Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of 35 C-Type Lectins in the Oriental Armyworm, Mythimna separata (Walker)

Simple Summary The oriental armyworm Mythimna separata is a lepidopteral agricultural pest that causes serious damage to many crops, such as maize, wheat, and sorghum. To control this pest, it is advisable to take comprehensive measures, including the use of chemical pesticides, microbial pesticides, and cultural practices. However, microbial pesticides (entomopathogens) can be eliminated by the insect immune system. C-type lectins (CTLs) are a family of pattern-recognition receptors that recognize carbohydrates and mediate immune responses. C-type lectins in the oriental armyworm have not yet been identified and characterized. In this study, a transcriptome of M. separata larvae was constructed and a total of 35 CTLs containing single or dual carbohydrate-recognition domains (CRDs) were identified from unigenes. Phylogenetic analyses, sequence alignments and structural predictions were performed. Gene expression profiles in different developmental stages, naïve larval tissues, and bacteria/fungi-challenged larvae were analyzed. Overall, our findings indicate that most dual-CRD CTLs are expressed in mid-late-stage larvae, pupae, and adults. Bacterial and fungal challenges can stimulate the expression of many CTLs in larval hemocytes, fat body, and midgut. Our data suggest the importance of CTLs in immune responses of M. separata. Abstract Insect C-type lectins (CTLs) play vital roles in modulating humoral and cellular immune responses. The oriental armyworm, Mythimna separata (Walker) (Lepidoptera: Noctuidae) is a migratory pest that causes significant economic loss in agriculture. CTLs have not yet been systematically identified in M. separata. In this study, we first constructed a transcriptome of M. separata larvae, generating a total of 45,888 unigenes with an average length of 910 bp. Unigenes were functionally annotated in six databases: NR, GO, KEGG, Pfam, eggNOG, and Swiss-Prot. Unigenes were enriched in functional pathways, such as those of signal transduction, endocrine system, cellular community, and immune system. Thirty-five unigenes encoding C-type lectins were identified, including CTL-S1~CTL-S6 (single CRD) and IML-1~IML-29 (dual CRD). Phylogenetic analyses showed dramatic lineage-specific expansions of IMLs. Sequence alignment and structural modeling identified potential ligand-interacting residues. Real-time qPCR revealed that CTL-Ss mainly express in eggs and early stage larvae, while IMLs mainly express in mid-late-stage larvae, pupae, and adults. In naïve larvae, hemocytes, fat body, and epidermis are the major tissues that express CTLs. In larvae challenged by Escherichia coli, Staphylococcus aureus, or Beauveria bassiana, the expression of different CTLs was stimulated in hemocytes, fat body and midgut. The present study will help further explore functions of M. separata CTLs.
Interventricular Differences of Signaling Pathways-Mediated Regulation of Cardiomyocyte Function in Response to High Oxidative Stress in the Post-Ischemic Failing Rat Heart

Standard heart failure (HF) therapies have failed to improve cardiac function or survival in HF patients with right ventricular (RV) dysfunction suggesting a divergence in the molecular mechanisms of RV vs. left ventricular (LV) failure. Here we aimed to investigate interventricular differences in sarcomeric regulation and function in experimental myocardial infarction (MI)-induced HF with reduced LV ejection fraction (HFrEF). MI was induced by LAD ligation in Sprague–Dawley male rats. Sham-operated animals served as controls. Eight weeks after intervention, post-ischemic HFrEF and Sham animals were euthanized. Heart tissue samples were deep-frozen stored (n = 3–5 heart/group) for ELISA, kinase activity assays, passive stiffness and Ca2+-sensitivity measurements on isolated cardiomyocytes, phospho-specific Western blot, and PAGE of contractile proteins, as well as for collagen gene expressions. Markers of oxidative stress and inflammation showed interventricular differences in post-ischemic rats: TGF-β1, lipid peroxidation, and 3-nitrotyrosine levels were higher in the LV than RV, while hydrogen peroxide, VCAM-1, TNFα, and TGF-β1 were increased in both ventricles. In addition, nitric oxide (NO) level was significantly decreased, while FN-1 level was significantly increased only in the LV, but both were unchanged in RV. CaMKII activity showed an 81.6% increase in the LV, in contrast to a 38.6% decrease in the RV of HFrEF rats. Cardiomyocyte passive stiffness was higher in the HFrEF compared to the Sham group as evident from significantly steeper Fpassive vs. sarcomere length relationships. In vitro treatment with CaMKIIδ, however, restored cardiomyocyte passive stiffness only in the HFrEF RV, but had no effect in the HFrEF LV. PKG activity was lower in both ventricles in the HFrEF compared to the Sham group. In vitro PKG administration decreased HFrEF cardiomyocyte passive stiffness; however, the effect was more pronounced in the HFrEF LV than HFrEF RV. In line with this, we observed distinct changes of titin site-specific phosphorylation in the RV vs. LV of post-ischemic rats, which may explain divergent cardiomyocyte stiffness modulation observed. Finally, Ca2+-sensitivity of RV cardiomyocytes was unchanged, while LV cardiomyocytes showed increased Ca2+-sensitivity in the HFrEF group. This could be explained by decreased Ser-282 phosphorylation of cMyBP-C by 44.5% in the RV, but without any alteration in the LV, while Ser-23/24 phosphorylation of cTnI was decreased in both ventricles in the HFrEF vs. the Sham group. Our data pointed to distinct signaling pathways-mediated phosphorylations of sarcomeric proteins for the RV and LV of the post-ischemic failing rat heart. These results implicate divergent responses for oxidative stress and open a new avenue in targeting the RV independently of the LV.
Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.
Cryochemical Production of Drug Nanoforms: Particle Size and Crystal Phase Control of the Antibacterial Medication 2,3-Quinoxalinedimethanol-1,4-dioxide (Dioxidine)

Increasing the effectiveness of known, well-tested drugs is a promising low-cost alternative to the search for new drug molecular forms. Powerful approaches to solve this problem are (a) an active drug particle size reduction down to the nanoscale and (b) thermodynamically metastable but kinetically stable crystal modifications of drug acquisition. The combined cryochemical method has been used for size and structural modifications of the antibacterial drug 2,3-quinoxalinedimethanol-1,4-dioxide (dioxidine). The main stage of the proposed technique includes the formation of a molecular vapor of the drug substance, combined with a carrier gas (CO2) flow, followed by a fast condensation of the drug substance and CO2 molecules on a cooled-by-liquid nitrogen surface of preparative cryostate. It was established that the molecular chemical structure of the drug substance remained unchanged during cryochemical modification; however, it led to a significant decrease of the drug particles’ size down to nanosizes and changes in the crystal structures of the solid drug nanoforms obtained. Varying carrier gas (CO2) flow led to changes in their solid phase composition. A higher dissolution rate and changes in antibacterial activity were demonstrated for cryomodified dioxidine samples in comparison to the properties of the initial pharmacopeia dioxidine.
Expression Profiling and Bioinformatics Analysis of CircRNA in Mice Brain Infected with Rabies Virus

Rabies virus (RABV) induces acute, fatal encephalitis in mammals including humans. The circRNAs are important in virus infection process, but whether circRNAs regulated RABV infection remains largely unknown. Here, mice brain with or without the RABV CVS-11 strain were subjected to RNA sequencing and a total of 30,985 circRNAs were obtained. Among these, 9021 candidates were shared in both groups, and 14,610 and 7354 circRNAs were expressed specifically to the control and experimental groups, indicating that certain circRNAs were specifically inhibited or induced on RABV infection. The circRNAs mainly derived from coding exons. In total, 636 circRNAs were differentially expressed in RABV infection, of which 426 significantly upregulated and 210 significantly downregulated (p < 0.05 and fold change ≥2). The expression of randomly selected 6 upregulated and 6 downregulated circRNAs was tested by RT-qPCR, and the expression trend of the 11 out of 12 circRNAs was consistent in RT- qPCR and RNA-seq analysis. Rnase R-resistant assay and Sanger sequencing were conducted to verify the circularity of circRNAs. GO analysis demonstrated that source genes of all differentially regulated circRNAs were mainly related to cell plasticity and synapse function. Both KEGG and GSEA analysis revealed that these source genes were engaged in the cGMP–PKG and MAPK signaling pathway, and HTLV-I infection. Also, pathways related to glucose metabolism and synaptic functions were enriched in KEGG analysis. The circRNA–miRNA–mRNA network was built with 25 of 636 differentially expressed circRNAs, 264 mRNAs involved in RABV infection, and 29 miRNAs. Several miRNAs and many mRNAs in the network were reported to be related to viral infection and the immune response, suggesting that circRNAs could regulate RABV infection via interacting with miRNAs and mRNAs. Taken together, this study first characterized the transcriptomic pattern of circRNAs, and signaling pathways and function that circRNAs are involved in, which may indicate directions for further research to understand mechanisms of RABV pathogenesis.
Myeloid-Specific Acly Deletion Alters Macrophage Phenotype In Vitro and In Vivo without Affecting Tumor Growth

Simple Summary Tumor cells show different metabolism compared to normal tissue. For instance, they increase ATP-citrate lyase (Acly) expression for increased proliferation. Acly is therefore currently being targeted for cancer therapy. However, targeting this enzyme may have side effects on other cells within the tumor microenvironment, including tumor-associated macrophages (TAMs) which are immune cells crucial for cancer progression. As Acly deletion previously showed increased pro-inflammatory responses of macrophages in vitro, we hypothesized that Acly-deficient TAMs may better control tumor growth. Here, we determined the effect of Acly deficiency specifically in pro-cancer anti-inflammatory macrophages and TAMs in two mouse models of cancer. While Acly is crucial for anti-inflammatory macrophage activation, Acly-deficient TAMs do not affect tumor growth. Together, our results indicate that targeting Acly as anti-cancer therapy has no adverse effects on TAMs. Abstract Cancer cells rely on ATP-citrate lyase (Acly)-derived acetyl-CoA for lipid biogenesis and proliferation, marking Acly as a promising therapeutic target. However, inhibitors may have side effects on tumor-associated macrophages (TAMs). TAMs are innate immune cells abundant in the tumor microenvironment (TME) and play central roles in tumorigenesis, progression and therapy response. Since macrophage Acly deletion was previously shown to elicit macrophages with increased pro- and decreased anti-inflammatory responses in vitro, we hypothesized that Acly targeting may elicit anti-tumor responses in macrophages, whilst inhibiting cancer cell proliferation. Here, we used a myeloid-specific knockout model to validate that absence of Acly decreases IL-4-induced macrophage activation. Using two distinct tumor models, we demonstrate that Acly deletion slightly alters tumor immune composition and TAM phenotype in a tumor type-dependent manner without affecting tumor growth. Together, our results indicate that targeting Acly in macrophages does not have detrimental effects on myeloid cells.
Variable-Order Fractional Models for Wall-Bounded Turbulent Flows

Modeling of wall-bounded turbulent flows is still an open problem in classical physics, with relatively slow progress in the last few decades beyond the log law, which only describes the intermediate region in wall-bounded turbulence, i.e., 30–50 y+ to 0.1–0.2 R+ in a pipe of radius R. Here, we propose a fundamentally new approach based on fractional calculus to model the entire mean velocity profile from the wall to the centerline of the pipe. Specifically, we represent the Reynolds stresses with a non-local fractional derivative of variable-order that decays with the distance from the wall. Surprisingly, we find that this variable fractional order has a universal form for all Reynolds numbers and for three different flow types, i.e., channel flow, Couette flow, and pipe flow. We first use existing databases from direct numerical simulations (DNSs) to lean the variable-order function and subsequently we test it against other DNS data and experimental measurements, including the Princeton superpipe experiments. Taken together, our findings reveal the continuous change in rate of turbulent diffusion from the wall as well as the strong nonlocality of turbulent interactions that intensify away from the wall. Moreover, we propose alternative formulations, including a divergence variable fractional (two-sided) model for turbulent flows. The total shear stress is represented by a two-sided symmetric variable fractional derivative. The numerical results show that this formulation can lead to smooth fractional-order profiles in the whole domain. This new model improves the one-sided model, which is considered in the half domain (wall to centerline) only. We use a finite difference method for solving the inverse problem, but we also introduce the fractional physics-informed neural network (fPINN) for solving the inverse and forward problems much more efficiently. In addition to the aforementioned fully-developed flows, we model turbulent boundary layers and discuss how the streamwise variation affects the universal curve.
Depth-Camera Based Energy Expenditure Estimation System for Physical Activity Using Posture Classification Algorithm

Insufficient physical activity is common in modern society. By estimating the energy expenditure (EE) of different physical activities, people can develop suitable exercise plans to improve their lifestyle quality. However, several limitations still exist in the related works. Therefore, the aim of this study is to propose an accurate EE estimation model based on depth camera data with physical activity classification to solve the limitations in the previous research. To decide the best location and amount of cameras of the EE estimation, three depth cameras were set at three locations, namely the side, rear side, and rear views, to obtain the kinematic data and EE estimation. Support vector machine was used for physical activity classification. Three EE estimation models, namely linear regression, multilayer perceptron (MLP), and convolutional neural network (CNN) models, were compared and determined the model with optimal performance in different experimental settings. The results have shown that if only one depth camera is available, optimal EE estimation can be obtained using the side view and MLP model. The mean absolute error (MAE), mean square error (MSE), and root MSE (RMSE) of the classification results under the aforementioned settings were 0.55, 0.66, and 0.81, respectively. If higher accuracy is required, two depth cameras can be set at the side and rear views, the CNN model can be used for light-to-moderate activities, and the MLP model can be used for vigorous activities. The RMSEs for estimating the EEs of standing, walking, and running were 0.19, 0.57, and 0.96, respectively. By applying the different models on different amounts of cameras, the optimal performance can be obtained, and this is also the first study to discuss the issue.
ASSURED Point-of-Need Food Safety Screening: A Critical Assessment of Portable Food Analyzers

Standard methods for chemical food safety testing in official laboratories rely largely on liquid or gas chromatography coupled with mass spectrometry. Although these methods are considered the gold standard for quantitative confirmatory analysis, they require sampling, transferring the samples to a central laboratory to be tested by highly trained personnel, and the use of expensive equipment. Therefore, there is an increasing demand for portable and handheld devices to provide rapid, efficient, and on-site screening of food contaminants. Recent technological advancements in the field include smartphone-based, microfluidic chip-based, and paper-based devices integrated with electrochemical and optical biosensing platforms. Furthermore, the potential application of portable mass spectrometers in food testing might bring the confirmatory analysis from the laboratory to the field in the future. Although such systems open new promising possibilities for portable food testing, few of these devices are commercially available. To understand why barriers remain, portable food analyzers reported in the literature over the last ten years were reviewed. To this end, the analytical performance of these devices and the extent they match the World Health Organization benchmark for diagnostic tests, i.e., the Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end-users (ASSURED) criteria, was evaluated critically. A five-star scoring system was used to assess their potential to be implemented as food safety testing systems. The main findings highlight the need for concentrated efforts towards combining the best features of different technologies, to bridge technological gaps and meet commercialization requirements.
Electroconvulsive Therapy and Age: Effectiveness, Safety and Tolerability in the Treatment of Major Depression among Patients under and over 65 Years of Age

Electroconvulsive therapy (ECT) remains the most effective therapy in treatment-resistant depression. However, the safety of ECT has been consistently questioned, particularly among elderly patients. We assessed the efficacy and safety of ECT in patients before and after 65 years old. The study was conducted between 2015 and 2018 and included 91 patients (61 under and 29 over 65 years old) with major depression undergoing ECT. The Hamilton Depression Rating Scale was used to evaluate efficacy. Cognitive functions were assessed using: MMSE, RAVLT, Trail Making Test, Stroop Test and Autobiographical Memory Interview-Short Form. ECT was more effective in older patients as compared to younger (p < 0.001). No serious adverse events were observed in either group. Increased blood pressure and arrhythmias were more common in the older compared to the younger group (p = 0.044 and p = 0.047, respectively), while disturbances of consciousness did not differ between groups (p = 0.820). Most of the cognitive functions remained unchanged compared to baseline, whereas the outcomes of MMSE, RAVLT and Stroop tests showed greater improvements in the older compared to the younger group (all p < 0.05). The decline in the retrieval consistency of autobiographical memory was more pronounced in the younger group (p = 0.024). ECT is a highly effective, safe and well-tolerated method of treating depression regardless of age.
The Physicochemical and Antibacterial Properties of Chitosan-Based Materials Modified with Phenolic Acids Irradiated by UVC Light

This paper concerns the physicochemical properties of chitosan/phenolic acid thin films irradiated by ultraviolet radiation with wavelengths between 200 and 290 nm (UVC) light. We investigated the preparation and characterization of thin films based on chitosan (CTS) with tannic (TA), caffeic (CA) and ferulic acid (FA) addition as potential food-packaging materials. Such materials were then exposed to the UVC light (254 nm) for 1 and 2 h to perform the sterilization process. Different properties of thin films before and after irradiation were determined by various methods such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimeter (DSC), mechanical properties and by the surface free energy determination. Moreover, the antimicrobial activity of the films and their potential to reduce the risk of contamination was assessed. The results showed that the phenolic acid improving properties of chitosan-based films, short UVC radiation may be used as sterilization method for those films, and also that the addition of ferulic acid obtains effective antimicrobial activity, which have great benefit for food packing applications.