Miracle-dz/UniFAR-FTUs huggingface dataset:
Melibiose Confers a Neuroprotection against Cerebral Ischemia/Reperfusion Injury by Ameliorating Autophagy Flux via Facilitation of TFEB Nuclear Translocation in Neurons

Autophagic/lysosomal dysfunction is a critical pathogenesis of neuronal injury after ischemic stroke. Trehalose has been validated to restore the impaired autophagy flux by boosting transcription factor EB (TFEB) nuclear translocation, but orally administrated trehalose can be greatly digested by intestinal trehalase before entering into brain. Melibiose (MEL), an analogue of trehalose, may thoroughly exert its pharmacological effects through oral administration due to absence of intestinal melibiase. The present study was to investigate whether melibiose could also confer a neuroprotection by the similar pharmacological mechanism as trehalose did after ischemic stroke. The rats were pretreated with melibiose for 7 days before middle cerebral artery occlusion (MCAO) surgery. Twenty-four hours following MCAO/reperfusion, the cytoplasmic and nuclear TFEB, and the proteins in autophagic/lysosomal pathway at the penumbra were detected by western blot and immunofluorescence, respectively. Meanwhile, the neurological deficit, neuron survival, and infarct volume were assessed to evaluate the therapeutic outcomes. The results showed that the neurological injury was significantly mitigated in MCAO+MEL group, compared with that in MCAO group. Meanwhile, nuclear TFEB expression in neurons at the penumbra was significantly promoted by melibiose. Moreover, melibiose treatment markedly enhanced autophagy flux, as reflected by the reinforced lysosomal capacity and reduced autophagic substrates. Furthermore, the melibiose-elicited neuroprotection was prominently counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Contrarily, reinforcement of lysosomal capacity with EN6 further improved the neurological performance upon melibiose treatment. Our data suggests that melibiose-augmented neuroprotection may be achieved by ameliorating autophagy flux via facilitation of TFEB nuclear translocation in neurons after ischemic stroke.
Sensing of Microvascular Vasomotion Using Consumer Camera

In this paper, we will introduce a method for observing microvascular waves (MVW) by extracting different images from the available images in the video taken with consumer cameras. Microvascular vasomotion is a dynamic phenomenon that can fluctuate over time for a variety of reasons and its sensing is used for variety of purposes. The special device, a side stream dark field camera (SDF camera) was developed in 2015 for the medical purpose to observe blood flow from above the epidermis. However, without using SDF cameras, smart signal processing can be combined with a consumer camera to analyze the global motion of microvascular vasomotion. MVW is a propagation pattern of microvascular vasomotions which reflects biological properties of vascular network. In addition, even without SDF cameras, MVW can be analyzed as a spatial and temporal pattern of microvascular vasomotion using a combination of advanced signal processing with consumer cameras. In this paper, we will demonstrate that such vascular movements and MVW can be observed using a consumer cameras. We also show a classification using it.
Under-5 Mortality and Its Associated Factors in Northern Nigeria: Evidence from 22,455 Singleton Live Births (2013–2018)

The northern geopolitical zones (NGZs) continue to report the highest under-5 mortality rates (U5MRs) among Nigeria’s six geopolitical zones. This study was designed to identify factors related to under-5 mortality (U5M) in the NGZs. The NGZ populations extracted from the 2018 Nigeria Demographic and Health Survey were explored to assess the factors associated with U5M using logistic regression, generalised linear latent, and mixed models. Between 2013 and 2018, the northwest geopolitical zone reported the highest U5MR (179 deaths per 1000 live births; 95% confidence interval [CI]: 163–194). The adjusted model showed that geopolitical zone, poor household, paternal occupation, perceived children’s body size at birth, caesarean delivery, and mothers and fathers’ education were highly associated with increased odds of U5M. Other significant factors that influenced U5M included children of fourth or higher birth order with shorter interval ≤ 2 years (adjusted odds ratio [aOR] = 1.68; CI: 1.42–1.90) and mothers who did not use contraceptives (aOR = 1.41, CI: 1.13–1.70). Interventions are needed and should primarily spotlight children residing in low-socioeconomic households. Educating mothers on the benefits of contraceptive use, child spacing, timely and safe caesarean delivery and adequate care for small-sized babies may also reduce U5M in Nigeria, particularly in the NGZs.
Genetic Parameters for Maternal Performance Traits in Commercially Farmed New Zealand Beef Cattle

Simple Summary Enhancing maternal performance in a beef cattle enterprise can increase overall profitability. Knowledge of the degree of genetic variation in relevant traits is required to inform breeding decisions in commercial environments. The objective of this research was to examine the inheritance of maternal performance traits and to evaluate the trait complementarity among reproduction, live weight, hip height, body condition score and maternal weaning weight in 15-month-old heifers, 2-year-old cows and mature cows using data collected on commercial New Zealand hill country farms. Results from this study indicate that almost no genetic variation exists for pregnancy outcomes in 15-month-old heifers and mature cows under New Zealand farming conditions but there is potential to improve reproductive performance in 2-year-old cows through genetic selection. Cows with greater genetic potential for rebreeding performance after their first calving season were more likely to have greater live weight, hip height and body condition score as heifers but were unlikely to become larger cows at maturity. Cows with genetics for greater maternal weaning weight were more likely to carry lower body condition and those animals tended to show greater reproductive performance. Abstract Maternal performance is a major driver of profitability in cow-calf beef cattle enterprises. The aim of this research was to evaluate the inheritance of maternal performance traits and examine the intercorrelation among reproduction, live weight, hip height, body condition and maternal contribution to calf weaning weight in 15-month-old heifers, 2-year-old cows and mature cows in New Zealand beef herds. Data were collected on a total of 14,241 cows and their progeny on five commercial New Zealand hill country farms. Heritabilities were low for reproductive traits in heifers and mature cows (0–0.06) but were greater in 2-year-old cows (0.12–0.21). Body condition scores were lowly (0.15–0.26) and live weights (0.42–0.48) and hip heights (0.47–0.65) highly heritable in heifers, 2-year-old cows and mature cows. Results indicate that 2-year-old cows with higher genetic potential for rebreeding ability may have greater genetic merit for live weight, hip height and body condition as heifers (rg = 0.19–0.54) but are unlikely to be larger cows at maturity (rg = −0.27–−0.10). The maternal genetic effect on weaning weight had a heritability of 0.20 and was negatively genetically correlated with body condition score in lactating cows (rg = −0.55–−0.40) but positively genetically correlated with rebreeding performance (rg = 0.48).
Antitumor and Antioxidant Activity of S-Methyl Methionine Sulfonium Chloride against Liver Cancer Induced in Wistar Albino Rats by Diethyl Nitrosamine and Carbon Tertrachloride

Liver disease, especially liver cancer, has become a threat facing the world. Now, antioxidant products are garnering great attention for the treatment and prevention of many diseases. S-Methyl methionine sulfonium chloride (MMSC) is a methionine derivative and is present in many vegetables and has anti-inflammatory effects and antioxidants. This is the first study aiming to investigate the antitumor activity of the MMSC. This study was carried out on 60 male Wistar albino rats (4–6 weeks old age) and divided into four groups, with the first group as normal control, second group as hepatocarcinoma induced by diethyl nitrosamine and carbon tetrachloride (DEN/CCL4) group, third group as normal rats treated with MMSC, and fourth group as hepatocellular carcinoma (HCC) induced rats treated with MMSC. Our findings revealed that MMSC administration after HCC induction significantly improved (p < 0.05) the liver function biomarkers, including AST, GGT, albumin, globulin, and albumin/globulin ratio (A/G), in comparison with those in the HCC group. Moreover, the histopathological changes of the liver tissue in the HCC group were improved by MMSC treatment. Likewise, the expression levels of tumor necrosis factor-alpha (TNF-α), induced nitric oxide synthase (iNOS), transforming growth factor (TGF-1β), and glypican 3 (GP3) were downregulated by MMSC treatment after HCC induction in comparison with those in the HCC-induced group. In conclusion, MMSC showed antitumor activity against HCC induction by DEN/CCl4 through decreasing lipid peroxide formation, the expression level of an inflammatory cytokines such as (TNF-α), immunoregulatory cytokines such as (TGF-1β), induced nitric oxide synthase, and glypican 3.
Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.
Preliminary Effect and Acceptability of an Intervention to Improve End-of-Life Care in Long-Term-Care Facilities: A Feasibility Study

The number of deaths of older adults in long-term care settings will increase with the aging population. Nurses and care workers in these settings face various challenges in providing end-of-life care, and interventions for quality end-of-life care may be useful. This feasibility study aims to explore the preliminary effect and acceptability of an intervention named the EOL Care Tool to improve end-of-life care in long-term-care facilities. We conducted a single-arm quasi-experimental study using mixed methods. This tool consisted of multiple components: professionalized lectures, newly developed structured documents, regular conferences regarding end-of-life care, and educational support from administrators. Twenty-four nurses and fifty-five care workers employed in a long-term care facility participated. For nurses, improvement in attitudes toward end-of-life care (p < 0.05) and interdisciplinary collaboration (p < 0.05) were shown quantitatively. Regarding acceptability, nurses and care workers evaluated the tool positively except for the difficulty of using the new documents. However, qualitative results showed that care workers felt the reluctance to address the work regarding end-of-life care. Therefore, a good preliminary effect and acceptability for nurses were indicated, while acceptability for care workers was only moderate. Revision to address the mentioned issues and evaluation of the revised tool with a more robust research design are required.
Development of New Meridianin/Leucettine-Derived Hybrid Small Molecules as Nanomolar Multi-Kinase Inhibitors with Antitumor Activity

Although the sea ecosystem offers a broad range of bioactivities including anticancer, none of the FDA-approved antiproliferative protein kinase inhibitors are derived from a marine source. In a step to develop new marine-inspired potent kinase inhibitors with antiproliferative activities, a new series of hybrid small molecules (5a–5g) was designed and synthesized based on chemical moieties derived from two marine natural products (Meridianin E and Leucettamine B). Over a panel of 14 cancer-related kinases, a single dose of 10 µM of the parent hybrid 5a possessing the benzo[d][1,3]dioxole moiety of Leucettamine B was able to inhibit the activity of FMS, LCK, LYN, and DAPK1 kinases with 82.5 ± 0.6, 81.4 ± 0.6, 75.2 ± 0.0, and 55 ± 1.1%, respectively. Further optimization revealed the most potent multiple kinase inhibitor of this new series (5g) with IC50 values of 110, 87.7, and 169 nM against FMS, LCK, and LYN kinases, respectively. Compared to imatinib (FDA-approved multiple kinase inhibitor), compound 5g was found to be ~ 9- and 2-fold more potent than imatinib over both FMS and LCK kinases, respectively. In silico docking simulation models of the synthesized compounds within the active site of FMS, LCK, LYN, and DAPK1 kinases offered reasonable explanations of the elicited biological activities. In an in vitro anticancer assay using a library of 60 cancer cell lines that include blood, lung, colon, CNS, skin, ovarian, renal, prostate, and breast cancers, it was found that compound 5g was able to suppress 60 and 70% of tumor growth in leukemia SR and renal RXF 393 cell lines, respectively. Moreover, an ADME study indicated a suitable profile of compound 5g concerning cell permeability and blood-brain barrier (BBB) impermeability, avoiding possible CNS side effects. Accordingly, compound 5g is reported as a potential lead towards novel antiproliferative marine-derived kinase modulators.
Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants

At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due to its genetic tractability, the yeast Saccharomyces cerevisiae represents a valuable model organism for understanding human genetic variability. In the present review, we show how S. cerevisiae has been used to study variants of genes involved in different diseases and in different pathways, highlighting the versatility of this model organism.
Oxidative Degradation of Tetracycline by Magnetite and Persulfate: Performance, Water Matrix Effect, and Reaction Mechanism

This study presents a strategy to remove tetracycline by using magnetite-activated persulfate. Magnetite (Fe3O4) was synthesized at high purity levels—as established via X-ray diffractometry, transmission electron microscopy, and N2 sorption analyses—and tetracycline was degraded within 60 min in the presence of both magnetite and persulfate (K2S2O8), while the use of either substance yielded limited degradation efficiency. The effects of magnetite and persulfate dosage, the initial concentration of tetracycline, and the initial pH on the oxidative degradation of tetracycline were interrogated. The results demonstrate that the efficiency of tetracycline removal increased in line with magnetite and persulfate dosage. However, the reaction rate increased only when increasing the magnetite dosage, not the persulfate dosage. This finding indicates that magnetite serves as a catalyst in converting persulfate species into sulfate radicals. Acidic conditions were favorable for tetracycline degradation. Moreover, the effects of using a water matrix were investigated by using wastewater treatment plant effluent. Comparably lower removal efficiencies were obtained in the effluent than in ultrapure water, most likely due to competitive reactions among the organic and inorganic species in the effluent. Increased concentrations of persulfate also enhanced removal efficiency in the effluent. The tetracycline degradation pathway through the magnetite/persulfate system was identified by using a liquid chromatograph-tandem mass spectrometer. Overall, this study demonstrates that heterogeneous Fenton reactions when using a mixture of magnetite and persulfate have a high potential to control micropollutants in wastewater.
Hematopoietic Prostaglandin D Synthase Inhibitor PK007 Decreases Muscle Necrosis in DMD mdx Model Mice

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and wasting due to the lack of dystrophin protein. The acute phase of DMD is characterized by muscle necrosis and increased levels of the pro-inflammatory mediator, prostaglandin D2 (PGD2). Inhibiting the production of PGD2 by inhibiting hematopoietic prostaglandin D synthase (HPGDS) may alleviate inflammation and decrease muscle necrosis. We tested our novel HPGDS inhibitor, PK007, in the mdx mouse model of DMD. Our results show that hindlimb grip strength was two-fold greater in the PK007-treated mdx group, compared to untreated mdx mice, and displayed similar muscle strength to strain control mice (C57BL/10ScSn). Histological analyses showed a decreased percentage of regenerating muscle fibers (~20% less) in tibialis anterior (TA) and gastrocnemius muscles and reduced fibrosis in the TA muscle in PK007-treated mice. Lastly, we confirmed that the DMD blood biomarker, muscle creatine kinase activity, was also reduced by ~50% in PK007-treated mdx mice. We conclude that our HPGDS inhibitor, PK007, has effectively reduced muscle inflammation and fibrosis in a DMD mdx mouse model.
The COVID-19 Clinician Cohort (CoCCo) Study: Empirically Grounded Recommendations for Forward-Facing Psychological Care of Frontline Doctors

This study aimed to develop empirically grounded recommendations and a coherent model of psychological care derived from the experiences and psychological care needs of COVID-19 frontline doctors, using semi-structured interviews and thematic analysis. Participants were UK frontline doctors specialising in Emergency Medicine, Anaesthetics, or Intensive Care (n = 31) purposively sampled for maximum variation on gender, specialty, ethnicity, and trauma-related distress; most worked in ICU during the pandemic (71%). Four themes were derived: (1) ‘coping strategies’, participants used many, including exercise, mindfulness, and “wait until it gets really bad”; (2) ‘sources of support’, participants valued embedded psychological support, digital services, and informal conversations with colleagues or family, though there was little opportunity; (3) ‘organisational influences on wellbeing’, participants reported a love–hate relationship for concepts like ‘wellbeing’, seen as important but insulting when basic workplace needs were unmet; (4) ‘improving engagement with support’, analysis suggests we must reduce physical and psychological barriers to access and encourage leaders to model psychologically supportive behaviours. Doctors’ frontline COVID-19 working experiences shine a ‘spotlight’ on pre-existing problems such as lack of physical resources and access to psychological care. Empirically grounded recommendations and a model of incremental psychological care are presented for use in clinical services.
Untargeted Metabolomics of Rind Essential Oils Allowed to Differentiate Two Closely Related Clementine Varieties

Chemical characterization of clementine varieties (Citrus clementina Hort. ex Tan.) essential oils (EO) can lead to variety identification and valorization of their potential use in food and aroma industries. The goal of this study was the chemometric discrimination between two very closely related and morphologically identical clementine varieties, Clemenules (NL) and Clemenpons (PO), based on their rind EO, to identify the differential volatile organic compounds (VOCs) and to determine their antioxidant capacity. EO rind volatile profile was determined by gas chromatography coupled to mass spectrometry in Citrus fruit at different ripening stages grown two independent years in two different locations. Untargeted metabolomics and multivariate data analysis showed an evolution of EO volatile profiles markedly parallel in both varieties. Although EO qualitative composition was identical in both varieties, PLS-DA allowed the identification of characteristic VOCs, quantitatively discriminating them along all the ripening process. PO showed higher accumulation of several mono- and sesquiterpene compounds such as trans-carveol, while NL showed higher levels of aldehyde and alcohol non-terpenoids like dodecanal. Both varieties evinced identical EO antioxidant activities, indicating a similar value for food preservation. Hence, untargeted metabolomics approach based on rind EO volatiles was revealed as a powerful technique able to differentiate between morphologically undistinguishable Citrus varieties.