-Tosyl Hydrazone Benzopyran, a New Ligand of PPARα Obtained from Mapping the Conformational Space of Its Active Site.

We report here a new ligand for the peroxisome-proliferator-activated receptor type α (PPARα), an N-tosyl hydrazone benzopyran that was designed throughout the mapping of the polar zone of the binding site of PPARα; such a compound displays a strong activity on this receptor that is comparable to that of the reference compound WY-14643. For the design of the -tosyl hydrazone benzopyran, we have carried out an exhaustive conformational study of WY-14643 and a previously reported hydrazine benzopyran derivative using conformational potential energy surfaces (PES). This study allowed us to map in a systematic way the entire binding site of the PPARα.

The backpack quotient filter: A dynamic and space-efficient data structure for querying -mers with abundance.

Genomic data sequencing is crucial for understanding biological systems. As genomic databases like the European Nucleotide Archive expand exponentially, efficient data manipulation is essential. A key challenge is querying these databases to determine the presence or absence of specific sequences and their abundance within datasets.

Cytotoxicity, Antiadipogenic, Low-Density Lipoprotein Oxidation Inhibitory Activities, and Acute Toxicity Study of Hydroethanolic Leaf and Bark Extracts.

Obesity is increasingly taking an important stage as a cause of death worldwide, and interventions with a good cost-effectiveness ratio are needed. is one of these natural products with health benefits. Objective.

Impact on meningococcal disease of different vaccination strategies with 4CMenB and MenACWY-CRM197 in infants and adolescents in Argentina.

Background: Invasive meningococcal disease (IMD) is a life-threatening disease, primarily affecting infants and children. Argentina introduced routine meningococcal vaccination in infants and adolescents in 2017, with MenACWY vaccination targeting serogroups A, C, W, and Y (current National Immunization Program [cNIP]). Serogroup B, more prevalent since 2015, became predominant in children.

Nanobodies as innovative immune checkpoint modulators: advancing cancer immunotherapy.

The immune system relies on a delicate balance between attacking harmful pathogens and preserving the body's own tissues, a balance maintained by immune checkpoints. These checkpoints play a critical role in preventing autoimmune diseases by restraining excessive immune responses while allowing the immune system to recognize and destroy abnormal cells, such as tumors. In recent years, immune checkpoint inhibitors (ICIs) have become central to cancer therapy, enabling the immune system to target and eliminate cancer cells that evade detection.

binary toxin CDT induces biofilm-like persisting microcolonies.

Clinical symptoms of infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of with higher relapse rates.

Description of Cohnella rhizoplanae sp. nov., isolated from the root surface of soybean (Glycine max).

A Gram-staining-positive, aerobic bacterium, designated strain JJ-181, was isolated from the root surface of soybean. Based on the 16S rRNA gene sequence similarities, strain JJ-181 was grouped into the genus Cohnella, most closely related to Cohnella hashimotonis F6_2S_P_1 (98.85%) and C.

Naturally acquired IgG responses to do not target the conserved termini of the malaria vaccine candidate Merozoite Surface Protein 2.

Introduction: Malaria remains a significant burden, and a fully protective vaccine against is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen Merozoite Surface Protein 2 (MSP2) are associated with protection from malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to study the genetic diversity and immune responses towards antigens from clinical isolates with unprecedented detail.

Encapsulation of anti-VEGF nanobody into niosome nanoparticles: a novel approach to enhance circulation half life and efficacy.

This study aimed to encapsulate an anti-VEGF nanobody (Nb) within niosome nanoparticles (NNPs) to enhance its circulation half life. Key parameters such as encapsulation efficiency, stability, Nb release, cytotoxicity, and cell migration inhibition in HUVEC cells were evaluated, along with pharmacokinetic studies in mice. Nb-loaded NNPs (Nb-NNPs) were successfully prepared with an encapsulation efficiency of 78.

A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.

Non-Polio Enterovirus Inhibitors: Scaffolds, Targets, and Potency─What's New?

Enterovirus (EV) is a genus that includes a large diversity of viruses spread around the world. They are the main cause of numerous diseases with seasonal clusters, like hand-foot-mouth disease (HFMD). A vaccine is marketed in China for the prevention of HFMD caused by EV-A71.

A High Resolution Melting Analysis (HRM) PCR assay for the detection and identification of Old World Leishmania species.

Background: Cutaneous Leishmaniases (CL), highly endemic in Africa and Mediterranean region, are caused by different Leishmania parasite species. Accurate species identification is crucial for effective diagnosis, treatment, and control of these diseases, but traditionally relies on DNA-based methods. High Resolution Melting analysis PCR (HRM PCR) provides rapid results and precise differentiation based on nucleotide variations.

Optimization of Clozapine Treatment: Study of Variables Affecting Response in Uruguayan Patients With Schizophrenia.

Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.

The protein structurome of Orthornavirae and its dark matter.

Unlabelled: Metatranscriptomics is uncovering more and more diverse families of viruses with RNA genomes comprising the viral kingdom Orthornavirae in the realm Riboviria. Thorough protein annotation and comparison are essential to get insights into the functions of viral proteins and virus evolution. In addition to sequence- and hmm profile‑based methods, protein structure comparison adds a powerful tool to uncover protein functions and relationships.

Immunometabolic reprogramming in macrophages infected with active and dormant : differential modulation of respiration, glycolysis, and fatty acid utilization.

Dormancy is an adaptation in which cells reduce their metabolism, transcription, and translation to stay alive under stressful conditions, preserving the capacity to reactivate once the environment reverts to favorable conditions. Dormancy and reactivation of () are closely linked to intracellular residency within macrophages. Our previous work showed that murine macrophages rely on the viable but not cultivable (VBNC-a dormancy phenotype) fungus from active , with striking differences in immunometabolic gene expression.

Facing stress and inflammation: From the cell to the planet.

As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders.

Performance of Ertapenem-Supplemented MacConkey Agar (MacErt) for Detecting Carbapenemase-Producing Enterobacterales.

Background and objectives Antimicrobial resistance (AMR) is a growing global threat, with carbapenemase-producing Enterobacterales (CPEs) representing a critical public health challenge. Rapid and accurate detection of CPEs is essential for controlling fatal bacterial AMR infections. This study evaluated the performance of MacConkey media supplemented with ertapenem (MacErt1 and MacErt2) for the detection of CPEs.

Ultrasound-Guided Percutaneous Fasciotomies for Patients With Chronic Exertional Compartment Syndrome.

Chronic exertional compartment syndrome is a well-described potential cause of leg pain in high-level athletes and soldiers. Surgical treatment of chronic exertional compartment syndrome usually involves fasciotomy, with a reported rate of complications of up to 16%, including failure of complete compartmental release and delayed return to normal daily activity, which can take up to 6 to 12 weeks. The use of a minimally invasive approach under ultrasound guidance seems to improve clinical outcomes in young active patients.

A systematic review and meta-analysis: rising prevalence of colistin resistance in ICU-acquired Gram-negative bacteria.

Colistin is a last-resort treatment for multidrug-resistant Gram-negative bacterial infections, particularly in critically ill patients. Nevertheless, it remains a major threat to public health. We assessed the proportion of colistin-resistant Gram-negative isolates from intensive care unit (ICU) infections in different years, areas, pathogens, and antimicrobial susceptibility tests (AST).

What is the lower limb length discrepancy after arthroplasty for proximal femoral fracture? A prospective, multicenter observational study of 590 hips.

Introduction: Lower limb length discrepancy (LLD) following hip arthroplasty after proximal femoral fracture (PFFA) is little studied. The aim of this work was to answer the following questions: 1) What are the incidence and mean values ​​of LLD after PFFA? 2) What are the clinical consequences (tolerance) of LLD after PFFA? 3) Can we identify risk factors for LLD after PFFA? 4) Is there a significant difference in terms of LLD after PFFA to treat intra- versus extra-capsular fractures?

Hypothesis: LLD after proximal femoral fracture arthroplasty is rare but has good clinical tolerance, given the low functional demands of the patients.

Patients And Methods: This is a multicenter prospective observational cohort study (15 centers), including 590 patients, operated on for hip arthroplasty for proximal femur fracture between May 2022 and June 2023.

The importance of microbiology reference laboratories and adequate funding for infectious disease surveillance.

Microbiology reference laboratories perform a crucial role within public health systems. This role was especially evident during the COVID-19 pandemic. In this Viewpoint, we emphasise the importance of microbiology reference laboratories and highlight the types of digital data and expertise they provide, which benefit national and international public health.

From the 100 Day Mission to 100 lines of software development: how to improve early outbreak analytics.

Since the COVID-19 pandemic, considerable advances have been made to improve epidemic preparedness by accelerating diagnostics, therapeutics, and vaccine development. However, we argue that it is crucial to make equivalent efforts in the field of outbreak analytics to help ensure reliable, evidence-based decision making. To explore the challenges and key priorities in the field of outbreak analytics, the Epiverse-TRACE initiative brought together a multidisciplinary group of experts, including field epidemiologists, data scientists, academics, and software engineers from public health institutions across multiple countries.

Radiation Segmentectomy and Modified Radiation Lobectomy for Unresectable Early-Stage Intrahepatic Cholangiocarcinoma.

Purpose: To validate the safety and efficacy of radiation segmentectomy (RS) and modified radiation lobectomy (mRL) in intrahepatic cholangiocarcinoma (iCCA) and to evaluate long-term outcomes in patients with unresectable, early-stage iCCA.

Materials And Methods: A single-institution, retrospective study of patients with unresectable, solitary iCCA without extrahepatic disease or vascular involvement (stage I) treated with RS and mRL was performed. Fifteen patients met inclusion criteria (median age 65.