IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers.

The Ubiquitin Ligase CHIP Accelerates Papillary Thyroid Carcinoma Metastasis via the Transgelin-Matrix Metalloproteinase-9 Axis.

The carboxyl-terminus of Hsp70-interacting protein (CHIP) plays crucial roles in tumorigenesis and immunity, with previous studies suggesting a double-edged sword in thyroid cancer. However, its precise functions and underlying molecular mechanisms in thyroid cancer remained unclear. Here, we demonstrate through immunohistochemistry (IHC) that CHIP expression progressively increases from normal thyroid tissue to primary papillary thyroid carcinoma (PTC) and lymph node metastases, with CHIP levels positively correlating with lymph node metastasis ( = 0.

Induction of M1 polarization in BV2 cells by propofol intervention promotes perioperative neurocognitive disorders through the NGF/CREB signaling pathway: an experimental research.

Nerve growth factor (NGF) is critical in regulating the homeostasis of microglial cells. It activates various signaling pathways that mediate the phosphorylation of cAMP response element-binding protein (CREB) at key regulatory sites. The decrease in phosphorylated CREB (p-CREB) expression is linked to neuroinflammatory responses.

HER2 regulates autophagy and promotes migration in gastric cancer cells through the cGAS-STING pathway.

In gastric cancer, the relationship between human epidermal growth factor receptor 2 (HER2), the cyclic GMP-AMP synthase-stimulator of the interferon genes (cGAS-STING) pathway, and autophagy remains unclear. This study examines whether HER2 regulates autophagy in gastric cancer cells via the cGAS-STING signaling pathway, influencing key processes such as cell proliferation and migration. Understanding this relationship could uncover new molecular targets for diagnosis and treatment.

Exploration of the Combined Mechanism of Direct and Indirect Effects of Paeoniflorin in the Treatment of Cholestasis.

Cholestasis is a multifactorial hepatobiliary disorder, characterized by obstruction of bile flow and accumulation of bile, which in turn causes damage to liver cells and other tissues. In severe cases, it can result in the development of life-threatening conditions, including cirrhosis and liver cancer. Paeoniflorin (PF) has been demonstrated to possess favourable therapeutic potential for the treatment of cholestasis.

TBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis.

TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells.

Structure-Guided Optimization and Preclinical Evaluation of 6--Benzylguanine-Based Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of motivated us to find improved Pin1 inhibitors.

Development of a replication competent murine norovirus reporter system.

Unlabelled: Caliciviruses are significant agricultural and human pathogens that are poorly understood due to the dearth of molecular tools, including reporter systems. We report the development of a stable, faithful, and robust luciferase-based reporter system for a model calicivirus, murine norovirus (MNoV). Genetic insertion of a HiBiT tag, an 11 amino acid fragment of nanolucifersase, at the junction of the nonstructural proteins NS4 and NS5 yields infectious virus.

Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.

OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on the surface of activated T cells. Upon interaction with its cognate ligand, OX40L, OX40 transmits costimulatory signals to antigen-primed T cells, promoting their activation, differentiation, and survivalprocesses essential for the establishment of adaptive immunity. Although the OX40-OX40L interaction has been extensively studied in the context of disease treatment, developing a substitute for the naturally expressed membrane-bound OX40L, particularly a multimerized OX40L trimers, that effectively regulates OX40-driven T cell responses remains a significant challenge.

Loss of increases type I interferon signalling and reduces pancreatic tumour growth by enhancing immune cell infiltration.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and despite low incidence rates, it remains the sixth leading cause of cancer related deaths worldwide. Immunotherapy, which aims to enhance the immune system's ability to recognize and eliminate cancer cells, has emerged as a promising approach in the battle against PDAC. PARP7, a mono-ADP-ribosyltransferase, is a negative regulator of the type I interferon (IFN-I) pathway and has been reported to reduce anti-tumour immunity.

Active Ingredients and Potential Mechanism of Additive Sishen Decoction in Treating Rheumatoid Arthritis with Network Pharmacology and Molecular Dynamics Simulation and Experimental Verification.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which macrophages produce cytokines that enhance inflammation and contribute to the destruction of cartilage and bone. Additive Sishen decoction (ASSD) is a widely used traditional Chinese medicine for the treatment of RA; however, its active ingredients and the mechanism of its therapeutic effects remain unclear.

Methods: To predict the ingredients and key targets of ASSD, we constructed "drug-ingredient-target-disease" and protein-protein interaction networks.

Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and mitigating oxidative stress is crucial in managing MI. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in combating oxidative stress and facilitating cardiac remodeling post-MI. Here, we engineered Cerium oxide (CeO) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids.

Depression-related innate immune genes and pan-cancer gene analysis and validation.

Background: Depression, a prevalent chronic mental disorder, presents complexities and treatment challenges that drive researchers to seek new, precise therapeutic targets. Additionally, the potential connection between depression and cancer has garnered significant attention.

Methods: This study analyzed depression-related gene expression data from the GEO database.

iRGD-Targeted Biosynthetic Nanobubbles for Ultrasound Molecular Imaging of Osteosarcoma.

Purpose: Osteosarcoma is the most common primary malignant tumor of the bone. However, there is a lack of effective means for early diagnosis due to the heterogeneity of tumors and the complexity of tumor microenvironment. αvβ3 integrin, a crucial role in the growth and spread of tumors, is not only an effective biomarker for cancer angiogenesis, but also highly expressed in many tumor cells.

A vacuolar invertase gene modulates sugar metabolism and postharvest fruit quality and stress resistance in tomato.

Sugars act as signaling molecules to modulate various growth processes and enhance plant tolerance to various abiotic and biotic stresses. Moreover, sugars contribute to the postharvest flavor in fleshy fruit crops. To date, the regulation of sugar metabolism and its effect in plant growth, fruit ripening, postharvest quality, and stress resistance remains not fully understood.

Molecular dynamics of chemotactic signalling orchestrates dental pulp stem cell fibrosis during aging.

Aging often triggers dental pulp fibrosis, resulting in clinical repercussions such as increased susceptibility to dental infections, compromised tooth vitality, and reduced responsiveness to dental interventions. Despite its prevalence, the precise molecular mechanisms underlying this condition remains unclear. Leveraging single-cell transcriptome analysis from both our own and publicly available datasets, we identified Ccrl2 macrophages as particularly vulnerable during the early stages of aging.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of Oxytocin (OT)-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (T) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats.

PPARG/SPP1/CD44 signaling pathway in alveolar macrophages: Mechanisms of lipid dysregulation and therapeutic targets in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. It is characterized by inflammation and fibrosis in the lung parenchyma and interstitium. Given its poor prognosis and limited treatment options, understanding the underlying molecular mechanisms is crucial.

One-Step Synthesis of Carboxylated Polyethylene Glycol-Modified Polystyrene Microspheres and Their Application in the Luminescent Oxygen Channel Immunoassay.

As one of the key diagnostic methods for detecting biomarkers and antigen-antibody interactions, the luminescent oxygen channel immunoassay (LOCI) has been widely applied in bioanalysis and other fields. In the context of LOCI, the performance of the prepared donor polystyrene (PS) microspheres significantly impacts the detection signal values. In this study, an attempt was made to synthesize PS microspheres via one-step polymerization of styrene with an amphiphilic monomer (PEOOH), followed by swelling the silicon phthalocyanine photosensitizer into the PS microspheres, resulting in the functionalization of the PS microspheres with polyethylene glycol segments.

An electrochemical microsensor of the SARS-CoV-2 nucleocapsid protein based on a surface-imprinted acupuncture needle.

A novel electrochemical microsensor was constructed on a traditional acupuncture needle (AN) and used to monitor a biomarker of the SARS-CoV-2-N protein. The reversible interaction of the borate bond between the -diol in this glycoprotein and the phenylboronic acid in 4-mercaptophenylboronic acid (4-MPBA) was accomplished. This interaction was applied to anchor the SARS-CoV-2-N protein onto 4-MPBA, which was covalently self-assemblied onto electrodeposited AuNPs by the S-Au bond.

OsCYP22 Interacts With OsCSN5 to Affect Rice Root Growth and Auxin Signalling.

Beyond structural support, plant root systems play crucial roles in the absorption of water and nutrients, fertiliser efficiency and crop yield. However, the molecular mechanism regulating root architecture in rice remains largely unknown. In this study, a short-root rice mutant was identified and named Oscyp22.

PerC B-Cells Activation via Thermogenetics-Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells.

During cancer peritoneal metastasis (PM), conventional antigen-presenting cells (dendritic cells, macrophages) promote tumorigenesis and immunosuppression in peritoneal cavity. While intraperitoneal immunotherapy (IPIT) has been used in clinical investigations to relieve PM, the limited knowledge of peritoneal immunocytes has hindered the development of therapeutic IPIT. Here, a dendritic cell-independent, next-generation IPIT is described that activates peritoneal cavity B (PerC B) cell subsets for intraperitoneal anti-tumor immunity via exogenous antigen presentation.

Mechanisms of Low Temperature-Induced Growth Hormone Resistance via TRPA1 Channel Activation in Male Nile Tilapia.

Low temperatures significantly impact growth in ectothermic vertebrates, though the underlying mechanisms remain poorly understood. This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) channels in mediating low temperature effects on growth performance and growth hormone (GH) resistance in Nile tilapia (Oreochromis niloticus). Prolonged exposure to low temperature (16°C for 35 days) impaired growth performance and induced GH resistance, characterized by elevated serum GH levels and decreased insulin-like growth factor-1 (IGF-1) levels.

Utilizing 4-Sulfonylcalix[4]arene as a Selective Mobile Phase Additive for the Capture of Methylated Peptides.

Protein methylation has attracted increasing attention due to its significant regulatory roles in various biological processes. However, the diversity of methylation forms, subtle differences between methylated and nonmodified sites, and their ultralow abundances pose substantial challenges for capturing and isolating methylated peptides from biological samples. Herein, we develop a chromatographic method that utilizes 4-sulfonylcalix[4]arene (SC4A) as a mobile phase additive and Click-Maltose as the stationary phase to separate methylated/nonmethylated peptides through the adsorption of the SC4A-(Me3) complex.