Miracle-dz/UniFAR-FTUs huggingface dataset:
MPI8 is Potent against SARS‐CoV‐2 by Inhibiting Dually and Selectively the SARS‐CoV‐2 Main Protease and the Host Cathepsin L

A number of inhibitors have been developed for the SARS-CoV-2 main protease (MPro) as potential COVID-19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition of TMPRSS2, furin, and cathepsins B/K/L by more than a dozen of previously developed MPro inhibitors including MPI1-9, GC376, 11a, 10-1, 10-2, and 10- 3. MPI1-9, GC376 and 11a all contain an aldehyde for the formation of a reversible covalent hemiacetal adduct with the MPro active site cysteine and 10-1, 10-2 and 10-3 contain a labile ester to exchange with the MPro active site cysteine for the formation of a thioester. Our data revealed that all these inhibitors are inert toward TMPRSS2 and furin. Diaryl esters also showed low inhibition of cathepsins. However, all aldehyde inhibitors displayed high potency in inhibiting three cathepsins. Their determined IC50 values vary from 4.1 to 380 nM for cathepsin B, 0.079 to 2.3 nM for cathepsin L, and 0.35 to 180 nM for cathepsin K. All aldehyde inhibitors showed similar inhibition levels toward cathepsin L. A cellular analysis indicated high potency of MPI5 and MPI8 in inhibiting lysosomal activity, which is probably attributed to their inhibition of cathepsins. Among all aldehyde inhibitors, MPI8 shows the best selectivity toward cathepsin L. With respect to cathepsins B and K, the selective indices are 192 and 150, respectively. MPI8 is the most potent compound among all aldehyde inhibitors in cellular MPro inhibition potency and anti-SARS-CoV-2 activity in Vero E6 cells. Cathepsin L has been demonstrated to play a critical role in the SARS-CoV-2 cell entry. By selectively inhibiting both SARS-CoV-2 MPro and the host cathepsin L, MPI8 potentiates dual inhibition effects to synergize its overall antiviral potency and efficacy. Due to its high selectivity toward cathepsin L that reduces potential toxicity toward host cells and high cellular and antiviral potency, we urge serious consideration of MPI8 for preclinical and clinical investigations for treating COVID-19.
Interferon-gamma and TNF-alpha synergistically enhance the immunomodulatory capacity of Endometrial-Derived Mesenchymal Stromal Cell secretomes by differential microRNA and extracellular vesicle release

Endometrial Mesenchymal Stromal Cells (endMSCs) can be easily isolated from menstrual blood by plastic adherence. These cells have a potent pro-angiogenic and immunomodulatory capacity, and their therapeutic effect is mediated by paracrine mechanisms where secretome have a key role. In this paper, we aimed to evaluate different priming conditions in endMSCs using pro-inflammatory cytokines and Toll-Like Receptor ligands. Our in vitro results revealed a synergistic and additive effect of IFNγ and TNFα on endMSCs. The combination of these pro-inflammatory cytokines significantly increased the release of Indoleamine 2,3-dioxygenase (IDO1) in endMSCs. Additionally, this study was focused on the phenotype of IFNγ/TNFα-primed endMSCs (endMSCs*). Here we found that immune system-related molecules such as CD49d, CD49e, CD54, CD56, CD58, CD63, CD126, CD152, or CD274 were significantly altered in endMSCs* when compared to control cells. Afterward, our study was completed with the characterization of released miRNAs by Next Generation Sequencing (NGS). Briefly, our system biology approaches demonstrated that endMSCs* showed an increased release of 25 miRNAs whose target genes were involved in immune response and inflammation. Finally, the cellular and molecular characterization was completed with in vitro functional assays. In summary, the relevance of our results lies in the therapeutic potential of endMSCs*. The differences in cell surface molecules involved in migration, adhesion and immunogenicity, allowed us to hypothesize that endMSCs* may have an optimal homing and migration capacity towards inflammatory lesions. Secondly, the analysis of miRNAs, target genes and the subsequent lymphocyte activation assays demonstrated that IFNγ/TNFα-primed secretome may exert a potent effect on the regulation of adverse inflammatory reactions.
Genetic analysis of praziquantel response in schistosome parasites implicates a Transient Receptor Potential channel

Mass treatment with praziquantel (PZQ) monotherapy is the mainstay for schistosomiasis treatment. This drug shows imperfect cure rates in the field and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in Schistosoma mansoni populations is unknown. We examined the genetic basis of variation in PZQ response in a S. mansoni population (SmLE-PZQ-R) selected with PZQ in the laboratory: 35% of these worms survive high dose (73 µg/mL) PZQ treatment. We used genome wide association to map loci underlying PZQ response. The major chr. 3 peak contains a transient receptor potential (Sm.TRPMPZQ) channel (Smp_246790), activated by nanomolar concentrations of PZQ. PZQ response shows recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPMPZQ SNP enriched populations of PZQ-resistant (PZQ-ER) and sensitive (PZQ-ES) parasites showing >377 fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents better than PZQ-ES. Resistant parasites show 2.25-fold lower expression of Sm.TRPMPZQ than sensitive parasites. Specific chemical blockers of Sm.TRPMPZQ enhanced PZQ resistance, while Sm.TRPMPZQ activators increased sensitivity. A single SNP in Sm.TRPMPZQ differentiated PZQ-ER and PZQ-ES lines, but mutagenesis showed this was not involved in PZQ-response, suggesting linked regulatory changes. We surveyed Sm.TRPMPZQ sequence variation in 259 parasites from the New and Old World revealing one nonsense mutation that results in a truncated protein with no PZQ-binding site. Our results demonstrate that Sm.TRPMPZQ underlies variation in PZQ response in S. mansoni and provides an approach for monitoring emerging PZQ-resistance alleles in schistosome elimination programs. One Sentence Summary A transient receptor potential channel determines variation in praziquantel-response in Schistosoma mansoni.
Associative learning drives longitudinally graded presynaptic plasticity of neurotransmitter release along axonal compartments

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which was required to maintain responsivity to odors in untrained conditions. Downstream from the mushroom body, a set of MBONs that receive their input from the γ3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which discriminative effects influence appetitive memory and decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.
Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism

Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat. Coordination among multiple OADs is essential for generating mechanical forces to bend microtubule doublets (MTDs). Using electron microscopy, we determined high-resolution structures of Tetrahymena thermophila OAD arrays bound to MTDs in two different states. OAD preferentially binds to MTD protofilaments with a pattern resembling the native tracks for its distinct microtubule-binding domains. Upon MTD binding, free OADs are induced to adopt a stable parallel conformation, primed for array formation. Extensive tail-to-head (TTH) interactions between OADs are observed, which need to be broken for ATP turnover by the dynein motor. We propose that OADs in an array sequentially hydrolyze ATP to slide the MTDs. ATP hydrolysis in turn relaxes the TTH interfaces to effect free nucleotide cycles of downstream OADs. These findings lead to a model explaining how conformational changes in the axoneme produce coordinated action of dyneins. Outer-arm dyneins (OADs) assemble in large arrays on the ciliary axoneme to drive rhythmic beating. Cryo-EM structures of microtubule-bound Tetrahymena thermophila OAD arrays reveal details of this complex assembly and suggest a model for its mechanism of coordinated action.
Spinosad for control of brinjal shoot and fruit borer: Efficacy and economics

Brinjal is one of the important vegetable crops in India. Brinjal shoot and fruit borer (BSFB) (Leucinodes orbonalis) is important insect pest of brinjal, because it causes huge yield losses. Field experiment was conducted to evaluate the efficacy and economics of the naturally derived insecticide, Spinosad 45%SC over the locally used insecticides against the BSFB. The result of the experiment confirms that the shoot infestation was lowest in the Spinosad treated field and the yield was also higher with its application over the control and other treatment.
Differentially Localized Survivin and STAT3 as Markers of Gastric Cancer Progression: Association with H. pylori

Background: Localization and differential expression of STAT3 and survivin in cancer cells are often related to distinct cellular functions. The involvement of survivin and STAT3 in gastric cancer has been reported in separate studies but without clear understanding of their kinetics in cancer progression. Methods: We examined intracellular distribution of STAT3 and survivin in gastric adenocarcinoma and compared it with normal and pre-cancer tissues using immunoblotting and immunohistochemistry. Results: Analysis of a total of 156 gastric samples comprising 61 histologically normal, 30 pre-cancerous tissues [comprising intestinal metaplasia (IM) and dysplasia (dys)] and 65 adenocarcinomas, collected as endoscopic biopsies from treatment naïve study participants revealed a significant (p <0.001) increase in overall protein levels. Survivin expression was detectable both in cytoplasmic (90.8%) and nuclear compartments (87.7%) in gastric adenocarcinomas lesions. Pre-cancerous dysplastic gastric lesions exhibited a moderate survivin expression (56.7%) localized in cytoplasmic compartment. Similarly, STAT3 and pSTAT3 expression was detected at high level in gastric cancer lesions. The levels of compartmentalized expression of survivin and STAT3/pSTAT3 correlated in precancerous and in adenocarcinoma lesions. Though, overexpression of these proteins was found associated with the tobacco use, and alcohol consumption, their expression invariably and strongly correlated with concurrent H. pylori infection. ROC analysis of nuclear survivin, STAT3 and pSTAT3 in different study groups showed acceptable positive and negative predictive values with AUC above 0.8 (p<0.001). Conclusion: Overall, our results suggest that overall increase in survivin and STAT3 and their subcellular localization are key determinants of This article is protected by copyright. All rights reserved. Pandey A. et al 2018 gastric cancer progression, which can be collectively used as potential disease biomarkers and therapeutic targets for gastric cancer. Abbreviation: STAT3–signal transducer and activator of transcription-3; pSTAT3phosphorylated STAT3 (Y705); ROC – receiver operating characteristics; AUC – area under curve, Hp – Helicobacter pylori, IHC – immunohistochemistry; IM – intestinal metaplasia; Dys – dysplasia; DC – diffuse adenocarcinoma; IC – intestinal adenocarcinoma
Running title: IRRADIATION DOSE ON A. fraterculus Academy Section: ECOSYSTEMS

Anastrepha fraterculus (Wiedemann, 1830) (Diptera: Tephritidae) is a major fruit pest, which is basicaly controlled using insecticides, which represents a risk to benefi cial arthropods, human health and food contamination. The sterile insect technique (SIT) is a potential alternative tool for the management of this pest, however, only confl icting data is found regarding the optimal dose to achieve sterility. Thus, this study evaluated the effect of gamma radiation doses (0, 40, 50, 60 and 70 Gy) on male and female reproductive sterility, gonads morphometry, emergence, fl ight ability, and longevity under nutritional stress of A. fraterculus. Full female sterility was achieved at 50 Gy, while full male sterility was achieved at 70 Gy. Both ovarian and testicular sizes were affected by irradiation, while no infl uence was observed on the quality parameters evaluated. Our results suggest that 70 Gy applied 48 h before adult emergence can be used to sterilize A. fraterculus in a SIT programme.
A study to assess the peer acceptance of sensory challenged and Non-disabled children in an inclusive education environment

The purpose of the study was to assess the peer acceptance of sensory challenged and non-disabled children in an inclusive education environment. A self structured tool developed by the investigator was used to assess the peer acceptance of sensory challenged and non-disabled children. Purposive sampling procedure was used to select the schools catering to the educational needs of both sensory challenged and non-disabled children attending inclusive schools in Bangalore city. 100 sensory challenged and 100 non-disabled children aged between 10-15 years were selected for the study. The research design included a quasi experimental design. Data collected was analyzed using both descriptive and inferential statistics. The post assessment data revealed that the intervention programme had a positive influence on peer acceptance of sensory challenged and non-disabled children in an inclusive education environment. © 2016 Elixir All rights reserved. Elixir Soc. Sci 98 (2016) 42584-42586 Social Science Available online at www.elixirpublishers. com (Elixir International Journal) Asha.S. C and Venkat Lakshmi. H/ Elixir Soc. Sci 98 (2016) 42584-42586 42585 2. The study was limited to the schools catering to the inclusive educational needs of sensory challenged children in Bangalore City.
Decision Support for Diagnosing Thyroid Diseases using Machine Learning

- This research was carried out to compare the applicability of machine learning techniques in a way to support decision making in Thyroid disease diagnosis. In this research work, two types of machine learning algorithms; Multilayer perceptron Neural Network with Back-propagation and Random Forest were used, and a comparison of their performance was done to identify the most suitable machine learning algorithm which can be used to assist the diagnostic process of Thyroid diseases. Each of the models developed under the two machine learning techniques were trained and tested using two thyroid datasets from the UCI machine learning repository. The performance of the models was evaluated using the performance measures, Accuracy (%), Mean Absolute Error, Root Mean Squared Error, True Positive rate, False Positive rate, Precision and Recall.
Proximate and anti-nutrient profiles of tubers of Dioscorea bulbifera from Rivers State , Nigeria : Nutritional and health implications of consumption

The proximate and anti-nutrient profiles of Dioscorea bulbifera tubers were determined. The proximate profile included high crude fiber (18.17±6.28% per wet weight and 20.34±6.67% per dry weight) and total carbohydrate (60.83±3.82% per wet weight and 68.41±5.78% per dry weight). The anti-nutrients composition included tannins, cyanogenic glycosides, oxalates, phytates and saponins. These results support the medicinal uses of Dioscorea bulbifera tubers, and suggest its potentials as food, after
The Possibility of Assessing Pain with Biomarkers in Psychiat- ric Disorders

In this paper, we present a systematic literature review, define methods for identifying biomarkers that are characteristic of pain, and consider their possible use for assessing pain in mental disorders. The PubMed, Scope, and Cochrane databases were searched for the occurrence of the subject “pain biomarkers in psychiatric disorders” between 2011 and 2021. Two independent researchers searched available databases for full-text, peer-reviewed studies and review publications using the following keywords: pain biomarkers, pain neuroimaging, pain metabolomics, pain and psychiatric disorders, pain electroencephalography (EEG), serum pain biomarkers, saliva biomarkers, and pain diagnosis. Full-text articles, clinical studies, randomized controlled trials, and systematic re-views, were included in the search. The PRISMA method was used to systematically review the literature. The literature search identified 283 studies through the initially assumed inclusion and exclusion criteria. In successive selection steps, 11 studies were selected for analysis. There are three main areas of possible use of biomarkers for clinically assessing pain in psychiatric patients, i.e., neuroimaging, changes in metabolite levels in body fluids, and changes in gene expression. Despite significant advancements in research, the described biomarkers are in phases of clinical trials for assessing the intensity and occurrence of pain. Discussion: Pain is a significant and disruptive symptom in patients with mental disorders. Recently, studies have proposed new possibilities for pain diagnostics by determining pain biomarkers. Biomarker research is a dynamically growing field of study. We present examples of pain diagnosis based on biomarkers from various neuroimaging methods, as well as blood and urine analyses. The possibility of new, effective techniques gives hope for the correct diagnosis of pain, especially in patients with mental disorders, which would allow for appropriate and adequate therapeutic therapies. However, the possibilities of use in clinical practice are limited to a few methods. Assessment of pain biomarkers in body fluids (serum, saliva, and urine) appears to be the most practical and promising clinical use method. Keywords: pain assessment; pain biomarkers, psychiatric disorders
Flocculation Characterization of a Bioflocculant from Bacillus licheniformis

In this work, the effects of different factors on the flocculating activity and flocculation mechanism of bioflocculant XMMBF from Bacillus licheniformis are investigated. The results show that the optimum concentration of bioflocculant for kaolin clay sedimentation is 4 mg/L. Both monovalent and bivalent cations increase the flocculating activity, whereas trivalent cations inhibit it. The optimum pH and concentration of kaolin clay suspension are 5–11 and 2–10 g/L, respectively. The adsorption of XMMBF on kaolin clay is described using the Langmuir adsorption model. Infrared spectrum shows the carboxyl groups, amino groups, and hydrogen bonds in XMMBF prefer the flocculation process. The zeta potential of kaolin clay can be changed from −26.26 to −1.08 mV by both Ca2+ and XMMBF. The formation of ionic bonds in the floc can be related to its sensitivity to HCl. Finally, through the help of SEM pictures, the flocculation mechanism of XMMBF is proposed.
Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease

The role of apolipoprotein E4 (APOE4) in the risk of Alzheimer's disease (AD) and Lewy body disease (LBD), and their relationship with β-amyloid deposition and cognitive dysfunction, remain unclear. Using amyloid and dopamine transporter imaging, we enrolled 126 controls and 208 patients with typical AD (pure AD and Lewy body variant of AD), AD with dementia with Lewy bodies, or typical LBD (dementia with Lewy bodies with amyloid deposition and pure LBD). APOE4 was associated with an increased risk of all disease subtypes except pure LBD. APOE4 was associated with increased frontal β-amyloid burden, and typical LBD was associated with increased occipital β-amyloid levels through its interaction with APOE4. APOE4 was associated with deteriorated general cognition and memory dysfunction via its interaction with typical LBD and AD, respectively. In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.
Learning meaningful controls for fluids

While modern fluid simulation methods achieve high-quality simulation results, it is still a big challenge to interpret and control motion from visual quantities, such as the advected marker density. These visual quantities play an important role in user interactions: Being familiar and meaningful to humans, these quantities have a strong correlation with the underlying motion. We propose a novel data-driven conditional adversarial model that solves the challenging and theoretically ill-posed problem of deriving plausible velocity fields from a single frame of a density field. Besides density modifications, our generative model is the first to enable the control of the results using all of the following control modalities: obstacles, physical parameters, kinetic energy, and vorticity. Our method is based on a new conditional generative adversarial neural network that explicitly embeds physical quantities into the learned latent space, and a new cyclic adversarial network design for control disentanglement. We show the high quality and versatile controllability of our results for density-based inference, realistic obstacle interaction, and sensitive responses to modifications of physical parameters, kinetic energy, and vorticity. Code, models, and results can be found at https://github.com/RachelCmy/den2vel.
Atypical presentation of a fish bone foreign body: A case report and review of the literature

Our aim is to present the importance of mobile Handheld Lung Ultrasound (HLUS) in COVID-19 patients at the bedside, which is a pre-screening tool with high diagnostic value that can provide triage of symptomatic patients at home (pre-hospital), emergency services, Intensive Care Units (ICU). In this context, the current role and importance of HLUS at the bedside in COVID-19 pneumonia has been summarized.
Hemato-biochemical and pathological alterations of chronic nephritis in a dog

The present study was carried out to investigate the haemato-biochemical, gross and histopathological changes of chronic nephritis in a dog. Decreased value of Hb, PCV, TEC and platelat counts were observed in haematological evaluation. Increase value of BUN and creatinine was found in biochemical estimation. On necropsy, the kidneys were reduced in size and after removal of the capsule cortex showed an uneven and pitted appearance with multifocal petecheal haemorrhages. Histopathological examination revealed different stages of tubular degeneration and necrosis, widening of the bowman’s space, decrease glomarular cellularity, presence of infiltrating cells predominantly lymphocytes and plasma cells. Other histopathological findings include focal area of fibrosis, dystrophic calcification, vascular congestion and focal hemarrhages in the interstitial spaces.