Evaluating amyloid-beta aggregation and toxicity in transgenic Caenorhabditis elegans models of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, clinically characterized by memory loss, cognitive decline, and behavioral disturbances. Its pathogenesis is not fully comprehended but involves intracellular depositions of amyloid beta peptide (Aβ) and neurofibrillary tangles of hyperphosphorylated tau. Currently, pharmacological interventions solely slow the progression of symptoms.

Evaluating polyglutamine protein aggregation and toxicity in transgenic Caenorhabditis elegans models of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by a repeat of the cytosine-adenine-guanine trinucleotide (CAG) in the huntingtin gene (HTT). This results in the translation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD leads to neuronal cell loss, motor abnormalities, and dementia.

Identifying proteomic prognostic markers for Alzheimer's disease with survival machine learning: The Framingham Heart Study.

Background: Protein abundance levels, sensitive to both physiological changes and external interventions, are useful for assessing the Alzheimer's disease (AD) risk and treatment efficacy. However, identifying proteomic prognostic markers for AD is challenging by their high dimensionality and inherent correlations.

Methods: Our study analyzed 1128 plasma proteins, measured by the SOMAscan platform, from 858 participants 55 years and older (mean age 63 years, 52.

Determinants of dementia diagnosis in U.S. primary care in the past decade: A scoping review.

Background: Alzheimer's disease and related dementias (ADRD) are chronically underdiagnosed in the U.S., particularly among minoritized racial and ethnic groups.

Spatiotemporal metabolic mapping of ex-situ preserved hearts subjected to dialysis by integration of bio-SPME sampling with non-targeted metabolipidomic profiling.

Background: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.

Distinct clinical outcomes based on multiple serum cytokine and chemokine profiles rather than autoantibody profiles and ultrasound findings in rheumatoid arthritis: a prospective ultrasound cohort study.

Objectives: To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and serum cytokine and chemokine profiles as predictors of clinical outcomes in rheumatoid arthritis (RA).

Patients And Methods: We included 200 patients with RA treated with biological and targeted synthetic disease-modifying antirheumatic drugs in a prospective multicentre ultrasound cohort study. Their serum levels of multiple cytokines and chemokines, rheumatoid factors, and serum autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) and anti-carbamylated protein antibodies) were measured at baseline, 3 months and 12 months.

Urine proteomics defines an immune checkpoint-associated nephritis signature.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.

Biomarkers and Social Determinants in atherosclerotic Arterial Diseases: A Scoping Review.

Background: Arterial diseases like coronary artery disease, carotid stenosis, peripheral artery disease, and abdominal aortic aneurysm have high morbidity and mortality, making them key research areas. Their multifactorial nature complicates patient treatment and prevention. Biomarkers offer insights into the biochemical and molecular processes, while social factors also significantly impact patients' health and quality of life.

Advances in IgY antibody dosage form design and delivery strategies: Current status and future perspective.

Immunoglobulin Y (IgY), a unique type of antibody found in birds, is attracting increasing attention for a broad range of biomedical applications. Rational IgY protection, dosage form design, and delivery are highly essential to transform functional IgY antibodies into desired IgY products for therapeutic and prophylactic administration. Although progress has been made in this field, it remains in the early stages, highlighting the fundamental research and development needed in this aspect of IgY technology.

Heterologous expression of a recombinant ACE inhibitory peptide LYPVK and its potential antihypertensive action mechanism.

Enzymatic hydrolysis approach is commonly employed for preparation of active peptides, while the limited purity and yield of produced peptides hinder further development of action mechanisms. This study presents the biotechnological approach for the efficient production of recombinant angiotensin converting enzyme (ACE) inhibitory peptide LYPVK and investigates its potential antihypertensive action mechanism. DNA encoding sequence of recombinant peptide was designed to form in tandem, which was expressed in Escherichia coli BL21 (DE3).

Manzamine A: A Promising Marine-Derived Cancer Therapeutic for Multi-targeted Interactions with E2F8, SIX1, AR, GSK-3β, and V-ATPase - A Systematic Review.

Manzamine A, a natural compound derived from various sponge genera, features a β-carboline structure and exhibits a range of biological activities, including anti-inflammatory and antimalarial effects. Its potential as an anticancer agent has been explored in several tumor models, both in vitro and in vivo, showing effects through mechanisms such as cytotoxicity, regulation of the cell cycle, inhibition of cell migration, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis through multi-target interactions of E2F transcriptional factors, ribosomal S6 kinases, androgen receptor (AR), SIX1, GSK-3β, V-ATPase, and p53/p21/p27 cascades. This systematic review evaluates existing literature on the potential application of this marine alkaloid as a novel cancer therapy, highlighting its promising ability to inhibit cancer cell growth while causing minimal side effects.

Exploring the mechanism and drug candidates of alveolar echinococcosis affecting liver fibrosis through analysis of existing microarray data.

Echinococcosis, a zoonotic disease, significantly impacts the liver, with alveolar echinococcosis (AE) often leading to liver fibrosis and, in severe cases, cirrhosis. However, the molecular mechanisms by which AE infection promotes liver fibrosis remain incompletely understood. This study utilized bioinformatic analysis of existing microarray data to explore the shared mechanisms between AE and liver fibrosis and to identify potential therapeutic drug candidates.

Downregulation of the Phosphatase PHLPP1 Contributes to NNK-induced Malignant Transformation of Human Bronchial Epithelial Cells (HBECs).

Cigarette smoking (CS) is one of the greatest health concerns, which can cause lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, and has been well-documented for its carcinogenic activity in both epidemiological and laboratory studies. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and phosphatase and tensin homolog (PTEN) are two well-known phosphatase tumor suppressors that have been reported to be downregulated in human lung cancer tissues.

Automated scoring to assess RAD51-mediated homologous recombination in ovarian patient-derived tumor organoids.

PARP inhibitors (PARPi) have been shown to improve progression-free survival, particularly in homologous recombination deficient (HRD) ovarian cancers. Identifying patients eligible to PARPi is currently based on next-generation sequencing (NGS), but the persistence of genomic scars in tumors after restoration of HR or epigenetic changes can be a limitation. Functional assays could thus be used to improve this profiling and faithfully identify HRD tumors.

Variation in venom yield, protein concentration and regeneration toxicity in the scorpion Buthus lienhardi.

Scorpion venom research aims to develop treatments for dangerous species and identify candidates for new drugs. The extraction of high-quality venom, which is essential, requires mastery of the extraction and maintenance of scorpions. It is in this perspective that we have undertaken this present work which aims to contribute to scientifically mastering venom yields and the factors that influence them in scorpions.

Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: A game-changing meta-analysis.

Background: Radiofrequency ablation (RFA) is an emerging treatment option for small, low-risk papillary thyroid carcinoma (PTC). This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety profiles of RFA for primary T1a vs. T1b PTC.

Dynamic behavior of cell-cell adhesion factors in collective cell migration.

Collective cell migration is a fundamental process underlying various biological phenomena, including embryonic development and cancer cell invasion. The cohesive yet flexible movement of cell collectives largely depends on the coordinated regulation of cell-cell and cell-substrate adhesions. In this review, we summarize the regulation of key cell-cell junction components, such as cadherins and zonula occludens proteins during collective cell migration, with a particular focus on the recently discovered multifaceted roles of ZO-1 in both cell-cell and cell-substrate interactions.

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Characterisation and anaerobic digestion of fat, oil and grease (FOG) waste from wastewater treatment plants.

The materials removed in the oil separation units of wastewater treatment plants can be referred to as fat, oil and grease (FOG) waste. FOG waste accumulation in treatment plants can cause clogging of pipes, production of excessive scums and foams, and negatively affect air/liquid oxygen transfer. While conventional disposal routes of this material can be limited by its water and organic content, FOG can represent a source of bio-energy other than bio-diesel production.

Conductive materials enhance anaerobic membrane bioreactor (AnMBR) treating waste leachate at high organic loading rates.

The treatment of landfill leachate using anaerobic membrane bioreactors (AnMBRs) often faces challenges such as poor removal efficiency, low methane yield and membrane fouling. This study applied AnMBRs with incrementally adding conductive materials to enhance the treatment of landfill leachate under high organic loading rates(35 kg COD/(m∙d)). With 50 g/L activated carbon, COD removal percentages and methane yield increased to 81.

Energy metabolism, antioxidant defense system, metal transport, and ion homeostasis are key contributors to Cd tolerance in SSSL derived from wild rice.

Cadmium (Cd) toxicity poses major challenges to rice cultivation, affecting plant growth and development. Wild rice and nanoparticles offer promising strategies to enhance Cd tolerance, yet little is known about their combined effects. This study evaluates the single segment substitution line (SG004) from Oryza glumaepatula (wild rice) and its response to Cd stress compared to cultivated rice (HJX74).

Advancing protein structure prediction beyond AlphaFold2.

Accurate prediction of protein structures is essential for understanding their biological functions. The release of AlphaFold2 in 2021 marked a significant breakthrough, delivering unprecedented accuracy. However, challenges remain, particularly for proteins with limited evolutionary data or complex molecular interactions.

Specific Rosetta-based protein-peptide prediction protocol allows the design of novel cholinesterase inhibitor peptides.

The search for novel cholinesterase inhibitors is essential for advancing treatments for neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employed the Rosetta pepspec module, originally developed for designing peptides targeting protein-protein interactions, to design de novo peptides targeting the peripheral aromatic site (PAS) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A total of nine peptides were designed for human AChE (hAChE), T.

Mechanically robust, mouldable, dynamically crosslinked hydrogel flap with multiple functionalities for accelerated deep skin wound healing.

Deep cutaneous wounds, which are difficult to heal and specifically occur on dynamic body surfaces, remain a substantial healthcare challenge in clinical practice because of multiple underlying factors, including excessive reactive oxygen species, potential bacterial infection, and extensive degradation of the extracellular matrix (ECM) which further leads to the progressive deterioration of the wound microenvironment. Any available individual wound therapy, such as antibiotic-loaded cotton gauze, cannot address all these issues. Engineering an advanced multifunctional wound dressing is the current need to promote the overall healing process of such wounds.