Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Insights into Mitochondrial Neurodevelopmental and Neurodegenerative Disorders: Their Biosignatures from Mass Spectrometry-Based Metabolomics

Mitochondria are dynamic multitask organelles that function as hubs for many metabolic pathways. They produce most ATP via the oxidative phosphorylation pathway, a critical pathway that the brain relies on its energy need associated with its numerous functions, such as synaptic homeostasis and plasticity. Therefore, mitochondrial dysfunction is a prevalent pathological hallmark of many neurodevelopmental and neurodegenerative disorders resulting in altered neurometabolic coupling. With the advent of mass spectrometry (MS) technology, MS-based metabolomics provides an emerging mechanistic understanding of their global and dynamic metabolic signatures. In this review, we discuss the pathogenetic causes of mitochondrial metabolic disorders and the recent MS-based metabolomic advances on their metabolomic remodeling. We conclude by exploring the MS-based metabolomic functional insights into their biosignatures to improve diagnostic platforms, stratify patients, and design novel targeted therapeutic strategies.
A Minor Role of Host Fruit on the Parasitic Performance of Aganaspis daci (Hymenoptera: Figitidae) on Medfly Larvae

Simple Summary The medfly, Ceratitis capitata, is one of the main pests of citrus and other fruits worldwide. One of the most promising parasitoids for the control of this pest is Aganaspis daci, which has been recently discovered in the Mediterranean Basin. The development of fruit pests is strongly affected by the host fruit and this is also expected to affect the parasitic performance of their natural enemies. Therefore, in this study, we measured both the olfactory and parasitic response of female Aganaspis daci to different fruit species that can host medfly larvae. This parasitoid was more attracted to apples and uninfested fruit and showed very similar parasitic activity among the different tested fruits. However, the parasitic performance differed significantly depending on the environmental conditions under which the assays were conducted, showing good results in the laboratory and a much poorer performance in greenhouse trials. We conclude that A. daci may be a good candidate to control the medfly in a range of different crops, but only when climatic conditions allow normal activity of this species. Abstract Host fruit is known to strongly affect the performance of both fruit pests and their potential natural enemies. This is particularly important in the control of tephritid fruit flies, whose larvae develop inside the fruit and thus create a set of foraging problems for parasitoids. In the present study, we assessed the response of female Aganaspis daci (Weld) (Hymenoptera: Figitidae), one of the most promising parasitoids for tephritid biocontrol in the Mediterranean Basin, to different potential host fruit species. We measured the olfactory response to medfly-infested and uninfested fruits, and several biological parameters of A. daci when different infested fruits were offered under both laboratory and greenhouse conditions. Our results showed that this parasitoid was significantly more attracted to apples and uninfested fruit. Moreover, parasitic activity was similar among the tested fruits under both conditions, showing very high values in the laboratory and a much poorer performance when conditions were variable. This suggests that A. daci may be a good candidate to be included in mass releases against the medfly regardless of the affected crop, but only when climate conditions are not expected to hinder its normal activity.
Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management

Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.
Pediatric Asthma Attack and Home Paint Exposure

Although asthma mortality has been declining for the past several decades, asthma morbidity is on the rise, largely due to deteriorating indoor air quality and comorbidities, such as allergies. Consumer products and building materials including paints emit volatile organic compounds (VOCs), such as propylene glycol (PG), which is shown to dehydrate respiratory tracts and can contributor to airway remodeling. We hypothesize that paint exposure increases the risk of asthma attacks among children because high levels of VOCs persist indoors for many weeks after painting. Children 1–15 years old visiting two of the University of Miami general pediatric clinics were screened for their history of asthma and paint exposure by interviewing their parents and/or guardians accompanying them to the clinic. They were also asked questions about asthma diagnosis, severity of asthma and allergies and their sociodemographics. The risk of asthma attack among asthmatic children was modeled with respect to paint exposure adjusting for potential confounders using multivariate logistic regressions. Of 163 children, 36 (22%) reported physician-diagnosed asthma and of these, 13 (33%) had an asthma attack during the last one year. Paint exposure was marginally significant in the univariate analysis (OR = 4.04; 95% CI = 0.90–18.87; p < 0.1). However, exposed asthmatic children were 10 times more likely to experience an asthma attack than unexposed asthmatic children (OR = 10.49; CI = 1.16–94.85, p < 0.05) when adjusted for other risk factors. Given paint is one of the sources of indoor VOCs, multiple strategies are warranted to manage the health effects of VOC exposure from paint, including the use of zero-VOC water-based paint, exposure avoidance and clinical interventions.
Cardiovascular and Renal Disease in Chronic Critical Illness

With advances in critical care, patients who would have succumbed in previous eras now survive through hospital discharge. Many survivors suffer from chronic organ dysfunction and induced frailty, representing an emerging chronic critical illness (CCI) phenotype. Persistent and worsening cardiovascular and renal disease are primary drivers of the CCI phenotype and have pathophysiologic synergy, potentiating one another and generating a downward spiral of worsening disease and clinical outcomes manifest as cardio-renal syndromes. In addition to pharmacologic therapies (e.g., diuretics, beta adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and blood pressure control), special consideration should be given to behavioral modifications that avoid the pitfalls of polypharmacy and suboptimal renal and hepatic dosing, to which CCI patients may be particularly vulnerable. Smoking cessation, dietary modifications (e.g., early high-protein nutrition and late low-sodium diets), and increased physical activity are advised. Select patients benefit from cardiac re-synchronization therapy or renal replacement therapy. Coordinated, patient-centered care bundles may improve compliance with standards of care and patient outcomes. Given the complex, heterogeneous nature of cardiovascular and renal disease in CCI and the dismal long-term outcomes, further research is needed to clarify pathophysiologic mechanisms of cardio-renal syndromes in CCI and develop targeted therapies.
Cruciate Ligament Cell Sheets Can Be Rapidly Produced on Thermoresponsive poly(glycidyl ether) Coating and Successfully Used for Colonization of Embroidered Scaffolds

Anterior cruciate ligament (ACL) cell sheets combined with biomechanically competent scaffolds might facilitate ACL tissue engineering. Since thermoresponsive polymers allow a rapid enzyme-free detachment of cell sheets, we evaluated the applicability of a thermoresponsive poly(glycidyl ether) (PGE) coating for cruciate ligamentocyte sheet formation and its influence on ligamentocyte phenotype during sheet-mediated colonization of embroidered scaffolds. Ligamentocytes were seeded on surfaces either coated with PGE or without coating. Detached ligamentocyte sheets were cultured separately or wrapped around an embroidered scaffold made of polylactide acid (PLA) and poly(lactic-co-ε-caprolactone) (P(LA-CL)) threads functionalized by gas-phase fluorination and with collagen foam. Ligamentocyte viability, protein and gene expression were determined in sheets detached from surfaces with or without PGE coating, scaffolds seeded with sheets from PGE-coated plates and the respective monolayers. Stable and vital ligamentocyte sheets could be produced within 24 h with both surfaces, but more rapidly with PGE coating. PGE did not affect ligamentocyte phenotype. Scaffolds could be colonized with sheets associated with high cell survival, stable gene expression of ligament-related type I collagen, decorin, tenascin C and Mohawk after 14 d and extracellular matrix (ECM) deposition. PGE coating facilitates ligamentocyte sheet formation, and sheets colonizing the scaffolds displayed a ligament-related phenotype.
Diversity of Aerobic Anoxygenic Phototrophs and Rhodopsin-Containing Bacteria in the Surface Microlayer, Water Column and Epilithic Biofilms of Lake Baikal

The diversity of aerobic anoxygenic phototrophs (AAPs) and rhodopsin-containing bacteria in the surface microlayer, water column, and epilithic biofilms of Lake Baikal was studied for the first time, employing pufM and rhodopsin genes, and compared to 16S rRNA diversity. We detected pufM-containing Alphaproteobacteria (orders Rhodobacterales, Rhizobiales, Rhodospirillales, and Sphingomonadales), Betaproteobacteria (order Burkholderiales), Gemmatimonadetes, and Planctomycetes. Rhodobacterales dominated all the studied biotopes. The diversity of rhodopsin-containing bacteria in neuston and plankton of Lake Baikal was comparable to other studied water bodies. Bacteroidetes along with Proteobacteria were the prevailing phyla, and Verrucomicrobia and Planctomycetes were also detected. The number of rhodopsin sequences unclassified to the phylum level was rather high: 29% in the water microbiomes and 22% in the epilithon. Diversity of rhodopsin-containing bacteria in epilithic biofilms was comparable with that in neuston and plankton at the phyla level. Unweighted pair group method with arithmetic mean (UPGMA) and non-metric multidimensional scaling (NMDS) analysis indicated a distinct discrepancy between epilithon and microbial communities of water (including neuston and plankton) in the 16S rRNA, pufM and rhodopsin genes.
Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase

Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. In particular, it has been proposed that an electrostatic interaction may be responsible for the initial contact between prefibrillar oligomers and GM1 contained in lipid rafts. Based on this evidence, the aim of our work was to investigate whether the neurotoxic action induced by calcitonin prefibrillar oligomers could be counteracted by treatment with neuraminidase, an enzyme that removes sialic acid residues from gangliosides. Therefore, we studied cell viability in HT22 cell lines and evaluated the effects on synaptic transmission and long-term potentiation by in vitro extracellular recordings in mouse hippocampal slices. Our results showed that treatment with neuraminidase alters the surface charges of lipid rafts, preventing interaction between the calcitonin prefibrillar oligomers and GM1, and suggesting that the enzyme, depending on the concentration used, may have a partial or total protective action in terms of cell survival and modulation of synaptic transmission.
Pharmaceutical Drug Metformin and MCL1 Inhibitor S63845 Exhibit Anticancer Activity in Myeloid Leukemia Cells via Redox Remodeling

Metabolic landscape and sensitivity to apoptosis induction play a crucial role in acute myeloid leukemia (AML) resistance. Therefore, we investigated the effect of metformin, a medication that also acts as an inhibitor of oxidative phosphorylation (OXPHOS), and MCL-1 inhibitor S63845 in AML cell lines NB4, KG1 and chemoresistant KG1A cells. The impact of compounds was evaluated using fluorescence-based metabolic flux analysis, assessment of mitochondrial Δψ and cellular ROS, trypan blue exclusion, Annexin V-PI and XTT tests for cell death and cytotoxicity estimations, also RT-qPCR and Western blot for gene and protein expression. Treatment with metformin resulted in significant downregulation of OXPHOS; however, increase in glycolysis was observed in NB4 and KG1A cells. In contrast, treatment with S63845 slightly increased the rate of OXPHOS in KG1 and KG1A cells, although it profoundly diminished the rate of glycolysis. Generally, combined treatment had stronger inhibitory effects on cellular metabolism and ATP levels. Furthermore, results revealed that treatment with metformin, S63845 and their combinations induced apoptosis in AML cells. In addition, level of apoptotic cell death correlated with cellular ROS induction, as well as with downregulation of tumor suppressor protein MYC. In summary, we show that modulation of redox-stress could have a potential anticancer activity in AML cells.
TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts

TRPM7 plays an important role in cellular Ca2+, Zn2+ and Mg2+ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca2+ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg2+ ([Mg2+]i), were reduced by elevated [Mg2+]i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg2+]i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca2+ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca2+ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca2+ uptake and as an independent Ca2+ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca2+ transport in amelogenesis.
Multi-Dimension and Multi-Feature Hybrid Learning Network for Classifying the Sub Pathological Type of Lung Nodules through LDCT

In order to develop appropriate treatment and rehabilitation plans with regard to different subpathological types (PILs and IAs) of lung nodules, it is important to diagnose them through low-dose spiral computed tomography (LDCT) during routine screening before surgery. Based on the characteristics of different subpathological lung nodules expressed from LDCT images, we propose a multi-dimension and multi-feature hybrid learning neural network in this paper. Our network consists of a 2D network part and a 3D network part. The feature vectors extracted from the 2D network and 3D network are further learned by XGBoost. Through this formation, the network can better integrate the feature information from the 2D and 3D networks. The main learning block of the network is a residual block combined with attention mechanism. This learning block enables the network to learn better from multiple features and pay more attention to the key feature map among all the feature maps in different channels. We conduct experiments on our dataset collected from a cooperating hospital. The results show that the accuracy, sensitivity and specificity of our network are 83%, 86%, 80%, respectively It is feasible to use this network to classify the subpathological type of lung nodule through routine screening.
A Tentative Study of the Effects of Heat-Inactivation of the Probiotic Strain Shewanella putrefaciens Ppd11 on Senegalese Sole (Solea senegalensis) Intestinal Microbiota and Immune Response

Concerns about safety, applicability and functionality associated with live probiotic cells have led to consideration of the use of non-viable microorganisms, known as paraprobiotics. The present study evaluated the effects of dietary administration of heat-inactivated cells of the probiotic strain Shewanella putrefaciens Ppd11 on the intestinal microbiota and immune gene transcription in Solea senegalensis. Results obtained were evaluated and compared to those described after feeding with viable Pdp11 cells. S. senegalensis specimens were fed with basal (control) diet or supplemented with live or heat inactivated (60 °C, 1 h) probiotics diets for 45 days. Growth improvement was observed in the group receiving live probiotics compared to the control group, but not after feeding with a probiotic heat-inactivated diet. Regarding immune gene transcription, no changes were observed for tnfα, il-6, lys-c1, c7, hsp70, and hsp90aa in the intestinal samples based on the diet. On the contrary, hsp90ab, gp96, cd4, cd8, il-1β, and c3 transcription were modulated after probiotic supplementation, though no differences between viable and heat-inactivated probiotic supplemented diets were observed. Modulation of intestinal microbiota showed remarkable differences based on the viability of the probiotics. Thus, higher diversity in fish fed with live probiotic cells, jointly with increased Mycoplasmataceae and Spirochaetaceae to the detriment of Brevinemataceae, was detected. However, microbiota of fish receiving heat-inactivated probiotic cells showed decreased Mycoplasmataceae and increased Brevinemataceae and Vibrio genus abundance. In short, the results obtained indicate that the viable state of Pdp11 probiotic cells affects growth performance and modulation of S. senegalensis intestinal microbiota. On the contrary, minor changes were detected in the intestinal immune response, being similar for fish receiving both, viable and inactivated probiotic cell supplemented diets, when compared to the control diet.
Iron at the Interface of Hepatocellular Carcinoma

Cancer incidence and mortality are rapidly growing, with liver cancer being the sixth most diagnosed cancer worldwide and the third leading cause of cancer death in 2020. A number of risk factors have been identified that trigger the progression to hepatocellular carcinoma. In this review, we focus on iron as a potential risk factor for liver carcinogenesis. Molecules involved in the regulation of iron metabolism are often upregulated in cancer cells, in order to provide a supply of this essential trace element for all stages of tumor development, survival, proliferation, and metastasis. Thus, cellular and systemic iron levels must be tightly regulated to prevent or delay liver cancer progression. Disorders associated with dysregulated iron metabolism are characterized with increased susceptibility to hepatocellular carcinoma. This review discusses the association of iron with metabolic disorders such as hereditary hemochromatosis, non-alcoholic fatty liver disease, obesity, and type 2 diabetes, in the background of hepatocellular carcinoma.
Spongostan™ Leads to Increased Regeneration of a Rat Calvarial Critical Size Defect Compared to NanoBone® and Actifuse

Bone substitute materials are becoming increasingly important in oral and maxillofacial surgery. Reconstruction of critical size bone defects is still challenging for surgeons. Here, we compared the clinically applied organic bone substitute materials NanoBone® (nanocrystalline hydroxyapatite and nanostructured silica gel; n = 5) and Actifuse (calcium phosphate with silicate substitution; n = 5) with natural collagen-based Spongostan™ (hardened pork gelatin containing formalin and lauryl alcohol; n = 5) in bilateral rat critical-size defects (5 mm diameter). On topological level, NanoBone is known to harbour nanopores of about 20 nm diameter, while Actifuse comprises micropores of 200–500 µm. Spongostan™, which is clinically applied as a haemostatic agent, combines in its wet form both nano- and microporous topological features by comprising 60.66 ± 24.48 μm micropores accompanied by nanopores of 32.97 ± 1.41 nm diameter. Micro-computed tomography (µCT) used for evaluation 30 days after surgery revealed a significant increase in bone volume by all three bone substitute materials in comparison to the untreated controls. Clearly visual was the closure of trepanation in all treated groups, but granular appearance of NanoBone® and Actifuse with less closure at the margins of the burr holes. In contrast, transplantion of Spongostan™ lead to complete filling of the burr hole with the highest bone volume of 7.98 ccm and the highest bone mineral density compared to all other groups. In summary, transplantation of Spongostan™ resulted in increased regeneration of a rat calvarial critical size defect compared to NanoBone and Actifuse, suggesting the distinct nano- and microtopography of wet Spongostan™ to account for this superior regenerative capacity. Since Spongostan™ is a clinically approved product used primarily for haemostasis, it may represent an interesting alternative in the reconstruction of defects in the maxillary region.
“Exact” and Approximate Methods for Bayesian Inference: Stochastic Volatility Case Study

We conduct a case study in which we empirically illustrate the performance of different classes of Bayesian inference methods to estimate stochastic volatility models. In particular, we consider how different particle filtering methods affect the variance of the estimated likelihood. We review and compare particle Markov Chain Monte Carlo (MCMC), RMHMC, fixed-form variational Bayes, and integrated nested Laplace approximation to estimate the posterior distribution of the parameters. Additionally, we conduct the review from the point of view of whether these methods are (1) easily adaptable to different model specifications; (2) adaptable to higher dimensions of the model in a straightforward way; (3) feasible in the multivariate case. We show that when using the stochastic volatility model for methods comparison, various data-generating processes have to be considered to make a fair assessment of the methods. Finally, we present a challenging specification of the multivariate stochastic volatility model, which is rarely used to illustrate the methods but constitutes an important practical application.