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Traditionally, alkaline water electrolysis (AWE) uses diaphragms to separate anode and cathode and is operated with 5-7 M KOH feed solutions. The ban of asbestos diaphragms led to the development of polymeric diaphragms, which are now the state of the art material. A promising alternative is the ion solvating membrane. Recent developments show that high conductivities can also be obtained in 1 M KOH. A third technology is based on anion exchange membranes (AEM); because these systems use 0-1 M KOH feed solutions to balance the trade-off between conductivity and the AEM's lifetime in alkaline environment, it makes sense to treat them separately as AEM WE. However, the lifetime of AEM increased strongly over the last 10 years, and some electrode-related issues like oxidation of the ionomer binder at the anode can be mitigated by using KOH feed solutions. Therefore, AWE and AEM WE may get more similar in the future, and this review focuses on the developments in polymeric diaphragms, ion solvating membranes, and AEM.
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Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.
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Tecido Adiposo , Macrófagos , Cicatrização , Cicatrização/fisiologia , Macrófagos/metabolismo , Animais , Tecido Adiposo/citologia , Humanos , Camundongos , Estresse Mecânico , Células-Tronco/citologia , Células-Tronco/metabolismo , Células Cultivadas , Masculino , Fator Estimulador de Colônias de Macrófagos/metabolismo , Transplante de Células-Tronco/métodos , Inflamação/terapia , Camundongos Endogâmicos C57BLRESUMO
The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.
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Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Pluripotentes Induzidas , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Células-Tronco Pluripotentes Induzidas/citologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Urina/citologia , Medicina Regenerativa/métodosRESUMO
BACKGROUND: Drowning is the leading cause of death among children in rural Bangladesh. While survival swimming for children ages 6 years and above is recommended in low-income and middle-income countries, research into the long-term retention of survival swimming skills is absent. METHODS: The retention of four survival swimming skills, including swimming for 25 m, floating/treading for 30 s, reach rescue skills and throw rescue skills, was observed among those trained under the SwimSafe programme more than 10 years ago. Information about the practice of survival swimming skills among SwimSafe graduates and whether they recommended such lessons for others was also collected through surveys. A multistage sampling strategy was used. Descriptive statistics on the retention of survival swimming skills and other variables and ORs from logistic regression analysis were reported. RESULTS: A total of 3603 SwimSafe graduates were observed. The retention of swimming and floating/treading skills was 88.4% and 89.7%, respectively, and that of swimming and floating/treading skills combined was 84.2%. While 87.7% of the graduates retained reach rescue skills, the retention of throw rescue skills was lower (71.9%). Approximately 60.6% of the graduates retained all four survival swimming skills. The majority of the graduates (70.3%) rarely practised swimming following graduation. Overall, 61.7% of the graduates recommended other children to learn survival swimming skills. CONCLUSION: The majority of the SwimSafe graduates retained swimming and floating/treading skills for over 10 years despite minimal practice. Retention of throw rescue skills was lower. Therefore, refresher training and awareness campaigns focused on survival swimming skills are recommended.
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INTRODUCTION: Wearing a helmet reduces the risk of head injuries substantially in the event of a motorcycle crash. Countries around the world are committed to promoting helmet use, but the progress has been slow and uneven. There is an urgent need for large-scale data collection for situation assessment and intervention evaluation. METHODS: This study proposes a scalable, low-cost algorithm to estimate helmet-wearing rates. Applying the state-of-the-art deep learning technique for object detection to images acquired from Google Street View, the algorithm has the potential to provide accurate estimates at the global level. RESULTS: Trained on a sample of 3995 images, the algorithm achieved high accuracy. The out-of-sample prediction results for all three object classes (helmets, drivers, and passengers) reveal a precision of 0.927, a recall value of 0.922, and a mean average precision at 50 (mAP50) of 0.956. DISCUSSION: The remarkable model performance suggests the algorithm's capacity to generate accurate estimates of helmet-wearing rates from an image source with global coverage. The significant enhancement in the availability of helmet usage data resulting from this approach could bolster progress tracking and facilitate evidence-based policymaking for helmet wearing globally.
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Aprendizado Profundo , Dispositivos de Proteção da Cabeça , Dispositivos de Proteção da Cabeça/estatística & dados numéricos , Humanos , Algoritmos , Acidentes de Trânsito/prevenção & controle , Traumatismos Craniocerebrais/prevenção & controleRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF 1) is an autosomal-dominant tumor predisposition genetic disease affecting approximately 1 in 3000 live births. The condition could present various manifestations ranging from skin abnormalities to neurological tumors. The musculoskeletal system could also be frequently affected, and scoliosis is the most common orthopedic manifestation. Characterized by the early-onset and rapid progression tendency, NF 1-related dystrophic scoliosis presented discrepancies from idiopathic scoliosis in terms of natural history, clinical features, and management outcomes and thus required special attention. In the current study, the authors conducted a systemic review to outline the body of evidence of the natural history, clinical characteristics, surgical outcomes, and surgical complications of NF 1-induced scoliosis, aiming to provide an elucidative insight into this condition. METHOD: Systemic review and meta-analysis were conducted according to the latest Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. The search was performed in Medline, Embase, and Web of Science Core Collection up to December 27, 2022, using related keywords. Clinical features such as frequencies, segmental involvement, and hereditary information were summarized and described qualitatively. Meta-analysis was conducted using R software and the 'meta' package to yield an overall outcome of efficacy and safety of surgical management, precisely, spinal fusion procedure and growing rods procedure. Corrective rate of Cobb angle, sagittal kyphosis angle, and T1-S1 length post-operative and at the last follow-up was used to evaluate the efficacy, and the occurrence of surgery-related complications was used to evaluate the safety. RESULT: A total of 37 articles involving 1023 patients were included. Approximately 26.6% of the NF 1 patients would present with scoliosis. Patients tend to develop scoliosis at an earlier age. The thoracic part turned out to be the most affected segment. No obvious correlation between scoliosis and genotype or hereditary type was observed. Both spinal fusion and growing rod surgery have shown acceptable treatment outcomes, with spinal fusion demonstrating better performance in terms of effectiveness and safety. The growing rods technique seemed to allow a better lengthening of the spine. The mainstay post-operative complications were implant-related complications but could be managed with limited revision surgery. Severe neurological deficits were rarely reported. CONCLUSION: Scoliosis, especially the subtype characterized by dystrophic bony changes, is a significant orthopedic manifestation of NF1. It has an early onset, a tendency to persistently and rapidly progress, and is challenging to deal with. The current review outlines the available evidence from the perspective of natural history, clinical features, and the treatment efficacy and safety of the mainstay surgical options. Patients with NF1 scoliosis will benefit from a better understanding of the disease and evidence based treatment strategies.
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Neurofibromatose 1 , Escoliose , Humanos , Escoliose/cirurgia , Escoliose/etiologia , Neurofibromatose 1/cirurgia , Neurofibromatose 1/complicações , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
BACKGROUND: A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects. METHODS: A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson's staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed. RESULTS: The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation. CONCLUSIONS: This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.
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Regeneração Óssea , Periósteo , Animais , Suínos , Regeneração Óssea/genética , Perfilação da Expressão Gênica , Regeneração Tecidual Guiada/métodos , Modelos Animais , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
BACKGROUND: Aesthetic improvement of the chin is increasingly requested by patients, including those of Chinese origin. METHODS: A randomized, evaluator-blinded, no-treatment controlled study evaluated the effectiveness and safety of a flexible hyaluronic acid (HA) filler, Restylane® DefyneTM (HADEF), in the correction of chin retrusion in a Chinese adult population over 12 months after treatment. On Day 1, subjects were randomized 3:1 into two groups, HADEF or delayed-treatment controls, and those in the HADEF group were administered treatment. An optional touch-up treatment was administered 1 month after treatment to obtain optimal chin augmentation. The initially untreated control group was offered delayed-treatment after 6 months (including 1-month touch-up). RESULTS: HADEF was superior to no-treatment in improving chin retrusion according to the blinded evaluator at 6 months [Galderma Chin Retrusion Scale (GCRS) responder rate (≥ 1-point improvement from baseline) of 81% vs. 5% for untreated controls; p < 0.001, meeting the primary effectiveness objective. A majority of subjects maintained improvement at 12 months (61% in the HADEF group). All subjects reported satisfaction with results at 6 months after treatment with HADEF and aesthetic improvement rates per the global aesthetic improvement scale (GAIS) were high for 12 months following treatment, with an acceptable safety profile. CONCLUSIONS: These results demonstrated HADEF to be effective and safe for the correction of mild-to-moderate chin retrusion in Chinese subjects, confirming findings previously observed in a western population. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Técnicas Cosméticas , Preenchedores Dérmicos , População do Leste Asiático , Adulto , Humanos , Queixo , Preenchedores Dérmicos/efeitos adversos , Ácido Hialurônico , Envelhecimento da Pele , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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The automatic segmentation of auricular acupoint divisions is the basis for realizing intelligent auricular acupoint therapy. However, due to the large number of ear acupuncture areas and the lack of clear boundary, existing solutions face challenges in automatically segmenting auricular acupoints. Therefore, a fast and accurate automatic segmentation approach of auricular acupuncture divisions is needed. A deep learning-based approach for automatic segmentation of auricular acupoint divisions is proposed, which mainly includes three stages: ear contour detection, anatomical part segmentation and keypoints localization, and image post-processing. In the anatomical part segmentation and keypoints localization stages, K-YOLACT was proposed to improve operating efficiency. Experimental results showed that the proposed approach achieved automatic segmentation of 66 acupuncture points in the frontal image of the ear, and the segmentation effect was better than existing solutions. At the same time, the mean average precision (mAP) of the anatomical part segmentation of the K-YOLACT was 83.2%, mAP of keypoints localization was 98.1%, and the running speed was significantly improved. The implementation of this approach provides a reliable solution for the accurate segmentation of auricular point images, and provides strong technical support for the modern development of traditional Chinese medicine.
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Acupuntura Auricular , Aprendizado Profundo , Pontos de Acupuntura , Acupuntura Auricular/métodos , Processamento de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: Bifid nose is a rare congenital deformity and the etiology is unknown. The purpose of this study was to report genetic variation in family of patients with bifid nose. METHODS: Twenty-three consecutive patients who were diagnosed with mild bifid nose were operated with z-plasty from 2009 to 2021. Three underage patients (a pair of twins and a girl) from two family lines, who came to our hospital for surgical treatment, were enrolled. Whole exome sequencing and Sanger sequencing were conducted. Z-shaped flaps were created and the cartilago alaris major were re-stitched. Photographs and CT scan before and after surgery were obtained. Clinical outcomes, complications and patients' satisfaction were evaluated and analyzed. The follow-up time ranges from 2 to 3 years (2.4 ± 1.2 years). RESULTS: Most patients were satisfied with the outcome (96.2%). The nasal deformities were corrected successfully with z-plasty technique in one-stage. FREM1 c.870_876del and c.2 T > C were detected with Whole exome sequencing, which have not been reported before. The results of Sanger sequencing were consistent with those of Whole exome sequencing. CONCLUSIONS: The newly detected mutations of FREM1 have a certain heritability, and are helpful to make an accurate diagnosis and provide a better understanding of bifid nose mechanism. Z-plasty technique can be an effective technical approach for correcting mild bifid nose deformity.
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Doenças Nasais , Nariz , Feminino , Humanos , Mutação , Nariz/anormalidades , Nariz/cirurgia , Doenças Nasais/diagnóstico , Doenças Nasais/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Road traffic crashes cause 1.19 million deaths and millions more injuries annually. The persistently high burden has drawn attention from national and international stakeholders worldwide. Unsafe road infrastructure is one of the major risk factors for traffic safety, particularly in low- and middle-income countries. METHODS: Aiming to eliminate high-risk roads in all countries, the International Road Assessment Programme (iRAP) developed a robust and evidence-based approach to support country transportation agencies. RESULTS: Thus far, the iRAP protocols have been used to collect 1.8 million kilometers of Crash Risk Mapping and 1.5 million kilometers of Star Rating and FSI estimations in 128 countries. Deploying an observational before-and-after (or pre-post) study design, this report estimated the fatal and series injuries (FSI) saved through use of the iRAP protocols. The study is based on 441,753 kilometers of assessed roads from 1,039 projects in 74 countries. Our results show that the implementation of iRAP's proposed countermeasures saves about 159,936 FSI annually. Throughout the lifetime of the implemented countermeasures, a total of 3.2 million FSI could be saved. CONCLUSION: While quantifying the success of the iRAP protocols, our results suggest an opportunity to save many millions more lives on the roads through expanding iRAP implementation to more regions and countries.
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Acidentes de Trânsito , Ferimentos e Lesões , Humanos , Acidentes de Trânsito/prevenção & controle , Meios de Transporte , Fatores de Risco , Proteína Antagonista do Receptor de Interleucina 1 , Avaliação de Programas e Projetos de Saúde , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Myofibroblasts contribute to the excessive production, remodeling and cross-linking of the extracellular matrix that characterizes the progression of skin fibrosis. An important insight into the pathogenesis of tissue fibrosis has been the discovery that increased matrix stiffness during fibrosis progression is involved in myofibroblast activation. However, mechanistic basis for this phenomenon remains elusive. OBJECTIVE: To explore the role of fibroblast activation protein-α (FAPα) in mechanical stiffness-induced skin fibrosis progression. METHODS: RNA-seq was performed to compare differential genes of mouse dermal fibroblasts (MDFs) grown on low or high stiffness plates. This process identified FAPα, which is a membrane protein usually overexpressed in activated fibroblasts, as a suitable candidate. In vitro assay, we investigate the role of FAPα in mechanical stiffness-induced MDFs activation and downstream pathway. By establishing mouse skin fibrosis model and intradermally administrating FAPα adeno-associated virus (AAV) or a selective Fap inhibitor FAPi, we explore the role of FAPα in skin fibrosis in vivo. RESULTS: We show that FAPα, a membrane protein highly expressed in myofibroblasts of skin fibrotic tissues, is regulated by increased matrix stiffness. Genetic deletion or pharmacological inhibition of FAPα significantly inhibits mechanical stiffness-induced activation of myofibroblasts in vitro. Mechanistically, FAPα promotes myofibroblast activation by stimulating the PI3K-Akt pathway. Furthermore, we showed that administration of the inhibitor FAPi or FAPα targeted knockdown ameliorated the progression of skin fibrosis. CONCLUSION: Taken together, we identify FAPα as an important driver of mechanical stiffness-induced skin fibrosis and a potential therapeutic target for the treatment of skin fibrosis.
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Endopeptidases , Proteínas Proto-Oncogênicas c-akt , Dermatopatias , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Fibrose , Transdução de Sinais , Dermatopatias/patologia , Fibroblastos/metabolismo , Miofibroblastos/patologiaRESUMO
Lead halide perovskite nanocrystals (LHP NCs) with outstanding optical properties have been regarded as promising alternatives to traditional phosphors for lighting and next-generation display technology. However, the practical applications of LHP NCs are seriously hindered by their poor stability upon exposure to moisture, oxygen, light, and heat. Hence, various strategies have been proposed to solve this issue. In this review, we have focused our attention on improving the stability of LHP NCs via SiO2 coating because it has the advantages of simple operation, less toxicity, and easy repetition. SiO2 coating is classified into four types: (a) in situ hydrolytic coating, (b) mesoporous silica loading, (c) mediated anchoring, and (d) double coating. The potential applications of SiO2-coated LHP NCs in the field of optoelectronics, biology, and catalysis are presented to elucidate the reliability and availability of SiO2 coating. Finally, the future development and challenges in the preparation of SiO2-coated LHP NCs are analyzed in order to promote the commercialization process of LHP NC-related commodities.
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Objective: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. Methods: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. Results: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. Conclusion: Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
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Neurofibromatose 1 , Humanos , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Proteínas Ativadoras de GTPase , Mutação , Predisposição Genética para Doença , Terapia GenéticaRESUMO
Diazinon (DZN) is a member of organophosphorus insecticides that has cytotoxic effects on different organs. n-Acetyl cysteine (NAC) is a widely used antioxidant in clinical, in vivo and in vitro studies. We evaluated the protective role of NAC against DZN-induced toxicity in kidney tissue of Wistar rats. 30 male Wistar rats were divided into 5 groups of control, single dose of DZN, continuous dose of DZN, single doses of DZN + NAC and continuous doses of DZN + NAC. Kidney function test (blood urea nitrogen, creatinine and uric acid) was provided. Levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and total sulfhydryl (T-SH) were determined in renal tissues. Renal cells apoptosis was detected using TUNEL assay. The mRNA expressions of apoptosis, oxidative stress and inflammatory mediators, including B-cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (Bax), superoxide dismutase (SOD), catalase (CAT), Interleukin 10 (IL-10), Tumor necrosis factor-α (TNF-α), Caspase-3 and Caspase-8 were analyzed in kidney tissues using Real Time PCR method. Chronic exposure to DZN was associated with severe morphological changes in the kidney, as well as impairment of its function and decreased kidney weights. Continues treatment with DZN significantly decreased the percentage of renal apoptotic cells as compared to rats treated with continuous dose of DZN alone (17.69 ± 3.67% vs. 39.46% ± 2.44%; p < 0.001). Continuous exposure to DZN significantly decreased TAC and T-SH contents, as well as SOD and CAT expression, but increased MDA contents in the kidney tissues (p < 0.001). A significant increase was observed in mRNA expression of Bax, Caspase-3, Caspase-8, as well as TNF-α following exposure to DZN, but the expression of IL-10 and Bcl2 was significantly decreased. NAC can protect kidney tissue against DZN-induced toxicity by elevating antioxidants capacity, mitigating oxidative stress, inflammation and apoptosis.
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Bifid nose is a rare congenital malformation, and few cases have been reported due to its low incidence. Herein, we report a new surgical procedure to treat patients with excess dorsal nasal tissue and an underfilled tip. A total of 22 patients with bifid nose deformities underwent surgery at our institution between 2012 and 2022. They were characterized by a broad nasal dorsum and a missing or underdeveloped nasal tip. We designed an innovative island flap of nasal dorsum as a new surgical method for treating this bifid nose deformity. Nasal length, tip projection, and photographs of nose morphology were obtained before and after the surgery. Outcomes, complications, indications, and patient satisfaction were analyzed and interviewed. The follow-up time ranges from 6 to 33 months (8.7 ± 5.5 months). The deformity was successfully corrected with an improved nasal appearance. Nasal length increased from initially 4.2 ± 0.3 mm to 4.6 ± 0.3 mm. Tip projection reached 19.9 ± 4.0 mm, which was 15.7 ± 2.9 mm before surgery. No severe complications were observed except poor venous reflux within postoperative 72 hours in four cases. Six patients (27.3%) got moderate healing and acceptable scars, and 14 patients (63.6%) got good healing. Most patients were very satisfied with the outcome (93.9%). The newly designed nasal dorsum island flap is a safe and effective technical approach to correct nose deformity featured by broad nasal dorsum and a missing or underdeveloped nasal tip.
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This paper introduces a novel approach to bipedal robot gait generation by proposing a higher-order form through the parameter equation of first-order Bessel interpolation. The trajectory planning for the bipedal robot, specifically for stepping up or down stairs, is established based on a three-dimensional interpolation equation. The experimental prototype, Roban, is utilized for the study, and the structural sketch of a single leg is presented. The inverse kinematics expression for the leg is derived using kinematic methods. Employing a position control method, the angle information is transmitted to the robot's joints, enabling the completion of both downstairs simulation experiments and physical experiments with the Roban prototype. The analysis of the experimental process reveals a noticeable phenomenon of hip and ankle joint tilting in the robot. This observation suggests that low-cost bipedal robots driven by servo motors exhibit low stiffness characteristics in their joints.
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Obesity-related metabolic diseases, including obesity, diabetes, hyperlipidemia, and non-alcoholic fatty liver diseases pose a significant threat to health. However, comprehensive pathogenesis exploration and effective therapy development are impeded by the limited availability of human models. Notably, advances in organoid technology enable the generation of adipose organoids that recapitulate structures and functions of native human adipose tissues to investigate mechanisms and develop corresponding treatments for obesity-related metabolic diseases. Here, we review the general principles, sources, and three-dimensional techniques for engineering adipose organoids, along with strategies to promote maturation. We also outline the application of white adipose organoids, primarily for disease modeling and drug screening, and highlight the therapeutic potential of thermogenic beige and brown adipose organoids in promoting weight loss and glucose and lipid metabolic homeostasis. We also discuss the challenges and prospects in the establishment and bench-to-bedside of adipose organoids, as well as their potential applications.
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Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Doenças Metabólicas/metabolismo , TermogêneseRESUMO
Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis.