Miracle-dz/UniFAR-FTUs huggingface dataset:
New Pharmacological Approaches for the Treatment of Neurotrophic Keratitis

Neurotrophic keratitis (NK) is a rare degenerative condition that is caused by damage to the trigeminal nerve, with partial or complete loss of corneal sensory innervation. The loss of innervation leads to impaired healing of corneal epithelium, which subsequently results in punctate epithelial erosions, persistent epithelial defects, corneal ulcers and corneal perforation. Management of NK is often supportive and aims to promote epithelial healing and prevent progression of disease. Multiple novel pharmacological approaches have been proposed to address the underlying pathophysiology of NK, which are discussed in this paper.
Activating Effects of the Bioactive Compounds From Coffee By-Products on FGF21 Signaling Modulate Hepatic Mitochondrial Bioenergetics and Energy Metabolism in vitro

Coffee by-products contain bioactive compounds that have been shown to have the capacity to modulate human metabolism. The goal of this study was to investigate the effects of the main bioactive compounds in coffee by-products and two aqueous extracts from the coffee husk and silverskin on the activation of fibroblast growth factor 21 (FGF21) signaling and the subsequent regulation of mitochondrial bioenergetics and lipid and glucose metabolism. HepG2 cells treated with palmitic acid (PA) were used in a non-alcoholic fatty liver disease (NAFLD) cell model. The bioactive compounds from coffee by-products (50 μmol L−1) and the aqueous extracts from the coffee silverskin and coffee husk (100 μg mL−1) increased ERK1/2 phosphorylation and the secretion of FGF21 (1.3 to 1.9-fold). Coffee by-products' bioactive compounds counteracted inflammation and PA-triggered lipotoxicity. Oxidative stress markers (ROS, mitochondrial superoxide, and NADPH oxidase) and the activity of antioxidant enzymes (superoxide dismutase and catalase) were modulated through the activation of Nrf2 signaling. Mitochondrial bioenergetics were regulated by enhancing respiration and ATP production via PGC-1α, and the expression of oxidative phosphorylation complexes increased. Coffee by-products' bioactive compounds decreased lipid accumulation (23–41%) and fatty acid synthase activity (32–65%) and triggered carnitine palmitoyltransferase-1 activity (1.3 to 1.7-fold) by activating AMPK and SREBP-1c pathways. The GLUT2 expression and glucose uptake were increased (58–111%), followed by a promoted glucokinase activity (55–122%), while glucose production and phosphoenolpyruvate carboxykinase activity were reduced due to IRS-1/Akt1 regulation. The bioactive compounds from coffee by-products, primarily chlorogenic and protocatechuic acids, could regulate hepatic mitochondrial function and lipid and glucose metabolism by activating FGF21 and related signaling cascades.
Biochar Amendment and Nitrogen Fertilizer Contribute to the Changes in Soil Properties and Microbial Communities in a Paddy Field

Biochar amendment can influence the abundance, activity, and community structure of soil microbes. However, scare information is present about the effect of the combined application of biochar with synthetic nitrogen (N) fertilizer under paddy field condition. We aimed to resolve this research gap in rice field conditions through different biochar in combination with N fertilizers on soil nutrients, soil microbial communities, and rice grain yield. The present study involves eight treatments in the form of biochar (0, 10, 20, and 30 t ha–1) and N (135 and 180 kg ha–1) fertilizer amendments. The soil microbial communities were characterized using high-throughput sequencing of 16S and Internal transcribed spacer (ITS) ribosomal RNA gene amplicons. Experiential findings showed that the treatments had biochar amendments along with N fertilizer significantly advanced soil pH, soil organic carbon (SOC), total nitrogen (TN), soil microbial carbon (SMBC), soil microbial nitrogen (SMBN), and rice grain yield in comparison to sole N application. Furthermore, in comparison with control in the first year (2019), biochar amendment mixed with N fertilizer had more desirable relative abundance of microorganism, phyla Acidobacteria, Actinobacteria, Proteobacteria, and Verrucomicrobia with better relative abundance ranging from 8.49, 4.60, 46.30, and 1.51% in T7, respectively. Similarly, during 2020, bacteria phyla Acidobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Planctomycetes, and Verrucomicrobia were resulted in higher and ranging from 8.69, 5.18, 3.5, 1.9, 4.0, and 1.6%, in biochar applied treatments, respectively, as compared to control (T1). Among the treatments, Sphingopyxis and Thiobacillus bacterial genus were in higher proportion in T7 and T3, respectively, as compared to other treatments and Bacillus was higher in T6. Interestingly, biochar addition significantly decreased the soil fungi phyla Ascomycota, Basidiomycota, Chytridiomycota, and Rozellomycota, in 2020 as compared to 2019. Whereas biochar addition to soil decreased Echria, Kohlmeyeriopsis, and Westerdykella fungal genus as compared to non-biochar treatments. The redundancy analysis showed that soil biochemical traits were positively correlated with soil bacteria. In addition, correlation analysis showed that soil bacteria including Acidobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, and Proteobacteria strongly correlated with rice grain yield. This study demonstrated that soil nutrients and bacteria contribute to an increase in rice yield in combined biochar amendment with lower N treatments.
Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.
A Positive Climatic Trend in the Global Offshore Wind Power

The climatic variation of offshore wind energy has a close relationship with the long-term plan of energy utilization. However, the work on this aspect is scarce and mainly focuses on the variation of wind power density (WPD). There is little research on the climatic trends of effective wind speed occurrence (EWSO) and occurrence of energy level greater than 200 W/m2 (rich level occurrence, RLO), which are directly related to the available rate and richness of wind energy. Based on the ERA-Interim wind product from the ECMWF, this study calculated the climatic trends of series of key factors of wind energy in the global oceans, including the WPD, EWSO, and RLO. The results show that the wind energy exhibits a positive trend globally for the past 36 years, with overall annual increasing trends in WPD, EWSO, and RLO, of 0.698 (W/m2)/yr, 0.076%/yr, and 0.090%/yr separately. The annual trend exhibits evident regional differences. The areas with significant increasing trends are mainly distributed in the mid- low-latitude waters of global oceans and part of the southern hemisphere westerlies. The annual increasing trend of WPD is strongest in the southern westerlies, especially in the extratropical South Pacific (ETSP), of about 1.64 (W/m2)/yr. The annual increasing trends of EWSO and RLO are strongest in the tropical waters, especially the tropical Pacific Ocean (TPO), of 0.17%/yr and 0.19%/yr separately. The annual and seasonal WPD, EWSO, and RLO in most global oceans have significant increasing trends or no significant variation, meaning that the wind energy trends are rich or stable, which is beneficial for energy development. The climatic trends of wind energy are dominated by different time periods. There is no evident abrupt change of wind energy in the extratropical waters globally and tropical Atlantic Ocean (TAO). The abrupt periods of wind energy in the TIO and TPO occurred in the end of the 20th century and the beginning of the 21st century. The wind energy of the South China Sea, Arabian Sea, and the Bay of Bengal and nino3 index share a common period of approximately 5 years. The offshore wind energy was controlled by an oscillating phenomenon.
Is Virtual Reality Training More Effective Than Traditional Physical Training on Balance and Functional Mobility in Healthy Older Adults? A Systematic Review and Meta-Analysis

Objective The studies showed the benefits of virtual reality training (VRT) for functional mobility and balance in older adults. However, a large variance in the study design and results is presented. We, thus, completed a systematic review and meta-analysis to quantitatively examine the effects of VRT on functional mobility and balance in healthy older adults. Methods We systematically reviewed the publications in five databases. Studies that examine the effects of VRT on the measures of functional mobility and balance in healthy older adults were screened and included if eligible. Subgroup analyses were completed to explore the effects of different metrics of the intervention design (e.g., session time) on those outcomes related to functional mobility and balance. Results Fifteen studies of 704 participants were included. The quality of these studies was good. Compared to traditional physical therapy (TPT), VRT induced greater improvement in TUG (MD = −0.31 s, 95% CI = −0.57 to −0.05, p = 0.02, I2 = 6.34%) and one-leg stance with open eyes (OLS-O) (MD = 7.28 s, 95% CI = 4.36 to 10.20, p = 0.00, I2 = 36.22%). Subgroup analyses revealed that immersive VRT with more than 800 min of total intervention time over 8 weeks and at least 120 min per week and/or designed by the two motor-learning principles was optimal for functional mobility and balance. Conclusion Virtual reality training can significantly improve functional mobility and balance in healthy older adults compared to TPT, and the findings provided critical knowledge of the optimized design of VRT that can inform future studies with more rigorous designs. Systematic Review Registration [https://www.crd. york.ac. uk/PROSPERO/], identifier [CRD42021297085].
Role of the Basolateral Na+/H+ Exchanger-2 (NHE2) in Ionocytes of Seawater- Acclimated Medaka (Oryzias latipes)

Ionocytes in the skin and gills of seawater (SW) fishes are responsible for acid-base regulation and salt secretion. Na+/H+ exchangers (NHEs) are considered the major acid (H+)-secreting transporters in ionocytes of SW fishes. However, the subcellular localization and function of a specific NHE isoform (NHE2) have never clearly been revealed. In this study, we cloned and sequenced NHE2 from an SW-acclimated medaka (Oryzias latipes) and examined its functions in medaka embryos. A phylogenetic analysis showed that the evolutionary relationships of mammalian NHE2 and NHE4 are close to those of fish NHE2. A gene structure analysis showed that tetrapod NHE4 might be a tandem duplication of fish NHE2. Immunohistochemistry with a medaka-specific antibody localized NHE2 to the basolateral membrane of ionocytes. Lost-of-function experiments with photo-activated morpholino oligonucleotides showed that both H+ and Cl– secretion by ionocytes were suppressed in NHE2-knockdown embryos, suggesting that the basolateral NHE2 facilitates acid and salt secretion by ionocytes of medaka in seawater.
Comparative Transcriptome Profiling Analysis Reveals the Adaptive Molecular Mechanism of Yellow-Green Leaf in Rosa beggeriana ‘Aurea’

Rosa beggeriana ‘Aurea’ is a yellow-green leaf (yl) mutant and originated from Rosa beggeriana Schrenk by 60Co-γ irradiation, which is an important ornamental woody species. However, the molecular mechanism of the yl mutant remains unknown. Herein, comparative transcriptome profiling was performed between the yl type and normal green color type (WT) by RNA sequencing. A total of 3,372 significantly differentially expressed genes (DEGs) were identified, consisting of 1,585 upregulated genes and 1,787 downregulated genes. Genes that took part in metabolic of biological process (1,090), membrane of cellular component (728), catalytic (1,114), and binding of molecular function (840) were significantly different in transcription level. DEGs involved in chlorophyll biosynthesis, carotenoids biosynthesis, cutin, suberine, wax biosynthesis, photosynthesis, chloroplast development, photosynthesis-antenna proteins, photosystem I (PSI) and photosystem II (PSII) components, CO2 fixation, ribosomal structure, and biogenesis related genes were downregulated. Meanwhile, linoleic acid metabolism, siroheme biosynthesis, and carbon source of pigments biosynthesis through methylerythritol 4-phosphate (MEP) pathways were upregulated. Moreover, a total of 147 putative transcription factors were signification different expression, involving NAC, WRKY, bHLH, MYB and AP2/ERF, C2H2, GRAS, and bZIP family gene. Our results showed that the disturbed pigments biosynthesis result in yl color by altering the ratio of chlorophylls and carotenoids in yl mutants. The yl mutants may evoke other metabolic pathways to compensate for the photodamage caused by the insufficient structure and function of chloroplasts, such as enhanced MEP pathways and linoleic acid metabolism against oxidative stress. This research can provide a reference for the application of leaf color mutants in the future.
The Characteristics of the HIV-1 Env Glycoprotein Are Linked With Viral Pathogenesis

The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution of host, immune, and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has been concentrated on in many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller individuals contemporary to LTNPs or recent, named Old and Modern progressors. We studied the Env expression, the fusion and cell-to-cell transfer capacities, as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4, and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs from virus of patients presenting viremic control and the non-progressor clinical phenotype showed poor viral functions and shorter sequences, whereas functional Envs were associated with virus of patients lacking virological control and with progressor clinical phenotypes. These correlations support the role of Env genotypic and phenotypic characteristics in the in vivo HIV-1 infection and pathogenesis.
Full-Length Transcriptome Sequences Provide Insight Into Hermaphroditism of Freshwater Pearl Mussel Hyriopsis schlegelii

The freshwater mussel Hyriopsis schlegelii is a cultured bivalve in China, and the quality of the pearls produced is affected by the type of gonads. However, because of the lack of a published genome and the complexity of sex determination, research on sex reversal and development of this species is limited. In this study, Illumina RNA-seq and PacBio Isoform Sequencing (Iso-Seq) were combined to analyze the gonads of H. schlegelii. A total of 201,481 high-quality transcripts were generated. The study identified 7,922 differentially expressed genes in three comparison group (females versus males, hermaphrodites versus females, and hermaphrodites versus males). Twenty-four genes were identified as potential sex-related genes, including sox9 and wnt4 involved in sex determination, and vtg, cyp17a1 and 17β-hsd2 involved in gonadal development. We also speculated a possible pathways for the formation of hermaphroditism in H. schlegelii. The data provide a clear view of the transcriptome for H. schlegelii gonads and will be valuable in elucidating the mechanisms of gonad development.
Identification of Branched and Linear Forms of PFOA and Potential Precursors: A User-Friendly SMILES Structure-based Approach

Perfluorooctanoic acid (PFOA) and related compounds are per- and polyfluorinated alkyl substances (PFASs) of concern from toxicological, environmental, and regulatory perspectives. In 2019, the Conference of the Parties to the Stockholm Convention on Persistent Organic Pollutants listed PFOA, its salts, and PFOA-related compounds in Annex A to the Convention. Additionally, the listing specifically included PFOA branched isomers and compounds containing a perfluoroheptyl (C7F15)C moiety, with some noted exclusions. A draft updated “Indicative List” of 393 PFASs (335 with defined structures), each specified as falling within or outside the listing, was released for comment in 2021. The U.S. Environmental Protection Agency’s CompTox Chemicals Dashboard has published a curated PFAS list containing more than 10,700 structures. Applying the PFOA and related compounds listing definition to screen this list required a structure-based approach capable of discerning salts and branched or linear forms of the (C7F15)C moiety. A PFOA SMILES workflow and associated Excel macro file, developed to address this need, applies a series of text substitution rules to a set of canonicalized SMILES structure representations to convert branched forms of the (C7F15)C moiety to linear forms to aid their detection. The approach correctly classified each Stockholm Convention draft Indicative List structure relative to the PFOA and related compounds definition, and accurately discerned branched and linear forms of the (C7F15)C moiety in over 10,700 PFAS structures with 100% sensitivity (no false negatives) and 99.7% accuracy (35 false positives). Approximately 20% of structures in the large PFAS list fell within the PFOA and related compounds definition, and 10% of those were branched. The present work highlights the need to computationally detect branched forms of PFASs and promotes the use of unambiguous, structure-based definitions, along with tools that are publicly available and easy to use, to support clear communication and regulatory action within the PFAS community.
Investigating the Impact of Environment and Data Aggregation by Walking Bout Duration on Parkinson’s Disease Classification Using Machine Learning

Parkinson’s disease (PD) is a common neurodegenerative disease. PD misdiagnosis can occur in early stages. Gait impairment in PD is typical and is linked with an increased fall risk and poorer quality of life. Applying machine learning (ML) models to real-world gait has the potential to be more sensitive to classify PD compared to laboratory data. Real-world gait yields multiple walking bouts (WBs), and selecting the optimal method to aggregate the data (e.g., different WB durations) is essential as this may influence classification performance. The objective of this study was to investigate the impact of environment (laboratory vs. real world) and data aggregation on ML performance for optimizing sensitivity of PD classification. Gait assessment was performed on 47 people with PD (age: 68 ± 9 years) and 52 controls [Healthy controls (HCs), age: 70 ± 7 years]. In the laboratory, participants walked at their normal pace for 2 min, while in the real world, participants were assessed over 7 days. In both environments, 14 gait characteristics were evaluated from one tri-axial accelerometer attached to the lower back. The ability of individual gait characteristics to differentiate PD from HC was evaluated using the Area Under the Curve (AUC). ML models (i.e., support vector machine, random forest, and ensemble models) applied to real-world gait showed better classification performance compared to laboratory data. Real-world gait characteristics aggregated over longer WBs (WB 30–60 s, WB > 60 s, WB > 120 s) resulted in superior discriminative performance (PD vs. HC) compared to laboratory gait characteristics (0.51 ≤ AUC ≤ 0.77). Real-world gait speed showed the highest AUC of 0.77. Overall, random forest trained on 14 gait characteristics aggregated over WBs > 60 s gave better performance (F1 score = 77.20 ± 5.51%) as compared to laboratory results (F1 Score = 68.75 ± 12.80%). Findings from this study suggest that the choice of environment and data aggregation are important to achieve maximum discrimination performance and have direct impact on ML performance for PD classification. This study highlights the importance of a harmonized approach to data analysis in order to drive future implementation and clinical use. Clinical Trial Registration [09/H0906/82].
Dyadic Profiles of Couples Coping With Body Image Concerns After Breast Cancer: Preliminary Results of a Cluster Analysis

Breast cancer treatments have multiple adverse effects, including concerns about body appearance and function that are experienced by most patients. Altered body image negatively affects mental health, social, and relationship functioning. While the relationship with a partner is critical for patients’ psychological wellbeing and partners can promote positive body image, limited research has investigated individual and relational factors affecting the experience of both. This cross-sectional study aimed at (1) exploring rates of body image concerns among breast cancer patients, and (2) identifying dyadic profiles among participating dyads. Couples composed by patients who had undergone surgery and their romantic partners (n = 32) were recruited from the Breast Unit of a hospital in northern Italy. Both partners completed measures of personality characteristics (BFQ-2), psychological distress (HADS), coping flexibility (PACT), dyadic coping (DCQ), and closeness (IOS). Body image (BIS) and adjustment to cancer (Mini-MAC) measures were completed by patients only. K-mean cluster analyses identified 2-cluster solution among patients and partners, respectively. “Active patients” (cluster-1) reported low rates of body image concerns (p < 0.001), anxious preoccupation, negative dyadic coping, and self-oriented stress communication (p < 0.05), compared to “worried patients” (cluster-2). “Comfortable partners” (cluster-1) reported lower anxiety and depression (p < 0.001), self-oriented negative dyadic coping and closeness (p < 0.05) than “uncomfortable partners” (cluster-2). Three different dyadic profiles emerged: functional, dysfunctional, and ambivalent. Significant variations (p < 0.05) by anxiety, depression, and delegating dyadic coping existed. Results indicate there are groups of couples at greater risk for impaired psychological distress and body image concerns, which should be addressed in the context of dyadic psychosocial interventions.