Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide.

Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (HO)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (HS) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. Isolated neural retinas from cows were exposed to oxidative damage using HO (100 µM) for 10 min.

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies.

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited.

Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.

Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior.

Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3'-Processing Suppression.

: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3'-processing (3'P), thereby establishing its dual-targeting capability.

Pathogen Detection and Resistome Analysis in Healthy Shelter Dogs Using Whole Metagenome Sequencing.

According to the Humane Society, 25 to 40 percent of pet dogs in the United States are adopted from animal shelters. Shelter dogs can harbor bacterial, viral, fungal, and protozoal pathogens, posing risks to canine and human health. These bacterial pathogens may also carry antibiotic resistance genes (ARGs), serving as a reservoir for antimicrobial resistance (AMR) transmission.

Flaviviruses-Induced Neurological Sequelae.

Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological diseases during acute infection, from mild, flu-like symptoms to severe and fatal encephalitis. A total of 20-50% of patients who recovered from acute flavivirus infections experienced long-term cognitive issues.

Integrating Remote Sensing and Soil Features for Enhanced Machine Learning-Based Corn Yield Prediction in the Southern US.

Efficient and reliable corn ( L.) yield prediction is important for varietal selection by plant breeders and management decision-making by growers. Unlike prior studies that focus mainly on county-level or controlled laboratory-scale areas, this study targets a production-scale area, better representing real-world agricultural conditions and offering more practical relevance for farmers.

Conjugation of Short-Chain Fatty Acids to Bicyclic-Amines for Analysis by Liquid Chromatography Tandem Mass Spectroscopy.

Conjugation of short-chain fatty acids (SDFAs) to amines containing ring structures allows for better measurement by liquid chromatography tandem mass spectroscopy (LC-MS/MS). However, collision-induced dissociation (CID) results in breaking the conjugate back to the original SCFA and amine. We therefore set out to find an amine that would remain on the SCFA after CID and create a unique daughter for selectivity of measurement.

Hydrogen-Bonded Di(hydroperoxy)alkane Adducts of the Type CyP=O·(HOO)CHR (R = Alkyl).

Five representatives of a novel type of di(hydroperoxy)alkane adducts of phosphine oxides have been synthesized and fully characterized, including their solubility in organic solvents. The phosphine oxide CyPO () has been used in combination with the corresponding aldehydes to create the adducts CyPO·(HOO)CHCH (), CyPO·(HOO)CHCHCH (), CyPO·(HOO)CH(CH)CH (), CyPO·(HOO)CH(CH)CH (), and CyPO·(HOO)CH(CH)CH (). All adducts crystallize easily and contain the peroxide and phosphine oxide hydrogen-bonded in 1:1 ratios.

Genetic Algorithm-Enhanced Direct Method in Protein Crystallography.

Direct methods based on iterative projection algorithms can determine protein crystal structures directly from X-ray diffraction data without prior structural information. However, traditional direct methods often converge to local minima during electron density iteration, leading to reconstruction failure. Here, we present an enhanced direct method incorporating genetic algorithms for electron density modification in real space.

Modeling, Design, and Laboratory Testing of a Passive Friction Seismic Metamaterial Base Isolator (PFSMBI).

This paper focuses on the theoretical and analytical modeling of a novel seismic isolator termed the Passive Friction Mechanical Metamaterial Seismic Isolator (PFSMBI) system, which is designed for seismic hazard mitigation in multi-story buildings. The PFSMBI system consists of a lattice structure composed of a series of identical small cells interconnected by layers made of viscoelastic materials. The main function of the lattice is to shift the fundamental natural frequency of the building away from the dominant frequency of earthquake excitations by creating low-frequency bandgaps (FBGs) below 20 Hz.

Assessing Corrosion Effects on the Electrical Performance of Wearable Photovoltaic Cells: A Comparative Analysis of Current Consistency and Resistance.

Wearable photovoltaic (PV) cells offer a sustainable and lightweight solution for energy-harvesting applications, including safety gear and protective textiles. Despite their growing adoption, the application of PV cells in marine environments is limited due to the corrosive conditions that can degrade performance. This study evaluates the impact of corrosion on commercially sourced PV cells by analyzing maximum current and electrical resistance.

A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).

Targeting Bacterial Cell Division with Benzodioxane-Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens.

The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, constitutes a priority in the list of AMR-threatening pathogens. To counteract this fundamental problem, the bacterial cell division cycle and the crucial proteins involved in this process emerged as novel attractive targets. FtsZ is an essential cell division protein, and FtsZ inhibitors, especially the benzamide derivatives, have been exploited in the last decade.

Dissecting the Binding Affinity of Anti-SARS-CoV-2 Compounds to Human Transmembrane Protease, Serine 2: A Computational Study.

The human transmembrane protease, serine 2 (TMPRSS2), essential for SARS-CoV-2 entry, is a key antiviral target. Here, we computationally profiled the TMPRSS2-binding affinities of 15 antiviral compounds. Molecular dynamics (MD) simulations for the docked complexes revealed that three compounds exited the substrate-binding cavity (SBC), suggesting noncompetitive inhibition.

Luminescence Properties of Hoechst 33258 in Polyvinyl Alcohol Films.

We report a comprehensive investigation of the photophysical properties of Hoechst 33258 (HOE) embedded in polyvinyl alcohol (PVA) films. HOE displays a bright, highly polarized, blue fluorescence emission centered at 430 nm, indicating effective immobilization within the polymer matrix of PVA. Its fluorescence quantum yield is notably high (~0.

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine-Biology Is Still King.

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint risk-of-recurrence and BluePrint molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC.

Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy.

Glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients.

Surgical Outcomes and Associated Morbidity of Active and Expectant Management of Second-Trimester Placenta Accreta Spectrum (PAS).

Management of second-trimester placenta accreta spectrum (PAS) is currently center-dependent with minimal evidence-based practices. This study aims to analyze outcomes of hysterectomy as second-trimester active management (AM) versus cesarean hysterectomy as expectant management (EM) in cases of PAS with intraoperative and postoperative outcomes. This study is a retrospective case-control study of patients with a pathology-confirmed diagnosis of PAS managed at a single center over 16 years (2005-2020).

Research Progress and Clinical Translation Potential of Coronary Atherosclerosis Diagnostic Markers from a Genomic Perspective.

Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment.

Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children.

Background: Clindamycin resistance among community-associated methicillin-resistant (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children's hospital.

Age-Related Changes in Gut Health and Behavioral Biomarkers in a Beagle Dog Population.

The gut and the gut microbiome communicate with the nervous system through the gut-brain axis via neuroimmune and neuroendocrine mechanisms. Despite existing research, studies exploring this link in aging dogs are limited. This study aims to examine multiple blood and fecal biomarkers of intestinal health, along with various behavioral indicators based on saliva, blood, observations, and activity, in different age populations (junior: <2 y.

A Review of Neoadjuvant Therapy for Localized and Locally Advanced Renal Cell Carcinoma.

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma (RCC). However, the roles of VEGFR-TKIs and IOs in the neoadjuvant setting for locoregional/locally advanced RCC remain undefined, where the goals may be primary tumor downsizing/downstaging and potentially eradicating micrometastatic disease. This review will examine VEGFR-TKI monotherapy, IO monotherapy, and VEGFR-TKI/IO combination regimens in a preoperative setting with a focus on the efficacy, toxicity, surgical, and long-term implications.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.

The human nuclear receptor (NR) superfamily consists of 48 genes that are ligand-activated transcription factors that play a key role in maintaining cellular homeostasis and in pathophysiology. NRs are important drug targets for both cancer and non-cancer endpoints as ligands for these receptors can act as agonists, antagonists or inverse agonists to modulate gene expression. With two exceptions, the classical mechanism of action of NRs involves their interactions as monomers, dimers or heterodimers with their cognate response elements (cis-elements) in target gene promoters.