From Psychoactivity to Antimicrobial Agents: Multifaceted Applications of Synthetic Cathinones and Extracts.

The emergence of new psychoactive substances (NPS) in the global drug market since the 2000s has posed major challenges for regulators and law enforcement agencies. Among these, synthetic cathinones have gained prominence due to their stimulant effects on the central nervous system, leading to widespread recreational use. These compounds, often marketed as alternatives to illicit stimulants such as amphetamines and cocaine, have been linked to numerous cases of intoxication, addiction and death.

Bioimaging marine crustacean brain: quantitative comparison of micro-CT preparations in an Alpheid snapping shrimp.

Non-invasive bioimaging techniques like X-ray micro-computed tomography (μCT), combined with contrast-enhancing techniques, allow the 3D visualization of the central nervous system , without the destruction of the sample. However, quantitative comparisons of the most common fixation and contrast-enhancing protocols are rare, especially in marine invertebrates. Using the snapping shrimp () as a model, we test three common fixation and staining agents combinations to prepare specimens prior to μCT scanning.

Dynamic Expression of Genes Encoding Ubiquitin Conjugating Enzymes (E2s) During Neuronal Differentiation and Maturation: Implications for Neurodevelopmental Disorders and Neurodegenerative Diseases.

The ubiquitination process plays a crucial role in neuronal differentiation and function. Numerous studies have focused on the expression and functions of E3 ligases during these different stages, far fewer on E2 conjugating enzymes. In mice, as in humans, these E2s belong to 17 conjugating enzyme families.

Treating Cognition in Schizophrenia: A Whole Lifespan Perspective.

Cognitive impairment is a core feature of schizophrenia, affecting attention, memory, and executive function and contributing significantly to the burden of the disorder. These deficits often begin before the onset of psychotic symptoms and persist throughout life, making their treatment essential for improving outcomes and functionality. This work aims to explore the impact of these impairments at different life stages and the interventions that have been developed to mitigate their effects.

QCD challenges from pp to AA collisions: 4th edition.

This paper is a write-up of the ideas that were presented, developed and discussed at the fourth International Workshop on QCD Challenges from pp to AA, which took place in February 2023 in Padua, Italy. The goal of the workshop was to focus on some of the open questions in the field of high-energy heavy-ion physics and to stimulate the formulation of concrete suggestions for making progresses on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.

N-Terminal Fragments of TDP-43-In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells.

Dual-Action Therapeutics: DNA Alkylation and Antimicrobial Peptides for Cancer Therapy.

Cancer remains one of the most difficult diseases to treat, requiring continuous research into innovative therapeutic strategies. Conventional treatments such as chemotherapy and radiotherapy are effective to a certain extent but often have significant side effects and carry the risk of resistance. In recent years, the concept of dual-acting therapeutics has attracted considerable attention, particularly the combination of DNA alkylating agents and antimicrobial peptides.

Anticancer Activity of Metallodrugs and Metallizing Host Defense Peptides-Current Developments in Structure-Activity Relationship.

This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action.

Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?

Michael acceptors represent a class of compounds with potential anti-cancer properties. They act by binding to nucleophilic sites in biological molecules, thereby disrupting cancer cell function and inducing cell death. This mode of action, as well as their ability to be modified and targeted, makes them a promising avenue for advancing cancer therapy.

Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: transmission dynamics and epidemiological insights.

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants.

Materials And Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior.

Respiratory Viral Coinfections in Pediatric Patients in the Primary Care Setting: A Multicenter Prospective Study Within the COPEDICAT Network.

Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the coronavirus disease 2019 (COVID-19) pandemic are scarce. We conducted a 2-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.

In-Host Flat-like Quasispecies: Characterization Methods and Clinical Implications.

The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies.

No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.

Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively.

Descemet Membrane Endothelial Keratoplasty (DMEK) Anesthesia Analysis.

Purpose: Comparison of safety and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in topical, peribulbar, or general anesthesia.

Methods: Retrospective, post hoc matched study of 346 patients who received DMEK surgery with different types of anesthesia (n = 54 topical, n = 137 peribulbar, n = 155 general anesthesia). Outcome criteria were intraoperative complications, endothelial cell count (ECC), central corneal thickness (CCT) and graft rejection rate, rebubbling rate, and visual acuity (VA).

Body Composition and Anthropometric Measurements in Children and Adolescents with Autism Spectrum Disorder: A Case-Control Study in Lebanon.

The occurrence of overweight and obesity among individuals with Autism Spectrum Disorder (ASD) has become a worldwide epidemic. However, there is limited research on this topic in the Lebanese population. Therefore, this study aimed to assess the differences in anthropometric measurements and body composition variables among Lebanese children, pre-adolescents, and adolescents diagnosed with ASD in contrast to typically developing peers across various developmental stages.

Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2.

The phrase "Let food be thy medicine…" means that food can be a form of medicine and medicine can be a form of food; in other words, that the diet we eat can have a significant impact on our health and well-being. Today, this phrase is gaining prominence as more and more scientific evidence suggests that one's diet can help prevent and treat disease. A diet rich in fruits, vegetables, whole grains, and lean protein can help reduce the risk of heart disease, cancer, diabetes, and other health problems and, on the other hand, a diet rich in processed foods, added sugars, and saturated fats can increase the risk of the same diseases.

Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences.

Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents.

Upregulation of Integrin beta-3 in astrocytes upon Alzheimer's disease progression in the 5xFAD mouse model.

Integrins are receptors that have been linked to various brain disorders, including Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. While Integrin beta-3 (ITGB3) is known to participate in multiple cellular processes such as adhesion, migration, and signaling, its specific role in AD remains poorly understood, particularly in astrocytes, the main glial cell type in the brain. In this study, we investigated alterations in ITGB3 gene and protein expression during aging in different brain regions of the 5xFAD mouse model of AD and assessed the interplay between ITGB3 and astrocytes.

Neutrophil to Lymphocyte Ratio as a Prognostic Marker in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with a difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocyte count as lymphocytes and neutrophils. The neutrophil-to-lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS.

Chemistry of Hydrogen Sulfide-Pathological and Physiological Functions in Mammalian Cells.

Hydrogen sulfide (HS) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of hydrogen sulfide (HS) in the human body. HS is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO).

Chemical Insights into Oxidative and Nitrative Modifications of DNA.

This review focuses on DNA damage caused by a variety of oxidizing, alkylating, and nitrating species, and it may play an important role in the pathophysiology of inflammation, cancer, and degenerative diseases. Infection and chronic inflammation have been recognized as important factors in carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine.