Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 614
Filter
Add more filters

Publication year range
1.
Chem Rev ; 124(10): 6393-6443, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38669641

ABSTRACT

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.

2.
FASEB J ; 38(10): e23626, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38739537

ABSTRACT

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.


Subject(s)
Adipose Tissue , Macrophages , Wound Healing , Wound Healing/physiology , Macrophages/metabolism , Animals , Adipose Tissue/cytology , Humans , Mice , Stress, Mechanical , Stem Cells/cytology , Stem Cells/metabolism , Cells, Cultured , Male , Macrophage Colony-Stimulating Factor/metabolism , Stem Cell Transplantation/methods , Inflammation/therapy , Mice, Inbred C57BL
3.
J Biomed Sci ; 31(1): 47, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724973

ABSTRACT

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.


Subject(s)
Cell- and Tissue-Based Therapy , Induced Pluripotent Stem Cells , Precision Medicine , Humans , Precision Medicine/methods , Induced Pluripotent Stem Cells/cytology , Cell- and Tissue-Based Therapy/methods , Drug Evaluation, Preclinical/methods , Urine/cytology , Regenerative Medicine/methods
4.
BMC Public Health ; 24(1): 1645, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902622

ABSTRACT

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.


Subject(s)
Deep Learning , Head Protective Devices , Head Protective Devices/statistics & numerical data , Humans , Algorithms , Accidents, Traffic/prevention & control , Craniocerebral Trauma/prevention & control
5.
Eur Spine J ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38526628

ABSTRACT

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.

6.
Chem Soc Rev ; 52(12): 4046-4070, 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37249036

ABSTRACT

To meet challenges associated with climate changes due to the continuous increase in global energy demand, implementation of hydrogen and fuel cell technologies, especially the polymer electrolyte membrane type, are recognized as potential solutions. The high temperature polymer electrolyte membrane fuel cell based on acid doped polybenzimidazoles has attracted enormous R&D attention due to the simplified construction and operation of the power system. In order to improve the reliability and lifetime of the technology, studies on material degradation and mitigation are essential. The present work is a comprehensive review of the current knowledge on degradation mechanisms of the fuel cell components including the acid loss, polymer oxidation and catalyst instability due to the metal dissolution and carbon support corrosion. The durability results are updated according to the categories of steady state and dynamic operations. Durability protocols, diagnostic techniques and mitigation strategies are also discussed.

7.
Aesthetic Plast Surg ; 48(5): 1030-1036, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38315229

ABSTRACT

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 .


Subject(s)
Cosmetic Techniques , Dermal Fillers , East Asian People , Adult , Humans , Chin , Dermal Fillers/adverse effects , Hyaluronic Acid , Skin Aging , Treatment Outcome
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(1): 114-120, 2024 Feb 25.
Article in Zh | MEDLINE | ID: mdl-38403611

ABSTRACT

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.


Subject(s)
Acupuncture, Ear , Deep Learning , Acupuncture Points , Acupuncture, Ear/methods , Image Processing, Computer-Assisted/methods
9.
Hum Brain Mapp ; 44(5): 2062-2084, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36583399

ABSTRACT

Magnetic resonance imaging (MRI) has been one of the primary instruments to measure the properties of the human brain non-invasively in vivo. MRI data generally needs to go through a series of processing steps (i.e., a pipeline) before statistical analysis. Currently, the processing pipelines for multi-modal MRI data are still rare, in contrast to single-modal pipelines. Furthermore, the reliability and validity of the output of the pipelines are critical for the MRI studies. However, the reliability and validity measures are not available or adequate for almost all pipelines. Here, we present PhiPipe, a multi-modal MRI processing pipeline. PhiPipe could process T1-weighted, resting-state BOLD, and diffusion-weighted MRI data and generate commonly used brain features in neuroimaging. We evaluated the test-retest reliability of PhiPipe's brain features by computing intra-class correlations (ICC) in four public datasets with repeated scans. We further evaluated the predictive validity by computing the correlation of brain features with chronological age in three public adult lifespan datasets. The multivariate reliability and predictive validity of the PhiPipe results were also evaluated. The results of PhiPipe were consistent with previous studies, showing comparable or better reliability and validity when compared with two popular single-modality pipelines, namely DPARSF and PANDA. The publicly available PhiPipe provides a simple-to-use solution to multi-modal MRI data processing. The accompanied reliability and validity assessments could help researchers make informed choices in experimental design and statistical analysis. Furthermore, this study provides a framework for evaluating the reliability and validity of image processing pipelines.


Subject(s)
Brain , Magnetic Resonance Imaging , Adult , Humans , Reproducibility of Results , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Image Processing, Computer-Assisted/methods
10.
Cancer Immunol Immunother ; 72(12): 4415-4429, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37938367

ABSTRACT

Dermatofibrosarcoma protuberans (DFSP) stands as a rare and locally aggressive soft tissue tumor, characterized by intricated molecular alterations. The imperative to unravel the complexities of intratumor heterogeneity underscores effective clinical management. Herein, we harnessed single-cell RNA sequencing (scRNA-seq) to conduct a comprehensive analysis encompassing samples from primary sites, satellite foci, and lymph node metastases. Rigorous preprocessing of raw scRNA-seq data ensued, and employing t-distributed stochastic neighbor embedding (tSNE) analysis, we unveiled seven major cell populations and fifteen distinct subpopulations. Malignant cell subpopulations were delineated using infercnv for copy number variation calculations. Functional and metabolic variations of diverse malignant cell populations across samples were deciphered utilizing GSVA and the scMetabolism R packages. Additionally, the exploration of differentiation trajectories within diverse fibroblast subpopulations was orchestrated through pseudotime trajectory analyses employing CytoTRACE and Monocle2, and further bolstered by GO analyses to elucidate the functional disparities across distinct differentiation states. In parallel, we segmented the cellular components of the immune microenvironment and verified the presence of SPP1+ macrophage, which constituted the major constituent in lymph node metastases. Remarkably, the CellChat facilitated a comprehensive intercellular communication analysis. This study culminates in an all-encompassing single-cell transcriptome atlas, propounding novel insights into the multifaceted nature of intratumor heterogeneity and fundamental molecular mechanisms propelling metastatic DFSP.


Subject(s)
Dermatofibrosarcoma , Skin Neoplasms , Humans , Dermatofibrosarcoma/genetics , Dermatofibrosarcoma/pathology , Dermatofibrosarcoma/secondary , Lymphatic Metastasis , DNA Copy Number Variations , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Sequence Analysis, RNA , Tumor Microenvironment/genetics
11.
BMC Plant Biol ; 23(1): 554, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37940874

ABSTRACT

BACKGROUND: Wheat powdery mildew is an obligate biotrophic pathogen infecting wheat, which can pose a serious threat to wheat production. In this study, transcriptome sequencing was carried out on wheat leaves infected by Blumeria graminis f. sp. tritici from 0 h to 7 d. RESULTS: KEGG and GO enrichment analysis revealed that the upstream biosynthetic pathways and downstream signal transduction pathways of salicylic acid, jasmonic acid, and ethylene were highly enriched at all infection periods. Trend analysis showed that the expressions of hormone-related genes were significantly expressed from 1 to 4 d, suggesting that 1 d-4 d is the main period in which hormones play a defensive role. During this period of time, the salicylic acid pathway was up-regulated, while the jasmonic acid and ethylene pathways were suppressed. Meanwhile, four key modules and 11 hub genes were identified, most of which were hormone related. CONCLUSION: This study improves the understanding of the dynamical responses of wheat to Blumeria graminis f. sp. tritici infestation at the transcriptional level and provides a reference for screening core genes regulated by hormones.


Subject(s)
Plant Diseases , Triticum , Triticum/genetics , Triticum/metabolism , Ethylenes/metabolism , Hormones/metabolism , Salicylic Acid/metabolism
12.
J Transl Med ; 21(1): 164, 2023 03 02.
Article in English | MEDLINE | ID: mdl-36864460

ABSTRACT

Fibrosis, a process caused by excessive deposition of extracellular matrix (ECM), is a common cause and outcome of organ failure and even death. Researchers have made many efforts to understand the mechanism of fibrogenesis and to develop therapeutic strategies; yet, the outcome remains unsatisfactory. In recent years, advances in epigenetics, including chromatin remodeling, histone modification, DNA methylation, and noncoding RNA (ncRNA), have provided more insights into the fibrotic process and have suggested the possibility of novel therapy for organ fibrosis. In this review, we summarize the current research on the epigenetic mechanisms involved in organ fibrosis and their possible clinical applications.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Humans , DNA Methylation/genetics , Extracellular Matrix/genetics , Protein Processing, Post-Translational , Research Personnel
13.
Stem Cells ; 40(1): 59-73, 2022 03 03.
Article in English | MEDLINE | ID: mdl-35511865

ABSTRACT

Increased neurogenesis elicits antidepressive-like effects. The antidiabetic drug metformin (Met) reportedly promotes hippocampal neurogenesis, which ameliorates spatial memory deficits and depression-like behaviors. However, the precise molecular mechanisms underpinning Met-induced neuronal differentiation of neural stem cells (NSCs) remain unclear. We showed that Met enhanced neuronal differentiation of NSCs via Gadd45g but not Gadd45a and Gadd45b. We further found that Gadd45g increased demethylation of neurogenic differentiation 1 promoter by regulating the activity of passive and active DNA demethylation enzymes through an adenylate-activated protein kinase -independent mechanism in Met-treated NSCs. Importantly, genetic deficiency of Gadd45g decreased hippocampal neurogenesis, which could contribute to spatial memory decline, and depression-like behaviors in the adult mice, whereas forced expression of Gadd45g alleviated the depressive-like behaviors. Our findings provide a model that Gadd45g-mediated DNA demethylation contributes to Met-induced neuronal genesis and its antidepressant-like effects and propose the concept that targeting Gadd45g regulation of neurogenesis might serve as a novel antidepressant strategy.


Subject(s)
Metformin , Neural Stem Cells , Animals , Antidepressive Agents/metabolism , Antidepressive Agents/pharmacology , Antigens, Differentiation/genetics , Antigens, Differentiation/metabolism , DNA Demethylation , Hippocampus/metabolism , Metformin/metabolism , Metformin/pharmacology , Mice , Neural Stem Cells/metabolism , Neurogenesis
14.
Exp Dermatol ; 32(12): 2112-2120, 2023 12.
Article in English | MEDLINE | ID: mdl-37859506

ABSTRACT

Skin expands and regenerates in response to mechanical stretch. This important homeostasis process is critical for skin biology and can be exploited to generate extra skin for reconstructive surgery. Atmospheric oxygen uptake is important in skin homeostasis. However, whether and how cutaneous atmospheric oxygen uptake changes during mechanical stretch remains unclear, and relevant research tools to quantify oxygen flux are limited. Herein, we used the scanning micro-optrode technique (SMOT), a non-invasive self-referencing optical fiber microsensor, to achieve real-time measurement of cutaneous oxygen uptake from the atmosphere. An in vivo mechanical stretch-induced skin expansion model was established, and an in vitro Flexcell Tension system was used to stretch epidermal cells. We found that oxygen influx of skin increased dramatically after stretching for 1 to 3 days and decreased to the non-stretched level after 7 days. The enhanced oxygen influx of stretched skin was associated with increased epidermal basal cell proliferation and impaired epidermal barrier. In conclusion, mechanical stretch increases cutaneous oxygen uptake with spatial-temporal characteristics, correlating with cell proliferation and barrier changes, suggesting a fundamental mechanistic role of oxygen uptake in the skin in response to mechanical stretch. Optical fiber microsensor-based oxygen uptake detection provides a non-invasive approach to understand skin homeostasis.


Subject(s)
Optical Fibers , Skin , Epidermis , Cell Proliferation , Oxygen , Stress, Mechanical
15.
FASEB J ; 36(7): e22392, 2022 07.
Article in English | MEDLINE | ID: mdl-35716070

ABSTRACT

N6 -methyladenosine (m6 A) is the most abundant mRNA modification affecting diverse biological processes. However, the functions and precise mechanisms of m6 A signaling in adult hippocampal neurogenesis and neurogenesis-related depression remain largely enigmatic. We found that depletion of Mettl3 or Mettl14 in neural stem cells (NSCs) dramatically reduced m6 A abundance, proliferation, and neuronal genesis, coupled with enhanced glial differentiation. Conversely, overexpressing Mettl3 promoted proliferation and neuronal differentiation. Mechanistically, the m6 A modification of Lrp2 mRNA by Mettl3 enhanced its stability and translation efficiency relying on the reader protein Ythdc2, which in turn promoted neurogenesis. Importantly, mice lacking Mettl3 manifested reduced hippocampal neurogenesis, which could contribute to spatial memory decline, and depression-like behaviors. We found that these defective behaviors were notably reversed by Lrp2 overexpression. Moreover, Mettl3 overexpression in the hippocampus of depressive mice rescues behavioral defects. Our findings uncover the biological role of m6 A modification in Lrp2-mediated neurogenesis via m6 A-binding protein Ythdc2, and propose a rationale that targeting Mettl3-Ythdc2-Lrp2 axis regulation of neurogenesis might serve as a promising antidepressant strategy.


Subject(s)
Adenosine , Low Density Lipoprotein Receptor-Related Protein-2 , Methyltransferases , Neurogenesis , RNA Helicases , Adenosine/analogs & derivatives , Adenosine/metabolism , Animals , Low Density Lipoprotein Receptor-Related Protein-2/metabolism , Methyltransferases/metabolism , Mice , Neurogenesis/physiology , RNA Helicases/metabolism , RNA, Messenger/genetics
16.
Br J Dermatol ; 188(1): 64-74, 2023 01 23.
Article in English | MEDLINE | ID: mdl-36689509

ABSTRACT

BACKGROUND: The aetiologies of large-to-giant congenital melanocytic naevi (LGCMN) remain ambiguous. A previous study discovered signatures associated with deficient mismatch repair (dMMR) in patients with LGCMN. However, a screening diagnostic immunohistochemistry (IHC) panel of dMMR in patients with LGCMN has not been performed to date. OBJECTIVES: To identify the MMR status and aetiologies of LGCMN. METHODS: A total of 110 patients with CMN, including 30 giant CMN, 30 large CMN, 30 medium CMN and 20 small CMN, underwent diagnostic IHC (for MSH6, MSH2, PMS2 and MLH1) screening of dMMR. The control group comprised normal skin samples from 20 healthy people. MMR proteins with little effect (MSH3 and PMS1) on the MMR system were stained in all samples. The surgical procedures conducted on each patient were noted because they might alter the behaviour of CMN and confound the results. Binary logistic regression analyses were performed between the phenotypic data and MMR status to identify associations. Whole-exome sequencing was performed on the main naevi, satellite naevi and normal skin tissues of four patients to detect variants. Mutational signature analyses were conducted to explore the aetiologies of LGCMN. RESULTS: dMMR was detected in 37% (11 of 30) of giant, 23% (7 of 30) of large and 7% (2 of 30) of medium CMNs, but were not identified in small CMNs or normal skin tissues. Moreover, multiple LGCMNs had a much higher dMMR rate than did single LGCMNs. The regression analyses showed that MMR status was significantly associated with CMN size and the presence of satellites, but was not correlated with age, sex, location, satellite diversity or tissue expansion. Notably, the pattern of protein loss in LGCMN mainly consisted of PMS2 loss. Mutational signature analyses detected dMMR-related signatures in patients with LGCMN. Additionally, rare deleterious germline mutations in DNA repair genes were detected in LGCMN, mainly in MSH6, ATM, RAD50, BRCA1 and ERCC8. These germline mutations were single-patient variants with unknown significance. CONCLUSIONS: dMMR is one of the aetiologies underlying LGCMN, particularly in patients with giant main lesions and multiple satellite lesions. Further studies are necessary to investigate the role of the DNA repair system, particularly MMR, in LGCMN.


Subject(s)
Nevus, Pigmented , Skin Neoplasms , Humans , DNA Mismatch Repair , Mismatch Repair Endonuclease PMS2/genetics , Mismatch Repair Endonuclease PMS2/metabolism , DNA-Binding Proteins/genetics , Transcription Factors/genetics , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism
17.
PLoS Comput Biol ; 18(9): e1010463, 2022 09.
Article in English | MEDLINE | ID: mdl-36067157

ABSTRACT

BACKGROUND: Based on the principles of equity and effectiveness, the World Health Organization and COVAX formulate vaccine allocation as a mathematical optimization problem. This study aims to solve the optimization problem using agent-based simulations. METHODS: We built open-sourced agent-based models to simulate virus transition among a demographically representative sample of 198 million people in 148 countries using advanced computational services. All countries continuing their current vaccine progress is defined as the baseline scenario. Comparison scenarios include achieving minimum vaccination rates and allocating vaccines based on pandemic levels. FINDINGS: The simulations are fitted using the pandemic data from 148 countries from January 2020 to June 2021. Under the baseline scenario, the world will add 24.36 million cases and 468,945 deaths during the projection period of three months. Inoculating at least 10%, 20%, and 26% of populations in all countries requires 1.12, 3.31, and 5.00 million additional vaccine doses every day, respectively. Achieving these benchmarks reduces new cases by 0.56, 2.74, and 3.32 million, respectively. If allocated by the current global distribution, 5.00 million additional vaccine doses will only avert 1.45 million new cases. If those 5.00 million vaccines are allocated based on projected cases in each country, the averted cases will increase more than six-fold to 9.20 million. Similar differences between allocation methods are observed in averted deaths. CONCLUSION: The global distribution of COVID-19 vaccines can be optimized to achieve better outcomes in terms of both equity and effectiveness. Alternative vaccine allocation methods may avert several times more cases and deaths than the current global distribution. With reasonable requirements on additional vaccines, COVAX could adopt alternative allocation strategies that reduce cross-country inequity and save more lives.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Computer Simulation , Global Health , Humans , Vaccination , World Health Organization
18.
J Fluoresc ; 33(6): 2241-2252, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37010649

ABSTRACT

Cyclodextrin (CD) is an important guest material owing to the water solubility and biocompatibility. In the paper, an organic small molecule was synthesized. According to supramolecular self-assembly, the organic molecule was bounded to the cavity of Poly ß-cyclodextrin, which was characterized by IR, SEM and TEM et al. After self-assembly interaction, the morphology has changed obviously comparing with precursors. Simultaneously, the supramolecular self-assembly complex exhibited good water solubility. Moreover, By Gaussian calculation, the high binding activity between organic molecule and cyclodextrin was confirmed. By fluorescence investigation, the supramolecular system showed high fluorescence sensing activity for Zn2+ in pure water environment, which could track the dynamic change of Zn2+ in organisms. In addition, the supramolecular system exhibited low cytotoxicity. The work provided an interesting pathway for constructing water-soluble and low cytotoxic fluorescence sensor for Zn2+.

19.
Clin Exp Dermatol ; 48(12): 1317-1327, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37566911

ABSTRACT

Heterogeneous dermal fibroblasts are the main components that constitute the dermis. Distinct fibroblast subgroups show specific characteristics and functional plasticity that determine dermal structure during skin development and wound healing. Although researchers have described the roles of fibroblast subsets, this is not completely understood. We review recent evidence supporting understanding about the heterogeneity of fibroblasts. We summarize the origins and the identified profiles of fibroblast subpopulations. The characteristics of fibroblast subpopulations in both healthy and diseased states are highlighted, and the potential of subpopulations to be involved in wound healing in different ways was discussed. Additionally, we review the plasticity of subpopulations and the underlying signalling mechanisms. This review may provide greater insights into potential novel therapeutic targets and tissue regeneration strategies for the future.


Subject(s)
Dermis , Skin , Humans , Wound Healing , Fibroblasts , Signal Transduction
20.
BMC Pediatr ; 23(1): 631, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097983

ABSTRACT

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.


Subject(s)
Nose Diseases , Nose , Female , Humans , Mutation , Nose/abnormalities , Nose/surgery , Nose Diseases/diagnosis , Nose Diseases/surgery , Tomography, X-Ray Computed
SELECTION OF CITATIONS
SEARCH DETAIL