Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of the Masculinizing Function of the Helicoverpa armigera Masc Gene

The Masculinizer (Masc) gene has been known to control sex development and dosage compensation in lepidopterans. However, it remains unclear whether its ortholog exists and plays the same roles in distantly related lepidopterans such as Helicoverpa armigera. To address this question, we cloned Masc from H. armigera (HaMasc), which contains all essential functional domains of BmMasc, albeit with less than 30% amino acid sequence identity with BmMasc. Genomic PCR and qPCR analyses showed that HaMasc is a Z chromosome-linked gene since its genomic content in males (ZZ) was two times greater than that in females (ZW). RT-PCR and RT-qPCR analyses revealed that HaMasc expression was sex- and stage-biased, with significantly more transcripts in males and eggs than in females and other stages. Transfection of a mixture of three siRNAs of HaMasc into a male embryonic cell line of H. armigera led to the appearance of female-specific mRNA splicing isoforms of H. armigera doublesex (Hadsx), a downstream target gene of HaMasc in the H. armigera sex determination pathway. The knockdown of HaMasc, starting from the third instar larvae resulted in a shift of Hadsx splicing from male to female isoforms, smaller male pupa and testes, fewer but larger/longer spermatocytes and sperm bundles, delayed pupation and internal fusion of the testes and follicles. These data demonstrate that HaMasc functions as a masculinizing gene in the H. armigera sex-determination cascade.
Efficient Selection of Recombinant Fluorescent Vaccinia Virus Strains and Rapid Virus Titer Determination by Using a Multi-Well Plate Imaging System

Engineered vaccinia virus (VACV) strains are used extensively as vectors for the development of novel cancer vaccines and cancer therapeutics. In this study, we describe for the first time a high-throughput approach for both fluorescent rVACV generation and rapid viral titer measurement with the multi-well plate imaging system, IncuCyte®S3. The isolation of a single, well-defined plaque is critical for the generation of novel recombinant vaccinia virus (rVACV) strains. Unfortunately, current methods of rVACV engineering via plaque isolation are time-consuming and laborious. Here, we present a modified fluorescent viral plaque screening and selection strategy that allows one to generally obtain novel fluorescent rVACV strains in six days, with a minimum of just four days. The standard plaque assay requires chemicals for fixing and staining cells. Manual plaque counting based on visual inspection of the cell culture plates is time-consuming. Here, we developed a fluorescence-based plaque assay for quantifying the vaccinia virus that does not require a cell staining step. This approach is less toxic to researchers and is reproducible; it is thus an improvement over the traditional assay. Lastly, plaque counting by virtue of a fluorescence-based image is very convenient, as it can be performed directly on the computer.
Design Approach for Reducing Cross-Axis Sensitivity in a Single-Drive Multi-Axis MEMS Gyroscope

In this paper, a new design technique is presented to estimate and reduce the cross-axis sensitivity (CAS) in a single-drive multi-axis microelectromechanical systems (MEMS) gyroscope. A simplified single-drive multi-axis MEMS gyroscope, based on a mode-split approach, was analyzed for cross-axis sensitivity using COMSOL Multiphysics. A design technique named the “ratio-matching method” of drive displacement amplitudes and sense frequency differences ratios was proposed to reduce the cross-axis sensitivity. Initially, the cross-axis sensitivities in the designed gyroscope for x and y-axis were calculated to be 0.482% and 0.120%, respectively, having an average CAS of 0.301%. Using the proposed ratio-matching method and design technique, the individual cross-axis sensitivities in the designed gyroscope for x and y-axis were reduced to 0.018% and 0.073%, respectively. While the average CAS was reduced to 0.045%, showing a reduction rate of 85.1%. Moreover, the proposed ratio-matching method for cross-axis sensitivity reduction was successfully validated through simulations by varying the coupling spring position and sense frequency difference variation analyses. Furthermore, the proposed methodology was verified experimentally using fabricated single-drive multi-axis gyroscope.
SURFACE SOLID DISPERSION OF DOMPERIDONE FOR DISSOLUTION RATE ENHANCEMENT

The main objective of the study was to enhance the dissolution rate of poorly water soluble drug Domperidone by Surface solid dispersion (SSD) technique. Water-insoluble carriers like Sodium starch glycolate (SSG), Crospovidone, Avicel PH 102, Pre-gelatinized starch, Cab – osil M5 and Florite R were used in different ratios to prepare SSD by solvent evaporation method. SSD prepared with Florite R as carrier in the ratio of 1:10 showed the highest dissolution rate as compared to pure drug. Increase in the dissolution rate may be attributed to the reduced particle size of drug deposited on the surface of carrier and enhanced wettability of the drug particles by the carrier. The optimized formulation was evaluated by X-ray diffractometry (XRD), Differential scanning colorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). These tablets, apart from fulfilling the official and other specifications, exhibited higher rates of dissolution and dissolution efficiency values compared to their commercial counter parts. Mathematical modeling of dissolution data shows fitting into first order kinetics. Accelerated stability studies performed on optimized formulation indicated no significant change in the drug content and dissolution rate.
Ciclesonide Inhaler Treatment for Mild-to-Moderate COVID-19: A Randomized, Open-Label, Phase 2 Trial

Although some intravenous drugs have been used to treat coronavirus disease 2019 (COVID-19), no effective antiviral agents are currently available in the outpatient setting. We aimed to evaluate the efficacy and adverse events of 14-day ciclesonide treatment vs. standard care for patients with mild-to-moderate COVID-19. A randomized, open-label, multicenter clinical trial of ciclesonide inhalers was conducted in patients with mild-to-moderate COVID-19. Patients were enrolled within 3 days of diagnosis or within 7 days from symptom onset and randomly assigned to receive either ciclesonide (320 µg inhalation twice per day for 14 days) or standard care. The primary endpoint was the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eradication rate on day 14 from study enrollment. Clinical status was assessed once daily, and serial nasopharyngeal viral load was evaluated by quantitative reverse transcription polymerase chain reaction. There were 35 and 26 patients in the ciclesonide and standard care groups, respectively. The SARS-CoV-2 eradication rate at day 14 was significantly higher in the ciclesonide group (p = 0.021). In multivariate analysis, SARS-CoV-2 negative conversion within 14 days was 12 times more likely in the ciclesonide group (95% confidence interval, 1.187–125.240). Additionally, the clinical failure rate (high-flow nasal oxygen therapy or mechanical ventilation) was significantly lower in the ciclesonide group (p = 0.034). In conclusion, ciclesonide inhalation shortened SARS-CoV-2 viral shedding duration, and it may inhibit the progression to acute respiratory failure in patients with mild-to-moderate COVID-19. Clinical Trial Registration NCT04330586.
Assessment of Human Exposure to Deoxynivalenol, Ochratoxin A, Zearalenone and Their Metabolites Biomarker in Urine Samples Using LC-ESI-qTOF

Human are exposed to a wide range of mycotoxins through dietary food intake, including processed food. Even most of the mycotoxin exposure assessment studies are based on analysis of foodstuffs, and evaluation of dietary intake through food consumption patterns and human biomonitoring methods are rising as a reliable alternative to approach the individual exposures, overcoming the limitations of the indirect dietary assessment. In this study, human urine samples were analyzed, seeking the presence of deoxynivalenol (DON), ochratoxin A (OTA), zearalenone (ZEA), and their metabolites. For this purpose, 40 urine samples from female and male adult residents in the city of Valencia (Spain) were evaluated by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-ESI-qTOF) after salting-out liquid–liquid extraction. Analytical data showed that 72.5% of analyzed samples were contaminated by at least one mycotoxin at variable levels. The most prevalent mycotoxins were de-epoxy DON (DOM-1) (53%), ZEA (40%), and α-zearalenol (αZOL) (43%), while OTA was only detected in one sample. The mean concentrations in positive samples were DON (9.07 ng/mL), DOM-1 (20.28 ng/mL), ZEA (6.70 ng/mL), ZEA-14 glucoside (ZEA-14-Glc) (12.43 ng/mL), αZOL (27.44 ng/mL), αZOL-14 glucoside (αZOL-14-Glc) (12.84 ng/mL), and OTA (11.73 ng/mL). Finally, probable daily intakes (PDIs) were calculated and compared with the established tolerable daily intakes (TDIs) to estimate the potential risk of exposure to the studied mycotoxins. The calculated PDI was below the TDI value established for DON in both female and male adults, reaching a percentage up to 30%; however, this percentage increased up to 92% considering total DON (DON + DOM-1). On the other hand, the PDI obtained for ZEA and its metabolites were higher than the TDI value fixed, but the low urine excretion rate (10%) considered should be highlighted. Finally, the PDI calculated in the detected positive sample for OTA exceeded the TDI value. The findings of the present study confirm the presence of the studied mycotoxins and their metabolites as some of the most prevalent in urine.
Source Ranging Using Attention-Based Convolutional Neural Network

Source ranging based on ship-radiated noise is a crucial task in many practical applications. Deep neural networks (DNNs) have shown outstanding performance but poor interpretability on source ranging, leading to the heavily hidden risks of blind trust in the AI black box. In this study, an attention-based convolutional neural network (ABCNN) is proposed for the ship ranging in an attempt to visualize the features of concern in neural networks. Acoustic data of four ships were collected during a sea trial conducted in January 2021 to validate the ship ranging performance of ABCNN. Results showed high accuracy in ship ranging using synthetic data and part of the experimental data as a training set for the proposed method. The attention mechanism visualized a concentration on the inherent features of ships and the waveguide effect of underwater acoustic channels.
Bipartite Consensus for Second-Order Multiagent Systems With Matrix-Weighted Signed Network

The second-order scalar-weighted consensus problem of multiagent systems has been well explored. However, in some practical antagonistic interaction networks, the interdependencies of multidimensional states of the agents must be described by matrix coupling. In order to highlight the influence of matrix coupling in the antagonistic interaction network, we investigate the second-order matrix-weighted bipartite consensus problem on undirected structurally balanced signed networks. Under the proposed bipartite consensus protocol, an algebraic condition is obtained for achieving second-order bipartite consensus via utilizing matrix-valued Gauge transformation and stability theory. Then, using the obtained criteria, a more direct algebraic graph condition is given for reaching bipartite consensus. Besides, because of the existence of negative (positive) semidefinite connections, the matrix-weighted network may have clustering phenomena, which means that matrix weights play a critical role in achieving consensus. An algebraic graph condition for admitting cluster bipartite consensus is provided. By designing matrix weights in practical scenarios, the required number of clusters can be obtained. Finally, the theoretical results are verified by five simulation examples.
Dramatic Course of Paediatric Cryptogenic Febrile Infection-Related Epilepsy Syndrome with Unusual Chronic Phase Presentation—A Case Report with Literature Study

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic, extremely rare epileptic encephalopathy. It strikes previously healthy school-aged children and is usually cryptogenic. Its dramatic onset with refractory status epilepticus is always preceded by a nonspecific febrile illness. The seizure activity in FIRES may last for several weeks with little to no response to antiepileptic treatment, usually resulting in the usage of anaesthetics. This acute phase is followed by a chronic, refractory epilepsy and cognitive deficit, that persist for the rest of the patient’s life. Still to this day no definite cause has been described. In this study we review the current finding in FIRES and describe a case of a 4-year-old patient with a dramatic course of the acute phase in FIRES and unusual presentation of the chronic phase, which is dominated by extrapyramidal symptoms such as dystonia. This case highlights that the clinical presentation of FIRES may differ from those frequently described in literature.
Development of Time-Resolved Fluorescence Immunochromatographic Assays for Simultaneously Detecting Tylosin and Tilmicosin in Milk in Group-Screening Manner

Tylosin and tilmicosin (T&T) residues in livestock products have received extensive attention from consumers. Time-resolved fluorescence immunochromatographic assay (TRFICA), as a fast, efficient and sensitive immunoassay method, has played an increasingly important role in the food safety field. Therefore, herein a quantitative and visual TRFICA was established for simultaneously detecting T&T in milk in a group-screening manner. Under the optimal conditions, the standard curve range of developed TRFICA based on the T&T was 1.87~7.47 ng/mL, and the half-maximal inhibition concentrations (IC50) were 4.06 ng/mL and 3.74 ng/mL, respectively. The limits of detection (LOD) of the TRFICA method were from 1.72 ng/mL to 1.39 ng/mL, and the visual cut-off values were 31.25 ng/mL and 62.50 ng/mL for T&T in milk, respectively. Moreover, the stability experiments showed that the strips could be stored at 4 °C for more than 6 months, the total detection time was less than 13 min, and the cross-reactivities (CRs) with related compounds were less than 0.1%, which concluded that the developed TRFICA method could be used in real milk sample detection.
Multidirectional Ring Top-Hat Transformation for Infrared Small Target Detection

Fast and robust detection of a small target in an infrared image is one of the key techniques in infrared search and track systems. The top-hat transformation is an important technology in the field of infrared target detection. Many algorithms have been proposed to improve the top-hat transformation by modifying different structural elements. However, these methods can cause a high false alarm rate under conditions of small dim targets, low signal-to-noise, and complex background. To overcome this limitation, considering both detection performance and speed, an effective and robust detection model using multidirectional structural elements is proposed in this article. First, the nonconcentric multidirectional ring structural elements are designed. Then, using the morphological transformation with designed structural elements, the background is suppressed, and a small target is enhanced in different directions. Finally, the results of the morphological transformations are fused to obtain the final result, further highlighting a small target. The experimental results demonstrate the robust performance of the proposed method for various backgrounds and targets. In addition, the proposed method can achieve a detection speed of up to 10.4 ms per frame under the image resolution of 240 $ \times $ 320 pixels. Therefore, the proposed method is suitable for real-time applications.
Rumor Detection Based on Improved Transformer

In the field of rumor detection, the existing Transformer-based methods ignore the location information and fail to effectively use the potential information of the text. Therefore, we propose a social media rumor detection method based on improved Transformer that improves the standard Transformer through two novel techniques. First, learnable relative positional encoding is used to endow the Transformer with the ability of direction- and distance-awareness. Second, absolute positional encoding is used, through which each word with different absolute positions is mapped to its corresponding representation space. The experimental results show that, compared with the current best benchmark method, the accuracy of this method on the three data sets of Twitter15, Twitter16 and Weibo has increased by 0.9%, 0.6%, and 1.4%, respectively. The improved Transformer is effective and can significantly improve the effect of social media rumor detection.
Novel Glutamate–Putrescine Ligase Activity in Haloferax mediterranei: A New Function for glnA-2 Gene

The genome of the halophilic archaea Haloferax mediterranei contains three ORFs that show homology with glutamine synthetase (GS) (glnA-1, glnA-2, and glnA-3). Previous studies have focused on the role of GlnA-1, suggesting that proteins GlnA-2 and GlnA-3 could play a different role to that of GS. Glutamine synthetase (EC 6.3.1.2) belongs to the class of ligases, including 20 subclasses of other different enzymes, such as aspartate–ammonia ligase (EC 6.3.1.1), glutamate–ethylamine ligase (EC 6.3.1.6), and glutamate–putrescine ligase (EC 6.3.1.11). The reaction catalyzed by glutamate–putrescine ligase is comparable to the reaction catalyzed by glutamine synthetase (GS). Both enzymes can bind a glutamate molecule to an amino group: ammonium (GS) or putrescine (glutamate–putrescine ligase). In addition, they present the characteristic catalytic domain of GS, showing significant similarities in their structure. Although these proteins are annotated as GS, the bioinformatics and experimental results obtained in this work indicate that the GlnA-2 protein (HFX_1688) is a glutamate–putrescine ligase, involved in polyamine catabolism. The most significant results are those related to glutamate–putrescine ligase’s activity and the analysis of the transcriptional and translational expression of the glnA-2 gene in the presence of different nitrogen sources. This work confirms a new metabolic pathway in the Archaea domain which extends the knowledge regarding the utilization of alternative nitrogen sources in this domain.
Antimicrobial and Antibiofilm Activity of Curcumin-Loaded Electrospun Nanofibers for the Prevention of the Biofilm-Associated Infections

Curcumin extracted from the rhizome of Curcuma Longa has been used in therapeutic preparations for centuries in different parts of the world. However, its bioactivity is limited by chemical instability, water insolubility, low bioavailability, and extensive metabolism. In this study, the coaxial electrospinning technique was used to produce both poly (ε-caprolactone) (PCL)–curcumin and core–shell nanofibers composed of PCL and curcumin in the core and poly (lactic acid) (PLA) in the shell. Morphology and physical properties, as well as the release of curcumin were studied and compared with neat PCL, showing the formation of randomly oriented, defect-free cylindrical fibers with a narrow distribution of the dimensions. The antibacterial and antibiofilm potential, including the capacity to interfere with the quorum-sensing mechanism, was evaluated on Pseudomonas aeruginosa PAO1, and Streptococcus mutans, two opportunistic pathogenic bacteria frequently associated with infections. The reported results demonstrated the ability of the Curcumin-loading membranes to inhibit both PAO1 and S. mutans biofilm growth and activity, thus representing a promising solution for the prevention of biofilm-associated infections. Moreover, the high biocompatibility and the ability to control the oxidative stress of damaged tissue, make the synthesized membranes useful as scaffolds in tissue engineering regeneration, helping to accelerate the healing process.
TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma

Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-β/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-β signaling into immune-activating IL-7 signaling. The effect of TGF-β on CD19 CAR-tTRII-I7R-T cells was assessed by western blotting. Target-specific killing by CD19 CAR-tTRII-I7R-T cells was evaluated by Eu-TDA assay. Daudi tumor-bearing NSG (NOD/SCID/IL2Rγ-/-) mice were treated with CD19 CAR-tTRII-I7R-T cells to analyze the in vivo anti-tumor effect. In vitro, CD19 CAR-tTRII-I7R-T cells had a lower level of phosphorylated SMAD2 and a higher level of target-specific cytotoxicity than controls in the presence of rhTGF-β1. In the animal model, the overall survival and recurrence-free survival of mice that received CD19 CAR-tTRII-I7R-T cells were significantly longer than in control mice. These findings strongly suggest that CD19 CAR-tTRII-I7R-T cell therapy provides a new strategy for long-lasting, TGF-β-resistant anti-tumor effects against B cell lymphoma, which may lead ultimately to increased clinical efficacy.
Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer

Simple Summary Triple-negative breast cancer (TNBC) is associated with a poor prognosis, and the development of better therapeutic strategies is required. Herein, we investigated the role of the anti-angiogenic thrombospondin-1 (TSP1) in TNBC. TSP1 expression in tumor biopsies from TNBC patients was associated with a bad prognosis and a weak content of tumor-infiltrating lymphocytes (TILs). In the 4T1 mouse TNBC model, TSP1 knockdown reduced TGF-β activation and enhanced the content of TILs. Moreover, TSP1 knockdown decreased lung metastasis in syngeneic Balb/c immunocompetent mice but not in immunodeficient nude mice. Finally, TSP1 knockdown enhanced anti-PD-1 immunotherapy efficacy. Thus, targeting TSP1 may be considered as a putative therapeutic strategy in TNBC in combination with immunotherapy. Abstract Triple-negative breast cancer (TNBC) is notoriously aggressive with a high metastatic potential, and targeted therapies are lacking. Using transcriptomic and histologic analysis of TNBC samples, we found that a high expression of thrombospondin-1 (TSP1), a potent endogenous inhibitor of angiogenesis and an activator of latent transforming growth factor beta (TGF-β), is associated with (i) gene signatures of epithelial–mesenchymal transition and TGF-β signaling, (ii) metastasis and (iii) a reduced survival in TNBC patients. In contrast, in tumors expressing low levels of TSP1, gene signatures of interferon gamma (IFN-γ) signaling and lymphocyte activation were enriched. In TNBC biopsies, TSP1 expression inversely correlated with the CD8+ tumor-infiltrating lymphocytes (TILs) content. In the 4T1 metastatic mouse model of TNBC, TSP1 silencing did not affect primary tumor development but, strikingly, impaired metastasis in immunocompetent but not in immunodeficient nude mice. Moreover, TSP1 knockdown increased tumor vascularization and T lymphocyte infiltration and decreased TGF-β activation in immunocompetent mice. Noteworthy was the finding that TSP1 knockdown increased CD8+ TILs and their programmed cell death 1 (PD-1) expression and sensitized 4T1 tumors to anti-PD-1 therapy. TSP1 inhibition might thus represent an innovative targeted approach to impair TGF-β activation and breast cancer cell metastasis and improve lymphocyte infiltration in tumors, and immunotherapy efficacy in TNBC.