A systematic review of the knowledge, attitude and practice of healthcare professionals and healthcare professional students towards household pharmaceutical waste disposal.

Background: Active pharmaceutical residues introduced into the environment through irresponsible household disposal of unused and expired medication can damage nature and health. Through medication take-back programmes, these risks can be mitigated. However, healthcare professionals' neglect of their responsibility to ensure proper disposal practices has perpetuated subpar norms among the public.

Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation.

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling are essential for cell growth and differentiation. However, the specific organization of FA components to exert spatiotemporal activation of FA proteins for force sensing and transduction remains unclear. In this study, we unveil the intricacies of FA protein nanoarchitecture and that its dynamics are coordinated by a molecular scaffold protein, BNIP-2, to initiate downstream signal transduction for cardiomyoblast differentiation.

Closing the Knowledge Gap of Post-Acquisition Sample Normalization in Untargeted Metabolomics.

Sample normalization is a crucial step in metabolomics for fair quantitative comparisons. It aims to minimize sample-to-sample variations due to differences in the total metabolite amount. When samples lack a specific metabolic quantity to accurately represent their total metabolite amounts, post-acquisition sample normalization becomes essential.

Insights into the regulation of CHIP E3 ligase-mediated ubiquitination of neuronal protein BNIP-H.

BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 homolog (BNIP-H or Caytaxin), a pivotal adaptor protein that facilitates cerebellar cortex growth and synaptic transmission, is posttranslationally modified to regulate neuronal function. This study reports the ubiquitination of BNIP-H by Carboxyl terminus of Hsc70-Interacting Protein (CHIP), a U-box containing E3 ligase that is also regulated autoubiquitination. Specifically, it was observed that CHIP autoubiquitinated itself primarily at Lys23 and Lys31 .

A Putative Frizzled 7-Targeting Compound Acts as a Firefly Luciferase Inhibitor.

The Frizzled family (FZD) of G protein-coupled receptors regulates WNT signaling mediating proliferative input. Dysregulation of FZD and exaggerated WNT/β-catenin signaling is frequently observed in intestinal cancers. Therefore, it is attractive to develop therapeutics targeting FZD for cancer treatment.

The dichotomous roles of microbial-modified bile acids 7-oxo-DCA and isoDCA in intestinal tumorigenesis.

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear.

A ZO-2 scaffolding mechanism regulates the Hippo signalling pathway.

Contact inhibition of proliferation is a critical cell density control mechanism governed by the Hippo signalling pathway. The biochemical signalling underlying cell density-dependent cues regulating Hippo signalling and its downstream effectors, YAP, remains poorly understood. Here, we reveal that the tight junction protein ZO-2 is required for the contact-mediated inhibition of proliferation.

Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to the resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy.

Stimulatory effect of eurycomanone from Jack roots on dopamine secretion in human neuroblastoma SH-SY5Y cell line.

Eurycomanone has been identified as the major bioactive compound contributing to (EL) aphrodisiac activity, however, its mechanism of action remains obscured. Presently, eurycomanone was isolated from EL root extract and its molecular structure was identified. The human neuroblastoma SH-SY5Y cell line was differentiated into human dopaminergic neuron-like cells.

HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.

HNF4A and HNF1A encode transcription factors that are important for the development and function of the pancreas and liver. Mutations in both genes have been directly linked to Maturity Onset Diabetes of the Young (MODY) and type 2 diabetes (T2D) risk. To better define the pleiotropic gene regulatory roles of HNF4A and HNF1A, we generated a comprehensive genome-wide map of their binding targets in pancreatic and hepatic cells using ChIP-Seq.

The reference genome of Macropodus opercularis (the paradise fish).

Amongst fishes, zebrafish (Danio rerio) has gained popularity as a model system over most other species and while their value as a model is well documented, their usefulness is limited in certain fields of research such as behavior. By embracing other, less conventional experimental organisms, opportunities arise to gain broader insights into evolution and development, as well as studying behavioral aspects not available in current popular model systems. The anabantoid paradise fish (Macropodus opercularis), an "air-breather" species has a highly complex behavioral repertoire and has been the subject of many ethological investigations but lacks genomic resources.

COVID-19 vaccine acceptance and uptake among caregivers of children aged 5-11 years in Ontario, Canada: A cross-sectional survey.

Introduction: Although COVID-19 vaccine safety in 5-11-year-old children has been documented, half of Ontarian children this age remain unvaccinated. This study aimed to assess caregivers' vaccine acceptance for 5-11-year-old children and identify factors associated with vaccine non-acceptance.

Methods: A multi-language self-administered survey was sent to caregivers of 5-11-year-old children through schools and community health centers within the Greater Toronto Area from April-July 2022.

Focal adhesions are controlled by microtubules through local contractility regulation.

Microtubules regulate cell polarity and migration via local activation of focal adhesion turnover, but the mechanism of this process is insufficiently understood. Molecular complexes containing KANK family proteins connect microtubules with talin, the major component of focal adhesions. Here, local optogenetic activation of KANK1-mediated microtubule/talin linkage promoted microtubule targeting to an individual focal adhesion and subsequent withdrawal, resulting in focal adhesion centripetal sliding and rapid disassembly.

Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids.

Human hippocampal organoids (hHOs) derived from human induced pluripotent stem cells (hiPSCs) have emerged as promising models for investigating neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. However, obtaining the electrical information of these free-floating organoids in a noninvasive manner remains a challenge using commercial multi-electrode arrays (MEAs). The three-dimensional (3D) MEAs developed recently acquired only a few neural signals due to limited channel numbers.

Structural basis for the distinct roles of non-conserved Pro116 and conserved Tyr124 of BCH domain of yeast p50RhoGAP.

p50RhoGAP is a key protein that interacts with and downregulates the small GTPase RhoA. p50RhoGAP is a multifunctional protein containing the BNIP-2 and Cdc42GAP Homology (BCH) domain that facilitates protein-protein interactions and lipid binding and the GAP domain that regulates active RhoA population. We recently solved the structure of the BCH domain from yeast p50RhoGAP (BCH) and showed that it maintains the adjacent GAP domain in an auto-inhibited state through the β5 strand.

Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis.

Inhibitory G alpha (GNAI or Gαi) proteins are critical for the polarized morphogenesis of sensory hair cells and for hearing. The extent and nature of their actual contributions remains unclear, however, as previous studies did not investigate all GNAI proteins and included non-physiological approaches. Pertussis toxin can downregulate functionally redundant GNAI1, GNAI2, GNAI3, and GNAO proteins, but may also induce unrelated defects.

The knowledge, attitude, and practice of the public regarding household pharmaceutical waste disposal: a systematic review (2013-2023).

Objective: The improper disposal of household pharmaceutical waste (HPW) is an emerging cause of environmental pollution. Behavioural practices are intricately linked to individuals' knowledge levels and attitudes. Thus, this systematic review aims to assess the knowledge, attitude, and practice (KAP) of HPW disposal among the public and to examine the interconnectedness of these KAP components.

ChloroDBPFinder: Machine Learning-Guided Recognition of Chlorinated Disinfection Byproducts from Nontargeted LC-HRMS Analysis.

High-resolution mass spectrometry (HRMS) is a prominent analytical tool that characterizes chlorinated disinfection byproducts (Cl-DBPs) in an unbiased manner. Due to the diversity of chemicals, complex background signals, and the inherent analytical fluctuations of HRMS, conventional isotopic pattern (Cl/Cl), mass defect, and direct molecular formula (MF) prediction are insufficient for accurate recognition of the diverse Cl-DBPs in real environmental samples. This work proposes a novel strategy to recognize Cl-containing chemicals based on machine learning.

2D/2D Heterojunction of BiOBr/BiOI Nanosheets for In Situ H O Production and Activation toward Efficient Photocatalytic Wastewater Treatment.

The presence of toxic organic pollutants in aquatic environments poses significant threats to human health and global ecosystems. Photocatalysis that enables in situ production and activation of H O presents a promising approach for pollutant removal; however, the processes of H O production and activation potentially compete for active sites and charge carriers on the photocatalyst surface, leading to limited catalytic performance. Herein, a hierarchical 2D/2D heterojunction nanosphere composed of ultrathin BiOBr and BiOI nanosheets (BiOBr/BiOI) is developed by a one-pot microwave-assisted synthesis to achieve in situ H O production and activation for efficient photocatalytic wastewater treatment.

Dystonin modifiers of junctional epidermolysis bullosa and models of epidermolysis bullosa simplex without dystonia musculorum.

The Lamc2jeb junctional epidermolysis bullosa (EB) mouse model has been used to demonstrate that significant genetic modification of EB symptoms is possible, identifying as modifiers Col17a1 and six other quantitative trait loci, several with strong candidate genes including dystonin (Dst/Bpag1). Here, CRISPR/Cas9 was used to alter exon 23 in mouse skin specific isoform Dst-e (Ensembl GRCm38 transcript name Dst-213, transcript ID ENSMUST00000183302.5, protein size 2639AA) and validate a proposed arginine/glutamine difference at amino acid p1226 in B6 versus 129 mice as a modifier of EB.

Functional analysis of Collagen 17a1: A genetic modifier of junctional epidermolysis bullosa in mice.

Previous work strongly implicated Collagen 17a1 (Col17a1) as a potent genetic modifier of junctional epidermolysis bullosa (JEB) caused by a hypomorphic mutation (Lamc2jeb) in mice. The importance of the noncollagenous domain (NC4) of COLXVII was suggested by use of a congenic reduction approach that restricted the modifier effect to 2-3 neighboring amino acid changes in that domain. The current study utilizes TALEN and CRISPR/Cas9 induced amino acid replacements and in-frame indels nested to NC4 to further investigate the role of this and adjoining COLXVII domains both as modifiers and primary risk effectors.

Subcellular Force Imbalance in Actin Bundles Induces Nuclear Repositioning and Durotaxis.

Durotaxis is a phenomenon in which cells migrate toward substrates of increasing stiffness. However, how cells assimilate substrate stiffness as a directional cue remains poorly understood. In this study, we experimentally show that mouse embryonic fibroblasts can discriminate between different substrate stiffnesses and develop higher traction forces at regions of the cell adhering to the stiffer pillars.

A novel HSPB1 mouse model of Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth Disease (CMT) is a commonly inherited peripheral polyneuropathy. Clinical manifestations for this disease include symmetrical distal polyneuropathy, altered deep tendon reflexes, distal sensory loss, foot deformities, and gait abnormalities. Genetic mutations in heat shock proteins have been linked to CMT2.