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(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/ß-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/ß-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.
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Alginatos , Gelatina , Hidrogéis , Regeneração , Pele , Cicatrização , Cicatrização/efeitos dos fármacos , Alginatos/química , Animais , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Pele/lesões , Pele/efeitos dos fármacos , Pele/metabolismo , Regeneração/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Masculino , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Ratos , Colágeno/química , Via de Sinalização Wnt/efeitos dos fármacos , HumanosRESUMO
Haematococcus pluvialis has been used to produce the ketocarotenoid antioxidant, astaxanthin. Currently, heterotrophic cultivation of H. pluvialis is limited by slow growth rates. This work aimed to address this challenge by exploring the mechanisms of acetate metabolism in Haematococcus. Chemical mutagenesis and screening identified H. pluvialis strain KREMS 23D-3 that achieved up to a 34.9% higher cell density than the wild type when grown heterotrophically on acetate. An integrative proteomics and phosphoproteomics approach was employed to quantify 4955 proteins and 5099 phosphorylation sites from 2505 phosphoproteins in the wild-type and mutant strains of H. pluvialis. Among them, 12 proteins were significantly upregulated and 22 significantly downregulated in the mutant while phosphoproteomic analysis identified 143 significantly upregulated phosphorylation sites on 106 proteins and 130 downregulated phosphorylation sites on 114 proteins. Upregulation of anaphase-promoting complex phosphoproteins and downregulation of a putative cell cycle division 20 phosphoprotein in the mutant suggests rapid mitotic progression, coinciding with higher cell division rates. Upregulated coproporphyrinogen oxidase and phosphorylated magnesium chelatase in the mutant demonstrated altered nitrogen partitioning toward chlorophyll biosynthesis. The large proportion of differentially expressed phosphoproteins suggests phosphorylation is a key regulator for protein expression and activity in Haematococcus. Taken together, this study reveals the regulation of interrelated acetate metabolic pathways in H. pluvialis and provides protein targets that may guide future strain engineering work.
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Secondary microbial methane could provide a valuable energy source if it were better understood. Although coal seam is an ideal environment for investigating secondary microbial methane, there are few studies to trace the secondary microbial methane of high-rank coals. Here, we collected co-produced water samples from coalbeds in the Qinshui Basin (China) and analyzed the microbial community structure by 16S ribosomal RNA (16S rRNA) amplicon sequencing analysis. 16S rRNA sequencing demonstrated abundant methanogens in coalbeds including 6 orders (Methanobacteriales, Methanococcales, Methanofastidiosales, Methanomassiliicoccale, Methanomicrobiales, and Methanosarciniales) and 22 genera of methanogens. Superheavy DIC (δ13CDIC ranging from -4.2 to 34.8) and abundance of methanogenic microbes in co-produced water revealed the generation of secondary biogenic methane in high-rank coal seams in the Qingshui Basin. Hydrogenotrophic methanogenesis is the main pathway for secondary biogenic methane production. In deeply buried coal seams, biogenic methane is dominated by CO2 and H2 reduction methanogenesis, and in shallow buried coal seams, it may be produced synergistically by hydrocarbon degradation and hydrogenotrophic methanogenic microbes. The study discussed here is important for a better understanding of the generation of secondary microbial methane in high-rank coal.
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Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether T cell-derived IFNγ directly kills infected and tumor target cells, and how this may be regulated. Here, we report that target cell expression of the kinases TBK1 and IKKε regulate IFNγ cytotoxicity by suppressing the ability of T cell-derived IFNγ to kill target cells. In tumor targets lacking TBK1 and IKKε, IFNγ induces expression of TNFR1 and the Z-nucleic acid sensor, ZBP1, to trigger RIPK1-dependent apoptosis, largely in a target cell-autonomous manner. Unexpectedly, IFNγ, which is not known to signal to NFκB, induces hyperactivation of NFκB in TBK1 and IKKε double-deficient cells. TBK1 and IKKε suppress IKKα/ß activity and in their absence, IFNγ induces elevated NFκB-dependent expression of inflammatory chemokines and cytokines. Apoptosis is thought to be non-inflammatory, but our observations demonstrate that IFNγ can induce an inflammatory form of apoptosis, and this is suppressed by TBK1 and IKKε. The two kinases provide a critical connection between innate and adaptive immunological responses by regulating three key responses: (1) phosphorylation of IRF3/7 to induce type I IFN; (2) inhibition of RIPK1-dependent death; and (3) inhibition of NFκB-dependent inflammation. We propose that these kinases evolved these functions such that their inhibition by pathogens attempting to block type I IFN expression would enable IFNγ to trigger apoptosis accompanied by an alternative inflammatory response. Our findings show that loss of TBK1 and IKKε in target cells sensitizes them to inflammatory apoptosis induced by T cell-derived IFNγ.
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Sarcopenia, a geriatric syndrome characterized by progressive loss of muscle mass and strength, and osteoarthritis, a common degenerative joint disease, are both prevalent in elderly individuals. However, the relationship and molecular mechanisms underlying these two diseases have not been fully elucidated. In this study, we screened microarray data from the Gene Expression Omnibus to identify associations between sarcopenia and osteoarthritis. We employed multiple statistical methods and bioinformatics tools to analyze the shared DEGs (differentially expressed genes). Additionally, we identified 8 hub genes through functional enrichment analysis, protein-protein interaction analysis, transcription factor-gene interaction network analysis, and TF-miRNA coregulatory network analysis. We also discovered potential shared pathways between the two diseases, such as transcriptional misregulation in cancer, the FOXO signalling pathway, and endometrial cancer. Furthermore, based on common DEGs, we found that strophanthidin may be an optimal drug for treating sarcopenia and osteoarthritis, as indicated by the Drug Signatures database. Immune infiltration analysis was also performed on the sarcopenia and osteoarthritis datasets. Finally, receiver operating characteristic (ROC) curves were plotted to verify the reliability of our results. Our findings provide a theoretical foundation for future research on the potential common pathogenesis and molecular mechanisms of sarcopenia and osteoarthritis.
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Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.
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PURPOSE: This study aimed to evaluate the clinical and radiological outcomes of modified suture-bridge technique fixation for anterior cruciate ligament (ACL) tibial avulsion fracture. METHOD: Minors who underwent arthroscopic reduction and modified suture bridge fixation of ACL tibial avulsion fracture between January 2018 and January 2022 were retrospectively analyzed. Postoperative MRI and X-ray examinations were performed to evaluate the presence of epiphyseal plate injury and fracture healing. Moreover, KT-1000 side-to-side difference, Lachman test, range of motion (ROM), the subjective Knee score of the International Knee Documentation Committee (IKDC), Lysholm Knee score, and Tegner activity grade score were evaluated preoperatively and at the minimum 1-year follow-up visit. RESULTS: A total of 16 participants met the inclusion criteria. They had a mean age of 12.6 years (range, 9-16 years); mean time to surgery, 6.9 days (range, 2-13 days) and had a minimum of 12 months clinical follow-up (mean, 25.4 months; range, 12-36 months) after surgery. Postoperative radiographs and MRI showed no injury to the epiphyseal plate, optimal reduction immediately after the operation, and bone union within three months in all patients. All of the following showed significant improvements (pre- vs. postoperatively): mean KT-1000 side-to-side difference (8.6 vs. 1.5; p < 0.05), Lachman tests (2 grade 9 and 3 grade 7 vs. 0 grade 12 and 1 grade 4; p < 0.05), IKDC subjective score (48.3 vs. 95.0; p < 0.05), mean Lysholm score (53.9 vs. 92.2; p < 0.05), mean Tegner activity score (3.2 vs. 8.3; p < 0.05) and mean ROM (42.9°vs 133.1°; p < 0.05). CONCLUSION: Arthroscopic reduction and modified suture bridge fixation for ACL tibial avulsion fracture is a dependable and recommended treatment that can effectively restore the stability and function of the knee and is worthy of clinical promotion.
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Lesões do Ligamento Cruzado Anterior , Fratura Avulsão , Técnicas de Sutura , Fraturas da Tíbia , Humanos , Estudos Retrospectivos , Adolescente , Masculino , Criança , Feminino , Fratura Avulsão/cirurgia , Fratura Avulsão/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Artroscopia/métodos , Resultado do Tratamento , Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior/diagnóstico por imagem , Amplitude de Movimento Articular , SeguimentosRESUMO
Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realistic in silico architecture of the extracellular spaces of the zebrafish brain using light and electron microscopy data. Simulations on realistic architectures demonstrate that tortuosity and receptor binding within these spaces are sufficient to reproduce experimentally measured morphogen dynamics. Importantly, this work demonstrates that hindered diffusion is a viable mechanism for gradient formation, without requiring additional regulatory control.
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Although the functions of tyrosine phosphatases in T-cell biology have been extensively studied, our knowledge on the contribution of serine/threonine phosphatases in T cells remains poor. Protein phosphatase 2A (PP2A) is one of the most abundantly expressed serine/threonine phosphatases. It is important in thymocyte development and CD4+ T-cell differentiation. Utilizing a genetic model in which its catalytic subunit alpha isoform (PP2A Cα) is deleted in T cells, we investigated its contribution to CD8+ T-cell homeostasis and effector functions. Our results demonstrate that T-cell intrinsic PP2A Cα is critically required for CD8+ T-cell homeostasis in secondary lymphoid organs and intestinal mucosal site. Importantly, PP2A Cα-deficient CD8+ T cells exhibit reduced proliferation and survival. CD8+ T-cell antibacterial response is strictly dependent on PP2A Cα. Expression of Bcl2 transgene rescues CD8+ T-cell homeostasis in spleens, but not in intestinal mucosal site, nor does it restore defective antibacterial responses. Finally, proteomics and phosphoproteomics analyses reveal potential targets dependent on PP2A Cα, including mTORC1 and AKT. Thus, PP2A Cα is a key modulator of CD8+ T-cell homeostasis and effector functions.
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Electrocatalytic CO2 reduction (eCO2R) in acid holds promise in renewable electricity-powered CO2 utilization with high efficiency, but the hydrogen evolution reaction (HER) often prevails and results in a low eCO2R selectivity. Here, using cobalt phthalocyanine/Ketjen black (CoPc/KB) as the model catalysts, we systematically study the effect of active site density, operational current density, and hydrated cations on the acidic eCO2R selectivity and decipher it through the componential dynamics of electric double layer (EDL). The optimal CoPc-4/KB demonstrates a near-unity CO Faradaic efficiency from 50 to 400 mA cm-2 and superb operational stability (>120 h) at 100 mA cm-2. Aided by in situ Raman and infrared spectroscopies, we reveal that the proper cations establish an electrostatic shield for mitigating bulk H+ penetration and mediate the interfacial water structure for suppressing HER. This study should elicit further profound thinking on robust eCO2R system design from the perspective of multiphasic and dynamic EDL.
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OBJECTIVE: Hypoglossal-facial nerve anastomosis (HFA) is the most commonly used surgical treatment for severe facial palsy that does not respond to conservative treatments. A major complication of HFA is the loss of tongue function. The authors aimed to evaluate whether anastomosing the transected hypoglossal nerve using the ramus descendens hypoglossi could prevent tongue deviation and dysfunction in patients undergoing HFA. METHODS: In this randomized trial, adult patients with severe peripheral facial palsy (House-Brackmann grade V or VI) who did not respond to at least 6 months of conservative treatment were randomized at a 1:1 ratio to undergo either HFA alone (control group) or HFA plus anastomosis between the hypoglossal nerve and descendens hypoglossi (intervention group). The primary endpoint was tongue deviation angle at 12 months. Key secondary endpoints included tongue disability (chewing difficulty, swallowing defect, and articulation defect), tongue disability index (TDI; range 1-4, with a higher score indicating more severe disability), and facial nerve function. RESULTS: Twenty patients were enrolled (10 in each group). At 12 months, the tongue deviation angle was significantly lower in the intervention group than in the control group (7.8° ± 5.1° vs 23.6° ± 9.6°, p < 0.001). Although not statistically significant, the intervention group had lower rates of chewing difficulty (1/10 vs 3/10, p = 0.58), swallowing defect (1/10 vs 5/10, p = 0.14), and articulation defect (2/10 vs 6/10, p = 0.17). TDI was significantly lower in the intervention group (1.5 ± 0.6 vs 2.5 ± 0.3, p < 0.001). The percentage of the patients achieving House-Brackmann grade II or III was 80% in each group. CONCLUSIONS: Anastomosis of the descendens hypoglossi to the transected hypoglossal nerve attenuated tongue deviation in patients undergoing HFA for facial palsy, without compromising facial nerve function. Clinical trial registration no: ChiCTR2000034372 (Chinese Clinical Trials Registry).
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Objective: This study focuses on enhancing the precision of epidemic time series data prediction by integrating Gated Recurrent Unit (GRU) into a Graph Neural Network (GNN), forming the GRGNN. The accuracy of the GNN (Graph Neural Network) network with introduced GRU (Gated Recurrent Units) is validated by comparing it with seven commonly used prediction methods. Method: The GRGNN methodology involves multivariate time series prediction using a GNN (Graph Neural Network) network improved by the integration of GRU (Gated Recurrent Units). Additionally, Graphical Fourier Transform (GFT) and Discrete Fourier Transform (DFT) are introduced. GFT captures inter-sequence correlations in the spectral domain, while DFT transforms data from the time domain to the frequency domain, revealing temporal node correlations. Following GFT and DFT, outbreak data are predicted through one-dimensional convolution and gated linear regression in the frequency domain, graph convolution in the spectral domain, and GRU (Gated Recurrent Units) in the time domain. The inverse transformation of GFT and DFT is employed, and final predictions are obtained after passing through a fully connected layer. Evaluation is conducted on three datasets: the COVID-19 datasets of 38 African countries and 42 European countries from worldometers, and the chickenpox dataset of 20 Hungarian regions from Kaggle. Metrics include Average Root Mean Square Error (ARMSE) and Average Mean Absolute Error (AMAE). Result: For African COVID-19 dataset and Hungarian Chickenpox dataset, GRGNN consistently outperforms other methods in ARMSE and AMAE across various prediction step lengths. Optimal results are achieved even at extended prediction steps, highlighting the model's robustness. Conclusion: GRGNN proves effective in predicting epidemic time series data with high accuracy, demonstrating its potential in epidemic surveillance and early warning applications. However, further discussions and studies are warranted to refine its application and judgment methods, emphasizing the ongoing need for exploration and research in this domain.
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Redes Neurais de Computação , Humanos , COVID-19/epidemiologia , Doenças Transmissíveis/epidemiologia , Análise de Fourier , Surtos de DoençasRESUMO
Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation of EV-related pathways in the liver pericentral zone, which was abrogated by glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs up-regulated the expression of EV-related genes such as Ras-related protein Rab-31 (RAB31) by enhancing histone 3 lysine 9 acetylation on the promoter region, which increased EV release. Functionally, these glycolysis-dependent EVs increased fibrotic gene expression in recipient HSC. Furthermore, EVs derived from glycolysis-deficient mice abrogated liver fibrosis amplification in contrast to glycolysis-competent mouse EVs. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the hepatic pericentral zone, which represents a potential therapeutic target.
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Vesículas Extracelulares , Glicólise , Células Estreladas do Fígado , Cirrose Hepática , Animais , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/genética , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Vesículas Extracelulares/metabolismo , Camundongos , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Humanos , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.
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BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. METHODS: We conducted a genome-wide interaction analysis of single nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than 3 drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies (GWAS). Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed effect meta-analyses were conducted. RESULTS: A potential novel region of association on 10p11.22, lead SNP rs7898449 (Pinteraction = 5.1 x 10-8 in the meta-analysis, Pinteraction = 2.1x10-9 in the case-control studies, Pinteraction = 0.91 cohort studies) was identified. A SNP correlated with this lead SNP is an eQTL for the NRP1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). CONCLUSIONS: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an eQTL for the NRP1, a protein that plays an important role in the development and progression of pancreatic cancer Impact: This work can provide insight into the etiology of pancreatic cancer particularly in heavy drinkers.
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During our collecting trip to Guangxi in 2016, we collected ten specimens of the genus Takydromus from the suburb of Guilin, northeastern Guangxi, South China, and found that they did not belong to any currently known species. Here, we described this new species, Takydromus guilinensis sp. nov., based on morphological and mitochondrial DNA (CO1 and cyt b) data. This new species is a sister taxon to T. intermedius with a p-distance of 0.070 in CO1 and 0.080 in cyt b. These two p-distances exceed not only the minimum value (0.067) between T. septentrionalis and T. stejnegeri but also the minimum value (0.079) between T. intermedius and T. yunkaiensis. Morphologically, this new species differs from other currently recognized Takydromus species from the same clade, more evidently in the longitudinal rows of dorsal scales, transverse rows of scales at the mid-body and mensural variables. The description of Takydromus guilinensis sp. nov. increases the total number of Takydromus species to 25, of which 16 can be found in China. Takydromus guilinensis sp. nov. is currently known only from Guilin, Guangxi, South China, where it is sympatric with the other four Takydromus species (T. septentrionalis, T. kuehnei, T. sexlineatus and T. intermedius).
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BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
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BACKGROUND: As a simple and safe alternative intervention, percutaneous balloon compression (PBC) has been gradually adopted by a growing number of neurosurgeons to treat trigeminal neuralgia. A pear-shaped opacity observed fluoroscopically, which indicates full suffusion of Meckel's cave conducting sufficient pressure against Gasserian ganglion, is believed to be the key to its success. Sometimes, a bitten pear may appear due to bubbles in the balloon but is usually ignored. OBJECTIVE: This study aims to investigate the effects of the bubbles on postoperative outcomes. METHODS: Patient data were obtained from the consecutive cases undergoing PBCs in our department between 2019 and 2021. Among them, pain and numbness were used to assess the efficacy of PBC based on Barrow Neurology Institute (BNI) scoring system. It was defined as an effective outcome if the postoperative pain intensity grade was lower than II. And those with numbness grade > II were regarded as numb incidence. RESULTS: We eventually recruited 59 cases, including 42 in full pear and 17 in bitten pear groups with follow-up time up to 44 months. The early effective rates were 95.2% and 82.4%, respectively (p > 0.05), which turned to 88.1% and 52.9% during the last follow-up period (p < 0.01). This result indicated that the bitten pear gave rise to a significantly higher recurrence. In terms of numbness, there was no significant difference. CONCLUSION: Gas does not yield enough pressure as liquid, and cannot exert enough pressure to the semilunar ganglion. Therefore, air evacuation should not be ignored before injection.
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Neuralgia do Trigêmeo , Neuralgia do Trigêmeo/cirurgia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , AdultoRESUMO
Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.