Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutrition and Frailty: Opportunities for Prevention and Treatment

Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.
Peripheral Blood T Cell Gene Expression Responses to Exercise and HMB in Sarcopenia

Background: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. Methods: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. Results: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. Conclusions: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.
Association of Ventilatory Disorders with Respiratory Symptoms, Physical Activity, and Quality of Life in Subjects with Prior Tuberculosis: A National Database Study in Korea

Tuberculosis (TB) survivors experience post-TB lung damage and ventilatory function disorders. However, the proportions of obstructive and restrictive ventilatory disorders as well as normal ventilation among subjects with prior TB are unknown. In addition, the impacts of ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and the quality of life in subjects with prior TB remain unclear. Subjects who participated in the Korean National Health and Nutritional Examination Survey 2007–2016 were enrolled in this study. We evaluated the impact of each ventilatory disorder and its severity on respiratory symptoms, physical activity limitations, and quality of life (measured by the EuroQoL five dimensions questionnaire [EQ-5D] index values) in subjects with prior TB. Among 1466 subjects with prior TB, 29% and 16% had obstructive ventilatory disorders and restrictive ventilatory disorders, respectively. Mild and moderate obstructive ventilatory disorders were not associated with respiratory symptoms, physical activity limitations, or EQ-5D index value compared with normal ventilation; however, severe obstructive ventilatory disorders were associated with more respiratory symptoms (adjusted odds ratio [aOR] = 13.62, 95% confidence interval [CI] = 4.64–39.99), more physical activity limitation (aOR = 218.58, 95% CI = 26.82–1781.12), and decreased EQ-5D index (adjusted coefficient = −0.06, 95% CI = (−0.12–−0.10) compared with normal ventilation. Mild restrictive ventilatory disorders were associated with more respiratory symptoms (aOR = 2.10, 95% CI = 1.07–4.14) compared with normal ventilation, while moderate (aOR = 5.71, 95% CI = 1.14–28.62) and severe restrictive ventilatory disorders (aOR = 9.17, 95% CI = 1.02–82.22) were associated with physical activity limitation compared with normal ventilation. In conclusion, among subjects with prior TB, 29% and 16% developed obstructive and restrictive ventilatory disorders, respectively. Severe obstructive ventilatory disorder was associated with more respiratory symptoms, more physical activity limitation, and poorer quality of life, while severe restrictive ventilatory disorder was associated with more physical activity limitations.
Functional Redundancy and Specialization of the Conserved Cold Shock Proteins in Bacillus subtilis

Many bacteria encode so-called cold shock proteins. These proteins are characterized by a conserved protein domain. Often, the bacteria have multiple cold shock proteins that are expressed either constitutively or at low temperatures. In the Gram-positive model bacterium Bacillus subtilis, two of three cold shock proteins, CspB and CspD, belong to the most abundant proteins suggesting a very important function. To get insights into the role of these highly abundant proteins, we analyzed the phenotypes of single and double mutants, tested the expression of the csp genes and the impact of CspB and CspD on global gene expression in B. subtilis. We demonstrate that the simultaneous loss of both CspB and CspD results in a severe growth defect, in the loss of genetic competence, and the appearance of suppressor mutations. Overexpression of the third cold shock protein CspC could compensate for the loss of CspB and CspD. The transcriptome analysis revealed that the lack of CspB and CspD affects the expression of about 20% of all genes. In several cases, the lack of the cold shock proteins results in an increased read-through at transcription terminators suggesting that CspB and CspD might be involved in the control of transcription termination.
Identification of Distant Regulatory Elements Using Expression Quantitative Trait Loci Mapping for Heat-Responsive Genes in Oysters

Many marine ectotherms, especially those inhabiting highly variable intertidal zones, develop high phenotypic plasticity in response to rapid climate change by modulating gene expression levels. Herein, we examined the regulatory architecture of heat-responsive gene expression plasticity in oysters using expression quantitative trait loci (eQTL) analysis. Using a backcross family of Crassostrea gigas and its sister species Crassostrea angulata under acute stress, 56 distant regulatory regions accounting for 6–26.6% of the gene expression variation were identified for 19 heat-responsive genes. In total, 831 genes and 164 single nucleotide polymorphisms (SNPs) that could potentially regulate expression of the target genes were screened in the eQTL region. The association between three SNPs and the corresponding target genes was verified in an independent family. Specifically, Marker13973 was identified for heat shock protein (HSP) family A member 9 (HspA9). Ribosomal protein L10a (RPL10A) was detected approximately 2 kb downstream of the distant regulatory SNP. Further, Marker14346-48 and Marker14346-85 were in complete linkage disequilibrium and identified for autophagy-related gene 7 (ATG7). Nuclear respiratory factor 1 (NRF1) was detected approximately 3 kb upstream of the two SNPs. These results suggested regulatory relationships between RPL10A and HSPA9 and between NRF1 and ATG7. Our findings indicate that distant regulatory mutations play an important role in the regulation of gene expression plasticity by altering upstream regulatory factors in response to heat stress. The identified eQTLs provide candidate biomarkers for predicting the persistence of oysters under future climate change scenarios.
Mechanisms of Anticancer Activity of a Fatty Acid Mixture Extracted from Hen Egg Yolks Enriched in Conjugated Linoleic Acid Diene (CLA) against WM793 Melanoma Cells

The conjugated linoleic acid (CLA) diene is a biologically active compound with proven health-promoting effects. In terms of anticancer properties, it has been shown that CLA reduces the proliferation of cancer cells. In this study, it has been demonstrated that a mixture of fatty acids, isolated from chicken egg yolk enriched in CLA isomers by biofortification, reduces (by 30.5%) the proliferation of human melanoma cancer cells line WM793 to a greater extent than a mixture of fatty acids not containing these isomers. At the same time, the tested fatty acid mixtures show no effect on human normal BJ fibroblast cells. For the first time, the genes with increased expression have been identified and the proteins have been activated by the fatty acid mixture of CLA-enriched egg yolk, mainly responsible for mitochondrial pathway-dependent apoptosis.
Potential Phosphorylation of Viral Nonstructural Protein 1 in Dengue Virus Infection

Dengue virus (DENV) infection causes a spectrum of dengue diseases that have unclear underlying mechanisms. Nonstructural protein 1 (NS1) is a multifunctional protein of DENV that is involved in DENV infection and dengue pathogenesis. This study investigated the potential post-translational modification of DENV NS1 by phosphorylation following DENV infection. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), 24 potential phosphorylation sites were identified in both cell-associated and extracellular NS1 proteins from three different cell lines infected with DENV. Cell-free kinase assays also demonstrated kinase activity in purified preparations of DENV NS1 proteins. Further studies were conducted to determine the roles of specific phosphorylation sites on NS1 proteins by site-directed mutagenesis with alanine substitution. The T27A and Y32A mutations had a deleterious effect on DENV infectivity. The T29A, T230A, and S233A mutations significantly decreased the production of infectious DENV but did not affect relative levels of intracellular DENV NS1 expression or NS1 secretion. Only the T230A mutation led to a significant reduction of detectable DENV NS1 dimers in virus-infected cells; however, none of the mutations interfered with DENV NS1 oligomeric formation. These findings highlight the importance of DENV NS1 phosphorylation that may pave the way for future target-specific antiviral drug design.
Cytological Spectrum of Pulmonary Histoplasmosis Diagnosed by Bronchoalveolar Lavage: 12 Years of Experience in French Guiana

Disseminated histoplasmosis is a major cause of mortality in HIV-infected patients. Rapid and efficient diagnosis of Histoplasma capsulatum is crucial. Cytopathology is available in most hospitals and represents a rapid diagnostic alternative. In this study, we reviewed 12 years of experience to describe the cytology of histoplasmosis diagnosed by bronchoalveolar lavage (BAL) in relation to patient characteristics. BAL-diagnosed pulmonary histoplasmosis concerned 17 patients (14 HIV+). BAL cellularity ranged from 76,000 to 125,000 cells/mL in HIV patients, and 117,000 to 160,000 cells/mL in non-HIV patients. Macrophages predominated in all HIV patients (from 60% to 88%), lymphocytic infiltrates ranged from 5% to 15%, and neutrophils were very heterogeneous (from 2% to 32%). The number of H. capsulatum at hot spots seemed greater in HIV-infected than in immunocompetent patients (9 to 375 vs. 4 to 10) and were inversely proportional to the CD4 counts. Yeasts were both intracellular and extracellular in 85.7% of the HIV patients. This is the most comprehensive series detailing the cytological aspects of BAL in the diagnosis of H. capsulatum, focusing on the number of yeasts and their clustering pattern. The cytological examination of the Gomori-Grocott-stained BAL allows a reliable diagnosis of histoplasmosis.
Investigating Ex Vivo Animal Models to Test the Performance of Intravitreal Liposomal Drug Delivery Systems

There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh porcine eyes obtained from the local slaughterhouse as a model for testing the intravitreal biodistribution and retention of liposomes with or without polyethylene glycol (PEG) conjugation and with different surface charges. The histology of the eyes was analyzed to localize the liposomes, and it was found that liposomes with PEG absorbed rapidly on the retina (within 1 h), with positively charged and PEG-coated liposomes being retained for at least 24 h. In parallel, fluorophotometry was employed on intact eyes, to determine the pharmacokinetics of the fluorophore calcein, as a substitute for a small hydrophilic therapeutic compound. We found a 4.5-fold increase in the vitreous half-life of calcein loaded in liposomes, compared with the free solution. Retinal toxicity was addressed using murine-derived retinal explant cultures. Liposomes were non-toxic up to 500 µg/mL. Toxicity was observed at 5 mg/mL for anionic and cationic liposomes, with 2-fold and 2.5-fold increased photoreceptor cell death, respectively. Overall, we could show that important ocular drug delivery considerations such as pharmacokinetics and biodistribution can be estimated in ex vivo porcine eyes, and may guide subsequent in vivo experiments.
Recent Progress of Two-Dimensional Materials for Ultrafast Photonics

Owing to their extraordinary physical and chemical properties, two-dimensional (2D) materials have aroused extensive attention and have been widely used in photonic and optoelectronic devices, catalytic reactions, and biomedicine. In particular, 2D materials possess a unique bandgap structure and nonlinear optical properties, which can be used as saturable absorbers in ultrafast lasers. Here, we mainly review the top-down and bottom-up methods for preparing 2D materials, such as graphene, topological insulators, transition metal dichalcogenides, black phosphorus, and MXenes. Then, we focus on the ultrafast applications of 2D materials at the typical operating wavelengths of 1, 1.5, 2, and 3 μm. The key parameters and output performance of ultrafast pulsed lasers based on 2D materials are discussed. Furthermore, an outlook regarding the fabrication methods and the development of 2D materials in ultrafast photonics is also presented.
Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.
Introducing Less-Invasive Surfactant Administration into a Level IV NICU: A Quality Improvement Initiative

Less-invasive surfactant administration (LISA), a newer technique of delivering surfactant via a thin catheter, avoids mechanical ventilation. LISA has been widely adopted in Europe but less so in the US. Our goal was to increase the percentage of surfactant delivered via LISA from 0% to 51% by 12/2020. Project planning and literature review started 12/2019, and included a standardized equipment kit and simulation training sessions. We began Plan–Do–Study–Act (PDSA) cycles in 6/2020. Initial exclusions for LISA were gestational age (GA) <28 weeks (w) or ≥36 w, intubation in the delivery room, or PCO2 >70 if known; GA exclusion is now <25 w. From 6 to 12/2020, 97 patients received surfactant, 35 (36%) via LISA. When non-LISA-eligible patients were excluded, 35/42 (83%) received LISA successfully. There were only 2/37 patients for whom LISA was not able to be performed. Three LISA infants required mechanical ventilation in the first week of life. Sedation remained an initial challenge but improved when sucrose was used routinely. LISA was safely and successfully introduced in our NICU.
Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic β-Cell

Medicinal plants are commonly used in the treatment of diabetes, particularly as they contain flavonoids and phenolic compounds. The present study aims to investigate the activities of a polyherbal formulation made from Urtica dioica, Apium graveolens, and Zingiber officinale (UAZ) against streptozotocin–nicotinamide ((STZ-NA)-induced type 2 diabetes in CD1 mice, glucose-induced type 2 diabetes (T2DM) in zebrafish, and high glucose-induced damage in RINm5F pancreatic β-cells. In fasting mice, plasma glucose, glycosylated hemoglobin (HbA1C), lipid hydroperoxides (LOOH), thiobarbituric acid reactive substances (TBARS), and lipid profiles were significantly increased, whereas insulin, enzymatic antioxidants, and carbohydrate metabolic enzymes were altered significantly in diabetic mice. Zebrafish had similar glucose levels, liver enzymes, and lipid profiles compared to mice. The study investigated the effects of the extract in enhancing cell viability, insulin secretion, and reducing lipid peroxidation and intracellular reactive oxygen species (ROS) levels in RINm5F cells damaged by high glucose. All the above biochemical parameters were enhanced in both mice and zebrafish treated; the combined extract UAZ normalized all the biochemical parameters. The medicinal plant extracts, used either separately or in combination, ameliorated the adverse effect of glucose on cell viability and functionality of beta-RINm5F cells.
Acceptance of COVID-19 Vaccination in Cancer Patients in Hong Kong: Approaches to Improve the Vaccination Rate

Emerging efficacy and safety data have led to the authorization of COVID-19 vaccines worldwide, but most trials excluded patients with active malignancies. This study evaluates the intended acceptance of COVID-19 vaccination in cancer patients in Hong Kong. Methods: 660 adult cancer patients received a survey, in paper or electronic format, between 31 January 2021 and 15 February 2021. The survey included patient’s clinical characteristics, perceptions of COVID-19 and vaccination, vaccine knowledge, cancer health literacy, and Hospital Anxiety and Depression scale (HADS). The primary outcome was the intended acceptance of COVID-19 vaccine in cancer patients. Multivariable analysis was performed to identify factors associated with intended acceptance. Results: The intended acceptance of COVID-19 vaccination was 17.9%. A total of 487 (73.8%) believed that vaccination could prevent them from infection. Over 70% worried about vaccine negative effects on cancer and its side effects. Factors associated with intended acceptance included higher level of “belief in vaccine on preventing them from getting COVID-19”, less worry about long-term side effects of vaccine, lower level of cancer health literacy, and normal HADS (Depression scale). Conclusions: To improve vaccine acceptance rate, public education campaigns specific to cancer patients to gain their trust in efficacy and relieve their worries are needed.
Synergistic Photoelectrochemical Synthesis of Formate from CO2 on {121̅} Hierarchical Co3O4

To propel the thermodynamically unfavorable conversion of greenhouse CO2 to renewable fuel with remarkable efficacy, we here proposed a visible-light-driven synergistic photoelectrochemical (PEC) synthesis of formate from CO2. Formate was the only C1 product photoelectrochemically generated on the fabricated hierarchical Co3O4 electrode. Results showed that up to 384.8 ± 7.4 μmol of formate was produced within 8 h owing to the synergistic PEC reduction process. This enhanced production of formate, outnumbering most of the reported work, was further found to be indispensable of the superior photocatalytic and electrocatalytic reduction performance of the as-prepared electrode. Research further elucidated that the photocatalytic activity was intimately related with the hierarchical Co3O4 microstructure, in which a single-crystalline microflower was interconnected by thin nanopetals on one-dimensional rhombus nanorod. Additionally, the construction of {121} facet allowed high Co3+ exposure on Co3O4 surface,.