrogel Formed under Mild Conditions for Medical Bare Metal Guide Wires.

Medical guide wires play a crucial role in the process of intravascular interventional therapy. However, it is essential for bare metal guide wires to possess both hydrophilic lubricity and coating durability, avoiding tissue damage caused by friction inside the blood vessel during the interventional procedure. Additionally, it is still a huge challenge for diverse metal materials to bind with polymer coatings easily.

Knockdown of LOX-1 ameliorates bone quality and generation of type H blood vessels in diabetic mice.

Our previous studies have shown that lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is expressed in liver sinusoidal endothelial cells, and oxidized low-density lipoprotein induces liver sinusoidal dysfunction and defenestration through the LOX-1/ROS/NF-kB pathway, revealing that LOX-1 can mediate liver sinusoidal barrier function, involved in the regulation of non-alcoholic fatty liver disease. Here, we investigated whether, in the context of bone metabolic diseases, LOX-1 could affect bone quality and type H blood vessels in diabetic mice. We used db/db mice as model and found that LOX-1 knockdown can ameliorate bone quality and type H blood vessel generation in db/db mice.

Intensified perfusion culture (IPC) reduced recombinant protein fragmentation.

Mammalian cells remain the mainstay of biological production host. In industry, cultivating and harvest strategies are sorted in batch mode (e.g.