Cutting-edge: bionanomaterial solutions in the battle against Severe Acute Respiratory Syndrome Coronavirus 2.

Amidst the ongoing COVID-19 pandemic, the imperative of our time resides in crafting stratagems of utmost precision to confront the relentless SARS-CoV-2 and quell its inexorable proliferation. A paradigm-shifting weapon in this battle lies in the realm of nanoparticles, where the amalgamation of cutting-edge nanochemistry begets a cornucopia of inventive techniques and methodologies designed to thwart the advances of this pernicious pathogen. Nanochemistry, an artful fusion of chemistry and nanoscience, provides a fertile landscape for researchers to craft innovative shields against infection.

Patient-derived Organoids and Xenografts Uncover Therapeutic Vulnerabilities in Colorectal Signet Ring Cell Carcinomas.

Purpose: Identifying therapeutic targets for Signet Ring Cell Carcinoma (SRCC) of the colon and rectum is a clinical challenge due to the lack of Patient-Derived Organoids (PDO) or Xenografts (PDX). We present a robust method to establish PDO and PDX models to answer address this unmet need. We demonstrate that these models identify novel therapeutic strategies targeting therapy resistance and peritoneal metastasis.

Economic impact of initial glaucoma treatment with selective laser trabeculoplasty on the Brazilian Public Health System.

Purpose: To evaluate the economic impact of the following initial treatment scenarios for glaucoma on the Brazilian Public Health System (SUS): (1) traditional continuous instillation of hypotensive eye drops and (2) single session of selective laser trabeculoplasty.

Methods: Economic impact was analyzed in three scenarios, from the least to the most conservative, for a hypothetical cohort of 5,000 individuals with open-angle glaucoma. Thereafter, projections were made on the basis of a glaucoma prevalence of 3% in the 2021 Brazilian population size.

Assessment of the content and quality of YouTube videos on retinopathy of prematurity: a cross-sectional study.

Purpose: This study aimed to evaluate the quality and reliability of YouTube videos as an educational resource about retinopathy of prematurity.

Methods: Videos were sourced from YouTube using the search terms "retinopathy of prematurity" and "premature retinopathy" with the default settings. Each video was assessed on the following metrics: views, likes, dislikes, comments, upload source, country of origin, view ratio, like ratio, and video power index.

Dispersal of Sensu Lato Conidia from Infected Citrus and Strawberry Under Simulated Rainfall and Different Laminar and Turbulent Wind Speeds.

Species of the complex cause postbloom fruit drop of citrus and anthracnose fruit rot of strawberries. produces acervuli in diseased citrus flowers and strawberry fruit, surviving asymptomatically on vegetative tissues. Previous studies have suggested that dispersal mechanisms other than windblown rain may be involved in dispersal of conidia of sensu lato.

Classification-based pathway analysis using GPNet with novel P-value computation.

Pathway analysis plays a critical role in bioinformatics, enabling researchers to identify biological pathways associated with various conditions by analyzing gene expression data. However, the rise of large, multi-center datasets has highlighted limitations in traditional methods like Over-Representation Analysis (ORA) and Functional Class Scoring (FCS), which struggle with low signal-to-noise ratios (SNR) and large sample sizes. To tackle these challenges, we use a deep learning-based classification method, Gene PointNet, and a novel $P$-value computation approach leveraging the confusion matrix to address pathway analysis tasks.

Targeting AXL inhibits the growth and metastasis of prostate cancer in bone.

Purpose: After failing primary and secondary hormonal therapy, castration-resistant and neuroendocrine prostate cancer metastatic to the bone is invariably lethal, although treatment with docetaxel and carboplatin can modestly improve survival. Therefore, agents targeting biologically relevant pathways in PCa and potentially synergizing with docetaxel and carboplatin in inhibiting bone metastasis growth are urgently needed.

Experimental Design: Phosphorylated (activated) AXL expression in human prostate cancer bone metastases was assessed by immunohistochemical staining.

Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma.

Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC.

Patients And Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment).

New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy.

Program Director Perspectives on DEI Initiatives in the Dermatology Residency Selection Process.

The American Academy of Dermatology (AAD) has maintained a commitment to diversity, equity, and inclusion (DEI) initiatives; however, a recent strike down of affirmative action by the US Supreme Court has caused similar efforts to be called into question. This prompted our investigation into dermatology program director (PD) perceptions of DEI programming and its integration into resident selection. A cross-sectional survey of PDs at US dermatology residency programs was conducted from April 2024 to July 2024 (N=30).

Iron Deficiency and All-Cause Hospitalization Risk in a Clinical Cohort of COPD.

Background: The impact of iron deficiency on COPD morbidity independent of anemia status is unknown. Understanding the association between iron deficiency, anemia status, and risk of hospitalization in COPD may inform an approach to these comorbidities.

Study Design And Methods: Adults ≥40 years from the Johns Hopkins COPD Precision Medicine Center of Excellence data repository with an outpatient iron profile and 1 year of subsequent follow-up time were included in the study.

Role of the Mobile Active Site Flap in IMP Dehydrogenase Inhibitor Binding.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising antibiotic target. This enzyme catalyzes the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), which is the rate-limiting step in guanine nucleotide biosynthesis. Bacterial IMPDH-specific inhibitors have been developed that bind to the NAD site.

Landau-Levich Scaling for Optimization of Quantum Dot Layer Morphology and Thickness in Quantum-Dot Light-Emitting Diodes.

Quantum dot (QD) light-emitting diodes (QLEDs) are promising candidates for next-generation displays because of their high efficiency, brightness, broad color gamut, and solution-processability. Large-scale solution-processing of electroluminescent QLEDs poses significant challenges, particularly concerning the precise control of the active layer's thickness and uniformity. These obstacles directly impact charge transport, leading to current leakage and reduced overall efficiency.

The multifaceted role of the inferior colliculus in sensory prediction, reward processing, and decision-making.

The inferior colliculus (IC) has traditionally been regarded as an important relay in the auditory pathway, primarily involved in relaying auditory information from the brainstem to the thalamus. However, this study uncovers the multifaceted role of the IC in bridging auditory processing, sensory prediction, and reward prediction. Through extracellular recordings in monkeys engaged in a sound duration-based deviation detection task, we observed a 'climbing effect' in neuronal firing rates, indicative of an enhanced response over sound sequences linked to sensory prediction rather than reward anticipation.

Distinct checkpoint and homolog biorientation pathways regulate meiosis I in Drosophila oocytes.

Mitosis and meiosis have two mechanisms for regulating the accuracy of chromosome segregation: error correction and the spindle assembly checkpoint (SAC). We have investigated the function of several checkpoint proteins in meiosis I of Drosophila oocytes. Increased localization of several SAC proteins was found upon depolymerization of microtubules by colchicine.

Do global health networks facilitate innovation, learning and sharing? A qualitative analysis of the Quality-of-Care Network in Bangladesh, Ethiopia, Malawi, and Uganda.

The Quality-of-Care Network (QCN), launched by WHO and partners, links global and national actors across several countries to improve maternal and newborn health. We conducted a prospective qualitative study to examine how QCN in Bangladesh, Ethiopia, Malawi and Uganda facilitated learning, sharing, and innovation within and between network countries. We conducted 227 key informant interviews with QCN actors at global, national, and facility levels iteratively in two to four rounds from June 2019 to March 2022.

Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.

ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.

chitinase-like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover.

bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase-like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion.

Hsp90, DnaK, and ClpB collaborate in protein reactivation.

Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis. Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s to reactivate inactive and aggregated proteins by a mechanism that requires a direct interaction between Hsp90 and Hsp70 both in vitro and in vivo. and yeast Hsp70s also collaborate in bichaperone systems with ClpB and Hsp104, respectively, to disaggregate and reactivate aggregated proteins and amyloids such as prions.

Subunit-specific conductance of single homomeric and heteromeric HCN pacemaker channels at femtosiemens resolution.

In mammals, the four subunit isoforms HCN1-4 assemble to form functional homotetrameric and heterotetrameric hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels. Despite the outstanding relevance of HCN channels for organisms, including generating electrical rhythmicity in cardiac pacemaker cells and diverse types of brain neurons, key channel properties are still elusive. In particular, the unitary conductance, of HCN channels is highly controversial.

Bacterial sensor evolved by decreasing complexity.

Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by signal binding to ligand-binding domains (LBDs). Cache domains are omnipresent LBDs found in bacteria, archaea, and eukaryotes, including humans.