Miracle-dz/UniFAR-FTUs huggingface dataset:
Transplantation of Wnt3a-modified neural stem cells promotes neural regeneration and functional recovery after spinal cord injury via Wnt-Gli2 pathway

Neural stem cell (NSCs) transplantation has great potential in the treatment of spinal cord injury (SCI). Previous studies have indicated that the Wnt pathway could regulate the expression of basic helix-loop-helix (bHLH) family factor Hes5 and Mash1 in NSCs, but not through the notch intracellular domain. This suggests that there are other signals involved in this process. The aim of this study was to investigate the role of Wnt-Gli2 pathway in the treatment of SCI by transplanting neural stem cells. NSCs were isolated from the striata of embryonic day 14 mice. Activation of the Wnt pathway was achieved using Wnt3a protein, while Gli2 was inhibited using Gli2-siRNA. Expression levels of Gli2 and bHLH factors were assessed using western blotting. NSCs proliferation was evaluated using CCK-8 assay, and neural differentiation was determined by immunofluorescence staining. Finally, the modified NSCs were transplanted into mice with SCI, and their effects were assessed using behavioral and histological tests. Our results demonstrated that Wnt3a promoted the expression of Mash1 through Gli2. Moreover, the expression of Ngn1 and Hes1 was up-regulated, while Hes5 was down-regulated. Wnt3a also promoted NSCs proliferation and neural differentiation through this signaling pathway. In vivo experiments showed that NSCs transplantation mediated by Wnt3a-Gli2 signaling increased the number of neurons and resulted in improved Basso Mouse Scale scores. In conclusion, our findings suggest that Gli2 plays a role in mediating the regulation of Wnt3a signaling on promoting NSCs proliferation and neural differentiation. This pathway is therefore important in NSCs-mediated SCI recovery.
Association of microRNA Polymorphisms with Toxicities Induced by Methotrexate in Children with Acute Lymphoblastic Leukemia

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5′-regulatory regions of genes. Recent studies have demonstrated a significant role of microRNAs (miRNAs) in the transport and metabolism of drugs and in the regulation of target genes. In the last few years, the number of annotated miRNAs has continually risen, in addition to the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.
Roles of peroxisome proliferator‐activated receptors in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC), the main pathological type of liver cancer, is linked to risk factors such as viral hepatitis, alcohol intake and non‐alcoholic fatty liver disease (NAFLD). Recent advances have greatly improved our understanding that NAFLD is playing a major risk factor for HCC. Peroxisome proliferator‐activated receptors (PPARs) are a class of transcription factors divided into three subtypes: PPARα (PPARA), PPARδ/β (PPARD) and PPARγ (PPARG). As important nuclear receptors, PPARs are involved in many physiological processes, and PPARs can improve NAFLD by regulating lipid metabolism, accelerating fatty acid oxidation and inhibiting inflammation. In recent years, some studies have shown that PPARs can participate in the occurrence and development of HCC by regulating metabolic pathways. In addition, PPAR modulators have been reported to inhibit the proliferation and metastasis of HCC cells and can enhance the curative effect of conventional treatments. This article reviews the role of PPARs in the occurrence and development of HCC, as well as its value in the diagnosis, treatment and prognosis of HCC, in order to provide directions for future research.
Propagação de Alternanthera dentata pelo processo de estaquia

-1 ), tres tipos de estacas (apicais, medianas e basais) e duas epocas do ano (chuvosa e seca). Foram avaliadas: porcentagem de estacas enraizadas, sobrevivencia de estacas, numero de brotos por estaca, comprimento medio da maior raiz (cm), massa seca de parte aerea (g) e de raiz (g). A dose de 1000 mg kg -1 de AIB pode ser indicada para propagacao de A. dentata Abstract The experiment was carried out aiming to evaluate the plant propagation of A. dentata through cutting process with indol-butyric acid (IBA) under different seasons and cutting types, in Bom Jesus County, Piaui State, Brazil. The experimental design was completely randomized with treatments distributed in a factorial arrangement (4 x 3 x 2) referring to IBA doses (0, 1000, 3000 e 5000 mg kg -1 ), cutting types (apical, median and basal) and year season (rainy and dry period). The following variables were evaluated for cuttings: rooting percentage, survival percentage, number of buds, length of longer root (cm), dry mass of shoots (g) and roots (g). The 1000 mg kg -1 IBA dose could be indicated for cutting propagation of A. dentata. Apical and median cutting are the most recommended for seedling production. Rainy season is the the most favorable for seedling production of A. dentata by cuttings.
The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene‐induced overexpression of AQP3 and Notch1 in HaCaT cells

The aim of this study was twofold: (1) evaluate the effect of benzo[a]pyrene (BaP) on expression levels of AQP3 and Notch1 genes in HaCaT cells exposed “in vitro” and (2) investigate the possible biological role of assessed genes by bioinformatics methods. Cells were exposed to increasing concentrations of BaP (0.0–4.0 μM) for 1–4 days. After treatments, cell viability and expression levels of AhR, CYP1A1, AQP3, and Notch1 genes were evaluated. The possible biological role of assessed genes was evaluated using bioinformatics tools. Low cytotoxicity in HaCaT cells dosed with BaP was detected. A significant overexpression (p < .05) of CYP1A1, AQP3, and Notch1 was found in exposed HaCaT cells. The gene expression upregulation was dependent on AhR activation. The bioinformatics analysis showed that these genes were enriched in related cancer signaling pathways. The findings suggest that AQP3 and Notch1 are upregulated by AhR activation in HaCaT cells exposed to BaP.
IGF2BP2 promotes glycolysis and hepatocellular carcinoma stemness by stabilizing CDC45 mRNA via m6A modification

ABSTRACT A growing number of studies have shown the prognostic importance of Cell division cycle protein 45 (CDC45) in hepatocellular carcinoma (HCC). This study aims to investigate the biological function and mechanism of CDC45 in HCC. The differential expression and prognostic significance of CDC45 in HCC and normal tissues were analyzed by bioinformatics. CDC45 was knocked down and the biological effects of CDC45 in HCC in vitro and in vivo were measured. Subsequently, using RNA m6A colorimetry and Methylated RNA Immunoprecipitation (MeRIP), the levels of m6A modification of total RNA and CDC45 were evaluated in cells. RIP was applied to establish that CDC45 and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) interact. A test using actinomycin D was performed to gauge the stability of the CDC45 mRNA. Furthermore, the regulatory role of IGF2BP2 on CDC45 expression in HCC progression was explored by overexpressing IGF2BP2. High expression of CDC45 was correlated with poor prognosis in HCC patients. Knocking down CDC45 inhibited HCC cell proliferation, migration, invasion, EMT, stemness, and glycolysis, and promoted apoptosis, which was verified through in vitro experiments. Additionally, IGF2BP2 was highly expressed in HCC cells, and it was found to interact with CDC45. Knocking down IGF2BP2 resulted in reduced stability of CDC45 mRNA. Moreover, overexpression of IGF2BP2 promoted HCC cell proliferation, migration, invasion, EMT, stemness, and glycolysis, while inhibiting apoptosis, which was reversed by knocking down CDC45. In general, IGF2BP2 promoted HCC glycolysis and stemness by stabilizing CDC45 mRNA via m6A modification.
Primary Systemic Vasculitides as a Cause of Group IV Pulmonary Hypertension

The primary systemic vasculitides are rare diseases characterized by vessel wall inflammation. Isolated pulmonary vasculitis, large-vessel vasculitis, and Behçet’s disease are mimickers of chronic thromboembolic pulmonary hypertension (CTEPH); group IV pulmonary hypertension (PH) can occur as a devastating complication in the course of these diseases. Pulmonary endarterectomy, balloon angioplasty, anticoagulation and pulmonary vasodilator agents are the main treatment options for CTEPH. There is no specific recommendation for the treatment of patients having group IV PH due to primary systemic vasculitides. We reviewed herein data about group IV PH due to primary systemic vasculitides.
Seismic attenuation structure associated with episodic tremor and slip zone beneath Shikoku and the Kii peninsula, southwestern Japan, in the Nankai subduction zone

The three‐dimensional seismic attenuation structure (frequency‐independent Q) beneath southwestern Japan was analyzed using t* estimated by applying the S coda wave spectral ratio method to the waveform data from a dense permanent seismic network. The seismic attenuation (Qp−1) structure is clearly imaged for the region beneath Shikoku, the Kii peninsula, and eastern Kyushu at depths down to approximately 50 km. At depths of 5 to 35 km, the seismic attenuation structure changes at the Median tectonic line and other geological boundaries beneath Shikoku and the southwestern Kii peninsula. High‐Qp zones within the lower crust of the overlying plate are found just above the slip regions at the centers of the long‐term slow‐slip events (SSEs) beneath the Bungo and Kii channels and central Shikoku. Beneath central Shikoku, within the overlying plate, a high‐Qp zone bounded by low‐Qp zones is located from the land surface to the plate interface of the subducting plate. The high‐Qp zone and low‐Qp zones correspond to high‐Vp and low‐Vp zones of previous study, respectively. The boundaries of the high‐ and low‐Qp zones are consistent with the segment boundaries of tremors (segment boundaries of short‐term SSEs). These results indicated that the locations of the long‐ and short‐term SSEs could be limited by the inhomogeneous distribution of the materials and/or condition of the overlying plate, which is formed due to geological and geographical process. The heterogeneity of materials and/or condition within the fore‐arc crust possibly makes an effect on inhomogeneous rheological strength distribution on the interface.
Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation

Abstract Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.
Sequence-ensemble-function relationships for disordered proteins in live cells

Intrinsically disordered protein regions (IDRs) are ubiquitous across all kingdoms of life and play a variety of essential cellular roles. IDRs exist in a collection of structurally distinct conformers known as an ensemble. An IDR’s amino acid sequence determines its ensemble, which in turn can play an important role in dictating molecular function. Yet a clear link connecting IDR sequence, its ensemble properties, and its molecular function in living cells has not been directly established. Here, we set out to test this sequence-ensemble-function paradigm using a novel computational method (GOOSE) that enables the rational design of libraries of IDRs by systematically varying specific sequence properties. Using ensemble FRET, we measured the ensemble dimensions of a library of rationally designed IDRs in human-derived cell lines, revealing how IDR sequence influences ensemble dimensions in situ. Furthermore, we show that the interplay between sequence and ensemble can tune an IDR’s ability to sense changes in cell volume - a de novo molecular function for these synthetic sequences. Our results establish biophysical rules for intracellular sequence-ensemble relationships, enable a new route for understanding how IDR sequences map to function in live cells, and set the ground for the design of synthetic IDRs with de novo function.
Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia

Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and IL‐10, in “FD” rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE).
Seismic and mechanical attributes of lithospheric deformation and subduction in western Canada

Convergent continental margins are regions of intense deformation caused by the interaction of oceanic plates with continents. The spatial extent of deformation is broadly commensurate with the specific time scale of the causative phenomenon. For example, subduction-related short-term deformation is limited to <200 km from the margin, whereas long-term plate convergence cause deformation over ∼1000 km landward. Deformation is thus manifested in multiple ways, with attributes depending on the scale of measurement. In this thesis we investigate the use of two geophysical approaches in the study of deformation: 1) The analysis of potential-field anomalies to derive estimates of the elastic thickness (Te) of the lithosphere, and 2) The structural study of past and present subduction systems using seismic observations and modelling. Both approaches involve the development of appropriate methodologies for data analysis and modelling, and their application to the western Canadian landmass. Our findings are summarized as follows: 1) We develop a wavelet-based technique to map variations in Te and its anisotropy; 2) We show how a step-wise transition in Te and its anisotropy from the Cordillera to the Craton is a major factor influencing lithospheric deformation; 3) We implement a waveform modelling tool that includes the effects of structural heterogeneity and anisotropy for teleseismic applications, and use it to model the signature of a fossil subduction zone in a Paleoproterozoic terrane; 4) We use teleseismic recordings to map slab edge morphology in northern Cascadia and show how slab window tectonism and slab stretching led to the creation of the oceanic Explorer plate; 5) We use seismic signals from the subducting oceanic crust to calculate elevated Poisson’s ratio and infer high pore-fluid pressures and a low-permeability plate boundary within the forearc region of northern Cascadia.
Characterization of Expression and Function of the Formins FHOD1, INF2, and DAAM1 in HER2-Positive Breast Cancer

Purpose Human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as trastuzumab, benefit patients with HER2-positive metastatic breast cancer; however, owing to traditional pathway activation or alternative signaling, resistance persists. Given the crucial role of the formin family in shaping the actin cytoskeleton during cancer progression, these proteins may function downstream of the HER2 signaling pathway. Our aim was to uncover the potential correlations between formins and HER2 expression using a combination of public databases, immunohistochemistry, and functional in vitro assays. Methods Using online databases, we identified a negative prognostic correlation between specific formins mRNA expression in HER2-positive cancers. To validate these findings at the protein level, immunohistochemistry was performed on HER2 subtype breast cancer tumors to establish the links between staining patterns and clinical characteristics. We then knocked down individual or combined formins in MDA-MB-453 and SK-BR-3 cells and investigated their effects on wound healing, transwell migration, and proliferation. Furthermore, we investigated the effects of erb-b2 receptor tyrosine kinase 2 (ERBB2)/HER2 small interfering RNA (siRNA)-mediated knockdown on the PI3K/Akt and MEK/ERK1 pathways as well as on selected formins. Results Our results revealed that correlations between INF2, FHOD1, and DAAM1 mRNA expression and ERBB2 in HER2-subtype breast cancer were associated with worse outcomes. Using immunohistochemistry, we found that high FHOD1 protein expression was linked to higher histological grades and was negatively correlated with estrogen and progesterone receptor positivity. Upon formins knockdown, we observed effects on wound healing and transwell migration, with a minimal impact on proliferation, which was evident through single and combined knockdowns in both cell lines. Notably, siRNA-mediated knockdown of HER2 affected FHOD1 and INF2 expression, along with the phosphorylated Akt/MAPK states. Conclusion Our study highlights the roles of FHOD1 and INF2 as downstream effectors of the HER2/Akt and HER2/MAPK pathways, suggesting that they are potential therapeutic targets in HER2-positive breast cancer.
Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men

Abstract Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women. Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.
Streptomyces global regulators AfsR and AfsS interact to co‐regulate antibiotic production and morphological development

Abstract Streptomyces species have a complex life cycle and are the producers of ~70% of commercial antibiotics. Global regulators AfsR and AfsS are widespread among Streptomyces and have been identified as key activators of antibiotic production in several species. However, their roles as repressors of antibiotic production are unclear; in particular, nothing is known regarding the regulatory mechanism of AfsS, despite many decades of research, because it has no DNA‐binding domain. Here, we demonstrate that AfsR and AfsS negatively regulate avermectin production and morphological development in the industrially important species S. avermitilis. AfsR directly represses ave structural genes (aveA1, aveA4), cluster‐situated activator gene aveR, and eight key developmental genes, whereas it directly activates afsS, aco (for autoregulator avenolide biosynthesis), and avaR1 (encoding avenolide receptor). GST pull‐down, microscale thermophoresis, co‐immunoprecipitation, and chromatin immunoprecipitation‐quantitative PCR assays demonstrated that AfsS interacts with AfsR to co‐regulate target genes involved in avermectin production and development and that this interaction requires intact AfsS repeated sequences and enhances the binding affinity of AfsR to target promoters. AfsR/AfsS interaction also occurs in model species S. coelicolor and S. roseosporus (producer of daptomycin, a cyclic lipopeptide antibiotic widely used for the treatment of human infections), suggesting that such interaction is conserved in Streptomyces species. The master developmental repressor BldD acts as a direct activator of both afsR and afsS. Deletion of afsR or afsS strongly enhances avermectin production in wild‐type and industrial S. avermitilis strains. Our findings demonstrate novel regulatory roles and mechanisms of AfsR and AfsS in Streptomyces and facilitate methods for antibiotic overproduction.