Cerebrospinal fluid (CSF) drains along the perivascular space, known as the glymphatic system, to the meninges, where meningeal lymphatic vessels (MLVs) remove toxic products with excess CSF from the brain. Macrophages are widely present in the leptomeninges and dura mater of meninges. However, whether leptomeningeal and dural macrophages play the same or distinct roles in maintaining optimal CSF drainage remains unclear. By intra-cisterna magna (i.c.m.) injection of clodronate liposomes (CLL...

Perilipin 2 expression is related to poor prognosis of patients with various malignant tumors. Perilipin 2 exists on the surface of lipid droplets (LDs), which store lipids that can be used as an energy source during cancer progression. However, the underlying mechanism of lipid metabolism involving LDs in the progression of lung adenocarcinoma is unclear. Herein, this study investigated the role of perilipin 2 in the regulation of lipid metabolism in lung adenocarcinoma, as well as patient p...

Spinal cord injury (SCI) often results in severe hypoxia and excessive activation of neuroinflammation, which aggravates neuropathology and neurological dysfunction. D-dopachrome tautomerase (D-DT), the homolog of macrophage migration inhibitory factor (MIF), is a key proinflammatory mediator implicated in inflammatory diseases of multiple tissues. However, its relation with hypoxia and the potential impact on neuroinflammation following SCI remain elusive. Herein, the dynamic expression of D...

Wilson's Disease (WD) is a copper metabolism disorder caused byATP7Bgene mutations, and hepatic steatosis is not uncommon in WD. Therefore, we investigated the effects of ATP7B deficiency and/or a high-fat diet (HFD) on the development of steatohepatitis in mouse models, and examined the relationship of hepatic steatosis with cardiometabolic factors in WD patients.A retrospective analysis of data was conducted on adults with WD. Atp7b gene knockout(KO) was achieved by CRISPR/Cas9 technology, ...

Super-resolution microscopy holds great promise for detailed structural analysis of proteins yet its application in the investigations of protein structures in situ remains sparse. Clathrin-coated pit-mediated endocytosis (CME) plays a key role in human cancer. We aimed to discover whether there are structural changes in clathrin pits in cancer? We used immunofluorescence (IF) combined with super-resolution structured illumination microscopy (SR-SIM) on normal and cancerous prostate tissue to...

Protein S-palmitoylation, a reversible posttranslational modification, is crucial for tumor progression. However, the palmitoylation landscape in tumor cells and its variability within different tumor cell populations remain underexplored. We analyzed protein palmitoylation using 23 palmitoyl-acyltransferases and 7 de-palmitoyl-acyltransferases. Through copy number variation, pseudotime, enrichment, and cell-cell communication analyses, we explored heterogeneity among epithelial cells in lung...

Although quality-of-life compromising afflictions, such as diabetic retinopathy (DR), are driven by vascular endothelial growth factor (VEGF), there is a growing appreciation that the concentration of VEGF is not the only influencer of vascular dysfunction within the retina. Activin A (activin), a ligand of the transforming growth factor-β superfamily, attenuated VEGF-induced vascular endothelial–cadherin disorganization, pore formation, and permeability of primary human retinal endothelial c...

Leber hereditary optic neuropathy (LHON) is a bilateral optic neuropathy associated with mitochondrial DNA (mtDNA) mutations characterized by parapapillary telangiectasia during the acute phase. However, its precise mechanism remains unclear. This study evaluated the effects of nitric oxide (NO) on retinal organoids (ROs) generated from induced pluripotent stem (iPS) cells derived from patients with LHON. Established iPS cells from three patients with the m.11778G>A mutation (patient group) a...

The mammalian kidney contains numerous nephrons connected to the collecting ducts, and each nephron consists of a glomerulus, a proximal tubule, the loop of Henle (LoH), and a distal tubule. Folliculin (FLCN) is a causative gene for Birt-Hogg-Dubé (BHD) syndrome, which is characterized by a variety of manifestations including renal cysts and cancer. Although deletion of Flcn in the mouse collecting duct and distal nephron leads to cyst formation, its precise role in the entire nephron remains...

Collagen VII is an essential anchoring protein in the basement membrane zone, maintaining the attachment of stratified and pseudostratified epithelia to the underlying interstitial matrix. However, collagen VII is largely unexplored in normal lungs and idiopathic pulmonary fibrosis (IPF), a disease characterized by excessive accumulation of extracellular matrix and aberrant re-epithelialization of fibrotic lung parenchyma. Analysis of collagen VII mRNA and protein in IPF distal lungs demonstr...

The angiofibrotic switch refers to the pathological transition from active angiogenesis to fibrosis, a process that contributes to disease progression in retinal and choroidal neovascular diseases such as age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). This switch marks the replacement of newly formed, fragile blood vessels with fibrotic tissue, ultimately leading to scarring and permanent vision loss. Understanding this process is crucial, as fibrosis res...

Lymphangioleiomyomatosis (LAM) is a rare systemic disease that affects young women and is classified as a low-grade metastasizing neoplasm. It is characterized by uncontrolled proliferation of LAM cells within the lung parenchyma, which results from loss-of-function mutations in tuberous sclerosis complex 2 (TSC2) or 1 (TSC1) and activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal cell growth leads to cyst formation and lung damage. Rapamycin-based therapy is the on...

Osteonecrosis of the femoral head (ONFH) is an orthopaedic disease with multifaceted pathogenesis. The role of long noncoding RNA (lncRNA) taurine-up-regulated gene 1 (TUG1) in ONFH remains unexplored. Thus, lncRNA expression profiles in subchondral bone from patients with ONFH and healthy controls were analyzed using microarray analysis, RT-qPCR, and bioinformatics. To evaluate the effect of TUG1 on osteogenic differentiation, TUG1 was overexpressed or knocked down in human bone marrow mesen...

The pathogenesis of Crohn's disease (CD) remains unclear, with mitochondrial dysfunction and ferroptosis emerging as important contributors. However, the specific mechanisms linking mitochondria, ferroptosis, and CD are not well understood. Through bioinformatics analysis using the Gene Expression Omnibus (GEO) database, AFG3L2 was identified as a key mitochondrial gene and subjected to functional enrichment and immune infiltration analyses. In vitro, we used lipopolysaccharide (LPS)-induced ...

FKBP prolyl isomerase 10 (FKBP10) plays a key role in fibrosis-driven progression of gluteal muscle contracture (GMC). This study investigated the molecular mechanism of FKBP10 in GMC progression. Exp...

Intestinal stem cell (ISC) signaling maintains the balance of self-renewal and differentiation. Herein, the role of phosphatidylinositol 3-kinase (PI3K) signaling in ISC responses to radiation was interrogated using Villin-Cre pik3r1lox/lox (p85ΔIEC) mice and p85α-deficient human enteroids (shp85α). Lethal whole-body irradiation in mice was performed to monitor PI3K-mediated survival responses. Rectal biopsies from patients with radiation proctitis were examined by immunohistochemistry for th...

Hepatoblastoma (HB) represents the most common primary malignancy of the liver in childhood. Cytogenetic studies uncovered characteristic copy number alterations in HB. The frequent gain of chromosome 2q and particularly the recurrent 2q24 amplification suggest the presence of a so far unidentified oncogenic driver within this amplicon. Herein, high-resolution copy number profiles from 76 patients with HB were generated by using molecular inversion probe array technology. 2q gain was present ...

The relationship among timing and severity of coronavirus disease 2019 (COVID-19) during pregnancy, placental pathology, and adverse pregnancy outcomes is not well understood. A prospective cohort study of 497 pregnant patients with COVID-19 whose placentas underwent systematic pathologic examination was conducted. The main exposure was timing of COVID-19 during pregnancy (first/second versus third trimester). The primary outcome was composite placental pathology that included high-grade mate...