Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder.

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T Itpr3/J (BTBR) mice, a well-established model for autism research.

Novel needle-type electrocoagulation and combination pharmacotherapy: Basic and clinical studies on efficacy and safety in treating keloids.

Background And Aim: Keloids cannot be effectively treated using monotherapy regimens. This study aimed to evaluate the efficacy and safety of ablation (a novel needle-assisted electrocoagulation technique) combined with pharmacotherapy (corticosteroid and 5-fluorouracil [5-FU] injections) in removing keloids and to investigate the underlying biological mechanisms.

Methods: The effects of energy consumption and duration of needle-assisted electrocoagulation on the ablation zone were tested in porcine liver tissue, which simulates human skin.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear.

Cognitive impairment in Alzheimer's disease FAD mouse model: Synaptic loss facilitated by activated microglia via C1qA.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by cognitive dysfunction. The connection between neuroinflammation and abnormal synaptic function in AD is recognized, but the underlying mechanisms remain unclear. In this study, we utilized a mouse model of AD, FAD mice aged 6-7 months, to investigate the molecular changes affecting cognitive impairment.

P2Y12 receptor mediates apoptosis and demyelination to affect functional recovery in mice with spinal cord injury.

Among diseases of the central nervous system (CNS), spinal cord injury (SCI) has a high fatality rate. It has been proven that P2Y G protein-coupled purinergic receptors have a neuroprotective role in apoptosis and regeneration inside the damaged spinal cord. The P2Y12 receptor (P2Y12R) has recently been linked to peripheral neuropathy and stroke.

Single-cell characterization of macrophages in uveal melanoma uncovers transcriptionally heterogeneous subsets conferring poor prognosis and aggressive behavior.

Uveal melanoma (UM) is the most frequent primary intraocular malignancy with high metastatic potential and poor prognosis. Macrophages represent one of the most abundant infiltrating immune cells with diverse functions in cancers. However, the cellular heterogeneity and functional diversity of macrophages in UM remain largely unexplored.

Upregulation of SLC12A3 and SLC12A9 Mediated by the HCP5/miR-140-5p Axis Confers Aggressiveness and Unfavorable Prognosis in Uveal Melanoma.

Perturbation of solute carriers (SLCs) has been implicated in metabolic disorders and cancer, highlighting the potential for drug discovery and therapeutic opportunities. However, there is relatively little exploration of the clinical relevance and potential molecular mechanisms underlying the role of the SLC12 family in uveal melanoma (UVM). Here, we performed an integrative multiomics analysis of the SLC12 family in multicenter UVM datasets and found that high expression of SLC12A3 and SLC12A9 was associated with unfavorable prognosis.

Integrated immunogenomic analysis of single-cell and bulk tissue transcriptome profiling unravels a macrophage activation paradigm associated with immunologically and clinically distinct behaviors in ovarian cancer.

Introduction: Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment, which plays a critical role in a variety of cancer types.

Objectives: To investigate the heterogeneity and the homeostasis of different macrophage subtypes, as well as their effect on biological and clinical manifestations of ovarian cancer (OV).

Method: Integrated immunogenomic analysis of single-cell and bulk tissuetranscriptome profiling was performed to systematically investigate the association between macrophage activation and prognostic and therapeutic efficacy.

Pan-cancer landscape of T-cell exhaustion heterogeneity within the tumor microenvironment revealed a progressive roadmap of hierarchical dysfunction associated with prognosis and therapeutic efficacy.

Background: T cells form the major component of anti-tumor immunity. A deeper understanding of T cell exhaustion (TEX) heterogeneity within the tumor microenvironment (TME) is key to overcoming TEX and improving checkpoint blockade immunotherapies in the clinical setting.

Methods: We conducted a comprehensive pan-cancer analysis of TEX subsets from 9564 tumor samples across 30 bulk solid cancer types.

A multi-omics deep learning model for hypoxia phenotype to predict tumor aggressiveness and prognosis in uveal melanoma for rationalized hypoxia-targeted therapy.

Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults and is characterized by aggressive behaviors and a lack of targeted therapies. Hypoxia-targeted therapy has become a promising new therapeutic strategy in tumors. Therefore, a better understanding of the tumor hypoxia microenvironment is critical to improve the treatment efficacy of UM.

iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor. The use of precision medicine for UM to enable personalized diagnosis, prognosis, and treatment require the development of computer-aided strategies and predictive tools that can identify novel high-confidence susceptibility genes (HSGs) and potential therapeutic drugs. In the present study, a computational framework via propagation modeling on integrated multi-layered molecular networks (abbreviated as iUMRG) was proposed for the systematic inference of HSGs in UM.

Transcriptional landscape of circulating platelets from patients with COVID-19 reveals key subnetworks and regulators underlying SARS-CoV-2 infection: implications for immunothrombosis.

Background: Thrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID-19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Platelets are essential cells that regulate hemostasis, thrombus formation and inflammation; however, the mechanism underlying the interaction between platelets and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear.

Results: The present study performed RNA sequencing on the RNA isolated from platelets obtained from 10 COVID-19 patients and eight healthy donors, and discovered that SARS-CoV-2 not only significantly altered the coding and non-coding transcriptional landscape, but also altered the function of the platelets, promoted thrombus formation and affected energy metabolism of platelets.

Computational elucidation of spatial gene expression variation from spatially resolved transcriptomics data.

Recent advances in spatially resolved transcriptomics (SRT) have revolutionized biological and medical research and enabled unprecedented insight into the functional organization and cell communication of tissues and organs i. Identifying and elucidating gene spatial expression variation (SE analysis) is fundamental to elucidate the SRT landscape. There is an urgent need for public repositories and computational techniques of SRT data in SE analysis alongside technological breakthroughs and large-scale data generation.

Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers.

Background: 5-Hydroxymethylcytosine (5hmC) is a significant DNA epigenetic modification. However, the 5hmC modification alterations in genomic regions encoding long non-coding RNA (lncRNA) and their clinical significance remain poorly characterized.

Results: A three-phase discovery-modeling-validation study was conducted to explore the potential of the plasma-derived 5hmC modification level in genomic regions encoding lncRNAs as a superior alternative biomarker for cancer diagnosis and surveillance.

Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes.

The emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level.

[Clinical Diagnosis and Treatment Recommendations for Immune Checkpoint Inhibitor-related Hematological Adverse Events].

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis.

Treatment and management of adrenal cancer in a specialized Australian endocrine surgical unit: approaches, outcomes and lessons learnt.

Background: Adrenocortical carcinoma is a rare and heterogeneous malignancy with poor outcomes. Recent research has suggested that outcomes may be improved by centralization of care in specialist centres. We review our evolving 21-year experience in managing adrenocortical carcinoma with a view towards outcomes and lessons learnt.

Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart Failure: Carvedilol or Metoprolol Evaluation Study.

Background: β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents.

Papillary thyroid cancer-derived exosomes contain miRNA-146b and miRNA-222.

Background: With the increasing diagnosis of indolent papillary thyroid cancer (PTC), the task of identifying those likely to suffer from recurrence is becoming ever more challenging. MicroRNA (miRNA/miR) in the circulation has been demonstrated as potential biomarkers of recurrence in PTC. This study aimed to investigate in vitro if extracellular miRNAs are contained in exosomes, and their potential effect on other cells.

Etiology-specific assessment of predictors of long-term survival in chronic systolic heart failure.

Background: We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF).

Methods And Results: Between 1995 and 2009 baseline characteristics, treatment and follow-up data from 2318 CHF-patients due to ischemic (ICM; 1100 patients) or dilated cardiomyopathy (DCM; 1218 patients) were prospectively compared. To calculate hazard ratios with 95%-confidence intervals cox regression was used.

Dissociated stimulus and response conflict effect in the Stroop task: evidence from evoked brain potentials and brain oscillations.

The Stroop task is a classic paradigm that can be used to examine cognitive control as it contains conditions with and without interference. Cumulative evidence suggests that both stimulus and response conflict contribute to the Stroop interference effect. However, it remains unclear whether there are dissociable event-related potential (ERP) or frequency band-specific electroencephalographic (EEG) power changes associated with stimulus conflict and response conflict.

Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer.

Micro-RNAs are dysregulated in medullary thyroid carcinoma (MTC) and preliminary studies have shown that miRNAs may enact a therapeutic effect through changes in autophagic flux. Our aim was to study the in vitro effect of miR-9-3p on MTC cell viability, autophagy and to investigate the mRNA autophagy gene profile of sporadic versus hereditary MTC. The therapeutic role of miR-9-3p was investigated in vitro using human MTC cell lines (TT and MZ-CRC-1 cells), cell viability assays, and functional mechanism studies with a focus on cell cycle, apoptosis, and autophagy.