miR-217-5p NanomiRs Inhibit Glioblastoma Growth and Enhance Effects of Ionizing Radiation via EZH2 Inhibition and Epigenetic Reprogramming.

: CSCs are critical drivers of the tumor and stem cell phenotypes of glioblastoma (GBM) cells. Chromatin modifications play a fundamental role in driving a GBM CSC phenotype. The goal of this study is to further our understanding of how stem cell-driving events control changes in chromatin architecture that contribute to the tumor-propagating phenotype of GBM.

Papillary Renal Neoplasm With Reverse Polarity: CT and MR Imaging Characteristics in 26 Patients.

Rationale And Objectives: To improve the diagnostic recognition of papillary renal neoplasm with reverse polarity (PRNRP) through comprehensive analysis of computed tomography (CT) and magnetic resonance imaging (MRI) findings.

Materials And Methods: A retrospective multi-center study was conducted on patients with pathologically confirmed PRNRPs from 2019 to 2024, encompassing six institutions. Clinical and pathological data were meticulously documented.

Heteroaryl Glutarimides and Dihydrouracils as Cereblon Ligand Scaffolds for Molecular Glue Degrader Discovery.

Stabilization of cereblon (CRBN)/neosubstrate complexes with molecular glues followed by degradation of those neosubstrates is an emerging strategy in drug discovery with compelling potential to target certain proteins that were previously considered to be undruggable. In this context, the discovery of novel CRBN ligands is an important area of ongoing research that holds promise to expand the scope of proteins that can be targeted through this mode of action. Herein, we describe the synthesis and evaluation of CRBN ligands featuring heteroaryl glutarimide and dihydrouracil scaffolds.

Single-cell data-driven design of armed oncolytic virus to boost cooperative innate-adaptive immunity against cancer.

Oncolytic viruses have been considered promising cancer immunotherapies. However, oncovirotherapy agents impart durable responses in only a subset of cancer patients. Thus, exploring the cellular and molecular mechanisms underlying the heterogeneous responses in patients can provide guidance to develop more effective oncolytic virus therapies.

Obtaining HBV core protein VLPs carrying SARS-CoV-2 nucleocapsid conserved fragments as vaccine candidates.

The Hepatitis B core antigen (HBcAg) has been used as a carrier of several heterologous protein fragments based on its capacity to form virus-like particles (VLPs) and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal domain of SARS-CoV-2 nucleocapsid (N) protein fused to HBcAg. The recombinant proteins, obtained in E.

Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R.

Study Question: What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)?

Summary Answer: Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels.

What Is Known Already: Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development.

Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon.

Current malaria diagnostics are invasive, lack sensitivity, and rapid tests are plagued by deletions in target antigens. Here we introduce the Cytophone, an innovative photoacoustic flow cytometer platform with high-pulse-rate lasers and a focused ultrasound transducer array to noninvasively detect and identify malaria-infected red blood cells (iRBCs) using specific wave shapes, widths, and time delays generated from the absorbance of laser energy by hemozoin, a universal biomarker of malaria infection. In a population of Cameroonian adults with uncomplicated malaria, we assess our device for safety in a cross-sectional cohort (n = 10) and conduct a performance assessment in a longitudinal cohort (n = 20) followed for 30 ± 7 days after clearance of parasitemia.

Diagnostic Utility of a 90-Gene Expression Assay (Canhelp-Origin) for Patients with Metastatic Cancer with an Unclear or Unknown Diagnosis.

Background: Metastatic cancers with unclear or unknown origins pose significant challenges in diagnosis and management, frequently leading to suboptimal outcomes. Studies have demonstrated that a 90-gene expression assay is effective in predicting the primary origin and guiding the site-specific therapy to improve prognosis. This study aimed to evaluate the clinical effectiveness of a 90-gene expression assay in patients with unclear or unknown diagnoses.

Defects-Rich Heterostructures Trigger Strong Polarization Coupling in Sulfides/Carbon Composites with Robust Electromagnetic Wave Absorption.

Defects-rich heterointerfaces integrated with adjustable crystalline phases and atom vacancies, as well as veiled dielectric-responsive character, are instrumental in electromagnetic dissipation. Conventional methods, however, constrain their delicate constructions. Herein, an innovative alternative is proposed: carrageenan-assistant cations-regulated (CACR) strategy, which induces a series of sulfides nanoparticles rooted in situ on the surface of carbon matrix.

Data-driven risk stratification and precision management of pulmonary nodules detected on chest computed tomography.

The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases.

Clinical characteristics and microbial signatures in the lower airways of diabetic and nondiabetic patients with pneumonia.

Background: The microbial signatures in diabetes with pneumonia and the risk factors of severe pneumonia (SP) in diabetic patients are not clear. Our study explored microbial signatures and the association between clinical characteristics and SP then constructed a risk model to find effective biomarkers for predicting pneumonia severity.

Methods: Our study was conducted among 273 patients with pneumonia diagnosed and treated in our hospital from January 2018 to May 2021.

Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34 cell therapy to induce fetal hemoglobin for sickle cell disease.

Sickle cell disease (SCD) is a common, severe genetic blood disorder. Current pharmacotherapies are partially effective and allogeneic hematopoietic stem cell transplantation is associated with immune toxicities. Genome editing of patient hematopoietic stem cells (HSCs) to reactivate fetal hemoglobin (HbF) in erythroid progeny offers an alternative potentially curative approach to treat SCD.

Optimization of fermentation parameters to improve the biosynthesis of selenium nanoparticles by Bacillus licheniformis F1 and its comprehensive application.

Background: Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount.

Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

Background: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT.

Methods: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy.

Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean ICs of 0.

Identification and affinity enhancement of T-cell receptor targeting a KRAS cancer neoantigen.

Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS from three predicted high affinity peptides.

Testing multiplexed anti-ASFV CRISPR-Cas9 in reducing African swine fever virus.

Unlabelled: African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication .

Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

Background And Objectives: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD.

Methods: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies.