Real-time detection of somatostatin release from single islets reveals hypersecretion in type 2 diabetes.

Aim: Somatostatin from pancreatic δ-cells is a paracrine regulator of insulin and glucagon secretion, but the release kinetics and whether secretion is altered in diabetes is unclear. This study aimed to improve understanding of somatostatin secretion by developing a tool for real-time detection of somatostatin release from individual pancreatic islets.

Methods: Reporter cells responding to somatostatin with cytoplasmic Ca concentration ([Ca]) changes were generated by co-expressing somatostatin receptor SSTR2, the G-protein Gα15 and a fluorescent Ca sensor in HeLa cells.

TRIM36 Inhibits the Development of AOM/DSS-Induced Colitis-Associated Colorectal Cancer by Promoting the Ubiquitination and Degradation of GRB7.

Colorectal cancer (CRC) is among the most common cancer types for both sexes. Tripartite motif 36 (TRIM36) has been reported to be aberrantly expressed in several cancer types, suggesting its involvement in cancer progression. However, the role of TRIM36 in the colorectal carcinogenesis remain unknown.

Artemisinin protected human bronchial epithelial cells from amiodarone-induced oxidative damage via 5'-AMP-activated protein kinase (AMPK) activation.

Background: Amiodarone, a common antiarrhythmic drug, is known for its severe side effects, including pulmonary toxicity, which involves oxidative stress and apoptosis. Artemisinin, an antimalarial drug, has shown cytoprotective properties by inhibiting oxidative stress and apoptosis. This study investigated the protective effects of artemisinin against amiodarone-induced toxicity in human bronchial epithelial cells (BEAS-2B) and mouse models.

Efficient synthesis of dihydronaphthalenes cerium-catalyzed annulation of 1-alkoxy substituted 1-isochromenes with cinnamic acids.

Dihydronaphthalenes play a crucial role in bioactive natural products and new drug discovery, and efficient and economic strategies to build them are needed. Herein, we disclose a highly efficient method to prepare dihydronaphthalenes a cerium-catalyzed cycloaddition of 1-isochromenes with cinnamic acids. This newly developed method not only features a broad and low-cost substrate scope and mild conditions but also exhibits very high functional group tolerance, including hydroxyl, borate ester and ester group substituents.

Characterization of the immune cell profile in metastatic nasopharyngeal carcinoma treated with chemotherapy and immune checkpoint inhibitors.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer, and immune checkpoint inhibitors (ICIs) have shown efficacy in its treatment. The combination of chemotherapy and ICIs represents a new trend in the standard care for metastatic NPC. In this study, we aim to clarify the immune cell profile and related prognostic factors in the ICI-based treatment of metastatic NPC.

Deep learning to optimize radiotherapy decisions for elderly patients with early-stage breast cancer: a novel approach for personalized treatment.

The use of routine adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) is controversial in elderly patients with early-stage breast cancer (EBC). This study aimed to evaluate the efficacy of adjuvant RT for elderly EBC patients using deep learning (DL) to personalize treatment plans. Five distinct DL models were developed to generate personalized treatment recommendations.

HER2-targeted ADC DX126-262 combined with chemotherapy demonstrates superior antitumor efficacy in HER2-positive gastric cancer.

Gastric cancer is a common malignant tumor with high incidence and mortality. The overexpression of Human epidermal growth factor receptor 2 (HER2) is associated with increased metastatic potential and poor clinical outcome in gastric cancer. Despite the proven clinical response rates of approved HER2-targeted therapies, including Trastuzumab combined with chemotherapy, their limited long-term clinical benefits and inevitable disease progression still pose significant challenges to the clinical treatment of gastric cancer.

MaGA20ox2f, an OsSD1 homolog, regulates flowering time and fruit yield in banana.

Unlabelled: Previous studies illustrated that two banana GA20 oxidase2 (MaGA20ox2) genes, and , are implicated in controlling banana growth and development; however, the biological function of each gene remains unknown. Ma04g15900 protein (termed MaGA20ox2f in this article) is the closest homolog to the Rice SD1 (encoded by 'green revolution gene', ) in the banana genome. The expression of is confined to leaves, peduncles, fruit peels, and pulp.

Molecular basis for shifted receptor recognition by an encephalitic arbovirus.

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.

A fetal oncogene NUAK2 is an emerging therapeutic target in glioblastoma.

Glioblastoma Multiforme (GBM) is the most prevalent and highly malignant form of adult brain cancer characterized by poor overall survival rates. Effective therapeutic modalities remain limited, necessitating the search for novel treatments. Neurodevelopmental pathways have been implicated in glioma formation, with key neurodevelopmental regulators being re- expressed or co-opted during glioma tumorigenesis.

Biological volume EM with focused Ga ion beam depends on formation of radiation-resistant Ga-rich layer at block face.

Volume electron microscopy (vEM) enables biologists to visualize nanoscale 3D ultrastructure of entire eukaryotic cells and tissues prepared by heavy atom staining and plastic embedding. The highest resolution vEM technique is focused ion-beam scanning electron microscopy (FIB-SEM), which provides nearly isotropic (~5-10 nm) spatial resolution at fluences of > 10,000 e /nm . However, it is not clear how such high resolution is achievable because serial block-face (SBF) SEM, which incorporates an in-situ ultramicrotome instead of a Ga FIB beam, results in radiation-induced collapse of similar specimen blocks at fluences of only ~20 e /nm .

Convergent state-control of endogenous opioid analgesia.

Pain is a dynamic and nonlinear experience shaped by injury and contextual factors, including expectations of future pain or relief . While µ opioid receptors are central to the analgesic effects of opioid drugs, the endogenous opioid neurocircuitry underlying pain and placebo analgesia remains poorly understood. The ventrolateral column of the posterior periaqueductal gray is a critical hub for nociception and endogenous analgesia mediated by opioid signaling .

Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice.

Introduction: In USA, six million individuals with Sub-Saharan ancestry carry two high-risk variants, which increase the risk for kidney diseases. Whether APOL1 high-risk variants are independent risk factors for cardiovascular diseases is unclear and requires further investigation.

Methods: We characterized a mouse model to investigate the role of APOL1 in dyslipidemia and cardiovascular diseases.

Bipolar and schizophrenia risk gene encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.

Human genomic studies have identified protein-truncating variants in associated with both bipolar disorder and schizophrenia, implicating a shared disease mechanism driven by loss-of-function. AKAP11, a protein kinase A (PKA) adaptor, plays a key role in degrading the PKA-RI complex through selective autophagy. However, the neuronal functions of AKAP11 and the impact of its loss-of-function remains largely uncharacterized.

Recessive but damaging alleles of muscle-specific ribosomal protein gene drive neonatal dilated cardiomyopathy.

The heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by rare compound heterozygous variants in RPL3L, a muscle-specific ribosomal protein that replaces the ubiquitous RPL3 in cardiac ribosomes. -linked heart failure represents the only known human disease arising from mutations in tissue-specific ribosomes, yet the underlying pathogenetic mechanisms remain poorly understood despite an increasing number of reported cases.

VISTA-induced tumor suppression by a four amino acid intracellular motif.

VISTA is a key immune checkpoint receptor under investigation for cancer immunotherapy; however, its signaling mechanisms remain unclear. Here we identify a conserved four amino acid (NPGF) intracellular motif in VISTA that suppresses cell proliferation by constraining cell-intrinsic growth receptor signaling. The NPGF motif binds to the adapter protein NUMB and recruits Rab11 endosomal recycling machinery.

A nucleotide code governs Lis1's ability to relieve dynein autoinhibition.

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.

MAIT cell deficiency exacerbates neuroinflammation in P301S human tau transgenic mice.

The role of immune cells in neurodegeneration remains incompletely understood. Our recent study revealed the presence of mucosal-associated invariant T (MAIT) cells in the meninges, where they express antioxidant molecules to maintain meningeal barrier integrity. Accumulation of misfolded tau proteins are a hallmark of neurodegenerative diseases.

Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1.

Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi.

Triglyceride metabolism controls inflammation and -associated disease states in microglia.

Microglia modulate their cell state in response to various stimuli. Changes to cellular lipids often accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimer's disease-associated genotype) result in accumulation of triglyceride-rich lipid droplets.

Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation.

Lymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins in Parkinson's disease (PD). This study investigates the role of neuronal LAG3 in mediating the binding, uptake, and propagation of α-synuclein (αSyn) preformed fibrils (PFFs). Using neuronal LAG3 conditional knockout mice and human induced pluripotent stem cells-derived dopaminergic (DA) neurons, we demonstrate that LAG3 expression is critical for pathogenic αSyn propagation.

Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease.

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohn's disease (CD) model (Tnf ), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host's immune susceptibility to drive region-specific disease. We identified , an intracellular bacterium and murine counterpart to the human sexually transmitted , as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD.

Vitrectomy for diabetic retinopathy: A review of indications, techniques, outcomes, and complications.

Diabetic retinopathy is one of the most severe forms of retinopathy and a leading cause of blindness all over the world. Of a greater concern is proliferative diabetic retinopathy which leads to vitreous haemorrhage and tractional retinal detachment in such cases. A majority of these cases require a surgical intervention to improve vision and prevent further vision loss.

Preliminary study on detection and diagnosis of focal liver lesions based on a deep learning model using multimodal PET/CT images.

Objectives: To develop and validate a deep learning model using multimodal PET/CT imaging for detecting and classifying focal liver lesions (FLL).

Methods: This study included 185 patients who underwent F-FDG PET/CT imaging at our institution from March 2022 to February 2023. We analyzed serological data and imaging.

Multidimensional morphological analysis of live sperm based on multiple-target tracking.

Manual semen evaluation methods are subjective and time-consuming. In this study, a deep learning algorithmic framework was designed to enable non-invasive multidimensional morphological analysis of live sperm in motion, improve current clinical sperm morphology testing methods, and significantly contribute to the advancement of assisted reproductive technologies. We improved the FairMOT tracking algorithm by incorporating the distance and angle of the same sperm head movement in adjacent frames, as well as the head target detection frame IOU value, into the cost function of the Hungarian matching algorithm.