Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary drivers of the hump-shaped latitudinal gradient of benthic polychaete species richness along the Southeastern Pacific coast

Latitudinal diversity gradients (LDG) and their explanatory factors are among the most challenging topics in macroecology and biogeography. Despite of its apparent generality, a growing body of evidence shows that ‘anomalous’ LDG (i.e., inverse or hump-shaped trends) are common among marine organisms along the Southeastern Pacific (SEP) coast. Here, we evaluate the shape of the LDG of marine benthic polychaetes and its underlying causes using a dataset of 643 species inhabiting the continental shelf (<200 m depth), using latitudinal bands with a spatial resolution of 0.5°, along the SEP (3–56° S). The explanatory value of six oceanographic (Sea Surface Temperature (SST), SST range, salinity, salinity range, primary productivity and shelf area), and one macroecological proxy (median latitudinal range of species) were assessed using a random forest model. The taxonomic structure was used to estimate the degree of niche conservatism of predictor variables and to estimate latitudinal trends in phylogenetic diversity, based on three indices (phylogenetic richness (PDSES), mean pairwise distance (MPDSES), and variation of pairwise distances (VPD)). The LDG exhibits a hump-shaped trend, with a maximum peak of species richness at ca. 42° S, declining towards northern and southern areas of SEP. The latitudinal pattern was also evident in local samples controlled by sampling effort. The random forest model had a high accuracy (pseudo-r2 = 0.95) and showed that the LDG could be explained by four variables (median latitudinal range, SST, salinity, and SST range), yet the functional relationship between species richness and these predictors was variable. A significant degree of phylogenetic conservatism was detected for the median latitudinal range and SST. PDSES increased toward the southern region, whereas VPD showed the opposite trend, both statistically significant. MPDSES has the same trend as PDSES, but it is not significant. Our results reinforce the idea that the south Chile fjord area, particularly the Chiloé region, was likely the evolutionary source of new species of marine polychaetes along SEP, creating a hotspot of diversity. Therefore, in the same way as the canonical LDG shows a decline in diversity while moving away from the tropics; on this case the decline occurs while moving away from Chiloé Island. These results, coupled with a strong phylogenetic signal of the main predictor variables suggest that processes operating mainly at evolutionary timescales govern the LDG.
Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

Cancer stem cells (CSCs) have been implicated in the development of chemoresistance, tumor recurrence and metastasis in breast cancer, thus emerging as a promising target for novel therapies. To identify novel stemness regulators that could potentially be targeted in luminal ER+ tumors, we performed RNA-sequencing (RNA-seq) in MCF-7 adherent monolayer cells and tumorspheres enriched in breast CSCs (bCSCs). We identified 1421 differentially expressed genes (DEGs), with 923 of them being upregulated and 498 downregulated in tumorspheres. Gene ontology and pathway enrichment analyses revealed that distinct gene networks underlie the biology of the two cell systems. We selected the transient receptor potential cation channel subfamily M member 4 (TRPM4) gene that had not been associated with cancer stemness before for further investigation. We confirmed that TRPM4 was overexpressed in tumorspheres and showed that its knock-down affected the stemness properties of bCSCs in vitro. TRPM4 inhibition revealed potential anti-tumor effects by directly targeting the bCSC subpopulation. We suggest that TRPM4 plays a key role in stemness mediation, and its inhibition may represent a novel therapeutic modality against bCSCs contributing in the improvement of breast cancer treatments.
PD-L1 Expression on Circulating Tumour-Derived Microvesicles as a Complementary Tool for Stratification of High-Grade Serous Ovarian Cancer Patients

Simple Summary PD-1/PD-L1 axis blockade immunotherapy leverages on assessment of tumour PD-L1 status by immunohistochemistry for identifying cancer patients’ who would benefit most from this therapy. Because some PD-L1 negative cancer patients also benefit from the treatment, it has been postulated that spatial heterogeneity of PD-L1 expression in tumour tissue may reduce the predictive value of the test. Here we demonstrate for the first time the presence of PD-L1+ circulating tumor–derived microvesicles in the blood stream of high grade serous ovarian cancer patients and propose the assessment of tumor-derived circulating PD-L1+ microvesicles to be inserted in predictive algorithms for complementing tumour PD-L1 status. Abstract Background: Ovarian cancer (OC) has recently attracted attention for the use of PD-1/PD-L1 axis blocking agents, with durable activity reported only in a subset of patients. The most used biomarker for sensitivity to the PD-1/PD-L1 axis blockade is tumour PD-L1 status by immunohistochemistry. However, patient stratification using this method suffers from intrinsic heterogeneity of OC, likely contributing to the unsatisfactory results obtained so far. Cells communicate with each other by releasing microvesicles (MVs) that carry parental cell surface features. Thus, we hypothesised that PD-L1+ tumour cells (TC) and infiltrating PD-L1+ leukocytes should shed MVs carrying surface PD-L1 that may serve as a proxy for the whole tumour PD-L1 status. Results: We showed for the first time the presence of measurable amounts of TC- and leukocyte-derived PD-L1+ MVs (range: 1.4–178.8 MVs/μL and 6.2–504.8 MVs/μL, respectively) in the plasma of high-grade serous OC (HGSOC) patients (n = 63), using a sensitive flow cytometry platform. The concentration of PD-L1+ MVs of either origin did not associate with the PD-L1 status of TCs and leukocytes in the tumour biopsies, suggesting that the circulating PD-L1+ MVs also included ones from locations not selected for immunohistochemistry analysis and represented the PD-L1 status of the whole tumour mass. In this study, we also describe the serendipitous discovery of circulating PD-L1+ MVs of platelet origin (10.3–2409.6 MVs/μL). Conclusions: The enumeration of circulating PD-L1+ MVs in HGSOC patients may provide a novel direction for assessing the tumour PD-L1 status and contribute to HGSOC patient stratification for immunotherapy interventions. The presence of circulating PD-L1+ MVs of platelet origin, a finding not yet reported in HGSOC patients, warrants further studies.
Potential Novel Biomarkers for Mastitis Diagnosis in Sheep

Simple Summary Inflammation of the mammary gland (mastitis) is an important disease of dairy sheep. Mastitis management depends mainly on the diagnosis. Conventional diagnostic methods including somatic cell count, California Mastitis Test, and microbial culture have limitations. Therefore researchers are looking for new diagnostic biomarkers of mastitis including specific proteins produced by the liver in case of disease (acute phase proteins), unique genetic sequences (miRNAs), or antimicrobial peptides produced by immune cells during inflammation (cathelicidines). Abstract This review aims to characterize promising novel markers of ovine mastitis. Mastitis is considered as one of the primary factors for premature culling in dairy sheep and has noticeable financial, productional, and animal welfare-related implications. Furthermore, clinical, and subclinical mammary infections negatively affect milk yield and alter the milk composition, thereby leading to lowered quality of dairy products. It is, therefore, crucial to control and prevent mastitis through proper diagnosis, treatment or culling, and appropriate udder health management particularly at the end of the lactation period. The clinical form of mastitis is characterized by abnormalities in milk and mammary gland tissue alteration or systemic symptoms consequently causing minor diagnostic difficulties. However, to identify ewes with subclinical mastitis, laboratory diagnostics is crucial. Mastitis control is primarily dependent on determining somatic cell count (SCC) and the California Mastitis Test (CMT), which aim to detect the quantity of cells in the milk sample. The other useful diagnostic tool is microbial culture, which complements SCC and CMT. However, all mentioned diagnostic methods have their limitations and therefore novel biomarkers of ovine subclinical mastitis are highly desired. These sensitive indicators include acute-phase proteins, miRNA, and cathelicidins measurements, which could be determined in ovine serum and/or milk and in the future may become useful in early mastitis diagnostics as well as a preventive tool. This may contribute to increased detection of ovine mammary gland inflammation in sheep, especially in subclinical form, and consequently improves milk quality and quantity.
Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats

Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.
Enhancement of the Aroma Compound 2-Acetyl-1-pyrroline in Thai Jasmine Rice (Oryza sativa) by Rhizobacteria under Salt Stress

Simple Summary The major aroma compound (2-acetyl-1-pyrroline) of the world-famous Thai jasmine rice, variety KDML105, has declined due to high soil salinity and agrochemical input. In this work, the rhizobacteria from rice were investigated for the aroma compound’s production, as well as their potential for increasing the compound content in Thai jasmine rice seedlings under saline conditions. Our results provide evidence that the addition of aroma compound-producing rhizobacteria increases the aroma content in the rice seedlings under salt stress. Sinomonas sp. strain ORF15-23 which colonize the rice roots, is a promising rhizobacteria in promoting the aroma level of the Thai jasmine rice grown under salt stress and could be developed as a bioinoculant for Thai jasmine rice cultivation in a salt-affected area. Abstract Thai jasmine rice (Oryza sativa L. KDML105), particularly from inland salt-affected areas in Thailand, is both domestically and globally valued for its unique aroma and high grain quality. The key aroma compound, 2-acetyl-1-pyrroline (2AP), has undergone a gradual degradation due to anthropogenic soil salinization driven by excessive chemical input and climate change. Here, we propose a cheaper and an ecofriendly solution to improve the 2AP levels, based on the application of plant growth-promoting rhizobacteria (PGPR). In the present study, nine PGPR isolates from rice rhizosphere were investigated for the 2AP production in liquid culture and the promotion potential for 2AP content in KDML105 rice seedlings under four NaCl concentrations (0, 50, 100, and 150 mM NaCl). The inoculation of 2AP-producing rhizobacteria resulted in an increase in 2AP content in rice seedling leaves with the maximum enhancement from Sinomonas sp. ORF15-23 at 50 mM NaCl (19.6 µg·kg−1), corresponding to a 90.2% increase as compared to the control. Scanning electron microscopy confirmed the colonization of Sinomonas sp. ORF15-23 in the roots of salinity-stressed KDML105 seedlings. Our results provide evidence that Sinomonas sp. ORF15-23 could be a promising PGPR isolate in promoting aroma level of Thai jasmine rice KDML105 under salt stress.
Leak Detection in Water Pipes Based on Maximum Entropy Version of Least Square Twin K-Class Support Vector Machine

Numerous novel improved support vector machine (SVM) methods are used in leak detection of water pipelines at present. The least square twin K-class support vector machine (LST-KSVC) is a novel simple and fast multi-classification method. However, LST-KSVC has a non-negligible drawback that it assigns the same classification weights to leak samples, including outliers that affect classification, these outliers are often situated away from the main leak samples. To overcome this shortcoming, the maximum entropy (MaxEnt) version of the LST-KSVC is proposed in this paper, called the MLT-KSVC algorithm. In this classification approach, classification weights of leak samples are calculated based on the MaxEnt model. Different sample points are assigned different weights: large weights are assigned to primary leak samples and outliers are assigned small weights, hence the outliers can be ignored in the classification process. Leak recognition experiments prove that the proposed MLT-KSVC algorithm can reduce the impact of outliers on the classification process and avoid the misclassification color block drawback in linear LST-KSVC. MLT-KSVC is more accurate compared with LST-KSVC, TwinSVC, TwinKSVC, and classic Multi-SVM.
One- and Two-Phase Software Requirement Classification Using Ensemble Deep Learning

Recently, deep learning (DL) has been utilized successfully in different fields, achieving remarkable results. Thus, there is a noticeable focus on DL approaches to automate software engineering (SE) tasks such as maintenance, requirement extraction, and classification. An advanced utilization of DL is the ensemble approach, which aims to reduce error rates and learning time and improve performance. In this research, three ensemble approaches were applied: accuracy as a weight ensemble, mean ensemble, and accuracy per class as a weight ensemble with a combination of four different DL models—long short-term memory (LSTM), bidirectional long short-term memory (BiLSTM), a gated recurrent unit (GRU), and a convolutional neural network (CNN)—in order to classify the software requirement (SR) specification, the binary classification of SRs into functional requirement (FRs) or non-functional requirements (NFRs), and the multi-label classification of both FRs and NFRs into further experimental classes. The models were trained and tested on the PROMISE dataset. A one-phase classification system was developed to classify SRs directly into one of the 17 multi-classes of FRs and NFRs. In addition, a two-phase classification system was developed to classify SRs first into FRs or NFRs and to pass the output to the second phase of multi-class classification to 17 classes. The experimental results demonstrated that the proposed classification systems can lead to a competitive classification performance compared to the state-of-the-art methods. The two-phase classification system proved its robustness against the one-phase classification system, as it obtained a 95.7% accuracy in the binary classification phase and a 93.4% accuracy in the second phase of NFR and FR multi-class classification.
Selection of Specific Nanobodies against Lupine Allergen Lup an 1 for Immunoassay Development

The declaration of lupine supplements is mandatory to avoid lupine allergy for sensitive individuals. However, reliable detection methods against lupine allergen remain critical to prevent the unintended consumption of allergen contaminated food. In this study, we have immunized an alpaca with lupine protein extracts and retrieved nanobodies (Nbs). Nevertheless, the target antigen has been recognized as Lup an 1, which has been classified as β-conglutin, and confirmed to connect with lupine allergy. After selection of the best Nb-pair, a sandwich enzyme-linked immunosorbent assay (ELISA) has been developed providing a linear range of 0.036–4.4 μg/mL with detection limit of 1.15 ng/mL. This immunoassay was confirmed by detecting the samples with spiked allergen, and a recovery from 86.25% to 108.45% with coefficient of variation (CV) less than 4.0% has been determined. Generally, this study demonstrated the selection of Nbs against allergen with crude protein content to develop the immunoassay for lupine surveillance in foods.
Preclinical Evidence for the Interplay between Oxidative Stress and RIP1-Dependent Cell Death in Neurodegeneration: State of the Art and Possible Therapeutic Implications

Neurodegenerative diseases are the most frequent chronic, age-associated neurological pathologies having a major impact on the patient’s quality of life. Despite a heavy medical, social and economic burden they pose, no causative treatment is available for these diseases. Among the important pathogenic factors contributing to neuronal loss during neurodegeneration is elevated oxidative stress resulting from a disturbed balance between endogenous prooxidant and antioxidant systems. For many years, it was thought that increased oxidative stress was a cause of neuronal cell death executed via an apoptotic mechanism. However, in recent years it has been postulated that rather programmed necrosis (necroptosis) is the key form of neuronal death in the course of neurodegenerative diseases. Such assumption was supported by biochemical and morphological features of the dying cells as well as by the fact that various necroptosis inhibitors were neuroprotective in cellular and animal models of neurodegenerative diseases. In this review, we discuss the relationship between oxidative stress and RIP1-dependent necroptosis and apoptosis in the context of the pathomechanism of neurodegenerative disorders. Based on the published data mainly from cellular models of neurodegeneration linking oxidative stress and necroptosis, we postulate that administration of multipotential neuroprotectants with antioxidant and antinecroptotic properties may constitute an efficient pharmacotherapeutic strategy for the treatment of neurodegenerative diseases.
In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer

The survival rates for breast cancer (BC) have improved in recent years, but resistance, metastasis, and recurrence still remain major therapeutic challenges for BC. The acidic tumor microenvironment (TME) has attracted attention because of its association with tumorigenesis, metastasis, drug resistance, and immune surveillance. In this study, we evaluated natural compounds from traditional herbal medicine used to treat cancer that selectively target genes regulated by extracellular acidosis. We integrated four transcriptomic data including BC prognostic data from The Cancer Genome Atlas database, gene expression profiles of MCF-7 cells treated with 102 natural compounds, patterns of gene profiles by acidic condition, and single-cell RNA-sequencing from BC patient samples. Bruceine D (BD) was predicted as having the highest therapeutic potential, having an information gain (IG) score of 0.24, to regulate reprogrammed genes driven by acidosis affecting the survival of BC patients. BD showed the highest IG on EMT (IG score: 0.11) and invasion (IG score: 0.1) compared to the other phenotypes with the CancerSEA database. BD also demonstrated therapeutic potential by interfering with the tumor cell–TME interactions by reducing the amyloid beta precursor protein and CD44 expression. Therefore, BD is a potential candidate to target the acidic TME induced metastatic process in BC.
Bilirubin as a Therapeutic Molecule: Challenges and Opportunities

There is strong evidence that serum free bilirubin concentration has significant effects on morbidity and mortality in the most significant health conditions of our times, including cardiovascular disease, diabetes, and obesity/metabolic syndrome. Supplementation of bilirubin in animal and experimental models has reproduced these protective effects, but several factors have slowed the application bilirubin as a therapeutic agent in human patients. Bilirubin is poorly soluble in water, and is a complex molecule that is difficult to synthesize. Current sources of this molecule are animal-derived, creating concerns regarding the risk of virus or prion transmission. However, recent developments in nanoparticle drug delivery, biosynthetic strategies, and drug synthesis have opened new avenues for applying bilirubin as a pharmaceutical agent. This article reviews the chemistry and physiology of bilirubin, potential clinical applications and summarizes current strategies for safe and efficient drug delivery.
Effect of Germination on Alfalfa and Buckwheat: Phytochemical Profiling by UHPLC-ESI-QTOF-MS/MS, Bioactive Compounds, and In-Vitro Studies of Their Diabetes and Obesity-Related Functions

Germination can be used to enhance nutritional value and health functions of edible seeds. Sprouts are considered healthier than raw seeds because they are richer in the basic nutritional components (carbohydrates, protein, vitamins, and minerals) and also contain more bioactive components responsible for various biological activities. The effect of sprouting on the antioxidant, antidiabetic, antiobesity activities, and metabolite profiles of alfalfa and buckwheat seeds was investigated in this study. DPPH radical scavenging activity was highest in buckwheat sprouts followed by alfalfa sprout, buckwheat seed, and alfalfa seed, respectively. ABTS radical scavenging potential showed a similar trend as DPPH with buckwheat sprouts exerting the best scavenging capacity. Alfalfa sprout and buckwheat seed exhibited the highest percentage inhibitory activity of α-glucosidase (96.6 and 96.5%, respectively). Alfalfa sprouts demonstrated the strongest inhibitory activity against pancreatic lipase (57.12%) while alfalfa seed showed the highest advanced glycation end products (AGEs) formation inhibitory potential (28.7%). Moreover, thirty-three (33) metabolites were characterized in the seed and sprout samples. Sprouts demonstrated a higher level of metabolites compared to raw seeds. Hence, depending on the type of seed and the target activity, sprouting is a good technique to alter the secondary metabolites and functional properties of edible seeds.