Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into Alexandrium minutum Nutrient Acquisition, Metabolism and Saxitoxin Biosynthesis through Comprehensive Transcriptome Survey

Simple Summary Alexandrium minutum is one of the causing organisms for the occurrence of harmful algae bloom (HABs) in marine ecosystems. This species produces saxitoxin, one of the deadliest neurotoxins which can cause human mortality. However, molecular information such as genes and proteins catalog on this species is still lacking. Therefore, this study has successfully characterized several new molecular mechanisms regarding A. minutum environmental adaptation and saxitoxin biosynthesis. Ultimately, this study provides a valuable resource for facilitating future dinoflagellates’ molecular response to environmental changes. Abstract The toxin-producing dinoflagellate Alexandrium minutum is responsible for the outbreaks of harmful algae bloom (HABs). It is a widely distributed species and is responsible for producing paralytic shellfish poisoning toxins. However, the information associated with the environmental adaptation pathway and toxin biosynthesis in this species is still lacking. Therefore, this study focuses on the functional characterization of A. minutum unigenes obtained from transcriptome sequencing using the Illumina Hiseq 4000 sequencing platform. A total of 58,802 (47.05%) unigenes were successfully annotated using public databases such as NCBI-Nr, UniprotKB, EggNOG, KEGG, InterPRO and Gene Ontology (GO). This study has successfully identified key features that enable A. minutum to adapt to the marine environment, including several carbon metabolic pathways, assimilation of various sources of nitrogen and phosphorus. A. minutum was found to encode homologues for several proteins involved in saxitoxin biosynthesis, including the first three proteins in the pathway of saxitoxin biosynthesis, namely sxtA, sxtG and sxtB. The comprehensive transcriptome analysis presented in this study represents a valuable resource for understanding the dinoflagellates molecular metabolic model regarding nutrient acquisition and biosynthesis of saxitoxin.
Surface-Modified Multifunctional Thymol-Loaded Biodegradable Nanoparticles for Topical Acne Treatment

The present work is focused on the development of novel surface-functionalized poly(lactic-co-glycolic acid) nanoparticles loaded with thymol (TH-NPs) for topical administration enhancing thymol anti-inflammatory, antioxidant and wound healing activities against acne. TH-NPs were prepared by solvent evaporation method using different surface functionalization strategies and obtaining suitable physicochemical parameters and a good short-term stability at 4 °C. Moreover, TH-NPs skin penetration and antioxidant activity were assessed in ex vivo pig skin models. Skin penetration of TH-NPs followed the follicular route, independently of the surface charge and they were able to enhance antioxidant capacity. Furthermore, antimicrobial activity against Cutibacterium acnes was evaluated in vitro by the suspension test showing improved antibacterial performance. Using human keratinocyte cells (HaCat), cytotoxicity, cellular uptake, antioxidant, anti-inflammatory and wound healing activities were studied. TH-NPs were non-toxic and efficiently internalized inside the cells. In addition, TH-NPs displayed significant anti-inflammatory, antioxidant and wound healing activities, which were highly influenced by TH-NPs surface modifications. Moreover, a synergic activity between TH-NPs and their surface functionalization was demonstrated. To conclude, surface-modified TH-NPs had proven to be suitable to be used as anti-inflammatory, antioxidant and wound healing agents, constituting a promising therapy for treating acne infection and associated inflammation.
Alisporivir Improves Mitochondrial Function in Skeletal Muscle of mdx Mice but Suppresses Mitochondrial Dynamics and Biogenesis

Mitigation of calcium-dependent destruction of skeletal muscle mitochondria is considered as a promising adjunctive therapy in Duchenne muscular dystrophy (DMD). In this work, we study the effect of intraperitoneal administration of a non-immunosuppressive inhibitor of calcium-dependent mitochondrial permeability transition (MPT) pore alisporivir on the state of skeletal muscles and the functioning of mitochondria in dystrophin-deficient mdx mice. We show that treatment with alisporivir reduces inflammation and improves muscle function in mdx mice. These effects of alisporivir were associated with an improvement in the ultrastructure of mitochondria, normalization of respiration and oxidative phosphorylation, and a decrease in lipid peroxidation, due to suppression of MPT pore opening and an improvement in calcium homeostasis. The action of alisporivir was associated with suppression of the activity of cyclophilin D and a decrease in its expression in skeletal muscles. This was observed in both mdx mice and wild-type animals. At the same time, alisporivir suppressed mitochondrial biogenesis, assessed by the expression of Ppargc1a, and altered the dynamics of organelles, inhibiting both DRP1-mediated fission and MFN2-associated fusion of mitochondria. The article discusses the effects of alisporivir administration and cyclophilin D inhibition on mitochondrial reprogramming and networking in DMD and the consequences of this therapy on skeletal muscle health.
Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study

ApoE abnormality represents a well-known risk factor for cardiovascular diseases. Beyond its role in lipid metabolism, novel studies demonstrate a complex involvement of apoE in membrane homeostasis and signaling as well as in nuclear transcription. Due to the large spread of apoE isoforms in the human population, there is a need to understand the apoE’s role in pathological processes. Our study aims to dissect the involvement of apoE in heart failure. We showed that apoE-deficient rats present multiple organ damages (kidney, liver, lung and spleen) besides the known predisposition for obesity and affected lipid metabolism (two-fold increase in tissular damages in liver and one-fold increase in kidney, lung and spleen). Heart tissue also showed significant morphological changes in apoE−/− rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE−/− rats fed a high-fat diet showed more damage and affected collagen content (~60% less total collagen content and double increase in collagen1/collagen3 ratio) compared with the left ventricle (no significant differences in total collagen content or collagen1/collagen3 ratio). In patients, we were able to find a correlation between the presence of ε4 allele and cardiomyopathy (χ2 = 10.244; p = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, p < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, p = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 allele is associated with right ventricle dysfunction, implying different regulatory mechanisms of fibroblasts and the extracellular matrix in both ventricles. This is essential to be considered and thoroughly investigated before the design of therapeutical strategies for patients with heart failure.
Best Farming Practices for the Welfare of Dairy Cows, Heifers and Calves

Simple Summary The evolving change in societal attitudes regarding animal care and use has led to two main streams of thought. On one hand, there is the concept of “animal rights”, emphasizing that animals should have the same rights as humans, and as such should never be used to benefit humans (e.g., for food, clothing, entertainment, education, research, and even pet ownership). Animals should be able to live a life free of human interference and exploitation. On the other hand, many people agree that humans are responsible for animals and for their care; animals can be used to benefit humans if properly cared for, and their needs are met; abuse and neglect are banned. This is the “animal welfare” (AW) point of view, based on humane treatment, ensuring the physical and mental fitness of animals, as required by current EU legislation. Now, the point is that to fulfill the basic requirements of animal welfare animals are ensured a life worth living, especially given that they can feel emotions. In view of ensuring not only compliance with minimum legislative requirements, but also optimal farming conditions (above minimum legislative requirements), growing attention is attributed to best farming practices. In this work, a list of best practices proposed by the Italian National Reference Centre for Animal Welfare (CReNBA) has been collected to ensure a good quality of life for dairy cows, heifers and calves kept in intensive rearing systems. Abstract The concept of animal welfare (AW) has many meanings. Traditionally, AW has been considered as freedom from disease and suffering. Nowadays, growing attention goes to the concept of “positive animal welfare” (PAW), which can be interpreted within the concept of quality of life (QoL), thinking about a “balance of positives over negatives” and a “life worth living”. In this vision, where the QoL represents a continuum between positives and negatives, the Italian National Reference Centre for Animal Welfare (CReNBA), within the Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna (IZSLER), has developed a welfare assessment protocol for dairy cows, heifers, and calves in loose housing systems, including both animal-based and non-animal-based indicators, in which not only hazards but also benefits are identified. This protocol is part of an integrated monitoring system called “ClassyFarm”, belonging to the Italian Ministry of Health and developed by IZSLER. The aim of this paper is to extrapolate from the mentioned protocol, a list of 38 best farming practices (on managerial and equipment factors) for ensuring a high level of welfare in dairy cattle. All stakeholders (veterinarians, farmers, competent authorities, consumers, etc.) can benefit of these best practices as a guide or toolbox to ensure a life worth living for these animals.
The Impact of Kinesiology Taping on a Greek Foot with a Hammertoe—A Case Report

Background and Objectives: Hammertoe, one of the most common toe deformities, causes pain due to overloading of the periarticular tissues and skin lesions. Additionally, it results in problems with footwear choice, an unattractive foot appearance and a deterioration in quality of life. The most common treatment for rigid and advanced deformities is surgery, and these procedures are widely described in literature. If the changes in the interphalangeal and metatarsophalangeal joints are flexible (that mean they undergo correction without causing pain) or surgery is not possible, conservative treatment should be considered. No research, however, has been found detailing this treatment method. Conservative treatment includes the Kinesiology Taping (KT) method, which involves applying taping to correct deformities. This report describes the effect of KT treatment in a female patient with hammertoes. Materials and Methods: Anthropometric foot measurements (3D scanner) and foot loadings (baropodometric platform) are presented before KT applying, immediately after tapes application and after tapes removal following one month of use. Results: After using KT application parameters such as: foot length, maximum foot load, load under the area of the metatarsals II-III changed. Conclusion: Kinesiology Taping seems to be a symptomatic form of treatment of the effects of lesser toes deformity, therefore it is a good alternative for patients who do not want or cannot undergo surgery.
Faecal Cortisol Metabolites as an Indicator of Adrenocortical Activity in Farmed Blue Foxes

Simple Summary The measurement of faecal cortisol metabolites (FCMs) is increasingly used to monitor physiological stress responses in different animal species. Before this method is applied in coming stress- and welfare-related studies of farmed blue foxes (Vulpes lagopus), a species-specific validation is first required. In the current study, a 5α-pregnane-3ß,11ß,21-triol-20-one enzyme immunoassay was found suited to measure FCMs and thus hypothalamus–pituitary–adrenal (HPA) axis activity in farmed blue foxes. FCMs can therefore serve as a valid indicator of stress in future welfare studies of blue foxes. Abstract Welfare studies of blue foxes would benefit from a measurement of faecal cortisol metabolites (FCMs) as a non-invasive, physiological stress parameter reflecting hypothalamus–pituitary–adrenal (HPA) axis activity. Before implementation, a species-specific validation of such a method is required. Therefore, we conducted a physiological validation of an enzyme immunoassay (EIA) to measure FCMs in blue foxes. Twenty individuals (nine males and eleven females) were injected with synthetic adrenocorticotrophic hormone (ACTH) and faecal samples were collected every third h for two days. The FCM baseline levels were assessed based on the first sampling day (control period, 144 samples), followed by the ACTH injection and the second day of sampling (treatment period, 122 samples). FCMs were analysed with a 5α-pregnane-3ß,11ß,21-triol-20-one EIA. We compared the estimated mean FCM concentrations of the treatment samples to the baseline average. All samples for the two periods were collected at the same time of the day, which enabled to test the data also with an hourly pairwise comparison. With the two statistical approaches, we tested whether a possible diurnal fluctuation in the FCM concentrations affected the interpretation of the results. Compared to the baseline levels, both approaches showed 2.4–3.2 times higher concentrations on time points sampled 8–14 h after the ACTH injection (p < 0.05). The estimated FCM concentrations also fluctuated slightly within the control period (p < 0.01). Inter-individual variations in FCM levels were marked, which highlights the importance of having a sufficient number of animals in experiments utilising FCMs. The sampling intervals of 3 h enabled forming of informative FCM curves. Taken together, this study proves that FCM analysis with a 5α-pregnane-3ß,11ß,21-triol-20-one EIA is a valid measurement of adrenocortical activity in the farmed blue foxes. Therefore, it can be utilised as a non-invasive stress indicator in future animal welfare studies of the species.
Ambient Air Pollution and Respiratory Health in Sub-Saharan African Children: A Cross-Sectional Analysis

Ambient air pollution is projected to become a major environmental risk in sub-Saharan Africa (SSA). Research into its health impacts is hindered by limited data. We aimed to investigate the cross-sectional relationship between particulate matter with a diameter ≤ 2.5 μm (PM2.5) and prevalence of cough or acute lower respiratory infection (ALRI) among children under five in SSA. Data were collected from 31 Demographic and Health Surveys (DHS) in 21 SSA countries between 2005–2018. Prior-month average PM2.5 preceding the survey date was assessed based on satellite measurements and a chemical transport model. Cough and ALRI in the past two weeks were derived from questionnaires. Associations were analysed using conditional logistic regression within each survey cluster, adjusting for child’s age, sex, birth size, household wealth, maternal education, maternal age and month of the interview. Survey-specific odds ratios (ORs) were pooled using random-effect meta-analysis. Included were 368,366 and 109,664 children for the analysis of cough and ALRI, respectively. On average, 20.5% children had reported a cough, 6.4% reported ALRI, and 32% of children lived in urban areas. Prior-month average PM2.5 ranged from 8.9 to 64.6 μg/m3. Pooling all surveys, no associations were observed with either outcome in the overall populations. Among countries with medium-to-high Human Development Index, positive associations were observed with both cough (pooled OR: 1.022, 95%CI: 0.982–1.064) and ALRI (pooled OR: 1.018, 95%CI: 0.975–1.064) for 1 μg/m3 higher of PM2.5. This explorative study found no associations between short-term ambient PM2.5 and respiratory health among young SSA children, necessitating future analyses using better-defined exposure and health metrics to study this important link.
Diagnostic Accuracy Study Comparing Hysterosalpingo-Foam Sonography and Hysterosalpingography for Fallopian Tube Patency Assessment

Introduction: Simplified ultrasound-based infertility protocols that appear to provide enough information to plan effective management have been described. Thus, the objective of this study is to compare the diagnostic accuracy of the hysterosalpingo-foam sonography (HyFoSy) in tubal patency testing with the traditional hysterosalpngography (HSG) for establishing a new diagnostic strategy in infertility. Material and Methods: Prospective observational diagnostic accuracy was performed in a private fertility clinic in which 106 women undergoing a preconceptionally visit were recruited. All of them had low risk for tubal disease, had performed an HSG and were negative for Chlamydia trachomatis antibody. Main outcome measures were tubal patency and pain grade. Results: Evaluation of tubal patency by HyFoSy showed a total concordance with the results of the previous HSG in 72.6% (n = 77), and a total discordance for 4.7% (n = 6), with the inter-test agreement Kappa equal to 0.57, which means moderate concordance. Among the patients, 59.1% did not report pain during the procedure, while the remaining 48.1% indicated pain in different degrees; patients usually report less pain and only 6.6% described more pain with HyFoSy than with HSG (OR 6.57 (CI 95% 3.11–13.89)). Clinical outcomes after performing HyFoSy were not affected. Conclusions: HyFoSy is in concordance with HSG regarding tubal patency results and it is a less painful technique than HSG. HyFoSy is more economical and can be performed in an exam room only equipped with an ultrasound scanner. Based on these results, HyFoSy could be the first-choice diagnostic option to assess tubal patency in patients with low risk of tubal disease.
Poor Mental Health in Caregivers of Children with Attention-Deficit/Hyperactivity Disorder and Its Relationships with Caregivers’ Difficulties in Managing the Children’s Behaviors and Worsened Psychological Symptoms during the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic has thrown out a challenge to caregivers of children with attention-deficit/hyperactivity disorder (ADHD). The present study examined the factors related to the poor general mental health state of the caregivers of children with ADHD during the COVID-19 pandemic, including (1) difficulties of caregivers in asking their child to adopt protective behaviors against COVID-19, (2) difficulties of caregivers in managing the child’s daily performance, and (3) worsened psychological symptoms in children. In total, 161 caregivers completed an online questionnaire to provide data regarding their general mental health state and difficulties in asking their child with ADHD to adopt protective behaviors against COVID-19 and in managing the child’s after-school learning, sleep routine, and internet use, as well as worsened psychological symptoms. The results of multivariate logistic regression analysis demonstrated that caregivers’ difficulties in managing ADHD children’s self-protective behaviors and after-school learning and the children’s worsened emotional symptoms were significantly associated with poor caregiver general mental health state. An intervention that enhances the mental health of caregivers of children with ADHD during the COVID-19 pandemic by addressing their difficulties in managing the children’s behaviors and psychological problems is warranted.
Peripheral Nerve Impairment in a Mouse Model of Alzheimer’s Disease

Sarcopenia, a geriatric syndrome involving loss of muscle mass and strength, is often associated with the early phases of Alzheimer’s disease (AD). Pathological hallmarks of AD including amyloid β (Aβ) aggregates which can be found in peripheral tissues such as skeletal muscle. However, not much is currently known about their possible involvement in sarcopenia. We investigated neuronal innervation in skeletal muscle of Tg2576 mice, a genetic model for Aβ accumulation. We examined cholinergic innervation of skeletal muscle in adult Tg2576 and wild type mice by immunofluorescence labeling of tibialis anterior (TA) muscle sections using antibodies raised against neurofilament light chain (NFL) and acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (ChAT). Combining this histological approach with real time quantification of mRNA levels of nicotinic acetylcholine receptors, we demonstrated that in the TA of Tg2576 mice, neuronal innervation is significantly reduced and synaptic area is smaller and displays less ChAT content when compared to wild type mice. Our study provides the first evidence of reduced cholinergic innervation of skeletal muscle in a mouse model of Aβ accumulation. This evidence sustains the possibility that sarcopenia in AD originates from Aβ-mediated cholinergic loss.
Fruit of Gardenia jasminoides Induces Mitochondrial Activation and Non-Shivering Thermogenesis through Regulation of PPARγ

The extract of the Gardenia jasminoides fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms. To investigate the role of GJFE on thermogenesis in mice, we used an acute cold exposure model. After 2 weeks of feeding, the cold tolerance of GJFE-fed mice was notably increased compared to PBS-fed mice. This was due to an increase in thermogenic proteins in the inguinal white adipose tissue of the cold-exposed mice. Moreover, GJFE significantly increased thermogenic factors such as peroxisome proliferator-activated receptor gamma (PPARγ), uncoupling protein 1 (UCP1), and PPARγ coactivator 1 alpha (PGC1α) in vitro as well. Factors related to mitochondrial abundance and functions were also induced by GJFE in white and beige adipocytes. However, the treatment of PPARγ inhibitor abolished the GJFE-induced changes, indicating that activation of PPARγ is critical for the thermogenic effect of GJFE. In conclusion, GJFE induces thermogenic action by activating mitochondrial function via PPARγ activation. Through these findings, we suggest GJFE as a potential anti-obesity agent with a novel mechanism involving thermogenic action in white adipocytes.