Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes.

Background And Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited.

Synthetic nanomaterials for spleen-specific mRNA delivery.

In recent years, mRNA vaccine has achieved increasing interest owing to its high potency, safety, ease of production, and low-cost manufacturing. Currently approved mRNA vaccines are administered intramuscularly to transfect local antigen-presenting cells (APCs) to initiate low to moderate immune responses. Spleen, the largest secondary lymphoid organ in the body which contains a large number of APCs close to B and T lymphocytes, could be the ideal site for effective initiation of an enhanced immune response.

Neurodevelopmental disorder-associated CYFIP2 regulates membraneless organelles and eIF2α phosphorylation via protein interactors and actin cytoskeleton.

De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice.

Expression and significance of Fractalkine/CX3CL1 in MPO-AAV-associated glomerulonephritis rats.

Objective: To investigate the expression and significance of Fractalkine (CX3CL1, FKN) in serum and renal tissue of myeloperoxidase and anti-neutrophil cytoplasmic antibody associated vasculitis (MPO-AAV) rats.

Methods: Thirty Wistar-Kyoto (WKY) rats were randomly divided into: Control group, MPO-AAV group (400 µg/kg MPO mixed with Freund's complete adjuvant i.p), MPO-AAV + Anti-FKN group (400 µg/kg MPO mixed with Freund's complete adjuvant i.

Cell-autonomous reduction of CYFIP2 changes dendrite length, dendritic protrusion morphology, and inhibitory synapse density in the hippocampal CA1 pyramidal neurons of 17-month-old mice.

The cytoplasmic FMR1-interacting protein 2 (CYFIP2) have diverse molecular functions in neurons, including the regulation of actin polymerization, mRNA translation, and mitochondrial morphology and function. Mutations in the gene are associated with early-onset epilepsy and neurodevelopmental disorders, while decreases in its protein levels are linked to Alzheimer's disease (AD). Notably, previous research has revealed AD-like phenotypes, such as dendritic spine loss, in the hippocampal CA1 pyramidal neurons of 12-month-old heterozygous mice but not of age-matched CA1 pyramidal neuron-specific conditional knock-out (cKO) mice.

Diastereoselective Synthesis of Pyrroloquinolines via N-H Functionalization of Indoles with Vinyl Sulfonium Salts.

A [2 + 4]/[1 + 2] annulation approach was successfully established to construct pyrroloquinoline-fused cyclopropane in a highly diastereoselective fashion (>20:1 dr). The tetracyclic 1,7-fused indoles were efficiently obtained from readily available starting materials under mild conditions. This methodology displays impressive substrate generality with two reaction components.

Evaluation of the mRNA release assay for diagnosis of TB in HIV-infected individuals.

HIV-infected individuals are susceptible to () infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application.

The emerging roles of Shank3 in cardiac function and dysfunction.

Shank3 is a member of the Shank family proteins (Shank1-3), which are abundantly present in the postsynaptic density (PSD) of neuronal excitatory synapses. As a core scaffold in the PSD, Shank3 plays a critical role in organizing the macromolecular complex, ensuring proper synaptic development and function. Clinically, various mutations of the gene are causally associated with brain disorders such as autism spectrum disorders and schizophrenia.

Cyr61 Mediates Angiotensin II-Induced Podocyte Apoptosis via the Upregulation of TXNIP.

Purpose: It is well documented that angiotensin II (Ang II) elevation promotes apoptosis of podocytes and , but the potential mechanism is still oscular. The current study is aimed at probing into the assignment of cysteine-rich protein 61 (Cyr61) in Ang II-induced podocyte apoptosis.

Methods: Podocytes were treated with Ang II (10 mol/L) for 48 hours to establish an injury model in vitro.

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation.

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer.

CYFIP2 p.Arg87Cys Causes Neurological Defects and Degradation of CYFIP2.

Here, we report the generation and comprehensive characterization of a knockin mouse model for the hotspot p.Arg87Cys variant of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) gene, which was recently identified in individuals diagnosed with West syndrome, a developmental and epileptic encephalopathy. The Cyfip2 mice recapitulated many neurological and neurobehavioral phenotypes of the patients, including spasmlike movements, microcephaly, and impaired social communication.

Effects of chronic kidney disease on cognitive function and α-klotho expression in hippocampus.

Background: Alpha-klotho (α-KL) is not only related to the regulation of calcium-phosphorus metabolism, and fibrosis in chronic kidney disease (CKD), it is also involved in the regulation of many cognitive disorders. We conducted this study to investigate the effects of CKD on cognitive dysfunction and α-KL.

Methods: Doxorubicin was used to induce a CKD model, which was validated by weight, 24-hour urine protein quantification, serum creatinine (Cr), blood urea nitrogen (BUN), and kidney hematoxylin-eosin (HE) staining.

Non-Invasive Prediction Models for Esophageal Varices and Red Signs in Patients With Hepatitis B Virus-Related Liver Cirrhosis.

Red signs are closely related to esophageal variceal bleeding, and, despite improvements in therapy, the mortality rate remains high. We aimed to identify non-invasive predictors of esophageal varices and red signs in patients with hepatitis B virus-related liver cirrhosis. This retrospective study included 356 patients with hepatitis B virus-related liver cirrhosis after applying inclusion and exclusion criteria among 661 patients.

Tumor-Infiltrated CD8+ T Cell 10-Gene Signature Related to Clear Cell Renal Cell Carcinoma Prognosis.

Clear cell renal cell carcinoma (ccRCC) usually affects multiple organs (e.g., bone and brain), and patient prognosis is usually poor.

Stereoselective Synthesis of Chiral Hydrophenanthridines via a One-Pot Stepwise Aza-Michael/Michael/Michael Process.

A one-pot, two-step aza-Michael/Michael/Michael process was developed to diastereospecifically construct C6a,C10a--hydrophenanthridines in a highly enantioselective manner (83-99% ee). The tricyclic products were provided in 50-99% isolated yields, sequentially promoted by bifunctional squaramide and diamine in a one-pot operation. This doubly annulative protocol indicated that the complicated polycyclic structures could be easily constructed via full employment of the available reaction sites of readily prepared precursors.

Correlation of Carotid Artery Intima-Media Thickness with Calcium and Phosphorus Metabolism, Parathyroid Hormone, Microinflammatory State, and Cardiovascular Disease.

The internal thickness of the carotid artery is the vertical distance between the intima of the carotid artery and the middle mold. Its normal thickness is less than 1 mm. It can be used to judge the degree of arteriosclerosis.

Inclusion of interleukin-6 improved performance of postoperative delirium prediction for patients undergoing coronary artery bypass graft (POD-CABG): A derivation and validation study.

Background: Patients undergoing coronary artery bypass graft (CABG) are at high risk for developing postoperative delirium (POD). A simple prediction rule may benefit patients from early identification of POD followed by adequate preventive strategies. The purpose of the current study was to develop and validate a POD prediction rule for patients undergoing CABG (POD-CABG), by considering all possible perioperative factors.

The Identification of a Tumor Infiltration CD8+ T-Cell Gene Signature That Can Potentially Improve the Prognosis and Prediction of Immunization Responses in Papillary Renal Cell Carcinoma.

Background: CD8+ T cells, vital effectors pertaining to adaptive immunity, display close relationships to the immunization responses to kill tumor cells. Understanding the effect exerted by tumor infiltration CD8+ T cells in papillary renal cell carcinoma (papRCC) is critical for assessing the prognosis process and responses to immunization therapy in cases with this disease.

Materials And Approaches: The single-cell transcriptome data of papRCC were used for screening CD8+ T-cell-correlated differentially expressed genes to achieve the following investigations.

A Prediction Rule Including Interleukin-6 in Pericardial Drainage Improves Prediction of New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting.

Objective: To test the hypothesis that a prediction rule including levels of interleukin-6 in pericardial drainage (pdIL-6) would improve the discrimination in classifying patients undergoing coronary artery bypass grafting (CABG) into different postoperative atrial fibrillation (POAF) risk levels.

Design: Prospective cohort study.

Setting: A university-affiliated tertiary hospital.