Miracle-dz/UniFAR-FTUs huggingface dataset:
State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated Na+ Channels by Anethole

Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. Anethole is thought to carry out its biological activities through direct interaction with ion channels. Anethole is beneficial for neurodegenerative Alzheimer’s and Parkinson’s diseases. Nevertheless, nothing has been investigated regarding the effects of anethole on voltage-gated Na+ channels (VGSCs), which are major players in neuronal function. We used cultured dorsal root ganglion neurons from neonatal rats as a source of natively expressed VGSCs for electrophysiological studies using the whole-cell patch-clamp technique. Our data show that anethole interacts directly with VGSCs. Anethole quickly blocks and unblocks (when removed) voltage-activated Na+ currents in this preparation in a fully reversible manner. Anethole’s binding affinity to these channels increases when the inactive states of these channels are populated, similar to lidocaine’s effect on the same channels. Our data show that anethole inhibits neuronal activity by blocking VGSCs in a state-dependent manner. These findings relate to the putative anesthetic activity attributable to anethole, in addition to its potential benefit in neurodegenerative diseases.
Composite Cryogels Based on Hydroxyapatite and Polyvinyl Alcohol and the Study of Physicochemical and Mechanical Properties

Nowadays, due to the increasing number of diseases and injuries related to bone tissue, there is an acute problem of creating a material that could be incorporated into the bone tissue structure and contribute to accelerated bone regeneration. Such materials can be represented by a polymeric matrix that holds the material in the bone and an inorganic component that can be incorporated into the bone structure and promote accelerated bone regeneration. Therefore, in this work we investigated polyvinyl alcohol-based composite cryogels containing an in situ deposited inorganic filler, hydroxyapatite. The freezing temperature was varied during the synthesis process. The composition of the components was determined by infrared spectroscopy and the phase composition by X-ray phase analysis, from which it was found that the main phase of the composite is hydroxyapatite and that the particle size decreases with increasing freezing temperature. The elemental composition of the surface is dominated by carbon, oxygen, phosphorus and calcium; no impurities of other elements not typical for polyvinyl alcohol/ hydroxyapatite cryogels were found. Higher mechanical properties and melting points were observed at −15 °C. Cryogenic treatment parameters did not affect cell viability; however, cell viability was above 80% in all samples.
Carvacrol Encapsulation in Chitosan–Carboxymethylcellulose–Alginate Nanocarriers for Postharvest Tomato Protection

Advancements in polymer science and nanotechnology hold significant potential for addressing the increasing demands of food security, by enhancing the shelf life, barrier properties, and nutritional quality of harvested fruits and vegetables. In this context, biopolymer-based delivery systems present themselves as a promising strategy for encapsulating bioactive compounds, improving their absorption, stability, and functionality. This study provides an exploration of the synthesis, characterization, and postharvest protection applications of nanocarriers formed through the complexation of chitosan oligomers, carboxymethylcellulose, and alginate in a 2:2:1 molar ratio. This complexation process was facilitated by methacrylic anhydride and sodium tripolyphosphate as cross-linking agents. Characterization techniques employed include transmission electron microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, thermal analysis, and X-ray powder diffraction. The resulting hollow nanospheres, characterized by a monodisperse distribution and a mean diameter of 114 nm, exhibited efficient encapsulation of carvacrol, with a loading capacity of approximately 20%. Their suitability for phytopathogen control was assessed in vitro against three phytopathogens—Botrytis cinerea, Penicillium expansum, and Colletotrichum coccodes—revealing minimum inhibitory concentrations ranging from 23.3 to 31.3 μg·mL−1. This indicates a higher activity compared to non-encapsulated conventional fungicides. In ex situ tests for tomato (cv. ‘Daniela’) protection, higher doses (50–100 μg·mL−1, depending on the pathogen) were necessary to achieve high protection. Nevertheless, these doses remained practical for real-world applicability. The advantages of safety, coupled with the potential for a multi-target mode of action, further enhance the appeal of these nanocarriers.
Inhibition of VHL by VH298 Accelerates Pexophagy by Activation of HIF-1α in HeLa Cells

Autophagy is a pivotal biological process responsible for maintaining the homeostasis of intracellular organelles. Yet the molecular intricacies of peroxisomal autophagy (pexophagy) remain largely elusive. From a ubiquitin-related chemical library for screening, we identified several inhibitors of the Von Hippel–Lindau (VHL) E3 ligase, including VH298, thereby serving as potent inducers of pexophagy. In this study, we observed that VH298 stimulates peroxisomal degradation by ATG5 dependently and escalates the ubiquitination of the peroxisomal membrane protein ABCD3. Interestingly, the ablation of NBR1 is similar to the curtailed peroxisomal degradation in VH298-treated cells. We also found that the pexophagy induced by VH298 is impeded upon the suppression of gene expression by the translation inhibitor cycloheximide. Beyond VHL inhibition, we discovered that roxadustat, a direct inhibitor of HIF-α prolyl hydroxylase, is also a potent inducer of pexophagy. Furthermore, we found that VH298-mediated pexophagy is blocked by silencing HIF-1α. In conclusion, our findings suggest that VH298 promotes pexophagy by modulating VHL-mediated HIF-α transcriptional activity.
Channel Features and API Frequency-Based Transformer Model for Malware Identification

Malicious software (malware), in various forms and variants, continues to pose significant threats to user information security. Researchers have identified the effectiveness of utilizing API call sequences to identify malware. However, the evasion techniques employed by malware, such as obfuscation and complex API call sequences, challenge existing detection methods. This research addresses this issue by introducing CAFTrans, a novel transformer-based model for malware detection. We enhance the traditional transformer encoder with a one-dimensional channel attention module (1D-CAM) to improve the correlation between API call vector features, thereby enhancing feature embedding. A word frequency reinforcement module is also implemented to refine API features by preserving low-frequency API features. To capture subtle relationships between APIs and achieve more accurate identification of features for different types of malware, we leverage convolutional neural networks (CNNs) and long short-term memory (LSTM) networks. Experimental results demonstrate the effectiveness of CAFTrans, achieving state-of-the-art performance on the mal-api-2019 dataset with an F1 score of 0.65252 and an AUC of 0.8913. The findings suggest that CAFTrans improves accuracy in distinguishing between various types of malware and exhibits enhanced recognition capabilities for unknown samples and adversarial attacks.
Impact of Medical School on the Relationship between Nutritional Knowledge and Sleep Quality—A Longitudinal Study of Students at Wroclaw Medical University in Poland

The aim of this study was to investigate the impact of the first year of medical school on the relationship between nutritional knowledge and sleep. To achieve this, first-year medical students at Wroclaw Medical University were invited to participate in the study during both the initial and final months of their first academic year. The study included 570 students in the initial period and 705 in the latter. The research questionnaire comprised the KomPAN, assessing nutritional knowledge, and the Pittsburgh Sleep Quality Index (PSQI), evaluating sleep quality. The majority of students demonstrated at least sufficient nutritional knowledge, while approximately two-thirds of students experienced poor sleep in both periods. Notably, sleep quality further deteriorated in the second period (PSQI total score: 6.86 vs. 7.38, p = 0.0157). This change was influenced mainly by a decrease in sleep duration and an increase in the use of sleep medications (both p < 0.0001). The significant difference in overall sleep quality between different nutritional knowledge levels emerged only in the second semester, where students with the highest nutritional knowledge slept the best, while those with the lowest slept the worst (p = 0.0001). Crucially, in both periods, the use of sleep medications was highest among individuals with insufficient nutritional knowledge. Throughout the academic year, the usage increased for all except those with the highest nutritional knowledge, who exhibited the best sleep (p < 0.0001). The escalating use of sleep medications among medical students warrants greater attention, and leveraging the relationship between nutritional knowledge and sleep could prove beneficial, as positive habits in one domain may positively influence the other.
The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair

The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such as mechanical stress, osmotic pressure, and temperature. TRPV4 enables the entry of cation ions, particularly calcium ions, into the cell. Activation of TRPV4 channels initiates calcium oscillations, which trigger intracellular signaling pathways involved in a plethora of cellular processes, including tissue repair. Widely expressed throughout the body, TRPV4 can be activated by a wide array of physicochemical stimuli, thus contributing to sensory and physiological functions in multiple organs. This review focuses on how TRPV4 senses environmental cues and thereby initiates and maintains calcium oscillations, critical for responses to organ injury, tissue repair, and fibrosis. We provide a summary of TRPV4-induced calcium oscillations in distinct organ systems, along with the upstream and downstream signaling pathways involved. In addition, we delineate current animal and disease models supporting TRPV4 research and shed light on potential therapeutic targets for modulating TRPV4-induced calcium oscillation to promote tissue repair while reducing tissue fibrosis.
Genetic Diversity of Grapevine Virus A in Three Australian Vineyards Using Amplicon High Throughput Sequencing (Amplicon-HTS)

Shiraz disease (SD) is one of the most destructive viral diseases of grapevines in Australia and is known to cause significant economic loss to local growers. Grapevine virus A (GVA) was reported to be the key pathogen associated with this disease. This study aimed to better understand the diversity of GVA variants both within and between individual SD and grapevine leafroll disease (LRD) affected grapevines located at vineyards in South Australia. Amplicon high throughput sequencing (Amplicon-HTS) combined with median-joining networks (MJNs) was used to analyze the variability in specific gene regions of GVA variants. Several GVAII variant groups contain samples from both vineyards studied, suggesting that these GVAII variants were from a common origin. Variant groups analyzed by MJNs using the overall data set denote that there may be a possible relationship between variant groups of GVA and the geographical location of the grapevines.
A Multi-Omics Analysis Revealed the Diversity of the MYB Transcription Factor Family’s Evolution and Drought Resistance Pathways

The MYB transcription factor family can regulate biological processes such as ABA signal transduction to cope with drought stress, but its evolutionary mechanism and the diverse pathways of response to drought stress in different species are rarely reported. In this study, a total of 4791 MYB family members were identified in 908,757 amino acid sequences from 12 model plants or crops using bioinformatics methods. It was observed that the number of MYB family members had a linear relationship with the chromosome ploidy of species. A phylogenetic analysis showed that the MYB family members evolved in subfamily clusters. In response to drought stress, the pathways of MYB transcription factor families exhibited species-specific diversity, with closely related species demonstrating a higher resemblance. This study provides abundant references for drought resistance research and the breeding of wheat, soybean, and other plants.
3D Road Boundary Extraction Based on Machine Learning Strategy Using LiDAR and Image-Derived MMS Point Clouds

The precise extraction of road boundaries is an essential task to obtain road infrastructure data that can support various applications, such as maintenance, autonomous driving, vehicle navigation, and the generation of high-definition maps (HD map). Despite promising outcomes in prior studies, challenges persist in road extraction, particularly in discerning diverse road types. The proposed methodology integrates state-of-the-art techniques like DBSCAN and RANSAC, aiming to establish a universally applicable approach for diverse mobile mapping systems. This effort represents a pioneering step in extracting road information from image-based point cloud data. To assess the efficacy of the proposed method, we conducted experiments using a large-scale dataset acquired by two mobile mapping systems on the Yıldız Technical University campus; one system was configured as a mobile LiDAR system (MLS), while the other was equipped with cameras to operate as a photogrammetry-based mobile mapping system (MMS). Using manually measured reference road boundary data, we evaluated the completeness, correctness, and quality parameters of the road extraction performance of our proposed method based on two datasets. The completeness rates were 93.2% and 84.5%, while the correctness rates were 98.6% and 93.6%, respectively. The overall quality of the road curb extraction was 93.9% and 84.5% for the two datasets. Our proposed algorithm is capable of accurately extracting straight or curved road boundaries and curbs from complex point cloud data that includes vehicles, pedestrians, and other obstacles in urban environment. Furthermore, our experiments demonstrate that the algorithm can be applied to point cloud data acquired from different systems, such as MLS and MMS, with varying spatial resolutions and accuracy levels.
Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment.

AIM The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes. METHODS We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography. RESULTS Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery. CONCLUSION This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.
Exploration of Extension Research to Promote Genetic Improvement in Cattle Production: Systematic Review

Simple Summary Genetic improvement in the cattle production industry is a driver of productive, economic and sustainable improvements. Farmers have genetic tools that make it easier for them to make decisions considering their social and productive reality. Although there are new techniques and tools to improve livestock genetics, and despite efforts to promote their use through agricultural extension, there is still a gap between the creation of these tools and their actual use by livestock farmers. This review was conducted to understand how genetic improvement tools in livestock production are being promoted globally. Most studies carried out surveys or interviews with farmers and stakeholders on both social and productive topics. Although social factors are known to affect whether these improvements are adopted or not, the use of social theories to understand this is still in its incipient. More research is needed to understand how to successfully promote the use of these genetic tools in specific productive regions. Abstract In the cattle industry, tools for genetic improvement play a crucial role in animal selection. The changing circumstances faced by farmers and the significant part agricultural extension plays in these changes must be considered. Despite progress in genetic selection tools and the push for their adoption through extension services, a disconnect persists between the development of new strategies and tools for genetic improvement and their adoption by livestock farmers. This systematic review is designed to globally investigate the methodology and outcomes of extension research aimed at advancing genetic improvement in beef cattle. Adhering to PRISMA guidelines, a search was conducted across four databases for studies published from January 2012 to June 2023. Twenty-one articles were selected and reviewed. The research design in the articles predominantly employed mixed methods, utilizing both quantitative and qualitative approaches. While social factors are acknowledged as influencers in the adoption process, the application of theories or frameworks from social sciences is still in its early stages. To successfully implement extension activities that promote the use of genetic tools in cattle for a specific production region, more participatory research is required where farmers are actively involved.
A meiosis-specific AAA+ assembly reveals repurposing of ORC during budding yeast gametogenesis

ORC (Orc1-6) is an AAA+ complex that loads the AAA+ MCM helicase to replication origins. Orc1, a subunit of ORC, functionally interacts with budding yeast Pch2, a meiosis-specific AAA+ protein. Pch2 regulates several chromosomal events of gametogenesis, but mechanisms that dictate Pch2 function remain poorly understood. We demonstrate that ORC directly interacts with an AAA+ Pch2 hexamer. The ORC-Pch2 assembly is established without Cdc6, a factor crucial for ORC-MCM binding. Biochemical analysis suggests that Pch2 utilizes ORC’s Cdc6-binding interface and employs its non-enzymatic NH2-terminal domain and AAA+ core to engage ORC. In contrast to phenotypes observed upon Orc1 impairment, nuclear depletion of other subunits of ORC does not lead to Pch2-like phenotypes, indicating that ORC integrity per se is not required to support Pch2 function. We thus reveal functional interplay between Pch2 and ORC, and uncover the repurposing of ORC to establish a non-canonical and meiosis-specific AAA+ assembly.
Evaluation of the Drug-Induced Liver Injury Potential of Saxagliptin through Reactive Metabolite Identification in Rats

A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin–cysteine adduct was also found in saxagliptin-administered male Sprague–Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury.
Rapid effects of valproic acid on the fetal brain transcriptome: Implications for brain development and autism

There is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration revealed that VPA significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders (NDDs) such as autism as well as neurogenesis, axon growth and synaptogenesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 399 autism risk genes was significantly altered by VPA as was expression of 252 genes that have been reported to play fundamental roles in the development of the nervous system but are not otherwise linked to autism. The goal of this study was to identify mouse genes that are: (a) significantly up- or down-regulated by VPA in the fetal brain and (b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain. The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in NDDs such as autism.