Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis, Pharmacological, and Biological Evaluation of 2-Furoyl-Based MIF-1 Peptidomimetics and the Development of a General-Purpose Model for Allosteric Modulators (ALLOPTML).

This work describes the synthesis and pharmacological evaluation of 2-furoyl-based Melanostatin (MIF-1) peptidomimetics as dopamine D2 modulating agents. Eight novel peptidomimetics were tested for their ability to enhance the maximal effect of tritiated N-propylapomorphine ([3H]-NPA) at D2 receptors (D2R). In this series, 2-furoyl-l-leucylglycinamide (6a) produced a statistically significant increase in the maximal [3H]-NPA response at 10 pM (11 ± 1%), comparable to the effect of MIF-1 (18 ± 9%) at the same concentration. This result supports previous evidence that the replacement of proline residue by heteroaromatic scaffolds are tolerated at the allosteric binding site of MIF-1. Biological assays performed for peptidomimetic 6a using cortex neurons from 19-day-old Wistar-Kyoto rat embryos suggest that 6a displays no neurotoxicity up to 100 μM. Overall, the pharmacological and toxicological profile and the structural simplicity of 6a makes this peptidomimetic a potential lead compound for further development and optimization, paving the way for the development of novel modulating agents of D2R suitable for the treatment of CNS-related diseases. Additionally, the pharmacological and biological data herein reported, along with >20 000 outcomes of preclinical assays, was used to seek a general model to predict the allosteric modulatory potential of molecular candidates for a myriad of target receptors, organisms, cell lines, and biological activity parameters based on perturbation theory (PT) ideas and machine learning (ML) techniques, abbreviated as ALLOPTML. By doing so, ALLOPTML shows high specificity Sp = 89.2/89.4%, sensitivity Sn = 71.3/72.2%, and accuracy Ac = 86.1%/86.4% in training/validation series, respectively. To the best of our knowledge, ALLOPTML is the first general-purpose chemoinformatic tool using a PTML-based model for the multioutput and multicondition prediction of allosteric compounds, which is expected to save both time and resources during the early drug discovery of allosteric modulators.
Neonatal AAV gene therapy rescues hearing in a mouse model of SYNE4 deafness

Genetic variants account for approximately half the cases of congenital and early‐onset deafness. Methods and technologies for viral delivery of genes into the inner ear have evolved over the past decade to render gene therapy a viable and attractive approach for treatment. Variants in SYNE4, encoding the protein nesprin‐4, a member of the linker of nucleoskeleton and cytoskeleton (LINC), lead to DFNB76 human deafness. Syne4−/− mice have severe‐to‐profound progressive hearing loss and exhibit mislocalization of hair cell nuclei and hair cell degeneration. We used AAV9‐PHP.B, a recently developed synthetic adeno‐associated virus, to deliver the coding sequence of Syne4 into the inner ears of neonatal Syne4−/− mice. Here we report rescue of hair cell morphology and survival, nearly complete recovery of auditory function, and restoration of auditory‐associated behaviors, without observed adverse effects. Uncertainties remain regarding the durability of the treatment and the time window for intervention in humans, but our results suggest that gene therapy has the potential to prevent hearing loss in humans with SYNE4 mutations.
Cellulose Dissolution in Mixtures of Ionic Liquids and Dimethyl Sulfoxide: A Quantitative Assessment of the Relative Importance of Temperature and Composition of the Binary Solvent

We studied the dissolution of microcrystalline cellulose (MCC) in binary mixtures of dimethyl sulfoxide (DMSO) and the ionic liquids: allylbenzyldimethylammonium acetate; 1-(2-methoxyethyl)-3-methylimidazolium acetate; 1,8-diazabicyclo [5.4. 0]undec-7-ene-8-ium acetate; tetramethylguanidinium acetate. Using chemometrics, we determined the dependence of the mass fraction (in %) of dissolved cellulose (MCC-m%) on the temperature, T = 40, 60, and 80 °C, and the mole fraction of DMSO, χDMSO = 0.4, 0.6, and 0.8. We derived equations that quantified the dependence of MCC-m% on T and χDMSO. Cellulose dissolution increased as a function of increasing both variables; the contribution of χDMSO was larger than that of T in some cases. Solvent empirical polarity was qualitatively employed to rationalize the cellulose dissolution efficiency of the solvent. Using the solvatochromic probe 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (WB), we calculated the empirical polarity ET(WB) of cellobiose (a model for MCC) in ionic liquid (IL)–DMSO mixtures. The ET(WB) correlated perfectly with T (fixed χDMSO) and with χDMSO (fixed T). These results show that there is ground for using medium empirical polarity to assess cellulose dissolution efficiency. We calculated values of MCC-m% under conditions other than those employed to generate the statistical model and determined the corresponding MCC-m% experimentally. The excellent agreement between both values shows the robustness of the statistical model and the usefulness of our approach to predict cellulose dissolution, thus saving time, labor, and material.
Synthesis of block copolypeptides by click chemistry

A novel synthetic methodology to diblock copolypeptides was developed by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) from alpha-omega-functionalized initiators combined with the Huisgen 1,3 dipolar cycloaddition (click chemistry). Poly(gamma-benzyl-L-glutamate) (PBLGlu) and poly(trifluoroacetyl-L-Lysine) (PTFALys) containing either an azide or an alkyne functional group in alpha-position were first synthesized by ROP of the corresponding NCA at room temperature in DMF as a solvent, using appropriate omega-amino-containing alpha-alkyne and a-azido difunctional initiators. The Copper(I) -catalyzed coupling reactions of alpha-azido-PBLGlu with the alpha-alkyne-PTFALys, on the one hand, and of the alpha-alkyne-PBLGlu with the alpha-azido-PTFALys, on the other hand were suitably accomplished in DMF. This afforded the targeted PBLGlu-b-PTFALys diblock copolypeptides pos- sessing a triazole group in between the two 1 blocks, as evidenced by SEC, IR, and NMR analysis. Block copolypeptides could be successfully purified by selective extraction with chloroform.
Robust Building Extraction for High Spatial Resolution Remote Sensing Images with Self-Attention Network

Building extraction from high spatial resolution remote sensing images is a hot spot in the field of remote sensing applications and computer vision. This paper presents a semantic segmentation model, which is a supervised method, named Pyramid Self-Attention Network (PISANet). Its structure is simple, because it contains only two parts: one is the backbone of the network, which is used to learn the local features (short distance context information around the pixel) of buildings from the image; the other part is the pyramid self-attention module, which is used to obtain the global features (long distance context information with other pixels in the image) and the comprehensive features (includes color, texture, geometric and high-level semantic feature) of the building. The network is an end-to-end approach. In the training stage, the input is the remote sensing image and corresponding label, and the output is probability map (the probability that each pixel is or is not building). In the prediction stage, the input is the remote sensing image, and the output is the extraction result of the building. The complexity of the network structure was reduced so that it is easy to implement. The proposed PISANet was tested on two datasets. The result shows that the overall accuracy reached 94.50 and 96.15%, the intersection-over-union reached 77.45 and 87.97%, and F1 index reached 87.27 and 93.55%, respectively. In experiments on different datasets, PISANet obtained high overall accuracy, low error rate and improved integrity of individual buildings.
Separation and characterization of cellulose from sugarcane tops and its saccharification by recombinant cellulolytic enzymes

Abstract In the present study, the cellulose from sugarcane tops (SCT) was separated and characterized for its purity. Approximately, 85% (w/w) of total cellulose present in raw SCT was recovered by using alkaline method. The monosaccharide analysis of SCT cellulose by HPLC showed 91% D-glucose, 7.5% D-xylose and 1.5% D-arabinose residues. Surface morphology study of dried cellulosic fibers by FESEM exhibited the fibrous structure. The FTIR analysis of separated cellulose displayed the peaks corresponding to the peaks obtained from commercial cellulose, confirming its purity. The crystallinity index (CrI) of separated cellulose increased to 49% after delignification and xylan extraction from 36% of raw SCT. The typical TGA curve of separated SCT cellulose showed decomposition and mass reduction at 327 °C resulting in single decomposition peak in TGA analysis, confirming its purity. CHNS analysis supported the purity of separated cellulose by confirming absence of nitrogen and sulfur. The separated cellulose was hydrolyzed by recombinant endo-β-1,4-glucanase (CtCel8A), cellobiohydrolase (CtCBH5A) from Clostridium themocellum and β-1,4-glucosidase (HtBgl) from Hungateiclostridium thermocellum at pH 5.8, 50 °C for 24 h, resulting in the production of 188 mg/g of total reducing sugar (TRS). The separated cellulose from SCT can be utilized as an alternative substrate for commercialization and for bioethanol production. GRAPHICAL ABSTRACT Highlights 85% of total cellulose recovery yield was obtained from raw sugarcane top (SCT) SCT cellulose contains 91%, D-glucose, 7.5% D-xylose and 1.5% D-arabinose residues Crystallinity index (CrI) of separated cellulose increased from 36% to 49% of raw SCT TGA curve of separated SCT cellulose showed the single decomposition peak at 327 °C Separated cellulose hydrolyzed by recombinant enzymes gave 188 mg/g TRS yield
Virus-Mediated Cell-Cell Fusion

Cell-cell fusion between eukaryotic cells is a general process involved in many physiological and pathological conditions, including infections by bacteria, parasites, and viruses. As obligate intracellular pathogens, viruses use intracellular machineries and pathways for efficient replication in their host target cells. Interestingly, certain viruses, and, more especially, enveloped viruses belonging to different viral families and including human pathogens, can mediate cell-cell fusion between infected cells and neighboring non-infected cells. Depending of the cellular environment and tissue organization, this virus-mediated cell-cell fusion leads to the merge of membrane and cytoplasm contents and formation of multinucleated cells, also called syncytia, that can express high amount of viral antigens in tissues and organs of infected hosts. This ability of some viruses to trigger cell-cell fusion between infected cells as virus-donor cells and surrounding non-infected target cells is mainly related to virus-encoded fusion proteins, known as viral fusogens displaying high fusogenic properties, and expressed at the cell surface of the virus-donor cells. Virus-induced cell-cell fusion is then mediated by interactions of these viral fusion proteins with surface molecules or receptors involved in virus entry and expressed on neighboring non-infected cells. Thus, the goal of this review is to give an overview of the different animal virus families, with a more special focus on human pathogens, that can trigger cell-cell fusion.
Polarization Switching DC-to-DC Converters

Abstract – On-chip DC-to-DC converters are critical to ensure regulated voltage for a variety of DC applications, including automotive and personal computer products. The converters have historically been limited to low power applications due to the size and cost constraints involved with the desire to have the converters integrated with the application circuit. The latest technology involves using switched-capacitors to allow for lower cost and monolithic integration. A new DC-to-DC converter design, utilizing a ferroelectric (FE) capacitor is researched, fabricated and tested. The inclusion of a FE, switched-capacitor results in an increase in the converter's output voltage due to the high dielectric constant (high-k) of the capacitor in conjunction with the resulting switching current as the polarization of the capacitor is reversed. In fact, the FE capacitor's effective capacitance resulting from the polarization switching provides the same behavior as a linear capacitor that is approximately 10 times the size (with respect to capacitance) as the FE capacitor. A proposed ferroelectric-based DC-to-DC step-down converter is analyzed, simulated, fabricated and tested. The results show the FE capacitor-based converter provides an output voltage and output impedance advantage over linear capacitor-based converters for equivalent capacitance levels.
Characterization and phylogenetic evolution of mitochondrial genome in Tibetan chicken

Abstract The objective of this study was to characterize mitochondrial genome and investigate phylogenetic evolution in Tibetan chicken. In this study, four haplotypes were identified based on D-loop sequencing in Tibetan chicken (n = 40), and each representative of four haplotypes was selected for total mitochondrial genome sequencing and analyzed together with published mitochondrial genome data of red jungle fowl. Four haplotypes belonged to three previously published clades, i.e., Clade A, clade B and clade E. Based on D-loop sequencing data, the average haplotype diversity and nucleotide diversity were 0.658 ± 0.065 and 0.00442 ± 0.00094, respectively. The mitochondrial genome of Tibetan chicken is 16,785 bp in size, consisting of 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes, 13 protein-coding genes and one non-coding control region (CR). Compared with the mitochondrial genome, a phylogenetic tree based on the D-loop sequence had a messy distribution, and no breed cluster pattern was observed in Tibetan chicken. The results indicate that Tibetan chicken populations in our study have relatively low nucleotide and haplotype diversity and likely share multiple maternal lineages. The D-loop sequence has limited power for the resolution of phylogenetic relationships in comparison with the complete mitochondrial genome.
Gaussian directional pattern for dorsal hand vein recognition

Abstract With the increasing needs in security systems, hand vein recognition is reliable as one of the important solutions for biometrics-based identification systems. This work presents an effective approach for dorsal hand vein recognition by analysing vein patterns. The methodology involves extraction of dorsal hand vein features based on Gaussian filter. In order to obtain effective pattern of dorsal hand vein vascular, we propose an innovative and robust Gaussian directional filter method to extract the dorsal hand vein patterns and to encode the vein features in binary code. A new coding scheme, namely Gaussian directional binary code, is then proposed for dorsal hand vein recognition. To evaluate the efficacy of the proposed approach, the normalised Hamming distance used in recognition is adopted. A total of 5120 dorsal hand vein images were collected from 256 persons to verify the validity of the proposed dorsal hand vein recognition approach. High accuracies (>99%) and low equal error rate (0·95%) have been obtained by the proposed method. Experimental results demonstrate that our proposed approach is feasible and effective for dorsal hand vein recognition.
MS-275, a class 1 histone deacetylase inhibitor augments glucagon-like peptide-1 receptor agonism to improve glycemic control and reduce obesity in diet-induced obese mice

Given its glycemic efficacy and ability to reduce the body weight, glucagon-like peptide 1 receptor (GLP-1R) agonism has emerged as a preferred treatment for diabetes associated with obesity. We here report that a small-molecule Class 1 histone deacetylase (HDAC) inhibitor Entinostat (MS-275) enhances GLP-1R agonism to potentiate glucose-stimulated insulin secretion and decrease body weight in diet-induced obese (DIO) mice. MS-275 is not an agonist or allosteric activator of GLP-1R but enhances the sustained receptor-mediated signaling through the modulation of the expression of proteins involved in the signaling pathway. MS-275 and liraglutide combined therapy improved fasting glycemia upon short-term treatment and a chronic administration causes a reduction of obesity in DIO mice. Overall, our results emphasize the therapeutic potential of MS-275 as an adjunct to GLP-1R therapy in the treatment of diabetes and obesity.
Regulated Necrotic Cell Death in Alternative Tumor Therapeutic Strategies

The treatment of tumors requires the induction of cell death. Radiotherapy, chemotherapy, and immunotherapy are administered to kill cancer cells; however, some cancer cells are resistant to these therapies. Therefore, effective treatments require various strategies for the induction of cell death. Regulated cell death (RCD) is systematically controlled by intracellular signaling proteins. Apoptosis and autophagy are types of RCD that are morphologically different from necrosis, while necroptosis, pyroptosis, and ferroptosis are morphologically similar to necrosis. Unlike necrosis, regulated necrotic cell death (RNCD) is caused by disruption of the plasma membrane under the control of specific proteins and induces tissue inflammation. Various types of RNCD, such as necroptosis, pyroptosis, and ferroptosis, have been used as therapeutic strategies against various tumor types. In this review, the mechanisms of necroptosis, pyroptosis, and ferroptosis are described in detail, and a potential effective treatment strategy to increase the anticancer effects on apoptosis- or autophagy-resistant tumor types through the induction of RNCD is suggested.
Roadside Air Quality Forecasting in Shanghai with a Novel Sequence-to-Sequence Model

The establishment of an effective roadside air quality forecasting model provides important information for proper traffic management to mitigate severe pollution, and for alerting resident’s outdoor plans to minimize exposure. Current deterministic models rely on numerical simulation and the tuning of parameters, and empirical models present powerful learning ability but have not fully considered the temporal periodicity of air pollutants. In order to take the periodicity of pollutants into empirical air quality forecasting models, this study evaluates the temporal variations of air pollutants and develops a novel sequence to sequence model with weekly periodicity to forecast air quality. Two-year observation data from Shanghai roadside air quality monitoring stations are employed to support analyzing and modeling. The results conclude that the fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations show obvious daily and weekly variations, and the temporal patterns are nearly consistent with the periodicity of traffic flow in Shanghai. Compared with PM2.5, the CO concentrations are more affected by traffic variation. The proposed model outperforms the baseline model in terms of accuracy, and presents a higher linear consistency in PM2.5 prediction and lower errors in CO prediction. This study could assist environmental researchers to further improve the technologies for urban air quality forecasting, and serve as tools for supporting policymakers to implement related traffic management and emission control policies.
In response to: Collet-Sicard Syndrome After Jefferson Fracture

We read with great interest the recent article by Shahrvini et al concerning Collect-Sicard syndrome after Jefferson fracture. 1 The authors present a detailed report of the syndrome in an aged woman after an accidental forward fall with head injury. This case is unique, as we found no ger-iatric patients with associated Jefferson fracture in our pre-vious review of Collect-Sicard syndrome. 2 In that report, the mean age of the 5 reported cases in the literature was 40 (range 18-58) years. The case reported by Shahrvini et al was caused by a 4-part fracture of the atlas, which the authors classify as a Jefferson fracture. According to the classification by Landells and Van Peteghem, this is a type II fracture. 3 They cite 4 other cases of 2- or 3-part atlas fracture. Before Jefferson, Quercioli was the first to describe a 4-part fracture of the atlas and neurological symptoms. 4 The authors exhibit very interesting CT signs of vocal cord paralysis and hypoglossal nerve injury, which have strong diagnostic evidence of neural damage. In these cases of Collect-Sicard syndrome, the classification of the type of atlas fracture is much less relevant than the degree of displacement of one of its joint masses with consequent compression of the bundle of the last 4 cranial nerves against the styloid process. It is essen-tial to highlight the displacement of the lateral masses of the atlas and to document the reduction of the space between them and the styloid processes. The patient reported by Shahrvini et al remained dependent on gastrostomy tube feeding, whereas younger patients in our review had com-plete (3/5) or partial (2/5) recovery. Because accidental or secondary falls are frequent in the elderly population, the possibility of Collect-Sicard syndrome must always be sus-pected, even if the patient manifests only partial symptoms in phonation and swallowing, to avoid bronchopneumonia infectious events.
Exogenous Salicylic Acid Modulates the Response to Combined Salinity-Temperature Stress in Pepper Plants (Capsicum annuum L. var. Tamarin)

Growers in the cultivated areas where the climate change threatens the agricultural productivity and livelihoods are aware that the current constraints for good quality water are being worsened by heatwaves. We studied the combination of salinity (60 mM NaCl) and heat shock stress (43 °C) in pepper plants (Capsicum annuum L. var. Tamarin) since this can affect physiological and biochemical processes distinctly when compared to separate effects. Moreover, the exogenous application of 0.5 mM salicylic acid (SA) was studied to determine its impacts and the SA-mediated processes that confer tolerance of the combined or stand-alone stresses. Plant growth, leaf Cl− and NO3− concentrations, carbohydrates, and polyamines were analyzed. Our results show that both salinity stress (SS) and heat stress (HS) reduced plant fresh weight, and SA only increased it for HS, with no effect for the combined stress (CS). While SA increased the concentration of Cl− for SS or CS, it had no effect on NO3−. The carbohydrates concentrations were, in general, increased by HS, and were decreased by CS, and for glucose and fructose, by SA. Additionally, when CS was imposed, SA significantly increased the spermine and spermidine concentrations. Thus, SA did not always alleviate the CS and the plant response to CS cannot be directly attributed to the full or partial sum of the individual responses to each stress.
Synthesis of MCM-41 with Different Pore Diameters without Addition of Auxiliary Organics

Swollen and highly ordered MCM-41 type materials with varied pores sizes, but with similar wall thicknesses, have been directly synthesized in the absence of auxilliary organics by controlling the preparation conditions. The most important parameter in the synthesis in order to control the pore opening is the cetyltrimethylammonium (CTMA+) concentration in the synthesis gel. Our results suggest that the mechanism of swelling is related with the replacement of some CTMA+ species by others cations in the interface formed between the liquid crystal and the silica surfaces. This approach could open new insights into the mechanism of formation of MCM-41 type materials as well as having in addition an important impact on the preparation of large mesoporous materials.