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1.
Comput Methods Programs Biomed ; 250: 108164, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718709

RESUMEN

BACKGROUND AND OBJECTIVE: Current automatic electrocardiogram (ECG) diagnostic systems could provide classification outcomes but often lack explanations for these results. This limitation hampers their application in clinical diagnoses. Previous supervised learning could not highlight abnormal segmentation output accurately enough for clinical application without manual labeling of large ECG datasets. METHOD: In this study, we present a multi-instance learning framework called MA-MIL, which has designed a multi-layer and multi-instance structure that is aggregated step by step at different scales. We evaluated our method using the public MIT-BIH dataset and our private dataset. RESULTS: The results show that our model performed well in both ECG classification output and heartbeat level, sub-heartbeat level abnormal segment detection, with accuracy and F1 scores of 0.987 and 0.986 for ECG classification and 0.968 and 0.949 for heartbeat level abnormal detection, respectively. Compared to visualization methods, the IoU values of MA-MIL improved by at least 17 % and at most 31 % across all categories. CONCLUSIONS: MA-MIL could accurately locate the abnormal ECG segment, offering more trustworthy results for clinical application.


Asunto(s)
Algoritmos , Electrocardiografía , Aprendizaje Automático Supervisado , Electrocardiografía/métodos , Humanos , Frecuencia Cardíaca , Bases de Datos Factuales , Procesamiento de Señales Asistido por Computador
2.
J Clin Transl Hepatol ; 12(3): 287-297, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38426194

RESUMEN

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

3.
Nat Chem ; 16(2): 229-238, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37884668

RESUMEN

Detecting genetic mutations such as single nucleotide polymorphisms (SNPs) is necessary to prescribe effective cancer therapies, perform genetic analyses and distinguish similar viral strains. Traditionally, SNP sensing uses short oligonucleotide probes that differentially bind the SNP and wild-type targets. However, DNA hybridization-based techniques require precise tuning of the probe's binding affinity to manage the inherent trade-off between specificity and sensitivity. As conventional hybridization offers limited control over binding affinity, here we generate heteromultivalent DNA-functionalized particles and demonstrate optimized hybridization specificity for targets containing one or two mutations. By investigating the role of oligo lengths, spacer lengths and binding orientation, we reveal that heteromultivalent hybridization enables fine-tuned specificity for a single SNP and dramatic enhancements in specificity for two non-proximal SNPs empowered by highly cooperative binding. Capitalizing on these abilities, we demonstrate straightforward discrimination between heterozygous cis and trans mutations and between different strains of the SARS-CoV-2 virus. Our findings indicate that heteromultivalent hybridization offers substantial improvements over conventional monovalent hybridization-based methods.


Asunto(s)
Ácidos Nucleicos , Hibridación de Ácido Nucleico/métodos , ADN/genética , Sondas de Oligonucleótidos , Mutación
4.
Biosci Trends ; 17(6): 427-444, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37981319

RESUMEN

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Inmunoterapia/métodos , Inmunidad , Factores Inmunológicos , Microambiente Tumoral
5.
Front Public Health ; 11: 1251609, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38074706

RESUMEN

Objective: We investigated the epidemiological surveillance of the intestinal colonization and nosocomial infection of carbapenem-resistant Enterobacteriales (CRE) isolates from inpatients, which can provide the basis for developing effective prevention. Methods: A total of 96 CRE strains were collected from 1,487 fecal samples of hospitalized children between January 2016 and June 2017, which were defined as the "CRE colonization" group. In total, 70 CRE clinical isolates were also randomly selected for the comparison analysis and defined as the "CRE infection" group. The antimicrobial susceptibility of all strains was determined by the microdilution broth method. Polymerase chain reaction (PCR) was used to analyze carbapenemase genes, plasmid typing, and integrons. Multilocus sequence typing was further used to determine clonal relatedness. Results: In the "CRE colonization" group, Klebsiella pneumoniae was mostly detected with a rate of 42.7% (41/96), followed by Escherichia coli (34.4%, 33/96) and Enterobacter cloacae (15.6%, 15/96). The ST11 KPC-2 producer, ST8 NDM-5 producer, and ST45 NDM-1 producer were commonly present in carbapenem-resistant K. pneumoniae (CRKPN), carbapenem-resistant E. coli (CRECO), and carbapenem-resistant E. cloacae (CRECL) isolates, respectively. In the "CRE infection" group, 70% (49/70) of strains were K. pneumoniae, with 21.4% E. cloacae (15/70) and 5.7% E. coli (4/70). The ST15 OXA-232 producer and ST48 NDM-5 producer were frequently observed in CRKPN isolates, while the majority of NDM-1-producing CRECL isolates were assigned as ST45. Phylogenetic analysis showed that partial CRE isolates from intestinal colonization and nosocomial infection were closely related, especially for ST11 KPC-2-producing CRKPN and ST45 NDM-1-producing CRECL. Furthermore, plasmid typing demonstrated that IncF and IncFIB were the most prevalent plasmids in KPC-2 producers, while IncX3/IncX2 and ColE were widely spread in NDM producer and OXA-232 producer, respectively. Then, class 1 integron intergrase intI1 was positive in 74.0% (71/96) of the "CRE colonization" group and 52.9% (37/70) of the "CRE infection" group. Conclusion: This study revealed that CRE strains from intestinal colonization and nosocomial infection showed a partial correlation in the prevalence of CRE, especially for ST11 KPC-2-producing CRKPN and ST45 NDM-1-producing CRECL. Therefore, before admission, long-term active screening of rectal colonization of CRE isolates should be emphasized.


Asunto(s)
Carbapenémicos , Infección Hospitalaria , Niño , Humanos , Carbapenémicos/farmacología , Estudios Retrospectivos , Escherichia coli/genética , Antibacterianos/farmacología , Infección Hospitalaria/epidemiología , Prevalencia , Filogenia , Klebsiella pneumoniae/genética
6.
Nat Biomed Eng ; 7(11): 1404-1418, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37957275

RESUMEN

Molecular forces generated by cell receptors are infrequent and transient, and hence difficult to detect. Here we report an assay that leverages the CRISPR-associated protein 12a (Cas12a) to amplify the detection of cellular traction forces generated by as few as 50 adherent cells. The assay involves the immobilization of a DNA duplex modified with a ligand specific for a cell receptor. Traction forces of tens of piconewtons trigger the dehybridization of the duplex, exposing a cryptic Cas12-activating strand that sets off the indiscriminate Cas12-mediated cleavage of a fluorogenic reporter strand. We used the assay to perform hundreds of force measurements using human platelets from a single blood draw to extract individualized dose-response curves and half-maximal inhibitory concentrations for a panel of antiplatelet drugs. For seven patients who had undergone cardiopulmonary bypass, platelet dysfunction strongly correlated with the need for platelet transfusion to limit bleeding. The Cas12a-mediated detection of cellular traction forces may be used to assess cell state, and to screen for genes, cell-adhesion ligands, drugs or metabolites that modulate cell mechanics.


Asunto(s)
Sistemas CRISPR-Cas , Tracción , Humanos , Adhesión Celular/fisiología , Proteínas , Proteínas Portadoras
7.
Front Public Health ; 11: 1207723, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37841725

RESUMEN

Introduction: Nurses experience significant physical and psychological stress that negatively influences their psychological well-being. The objective of this study was to explore the association between self-efficacy and psychological well-being among Chinese nurses and to assess the moderating effects of perceived social support (PSS). Methods: In 2020, a hospital-based cross-sectional study using a multistage random sampling approach was performed in five regions of Liaoning, China. Of the 1,200 surveyed nurses, 1,010 completed questionnaires that evaluated the demographic information, 14-item Hospital Anxiety and Depression Scale, General Self-Efficacy Scale, and Multidimensional Scale of Perceived Social Support. To examine the factors associated with mental health parameters, hierarchical multiple regression analysis was performed. The interactions were visualized using a simple slope analysis. Results: The mean depression and anxiety scores for Chinese nurses were 8.74 ± 3.50 and 6.18 ± 3.26, respectively. The association between self-efficacy and depression differed between the low perceived social support (PSS) group (1 SD below the mean, ß = -0.169, p < 0.01) and high PSS group (1 SD above the mean, ß = -0.077, p < 0.01). Similarly, the association between self-efficacy and anxiety differed between the low PSS group (1 SD below the mean, ß = -0.155, p < 0.01) and high PSS group (1 SD above the mean, ß = -0.044, p < 0.01). Conclusion: We found that Chinese nurses experienced high levels of anxiety and depression. Furthermore, PSS moderates the relationship between self-efficacy and psychological well-being. Therefore, interventions targeting self-efficacy and PSS should be implemented to improve the psychological well-being of nurses.


Asunto(s)
Enfermeras y Enfermeros , Bienestar Psicológico , Autoeficacia , Apoyo Social , Humanos , China , Estudios Transversales , Pueblos del Este de Asia , Enfermeras y Enfermeros/psicología
8.
bioRxiv ; 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37503090

RESUMEN

The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signaling. The past decade has witnessed the development of molecular probes which have revealed many aspects of receptor mechanotransduction. However, most force probes are immobilized on hard substrates, thus failing to reveal mechanics in the physiological context of cell membranes. In this report, we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We demonstrate that TCR-antigen bonds experience 5-10 pN forces, and the mechanical events are dependent on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. We tethered DOTS onto a microparticle to mechanically screen antigen in high throughput using flow cytometry. Finally, DOTS were anchored onto live B cell membranes thus producing the first quantification of TCR mechanics at authentic immune cell-cell junctions.

9.
J Gastrointest Oncol ; 14(2): 932-942, 2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37201094

RESUMEN

Background: The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. Methods: This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Results: Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). Conclusions: In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

10.
J Exp Clin Cancer Res ; 42(1): 133, 2023 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-37231509

RESUMEN

BACKGROUND: Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. METHODS: Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. RESULTS: Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways. CONCLUSIONS: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA. TRIAL REGISTRATION: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 .


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteogenómica , Ablación por Radiofrecuencia , Humanos , Ratones , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/metabolismo , Linfocitos T CD8-positivos/metabolismo , Fosfatidilinositol 3-Quinasas , Línea Celular Tumoral , Microambiente Tumoral
11.
Angew Chem Int Ed Engl ; 62(30): e202302967, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37186502

RESUMEN

Immune recognition occurs at specialized cell-cell junctions when immune cells and target cells physically touch. In this junction, groups of receptor-ligand complexes assemble and experience molecular forces that are ultimately generated by the cellular cytoskeleton. These forces are in the range of piconewton (pN) but play crucial roles in immune cell activation and subsequent effector responses. In this minireview, we will review the development of DNA based molecular tension sensors and their applications in mapping and quantifying mechanical forces experienced by immunoreceptors including T-cell receptor (TCR), Lymphocyte function-associated antigen (LFA-1), and the B-cell receptor (BCR) among others. In addition, we will highlight the use of DNA as a mechanical gate to manipulate mechanotransduction and decipher how mechanical forces regulate antigen discrimination and receptor signaling.


Asunto(s)
ADN , Mecanotransducción Celular , Membrana Celular , Sistema Inmunológico , Antígenos , Nanotecnología
12.
Angew Chem Int Ed Engl ; 62(23): e202302538, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-36995566

RESUMEN

Electroactive ionenes combining caged-shaped diazabicyclic cations and aromatic diimides were developed as interlayers in organic solar cells (OSCs). These ionenes reduce the work-function of air-stable metal electrodes (e.g., Ag, Cu and Au) by generating strong interfacial dipoles, and their optoelectronic and morphological characters can be modulated by aromatic diimides, leading to high conductivity and good compatibility with active layers. The optimal ionene exhibits superior charge-transport, desirable crystallinity, and weak visible-absorption, boosting the efficiency of benchmark PM6 : Y6-based OSCs up to 17.44 %. The corresponding normal devices show excellent stability at maximum power point test under one sun illumination for 1000 h. Replacing Y6 with L8-BO promotes the efficiency to 18.43 %, one of the highest in binary OSCs. Notably, high efficiencies >16 % are maintained as the interlayer thickness increasing to 105 nm, the best result with interlayer-thickness over 100 nm.

13.
J Clin Transl Hepatol ; 11(2): 441-451, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-36643031

RESUMEN

Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSC-derived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSC-associated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

14.
Front Public Health ; 10: 961870, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36203698

RESUMEN

Access to safe drinking water is critical to health and development issues, and residents' drinking behavior reflects their awareness of health and water hygiene. Random sampling and face-to-face questionnaires were used to investigate the drinking water behavior, sanitation and perceptions of drinking water among middle-aged and elderly residents in Tengchong, southwest Yunnan from July 1 to July 28, 2021. Differences between groups were assessed using the Chi-square test and t-test. Two binary logistic regression analyses were conducted to explore the influencing factors of drinking unboiled tap water and willingness to use filters. Results show that 35% of residents drink unboiled tap water, and 29.8% of respondents indicated a willingness to use filters. The model results showed a strong correlation between 60 and 79 years old (OR: 0.510, 95% CI: 0.303-0.858), 80 and above years old (OR: 0.118, 95% CI: 0.038-0.365), drinking water at a regular interval (OR: 0.397, 95% CI: 0.257-0.612), wanting to gain knowledge about drinking water (OR: 0.198, 95% CI: 0.099-0.395), Perceived health risks (PHR) (OR: 0.847, 95% CI: 0.771-0.929), having kidney stones (OR: 2.975, 95% CI: 1.708-5.253) and drinking unboiled tap water (p < 0.05). 60-79 years old (OR: 0.446, 95% CI: 0.244-0.815), 80 and above years old (OR: 0.228, 95% CI: 0.064-0.812), water storage (OR: 0.088, 95% CI: 0.026-0.300), middle school and above (OR: 2.238, 95% CI: 1.289-3.883), household water treatment (HWT) (OR: 33.704, 95% CI: 9.726-116.791), Perceived health risks (PHR) (OR:1.106, 95% CI: 1.009-1.213), water authority satisfaction (WAT) (OR:0.857, 95% CI: 0.769-0.956) and willingness to use filters were correlated (p < 0.05). Our findings suggested that a certain proportion of permanent middle-aged and elderly residents in rural areas still drink unboiled tap water, and residents are less willing to use filters. Residents' perception of drinking water can reflect residents' drinking water behavior and willingness to a certain extent. It is recommended that the government and Centers for Disease Control (CDC) should strengthen relevant measures such as knowledge popularization and health education, and regulate the water use behavior of middle-aged and elderly residents. Promote safe, economical and effective household water filtration facilities to ensure public health safety.


Asunto(s)
Agua Potable , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Conducta de Ingestión de Líquido , Educación en Salud , Humanos , Persona de Mediana Edad
15.
Biosci Trends ; 16(5): 377-380, 2022 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-36089338

RESUMEN

Hepatocellular carcinoma (HCC) remains a health challenge with increasing incidence worldwide. Radiofrequency ablation (RFA) is a potentially curative option for patients with early-stage HCC. However, the high rate of tumor recurrence limits long-term survival when the tumors are larger than 2 cm and undergoing insufficient RFA (iRFA). Notably, in situ tumor necrosis due to thermal ablation is assumed to be a source of antigens that induce antitumor immunity. Therefore, mounting studies and trials have attempted to provide a rational and effective therapeutic strategy combining RFA and immunotherapy to treat HCC. Nowadays, many controversies and challenges with this combined therapeutic strategy remain to be resolved, such as the indications for adjuvant immunotherapy along with RFA in early HCC, the sequence of the two treatments in advanced HCC, and the optimal timing of immunotherapy before or after RFA. In addition, individualized treatment strategies need to be perfected for patients with HCC.


Asunto(s)
Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/cirugía , Inmunoterapia , Recurrencia , Resultado del Tratamiento , Estudios Retrospectivos
16.
Biosci Trends ; 16(4): 267-281, 2022 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-35934785

RESUMEN

Recently, the emerging role of circular RNAs (circRNAs) in tumor development and progression has been a topic of great interest. Nevertheless, the effects of hepatic stellate cell (HSC)-derived exosomes in hepatocellular carcinoma (HCC) remain unclear. Here, we aim to explore the potential effect of HSC exosome-derived circWDR25 on the aggressiveness of HCC. Firstly, a microarray analysis of circRNAs was performed to profile and identify the differentially expressed circRNAs derived from HSC exosomes activated by HCC cells. Subsequently, the roles of circWDR25 in HCC tumor growth and aggressiveness were confirmed through in vitro and in vivo functional experiments. Moreover, RNA pull-down, dual-luciferase reporter assays, and fluorescent in situ hybridization (FISH) were performed to determine interactions in the circWDR25-miR-4474-3p-ALOX15 loop. Immunohistochemical analysis was also performed on a microarray of HCC tissues and peritumoral tissues. We found that overexpressed peritumoral circWDR25 was associated with survival and recurrence in patients with HCC and promoted the progression of HCC cells both in vitro and in vivo. Mechanistically, both exogenous and HSC exosomal-derived circWDR25 regulated the expression of ALOX15 by sponging miR-4474-3p and ultimately inducing an epithelial-to-mesenchymal transition (EMT) in HCC cells. Moreover, exogenous and HSC exosomal-derived circWDR25 promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells. In conclusion, circWDR25 facilitated HCC cell proliferation and invasion via the circWDR25/miR-4474-3p/ALOX15 and EMT axes and it promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells, thus providing insights into the mechanism of tumor aggressiveness mediated by HSC-derived exosomal circWDR25.


Asunto(s)
Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , MicroARNs , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Exosomas/genética , Exosomas/metabolismo , Exosomas/patología , Regulación Neoplásica de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Humanos , Hibridación Fluorescente in Situ , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética
17.
Environ Sci Pollut Res Int ; 29(57): 86722-86743, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35794333

RESUMEN

The sustainable development of human beings is facing severe challenges in the context of a new era. The effective reduction of carbon emission intensity is essential to achieve the goal of sustainable development. Obviously, green innovation is an important factor in mitigating carbon emission intensity. It is important to measure the effect of green innovation on carbon emission intensity for accelerating industrial transformation and building a circular economy system. Therefore, this paper uses the data of 30 provinces in China from 2000 to 2019, obtained by the State Intellectual Property Office, using fixed effects model quantile regression model and Spatial Durbin Model to empirically verify the theoretical hypothesis. The conclusions are as follows: (1) Green innovation inhibits carbon emission intensity. Instrumental variable model and robustness test support this conclusion. (2) For carbon emission intensity under different quantiles, green innovation has a more significant effect on provinces with high carbon emission intensity through "target accountability system" and "reverse coercive system." (3) There is a significant spatial correlation between green innovation in China's provinces. The reduction of carbon emission intensity in the region will benefit from the improvement of green innovation in surrounding cities.


Asunto(s)
Dióxido de Carbono , Carbono , Humanos , Carbono/análisis , Ciudades , Dióxido de Carbono/análisis , Desarrollo Sostenible , Industrias , China , Desarrollo Económico
18.
BMJ Open ; 12(5): e054170, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35580969

RESUMEN

OBJECTIVES: The harm of indoor air pollution to health has gradually attracted attention, but the effect of indoor air pollution from burning solid fuels on incidental non-fatal cardiovascular disease (CVD) is not well understood. Under these circumstances, this study examined the association between solid fuel use and incidental non-fatal CVD. DESIGN: The prospective cohort study was conducted in 2011, 2013, 2015 and 2018. SETTING: The nationally representative survey was conducted in 28 provinces of China. PARTICIPANTS: This study included 13 544 middle-aged and elderly adults without CVD in the baseline survey, and they were followed for 7 years. OUTCOME MEASURES: First incidence of non-fatal CVD (heart disease or stroke). METHODS: Based on longitudinal data, Cox proportional hazards models were used to assess the effects of solid fuel use and persistent use on incidental CVD events. RESULTS: During the 7-year follow-up period, there were 1533 non-fatal CVD cases. A total of 7310 (54%) participants used solid fuel for cooking at the baseline survey, and 2998 (41%) users continued to use solid fuel. Solid fuel use was associated with incidental non-fatal CVD (HR: 1.18; 95% CI: 1.05 to 1.32) compared with clean fuel, and persistent solid fuel use might lead to a higher risk of incidental non-fatal CVD (HR: 1.38; 95% CI: 1.18 to 1.61) and heart disease (HR: 1.49; 95% CI: 1.24 to 1.81). In the subgroup analysis, the relationship remained significant in the female, elderly, rural and hypertensive groups. However, we found no significant interaction between these risk factors and fuel use (all p<0.05). CONCLUSIONS: This cohort study provides evidence for the effects of solid fuel use on incidental non-fatal CVD in middle-aged and elderly Chinese adults. Advocating for the use of clean energy and ventilation stoves is important to cardiovascular health.


Asunto(s)
Contaminación del Aire Interior , Enfermedades Cardiovasculares , Cardiopatías , Adulto , Anciano , Contaminación del Aire Interior/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , China/epidemiología , Estudios de Cohortes , Culinaria , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos
19.
BMC Public Health ; 22(1): 955, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35549903

RESUMEN

BACKGROUND: As a group at high-risk for acquired immune deficiency syndrome (AIDS) infection, the psychological distress of transgender women cannot be ignored while preventing and controlling AIDS risks. Transgender women are a vulnerable group, and their psychological distress deserves attention. The purpose of this study was to evaluate the psychological distress of transgender women and further determine the influences of factors on the psychological distress of transgender women. METHODS: From March 2021 to August 2021, a cross-sectional survey was conducted in Shandong province, China. Data were collected by a questionnaire designed for transgender women, and the GHQ-12 scale was used to measure their psychological distress. The questionnaire combined sociodemographic characteristics, HIV/AIDS cognition, related behaviors, substance abuse, social support, gender identity and other factors. Univariate logistic regression and multivariate logistic regression models were used to explore the psychological factors of transgender women. RESULTS: In this study, the rate of transgender women with psychological distress was 20.08%. Earned monthly income between 10,000-15,000 yuan (OR:0.16, 95% CI:0.06-0.45) and a monthly income greater than 15,000 yuan (OR:0.07, 95% CI:0.01-0.43) were protective factors in the psychology of transgender women. Transgender women who never disclosed sexual orientation and identity (OR: 0.19, 95% CI: 0.06-0.58), who only disclosed their sexual orientation and identity to families or friends (OR: 0.41, 95% CI: 0.18-0.93) were also less likely to have psychological distress. Additionally, transgender women who did not desire to be identified with their sexual orientation and identity (OR: 3.31, 95%CI: 1.08-10.16) and who reported that the Internet did not play an essential role in helping determine sexual orientation (OR: 5.96, 95% CI: 2.91-12.20) were more likely to have psychological distress. CONCLUSION: Transgender women were at risk of psychological distress. Earning more money can help transgender women's psychological health. When formulating measures for transgender women, we should pay attention to enhance social inclusion and social acceptance of their gender identity and sexual orientation. Strengthening the role of the internet in transgender women's confirmation of sexual orientation and improving the social acceptance of transgender women will have a positive impact on the psychological status of transgender women.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Distrés Psicológico , Personas Transgénero , Estudios Transversales , Femenino , Identidad de Género , Humanos , Masculino , Conducta Sexual , Personas Transgénero/psicología
20.
Materials (Basel) ; 15(1)2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-35009475

RESUMEN

At present, the existing standards (AISC360-16, EN1994-1-1:2004, and JGJ138-2016) lack relevant provisions for steel-reinforced concrete (SRC) composite columns with high-strength steel. To investigate the axial compressive mechanical performance of short high-strength steel-reinforced concrete (HSSRC) columns, the axial load test was conducted on 12 short composite columns with high-strength steel and ordinary steel. The influences of steel strength, steel ratio, and the section form of steel on the failure modes, bearing capacity, and ductility of the specimens were studied. Afterward, the experimental data were compared with the existing calculation results. The results show: compared with the specimens with Q235 steel, the bearing capacity of the specimens with Q460 steel increases by 7.8-15.3%, the bearing capacity of the specimens with Q690 steel increases by 13.2-24.1%, but the ductility coefficient increases by 15.2-202.4%; with the increase of steel ratio, the bearing capacity and ductility of specimens are significantly improved. A change of the steel cross-section could influence the ductility of SRC columns more than their bearing capacity. Moreover, the calculation results show that present standards could not predict the bearing capacity of HSSRC columns. Therefore, a modified method for determining the effective strength of steel equipped in HSSRC columns was proposed. The results of the ABAQUS simulation also showed that the addition of steel fibers could significantly improve the bearing capacity of Q690 HSSRC columns. The research results provide a reference for engineering practices.

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