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1.
Front Cardiovasc Med ; 11: 1369642, 2024.
Article in English | MEDLINE | ID: mdl-38716483

ABSTRACT

Refractory heart failure (RHF), or end-stage heart failure, has a poor prognosis and high case fatality rate, making it one of the therapeutic difficulties in the cardiovascular field. Despite the continuous abundance of methods and means for treating RHF in modern medicine, it still cannot meet the clinical needs of patients with RHF. How to further reduce the mortality rate and readmission rate of patients with RHF and improve their quality of life is still a difficult point in current research. In China, traditional Chinese medicine (TCM) has been widely used and has accumulated rich experience in the treatment of RHF due to its unique efficacy and safety advantages. Based on this, we comprehensively summarized and analyzed the clinical evidence and mechanism of action of TCM in the treatment of RHF and proposed urgent scientific issues and future research strategies for the treatment of RHF with TCM, to provide reference for the treatment of RHF.

2.
Analyst ; 149(10): 2996-3007, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38602375

ABSTRACT

Electrical insulators used in transmission lines and outdoor substations are exposed to severe environmental pollution, which significantly increases the risk of power system failure, especially when the pollution layer is highly humid due to adverse weather conditions. The focus of this paper is to establish an effective method for assessing the moisture content (MC) in pollution layers as it serves as a crucial indicator for evaluating the risk of failure in insulators. Hyperspectral imaging (HSI) technology with a spectral range of 371.08-1037.89 nm was applied to determine significant changes in reflectance spectral characteristics in insulators during dynamic wetting and drying periods. Partial least squares regression (PLSR) models were utilized to evaluate the data presentation enhancement abilities of spectral transformation models and the data dimensionality reduction abilities of characteristic band selection methods. Furthermore, PLSR models were developed to calculate the MC along the pixel dimension to visually retrieve the dynamic wetting and drying processes of the pollution layer. The R-squared and root-mean-square error (RMSE) results in the cross-verification set and prediction set of the RE-RF(70%)-PLSR model with two characteristic bands with a wavelength of 543.28 nm and 848.01 nm were as follows: RCV2 = 0.9824, RMSECV = 0.0367, RP2 = 0.9818, RMSEP = 0.0369, respectively. This research contributes towards the visualization retrieval of the MC and offers an important technique for analyzing flashover evolution, optimizing insulator design, and preparing coating materials for insulators.

3.
Infect Dis Poverty ; 13(1): 28, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38610035

ABSTRACT

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.


Subject(s)
One Health , Animals , Asia , Capacity Building , Policy , Zoonoses/prevention & control
4.
Adv Mater ; : e2403403, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38631689

ABSTRACT

Efficient and robust n-i-p perovskite solar cells necessitate superior organic hole-transport materials with both mechanical and electronic prowess. Deciphering the structure-property relationship of these materials is crucial for practical perovskite solar cell applications. Through direct arylation, two high glass transition temperature molecular semiconductors, DBC-ETPA (202 °C) and TPE-ETPA (180 °C) are synthesized, using dibenzo[g,p]chrysene (DBC) and 1,1,2,2-tetraphenylethene (TPE) tetrabromides with triphenylene-ethylenedioxythiophene-dimethoxytriphenylamine (ETPA). In comparison to spiro-OMeTAD, both semiconductors exhibit shallower HOMO energy levels, resulting in increased hole densities (generated by air oxidation doping) and accelerated hole extraction from photoexcited perovskite. Experimental and theoretical studies highlight the more rigid DBC core, enhancing hole mobility due to reduced reorganization energy and lower energy disorder. Importantly, DBC-ETPA possesses a higher cohesive energy density, leading to lower ion diffusion coefficients and higher Young's moduli. Leveraging these attributes, DBC-ETPA is employed as the primary hole-transport layer component, yielding perovskite solar cells with an average efficiency of 24.5%, surpassing spiro-OMeTAD reference cells (24.0%). Furthermore, DBC-ETPA-based cells exhibit superior operational stability and 85 °C thermal storage stability.

5.
ACS Nano ; 18(13): 9500-9510, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38477715

ABSTRACT

Morphing textiles, crafted using electrochemical artificial muscle yarns, boast features such as adaptive structural flexibility, programmable control, low operating voltage, and minimal thermal effect. However, the progression of these textiles is still impeded by the challenges in the continuous production of these yarn muscles and the necessity for proper structure designs that bypass operation in extensive electrolyte environments. Herein, a meters-long sheath-core structured carbon nanotube (CNT)/nylon composite yarn muscle is continuously prepared. The nylon core not only reduces the consumption of CNTs but also amplifies the surface area for interaction between the CNT yarn and the electrolyte, leading to an enhanced effective actuation volume. When driven electrochemically, the CNT@nylon yarn muscle demonstrates a maximum contractile stroke of 26.4%, a maximum contractile rate of 15.8% s-1, and a maximum power density of 0.37 W g-1, surpassing pure CNT yarn muscles by 1.59, 1.82, and 5.5 times, respectively. By knitting the electrochemical CNT@nylon artificial muscle yarns into a soft fabric that serves as both a soft scaffold and an electrolyte container, we achieved a morphing textile is achieved. This textile can perform programmable multiple motion modes in air such as contraction and sectional bending.

6.
Theranostics ; 14(5): 2127-2150, 2024.
Article in English | MEDLINE | ID: mdl-38505619

ABSTRACT

Rationale: Immune checkpoint inhibitors targeting the programmed cell death (PD)-1/PD-L1 pathway have promise in patients with advanced melanoma. However, drug resistance usually results in limited patient benefits. Recent single-cell RNA sequencing studies have elucidated that MM patients display distinctive transcriptional features of tumor cells, immune cells and interstitial cells, including loss of antigen presentation function of tumor cells, exhaustion of CD8+T and extracellular matrix secreted by fibroblasts to prevents immune infiltration, which leads to a poor response to immune checkpoint inhibitors (ICIs). However, cell subgroups beneficial to anti-tumor immunity and the model developed by them remain to be further identified. Methods: In this clinical study of neoadjuvant therapy with anti-PD-1 in advanced melanoma, tumor tissues were collected before and after treatment for single-nucleus sequencing, and the results were verified using multicolor immunofluorescence staining and public datasets. Results: This study describes four cell subgroups which are closely associated with the effectiveness of anti-PD-1 treatment. It also describes a cell-cell communication network, in which the interaction of the four cell subgroups contributes to anti-tumor immunity. Furthermore, we discuss a newly developed predictive model based on these four subgroups that holds significant potential for assessing the efficacy of anti-PD-1 treatment. Conclusions: These findings elucidate the primary mechanism of anti-PD-1 resistance and offer guidance for clinical drug administration for melanoma.


Subject(s)
Melanoma , Humans , Melanoma/pathology , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , B7-H1 Antigen , Tumor Microenvironment
7.
Environ Sci Technol ; 58(13): 5739-5749, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38456395

ABSTRACT

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.


Subject(s)
Diethylhexyl Phthalate , Phthalic Acids , Humans , Pregnancy , Infant, Newborn , Female , Plasticizers , Meconium/metabolism , Diethylhexyl Phthalate/metabolism , Diethylhexyl Phthalate/toxicity , Phthalic Acids/metabolism , Hair/metabolism , Organophosphates , Biotransformation , Esters/metabolism , Environmental Exposure/analysis
9.
Biomol Biomed ; 2024 02 23.
Article in English | MEDLINE | ID: mdl-38400838

ABSTRACT

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial­mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-Cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.

10.
Cell Biol Toxicol ; 40(1): 9, 2024 02 05.
Article in English | MEDLINE | ID: mdl-38311675

ABSTRACT

Circular RNAs (circRNAs) have been documented to play crucial roles in the biology of various cancers. However, their investigation in melanoma is still at an early stage, particularly as a broader mechanism beyond acting as miRNA sponges needs to be explored. We report here that circFCHO2(hsa_circ_0002490), a circRNA encompassing exons 19 and 20 of the FCHO2 gene, exhibited a consistent overexpression in melanoma tissues. Furthermore, elevated circFCHO2 levels demonstrated a positive correlation with the malignant phenotype and poor prognosis among the 158 melanoma patients studied. Besides, we observed that heightened levels of circFCHO2 promoted melanoma cell proliferation, migration, and invasion in vitro, along with contributing to tumor growth in vivo. Furthermore, we found differences in the secondary structure of circFCHO2 compared to most other circular RNA structures. It has fewer miRNA binding sites, while it has more RNA binding protein binding sites. We therefore speculate that circFCHO2 may have a function of interacting with RNA binding proteins. Mechanistically, it was confirmed by fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), and western blotting assays that circFCHO2 interacts with dead end protein homolog 1 (DND1) and reverses the inhibition of the PI3K/AKT signaling pathway by binding to DND1. Our findings reveal that circFCHO2 drives melanoma progression by regulating the PI3K/AKT signaling pathway through direct binding to DND1 and may serve as a potential diagnostic biomarker and therapeutic target for the treatment of melanoma.


Subject(s)
Fatty Acid-Binding Proteins , Melanoma , Neoplasm Proteins , RNA, Circular , Humans , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , In Situ Hybridization, Fluorescence , Melanoma/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Circular/genetics , Neoplasm Proteins/genetics , Fatty Acid-Binding Proteins/genetics
11.
Angew Chem Int Ed Engl ; 63(17): e202401604, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38414115

ABSTRACT

Formamidinium lead triiodide serves as the optimal light-absorbing layer in single-junction perovskite solar cells. However, achieving operational stability of high-efficiency n-i-p type devices at elevated temperatures remains challenging. In this work, we implemented effective surface modifications on microcrystalline perovskite films. This involved the nucleophilic addition of formamidinium cations and coordination of residual PbI2 with triphenylmethane triisocyanate as well as subsequent polymerization. The in situ growth of a cross-linking network chemically anchored on the perovskite film in this approach effectively reduced trap densities, favorably altered surface work function, suppressing interface charge recombination and thus enhancing cell efficiency. Coupled with a high-melting-point air-doping promoter, we fabricated n-i-p type perovskite solar cells surpassing 25 % efficiency, demonstrating excellent operational stability at 65 °C.

12.
Physiol Rep ; 12(3): e15941, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38325910

ABSTRACT

The present study was designed to examine the effect of trans-spinal magnetic stimulation on bilateral respiratory and forelimb muscles in healthy subjects. Two wings of a figure-of-eight magnetic coil were placed on the dorsal vertebrae, from the fifth cervical to the second thoracic dorsal vertebra with a center at the seventh cervical vertebra. The surface electromyograms of bilateral diaphragm and biceps were recorded in response to trans-spinal magnetic stimulation with 20%-100% maximum output of the stimulatory device in male (n = 12) and female participants (n = 8). Trans-spinal magnetic stimulation can induce a co-activation of bilateral diaphragm and biceps when the stimulation intensity is above 60%. The onset latency was comparable between the left and right sides of the muscles, suggesting bilateral muscles could be simultaneously activated by trans-spinal magnetic stimulation. In addition, the intensity-response curve of the biceps was shifted upward compared with that of the diaphragm in males, indicating that the responsiveness of the biceps was greater than that of the diaphragm. This study demonstrated the feasibility of utilizing trans-spinal magnetic stimulation to co-activate the bilateral diaphragm and biceps. We proposed that this stimulatory configuration can be an efficient approach to activate both respiratory and forelimb muscles.


Subject(s)
Diaphragm , Forelimb , Humans , Animals , Male , Female , Diaphragm/physiology , Healthy Volunteers , Electromyography , Thoracic Vertebrae , Magnetic Phenomena , Electric Stimulation
13.
Environ Pollut ; 345: 123460, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38290655

ABSTRACT

Despite the increasing production, use, and ubiquitous occurrence of novel brominated flame retardants (NBFRs), little information is available regarding their fate in aquatic organisms. In this study, the bioaccumulation and biotransformation of two typical NBFRs, i.e., 1,2-bis (2,4,6-tribromophenoxyethane) (BTBPE) and 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH), were investigated in tissues of zebrafish (Danio rerio) being administrated a dose of target chemicals through their diet. Linear accumulation was observed for both BTBPE and TBECH in the muscle, liver, gonads, and brain of zebrafish, and the elimination of BTBPE and TBECH in all tissues followed pseudo-first-order kinetics, with the fastest depuration rate occurring in the liver. BTBPE and TBECH showed low bioaccumulation potential in zebrafish, with biomagnification factors (BMFs) < 1 in all tissues. Individual tissues' function and lipid content are vital factors affecting the distribution of BTBPE and TBECH. Stereoselective accumulation of TBECH enantiomers was observed in zebrafish tissues, with first-eluting enantiomers, i.e. E1-α-TBECH and E1-ß-TBECH, preferentially accumulated. Additionally, the transformation products (TPs) in the zebrafish liver were comprehensively screened and identified using high-resolution mass spectrometry. Twelve TPs of BTBPE and eight TPs of TBECH were identified: biotransformation pathways involving ether cleavage, debromination, hydroxylation, and methoxylation reactions for BTBPE and hydroxylation, debromination, and oxidation processes for TBECH. Biotransformation is also a vital factor affecting the bioaccumulation potential of these two NBFRs, and the environmental impacts of NBFR TPs should be further investigated in future studies. The findings of this study provide a scientific basis for an accurate assessment of the ecological and environmental risks of BTBPE and TBECH.


Subject(s)
Flame Retardants , Zebrafish , Animals , Zebrafish/metabolism , Bioaccumulation , Stereoisomerism , Biotransformation , Cyclohexanes/metabolism , Flame Retardants/analysis
14.
Adv Sci (Weinh) ; 11(13): e2304991, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38286661

ABSTRACT

Radiotherapy (RT) can induce tumor regression outside the irradiation field, known as the abscopal effect. However, the detailed underlying mechanisms remain largely unknown. A tumor-bearing mouse model is successfully constructed by inducing both subcutaneous tumors and lung metastases. Single-cell RNA sequencing, immunofluorescence, and flow cytometry are performed to explore the regulation of tumor microenvironment (TME) by RT. A series of in vitro assays, including luciferase reporter, RNA Pulldown, and fluorescent in situ hybridization (FISH) assays, are performed to evaluate the detailed mechanism of the abscopal effect. In addition, in vivo assays are performed to investigate combination therapy strategies for enhancing the abscopal effect. The results showed that RT significantly inhibited localized tumor and lung metastasis progression and improved the TME. Mechanistically, RT promoted the release of tumor-derived exosomes carrying circPIK3R3, which is taken up by macrophages. circPIK3R3 promoted Type I interferon (I-IFN) secretion and M1 polarization via the miR-872-3p/IRF7 axis. Secreted I-IFN activated the JAK/STAT signaling pathway in CD8+ T cells, and promoted IFN-γ and GZMB secretion. Together, the study shows that tumor-derived exosomes promote I-IFN secretion via the circPIK3R3/miR-872-3p/IRF7 axis in macrophages and enhance the anti-tumor immune response of CD8+ T cells.


Subject(s)
Exosomes , Lung Neoplasms , Melanoma , MicroRNAs , Animals , Mice , Antibodies , CD8-Positive T-Lymphocytes , Exosomes/radiation effects , In Situ Hybridization, Fluorescence , Interferons , Lung Neoplasms/radiotherapy , Macrophages/radiation effects , Melanoma/radiotherapy , MicroRNAs/genetics , Tumor Microenvironment , Interferon Regulatory Factor-7/immunology , Interferon Regulatory Factor-7/radiation effects
15.
Heliyon ; 10(1): e22742, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38192835

ABSTRACT

Background: Continuous light exposure increases sympathetic excitation in rats, leading to hypertension, left ventricular hypertrophy, and fibrosis. This study was aimed to investigate whether continuous light exposure causes destabilization of vital signs and gut microbiota (GM) in Sprague Dawley (SD) rats and whether clonidine hydrochloride (CH), a central sympathetic depressant drug, could prevent these changes. Methods: Eight-week-old male SD rats were divided into three groups with different interventions for 14 weeks: control group (CG), 2-mL pure water gavaged daily while on a normal 12-h light/dark cycle; continuous illumination group (CI), 2-mL pure water gavaged daily while receiving continuous exposure to light (300 lx); and drug administration group (DA), CH (10 µg/kg) gavaged daily while receiving continuous exposure to light (300 lx). Results: The results showed that blood pressure, heart rate, and body weight were significantly higher in the CI group than in the CG and DA groups (P < 0.05). Moreover, the Shannon index was higher in the DA group than in the CI group (P = 0.012). The beta diversity index in the CG group was significantly higher in the CI group (P = 0.039). The pairwise comparison results of the linear discriminant analysis effect size showed that Oscillospirales were enriched in the DA group, whereas the Prevotellaceae lineage (family level) > Prevotella (genus level) > Prevotellaceae_bacterium (species level) were enriched in the CI group. The Muribaculaceae family was more abundant in the CG group than in the CI group. Conclusion: Sympathetic nerve inhibition restored the abnormal vital signs and GM changes under continuous light exposure.

16.
J Neurotrauma ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38047526

ABSTRACT

Blast exposure can cause auditory deficits that have a lasting, significant impact on patients. Although the effects of blast on auditory functions localized to the ear have been well documented, the impact of blast on central auditory processing is largely undefined. Understanding the structural and functional alterations in the central nervous system (CNS) associated with blast injuries is crucial for unraveling blast-induced pathophysiological pathways and advancing development of therapeutic interventions. In this study, we used electrophysiology in combination with optogenetics assay, proteomic analysis, and morphological evaluation to investigate the impairment of synaptic connectivity in the auditory cortex (AC) of mice following blast exposure. Our results show that the long-range functional connectivity between the medial geniculate nucleus (MGN) and AC was impaired in the acute phase of blast injury. We also identified impaired synaptic transmission and dendritic spine alterations within 7 days of blast exposure, which recovered at 28 days post-blast. Additionally, proteomic analysis identified a few differentially expressed proteins in the cortex that are involved in synaptic signaling and plasticity. These findings collectively suggest that blast-induced alterations in the sound signaling network in the auditory cortex may underlie hearing deficits in the acute and sub-acute phases after exposure to shockwaves. This study may shed light on the perturbations underlying blast-induced auditory dysfunction and provide insights into the potential therapeutic windows for improving auditory outcomes in blast-exposed individuals.

17.
Cancer Biomark ; 38(4): 567-581, 2023.
Article in English | MEDLINE | ID: mdl-38073378

ABSTRACT

BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.


Subject(s)
Urinary Bladder Neoplasms , Humans , Prognosis , Urinary Bladder Neoplasms/genetics , CD8-Positive T-Lymphocytes , Databases, Factual , Gene Expression Profiling
18.
Nat Commun ; 14(1): 8119, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38065972

ABSTRACT

Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC+ Melanoma (MYC+MEL) and FGFBP2+NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC+MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/pathology , Skin Neoplasms/pathology , Lymphatic Metastasis , Gene Expression Profiling , Transcriptome , Tumor Microenvironment/genetics
19.
Front Cardiovasc Med ; 10: 1234271, 2023.
Article in English | MEDLINE | ID: mdl-37965087

ABSTRACT

Background: The causal link between Type 2 diabetes (T2D) and coronary atherosclerosis has been established through wet lab experiments; however, its analysis with Genome-wide association studies (GWAS) data remains unexplored. This study aims to validate this relationship using Mendelian randomization analysis and explore the potential mediation of VLDL in this mechanism. Methods: Employing Mendelian randomization analysis, we investigated the causal connection between T2D and coronary atherosclerosis. We utilized GWAS summary statistics from European ancestry cohorts, comprising 23,363 coronary atherosclerosis patients and 195,429 controls, along with 32,469 T2D patients and 183,185 controls. VLDL levels, linked to SNPs, were considered as a potential mediating causal factor that might contribute to coronary atherosclerosis in the presence of T2D. We employed the inverse variance weighted (IVW), Egger regression (MR-Egger), weighted median, and weighted model methods for causal effect estimation. A leave-one-out sensitivity analysis was conducted to ensure robustness. Results: Our Mendelian randomization analysis demonstrated a genetic association between T2D and an increased coronary atherosclerosis risk, with the IVW estimate at 1.13 [95% confidence interval (CI): 1.07-1.20]. Additionally, we observed a suggestive causal link between T2D and VLDL levels, as evidenced by the IVW estimate of 1.02 (95% CI: 0.98-1.07). Further supporting lipid involvement in coronary atherosclerosis pathogenesis, the IVW-Egger estimate was 1.30 (95% CI: 1.06-1.58). Conclusion: In conclusion, this study highlights the autonomous contributions of T2D and VLDL levels to coronary atherosclerosis development. T2D is linked to a 13.35% elevated risk of coronary atherosclerosis, and within T2D patients, VLDL concentration rises by 2.49%. Notably, each standard deviation increase in VLDL raises the likelihood of heart disease by 29.6%. This underscores the significant role of lipid regulation, particularly VLDL, as a mediating pathway in coronary atherosclerosis progression.

20.
Medicine (Baltimore) ; 102(44): e35784, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37933005

ABSTRACT

RATIONALE: Phacolytic glaucoma (PLG), a secondary open-angle glaucoma caused by high molecular weight proteins leaking through the capsule of a hypermature cataract. Leakage of liquefied lens cortex behind the posterior capsule is rare. In this paper, we review a case of phacolytic glaucoma in the lens cortex behind posterior capsule. PATIENT CONCERNS: This case report describes a 79-year-old male patient with a 7-year history of progressive blurred vision and a 1-day history of distended in his left eye. He underwent phacoemulsification combined with intraocular lens implantation at our facility 7 years ago. DIAGNOSES: The patient had lower vision (light perception vision) and increased intraocular pressure (IOP) (60 mmHg) in the left eye. Auxiliary inspection found that the left eye had deep anterior chamber depth (around 1 corneal thickness of the peripheral AC angle) as well as vitreous and aqueous humor opacity in the left eye. Combining the clinical symptoms and examinations, we made the diagnosis of PLG in the left eye. INTERVENTIONS: The patient underwent trabeculectomy and extracapsular cataract extraction of the left after a stable ocular condition, during the operation to see that white chyous cortex was visible under the posterior capsule and posterior capsule membrane of the lens was avulsed circularly. OUTCOMES: The postoperative condition was stable. During the follow up of 3 months, the IOP of the left eye was stable without ocular discomfort. LESSONS: This case reported a patient with phacolytic glaucoma in the lens cortex behind posterior capsule who underwent successful surgery, indicating spontaneous capsule rupture can occur in the posterior capsules in PLG and when this situation is detected during the operation, the posterior capsule tearing method can be applied to absorb the lens cortex sticking at the posterior surface of the posterior capsule.


Subject(s)
Cataract Extraction , Cataract , Glaucoma, Open-Angle , Glaucoma , Aged , Humans , Male , Cataract/complications , Glaucoma/surgery , Glaucoma, Open-Angle/surgery , Intraocular Pressure
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