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1.
Angew Chem Int Ed Engl ; : e202404295, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649323

RESUMO

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

2.
World J Gastrointest Oncol ; 16(4): 1514-1531, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660664

RESUMO

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

3.
PLoS Comput Biol ; 20(4): e1012012, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574114

RESUMO

Anti-cancer response of cell lines to drugs is in urgent need for individualized precision medical decision-making in the era of precision medicine. Measurements with wet-experiments is time-consuming and expensive and it is almost impossible for wide ranges of application. The design of computational models that can precisely predict the responses between drugs and cell lines could provide a credible reference for further research. Existing methods of response prediction based on matrix factorization or neural networks have revealed that both linear or nonlinear latent characteristics are applicable and effective for the precise prediction of drug responses. However, the majority of them consider only linear or nonlinear relationships for drug response prediction. Herein, we propose a Dual Branch Deep Neural Matrix Factorization (DBDNMF) method to address the above-mentioned issues. DBDNMF learns the latent representation of drugs and cell lines through flexible inputs and reconstructs the partially observed matrix through a series of hidden neural network layers. Experimental results on the datasets of Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) show that the accuracy of drug prediction exceeds state-of-the-art drug response prediction algorithms, demonstrating its reliability and stability. The hierarchical clustering results show that drugs with similar response levels tend to target similar signaling pathway, and cell lines coming from the same tissue subtype tend to share the same pattern of response, which are consistent with previously published studies.


Assuntos
Algoritmos , Redes Neurais de Computação , Reprodutibilidade dos Testes , Medicina de Precisão/métodos , Linhagem Celular Tumoral
4.
Anal Sci ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687414

RESUMO

Mustard gas, a representative of blister agents, poses a severe threat to human health. Although the structure of 2-chloroethyl ethyl sulfide (2-CEES) is similar to mustard gas, 2-CEES is non-toxic, rendering it a commonly employed simulant in related research. ZnFe2O4-based semiconductor gas sensors exhibit numerous advantages, including structural stability, high sensitivities, and easy miniaturization. However, they exhibit insufficient sensitivity at low concentrations and require high operating temperatures. Owing to the effect of electronic and chemical sensitization, the gas-sensing performance of a sensor may be remarkably enhanced via the sensitization method of noble metal loading. In this study, based on the morphologies of ZnFe2O4 hollow microspheres, a solvothermal method was adopted to realize different levels of Au loading. Toward 1 ppm of 2-CEES, the gas sensor based on 2 wt.% Au-loaded ZnFe2O4 hollow microspheres exhibited a response sensitivity twice that of the gas sensor based on pure ZnFe2O4; furthermore, the response/recovery times decreased. Additionally, the sensor displayed excellent linear response to low concentrations of 2-CEES, outstanding selectivity in the presence of several common volatile organic compounds, and good repeatability, as well as long-term stability. The Au-loaded ZnFe2O4-based sensor has considerable potential for use in detecting toxic chemical agents and their simulants.

5.
Cell Transplant ; 33: 9636897241235460, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38506426

RESUMO

This article presents a comprehensive review of the factors influencing the efficacy of mesenchymal stem cells (MSCs) transplantation and its association with platelet concentrates (PCs). It focuses on investigating the impact of PCs' composition, the age and health status of platelet donors, application methods, and environmental factors on the outcomes of relevant treatments. In addition, it delves into the strategies and mechanisms for optimizing MSCs transplantation with PCs, encompassing preconditioning and combined therapies. Furthermore, it provides an in-depth exploration of the signaling pathways and proteomic characteristics associated with preconditioning and emphasizes the efficacy and specific effects of combined therapy. The article also introduces the latest advancements in the application of biomaterials for optimizing regenerative medical strategies, stimulating scholarly discourse on this subject. Through this comprehensive review, the primary goal is to facilitate a more profound comprehension of the factors influencing treatment outcomes, as well as the strategies and mechanisms for optimizing MSCs transplantation and the application of biomaterials in regenerative medicine, offering theoretical guidance and practical references for related research and clinical practice.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteômica , Medicina Regenerativa , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais , Materiais Biocompatíveis/farmacologia
6.
Aesthet Surg J ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518754

RESUMO

BACKGROUND: Induction of beige fat for grafting is an emerging transplantation strategy. However, safety concerns associated with pharmaceutical interventions limits its wider application. Moreover, as a special type of fat with strong metabolic functions, the effect of metabolism of recipients after beige fat grafting has not been explored in plastic surgery domain. OBJECTIVES: To explore whether cold-induced inguinal white adipose tissue(iWAT) transplantation has a higher retention rate and beneficial effects on recipient metabolism. METHODS: The mice were subjected to cold stimulation for 48 hours to induce the browning of iWAT and harvested immediately. Subsequently, each C57/BL6 mouse received 0.2 ml cold-induced iWAT or normal iWAT transplantation. Fat grafts and recipients' iWAT, epididymal adipose tissue (epiWAT) and brown adipose tissue (BAT) were harvested at 8 weeks after operation. Immunofluorescence staining, real-time PCR and western blot were used for histological and molecular analysis. RESULTS: Cold-induced iWAT grafting has a higher retention rate (67.33%±1.74% vs. 55.83% ± 2.94%, P < 0.01) and more satisfactory structural integrity. Histological changes identified the better adipose tissue homeostasis after cold challenge, including abundant smaller adipocytes, higher levels of adipogenesis, angiogenesis, and proliferation, but lower levels of fibrosis. More importantly, cold-induced iWAT grafting suppressed the inflammation of epiWAT caused by conventional fat grafting, and activated the glucose metabolism and thermogenic activity of recipients' adipose tissues. CONCLUSIONS: Cold-induced iWAT grafting was an effective non-pharmacological intervention strategy to improve the retention rate and grafts' homeostasis. Furthermore, it improved the adverse effects caused by traditional fat grafting, but bring metabolic benefits.

8.
Huan Jing Ke Xue ; 45(2): 1026-1037, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471940

RESUMO

Quantifying the risk of soil heavy metal sources can identify the main pollution sources. It can provide a scientific basis for reducing the ecological and human health risks of soil heavy metals. Taking the shallow soil in a Pb-Zn mine watershed in northern Guangxi as a research object, ecological and human health risk assessments were conducted using potential ecological risk assessment (RI) and human health risk assessment (HRA), and the source apportionment of soil heavy metals was completed using the absolute principal component-multiple linear regression receptor (APCS-MLR) model and random forest (RF) model. Then, a combined risk assessment model, consisting of RI, HRA, and APCS-MLR, was used to quantify the risk of soil heavy metal sources. The results showed that the contents of Pb, Zn, Cu, and Cd exceeded the environmental screening values for agricultural land with mean values of 342.77, 693.34, 61.27, and 3.08 mg·kg-1, respectively, and there was a certain degree of contamination. Pb, Cr, and As were the main health risk impact factors, with higher health risks for children than for adults. Three sources were identified: mining activities (Source Ⅰ), soil parent material sources and original formation (Source Ⅱ), and unknown sources. Pb, Zn, Cu, and Cd were mainly derived from Source Ⅰ, and Cr and As were controlled by unknown sources and Source Ⅱ. The source risk assessment results of soil heavy metals indicated that the potential ecological risk and non-carcinogenic risk were mainly from Source Ⅰ and Source Ⅱ, and carcinogenic risk was mainly from unknown sources. The unknown sources had a high proportion in source apportionment and risk assessment, and should be further researched to provide scientific basis for soil heavy metal control. The combined risk assessment model based on source analysis, focusing on the risk characteristics of different sources, can accurately identify high-risk pollution sources. It is a more reasonable and reliable risk assessment method.


Assuntos
Metais Pesados , Poluentes do Solo , Adulto , Criança , Humanos , Solo , Monitoramento Ambiental , Cádmio , Chumbo , Poluentes do Solo/análise , China , Medição de Risco , Metais Pesados/análise
10.
Theranostics ; 14(5): 2246-2264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505620

RESUMO

Aim: Adipose tissue (AT) dysfunction that occurs in both obesity and lipodystrophy is associated with the development of cardiomyopathy. However, it is unclear how dysfunctional AT induces cardiomyopathy due to limited animal models available. We have identified vacuolar H+-ATPase subunit Vod1, encoded by Atp6v0d1, as a master regulator of adipogenesis, and adipose-specific deletion of Atp6v0d1 (Atp6v0d1AKO) in mice caused generalized lipodystrophy and spontaneous cardiomyopathy. Using this unique animal model, we explore the mechanism(s) underlying lipodystrophy-related cardiomyopathy. Methods and Results: Atp6v0d1AKO mice developed cardiac hypertrophy at 12 weeks, and progressed to heart failure at 28 weeks. The Atp6v0d1AKO mouse hearts exhibited excessive lipid accumulation and altered lipid and glucose metabolism, which are typical for obesity- and diabetes-related cardiomyopathy. The Atp6v0d1AKO mice developed cardiac insulin resistance evidenced by decreased IRS-1/2 expression in hearts. Meanwhile, the expression of forkhead box O1 (FoxO1), a transcription factor which plays critical roles in regulating cardiac lipid and glucose metabolism, was increased. RNA-seq data and molecular biological assays demonstrated reduced expression of myocardin, a transcription coactivator, in Atp6v0d1AKO mouse hearts. RNA interference (RNAi), luciferase reporter and ChIP-qPCR assays revealed the critical role of myocardin in regulating IRS-1 transcription through the CArG-like element in IRS-1 promoter. Reducing IRS-1 expression with RNAi increased FoxO1 expression, while increasing IRS-1 expression reversed myocardin downregulation-induced FoxO1 upregulation in cardiomyocytes. In vivo, restoring myocardin expression specifically in Atp6v0d1AKO cardiomyocytes increased IRS-1, but decreased FoxO1 expression. As a result, the abnormal expressions of metabolic genes in Atp6v0d1AKO hearts were reversed, and cardiac dysfunctions were ameliorated. Myocardin expression was also reduced in high fat diet-induced diabetic cardiomyopathy and palmitic acid-treated cardiomyocytes. Moreover, increasing systemic insulin resistance with rosiglitazone restored cardiac myocardin expression and improved cardiac functions in Atp6v0d1AKO mice. Conclusion: Atp6v0d1AKO mice are a novel animal model for studying lipodystrophy- or metabolic dysfunction-related cardiomyopathy. Moreover, myocardin serves as a key regulator of cardiac insulin sensitivity and metabolic homeostasis, highlighting myocardin as a potential therapeutic target for treating lipodystrophy- and diabetes-related cardiomyopathy.


Assuntos
Cardiomiopatias Diabéticas , Insuficiência Cardíaca , Resistência à Insulina , Lipodistrofia , Proteínas Nucleares , Transativadores , ATPases Vacuolares Próton-Translocadoras , Animais , Camundongos , Cardiomiopatias Diabéticas/genética , Modelos Animais de Doenças , Glucose/metabolismo , Resistência à Insulina/genética , Lipídeos , Obesidade/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo
11.
Materials (Basel) ; 17(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38399030

RESUMO

316 L stainless steel is an ideal bipolar plate material for a proton exchange membrane fuel cell (PEMFC). However, the thickening of the passivation film on the stainless steel surface and the dissolution of corrosive ions during operation will affect the durability of the PEMFC. Herein, a heterogeneous layer is prepared on the surface of 316 L stainless steel through dual ion implantation of molybdenum ion and carbon ion combined with heat treatment to promote the corrosion resistance and conductivity of the bipolar plate. The ion implantation technique resulted in a uniform distribution of Mo and C elements on the surface of 316 L stainless steel, with a modified layer depth of about 70-80 nm. The electrical conductivity of the ion implanted samples was significantly improved, and the interfacial contact resistance was reduced from 464.25 mΩ × cm2 to 42.49 mΩ × cm2. Heat treatment enhances the surface homogenization, repairs the defects of irradiation damage, and improves the corrosion resistance of stainless steel. The corrosion current density of (Mo+C)-600 samples decreased from 1.21 × 10-8 A/cm2 to 2.95 × 10-9 A/cm2 under the long-term corrosion condition of 4 h. These results can provide guidance for the modification of stainless steel bipolar plates.

12.
Polymers (Basel) ; 16(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38399835

RESUMO

There have been many studies on surface acoustic wave (SAW) sensors for detecting sulfur-containing toxic or harmful gases. This paper aims to give an overview of the current state of polymer films used in SAW sensors for detecting deleterious gases. By covering most of the important polymer materials, the structures and types of polymers are summarized, and a variety of devices with different frequencies, such as delay lines and array sensors for detecting mustard gas, hydrogen sulfide, and sulfur dioxide, are introduced. The preparation method of polymer films, the sensitivity of the SAW gas sensor, the limit of detection, the influence of temperature and humidity, and the anti-interference ability are discussed in detail. The advantages and disadvantages of the films are analyzed, and the potential application of polymer films in the future is also forecasted.

13.
J Cancer ; 15(1): 90-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164284

RESUMO

Background: Human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) has emerged as a hotspot for research and brought breakthroughs in the treatment of breast cancer and other solid tumors. While the occurrence of cardiac events (CEs) has yet not been systematically reported. Methods: The prospective clinical trials of marketed HER2-targeted ADCs were systematically searched in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to May 2023. Two investigators independently extracted data with priority given to ClinicalTrials.gov, followed by peer-reviewed articles. Stata 15.0 software was used to perform the meta-analysis. The effect statistics were estimated as pooled incidence with 95% confidence intervals (CI). The primary objectives were to assess the incidence of all-grade and ≥3 /serious grades CEs related to HER2-targeted ADC. Our study strictly adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and has been registered on PROSPERO (NO. CRD42023440448). Results: After conducting a comprehensive literature search, initially 7000 relevant studies were identified, and eventually a total of 47 trials involving 10594 patients were included for analysis. The pooled incidence of all-grade and ≥3/serious grades CEs respectively were 4.7% [95% CI, 3.7-5.8%] and 0.6% (95% CI, 0.5-0.8%). The pooled incidence of CEs leading to dosage discontinuation was 0.8% (95% CI, 0.4-1.3%). Subgroup analysis revealed a significantly higher incidence of all-grade CEs in T-DXd treatment compared to T-DM1 treatment (7.7% versus 3.6%; p=0.017), as well as in phase I/II trials compared to phase III trials (6.9% versus 3.2%; p=0.002) and combination therapy compared to monotherapy (7.6% versus 3.9%; p=0.013). The electrocardiogram QT corrected interval prolonged was identified as the CE with the highest pooled incidence, occurring at a rate of 5.9% (95% CI, 3.3-8.5%). Conclusions: The incidence of CEs associated with HER2-targeted ADC is relatively low. However, it is crucial to enhance surveillance measures, particularly for T-DXd treatment and combination therapy.

14.
Infect Agent Cancer ; 19(1): 3, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245747

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), which is featured with high morbidity and mortality worldwide, is a primary malignant tumor of the liver. Recently, there is a wealth of supporting evidence revealing that NK cell-related immune traits are strongly associated with the development of HCC, but the causality between them has not been proven. METHODS: Two-sample Mendelian randomization (MR) study was performed to probe the causal correlation between NK cell-related immune traits and HCC. Genetic variations in NK cell-related immune traits were extracted from recent genome-wide association studies (GWAS) of individuals with European blood lineage. HCC data were derived from the UK Biobank Consortium's GWAS summary count data, including a total of 372,184 female and male subjects, with 168 cases and 372,016 controls, all of whom are of European ancestry. Sensitivity analysis was mainly used for heterogeneity and pleiotropy testing. RESULTS: Our research indicated the causality between NK cell-related immune traits and HCC. Importantly, CD8+NKT cells had protective causal effects on HCC (OR = 0.9996;95%CI,0.9993-0.9999; P = 0.0489). CD16-CD56 caused similar effects on NK cells (OR = 0.9997;95%CI,0.9996-0.9999; P = 0.0117) as CD8+NKT cells. Intercepts from Egger showed no pleiotropy and confounding factors. Furthermore, insufficient evidence was found to support the existence of heterogeneity by Cochran's Q test. CONCLUSION: MR analysis suggested that low CD8+NKT cells and CD16-CD56 expression on NK cells were linked with a higher risk of HCC.

15.
Environ Pollut ; 344: 123405, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38244905

RESUMO

In recent years, nanomaterials have found extensive applications across diverse domains owing to their distinctive physical and chemical characteristics. It is of great importance in theoretical and practical terms to carry out the relationship between structural characteristics of nanomaterials and different cytotoxicity and to achieve practical assessment and prediction of cytotoxicity. This study investigated the intrinsic quantitative constitutive relationships between the cytotoxicity of nano-metal oxides on human normal lung epithelial cells and human lung adenocarcinoma cells. We first employed quasi-SMILES-based nanostructural descriptors by selecting the five physicochemical properties that are most closely related to the cytotoxicity of nanometal oxides, then established SMILES-based descriptors that can effectively describe and characterize the molecular structure of nanometal oxides, and then built the corresponding Nano-Quantitative Structure-Activity Relationship (Nano-QSAR) prediction models, finally, combined with the theory of reactive oxygen species (ROS) biotoxicity, to reveal the mechanism of toxicity and differences between the two cell types. The established model can efficiently and accurately predict the properties of targets, reveal the corresponding toxicity mechanisms, and guide the safe design, synthesis, and application of nanometal oxides.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Nanoestruturas , Humanos , Nanoestruturas/toxicidade , Óxidos/toxicidade , Pulmão
17.
J Cancer ; 14(17): 3275-3284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928419

RESUMO

Introduction: Trastuzumab emtansine(T-DM1) and trastuzumab deruxtecan (T-DXd, formerly DS-8201a), the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC), are commonly used in metastatic breast cancer. However, their real-world safety profile has not been adequately compared. Objective: We aimed to investigate the adverse event (AE) profile of T-DM1 and T-DXd reported by the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: All indications were searched for T-DM1 and T-DXd, as primary suspected drugs, from FAERS data (January 2004 to June 2023). Disproportionality analyses were performed by reporting odds ratios (ROR) and proportional reporting ratio (PRR). The odds ratio (OR) of fatal AEs associated with T-DM1 and T-DXd under different exposure factors were performed by univariate and multivariate logistical regression analysis. Results: 3723 and 2045 reports of T-DM1 and T-DXd were submitted to FAERS. Finally, 94 and 61 significant signals for T-DM1 and T-DXd were systematically analyzed. The valid AEs with the highest frequency and the strongest signal intensity for T-DM1 were platelet count decreased (n=108) and hepatopulmonary syndrome (ROR=680.42), respectively. Interstitial lung disease (n=262, ROR=82.55) and pneumonitis (n=89, ROR = 48.34) showed both high frequency and strong signal intensity for T-DXd. The proportion of AEs in each SOC system was different. T-DM1 had a greater proportion of valid AEs in the nervous system, musculoskeletal system, hepatobiliary system, ocular system, cardiac system and hematologic system(p<0.05). T-DXd had a greater proportion of valid AEs in the skin disorders, respiratory system, infestations, general system and gastrointestinal system(p<0.05). Furthermore, the analysis of fatal AEs in four systems revealed that T-DXd exhibited a significantly higher proportion of fatal outcomes in the hematologic and respiratory system compared to T-DM1. Conversely, T-DM1 had a significantly higher proportion of fatal outcomes in the hepatobiliary system. Neither T-DM1 nor T-DXd exhibited a high mortality ratio in the cardiac system. Logistic regression analysis indicated that advanced age (≥65 years) and male gender were identified as independent risk factors of fatal AEs for both T-DM1 and T-DXd. Additionally, the drug combination therapy, particularly with a CYP3A4 inhibitor, was found to be a risk factor for fatal AEs specifically related to T-DXd. Conclusions: Hematological and respiratory toxicity of T-DXd and hepatobiliary toxicity of T-DM1 exhibited a high incidence of fatal outcomes. It is crucial to identify high-risk factors and enhance the monitoring of AEs during clinical application.

18.
ACS Omega ; 8(41): 38690-38703, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37867671

RESUMO

The crucial role of competitive endogenous RNA (ceRNA) in the malignant biological behavior of tumors has been certificated. Nevertheless, the detailed function and molecular mechanism of ceRNA associated with cuproptosis in hepatocellular carcinoma (HCC) remains dismal. In this study, we first constructed a protein-protein interaction network and identified the module with the highest degree of aggregation degree. DLAT and PDHA1 were screened out of the module after differential expression and survival analysis. Next, we reverse-predicted the upstream miRNA and lncRNA from mRNA (DLAT, PDHA1) and successfully established the ceRNA network-SNHG3/miR-1306-5p/PDHA1. SNHG3 was identified to be an independent prognostic biomarker based on the outcome of univariate and multivariate Cox analyses. Subsequently, we implemented methylation, immune infiltration, and drug sensitivity analysis to investigate the potential biological functions of SNHG3 in HCC. In addition, SNHG3 expression was upregulated in liver cancer cell lines. In vitro functional assay revealed that SNHG3 knockdown significantly attenuated proliferation, migration, and invasion of liver cancer cells. In summary, SNHG3 exhibited oncogenic characterization via sponging miR-1306-5p to regulate PDHA1, which might function as a promising prognostic indicator and a potential therapeutic target for HCC and shed new light on the molecular mechanism of HCC progression.

19.
Sci Rep ; 13(1): 15656, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730828

RESUMO

A novel composite hydrogel (AM/CMC/B) synthesized from peanut shell biochar effectively adsorbs heavy metal Cd in water and reduces its toxicity to tobacco seedlings. The hydrogel, prepared via hydrothermal polymerization using acrylamide (AM), carboxymethyl cellulose (CMC), and peanut shell biochar (B), exhibited a maximum adsorption capacity of 164.83 mg g-1 for Cd2+ and followed a pseudo-second-order kinetic model. In pot experiments, the application of exogenous AM/CMC/B mitigated the inhibitory effects of Cd-contaminated soil on tobacco seedling growth. Addition of 10 mg kg-1 Cd resulted in improved phenotype, root system development, enhanced photosynthetic capacity, stomatal conductance (Gs), stomatal number, and increased antioxidant activity while reducing MDA content and leaf cell death. These findings highlight the potential of AM/CMC/B as an environmentally friendly adsorbent for Cd removal from water and for reducing Cd stress toxicity in tobacco and other plants.


Assuntos
Cádmio , Metais Pesados , Cádmio/toxicidade , Plântula , Nicotiana , Hidrogéis , Água , Metais Pesados/toxicidade , Acrilamida , Arachis , Carboximetilcelulose Sódica
20.
J Cancer Res Clin Oncol ; 149(15): 13753-13771, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37526663

RESUMO

PURPOSE: Chronic hepatitis B-liver cirrhosis-hepatocellular carcinoma (CLH), commonly called the "liver cancer trilogy", is a crucial evolutionary phase in the emergence of hepatocellular carcinoma (HCC) in China. Previous studies on early diagnostic biomarkers of HCC were limited to the end-stage of HCC and did not focus on the evolutionary process of CLH. METHODS: 11 monotonically changing differentially expressed genes (MCDEGs) highly correlated with CLH were screened through bioinformatic analysis and KPNA2 was identified for further research. The serum KPNA2 expression in different CLH states was detected by Enzyme linked immunosorbent assay (ELISA). A nomogram model was constructed using univariate and multivariate Cox regression methods. RESULTS: The single-cell RNA-seq and bulk RNA-seq revealed that KPNA2 related to immune infiltration in HCC and may participate in cell cycle pathways in HCC. The serum KPNA2 expression was monotonically upregulated in CLH and was valuable for diagnosing different CLH states. Besides, chronic hepatitis B(CHB) patients, liver cirrhosis (LC) patients, and HCC patients were classified into subgroups with distinct serum KPNA2 expressions. Accordingly, patients with different serum KPNA2 expressions displayed various clinicopathological features. The AUC value of the nomogram model was 0.959 in predicting the likelihood of developing HCC in CHB patients or LC patients. Finally, we found that KPNA2 expression was negatively correlated with the IC50 of four chemotherapeutic drugs in HCC. CONCLUSION: KPNA2 was a novel serum biomarker for diagnosing different CLH states, monitoring the dynamic evolution of CLH, and a new therapeutic target for intervening in the progression of CLH.

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