Abstract Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains leading cause of death in breast cancer. However, little known about dynamic changes during evolvement dissemination. In this study, 65 968 cells from four patients with paired metastatic axillary lymph nodes are profiled using single‐cell RNA sequencing (scRNA‐seq) spatial transcriptomics. A disseminated cell cluster high levels oxidative phosphorylation (OXPHOS), including upregulation cytochrome...

Abstract Soft gels that integrate the water retention of hydrogels and swelling resistance organogels are sought by researchers. Such materials have useful properties potential applications in stretchable biointegrated fields, such as tissue engineering, microfluidics, biomedical devices. This study reports a simple yet versatile method for assembling into covalently tethered hybrids to provide robust properties, excellent stretchability, tough interfacial bonds, enduring antiswelling, low...

Abstract Background Severe acute respiratory syndrome coronavirus 2 causes myocardial damage and arrhythmia in disease 2019 (COVID‐19) patients. Studying the changes of electrocardiogram is great significance for diagnosis patients with COVID‐19. Methods A retrospective analysis method was adopted to compare between COVID‐19 critically severe Univariate multivariate logistic regression were used analyze correlation levels serum indexes past medical history ST‐T atrial fibrillation. And ECG...

The pore-forming alpha-subunits of large conductance calcium- and voltage-activated potassium (BK) channels are encoded by a single gene that undergoes extensive alternative pre-mRNA splicing. However, the extent to which differential exon usage at site splicing may confer functionally distinct properties on BK is largely unknown. Here we demonstrated C2 in mouse channel C terminus generates five splice variants: ZERO, e20, e21(STREX), e22, novel variant deltae23. Splice variants display...

Large conductance calcium- and voltage-gated potassium (BK) channels are important regulators of physiological homeostasis their function is potently modulated by protein kinase A (PKA) phosphorylation. PKA regulates the channel through phosphorylation residues within intracellular C terminus pore-forming alpha-subunits. However, molecular mechanism(s) which alpha-subunit effects changes in activity unknown. Inhibition BK depends on only a single tetramer containing an alternatively spliced...

Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. recruited incident cases controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from membership Kaiser Permanente Southern California into Sunshine Study to simultaneously examine 25OHD, accounting genetic ancestry other factors. Higher lifetime...

Cancer stem cells (CSCs) are the most intractable subpopulation of triple-negative breast cancer (TNBC) cells, which have been associated with a high risk relapse and poor prognosis. However, eradication CSCs continues to be difficult. Here, we integrate multiomics data TNBC cohort (n = 360) identify vital markers CSCs. We discover that EMSY, inducing BRCAness phenotype, is preferentially expressed in CSCs, promotes ALDH+ enrichment, positively correlated relapse-free survival....

Abstract Neurons are highly specialized cells in which the integration and processing of electrical signals critically depends on precise localization ion channels. For large‐conductance Ca 2+ ‐ activated K + (BK) channels, targeting to presynaptic membranes hippocampal pyramidal was reported; however, functional evidence also suggests a somatodendritic localization. Therefore we re‐examined subcellular distribution BK channels mouse hippocampus using panel independent antibodies combined...

Abstract Breast cancer has become the most common in women, and nontriple negative breast (non‐TNBC) accounts for 80–90% of all invasive cancers. Early detection, diagnosis, treatment are considered key to a successful cure. Conventionally, imaging needle core biopsy used detection monitoring. However, small variations volume might be ignored imaging, traditional biopsies spatially temporally limited, leading significant delay thus prompting renewed focus on early accurate diagnosis. In this...

Triple-negative breast cancer (TNBC) has a poorer outcome than other subtypes of cancer, and the discovery dysregulated microRNA (miRNA) their role in tumor progression provided new avenue for elucidating mechanism involved TNBC. In this study, we identified that miR-3178 was significantly reduced TNBC, low expression correlated with poor overall survival TNBC but not non-TNBC. The ectopic overexpression suppressed cell proliferation, invasion, migration by inhibiting...

Calcium-activated potassium (BK) channels play a central role in regulating multiple physiological processes, from the control of blood flow to neuronal excitability. Coordinated regulation BK channel activity by changes actin cytoskeleton dynamics has been implicated several these processes and related disease states such as epilepsy stroke. However, how interact with is essentially unknown. Here we demonstrate noncanonical Src homology domain 3 (SH3) binding site motifs intracellular C...

Abstract Activation of oncogenes by promoter hypomethylation plays an important role in tumorigenesis. Zinc finger protein 57 (ZFP57), a member KRAB-ZFPs, could maintain DNA methylation embryonic stem cells (ESCs), although its and underlying mechanisms breast cancer are not well understood. In this study, we found that ZFP57 had low expression cancer, overexpression inhibit the proliferation inhibiting Wnt/β-catenin pathway. MEST was validated as direct target gene may be down-regulated...

S-palmitoylation is rapidly emerging as an important post-translational mechanism to regulate ion channels. We have previously demonstrated that large conductance calcium- and voltage-activated potassium (BK) channels are palmitoylated within alternatively spliced (STREX) insert. However, these studies also revealed additional site(s) for palmitoylation must exist outside of the STREX insert, although identity or functional significance cysteine residues unknown. Here, we demonstrate BK at a...

The anterior pituitary corticotroph is a major control point for the regulation of hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine response to stress. Although corticotrophs are known be electrically excitable, ion channels controlling electrical properties poorly understood. Here, we exploited lentiviral transduction system allow unequivocal identification live murine in culture. We demonstrate that display highly heterogeneous spontaneous action-potential firing patterns their...

Hyperuricemia is the main cause of gout and involved in occurrence multiple diseases, such as hypertension, metabolic disorders chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown beneficial effects on prevention or treatment hyperuricemia. In this study, urate-lowering effect two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) Limosilactobacillus fermentum 2644 (LF2644) hyperuricemic rats were investigated. A rat model was induced by...

To provide complementary information and reveal the molecular characteristics therapeutic insights of HER2-low breast cancer, we performed this multiomics study hormone receptor-negative (HR-) also known as triple-negative cancer (TNBC), identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), mesenchymal stem-like. These subgroups had distinct features potential targets were validated in external data sets. Interestingly, TKR subgroup (which exists both HR+ HR- cancer)...

Traumatic brain injury (TBI) results in significant morbidity and mortality throughout the world. In TBI patients suffering cognitive, emotional, behavioral deficits, leading cause derives from physical to central nervous system (CNS) that impairs function.Here, we applied a targeted approach understand potential mechanisms of neuron damage after TBI. Tau protein phosphorylation was compared tissues collected underwent surgery based on assessment extent by Glasgow Coma Scale (GCS).The...

Blacks have different dominant polymorphisms in the vitamin D-binding protein (DBP) gene that result higher bioavailable D than whites. This study tested whether lack of association between 25-hydroxyvitamin (25OHD) and multiple sclerosis (MS) risk blacks Hispanics is due to differences these common (rs7041, rs4588). We recruited incident MS cases controls (blacks 116 cases/131 controls; 183/197; whites 247/267) from Kaiser Permanente Southern California. AA rs7041 genotype (70.0%) whereas C...

Multiple mini-interview (MMI) is a 'multiple sample-based' approach comprising multiple focused encounters intended to access and assess range of attributes in order gain more objectively impressions an applicant's interpersonal skills, thoughtfulness general demeanour. It designed focus on four domains that are not considered be comprehensive, but vital for successful career the health sciences: critical thinking, ethical decision making, communication knowledge healthcare system....

Diabetic retinopathy (DR) is a major cause of vision loss worldwide. Here, we perform single-cell RNA sequencing thirteen human retina samples (from living and post-mortem donors) across non-diabetic, diabetic, DR states to create comprehensive transcriptomic atlas. We uncover three distinct microglial states: homeostatic, stress-response, inflammatory, along functional continuum, rather than discrete activation states, with dynamic transitions occurring throughout disease progression....

The human retina exhibits complex cellular heterogeneity which is critical for visual function, yet comprehensive ethnic-specific references are scarce in ophthalmic transcriptomics. lack of single-cell RNA sequencing (scRNA-seq) data from Asian populations particularly Chinese donors imposes significant limitations understanding population-specific retinal biology. We constructed the first transcriptomic atlas donors, generated through high-throughput scRNA-seq ~290,000 viable cells...

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase and scaffolding protein that primarily regulated by integrin signaling. FAK signaling increases cell motility in both normal cancer cells, often overexpressed and/or dysregulated many types of cancer. has three different domains: an N-terminal FERM domain, central domain (the traditional target for drug discovery), C-terminal focal adhesion targeting (FAT) domain. The FAT represents alternative approach to FAK, our aim identify...