Joint Distribution of Nuclear and Cytoplasmic mRNA Levels in Stochastic Models of Gene Expression: Analytical Results and Parameter Inference.

Common stochastic models of gene expression predict the gene-specific distribution of total mRNA per cell but lack subcellular resolution. Here, for a broad class of transcription initiation models, we derive an exact steady-state solution for the joint distribution of nuclear and cytoplasmic mRNA, and demonstrate that fitting this solution to spatially resolved mRNA data enhances parameter identifiability. By accounting for extrinsic noise, we use the model to precisely quantify bursty expression across thousands of human genes and link it to their biological functions.

Genomic and transcriptomic landscape of Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma: a multi-center study.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare indolent malignant neoplasm, which occurs almost exclusively in the liver or spleen and may arise from a common EBV-infected mesenchymal cell that differentiates along the follicular or fibroblastic dendritic cell pathway. Despite its rarity, it presents a pressing need for an improved understanding of its genetic underpinnings and potential treatment strategies for recurrent or disseminated cases. To address this, we conducted comprehensive whole-exome sequencing (WES) and transcriptome sequencing (mRNA-seq) analyses on 31 and 6 cases of EBV+ IFDCS, respectively, collected from multiple centers in China.

Harnessing the Power of a HO-Activated Theranostic Probe against Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (Dox) is a highly effective antitumor drug with established therapeutic benefits across various tumor types, whose non-negligible and potent side effect is the Dox-induced cardiotoxicity (DIC). Early diagnosis of DIC is difficult, and available therapeutic regimens are quite limited. Inspired by the unique structure and efficient anti-DIC bioactivity of the natural compound tanshinone IIA (Tan IIA), we rationally developed its fluorescently emissive analogue with preserved anti-DIC efficacy.

Dedifferentiated liposarcoma exhibiting myxoid liposarcoma-like morphology with DDIT3 co-amplifcation and STAT6 nuclear expression.

Dedifferentiated liposarcoma (DDLPS) arises from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) through progression into non-lipogenic sarcomas of varying histological grades, driven by amplification of the chromosome 12q13-15 region containing MDM2, CDK4, DDIT3, STAT6, GLI1, HMGA2, etc. DDLPS demonstrates marked morphological heterogeneity in its dedifferentiated components. We describe two DDLPS cases featuring a prominent arborizing vascular network, myxoid stroma, and STAT6 nuclear expression-features that complicate differentiation from solitary fibrous tumors (SFT), myxoid liposarcoma (MLPS), myxofibrosarcoma (MFS), GLI1-altered tumors, low-grade fibromyxoid sarcoma (LGFMS), soft tissue angiofibroma (STA), etc.

MMAE-Based Peptide-Drug Conjugates Targeting GPC3 for Precision Chemoradiotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), the third leading cause of cancer mortality, lacks effective therapies. Current chemoradiotherapy faces challenges from systemic toxicity and radiation side effects. We developed a series of GPC3-targeting peptide-drug conjugates (PDCs) integrating monomethyl auristatin E (MMAE) to enhance tumor-specific delivery.

Case Report: -rearranged mesenchymal neoplasms with S100 and CD34 co-expression: additional cases with distinct characteristics.

rearrangements are rarely documented in superficial soft tissue neoplasms exhibiting an infantile fibrosarcoma-like spindle cell tumor (IFS) pattern or stromal, resembling Neurotrophic Tyrosine Kinase Receptor()rearranged spindle cell tumors. Here, we present two cases of pediatric cutaneous soft tissue tumors with an IFS pattern, in which fusions involving related partner genes were identified. The tumors in both cases demonstrated similar morphology and consisted of ovoid and spindle cells with infiltrative boundaries.

Ethanol extract of Moschus attenuates glutamate-induced cytotoxicity in HT22 cells by regulating the Nrf2 and MAPK pathways.

Ethnopharmacological Relevance: Moschus is a traditional Chinese materia medica for treating central nervous system disorders. Oxidative stress is a key pathogenic mechanism of Alzheimer's disease (AD) and serves as a critical bridge linking various pathological processes of AD. Previous studies have shown that Moschus can exert neuroprotective effects by inhibiting glutamate-induced neuronal cell damage.

Identification of low-toxicity DNA topoisomerase I inhibitors with potential blood-brain barrier penetrability for glioblastoma therapy: structure-based virtual screening reveals promising novel Scaffolds.

Due to the blood-brain barrier (BBB), DNA topoisomerase I (Topo I) inhibitors often cause dose-limiting toxicity in glioblastoma (GBM) treatment. Therefore, developing low-toxicity Topo I inhibitors with enhanced BBB permeability holds a significant promise for improving GBM treatment outcomes. In this study, structure-based virtual screening methods combined with biological evaluations successfully identified three potent Topo I inhibitors, which exhibited IC values of approximately 25 µM against A172 cells.

Xanthohumol as a potential therapeutic strategy for acute myeloid leukemia: Targeting the FLT3/SRPK1 signaling axis.

Xanthohumol (XN) is an isoprene chalcone found in hops (Humulus lupulus L.), a food ingredient with a wide range of pharmacological activities. The aim of this study was to reveal the therapeutic effect of XN on acute myeloid leukemia (AML) and the potential underlying molecular mechanism.

A potent fluorescent probe for HOCl with dual NIR emissions: Achieving the early diagnosis of polystyrene microplastics-induced liver injury involved in ferroptosis.

Polystyrene microplastics (PS-MPs) are ubiquitous environmental contaminants that pose a significant threat to ecosystems and human health. The toxicity of PS-MPs to the liver is associated with a surge of reactive oxygen species (ROS). However, the specific type of ROS triggered by PS-MPs in the injured liver tissue remains inadequately known.

Gastric-type endocervical adenocarcinoma, superficial myofibroblastoma, sex cord-stromal tumors, and HSIL in Peutz-Jeghers syndrome: a rare case report, genetic characterization, and review of literature.

Peutz-Jeghers syndrome (PJS) is characterized by an increased risk of gynecologic tumors. Gastric-type endocervical adenocarcinoma (GEA) is a rare non-human papillomavirus (HPV)-related tumor. We reported an uncommon case of a 39-year-old woman with PJS who developed GEA, superficial cervical vaginal myofibroblastoma, sex cord-stromal tumors with annular tubules of the ovaries, and cervical and vaginal high-grade squamous interepithelial neoplasia (HSIL).

A robust HO-responsive AIEgen with multiple-task performance: Achieving food analysis, visualization of dual organelles and diagnosis of liver injury.

Drug- and alcohol-induced liver injury poses a serious threat to human health with long-lasting clinical, social and economic consequences. As a reactive oxygen species (ROS), hydrogen peroxide (HO) is widely-used as a molecular biomarker of liver injury. HO is also utilized as a processing aid in the food industry.

Luteolin Mitigates Acute Lung Injury Through Immune Modulation and Antinecroptosis Effects by Targeting the BTK and FLT3 Signaling Pathways.

Overactive immune responses and lung cell damage exacerbate acute lung injury (ALI). Luteolin, a flavonoid commonly found in traditional herbs, shows potential as an anti-ALI agent in pharmacological and clinical research, although its biological mechanism is not fully understood. This study aims to investigate whether luteolin can ameliorate ALI through its immune-modulatory and antinecroptosis mechanisms.

Primary large B-cell lymphoma of the central nervous system misdiagnosed as autoimmune encephalitis: a case report.

Primary central nervous system lymphomas (PCNSL) are rare, constituting 2 - 3% of intracranial malignancies. A 49-year-old male presented with a 20-day history of dizziness and a 15-day history of right-sided weakness. Physical examination revealed various abnormal signs.

Deterministic patterns in single-cell transcriptomic data.

We report the existence of deterministic patterns in statistical plots of single-cell transcriptomic data. We develop a theory showing that the patterns are neither artifacts introduced by the measurement process nor due to underlying biological mechanisms. Rather they naturally emerge from finite sample size effects.

Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion.

Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl) and hydrogen peroxide (HO).

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior: Two case reports.

Background: Eosinophilic solid and cystic (ESC) renal cell carcinoma (RCC), a unique and emerging subtype of RCC, has an indolent nature; in some rare instances, it may exhibit metastatic potential. Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.

Case Summary: Herein, we report two patients with ESC RCC.

A novel AIE-based mitochondria-targeting fluorescent probe for monitoring of the fluctuation of endogenous hypochlorous acid in ferroptosis models.

Ferroptosis is a way of cell death mainly due to the imbalance between the production and degradation of lipid reactive oxygen species, which is closely associated with various diseases. Endogenous hypochlorous acid (HOCl) mainly produced in mitochondria is regarded as an important signal molecule of ferroptosis. Therefore, monitoring the fluctuation of endogenous HOCl is beneficial to better understand and treat ferroptosis-related diseases.

A novel LD-targeting cysteine-activated fluorescent probe for diagnosis of APAP-induced liver injury and its application in food analysis.

Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM).

In Vivo Pharmacokinetic Study of Polysaccharide DPC1 after Oral and Intraperitoneal Administration.

(1) Background: is a medicinal plant, and its polysaccharides are used for immunomodulation and the treatment of hyperglycemia. Investigation of the tissue distribution and pharmacokinetics of polysaccharide can further elucidate its pharmacological mechanisms. (2) Methods: A fluorescence-labeling approach using rhodamine B (RhB) as a fluorescent molecular probe was used for the quantitative assessment of the polysaccharide from dried (DPC1) samples, and the pharmacokinetics and tissue distribution of DPC1 were evaluated in mice after intraperitoneal or oral administration.