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1.
Nature ; 580(7803): E7, 2020 04.
Article in English | MEDLINE | ID: mdl-32296181

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nature ; 579(7798): 265-269, 2020 03.
Article in English | MEDLINE | ID: mdl-32015508

ABSTRACT

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.


Subject(s)
Betacoronavirus/classification , Communicable Diseases, Emerging/complications , Communicable Diseases, Emerging/virology , Coronavirus Infections/complications , Coronavirus Infections/virology , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/virology , Adult , Betacoronavirus/genetics , COVID-19 , China , Communicable Diseases, Emerging/diagnostic imaging , Communicable Diseases, Emerging/pathology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Genome, Viral/genetics , Humans , Lung/diagnostic imaging , Male , Phylogeny , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , RNA, Viral/genetics , Recombination, Genetic/genetics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/pathology , Tomography, X-Ray Computed , Whole Genome Sequencing
3.
FASEB J ; 38(20): e70103, 2024 Oct 31.
Article in English | MEDLINE | ID: mdl-39400419

ABSTRACT

The healing of human skin wounds is susceptible to perturbation caused by excessive mechanical stretching, resulting in enlarged scars, hypertrophic scars, or even keloids in predisposed individuals. Keloids are fibro-proliferative scar tissues that extend beyond the initial wound boundary, consisting of the actively progressing periphery and the quiescent center. The stretch-associated outgrowth and enhanced angiogenesis are two features of the periphery of keloids. However, which cell population is responsible for transducing the mechanical stimulation to the progression of keloids remains unclear. Herein, through integrative analysis of single-cell RNA sequencing of keloids, we identified CD74+ fibroblasts, a previously unappreciated subset of fibroblasts with pro-angiogenic and stretch-induced proliferative capacities, as a key player in stretch-induced progression of keloids. Immunostaining of keloid cryosections depicted a predominant distribution of CD74+ fibroblasts in the periphery, interacting with the vasculature. In vitro tube formation assays on purified CD74+ fibroblasts ascertained their pro-angiogenic function. BrdU assays revealed that these cells proliferate upon stretching, through PIEZO1-mediated calcium influx and the downstream ERK and AKT signaling. Collectively, our findings propose a model wherein CD74+ fibroblasts serve as pivotal drivers of stretch-induced keloid progression, fueled by their proliferative and pro-angiogenic activities. Targeting the attributes of CD74+ fibroblasts holds promise as a therapeutic strategy for the management of keloids.


Subject(s)
Cell Proliferation , Fibroblasts , Keloid , Neovascularization, Pathologic , Keloid/metabolism , Keloid/pathology , Humans , Fibroblasts/metabolism , Neovascularization, Pathologic/metabolism , Antigens, Differentiation, B-Lymphocyte/metabolism , Stress, Mechanical , Male , Female , Cells, Cultured , Adult , Angiogenesis , Histocompatibility Antigens Class II
4.
Anal Chem ; 96(26): 10630-10638, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38912708

ABSTRACT

Paper-based lateral flow immunoassays (LFIAs) are cost-effective, portable, and simple methods for detection of diverse analytes, which however only provide qualitative or semiquantitative results and lack sufficient sensitivity. A combination of LFIA and electrochemical detection, namely, electrochemical lateral flow immunoassay (eLFIA), enables quantitative detection of analytes with high sensitivity, but the integration of external electrodes makes the system relatively expensive and unstable. Herein, the working, counter, and reference electrodes were prepared directly on the nitrocellulose membrane using screen printing, which remarkably simplified the structure of eLFIA and decreased the cost. Moreover, a horseradish peroxidase (HRP)-based electrochemical signal amplification strategy was used for further increasing the analytical sensitivity. HRP captured on the working electrode can catalyze the oxidation of tetramethylbenzidine (TMB) to form the TMB-TMBox precipitate on the electrode surface, which as an electrochemically active product can output an amplified current for quantification. We demonstrated that the eLFIA could detect low-abundant inflammatory biomarkers in human plasma samples with limits of detection of 0.17 and 0.54 pg mL-1 for interleukin-6 and C-reactive protein, respectively. Finally, a fully portable system was fabricated by integrating eLFIA with a flexible and wireless electrochemical workstation, realizing the point-of-care detection of interleukin-6.


Subject(s)
Biomarkers , C-Reactive Protein , Electrochemical Techniques , Electrodes , Interleukin-6 , Humans , Immunoassay/methods , Immunoassay/instrumentation , Electrochemical Techniques/instrumentation , Biomarkers/blood , Biomarkers/analysis , Interleukin-6/blood , Interleukin-6/analysis , C-Reactive Protein/analysis , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism , Limit of Detection , Inflammation/blood , Inflammation/diagnosis , Benzidines
5.
Exp Dermatol ; 33(7): e15148, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39051739

ABSTRACT

Cutaneous melanoma, a malignancy of melanocytes, presents a significant challenge due to its aggressive nature and rising global incidence. Despite advancements in treatment, the variability in patient responses underscores the need for further research into novel therapeutic targets, including the role of programmed cell death pathways such as necroptosis. The melanoma datasets used for analysis, GSE215120, GSE19234, GSE22153 and GSE65904, were downloaded from the GEO database. The melanoma data from TCGA were downloaded from the UCSC website. Using single-cell sequencing, we assess the heterogeneity of necroptosis in cutaneous melanoma, identifying distinct cell clusters and necroptosis-related gene expression patterns. A combination of 101 machine learning algorithms was employed to construct a necroptosis-related signature (NRS) based on key genes associated with necroptosis. The prognostic value of NRS was evaluated in four cohorts (one TCGA and three GEO cohorts), and the tumour microenvironment (TME) was analysed to understand the relationship between necroptosis, tumour mutation burden (TMB) and immune infiltration. Finally, we focused on the role of key target TSPAN10 in the prognosis, pathogenesis, immunotherapy relevance and drug sensitivity of cutaneous melanoma. Our study revealed significant heterogeneity in necroptosis among melanoma cells, with a higher prevalence in epithelial cells, myeloid cells and fibroblasts. The NRS, developed through rigorous machine learning techniques, demonstrated robust prognostic capabilities, distinguishing high-risk patients with poorer outcomes in all cohorts. Analysis of the TME showed that high NRS scores correlated with lower TMB and reduced immune cell infiltration, indicating a potential mechanism through which necroptosis influences melanoma progression. Finally, TSPAN10 has been identified as a key target for cutaneous melanoma and is highly associated with poor prognosis. The findings highlight the complex role of necroptosis in cutaneous melanoma and introduce the NRS as a novel prognostic tool with potential to guide therapeutic decisions.


Subject(s)
Melanoma , Necroptosis , Single-Cell Analysis , Skin Neoplasms , Tumor Microenvironment , Humans , Melanoma/genetics , Melanoma/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Necroptosis/genetics , Prognosis , Tumor Microenvironment/genetics , Sequence Analysis, RNA , Machine Learning , Melanoma, Cutaneous Malignant
6.
Exp Dermatol ; 33(4): e15070, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38570935

ABSTRACT

Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic and molecular contributors to cutaneous melanoma development, there remains a critical knowledge gap concerning the role of lipids, notably low-density lipoprotein (LDL), in this lethal skin cancer. This article endeavours to bridge this knowledge gap by delving into the intricate interplay between LDL metabolism and cutaneous melanoma, shedding light on how lipids influence tumour progression, immune responses and potential therapeutic avenues. Genes associated with LDL metabolism were extracted from the GSEA database. We acquired and analysed single-cell sequencing data (GSE215120) and bulk-RNA sequencing data, including the TCGA data set, GSE19234, GSE22153 and GSE65904. Our analysis unveiled the heterogeneity of LDL across various cell types at the single-cell sequencing level. Additionally, we constructed an LDL-related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes and highly correlated genes. The LRS serves as a valuable tool for assessing the prognosis, immunity and mutation status of patients with cutaneous melanoma. Furthermore, we conducted experiments on A375 and WM-115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/genetics , Skin Neoplasms/genetics , Prognosis , Algorithms , Machine Learning , Gene Expression Profiling , Lipids , Tumor Microenvironment/genetics
7.
Exp Dermatol ; 33(6): e15119, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38881438

ABSTRACT

This manuscript presents a comprehensive investigation into the role of lactate metabolism-related genes as potential prognostic markers in skin cutaneous melanoma (SKCM). Bulk-transcriptome data from The Cancer Genome Atlas (TCGA) and GSE19234, GSE22153, and GSE65904 cohorts from GEO database were processed and harmonized to mitigate batch effects. Lactate metabolism scores were assigned to individual cells using the 'AUCell' package. Weighted Co-expression Network Analysis (WGCNA) was employed to identify gene modules correlated with lactate metabolism. Machine learning algorithms were applied to construct a prognostic model, and its performance was evaluated in multiple cohorts. Immune correlation, mutation analysis, and enrichment analysis were conducted to further characterize the prognostic model's biological implications. Finally, the function of key gene NDUFS7 was verified by cell experiments. Machine learning resulted in an optimal prognostic model, demonstrating significant prognostic value across various cohorts. In the different cohorts, the high-risk group showed a poor prognosis. Immune analysis indicated differences in immune cell infiltration and checkpoint gene expression between risk groups. Mutation analysis identified genes with high mutation loads in SKCM. Enrichment analysis unveiled enriched pathways and biological processes in high-risk SKCM patients. NDUFS7 was found to be a hub gene in the protein-protein interaction network. After the expression of NDUFS7 was reduced by siRNA knockdown, CCK-8, colony formation, transwell and wound healing tests showed that the activity, proliferation and migration of A375 and WM115 cell lines were significantly decreased. This study offers insights into the prognostic significance of lactate metabolism-related genes in SKCM.


Subject(s)
Lactic Acid , Machine Learning , Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Melanoma/genetics , Melanoma/metabolism , Prognosis , Lactic Acid/metabolism , Single-Cell Analysis , Mutation , Transcriptome , Melanoma, Cutaneous Malignant , Cell Line, Tumor , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics
8.
Chemistry ; : e202403185, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39340304

ABSTRACT

With high specific surface area, excellent polysulfide conversion activity, and fast electron/ion transfer at the interface, MXene-derived heterostructures can be employed as catalysts for lithium-sulfur (Li-S) batteries to accelerate sulfur redox kinetics and suppress shuttle effect. However, the preparation of MXene-derived heterostructures often requires high-temperature reactions, which can easily lead to the oxidation of MXene and sacrifice the electrical conductivity. Herein, a catalytic two-dimensional heterostructure (ZnS/MXene) was successfully synthesized via a mild method. The MXene skeleton retains the original nanosheet structure without oxidation. The in situ-grown ZnS nanospheres prevent the restacking of MXene nanosheets, which not only increases the active sites, but also guarantees channels for the fast passage of lithium ions. The interfacial built-in electric field further promotes electron/ion migration, thereby expediting the polysulfide conversion and suppressing the shuttle effect. Consequently, the batteries using ZnS/MXene modified separators exhibit a high initial discharge capacity of 1230 mAh g-1 at 0.1 C and a low decaying rate of 0.082% per cycle after 500 cycles at 0.5 C. This work offers a reference for the fabrication of MXene-based heterostructure in Li-S batteries.

9.
Gynecol Oncol ; 190: 167-178, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39197416

ABSTRACT

OBJECTIVE: Ovarian cancer is the malignant tumor with the highest mortality rate in gynecology. We aimed to identify novel genes that promote ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions. METHODS: We screened SVIL as a hypoxia-associated target in ovarian cancer and explored the related molecular mechanisms. We assessed the effects of SVIL on ovarian cancer progression and metastasis in clinical samples and cellular hypoxia models. Further, we investigated the relevant pathways of SVIL and confirmed the effects of SVIL on ovarian cancer progression by using nude mouse in situ tumor models. RESULTS: We found that SVIL was significantly highly expressed in the hypoxic environment of ovarian cancer, and SVIL expression correlated with patient prognosis.CCK8, Wound-healing assay, Transwell assay, Western Blot, and apoptosis assays revealed that knockdown of SVIL inhibited the activation of the TGFß1/smad2/3 pathway, which attenuated the progression and epithelial-mesenchymal transition(EMT) of ovarian cancer and alleviated cisplatin resistance by increasing cisplatin-induced apoptosis. Furthermore, in a nude mouse ovarian cancer in situ model, we found that the knockdown of SVIL significantly inhibited tumor growth and metastasis. CONCLUSION: SVIL highly expressed in the hypoxic microenvironment can increase ovarian cancer progression and cisplatin resistance by activating TGFß1/smad2/3 pathway. Our study demonstrated that SVIL may be a novel target for the treatment of ovarian cancer.

10.
BMC Infect Dis ; 24(1): 571, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851671

ABSTRACT

OBJECTIVE: In this study, we examined the value of chest CT signs combined with peripheral blood eosinophil percentage in differentiating between pulmonary paragonimiasis and tuberculous pleurisy in children. METHODS: Patients with pulmonary paragonimiasis and tuberculous pleurisy were retrospectively enrolled from January 2019 to April 2023 at the Kunming Third People's Hospital and Lincang People's Hospital. There were 69 patients with pulmonary paragonimiasis (paragonimiasis group) and 89 patients with tuberculous pleurisy (tuberculosis group). Clinical symptoms, chest CT imaging findings, and laboratory test results were analyzed. Using binary logistic regression, an imaging model of CT signs and a combined model of CT signs and eosinophils were developed to calculate and compare the differential diagnostic performance of the two models. RESULTS: CT signs were used to establish the imaging model, and the receiver operating characteristic (ROC) curve was plotted. The area under the curve (AUC) was 0.856 (95% CI: 0.799-0.913), the sensitivity was 66.7%, and the specificity was 88.9%. The combined model was established using the CT signs and eosinophil percentage, and the ROC was plotted. The AUC curve was 0.950 (95% CI: 0.919-0.980), the sensitivity was 89.9%, and the specificity was 90.1%. The differential diagnostic efficiency of the combined model was higher than that of the imaging model, and the difference in AUC was statistically significant. CONCLUSION: The combined model has a higher differential diagnosis efficiency than the imaging model in the differentiation of pulmonary paragonimiasis and tuberculous pleurisy in children. The presence of a tunnel sign on chest CT, the absence of pulmonary nodules, and an elevated percentage of peripheral blood eosinophils are indicative of pulmonary paragonimiasis in children.


Subject(s)
Eosinophils , Paragonimiasis , Tomography, X-Ray Computed , Tuberculosis, Pleural , Humans , Paragonimiasis/diagnosis , Paragonimiasis/diagnostic imaging , Male , Female , Child , Retrospective Studies , Diagnosis, Differential , Tuberculosis, Pleural/diagnosis , Child, Preschool , Adolescent , ROC Curve , Sensitivity and Specificity
11.
Article in English | MEDLINE | ID: mdl-39110374

ABSTRACT

OBJECTIVE: The association between thyroid function, coagulation and venous thromboembolism (VTE) has been reported in observational studies with conflicting findings. This study aimed to elucidate the causal effects of thyroid function on coagulation and VTE from a genetic perspective. METHODS: Two sample Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies in a European population. Coagulation status was associated with nine coagulation-related factors (F VIII, F IX, F XI, Fibrinogen, Antithrombin-III, Thrombomodulin, Plasminogen activator inhibitor-1, Protein C and Protein S). Inverse variance weighting with random effect method was used as the main analytic approach with MR-Egger, weighted median, simple mode and weighted mode methods serving as complements. Sensitivity analyses including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis were conducted to further assess the reliability of results. RESULTS: No genetic causal effects of thyroid function on VTE (including pulmonary embolism and deep venous thrombosis) were found. Genetically, hyperthyroidism was suggestively related to decreased Antithrombin-III (ß: -0.04 [95% CI: -0.06 to - 0.01], p = 0.010) and Protein C (ß: -0.03 [95% CI: -0.06 to 0.00], p = 0.045). No notable associations were observed between other thyroid function parameters and coagulation-related factors. CONCLUSION: We provide suggestive genetic evidence supporting the causal effect of hyperthyroidism on decreased level of anticoagulant factors including Antithrombin-III and Protein C. However, whether this genetic causality could lead to clinically significant hypercoagulable state and increased risk of VTE in hyperthyroid population needs to be further addressed.

12.
BMC Pregnancy Childbirth ; 24(1): 77, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263003

ABSTRACT

OBJECTIVE: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB). METHODS: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared. RESULTS: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05). CONCLUSION: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.


Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Female , Humans , Pregnancy , Embryo Transfer , Fertilization , Retrospective Studies , Case-Control Studies
13.
Environ Toxicol ; 39(5): 2545-2559, 2024 May.
Article in English | MEDLINE | ID: mdl-38189554

ABSTRACT

Programmed cell death plays a pivotal role in maintaining tissue homeostasis, and recent advancements in cell biology have uncovered PANoptosis-a novel paradigm integrating pyroptosis, apoptosis, and necroptosis. This study investigates the implications of PANoptosis in melanoma, a formidable skin cancer known for its metastatic potential and resistance to conventional therapies. Leveraging bulk and single-cell transcriptome analyses, machine learning modeling, and immune correlation assessments, we unveil the molecular intricacies of PANoptosis in melanoma. Single-cell sequencing identifies diverse cell types involved in PANoptosis, while bulk transcriptome analysis reveals key gene sets correlated with PANoptosis. Machine learning algorithms construct a robust prognostic model, demonstrating consistent predictive power across diverse cohorts. Patients with different cohorts can be divided into high-risk and low-risk groups according to this PANoptosis score, with the high-risk group having a significantly worse prognosis. Immune correlation analyses unveil a link between PANoptosis and immunotherapy response, with potential therapeutic implications. Mutation analysis and enrichment studies provide insights into the mutational landscape associated with PANoptosis. Finally, we used cell experiments to verify the expression and function of key gene PARVA, showing that PARVA was highly expressed in melanoma cell lines, and after PARVA is knocked down, cell invasion, migration, and colony formation ability were significantly decreased. This study advances our understanding of PANoptosis in melanoma, offering a comprehensive framework for targeted therapeutic interventions and personalized medicine strategies in combating this aggressive malignancy.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/genetics , Gene Expression Profiling , Transcriptome , Skin Neoplasms/genetics , Apoptosis
14.
Mikrochim Acta ; 191(2): 114, 2024 01 29.
Article in English | MEDLINE | ID: mdl-38286853

ABSTRACT

The detection of botulinum neurotoxin A (BoNT/A) endopeptidase activity by pregnancy test paper based on human chorionic gonadotropin (hCG)-functionalized peptide-modified magnetic nanoparticles (MNs) is described for the first time. HCG-functionalized SNAP-25 peptide substrate with hydrolysis recognition sites was optimally designed. HCG can be recognized by pregnancy test strips. BoNT/A light chain (BoNT-LcA) is the central part of the endopeptidase function in holotoxin, which can specifically hydrolyze SNAP-25 peptide to release the hCG-peptide probe, and the hCG-peptide probe released can be quantitatively detected by pregnancy test strips, achieving indirect determination of BoNT/A. By quantifying the T-line color intensity of test strips, the visual detection limit for BoNT-LcA is 12.5 pg/mL, and the linear range of detection for BoNT-LcA and BoNT/A holotoxin was 100 pg/mL to 1 ng/mL and 25 to 250 ng/mL. The ability of the method to quantify BoNT/A was validated in human serum samples. This method shows the potential for sensitive detecting BoNT/A and has prospects for the diagnosis and prognosis of clinical botulism.


Subject(s)
Botulinum Toxins, Type A , Glycosides , Magnetite Nanoparticles , Pregnancy Tests , Triterpenes , Humans , Female , Pregnancy , Endopeptidases , Chorionic Gonadotropin
15.
Apoptosis ; 28(5-6): 840-859, 2023 06.
Article in English | MEDLINE | ID: mdl-36964478

ABSTRACT

Ferroptosis, a form of cell death caused by iron-dependent peroxidation of lipids, plays an important role in cancer. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of ferroptosis in tumor cells and are also closely related to tumor immunity. Immune cell infiltration in the tumor microenvironment affects the prognosis and clinical outcome of immunotherapy in melanoma patients, and immune cell classification may be able to accurately predict the prognosis of melanoma patients. However, the prognostic value of ferroptosis-related lncRNAs (FRLs) in melanoma has not been thoroughly explored, and it is difficult to define the immune characteristics of melanoma. We used The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) database, and the FerrDb database to identify FRLs. FRLs with prognostic value were evaluated in an experimental cohort utilizing univariate, LASSO (least absolute shrinkage and selection operator) and multivariate Cox regression, followed by in vitro assays evaluating the expression levels and the biological functions of three candidate FRLs. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were used to assess the validity of the risk model, and the drug sensitivity of FRLs was examined by drug sensitivity analysis. The differentially expressed genes between the high- and low-risk groups in the risk model were enriched in the immune pathway, and we further found immune gene signatures (IRGs) that could predict the prognosis of melanoma patients through a series of methods including single-sample Gene Set Enrichment Analysis (ssGSEA). Finally, two GEO cohorts were used to validate the predictive accuracy and reliability of these two signature models. Our findings suggest that FRLs and IRGs have the potential to predict the prognosis of patients with cutaneous melanoma.


Subject(s)
Ferroptosis , Melanoma , RNA, Long Noncoding , Skin Neoplasms , Humans , Melanoma/genetics , Skin Neoplasms/genetics , RNA, Long Noncoding/genetics , Ferroptosis/genetics , Reproducibility of Results , Apoptosis , Tumor Microenvironment/genetics , Melanoma, Cutaneous Malignant
16.
PLoS Biol ; 18(6): e3000644, 2020 06.
Article in English | MEDLINE | ID: mdl-32511236

ABSTRACT

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial T cells in humans and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by the MHC-Ib-related protein (MR1). However, the mechanisms responsible for MAIT cell antimicrobial activity are not fully understood, and the efficacy of these mechanisms against antibiotic resistant bacteria has not been explored. Here, we show that MAIT cells mediate MR1-restricted antimicrobial activity against Escherichia coli clinical strains in a manner dependent on the activity of cytolytic proteins but independent of production of pro-inflammatory cytokines or induction of apoptosis in infected cells. The combined action of the pore-forming antimicrobial protein granulysin and the serine protease granzyme B released in response to T cell receptor (TCR)-mediated recognition of MR1-presented antigen is essential to mediate control against both cell-associated and free-living, extracellular forms of E. coli. Furthermore, MAIT cell-mediated bacterial control extends to multidrug-resistant E. coli primary clinical isolates additionally resistant to carbapenems, a class of last resort antibiotics. Notably, high levels of granulysin and granzyme B in the MAIT cell secretomes directly damage bacterial cells by increasing their permeability, rendering initially resistant E. coli susceptible to the bactericidal activity of carbapenems. These findings define the role of cytolytic effector proteins in MAIT cell-mediated antimicrobial activity and indicate that granulysin and granzyme B synergize to restore carbapenem bactericidal activity and overcome carbapenem resistance in E. coli.


Subject(s)
Antigens, Differentiation, T-Lymphocyte/metabolism , Carbapenems/pharmacology , Cytotoxicity, Immunologic , Drug Resistance, Bacterial/drug effects , Escherichia coli/drug effects , Granzymes/metabolism , Mucosal-Associated Invariant T Cells/immunology , Anti-Infective Agents/pharmacology , Bacterial Load/drug effects , Cytotoxicity, Immunologic/drug effects , HeLa Cells , Humans , Kinetics
17.
BMC Endocr Disord ; 23(1): 145, 2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37430225

ABSTRACT

BACKGROUND: Pheochromocytoma (PCC) crisis is a rare life-threatening endocrine emergency. The diagnosis and treatment of PCC crisis, with acute respiratory distress syndrome (ARDS) as the first manifestation, is highly challenging, and traditional PCC management strategies are no longer suitable for these patients. CASE PRESENTATION: A 46-year-old female patient was admitted to the Intensive Care Unit (ICU) following sudden-onset acute respiratory distress and subsequent initiation of mechanical ventilation via endotracheal intubation. She was initially suspected of having a PCC crisis through the bedside critical care ultrasonic examination protocol. The computed tomography examination revealed a left adrenal neoplasm of 6.5cm × 5.9cm. The plasma-free metanephrine level was 100 times higher than the reference value. These findings were compatible with her PCC diagnosis. Alpha-blockers and fluid intake were started immediately. The endotracheal intubation was removed on the 11th day after admission to the ICU. The patient progressed to severe ARDS again, and invasive ventilation and continuous renal replacement therapy were needed. Despite aggressive therapy, her condition deteriorated. Therefore, she underwent veno-arterial extracorporeal membrane oxygenation (VA-ECMO)-assisted emergency adrenalectomy after multidisciplinary discussion. Postoperatively, the patient was supported by VA-ECMO for 7days. She was discharged from the hospital on day 30 after tumor resection. CONCLUSIONS: This case highlighted the challenges in diagnosing and managing ARDS associated with PCC crisis. The traditional preoperative preparation protocol and optimal operation timing for patients with PCC are not suitable for patients with PCC crisis. Patients with life-threatening PCC crisis may benefit from early tumor removal, and VA-ECMO could maintain hemodynamic stability during and after surgery.


Subject(s)
Adrenal Gland Neoplasms , Extracorporeal Membrane Oxygenation , Metoclopramide , Pheochromocytoma , Respiratory Distress Syndrome , Takotsubo Cardiomyopathy , Female , Humans , Middle Aged , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Metoclopramide/adverse effects , Pheochromocytoma/complications , Pheochromocytoma/diagnosis , Pheochromocytoma/surgery , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/etiology , Takotsubo Cardiomyopathy/therapy , Treatment Outcome
18.
Mediators Inflamm ; 2023: 1164147, 2023.
Article in English | MEDLINE | ID: mdl-37091902

ABSTRACT

Lumbar spinal stenosis (LSS), which can lead to irreversible neurologic damage and functional disability, is characterized by hypertrophy and fibrosis in the ligamentum flavum (LF). However, the underlying mechanism is still unclear. In the current study, the effect of Smurf1, a kind of E3 ubiquitin ligase, in promoting the fibrosis and oxidative stress of LF was investigated, and its underlying mechanism was explored. The expression of oxidative stress and fibrosis-related markers was assessed in the tissue of lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Next, the expression of the top 10 E3 ubiquitin ligases, obtained from Gene Expression Omnibus (GEO) dataset GSE113212, was assessed in LDH and LSS, and confirmed that Smurf1 expression was markedly upregulated in the LSS group. Furthermore, Smurf1 overexpression promotes the fibrosis and oxidative stress of LF cells. Subsequently, NRF2, an important transcription factor for oxidative stress and fibrosis, was predicted to be a target of Smurf1. Mechanistically, Smurf1 directly interacts with Nrf2 and accelerates Nrf2 ubiquitination and degradation. In conclusion, the current study suggests that Smurf1 facilitated the fibrosis and oxidative stress of LF and induced the development of LSS by promoting Nrf2 ubiquitination and degradation.


Subject(s)
Ligamentum Flavum , Spinal Stenosis , Humans , Spinal Stenosis/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Ligamentum Flavum/metabolism , Ligamentum Flavum/pathology , Fibrosis , Ubiquitination , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Lumbar Vertebrae/metabolism , Hypertrophy/metabolism , Hypertrophy/pathology , Oxidative Stress
19.
Sensors (Basel) ; 23(13)2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37448035

ABSTRACT

Artificial intelligence technologies such as computer vision (CV), machine learning, Internet of Things (IoT), and robotics have advanced rapidly in recent years. The new technologies provide non-contact measurements in three areas: indoor environmental monitoring, outdoor environ-mental monitoring, and equipment monitoring. This paper summarizes the specific applications of non-contact measurement based on infrared images and visible images in the areas of personnel skin temperature, position posture, the urban physical environment, building construction safety, and equipment operation status. At the same time, the challenges and opportunities associated with the application of CV technology are anticipated.


Subject(s)
Artificial Intelligence , Computers , Technology
20.
Int Wound J ; 20(10): 3974-3980, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37376826

ABSTRACT

A meta-analysis was conducted to comprehensively assess the effect of continuous nursing on wound infection and quality of life in patients with cancer-related stomas, providing an evidence-based rationale for the care of these patients. A computerised search of PubMed, Web of Science, Ovid, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data for randomised controlled trials (RCTs) on the effect of continuous nursing on wound infection and quality of life in patients with cancer-related stoma was conducted from the time the database was created to March 2023. The retrieved literature was screened, data were extracted, and the quality of the literature was evaluated according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Seventeen RCTs involving 1437 patients were included. Of the 1437 patients, 728 were in the continuous nursing group and 709 were in the control group. The results showed that continuous nursing significantly reduced the rate of wound infection in patients with cancer-related stomas (odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.16-0.53, p < 0.001) and improved their quality of life (standardised mean difference: 1.90. 95% CI: 1.32-2.47, p < 0.001). Available evidence suggests that continuous nursing for patients with cancer-related stomas can significantly reduce wound infections and improve their quality of life.


Subject(s)
Neoplasms , Surgical Stomas , Humans , Neoplasms/surgery , Surgical Wound Infection , Quality of Life , China
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