Optimization of a Piperidine CD4-Mimetic Scaffold Sensitizing HIV-1 Infected Cells to Antibody-Dependent Cellular Cytotoxicity.

The ability of the HIV-1 accessory proteins Nef and Vpu to decrease CD4 protects infected cells from antibody-dependent cellular cytotoxicity (ADCC) by limiting the exposure of vulnerable epitopes to envelope glycoprotein (Env). Small-molecule CD4 mimetics (CD4mcs) based on piperidine scaffolds represent a new family of agents capable of sensitizing HIV-1-infected cells to ADCC by exposing CD4-induced (CD4i) epitopes on Env that are recognized by non-neutralizing antibodies which are abundant in plasma of people living with HIV. Here, we employed the combined methods of parallel synthesis, structure-based design, and optimization to generate a new line of piperidine-based CD4mcs, which sensitize HIV-1 infected cells to ADCC activity.

Synthesis of Rapicone Based on Acyl Ketene-Alkyne Cycloaddition.

We report herein a concise route for the total synthesis of rapicone. The key strategy to form the ynone intermediate involves an Fe(III)/TEMPO-catalyzed aerobic oxidation of a 1,3-dihydroisobenzofuran moiety. This ether oxidation for the simultaneous installation of the keto aldehyde allowed the effective formation of the required ynone intermediate.

Folic-acid-targeted drug delivery system implementing Angelica gigas polysaccharide: A potential strategy for colorectal cancer treatment.

The study focuses on the development of folate-targeted conjugates utilizing Angelica gigas polysaccharide (F2) as a drug carrier for colorectal cancer therapy. We synthesized F2-C-5-FU conjugates by linking carboxymethyl-5-fluorouracil (C-5-FU) with folic acid (FA) through ester bonding. The drug release behavior of F2-C-5-FU-FA was pH-dependent, favoring release under alkaline conditions.

Aerobic bacterial group as an early-stage biomarker from faecal samples of patients with colorectal cancer without distant metastasis.

The current approaches for detecting most colorectal polyps and early neoplasms lack sufficient sensitivity and specificity, potentially hindering treatment and ultimately reducing survival rates. Here, we performed a metagenomic analysis to identify microbiome markers in stool samples from patients with early-stage colorectal cancer (CRC). We compared the composition of gut microbiota between patients with CRC and healthy individuals, specifically focusing on patients with early-stage CRC, defined as those without core mutations (KRAS, BRAF) for CRC diagnosis, stable microsatellite instability, and distant metastasis.

Prognostic value of gray-white matter ratio measured by brain MRI-based CT structures in comatose patients after cardiac arrest.

Background: Post-cardiac arrest care advancements have improved resuscitation outcomes, but many survivors still face severe neurological deficits or death from brain injury. Herein, we propose a consistent prognosis prediction approach using magnetic resonance imaging (MRI) to analyze anatomical regions represented by the gray and white matter, and subsequently apply it on computed tomography (CT) to calculate the gray-white matter ratio (GWR). We compared this novel method with traditional measures to validate its ability to predict the prognosis of patients resuscitated after cardiac arrest.

Trainee experience in virtual reality simulation in orbital surgery.

Purpose: To demonstrate the role of Virtual Reality (VR) in orbital surgery as an educational tool for surgical trainees.

Methods: A single-center prospective study was conducted from February 2021 to April 2023. Pre-operative magnetic resonance imaging and computed tomography scans were used to create patient-specific VR models of the orbit using ImmersiveTouch Software.

Modulatory Effect of Blood LDL Cholesterol on the Association between Cerebral Aβ and Tau Deposition in Older Adults.

Background: This study investigates the synergistic relationship between blood low-density lipoprotein cholesterol (LDL-C) and cerebral beta-amyloid (Aβ) in relation to tau deposition, a key factor in the pathology of Alzheimer's disease (AD), in older adults across a diverse cognitive spectrum.

Objectives: To examine whether higher levels of LDL-C in the blood moderate the association of cerebral Aβ with tau deposition in older adults, including those with normal cognition, mild cognitive impairment, and Alzheimer's disease dementia.

Design: Cross-sectional design.

A Flexible Membrane May Improve Bone Regeneration by Increasing Hydrophilicity and Conformability in Lateral Bone Augmentation.

Collagen membranes play a crucial role in guided bone regeneration (GBR) by preventing soft tissue infiltration and maintaining space for bone formation. This study investigated the impact of collagen membrane flexibility on GBR outcomes through in vitro and in vivo analyses. Flexible (0.

Exploratory Evaluation of Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR) With Central Nervous System-Active Drugs in Brain Metastases Treatment.

Purpose: Brain metastases (BMs) affect an increasing number of cancer patients and are typically managed with stereotactic radiosurgery (SRS). Our institution advocates the use of Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR), where radiation is delivered in high-dose pulses at extended intervals allowing for treatment adaptation and easy concurrent systemic therapy integration. We explore the integration of PULSAR with central nervous system (CNS)-active drugs (CNS-aDs).

Machine learning-based prediction of contralateral knee osteoarthritis development using the Osteoarthritis Initiative and the Multicenter Osteoarthritis Study dataset.

Having osteoarthritis in one knee is reported as an independent risk factor for developing contralateral knee osteoarthritis (KOA). However, no study has been designed to predict the development of contralateral KOA (cKOA). The authors hypothesized that specific risk factors for cKOA development exist and that it could be accurately predicted with the assistance of machine learning.

Factors affecting the occurrence of maxillary sinus fungus ball.

Objective: We identified patients who initially did not have a maxillary sinus fungus ball on computed tomography (CT) but developed it on a subsequent CT scan. We assessed potential risk factors for developing a maxillary sinus fungus ball between the two scans.

Patients And Methods: This study included 35 patients with 38 lesions who initially had no maxillary sinus fungus balls on CT but were later diagnosed with the condition and underwent surgery.

Combinatorial immunotherapy of anti-MCAM CAR-modified expanded natural killer cells and NKTR-255 against neuroblastoma.

Pediatric patients with recurrent metastatic neuroblastoma (NB) have a dismal 5-year survival. Novel therapeutic approaches are urgently needed. The melanoma cell adhesion molecule (MCAM/CD146/MUC18) is expressed in a variety of pediatric solid tumors, including NB, and constitutes a novel target for immunotherapy.

NaCTR: Natural product-derived compound-based drug discovery pipeline from traditional oriental medicine by search space reduction.

The drug discovery pipelines require enormous time and cost, albeit their infamously high risk of failures. Reducing such risk has therefore been the utmost goal in the process. Recently, natural products (NPs) in traditional oriental medicine (TOM) have come into the spotlight for their efficacy and safety supported throughout the history.

Novel reassortant H2N2 low pathogenic avian influenza virus in live bird markets in the Northeastern United States, 2019-2023.

The H2N2 avian influenza viruses (AIV) have been reported in the Northeast United States of America (USA) live bird market (LBM) system since 2014. In this study, we investigated the genetic evolution and characterized molecular markers of the recent H2N2 AIVs in LBMs in the Northeast USA. Phylogenetic analyses revealed that the LBM H2N2 lineage has evolved into three distinct subgroups (groups A.

Comparative genomic and phenotypic analysis of low- and high-virulent Acinetobacter baumannii strains: Insights into antimicrobial resistance and virulence potential.

Multi-drug resistant Acinetobacter baumannii poses a significant threat to public health. This study investigated the genomic features and phenotypic characteristics of two clinical A. baumannii strains, KBN10P01317 (low-virulent) and KBN10P01599 (high-virulent), which share the same sequence type and antimicrobial susceptibility profile.

Versatile platform of 3D/2D/1D:ZnFeO/NiAl-LDH/MWCNTs nanocomposite for photocatalytic purification of dinoseb and electrocatalytic O evolution reaction.

Integrating photocatalysis with electrocatalysis may represent a synergistic approach to address environmental and energy challenges. In this context, we explored synthesizing a series of nanocomposite materials using a solid-state approach involving simple grinding and subsequent thermal treatment for the photocatalytic purification of dinoseb and electrocatalytic oxygen evolution (OER). Interestingly, among the series of synthesized materials, 40 wt percentage of 3D/2D/1D:ZnFeO/NiAl-LDH/MWCNTs ternary nanocomposite (40-NZM) showed highly improved dinoseb detoxification and OER efficiencies compared to those of pure materials.