Miracle-dz/UniFAR-FTUs huggingface dataset:
The Protein Kinase Inhibitor Midostaurin Improves Functional Neurological Recovery and Attenuates Inflammatory Changes Following Traumatic Cervical Spinal Cord Injury

Traumatic spinal cord injury (SCI) impairs neuronal function and introduces a complex cascade of secondary pathologies that limit recovery. Despite decades of preclinical and clinical research, there is a shortage of efficacious treatment options to modulate the secondary response to injury. Protein kinases are crucial signaling molecules that mediate the secondary SCI-induced cellular response and present promising therapeutic targets. The objective of this study was to examine the safety and efficacy of midostaurin—a clinically-approved multi-target protein kinase inhibitor—on cervical SCI pathogenesis. High-throughput analyses demonstrated that intraperitoneal midostaurin injection (25 mg/kg) in C6/7 injured Wistar rats altered the local inflammasome and downregulated adhesive and migratory genes at 24 h post-injury. Treated animals also exhibited enhanced recovery and restored coordination between forelimbs and hindlimbs after injury, indicating the synergistic impact of midostaurin and its dimethyl sulfoxide vehicle to improve functional recovery. Furthermore, histological analyses suggested improved tissue preservation and functionality in the treated animals during the chronic phase of injury. This study serves as a proof-of-concept experiment and demonstrates that systemic midostaurin administration is an effective strategy for mitigating cervical secondary SCI damage.
Dysregulation of PI3K/Akt/PTEN Pathway in Canine Mammary Tumor

Simple Summary The importance of the PI3K/Akt/PTEN pathway in canine mammary tumor has recently been highlighted due to the finding of frequent PIK3CA mutation. Effect of PIK3CA mutation to expression of downstream molecules has never been investigated in canine mammary tumors. We found that frequency of PIK3CA H1047R mutation was 14.3% using Sanger sequencing in canine mammary tumors, and downstream molecules Akt2, p-Akt, and PTEN were dysregulated in mammary tumors when compared to normal mammary gland. However, we could not find any significant relevance between PIK3CA H1047R mutation and expression of downstream molecules, except a paradoxical higher level of PTEN in PIK3CA-mutated tumors. We suggest that dysregulation of PI3K/Akt/PTEN pathway components is a feature in canine mammary tumors, but not directly associated with PIK3CA H1047R mutation except for the expression of PTEN. Further study is necessary to find the role of PIK3CA mutation in the regulation of downstream molecules to improve our understanding and therapeutic approach for canine mammary tumors. Abstract The PI3K/Akt/PTEN axis is one of the most important signaling pathways in tumorigenesis. Recently, mutation of PIK3CA has been highlighted due to the similarities of mutational hotspots in both dogs and humans. PIK3CA H1047R (c.3140A > G) has been discovered as the most common mutational hot spot in canine mammary tumor in recent studies, while the feature of PIK3CA-mutated canine mammary tumor is obscure. Methods: A total of 83 mammary samples classified as normal (n = 13), adenoma (n = 25), low-grade carcinoma (n = 21), and high-grade carcinoma (n = 24) were included in this study. Genomic DNA from each sample was extracted, amplified by conventional PCR, and analyzed through Sanger sequencing. Analysis for the expression of PIK3CA, Akt, p-Akt, and PTEN was performed by immunohistochemistry, and of Akt2 by RNA in situ hybridization. Results: PIK3CA H1047R mutation was detected in 14.3% (10/70) of tumor samples. Dysregulation of p-Akt, Akt2, and PTEN was observed in mammary tumor samples, but only PTEN dysregulation was associated with PIK3CA H1047R mutation. Conclusions: The present study showed that dysregulation of components in the PI3K/Akt/PTEN pathway is a feature of canine mammary tumors, but this dysregulation is not directly correlated to the PIK3CA H1047R mutation except for PTEN expression.
Molecular gut content analysis indicates the inter‐ and intra‐guild predation patterns of spiders in conventionally managed vegetable fields

Abstract Inter‐ and intra‐guild interactions are important in the coexistence of predators and their prey, especially in highly disturbed vegetable cropping systems with sporadic food resources. Assessing the dietary range of a predator taxon characterized by diverse foraging behavior using conventional approaches, such as visual observation and conventional molecular approaches for prey detection, has serious logistical problems. In this study, we assessed the prey compositions and compare the dietary spectrum of a functionally diverge group of predators—spiders—to characterize their trophic interactions and assess biological control potential in Brassica vegetable fields. We used high‐throughput sequencing (HTS) and biotic interaction networks to precisely annotate the predation spectrum and highlight the predator–predator and predator–prey interactions. The prey taxa in the gut of all spider families were mainly enriched with insects (including dipterans, coleopterans, orthopterans, hemipterans, and lepidopterans) with lower proportions of arachnids (such as Araneae) along with a wide range of other prey factions. Despite the generalist foraging behavior of spiders, the community structure analysis and interaction networks highlighted the overrepresentation of particular prey taxa in the gut of each spider family, as well as showing the extent of interfamily predation by spiders. Identifying the diverse trophic niche proportions underpins the importance of spiders as predators of pests in highly disturbed agroecosystems. More specifically, combining HTS with advanced ecological community analysis reveals the preferences and biological control potential of particular spider taxa (such as Salticidae against lepidopterans and Pisauridae against dipterans), and so provides a valuable evidence base for targeted conservation biological control efforts in complex trophic networks.
Characterization of the Striatal Extracellular Matrix in a Mouse Model of Parkinson’s Disease

Parkinson’s disease’s etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies. The enriched striatal extracellular matrix from a mouse model of Parkinson’s disease was characterized by Raman spectroscopy. We found a matrix fingerprint of increased oxalate content and oxidative modifications. To uncover the effects of these changes on brain cells, we morphologically characterized the primary microglia used to repopulate this matrix and further quantified the effects on cellular mechanical stress by an intracellular fluorescence resonance energy transfer (FRET)-mechanosensor using the U-2 OS cell line. Our data suggest changes in microglia survival and morphology, and a decrease in cytoskeletal tension in response to the modified matrix from both hemispheres of 6-hydroxydopamine (6-OHDA)-lesioned animals. Collectively, these data suggest that the extracellular matrix is modified, and underscore the need for its thorough investigation, which may reveal new ways to improve therapies or may even reveal new therapies.
Suspension of Amorphous Calcium Phosphate Nanoparticles Impact Commitment of Human Adipose-Derived Stem Cells In Vitro

Simple Summary Calcium phosphate is an important component in natural bone. Bone defects caused by trauma or resection of tumors demand bone substitutes to close the defect. One viable option is to use a scaffold material seeded with stem cells. Stem cells can differentiate towards bone cells (osteoblasts), among other cell types. To trigger stem cells towards the osteoblast type of cell, particular supplementation of the culture medium is needed. This study tests whether calcium phosphate nanoparticles can induce a commitment towards the osteoblast type of cell. In addition, we test for other commitments, such as endothelial cell, chondrocyte, or adipocyte commitment. After 1 or 2 weeks, with either 5 or 50 µg/mL nanoparticles in the culture medium, gene expression is analyzed. We find a significant increase of two specific bone marker genes after two weeks in 50 µg/mL nanoparticles compared to 5 µg/mL for two out of three tested human donors of adipose-derived stem cells. Moreover, endothelial cell commitment is also induced. Hence, such nanoparticles have the potential to trigger osteogenic and endothelial cell commitment. Abstract Amorphous calcium phosphate (aCaP) nanoparticles may trigger the osteogenic commitment of adipose-derived stem cells (ASCs) in vitro. The ASCs of three human donors are investigated using basal culture medium DMEM to either 5 or 50 µg/mL aCaP nanoparticles suspension (control: no nanoparticles). After 7 or 14 days, stem cell marker genes, as well as endothelial, osteogenic, chondrogenic, and adipogenic genes, are analyzed by qPCR. Free calcium and phosphate ion concentrations are assessed in the cell culture supernatant. After one week and 5 µg/mL aCaP, downregulation of osteogenic markers ALP and Runx2 is found, and averaged across the three donors. Our results show that after two weeks, ALP is further downregulated, but Runx2 is upregulated. Endothelial cell marker genes, such as CD31 and CD34, are upregulated with 50 µg/mL aCaP and a 2-week exposure. Inter-donor variability is high: Two out of three donors show a significant upregulation of ALP and Runx2 at day 14 with 50 µg/mL aCaP compared to 5 µg/mL aCaP. Notably, all changes in stem cell commitment are obtained in the absence of an osteogenic medium. While the chemical composition of the culture medium and the saturation status towards calcium phosphate phases remain approximately the same for all conditions, gene expression of ASCs changes considerably. Hence, aCaP nanoparticles show the potential to trigger osteogenic and endothelial commitment in ASCs.
Effect of combined intrathecal/intravenous injection of bone marrow derived stromal cells in platelet-rich plasma on spinal cord injury in companion animals

Background: Companion animals are prone to spinal cord injuries commonly associated with severe locomotor and sensory complications, which can escalate to a state of irreversible paralysis. Stem cell therapies propose a hope for treating spinal cord injuries via differentiation into neurons and associated glial cells, halting the immune attacks, inhibiting apoptosis and necrosis, and secretion of neurotrophic factors that stimulate the regeneration process. Aim: The study aims to evaluate the use of autologous bone marrow derived stromal cells in platelet-rich plasma carrier for selected clinical cases having chronic spinal cord injuries in dogs and cats via a one-time combined intrathecal/intravenous injection. Methods: Cells were injected in five dogs and three cats suffering from disc protrusion leading to spinal cord injury and in thosewho did not respond to conventional treatment during a clinical trial. Results: Results indicated that the transplanted cells led to the restoration of the weight bearing locomotor function and spinal reflexes in a period less than 90 days with physical rehabilitation. The treatment showed minor changes in the magnetic resonance images of extruded discs. Conclusion: This study concluded that the combined intrathecal/intravenous injection of bone marrow stromal cells is a safe and promising procedure for treating chronic spinal cord injuries in companion animals.
EST‐SSR‐based landscape genetics of Pseudotaxus chienii, a tertiary relict conifer endemic to China

Abstract Pseudotaxus chienii, belonging to the monotypic genus Pseudotaxus (Taxaceae), is a relict conifer endemic to China. Its populations are usually small and patchily distributed, having a low capacity of natural regeneration. To gain a clearer understanding of how landscape variables affect the local adaptation of P. chienii, we applied EST‐SSR markers in conjunction with landscape genetics methods: (a) to examine the population genetic pattern and spatial genetic structure; (b) to perform genome scan and selection scan to identify outlier loci and the associated landscape variables; and (c) to model the ecological niche under climate change. As a result, P. chienii was found to have a moderate level of genetic variation and a high level of genetic differentiation. Its populations displayed a significant positive relationship between the genetic and geographical distance (i.e., “isolation by distance” pattern) and a strong fine‐scale spatial genetic structure within 2 km. A putatively adaptive locus EMS6 (functionally annotated to cellulose synthase A catalytic subunit 7) was identified, which was found significantly associated with soil Cu, K, and Pb content and the combined effects of temperature and precipitation. Moreover, P. chienii was predicted to experience significant range contractions in future climate change scenarios. Our results highlight the potential of specific soil metal content and climate variables as the driving force of adaptive genetic differentiation in P. chienii. The data would also be useful to develop a conservation action plan for P. chienii.
Predicting Aggressive Multiple Sclerosis With Intrathecal IgM Synthesis Among Patients With a Clinically Isolated Syndrome

Objective To determine the best method to measure intrathecal immunoglobulin (Ig) M synthesis (ITMS), a biomarker of worse prognosis in multiple sclerosis (MS). We compared the ability for predicting a poor evolution of 4 methods assessing ITMS (IgM oligoclonal bands [OCMBs], lipid-specific OCMBs [LS-OCMBs], Reibergram, and IgM index) in patients with a clinically isolated syndrome (CIS). Methods Prospective study with consecutive patients performed at a referral MS center. We used unadjusted and multivariate Cox regressions for predicting a second relapse, Expanded Disability Status Scale (EDSS) scores of 4 and 6, and development of secondary progressive MS (SPMS). Results A total of 193 patients were included, with a median (interquartile range) age of 31 (25–38) years and a median follow-up of 12.9 years. Among all methods, only OCMB, LS-OCMB, and Reibergram significantly identified patients at risk of some of the pre-established outcomes, being LS-OCMB the technique with the strongest associations. Adjusted hazard ratio (aHR) of LS-OCMB for predicting a second relapse was 2.50 (95% CI 1.72–3.64, p < 0.001). The risk of reaching EDSS scores of 4 and 6 and SPMS was significantly higher among patients with LS-OCMB (aHR 2.96, 95% CI 1.54–5.71, p = 0.001; aHR 4.96, 95% CI 2.22–11.07, p < 0.001; and aHR 2.31, 95% CI 1.08–4.93, p = 0.03, respectively). Conclusions ITMS predicts an aggressive MS at disease onset, especially when detected as LS-OCMB. Classification of Evidence This study provides Class II evidence that lipid-specific IgM oligoclonal bands can predict progression from CIS to MS and a worse disease course over a follow-up of at least 2 years.
Effects of Cold Exposure on Performance and Skeletal Muscle Fiber in Weaned Piglets

Simple Summary Muscle fiber is the basic unit of muscle composition. The type of skeletal muscle fiber can be transformed from fast-twitch to slow-switch or vice versa by internal and external factors. Low-temperature is one of the major environmental factors that influences the growth performance of animals. However, the influence of low-temperature on weaned piglets’ skeletal muscle fiber, and whether this influence is related to mitochondrial function and antioxidant capacity, has not been reported. Our results indicated that low temperature could negatively affect growth performance and nutrient digestibility in weaned piglets. Moreover, evidence was provided to show that low-temperature induces a shift toward oxidative muscle fibers, which may occur through mitochondrial function regulation and increased antioxidative capacity. Abstract Low-temperature is one of the most significant risks for the animal industry. In light of this, the present study aimed to explore the effects of low-temperature on growth performance, nutrient digestibility, myofiber types and mitochondrial function in weaned piglets. A total of sixteen 21-day-old male Duroc × Landrace × Yorkshire (DLY) piglets were randomly divided into a control group (CON, 26 ± 1 °C) and a low-temperature group (LT, 15 ± 1 °C), with eight duplicate piglets in each group. The trial period lasted for 21 days. We showed that LT not only increased the ADFI (p < 0.05), as well as increasing the diarrhea incidence and diarrhea index of weaned piglets in the early stage of the experiment (p < 0.01), but it also decreased the apparent digestibility of crude protein (CP), organic matter (OM) and dry matter (DM) (p < 0.05). Meanwhile, in the LT group, the mRNA expression of MyHC IIa (p < 0.05) in longissimus dorsi muscle (LM) and MyHC I (p < 0.01) in psoas muscle (PM) were increased, while the mRNA expression of MyHC IIx in PM was decreased (p < 0.05). In addition, LT increased the mRNA expression of mitochondrial function-related genes citrate synthase (CS) and succinate dehydrogenase-b (SDHB) in LM, as well as increased the mRNA expression of CS (p < 0.05) and carnitine palmitoyl transferase-1b (CPT-1b) (p < 0.01) in PM. Furthermore, LT increased the T-AOC activity in serum and LM (p < 0.01), as well as increased the T-SOD activity in PM (p < 0.05). Taken together, these findings showed that low-temperature could negatively affect the growth performance and nutrient digestibility, but resulted in a shift toward oxidative muscle fibers, which may occur through mitochondrial function regulation.
Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

Enteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold–oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10−7 M, ≥1.4 × 10−14 g/mL) initiates gold–oligonucleotide nanoconstruct disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow assays that utilise gold–oligonucleotide nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (<60 s), and could be interpreted with a bespoke software and hardware electronic interface. We anticipate that our methodology will translate in silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave the way forward in the clinical evaluation of disease and complement existing strategies to overcome antimicrobial resistance.
Design, Synthesis, Characterization and in vivo Antidiabetic Activity Evaluation of Some Chalcone Derivatives

Background Diabetes is one of the growing health problems worldwide, and scientists have been striving to find effective treatment methods. In this regard, chalcones have frequently been targeted by many researchers owing to their diverse biological activities. Methods Here, the Claisen–Schmidt condensation reaction was applied to synthesize five chalcone derivatives. The chalcone derivatives were evaluated for their relative antidiabetic activities in vivo using streptozotocin (STZ)-induced diabetic mice. Besides, the compounds were assessed for their reduction in postprandial hyperglycemia at 50 and 100 mg/kg dose levels against a standard drug, glibenclamide. In addition, the structure–activity relationship (SAR) was analyzed to determine the effect of structural modification in chalcones activity. Results A dose-dependent reduction in postprandial hyperglycemia was observed. The highest reduction in blood glucose level (BGL) was achieved by compound 3 at a dose of 100 mg/kg (39%). This was found to be even higher than glibenclamide (34.5%). In the STZ-induced diabetic animal model, all test compounds showed comparable efficacy with glibenclamide. The SAR analysis revealed that the incorporation of electron-donating groups at position 5 of the benzaldehyde ring and position 2 of the acetophenone ring is promising to increase the antihyperglycemic activities of chalcones. Conclusion The chalcone derivatives considered in this study could be used as potential lead compounds in the discovery of effective drugs to treat diabetes mellitus.
Functional and Stress Response Analysis of Heat Shock Proteins 40 and 90 of Giant River Prawn (Macrobrachium rosenbergii) under Temperature and Pathogenic Bacterial Exposure Stimuli

The aims of this research were to perform molecular characterization and biofunctional analyses of giant river prawn Hsp40 and Hsp90 genes (Mr-hsp40 and Mr-hsp90) under various stress conditions. Comparisons of the nucleotide and amino acid sequences of Mr-hsp40 and Mr-hsp90 with those of other species showed the highest similarity scores with crustaceans. Under normal conditions, expression analysis using quantitative real-time RT-PCR (qRT-PCR) indicated that Mr-hsp40 was highly expressed in the gills and testis, and Mr-hsp90 expression was observed in all tissues, with the highest expression in the ovary. The expression patterns of Mr-hsp40 and Mr-hsp90 transcripts under Aeromonas hydrophila challenge and heat–cold shock conditions were examined in gills, the hepatopancreas and hemocytes, at 0, 3, 6, 12, 24, 48 and 96 h by qRT-PCR. Under bacterial challenge, Mr-hsp40 displayed variable expression patterns in all tissues examined during the tested periods. In contrast, upregulated expression of Mr-hsp90 was quickly observed from 3 to 12 h in the gills and hepatopancreas, whereas obviously significant upregulation of Mr-hsp90 was observed in hemocytes at 12–96 h. Under temperature shock conditions, upregulation of Mr-hsp40 expression was detected in all tested tissues, while Mr-hsp90 expression was quickly upregulated at 3–48 h in all tissues in response to 35 °C conditions, and conditions of 35 and 25 °C stimulated its expression in gills and the hepatopancreas at 12 and 48 h, respectively. Silencing analyses of these two genes were successfully conducted under normal, high-temperature (35 °C) and A. hydrophila infection conditions. Overall, knockdown of Mr-hsp40 and Mr-hsp90 effectively induced more rapid and higher mortality than in the PBS control and GFP induction groups in temperature and infectious treatments. Evidence from this study clearly demonstrated the significant functional roles of Mr-hsp40 and Mr-hsp90, which are crucially involved in cellular stress responses to both temperature and pathogenic bacterial stimuli.