The Force Awakening in HbA1c Control: A Systematic Review and Meta-Analysis on the Efficacy of High-Intensity and Endurance Exercise in Patients With Type 2 Diabetes Mellitus.

The increase in the global prevalence of type 2 diabetes mellitus (DM2), driven mainly by obesity and physical inactivity, has increased interest in various nonpharmacological therapies. This systematic review aims to establish the effectiveness of high-intensity interval training (HIIT) and resistance exercise (RE) compared with continuous aerobic exercise in improving control in patients with DM2. We conducted a comprehensive search for clinical trials using databases such as MEDLINE (PubMed) and Web of Science.

ClearDepth: a simple, robust, and low-cost method to assess root depth in soil.

Root depth is a major determinant of plant performance during drought and a key trait for strategies to improve soil carbon sequestration to mitigate climate change. While the model Arabidopsis thaliana offers numerous advantages for studies of root system architecture and root depth, its small and fragile roots severely limit the use of the methods and techniques currently available for such studies in soils. To overcome this, we have developed ClearDepth, a conceptually simple, non-destructive, sensitive, and low-cost method to estimate the root depth of Arabidopsis in relatively small pots that are amenable to mid- and large-scale studies.

Modeling Glioma Intratumoral Heterogeneity with Primary Human Neural Stem and Progenitor Cells.

Glioblastoma multiforme (GBM) is a deadly form of glioma notable for its significant intratumoral heterogeneity, which is believed to drive therapy resistance. GBM has been observed to mimic a neural stem cell hierarchy reminiscent of normal brain development. However, it is still unclear how cell-of-origin shapes intratumoral heterogeneity.

Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.

While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding.

Sleeve Gastrectomy Reduces Oxidative Stress and Reverses Mitochondrial Dysfunction Associated with Metabolic Syndrome.

Introduction: Previous studies have detected mitochondrial alterations in tissues of individuals with obesity and type 2 diabetes mellitus (T2DM). Metabolic surgery could be an effective treatment to improve mitochondrial morphology and reduce oxidative stress (OS).

Methods: An experimental study was carried out using 48 male Wistar rats, divided into 6 groups (n = 8): control (C), induced Metabolic Syndrome (MS); intervention with sleeve gastrectomy (SG), MS + SG with 6 weeks postoperatively (MS + SG6), MS + SG with 12 weeks postoperatively (MS + SG12), and MS + SG with 24 weeks postoperatively (MS + SG24).

How diverse a monocentric chromosome can be? Repeatome and centromeric organization of Juncus effusus (Juncaceae).

Juncus is the largest genus of Juncaceae and was considered holocentric for a long time. Recent findings, however, indicated that 11 species from different clades of the genus have monocentric chromosomes. Thus, the Juncus centromere organization and evolution need to be reassessed.

CXCR2 inhibition in G-MDSCs enhances CD47 blockade for melanoma tumor cell clearance.

The use of colony-stimulating factor-1 receptor (CSF1R) inhibitors has been widely explored as a strategy for cancer immunotherapy due to their robust depletion of tumor-associated macrophages (TAMs). While CSF1R blockade effectively eliminates TAMs from the solid tumor microenvironment, its clinical efficacy is limited. Here, we use an inducible CSF1R knockout model to investigate the persistence of tumor progression in the absence of TAMs.

FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment.

Preclinical murine data indicate that fragment crystallizable (Fc)-dependent depletion of intratumoral regulatory T cells (Treg) is a major mechanism of action of anti-CTLA-4. However, the two main antibodies administered to patients (ipilimumab and tremelimumab) do not recapitulate these effects. Here, we investigate the underlying mechanisms responsible for the limited Treg depletion observed with these therapies.

Reduced expression of GluN2A induces a delay in neuron maturation.

NMDA receptors (NMDARs) play an important role in synaptic plasticity both in physiological and pathological conditions. GluN2A and GluN2B are the most expressed NMDAR regulatory subunits, in the hippocampus and other cognitive-related brain structures. GluN2B is characteristic of immature structures and GluN2A of mature ones.

Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia.

Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes.

Effect of temperature and nucleotide on the binding of BiP chaperone to a protein substrate.

BiP (immunoglobulin heavy-chain binding protein) is a Hsp70 monomeric ATPase motor that plays broad and crucial roles in maintaining proteostasis inside the cell. Structurally, BiP is formed by two domains, a nucleotide-binding domain (NBD) with ATPase activity connected by a flexible hydrophobic linker to the substrate-binding domain. While the ATPase and substrate binding activities of BiP are allosterically coupled, the latter is also dependent on nucleotide binding.

Evaluation of the generation of reactive oxygen species and antibacterial activity of honey as a function of its phenolic and mineral composition.

The antibacterial activity (ABA) of honey is associated with the generation of reactive oxygen species (ROS), where polyphenols (PFs) play a key role due to their pro-oxidant action modulated by metallic cations. In this work, the contents of PFs, HO, OH radicals, Cu, Fe, Mn, Zn, and ABA against Staphylococcus epidermidis and Pseudomonas aeruginosa were determined in honeys from central Chile. Then, their relationships were evaluated through partial least squares regression.

Effect of surfactants on the sorption-desorption, degradation, and transport of chlorothalonil and hydroxy-chlorothalonil in agricultural soils.

The fungicide chlorothalonil (CTL) and its metabolite hydroxy chlorothalonil (OH-CTL) constitute a risk of soil and water contamination, highlighting the need to find suitable soil remediation methods for these compounds. Surfactants can promote the bioavailability of organic compounds for enhanced microbial degradation, but the performance depends on soil and surfactant properties, sorption-desorption equilibria of contaminants and surfactants, and possible adverse effects of surfactants on microorganisms. This study investigated the influence of five surfactants [e.

SARS-CoV-2 infection in newborn infants: descriptive epidemiological analysis of cases reported to the Colombian national surveillance system during the first pandemic year, March 2020-February 2021.

Objective: To describe the clinical and epidemiological characteristics of newborn infants with SARS-CoV-2 infection notified in the Colombian Public Health Surveillance System.

Design: This epidemiological descriptive analysis was conducted using the data of all cases of newborn infants with confirmed SARS-CoV-2 infection notified in the surveillance system. Absolute frequencies and central tendency measures were calculated and a bivariate analysis comparing variables of interest with symptomatic and asymptomatic disease was performed.

Differential Repeat Accumulation in the Bimodal Karyotype of L.

The genus presents a bimodal karyotype with = 30 (5L, large, +25S, small chromosomes). Bimodality within this genus is generally attributed to allopolyploidy in the ancestral form of Agavoideae. However, alternative mechanisms, such as the preferential accumulation of repetitive elements at the macrochromosomes, could also be important.

FcyRIIB is a novel immune checkpoint in the tumor microenvironment limiting activity of Treg-targeting antibodies.

Despite pre-clinical murine data supporting T regulatory (Treg) cell depletion as a major mechanism by which anti-CTLA-4 antibodies function in vivo, the two main antibodies tested in patients (ipilimumab and tremelimumab) have failed to demonstrate similar effects. We report analogous findings in an immunocompetent murine model humanized for CTLA-4 and Fcy receptors (hCTLA-4/hFcyR mice), where both ipilimumab and tremelimumab fail to show appreciable Treg depletion. Immune profiling of the tumor microenvironment (TME) in both mice and human samples revealed upregulation of the inhibitory Fcy receptor, FcyRIIB, which limits the ability of the antibody Fc fragment of human anti-CTLA-4 antibodies to induce effective antibody dependent cellular cytotoxicty/phagocytosis (ADCC/ADCP).

Temperature dependent mechanical unfolding and refolding of a protein studied by thermo-regulated optical tweezers.

Temperature is a useful system variable to gather kinetic and thermodynamic information from proteins. Usually, free energy and the associated entropic and enthalpic contributions are obtained by quantifying the conformational equilibrium based on melting experiments performed in bulk conditions. Such experiments are suitable only for those small single-domain proteins whose side reactions of irreversible aggregation are unlikely to occur.

A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity.

Glucokinase (GCK) is the pancreatic β-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously described reduce the functionality of the human pancreatic β-cell, leading to diabetic clinical phenotypes.

Impaired fasting glucose, oxidative distress, and cognitive impairment. Is this the starting point on DBT cognitive decline?

Different studies performed in human patients, animal models, and cell cultures, show a correlation between type 2 diabetes (DBT2) and certain neurodegenerative pathologies. Also, it was proposed that increased inflammation and- or oxidative distress are a possible cause of DBT2-accelerated cognitive decline. The onset of DBT2 is characterized by an increase in blood glucose levels due to (an inability of the body's cells to use insulin properly) called impaired fasting glucose (IFG).

Zidebactam restores sulbactam susceptibility against carbapenem-resistant isolates.

Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially . Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant (CRAB) isolates.

Initial Description of the Genome of , a Halophile Grass.

The use of wild plant species or their halophytic relatives has been considered in plant breeding programs to improve salt and drought tolerance in crop plants. serves as halophyte model for identification and isolation of novel stress adaptation genes. perennial monocot grass, grows in damp or arid areas, often salt-impregnated places and wasteland in cultivated areas, can survive periodically high water salinity, and tolerate high salt concentrations in the soil up to 1,100 mM sodium chloride.

Morphological Biomarkers in the Amygdala and Hippocampus of Children and Adults at High Familial Risk for Depression.

Major Depressive Disorder (MDD) is highly familial, and the hippocampus and amygdala are important in the pathophysiology of MDD. Whether morphological markers of risk for familial depression are present in the hippocampus or amygdala is unknown. We imaged the brains of 148 individuals, aged 6 to 54 years, who were members of a three-generation family cohort study and who were at either high or low familial risk for MDD.