Miracle-dz/UniFAR-FTUs huggingface dataset:
Thymic atrophy creates holes in Treg‐mediated immuno‐regulation via impairment of an antigen‐specific clone

Age‐related thymic atrophy results in reduced output of naïve conventional T (Tcon) cells. However, its impact on regulatory T (Treg) cells is insufficiently understood. Given evidence that thymic Treg (tTreg) cell generation is enhanced in the aged, atrophy thymus and that the aged periphery accumulates peripheral Treg (pTreg) cells, we asked why these Treg cells are unable to effectively attenuate increased autoreactivity‐induced chronic inflammation in the elderly. We designed a mock‐self‐antigen chimera mouse model, in which membrane‐bound ovalbumin (mOVA) transgenic mice, bearing a FoxN1‐floxed gene for induction of conditional thymic atrophy, received OVA‐specific (OT‐II) T‐cell receptor (TCR) transgenic progenitor cells. The chimeric mice with thymic atrophy exhibited a significant decrease in OVA‐specific tTreg and pTreg cells but not polyclonal (pan)‐Treg cells. These OVA‐specific pTreg cells were significantly less able to suppress OVA‐specific stimulation‐induced proliferation in vitro and exhibited lower FoxP3 expression. Additionally, we conducted preliminary TCR repertoire diversity sequencing for Treg cells among recent thymic emigrants (RTEs) from RagGFP‐FoxP3RFP dual‐reporter mice and observed a trend for decreased diversity in mice with thymic atrophy compared to littermates with normal thymus. These data indicate that although the effects of age‐related thymic atrophy do not affect pan‐Treg generation, certain tissue‐specific Treg clones may experience abnormal agonist selection. This, combined with enhanced pan‐pTreg cells, may greatly contribute to age‐related chronic inflammation, even in the absence of acute autoimmune disease in the elderly.
Defect‐related Si diffusion in GaAs on Si

Preferential diffusion channels of silicon are evidenced in GaAs grown by metalorganic vapor phase epitaxy on Si(100). The density of these diffusion channels is found to be consistent with the measured dislocation density. In addition, combining scanning electron microscopy and x‐ray fluorescence it is shown that a large amount of Si emerges at the surface inside small 〈011〉 overgrowth oriented defects (≊1 μm) present at the GaAs/Si surface.
Targeting Ovarian Cancer Stem Cells by Dual Inhibition of HOTAIR and DNA Methylation

Ovarian cancer is a chemoresponsive tumor with very high initial response rates to standard therapy consisting of platinum/paclitaxel. However, most women eventually develop recurrence, which rapidly evolves into chemoresistant disease. Persistence of ovarian cancer stem cells (OCSCs) at the end of therapy has been shown to contribute to resistant tumors. In this study, we demonstrate that the long noncoding RNA HOTAIR is overexpressed in HGSOC cell lines. Furthermore, HOTAIR expression was upregulated in OCSCs compared with non-CSC, ectopic overexpression of HOTAIR enriched the ALDH+ cell population and HOTAIR overexpression increased spheroid formation and colony-forming ability. Targeting HOTAIR using peptide nucleic acid-PNA3, which acts by disrupting the interaction between HOTAIR and EZH2, in combination with a DNMT inhibitor inhibited OCSC spheroid formation and decreased the percentage of ALDH+ cells. Disrupting HOTAIR-EZH2 with PNA3 in combination with the DNMTi on the ability of OCSCs to initiate tumors in vivo as xenografts was examined. HGSOC OVCAR3 cells were treated with PNA3 in vitro and then implanted in nude mice. Tumor growth, initiation, and stem cell frequency were inhibited. Collectively, these results demonstrate that blocking HOTAIR–EZH2 interaction combined with inhibiting DNA methylation is a potential approach to eradicate OCSCs and block disease recurrence.
Coast‐wide evidence of low pH amelioration by seagrass ecosystems

Global‐scale ocean acidification has spurred interest in the capacity of seagrass ecosystems to increase seawater pH within crucial shoreline habitats through photosynthetic activity. However, the dynamic variability of the coastal carbonate system has impeded generalization into whether seagrass aerobic metabolism ameliorates low pH on physiologically and ecologically relevant timescales. Here we present results of the most extensive study to date of pH modulation by seagrasses, spanning seven meadows (Zostera marina) and 1000 km of U.S. west coast over 6 years. Amelioration by seagrass ecosystems compared to non‐vegetated areas occurred 65% of the time (mean increase 0.07 ± 0.008 SE). Events of continuous elevation in pH within seagrass ecosystems, indicating amelioration of low pH, were longer and of greater magnitude than opposing cases of reduced pH or exacerbation. Sustained elevations in pH of >0.1, comparable to a 30% decrease in [H+], were not restricted only to daylight hours but instead persisted for up to 21 days. Maximal pH elevations occurred in spring and summer during the seagrass growth season, with a tendency for stronger effects in higher latitude meadows. These results indicate that seagrass meadows can locally alleviate low pH conditions for extended periods of time with important implications for the conservation and management of coastal ecosystems.
Bioinformatics tools developed to support BioCompute Objects

Abstract Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount of data generated by sequencing experiments, an increase in the complexity of bioinformatics analysis reporting and an increase in the types of data generated. These increases in volume, diversity and complexity of the data generated and their analysis expose the necessity of a structured and standardized reporting template. BioCompute Objects (BCOs) provide the requisite support for communication of HTS data analysis that includes support for workflow, as well as data, curation, accessibility and reproducibility of communication. BCOs standardize how researchers report provenance and the established verification and validation protocols used in workflows while also being robust enough to convey content integration or curation in knowledge bases. BCOs that encapsulate tools, platforms, datasets and workflows are FAIR (findable, accessible, interoperable and reusable) compliant. Providing operational workflow and data information facilitates interoperability between platforms and incorporation of future dataset within an HTS analysis for use within industrial, academic and regulatory settings. Cloud-based platforms, including High-performance Integrated Virtual Environment (HIVE), Cancer Genomics Cloud (CGC) and Galaxy, support BCO generation for users. Given the 100K+ userbase between these platforms, BioCompute can be leveraged for workflow documentation. In this paper, we report the availability of platform-dependent and platform-independent BCO tools: HIVE BCO App, CGC BCO App, Galaxy BCO API Extension and BCO Portal. Community engagement was utilized to evaluate tool efficacy. We demonstrate that these tools further advance BCO creation from text editing approaches used in earlier releases of the standard. Moreover, we demonstrate that integrating BCO generation within existing analysis platforms greatly streamlines BCO creation while capturing granular workflow details. We also demonstrate that the BCO tools described in the paper provide an approach to solve the long-standing challenge of standardizing workflow descriptions that are both human and machine readable while accommodating manual and automated curation with evidence tagging. Database URL: https://www.biocomputeobject. org/resources
Physical exercise and prevention of falls. Effects of a Pilates training method compared with a general physical activity program

Abstract Introduction: Falls are the leading cause of injury-related mortality and morbidity in the elderly. Physical activity plays a key role in the prevention of falls and stimulates postural control. The aim of this study was to compare a general physical activity program for the elderly with a Pilates program to evaluate the effects on balance and on reducing the risk of falling. Materials and Methods: Forty-six subjects were enrolled in this study, but only 41 were included in the study. The subjects were divided into 2 groups: Pilates group (P-G) and a group following a nonspecific program of physical activity (Pa-G). Each subject underwent the hand grip test, Berg balance scale test, and posturographic analysis. Results: Spearman correlation coefficient showed correlations between the following parameters: BBS versus hand grip test (r = 0.68); BBS versus ellipse surface area (r = −0.75). There were significant differences between groups after the exercise program: both groups showed an improvement in performance but the P-G recorded significantly better results than the Pa-G. Discussion and conclusions: This study confirmed that physical activity improves both balance and strength. However, our data show that Pilates has a greater effect on these physical abilities than a general physical activity program.
Occurrence and impact of fungicides residues on fermentation during wine production– A review

ABSTRACT Continuous fungicide spraying is required to eliminate fungal pathogens on grapes. However, this practice is associated with several risks, including contamination and environmental imbalance, as well as toxicity to operators and the induction of resistance in pathogens. In addition, a strong correlation has been reported between the presence of fungicides and the occurrence of issues during alcoholic fermentation, resulting in negative impacts on the sensory quality of the final products. Numerous studies have evaluated residue concentrations of phytosanitary products in grapes, juices, and wines, and a significant number of studies have assessed the impact of different agrochemicals on bioprocesses. However, a review compiling the key results of these studies is currently lacking. This review incorporates results obtained in the last decade from research on the presence of fungicide residues, including azoxystrobin, boscalid, captan, copper, fenhexamid, folpet, pyraclostrobin, pyrimethanil and tebuconazole, and their effects on fermentation kinetics. Practical solutions to mitigate these problems, both in vineyards and industry, are also presented and discussed. This review highlights the constant high fungicidal agent concentrations (greater than 1 or 2 mg L−1) used throughout the winemaking process, with the impact of residues being of particular concern, especially with regard to their effect on yeast activity and the fermentation process. Thus, the adoption of methodologies that allow winemakers to control and trace these residues is an important step in avoiding or reducing fermentation problems throughout the winemaking process.
Participatory health education on school (re)inclusion of the adolescent cancer survivor.

OBJECTIVES to analyze school (re)inclusion of an adolescent cancer survivor before/after participatory health education with adolescents. METHODS qualitative and participatory research that included data from the medical record of an adolescent rhabdomyosarcoma survivor and Talking Map dynamics (to diagnose the demand for learning and assess changes). The body-knowledge dynamics were applied in the educational intervention. In a public school in Rio de Janeiro, the adolescent (reference case) and nine people (four teachers and five teenagers) generated empirical materials, which became the content analysis objects. RESULTS strangeness to changes in an adolescent cancer survivor's body image, bullying, and acceptance were problematized in educational body-knowledge dynamics through relationships between changes and barriers to welcoming. The participatory educational process was essential in raising awareness by promoting re-inclusive actions. CONCLUSIONS participatory-problematizing education contributed to constructing a new collective identity and improvement in school interaction among peers.
The effect of single biome occupancy on the estimation of biome shifts and the detection of biome conservatism

Biome conservatism is often regarded as common in diversifying lineages, based on the detection of low biome shift rates or high phylogenetic signal. However, many studies testing biome conservatism utilise a single-biome-per-species approach, which may influence the detection of biome conservatism. Meta-analyses show that biome shift rates are significantly lower (less than a tenth), when single biome occupancy approaches are adopted. Using New Zealand plant lineages, estimated biome shifts were also significantly lower (14–67% fewer biome shifts) when analysed under the assumption of a single biome per species. Although a single biome approach consistently resulted in lower biome shifts, it detected fewer instances of biome conservatism. A third of clades (3 out of 9) changed status in biome conservatism tests between single and multiple biome occupancy approaches, with more instances of significant biome conservatism when using a multiple biome occupancy approach. A single biome approach may change the likelihood of finding biome conservatism because it assumes biome specialisation within species, falsely recognises some biome shift types and fails to include other biome shift types. Our results indicate that the degree of biome fidelity assumed has a strong influence on analyses assessing biome shift rates, and biome conservatism testing. We advocate analyses that allow species to occupy multiple biomes.
How properties of interacting depletant particles control aggregation of hard-sphere colloids

We present a numerical study of the effective potential Veff between two hard-sphere colloids dispersed in an implicit solvent in the presence of interacting depletant particles, for several values of temperature and depletant density, approaching the depletant gas-liquid critical point. We investigate the stability of a system of particles interacting via the pair-wise additive Veff to evaluate the locus of colloidal aggregation in the phase-diagram of the depletant, and its dependence on the colloids size. We assess how the excluded volume depletion forces are modified by depletant attraction and discuss under which conditions critical fluctuations of the depletant, in the form of critical Casimir forces, can be used to effectively manipulate colloidal aggregation.
Trifunctional Electrolyte Additive Hexadecyltrioctylammonium Iodide for Lithium-Sulfur Batteries with Extended Cycle Life.

Lithium-sulfur (Li-S) battery with a very high theoretical energy density (∼2500 Wh kg-1) is a very promising alternative to the commercial lithium-ion battery as the next-generation energy storage device. However, the Li-S battery suffers from shuttle effect and Li dendrites growth due to the solubility of polysulfides in the electrolyte system and the inhomogeneous deposition of Li, resulting in short cycling life span, which is the major obstacle in its practical application. Herein, we report an additive, hexadecyltrioctylammonium iodide (HTOA-I), in the conventional electrolyte system, which shows trifunctional effect on extending Li-S battery cycle life. It can not only help us to form a protective solid-electrolyte interface (SEI) on the surface of Li anode so as to reduce the contact of polysulfides with Li but also hinder the shuttling of polysulfides to the Li anode due to the strong combination of large-sized HTOA+ with polysulfide anions (Sn2-), which retard the migration of Sn2- and cause homogeneous Li deposition owing to the large size and stronger trend of HTOA+ to be absorbed on Li anode as well. A new method of phosphorescence analysis for direct observation of polysulfides shuttling has been put forward for the first time, which can be further developed in future studies. The cell with the HTOA-I-added electrolyte system shows high cycling stability, retaining 83.4% of the initial capacity after 200 cycles at 1 A g-1 and achieving 689 mAh g-1 even after 1000 cycles. This cost-effective and facile approach will not increase the complexity of the battery manufacturing process. Compared to other electrolyte additives, the additive in our work, HTOA-I, has better positive effects on extending cycle life. This trifunctional electrolyte additive will inspire the design of other new additives and further promote the development of Li-S batteries.
Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas

Purpose: To investigate the toxicity profile and establish an optimal dosing schedule of zotiraciclib with temozolomide in patients with recurrent high-grade astrocytoma. Patients and Methods: This two-stage phase I trial determined the MTD of zotiraciclib combined with either dose-dense (Arm1) or metronomic (Arm2) temozolomide using a Bayesian Optimal Interval design; then a randomized cohort expansion compared the progression-free survival rate at 4 months (PFS4) of the two arms for an efficient determination of a temozolomide schedule to combine with zotiraciclib at MTD. Pharmacokinetic and pharmacogenomic profiling were included. Patient-reported outcome was evaluated by longitudinal symptom burden. Results: Fifty-three patients were enrolled. Dose-limiting toxicities were neutropenia, diarrhea, elevated liver enzymes, and fatigue. MTD of zotiraciclib was 250 mg in both arms and thus selected for the cohort expansion. Dose-dense temozolomide plus zotiraciclib (PSF4 40%) compared favorably with metronomic temozolomide (PFS4 25%). Symptom burden worsened at cycle 2 but stabilized by cycle 4 in both arms. A significant decrease in absolute neutrophil count and neutrophil reactive oxygen species production occurred 12–24 hours after an oral dose of zotiraciclib but both recovered by 72 hours. Pharmacokinetic/pharmacogenomic analyses revealed that the CYP1A2_5347T>C (rs2470890) polymorphism was associated with higher AUCinf value. Conclusions: Zotiraciclib combined with temozolomide is safe in patients with recurrent high-grade astrocytomas. Zotiraciclib-induced neutropenia can be profound but mostly transient, warranting close monitoring rather than treatment discontinuation. Once validated, polymorphisms predicting drug metabolism may allow personalized dosing of zotiraciclib.
A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus pneumoniae

Significance During infection, microbes must survive the hostile environmental conditions of the human host. When exposed to stresses, bacteria activate an intracellular response, known as the stringent response pathway, to ensure their survival. This study connects two fundamental pathways important for cellular growth in a Gram-positive pathogen: it demonstrates that enzymes responsible for cell wall biosynthesis are connected to the stringent response pathway via their ability to ameliorate errors in protein translation. Our study was performed on S. pneumoniae, where the MurM cell wall biosynthesis enzyme, a tRNA-dependent amino acyl transferase, is linked to penicillin resistance. We now demonstrate the importance of MurM in translation quality control and establish that it serves as a gatekeeper of the stringent response pathway. Survival in the human host requires bacteria to respond to unfavorable conditions. In the important Gram-positive pathogen Streptococcus pneumoniae, cell wall biosynthesis proteins MurM and MurN are tRNA-dependent amino acyl transferases which lead to the production of branched muropeptides. We demonstrate that wild-type cells experience optimal growth under mildly acidic stressed conditions, but ΔmurMN strain displays growth arrest and extensive lysis. Furthermore, these stress conditions compromise the efficiency with which alanyl-tRNAAla synthetase can avoid noncognate mischarging of tRNAAla with serine, which is toxic to cells. The observed growth defects are rescued by inhibition of the stringent response pathway or by overexpression of the editing domain of alanyl-tRNAAla synthetase that enables detoxification of tRNA misacylation. Furthermore, MurM can incorporate seryl groups from mischarged Seryl-tRNAAlaUGC into cell wall precursors with exquisite specificity. We conclude that MurM contributes to the fidelity of translation control and modulates the stress response by decreasing the pool of mischarged tRNAs. Finally, we show that enhanced lysis of ΔmurMN pneumococci is caused by LytA, and the murMN operon influences macrophage phagocytosis in a LytA-dependent manner. Thus, MurMN attenuates stress responses with consequences for host–pathogen interactions. Our data suggest a causal link between misaminoacylated tRNA accumulation and activation of the stringent response. In order to prevent potential corruption of translation, consumption of seryl-tRNAAla by MurM may represent a first line of defense. When this mechanism is overwhelmed or absent (ΔmurMN), the stringent response shuts down translation to avoid toxic generation of mistranslated/misfolded proteins.
Aconiti lateralis Radix Praeparata inhibits Alzheimer’s disease by regulating the complex regulation network with the core of GRIN1 and MAPK1

Abstract Context Current medicine for Alzheimer’s disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal. Objective Analysing the anti-AD effect of Fuzi and its potential molecular mechanism. Materials and methods AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CVs and LCPs). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis. Results Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCPs = 1.2533, p ≤ 0.05), and in 1.6–100 mg/mL increased CV (CVs from 1.1673 to 1.3321, p ≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_p ≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p ≤ 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the “Alzheimer’s disease” pathway. Discussion and conclusions These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.