Exploring the druggability of the UEV domain of human TSG101 in search for broad-spectrum antivirals.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics.

Activation-derepression synergy enables a bHLH network to coordinate a signal-specific fate response.

Stem cells integrate multiple environmental signals to activate appropriate fate programs. To ensure coherent responses, alternative fates must be concomitantly inactivated. However, mechanisms that coordinate fates in a signal-specific manner are not fully understood.

Responsive deep eutectic solvents: mechanisms, applications and their role in sustainable chemistry.

In an era so focused on sustainability, it is important to improve chemical processes by developing and using more environmentally friendly solvents and technologies. Deep eutectic solvents (DES) have proven to be a promising replacement for conventional solvents. In recent years, a new type of DES has emerged that responds to various stimuli.

Chemical Synthesis of Monolignols: Traditional Methods, Recent Advances, and Future Challenges in Sustainable Processes.

Monolignols represent pivotal alcohol-based constituents in lignin synthesis, playing indispensable roles in plant growth and development with profound implications for industries reliant on wood and paper. Monolignols and their derivates have multiple applications in several industries. Monolignols exhibit antioxidant activity due to their ability to donate hydrogen atoms or electrons to neutralize free radicals, thus preventing oxidative stress and damage to cells.

Fungerps: discovery of the glucan synthase inhibitor enfumafungin and development of a new class of antifungal triterpene glycosides.

Covering: up to 2024Fungal pathogens are a major threat to public health, with emerging resistance to all three classes of antifungals that are currently available and increased incidence of invasive fungal infections among hospitalized patients. Ibrexafungerp is a semi-synthetic analog of enfumafungin and the first antifungal agent approved in more than 20 years since the launch of caspofungin, the first of echinocandins. This new drug approval was made possible after a long arduous journey lasting 25 years by dedicated and talented medicinal chemists from two companies that undertook tedious atom-by-atom chemical modification of the natural product enfumafungin, a glycosylated fernane-type triterpenoid isolated from the fungus .

Reply to Grant, W.B. Comment on "Vicente, F.; Pereira, P.C. Pork Meat Composition and Health: A Review of the Evidence. 2024, , 1905".

Our most recent paper, "Pork Meat Composition and Health: A Review of the Evidence", is, as stated in title, a review [...

Open-mouth jaw locking in a 5-year-old Persian cat: a case report.

Open-mouth jaw locking is an uncommon condition in feline patients. A 5-year-old neutered male Persian cat was evaluated for an acute inability to close its mouth and ptyalism. The general physical examination was unremarkable.

Electrogeneration and Characterization of Poly(methylene blue) Thin Films on Stainless Steel 316 Electrodes-Effect of pH.

Methylene blue was electropolymerized on the surface of stainless steel 316. The addition of sodium oxalate and working at a pH near 11 allowed us to obtain steel electrodes coated with an electroactive polymer. This polymer shows electrochromic properties like those of the monomer, but also exhibits electroactivity at more positive potentials, which is associated with the active centers in the bridges between monomeric units.

Effect of Postbiotic Supplementation on Nutrient Digestibility and Milk Yield during the Transition Period in Dairy Cows.

The metabolites secreted by probiotics or released after their lysis are called postbiotics. They provide physiological benefits to the host, preventing the colonisation of pathogens by improving the intestinal environment for beneficial commensal bacteria, which reduces the incidence of digestive disorders and improves the immune system. The aim of this work was to evaluate the addition of postbiotics to dairy cow rations during the transition period on nutrient digestibility, composition, and milk yield.

Development of a Gold Nanoparticle-Based Sensor for Authentication of Organic Milk Based on Differential Levels of miRNA.

Dairy production systems significantly impact environmental sustainability, animal welfare, and human health. Intensive farming maximizes output through high-input practices, raising concerns about environmental degradation, animal welfare, and health risks from antibiotic residues. Conversely, organic farming emphasizes sustainable practices, animal welfare, and minimal synthetic inputs, potentially enhancing biodiversity, soil health, and milk quality.

Identification of novel small molecule-based strategies of COL7A1 upregulation and readthrough activity for the treatment of recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic disease caused by loss of function mutations in the gene coding for collagen VII (C7) due to deficient or absent C7 expression. This disrupts structural and functional skin architecture, leading to blistering, chronic wounds, inflammation, important systemic symptoms affecting the mouth, gastrointestinal tract, cornea, and kidney function, and an increased skin cancer risk. RDEB patients have an extremely poor quality of life and often die at an early age.

Repurposing the Open Global Health Library for the discovery of novel Mpro destabilizers with scope as broad-spectrum antivirals.

The SARS coronavirus 2 (SARS-CoV-2) epidemic remains globally active. The emergence of new variants of interest and variants of concern (VoCs), which are potentially more vaccine-resistant and less sensitive to existing treatments, is evident due to their high prevalence. The prospective spread of such variants and other coronaviruses with epidemic potential demands preparedness that can be met by developing fast-track workflows to find new candidates that target viral proteins with a clear and phenotype.

Pork Meat Composition and Health: A Review of the Evidence.

Meat has been part of the human diet for centuries and it is a recognizable source of high-biologic-value protein and several micronutrients; however, its consumption has been associated with an increased risk of non-communicable diseases (e.g., cardiovascular diseases, cancer).

Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds.

A Macroscopic Interpretation of the Correlation between Electrical Percolation and Mechanical Properties of Poly-(Ethylene Vinyl Acetate)/Zn Composites.

Elastic composites were prepared using a procedure involving hot plates and zinc powder that was directly dispersed into an EVA matrix. The correlation between the zinc content and the conductive properties of the material was studied via impedance spectroscopy, the thermal properties of the material were studied via differential calorimetry and the mechanical properties of the composites were studied via tensile strength curves, representing an important advancement in the characterization of this type of composite material. The composites' tensile strength and elongation at break decrease with the addition of filler since zinc particles act as stress-concentrating centres, while the composites' hardness and Young's modulus increase because of an increase in the stiffness of the material.

Mediterranean Dietary Pattern for Healthy and Active Aging: A Narrative Review of an Integrative and Sustainable Approach.

The global population is on a trajectory of continuous growth, with estimates projecting an increase from 7.7 billion in 2019 to approximately 9.7 billion by 2050.

Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive.

The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances.

The purpose of this study was to investigate the effects of a novel dietary supplement, including melatonin and magnesium, delivered via coffee pods on sleep quality, resting metabolic rate (RMR), and body composition in individuals with poor sleep quality disturbances. Using a double-blinded, randomized, crossover trial, we recruited 35 participants to a 4-week intervention with both supplements (1.9 mg melatonin + 200 mg elemental magnesium before sleep) and placebo conditions, considering a 7d washout period between treatments.

Valorization of Crab Shells as Potential Sorbent Materials for CO Capture.

This study delves into the potential advantage of utilizing crab shells as sustainable solid adsorbents for CO capture, offering an environmentally friendly alternative to conventional porous adsorbents, such as zeolites, silicas, metal-organic frameworks (MOFs), and porous carbons. The investigation focuses on crab shell waste, which exhibits inherent natural porosity and N-bearing groups, making them promising candidates for CO physisorption and chemisorption applications. Selective deproteinization and demineralization treatments were used to enhance textural properties while preserving the natural porous structure of the crab shells.

Multispectral and thermal infrared data, visual scores for severity of common rust symptoms, and genotypic single nucleotide polymorphism data of three F2-derived biparental doubled-haploid maize populations.

Three F2-derived biparental doubled haploid (DH) maize populations were generated for genetic mapping of resistance to common rust. Each of the three populations has the same susceptible parent, but a different resistance donor parent. Population 1 and 3 consist of 320 lines each, population 2 consists of 260 lines.

Uncovering the biotechnological capacity of marine and brackish water Planctomycetota.

An appealing strategy for finding novel bioactive molecules in Nature consists in exploring underrepresented and -studied microorganisms. Here, we investigated the antimicrobial and tumoral anti-proliferative bioactivities of twenty-three marine and estuarine bacteria of the fascinating phylum Planctomycetota. This was achieved through extraction of compounds produced by the Planctomycetota cultured in oligotrophic medium followed by an antimicrobial screening against ten relevant human pathogens including Gram-positive and Gram-negative bacteria, and fungi.

A yeast-based high-throughput screen identifies inhibitors of trypanosomatid HRG heme transporters with potent leishmanicidal and trypanocidal activity.

Objectives: New drugs are required to treat neglected diseases caused by trypanosomatid parasites such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi. An Achilles' heel of these parasites is their heme auxotrophy; they have an absolute dependence on scavenging this molecule from the host, and trypanosomatid HRG heme transporters (TrypHRG) play an important role in this process. As these proteins are essential for the parasites and have low similarity with their human orthologue, they have been proposed as attractive therapeutic targets.

Unveiling the bioactive potential of Actinomycetota from the Tagus River estuary.

The increase in global travel and the incorrect and excessive use of antibiotics has led to an unprecedented rise in antibiotic resistance in bacterial and fungal populations. To overcome these problems, novel bioactive natural products must be discovered, which may be found in underexplored environments, such as estuarine habitats. In the present work, estuarine actinomycetotal strains were isolated with conventional and iChip techniques from the Tagus estuary in Alcochete, Portugal, and analysed for different antimicrobial bioactivities.