Anthocyanin Profiles in the Tropical Fruits Eugenia jambolana and Inga edulis: A Comparative Study Using Paper Spray Ionization (PSI-MS), Tissue Spray Ionization (TSI-MS), and Direct Infusion (DI-MS).

Paper spray ionization (PSI-MS) and tissue spray ionization (TSI-MS) mass spectrometry are simple and rapid ambient ionization mass spectrometry techniques that offer numerous advantages over conventional analysis methods. This study aims to analyze the efficiency of detecting anthocyanins from Eugenia jambolana fruit peel and Inga edulis seeds using PSI-MS, TSI-MS, and DI-MS (direct infusion). DI-MS exhibited high efficiency, detecting all compounds in abundance, with anthocyanins malvidin 3,5-O-diglucoside (1) and petunidin 3,5-O-diglucoside (2) being the most prevalent. PSI-MS, however, struggled to detect delphinidin 3-O-glucoside and showed lower abundances for compounds 1, 2, 3 (delphinidin 3,5-O-diglucoside), and 4 (petunidin 3-O-glucoside) compared to DI-MS, attributed to the technique's challenges with molecular weight and polarity. TSI-MS was least effective, detecting only compounds 1, 2, and 3 at low intensities. The overall unique compounds identified across techniques were 134, emphasizing the importance of comprehensively employing multiple methods to analyze anthocyanins in these edible plants.

Energetic and Electronic Properties of UO0/± and UF0/±.

High-level electronic structure calculations were conducted to examine the bonding and spectroscopic properties of the UO0/± and UF0/± diatomic molecules. The low-lying Ω states were described by using multireference SO-CASPT2 calculations. The adiabatic electronic affinity (AEA), adiabatic ionization energy (IE), and bond dissociation energy (BDE) were calculated at the Feller-Peterson-Dixon (FPD) level. The ground state of UO is predicted to be 5I4, and that of UF is 4I9/2. The calculated AEAs of UO and UF are 1.123 and 0.453 eV, respectively, and the corresponding IEs are 5.976 and 6.278 eV. The BDE of UO (749.5 kJ/mol) is predicted to be considerably higher than that of UF (627.2 kJ/mol), and both are higher than those predicted for UB, UC, and UN. NBO calculations show strong ionic character for the ground states of UO and UF and bond orders that range from 2 to 3 and from 1 to 2, respectively. Comparisons of the calculated properties to those of the series comprising UB, UC, and UN diatomic molecules are given.

Spatial colocalization and combined survival benefit of natural killer and CD8 T cells despite profound MHC class I loss in non-small cell lung cancer.

Background: MHC class I (MHC-I) loss is frequent in non-small cell lung cancer (NSCLC) rendering tumor cells resistant to T cell lysis. NK cells kill MHC-I-deficient tumor cells, and although previous work indicated their presence at NSCLC margins, they were functionally impaired. Within, we evaluated whether NK cell and CD8 T cell infiltration and activation vary with MHC-I expression. Methods: We used single-stain immunohistochemistry (IHC) and Kaplan-Meier analysis to test the effect of NK cell and CD8 T cell infiltration on overall and disease-free survival. To delineate immune covariates of MHC-I-disparate lung cancers, we used multiplexed immunofluorescence (mIF) imaging followed by multivariate statistical modeling. To identify differences in infiltration and intercellular communication between IFNγ-activated and non-activated lymphocytes, we developed a computational pipeline to enumerate single cell neighborhoods from mIF images followed by multivariate discriminant analysis. Results: Spatial quantitation of tumor cell MHC-I expression revealed intra- and inter-tumoral heterogeneity, which was associated with the local lymphocyte landscape. IHC analysis revealed that high CD56+ cell numbers in patient tumors were positively associated with disease-free survival (DFS) (HR=0.58, p=0.064) and overall survival (OS) (HR=0.496, p=0.041). The OS association strengthened with high counts of both CD56+ and CD8+ cells (HR=0.199, p<1×10-3). mIF imaging and multivariate discriminant analysis revealed enrichment of both CD3+CD8+ T cells and CD3-CD56+ NK cells in MHC-I-bearing tumors (p<0.05). To infer associations of functional cell states and local cell-cell communication, we analyzed spatial single cell neighborhood profiles to delineate the cellular environments of IFNγ+/- NK cells and T cells. We discovered that both IFNγ+ NK and CD8 T cells were more frequently associated with other IFNγ+ lymphocytes in comparison to IFNγ- NK cells and CD8 T cells (p<1×10-30). Moreover, IFNγ+ lymphocytes were most often found clustered near MHC-I+ tumor cells. Conclusions: Tumor-infiltrating NK cells and CD8 T cells jointly affected control of NSCLC tumor progression. Co-association of NK and CD8 T cells was most evident in MHC-I-bearing tumors, especially in the presence of IFNγ. Frequent co-localization of IFNγ+ NK cells with other IFNγ+ lymphocytes in near-neighbor analysis suggests NSCLC lymphocyte activation is coordinately regulated.

Ferroptosis as an emerging target in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.

Wild-Type α-Synuclein Structure and Aggregation: A Comprehensive Coarse-Grained and All-Atom Molecular Dynamics Study.

α-Synuclein (α-syn) is a 140 amino acid intrinsically disordered protein (IDP) and the primary component of cytotoxic oligomers implicated in the etiology of Parkinson's disease (PD). While IDPs lack a stable three-dimensional structure, they sample a heterogeneous ensemble of conformations that can, in principle, be assessed through molecular dynamics simulations. However, describing the structure and aggregation of large IDPs is challenging due to force field (FF) accuracy and sampling limitations. To cope with the latter, coarse-grained (CG) FFs emerge as a potential alternative at the expense of atomic detail loss. Whereas CG models can accurately describe the structure of the monomer, less is known about aggregation. The latter is key for assessing aggregation pathways and designing aggregation inhibitor drugs. Herein, we investigate the structure and dynamics of α-syn using different resolution CG (Martini3 and Sirah2) and all-atom (Amber99sb and Charmm36m) FFs to gain insight into the differences and resemblances between these models. The dependence of the magnitude of protein-water interactions and the putative need for enhanced sampling (replica exchange) methods in CG simulations are analyzed to distinguish between force field accuracy and sampling limitations. The stability of the CG models of an α-syn fibril was also investigated. Additionally, α-syn aggregation was studied through umbrella sampling for the CG models and CG/all-atom models for an 11-mer peptide (NACore) from an amyloidogenic domain of α-syn. Our results show that despite the α-syn structures of Martini3 and Sirah2 with enhanced protein-water interactions being similar, major differences exist concerning aggregation. The Martini3 fibril is not stable, and the binding free energy of α-syn and NACore is positive, opposite to Sirah2. Sirah2 peptides in a zwitterionic form, in turn, display termini interactions that are too strong, resulting in end-to-end orientation. Sirah2, with enhanced protein-water interactions and neutral termini, provides, however, a peptide aggregation free energy profile similar to that found with all-atom models. Overall, we find that Sirah2 with enhanced protein-water interactions is suitable for studying protein-protein and protein-drug aggregation.

Synthesis, Characterization, and Study of the Antimicrobial Potential of Dimeric Peptides Derived from the C-Terminal Region of Lys49 Phospholipase A2 Homologs.

Currently, the search for new alternatives to conventional antibiotics to combat bacterial resistance is an urgent task, as many microorganisms threaten human health due to increasing bacterial resistance to traditional medicines. Thus, new molecules such as antimicrobial peptides have emerged as promising alternatives because of their low induction of resistance and broad spectrum of action. In this context, in the past few years, our research group has synthesized and characterized a peptide derived from the C-terminal region of the Lys49 PLA2-like BthTX-I, named p-BthTX-I. After several studies, the peptide (p-BthTX-I)2K was proposed as the molecule with the most considerable biotechnological potential. As such, the present work aimed to evaluate whether the modifications made on the peptide (p-BthTX-I)2K can be applied to other molecules originating from the C-terminal region of PLA2-like Lys49 from snake venoms. The peptides were obtained through the solid-phase peptide synthesis technique, and biochemical and functional characterization was carried out using dichroism techniques, mass spectrometry, antimicrobial activity against ESKAPE strains, hemolytic activity, and permeabilization of lipid vesicles. The antimicrobial activity of the peptides was promising, especially for the peptides (p-AppK)2K and (p-ACL)2K, which demonstrated activity against all strains that were tested, surpassing the model molecule (p-BthTX-I)2K in most cases and maintaining low hemolytic activity. The modifications initially proposed for the (p-BthTX-I)2K peptide were shown to apply to other peptides derived from Lys49 PLA2-like from snake venoms, showing promising results for antimicrobial activity. Future assays comparing the activity of the dimers obtained through this strategy with the monomers of these peptides should be carried out.

RELACIÓN ENTRE INGESTA ALIMENTICIA Y ESTRÉS ACADÉMICO, REACCIONES FISICAS, PSICOLÓGICAS Y COMPORTAMENTALES EN ESTUDIANTES DE LA UNIVERSIDAD AUTÓNOMA DE CHIHUAHUA, MÉXICO / RELATIONSHIP BETWEEN FOOD INTAKE AND ACADEMIC STRESS, PHYSICAL, PSYCHOLOGICAL AND BEHAVIORAL REACTIONS IN STUDENTS OF THE AUTONOMOUS UNIVERSITY OF CHIHUAHUA, MÉXICO

l estrés académico puede presentarse en estudiantes sometidos a diversas exigencias y requisitos universitarios, provocando diferentes reacciones de estrés, físicas, psicológicas y comportamentales, reduciendo su calidad de vida y provocando consecuencias como: depresión, tristeza, fatiga y dolores de cabeza, afectando su estado nutricional. Se investigó la relación entre ingesta de alimentos y estrés académico en estudiantes del cuarto semestre de la Licenciatura en Medicina de la Universidad Autónoma de Chihuahua. La población de estudio, dado el carácter piloto de la investigación, se realizó mediante muestreo simple, aleatorio, sin reemplazo, con un diseño mixto, descriptivo, comparativo y transversal, utilizándose el cálculo del tamaño muestral con un intervalo de confianza de 95%, resultando N=117; 51 hombres y 66 mujeres entre 19 y 43 años de la generación 2019, a quienes se les aplicó el inventario SISCO de estrés académico. Se encontró mayor frecuencia en situaciones que provocan preocupación y nerviosismo, sobrecarga de tareas y trabajo, inquietud, problemas de concentración, fatiga crónica y apatía. Las estrategias más utilizadas fueron: desarrollo de planes y ejecución de tareas y capacidad asertiva. El 92.2% (n=108) de la población encuestada manifestó preocupación y nerviosismo, resultando 52,1% (n=61) en mujeres y 40.1% (n=47) en hombres. El 38.5% (n=45) de las mujeres entre 21 y 43 años, muestran una mayor relación entre aumentar o reducir el consumo de alimentos en correspondencia con sentimientos de depresión y tristeza. El estrés académico, suele estar relacionado con diferentes manifestaciones psicológicas, físicas y conductuales, que pueden influir directamente en la población estudiantil, afectando gravemente sus hábitos alimenticios y nutricionales

Academic stress can occur in students subjected to various university demands and requirements, causing different, causing different physical, psychological and behavioral reactions. Reducing quality of life and causing consequences such as: depression, sadness, fatigue and headaches, affecting their nutritional status. The relationship between food intake and academic stress was investigated in students in the fourth semester of the Bachelor of Medicine at the Autonomous University of Chihuahua. The study population, given the pilot nature of the research, was carried out through simple, random sampling, without replacement, with a mixed, descriptive, comparative and transversal design, using the sample size calculation with a 95% confidence interval resulting in N=117; 51 men and 66 women between the ages of 19 and 43, from the 2019 generation, to whom the SISCO inventory of academic stress was applied. A greater frequency was found in situations that cause worry and nervousness, overload of tasks and work, restlessness, concentration problems, chronic fatigue and listlessness. The most used strategies were plan development and execution of tasks and assertive ability. 92.2% (n=108) of the surveyed population expressed concern and nervousness, in 52.1% (n=61) women and 40.1% (n=47) men. The 38.5% (n=45) of women between 21 and 43 years old show a greater relationship between increasing or reducing food consumption in correspondence with feelings of depression and sadness. Academic stress is usually related to different psychological, physical and behavioral manifestations, which can directly influence the student population, seriously affecting their eating and nutritional habits

Current knowledge and practice of Candida auris screening in France: A nationwide survey from the French Society of Medical Mycology (SFMM).

Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission.

Vacuum fractional distillation of Cunila galioides Benth. essential oil: chemical composition and biological activities of raw oil and its fractions.

This work aimed to rectify Cunila galioides essential oil and evaluate the raw oil and the fractions' antifungal, allelopathic, and antioxidant activities. The results showed that the raw essential oil and the bottom fraction were primarily composed of linalyl propionate (42.9 wt.% and 60.2 wt.%). The top fraction was composed mainly of limonene (45.7 wt.%). The antioxidant activity changed with the radical and the fraction. The bottom had a weaker antifungal effect than the raw oil and the top. Nevertheless, the essential oil and the fractions had a similar antifungal activity at 0.50 % v/v and higher. Similar behavior was observed for the allelopathic tests. No difference occurred between the raw oil and the fractions, with reduced germination percentages and speed at 0.25 % v/v and complete inhibition at 0.50 % v/v. The oil can be rectified, and the fractions may be used without harming their biological activity.

Enhancing Gene Co-Expression Network Inference for the Malaria Parasite Plasmodium falciparum.

BACKGROUND: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. Improving the functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance. RESULTS: Genes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks in P. falciparum have been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for all P. falciparum genes. We evaluate each inferred network based on how well it predicts existing gene-Gene Ontology (GO) term annotations using network clustering and leave-one-out crossvalidation. We assess overlaps of the different networks' edges (gene co-expression relationships), as well as predicted functional knowledge. The networks' edges are overall complementary: 47-85% of all edges are unique to each network. In terms of the accuracy of predicting gene functional annotations, all networks yielded relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached was below 15%. All networks having low recall means that none of them capture a large amount of all existing gene-GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene-gene interactions and predicted gene-GO term annotations for future use and wet lab validation by the malaria community. CONCLUSIONS: The different networks seem to capture different aspects of the P. falciparum biology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible. SUPPLEMENTARY DATA: Attached.

Essential dynamics of ubiquitin in water and in a natural deep eutectic solvent.

Natural deep eutectic solvents (NADESs) comprised of osmolytes are of interest as potential biomolecular (cryo)protectants. However, the way these solvents influence the structure and dynamics of biomolecules as well as the role of water remains poorly understood. We carried out principal component analysis of various secondary structure elements of ubiquitin in water and a betaine : glycerol : water (1 : 2 : ζ; ζ = 0, 1, 2, 5, 10, 20, 45) NADES, from molecular dynamics trajectories, to gain insight into the protein dynamics as it undergoes a transition from a highly viscous anhydrous to an aqueous environment. A crossover of the protein's essential dynamics at ζ ∼ 5, induced by solvent-shell coupled fluctuations, is observed, indicating that ubiquitin might (re)fold in the NADES upon water addition at ζ > ∼5. Further, in contrast to water, the anhydrous NADES preserves ubiquitin's essential modes at high temperatures explaining the protein's seemingly enhanced thermal stability.

Minimally destructive hDNA extraction method for retrospective genetics of pinned historical Lepidoptera specimens.

The millions of specimens stored in entomological collections provide a unique opportunity to study historical insect diversity. Current technologies allow to sequence entire genomes of historical specimens and estimate past genetic diversity of present-day endangered species, advancing our understanding of anthropogenic impact on genetic diversity and enabling the implementation of conservation strategies. A limiting challenge is the extraction of historical DNA (hDNA) of adequate quality for sequencing platforms. We tested four hDNA extraction protocols on five body parts of pinned false heath fritillary butterflies, Melitaea diamina, aiming to minimise specimen damage, preserve their scientific value to the collections, and maximise DNA quality and yield for whole-genome re-sequencing. We developed a very effective approach that successfully recovers hDNA appropriate for short-read sequencing from a single leg of pinned specimens using silica-based DNA extraction columns and an extraction buffer that includes SDS, Tris, Proteinase K, EDTA, NaCl, PTB, and DTT. We observed substantial variation in the ratio of nuclear to mitochondrial DNA in extractions from different tissues, indicating that optimal tissue choice depends on project aims and anticipated downstream analyses. We found that sufficient DNA for whole genome re-sequencing can reliably be extracted from a single leg, opening the possibility to monitor changes in genetic diversity maintaining the scientific value of specimens while supporting current and future conservation strategies.

Novel Mouse Model of Myocardial Infarction, Plaque Rupture, and Stroke Shows Improved Survival With Myeloperoxidase Inhibition.

BACKGROUND: Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke. METHODS: We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with Ldlr knockout (designated SR-BI∆CT/∆CT/Ldlr-/-). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI∆CT/∆CT/Ldlr-/- mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions. RESULTS: SR-BI∆CT/∆CT/Ldlr-/- mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions. CONCLUSIONS: WD-fed SR-BI∆CT/∆CT/Ldlr-/- mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.

IL-1ß Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice.

BACKGROUND: Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions is the global leading cause of death. The most common and effective means to reduce these major adverse cardiovascular events, including myocardial infarction and stroke, is aggressive lipid lowering via a combination of drugs and dietary modifications. However, we know little regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering. METHODS: Smooth muscle cell lineage-tracing Apoe-/- mice were fed a high-cholesterol Western diet for 18 weeks and then a zero-cholesterol standard laboratory diet for 12 weeks before treating them with an IL (interleukin)-1ß or control antibody for 8 weeks. We assessed lesion size and remodeling indices, as well as the cellular composition of aortic and brachiocephalic artery lesions, indices of plaque stability, overall plaque burden, and phenotypic transitions of smooth muscle cell and other lesion cells by smooth muscle cell lineage tracing combined with single-cell RNA sequencing, cytometry by time-of-flight, and immunostaining plus high-resolution confocal microscopic z-stack analysis. RESULTS: Lipid lowering by switching Apoe-/- mice from a Western diet to a standard laboratory diet reduced LDL cholesterol levels by 70% and resulted in multiple beneficial effects including reduced overall aortic plaque burden, as well as reduced intraplaque hemorrhage and necrotic core area. However, contrary to expectations, IL-1ß antibody treatment after diet-induced reductions in lipids resulted in multiple detrimental changes including increased plaque burden and brachiocephalic artery lesion size, as well as increasedintraplaque hemorrhage, necrotic core area, and senescence as compared with IgG control antibody-treated mice. Furthermore, IL-1ß antibody treatment upregulated neutrophil degranulation pathways but downregulated smooth muscle cell extracellular matrix pathways likely important for the protective fibrous cap. CONCLUSIONS: Taken together, IL-1ß appears to be required for the maintenance of standard laboratory diet-induced reductions in plaque burden and increases in multiple indices of plaque stability.

Role of Histidine 310 in Amydetes vivianii firefly luciferase pH and metal sensitivities and improvement of its color tuning properties.

Firefly luciferases emit yellow-green light and are pH-sensitive, changing the bioluminescence color to red in the presence of heavy metals, acidic pH and high temperatures. These pH and metal-sensitivities have been recently harnessed for intracellular pH indication and toxic metal biosensing. However, whereas the structure of the pH sensor and the metal binding site, which consists mainly of two salt bridges that close the active site (E311/R337 and H310/E354), has been identified, the specific role of residue H310 in pH and metal sensing is still under debate. The Amydetes vivianii firefly luciferase has one of the lowest pH sensitivities among the group of pH-sensitive firefly luciferases, displaying high bioluminescent activity and special spectral selectivity for cadmium and mercury, which makes it a promising analytical reagent. Using site-directed mutagenesis, we have investigated in detail the role of residue H310 on pH and metal sensitivity in this luciferase. Negatively charged residues at position 310 increase the pH sensitivity and metal sensitivity; H310G considerably increases the size of the cavity, severely impacting the activity, H310R closes the cavity, and H310F considerably decreases both pH and metal sensitivities. However, no substitution completely abolished pH and metal sensitivities. The results indicate that the presence of negatively charged and basic side chains at position 310 is important for pH sensitivity and metals coordination, but not essential, indicating that the remaining side chains of E311 and E354 may still coordinate some metals in this site. Furthermore, a metal binding site search predicted that H310 mutations decrease the affinity mainly for Zn, Ni and Hg but less for Cd, and revealed the possible existence of additional binding sites for Zn, Ni and Hg.

Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Reducing Variability in Practice through a Collaborative Telemedicine Initiative.

OBJECTIVE: This study aimed to assess the viability of implementing a tele-educational training program in neurocritical care for newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia (TH), with the goal of reducing practice variation. STUDY DESIGN: Prospective study including newborns with HIE treated with TH from 12 neonatal intensive care units in Brazil conducted from February 2021 to February 2022. An educational intervention consisting of 12 biweekly, 1-hour, live videoconferences was implemented during a 6-month period in all centers. Half of the centers had the assistance of a remote neuromonitoring team. The primary outcome was the rate of deviations from TH protocol, and it was evaluated during a 3-month period before and after the intervention. Logistic regression via generalized estimating equations was performed to compare the primary and secondary outcomes. Protocol deviations were defined as practices not in compliance with the TH protocol provided. A subanalysis evaluated the differences in protocol deviations and clinical variables between centers with and without neuromonitoring. RESULTS: Sixty-six (39.5%) newborns with HIE were treated with TH during the preintervention period, 69 (41.3%) during the intervention period and 32 (19.1%) after intervention. There was not a significant reduction in protocol deviations between the pre- and postintervention periods (37.8 vs. 25%, p = 0.23); however, a decrease in the rates of missing Sarnat examinations within 6 hours after birth was seen between the preintervention (n = 5, 7.6%) and postintervention (n = 2, 6.3%) periods (adjusted odds ratio [aOR]: 0.36 [0.25-0.52], p < 0.001). Centers with remote neuromonitoring support had significantly lower rates of seizures (27.6 vs. 57.5%; aOR: 0.26 [0.12-0.55], p < 0.001) and significant less seizure medication (27.6 vs. 68.7%; aOR: 0.17 [0.07-0.4], p < 0.001). CONCLUSION: This study shows that implementing a tele-educational program in neonatal neurocritical care is feasible and may decrease variability in the delivery of care to patients with HIE treated with TH. KEY POINTS: · Neurocritical care strategies vary widely in low- and middle-income countries.. · Heterogeneity of care may lead to suboptimal efficacy of neuroprotective strategies.. · Tele-education and international collaboration can decrease the variability of neurocritical care provided to infants with HIE..

Unearthing the soil-borne microbiome of land plants.

Plant-soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate organisms consistently associated with land plants (i.e., their consistent soil-borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.

Acute Aseptic Meningitis Temporally Associated with Intravenous Polyclonal Immunoglobulin Therapy: A Systematic Review.

An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.

Eco-Friendly Cork-Polyurethane Biocomposites for Enhanced Impact Performance: Experimental and Numerical Analysis.

Cork composites are byproducts from wine stopper production, resulting from the agglomeration of cork granules with a thermoset resin. The resulting compound is a versatile and durable material with numerous industrial applications. Due to its unique properties, such as low-density, high-strength, excellent energy absorption, and good thermal and acoustic insulators, cork composites find room for application in demanding industries such as automotive, construction, and aerospace. However, agglomerated cork typically has a polyurethane matrix derived from petrochemical sources. This study focuses on developing eco-friendly porous polyurethane biocomposites manufactured with the used cooking oil polyol modified with cork. Since cork and polyurethane foam are typically used for impact shock absorption, the manufactured samples were subjected to impact loading. The assessment of crashworthiness is performed through 100 J impact tests. A finite element numerical model was developed to simulate the compression of these new composites under impact, and the model validation was performed. The highest specific absorbed energy was obtained for petrochemical polyol composites with the 3% addition of natural or modified cork. The research conducted in this study showcased the feasibility of substituting certain petrochemical components used for the synthesis of the polyurethane matrix with ecological waste vegetable oil components.

Shear thickening fluid (STF) in engineering applications and the potential of cork in STF-based composites.

Shear thickening fluids (STFs) are a unique type of fluids that can quickly transform into a solid-like state when subjected to forces (rate dependent). These fluids are created by dispersing micro and nanoparticles within a medium. When the force is removed, they return to their original liquid state. Shear thickening fluids can absorb a significant amount of impact energy, making them useful for reducing vibrations and serving as a damper. This study provides a comprehensive and brief overview of existing literature on shear thickening fluids, including their properties, classification, and the rheological mechanisms behind the shear thickening behaviour. It also examines the use of these fluids in various applications, such as improving resistance to stabs and spikes, protecting against low- and high-velocity impacts, and as a new medium for energy dissipation in industries such as battery safety, vibration control and adaptive structures. Lastly, this work reviews the promising combination of STFs with cork. Given the sustainability of cork and its energy absorption capacity, cork-STF composites are a promising solution for various impact-absorbing applications. Overall, the paper underscores the versatility and potential of STFs, and advocates for further research and exploration.