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1.
J Hazard Mater ; 479: 135718, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236532

RESUMO

The widespread use of rubber antioxidants, especially p-phenylenediamines (PPDs), has raised increasing concerns about their risk assessment. However, there is a notable lack of research on their transformation products (TPs). Photolysis, influenced by active components, plays a significant role in the environmental fates of PPDs. This study investigated four emerging PPDs (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), N, N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), and N-cyclohexyl-N'-phenyl-p-phenylenediamine (CPPD)) through a combination of experiments (photolysis kinetics, quenching experiments, acute toxicity test to Vibrio Fischeri (V. fischeri) and identification of photolytic products) and theoretical calculations. The results revealed different pathways for indirect photolysis mediated by the hydroxyl radicals (•OH) and singlet oxygen (1O2) of DPPD and IPPD under simulated sunlight irradiation. The effects of dissolved organic matter (DOM) and fulvic acid (FA) on the rates of photolysis of PPDs highlighted the complex interactions among the molecular structure, light absorption properties, and environmental variables. Quenching for reactive oxygen species (ROS) reduced photo-induced toxicity, whereas the addition of DOM and FA increased it, suggesting the crucial role of ROS in the formation of more toxic photolytic products. The study of photolysis pathways and the evaluation of the health risks provide a comprehensive understanding of the environmental effects of these pollutants.


Assuntos
Aliivibrio fischeri , Antioxidantes , Fenilenodiaminas , Fotólise , Poluentes Químicos da Água , Fenilenodiaminas/química , Fenilenodiaminas/toxicidade , Fenilenodiaminas/efeitos da radiação , Cinética , Aliivibrio fischeri/efeitos dos fármacos , Antioxidantes/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/efeitos da radiação , Borracha/química , Radical Hidroxila/química
2.
Technol Cancer Res Treat ; 23: 15330338241277584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39155627

RESUMO

Pyroptosis is a programmed cell death, which garners increasing attention by relating to immune and therapy response. However, the role of pyroptosis in colorectal cancer (CRC) remains unclear. Our study mainly to explore the role of pyroptosis in CRC. The mRNA expression data and corresponding clinical information of CRC patients were achieved from The Cancer Genome Atlas (TCGA). Pyroptosis-related genes (PRGs) were identified using DESeq2 R package and biological function was analyzed using cluster Profiler R package. A PRGs-based prognosis model was constructed by a univariate Cox and LASSO regression analyses. Then, the affecting of risk signature to clinicopathological characteristics, immune status and infiltrated immune cells, immune checkpoint and chemotherapy sensitivity was analyzed. qRT-PCR and IHC were performed for the expression level of PRGs. Moreover, a nomogram predict model was constructed. Total 57 PRGs were identified between 500 CRC samples and 44 normal samples. Those PRGs mainly enriched in immune-related and pyroptosis-related pathways. GABRD, NADK, TMEM240, RER1, AGRN, UBE2J2, CALML6, PLCH2, TMEM88B have been identified as gene signature and a prognostic model was constructed and validated. CRC patients with high-risk score showed poor survival, high TMB score, high proportion of CD4 + memory T cells, common lymphoid progenitors, cancer associated fibroblasts, mast cells, and neutrophils. The immune checkpoint related genes, CD160, CD200R1, CD244, CD28, CD40LG, CD44, CD48, CD80, CD86, HHLA2, ICOS, IDO1, TIGIT, TNFRSF25, TNFRSF4, TNFRSF9, TNFSF15, TNFSF18 also increased in high-risk score group. CRC patients with high-risk score more sensitive to docetaxel and rapamycin but resistance to gemcitabine and mitomycin. Moreover, a predictive nomogram for 1-, 3-, 5-year for CRC patients was established and validated. In the study, a PRGs-based prognostic model and a predictive model were constructed. These models are effective and robust in prediction the 1-, 3-, and 5-year survival of CRC patients.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Nomogramas , Piroptose , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Prognóstico , Piroptose/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Biomarcadores Tumorais/genética , Feminino , Masculino , Transcriptoma , Biologia Computacional/métodos , Bases de Dados Genéticas , Estimativa de Kaplan-Meier , Curva ROC , Pessoa de Meia-Idade
3.
Noncoding RNA Res ; 9(4): 1050-1060, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39022688

RESUMO

Long non-coding RNAs (LncRNAs) are a class of RNA molecules with nucleic acid lengths ranging from 200 bp to 100 kb that cannot code for proteins, which are diverse and widely expressed in both animals and plants. Scholars have found that lncRNAs can regulate human physiological processes at the gene and protein levels, mainly through the regulation of epigenetic, transcriptional and post-transcriptional levels of genes and proteins, as well as in the immune response by regulating the expression of immune cells and inflammatory factors, and thus participate in the occurrence and development of a variety of diseases. From the downstream targets of lncRNAs, we summarize the new research progress of lncRNA mechanisms other than miRNA sponges in recent years, aiming to provide new ideas and directions for the study of lncRNA mechanisms.

4.
Mol Immunol ; 173: 71-79, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067087

RESUMO

BACKGROUND: The treatment of food allergy (FA) needs improvement. The treatment of immune disorders can be improved by regulating epigenetic marks, which is a promising method. The objective of this research is to alleviate experimental FA by employing an inhibitor of DNA methyltransferase-1 (DNMT1). METHODS: Ovalbumin was used as the specific antigen to establish a mouse model of FA. Intestinal IL-35+ regulatory B cells (Breg cells) were isolated from FA mice, and characterized using immunological approaches. RESULTS: FA mice had a lower frequency of IL-35+ Breg cells, which was inversely correlated with their FA response. The quantity of IL-35 was lower in intestinal Breg cells from FA mice. Hypermethylation status was detected in the Il35 promoter, which was accompanied with high levels of H3K9me3. Enforced expression of DNMT1 hindered the promoter activity of the IL35 gene. Administration of an inhibitor of DNMT1 (RG108) restored the immune regulatory capacity of FA intestinal Bregs, and effectively suppressed the expression of DNMT1, and attenuated experimental FA. CONCLUSIONS: The elevated quantity of DNMT1 in intestinal Breg cells compromises the expression of IL-35 and affects the immune regulatory functions, which facilitates the development of FA. The immune regulatory functions of intestinal Breg cells are restored and experimental FA is attenuated by inhibiting DNMT1.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Hipersensibilidade Alimentar , Interleucinas , Regiões Promotoras Genéticas , Animais , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Hipersensibilidade Alimentar/imunologia , Camundongos , Interleucinas/imunologia , Interleucinas/metabolismo , Interleucinas/genética , Regiões Promotoras Genéticas/genética , Linfócitos B Reguladores/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Feminino , Ovalbumina/imunologia , Ftalimidas/farmacologia , Intestinos/imunologia , Triptofano/análogos & derivados
5.
Mol Cell Probes ; 75: 101961, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38579914

RESUMO

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.


Assuntos
Progressão da Doença , Neoplasias , RNA Longo não Codificante , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Regulação Neoplásica da Expressão Gênica , Animais , Transdução de Sinais
6.
Crit Rev Oncol Hematol ; 196: 104325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462151

RESUMO

Abscopal effects are characterized by the emergence of neoplasms in regions unrelated to the primary radiation therapy site, displaying a gradual attenuation or regression throughout the progression of radiation therapy, which have been of interest to scientists since Mole's proposal in 1953. The incidence of abscopal effects in radiation therapy is intricately linked to the immune system, with both innate and adaptive immune responses playing crucial roles. Biological factors impacting abscopal effects ultimately exert their influence on the intricate workings of the immune system. Although abscopal effects are rarely observed in clinical cases, the underlying mechanism remains uncertain. This article examines the biological and physical factors influencing abscopal effects of radiotherapy. Through a review of preclinical and clinical studies, this article aims to offer a comprehensive understanding of abscopal effects and proposes new avenues for future research in this field. The findings presented in this article serve as a valuable reference for researchers seeking to explore this topic in greater depth.


Assuntos
Neoplasias , Humanos , Neoplasias/radioterapia , Radioterapia/métodos
7.
Expert Rev Anticancer Ther ; 24(3-4): 155-167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299537

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/ß-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/ß-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment. METHODS: A comprehensive literature search was conducted to identify the relevant studies. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. The bivariate linear mixed models were used. RESULTS: The AUC (area under the curve), pooled sensitivity and specificity were 0.77, 0.42 and 0.98, respectively. The findings suggested that control type, sample source, research methods and thresholds were the potential sources of heterogeneity (p < 0.05). Additionally, this study also found that there were significant correlations between the hypermethylation of Wnt/ß-catenin signaling pathway-related ctDNA and tumor size, TNM stage, distant metastasis, and HBV infection(p < 0.05). CONCLUSION: This study confirmed that Wnt/ß-catenin signaling pathway-related ctDNA had the better diagnostic potential for liver cancer and might be an effective complementary tool for serum AFP assays in the early diagnosis of liver cancer. PROSPERO: (No. CRD42023404984).[Figure: see text].

8.
J Environ Manage ; 348: 119191, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37827074

RESUMO

This study aimed to remediate the problems of sludge floating and uneven mass transfer in up-flow partial denitrification/anammox (PDA) reactors and dissect the nitrogen removal mechanism. Two up-flow PDA reactors were operated, whereby in R1 combined biological carriers were added, while in R2 mechanical stirring was applied, the reactors were inoculated with PD sludge and anammox sludge. Results showed the TN removal rates at the end of the operation were 89% (R1) and 92% (R2). The addition of both strategies suppressed the occurrence of sludge upwelling and deterioration of settling performance, even when the granule diameter of the granular zone in R1 and R2 reached 1.921 and 2.006 mm, respectively. 16SrRNA sequencing revealed R1 had a higher abundance of anammox bacteria (AAOB, 14.53%-R1, 9.06%-R2, respectively), and R2 had a higher quantity of denitrifying bacteria (61.92%-R1, 67.11%-R2, respectively). And the nitrogen removal was contributed by anammox and denitrification in combination, with contributions of 82.17%, 17.83% (R1), and 85.07%, 14.93% (R2), respectively. In summary, both strategies prevented sludge flotation and uneven nitrogen mass transfer. However, mechanical agitation had a more substantial positive effect on the performance of PDA than the addition of biocarriers because it achieved a more adequate mass transfer.


Assuntos
Desnitrificação , Esgotos , Reatores Biológicos/microbiologia , Nitrogênio , Oxidação Anaeróbia da Amônia , Oxirredução
9.
BMC Cancer ; 23(1): 955, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814227

RESUMO

The interruption of normal cell cycle execution acts as an important part to the development of leukemia. It was reported that microRNAs (miRNAs) were closely related to tumorigenesis and progression, and their aberrant expression had been demonstrated to play a crucial role in numerous types of cancer. Our previous study showed that miR-1246 was preferentially overexpressed in chemo-resistant leukemia cell lines, and participated in process of cell cycle progression and multidrug resistant regulation. However, the underlying mechanism remains unclear. In present study, bioinformatics prediction and dual luciferase reporter assay indicated that CADM1 was a direct target of miR-1246. Evidently decreased expression of CADM1 was observed in relapsed primary leukemia patients and chemo-resistant cell lines. Our results furtherly proved that inhibition of miR-1246 could significantly enhance drug sensitivity to Adriamycin (ADM), induce cell cycle arrest at G0/G1 phase, promote cell apoptosis, and relieve its suppression on CADM1 in K562/ADM and HL-60/RS cells. Interference with CADM1 could reduce the increased drug sensitivity induced by miR-1246 inhibition, and notably restore drug resistance by promoting cell cycle progression and cell survival via regulating CDKs/Cyclins complexes in chemo-resistant leukemia cells. Above all, our results demonstrated that CADM1 attenuated the role of miR-1246 in promoting cell cycle progression and cell survival, thus influencing multidrug resistance within chemo-resistant leukemia cells via CDKs/Cyclins. Higher expression of miR-1246 and lower expression of CADM1 might be risk factors for leukemia.


Assuntos
Leucemia , MicroRNAs , Humanos , MicroRNAs/metabolismo , Células HL-60 , Doxorrubicina/farmacologia , Ciclo Celular/genética , Leucemia/tratamento farmacológico , Leucemia/genética , Ciclinas , Proliferação de Células , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Molécula 1 de Adesão Celular/genética
10.
Environ Technol ; : 1-14, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37345969

RESUMO

Partial denitrification granular sludge (PDGS) can provide long-term stable nitrite for anaerobic ammonia oxidation (anammox). The cultivation of ordinary activated sludge from wastewater treatment plants into PDGS can further promote the application of PD in practical engineering. In this study, the feasibility of fast start-up of PDGS was explored by inoculating waste sludge in up-flow anaerobic sludge blanket (UASB) reactor with synergistic control of nitrogen load rate (NLR, 0.05-0.65 kg N/m3/d) and electron donor starvation (EDS) (240-168 mg L-1), and system performance, particle characteristics and microbial structure were studied. The results showed that PD-UASB started successfully within 48 days, the average nitrite accumulation rate (NTR) and nitrate removal ratio (NRR) reached 79.6% and 82.5% after successful initiation, accompanied by high abundance of PD bacteria (Thauera, Pseudomonas, unclassflied commamonadaceae and Limnobacter) (25.3%). The increase of PD activity, and the difference between nitrate reductase (NAR) and nitrite reductase (NIR) contributed to nitrite production. Besides, the sludge shifted from flocculated (≤0.5 mm, 95.37%) to granulated state (0.5-2 mm, 64.74%), which could be due to the increase of extracellular polymers (EPS) (especially T-EPS) and metabolism of specific microorganisms (Bacteroidota and Chloroflexi, 19.92%). Good sludge granulation promoted the settleability of PD (the SVI5 was 47.248 mL/ g. ss after successful start-up). In summary, good PD sludge granulation process could be achieved in a short time by synergistically controlling NLR and EDS.

11.
Clin Exp Immunol ; 213(2): 155-163, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37279535

RESUMO

The pathogenesis of immune tolerance disruption is not fully understood. Galectin-9 (Gal9) has immune regulatory functions. The objective of the present study is to assess the role of Gal9 in maintaining immune tolerance. Blood and intestinal biopsies were taken from patients with food allergy (FA). The status of tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cells) in the samples was evaluated and used as representative parameters of immune tolerance. An FA mouse model was established to assess the role of Gal9 in maintaining immune tolerance. We found that peripheral CD11c+ CD5+ CD1d+ tDC frequency was significantly lower in FA patients as compared to health control (HC) subjects. There was no significant change in CD11c+ DC frequency between the FA group and the HC group. The expression of IL-10 in peripheral tDCs was lower in the FA group than that in the HC group. A positive correlation was detected between the serum levels of IL-10 and Gal9. The expression of Gal9 was observed in intestinal biopsies, which was positively correlated with the serum levels of Gal9 as well as serum IL-10 levels. Peripheral Tr1 cells had lower frequencies in the FA group than in the non-FA (Con) group. tDCs demonstrated the ability to generate Tr1 cells, which was weaker in the FA group as compared with the Con group. Exposure of FA tDCs to Gal9 in culture restored the ability to generate Tr1 cells. In summary, the lower frequency of tDC and Tr1 cell of FA patients was associated with the levels of Gal9. The presence of Gal9 restored the capacity of tDC to generate Tr1 cells.


Assuntos
Hipersensibilidade Alimentar , Galectinas , Interleucina-10 , Animais , Camundongos , Células Dendríticas , Galectinas/metabolismo , Tolerância Imunológica , NF-kappa B/metabolismo , Linfócitos T Reguladores
12.
BMC Cancer ; 23(1): 557, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328795

RESUMO

BACKGROUND: Primary liver cancer is a malignant tumour of the digestive system, ranking second in cancer mortality in China. In different types of cancer, such as liver cancer, microRNAs (miRNAs) have been shown to be dysregulated. However, little is known about the role of miR-5195-3p in insulin-resistant liver cancer. METHODS AND RESULTS: In this study, in vitro and in vivo experiments were conducted to identify the altered biological behaviour of insulin-resistant hepatoma cells (HepG2/IR), and we proved that HepG2/IR cells had stronger malignant biological behaviour. Functional experiments showed that enhanced expression of miR-5195-3p could inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance of HepG2/IR cells, while impaired expression of miR-5195-3p in HepG2 cells resulted in the opposite effects. Bioinformatics prediction and dual luciferase reporter gene assays proved that SOX9 and TPM4 were the target genes of miR-5195-3p in hepatoma cells. CONCLUSIONS: In conclusion, our study demonstrated that miR-5195-3p plays a critical role in insulin-resistant hepatoma cells and might be a potential therapeutic target for liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Insulina/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Tropomiosina/genética , Tropomiosina/metabolismo
13.
RSC Adv ; 13(23): 15981-15992, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37250223

RESUMO

Proper treatment of hazardous contaminants in the air, land, and water is crucial to environmental remediation. Sonocatalysis, by using ultrasound and suitable catalysts, has shown its potential in organic pollutant removal. In this work, K3PMo12O40/WO3 sonocatalysts were fabricated via a facile solution method at room temperature. Techniques such as powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy, and X-ray photoelectron spectroscopy were used to characterize the structure and morphology of the products. By using the K3PMo12O40/WO3 sonocatalyst, an ultrasound-assisted advanced oxidation process has been developed for the catalytic degradation of methyl orange and acid red 88. Almost all dyes were degraded within 120 min of ultrasound baths, proving that the K3PMo12O40/WO3 sonocatalyst has the advantage of speeding up the decomposition of contaminants. The impacts of key parameters, including catalyst dosage, dye concentration, dye pH, and ultrasonic power were evaluated to understand and reach optimized conditions in sonocatalysis. The remarkable performance of K3PMo12O40/WO3 in the sonocatalytic degradation of pollutants provides a new strategy for the application of K3PMo12O40 in sonocatalysis.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37018603

RESUMO

Script event prediction aims to infer subsequent events given an incomplete script. It requires a deep understanding of events, and can provide support for a variety of tasks. Existing models rarely consider the relational knowledge between events, they regard scripts as sequences or graphs, which cannot capture the relational information between events and the semantic information of script sequences jointly. To address this issue, we propose a new script form, relational event chain, that combines event chains and relational graphs. We also introduce a new model, relational-transformer, to learn embeddings based on this new script form. In particular, we first extract the relationship between events from an event knowledge graph to formalize scripts as relational event chains, then use the relational-transformer to calculate the likelihood of different candidate events, where the model learns event embeddings that encode both semantic and relational knowledge by combining transformers and graph neural networks (GNNs). Experimental results on both one-step inference and multistep inference tasks show that our model can outperform existing baselines, indicating the validity of encoding relational knowledge into event embeddings. The influence of using different model structures and different types of relational knowledge is analyzed as well.

15.
Int Soc Work ; 66(1): 233-253, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650895

RESUMO

As the first review to systematically explore the scope and application of Chinese social work research ethics, this study incorporated web-crawling technology in the scoping review process and identified 18 eligible studies from 1168 publications from January 2020 to July 2021. Findings suggest that social work scholars are aware of research ethics when conducting human subjects research in the Chinese population. Yet, many failed to fully demonstrate practical considerations of internationally accepted ethical principles (e.g. respect for persons). We discuss education on research ethics, new challenges of the digital age, and considerations of Chinese culture in developing ethical protocols for social work research in China.

16.
Sensors (Basel) ; 22(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36366185

RESUMO

Currently, the online non-destructive testing (NDT) methods to measure the contact states of high-voltage circuit breakers (HVCBs) with SF6 gas as a quenching medium are lacking. This paper aims to put forward a novel method to detect the contact state of an HVCB based on the vibrational signal. First, for a 40.5-kV SF6 HVCB prototype, a mechanical vibration detection system along with a high-current generator to provide the test current is designed. Given this, vibration test experiments are carried out, and the vibration signal data under various currents and corresponding contact states are obtained. Afterward, a feature extraction method based on the frequency is designed. The state of the HVCB contacts is then determined using optimized deep neural networks (DNNs) along with the method of adaptive moment estimation (Adam) on the obtained experimental data. Finally, the hyperparameters for the DNNs are tuned using the Bayesian optimization (BO) technique, and a global HVCB contact state recognition model at various currents is proposed. The obtained results clearly depict that the proposed recognition model can accurately identify five various contact states of HVCBs for the currents between 1000 A and 3500 A, and the recognition accuracy rate is above 96%. The designed experimental and theoretical analysis in our study will provide the references for future monitoring and diagnosis of faults in HVCBs.


Assuntos
Redes Neurais de Computação , Vibração , Teorema de Bayes
17.
Commun Biol ; 5(1): 1248, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376440

RESUMO

To explore highly selective targeting molecules of colorectal cancer (CRC) is a challenge. We previously identified a twelve-amino acid peptide (LPKTVSSDMSLN, namely P-LPK) by phage display technique which may specifically binds to CRC cells. Here we show that P-LPK selectively bind to a panel of human CRC cell lines and CRC tissues. In vivo, Gallium-68 (68Ga) labeled P-LPK exhibits selective accumulation at tumor sites. Then, we designed a peptide-conjugated drug comprising P-LPK and camptothecin (CPT) (namely P-LPK-CPT), and found P-LPK-CPT significantly inhibits tumor growth with fewer side effects in vitro and in vivo. Furthermore, through co-immunoprecipitation and molecular docking experiment, the glutamine transporter solute carrier 1 family member 5 (SLC1A5) was identified as the possible target of P-LPK. The binding ability of P-LPK and SLC1A5 is verified by surface plasmon resonance and immunofluorescence. Taken together, P-LPK-CPT is highly effective for CRC and deserves further development as a promising anti-tumor therapeutic for CRC, especially SLC1A5-high expression type.


Assuntos
Camptotecina , Neoplasias Colorretais , Humanos , Camptotecina/farmacologia , Camptotecina/química , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Glutamina/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Antígenos de Histocompatibilidade Menor/metabolismo , Sistema ASC de Transporte de Aminoácidos/metabolismo
18.
Front Cell Dev Biol ; 10: 836041, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281088

RESUMO

Recently, the incidences of insulin resistance (IR) and IR-related complications have increased throughout the world, which also associate with poor prognosis in hepatocellular carcinoma (HCC). Numerous studies had been focused on the role of IR in tumorigenesis and prognosis of HCC. The proteomic analysis of IR related hepatocellular carcinoma had not been reported by now. In the present study, 196 differentially expressed proteins (DEPs) were identified between insulin resistant HepG2 cells and their parental cells, of which 109 proteins were downregulated and 87 proteins were upregulated. Bioinformatics analysis indicated that these DEPs were highly enriched in process of tumorigenesis and tumor progression. PPI network analysis showed that SOX9, YAP1 and GSK3ß as the key nodes, were involved in Wnt and Hippo signaling pathways. Survival analysis revealed that high expression of SOX9 and PRKD3 were strongly associated with reduced patient survival rate. parallel reaction monitoring (PRM) and Western blot analysis were applied to verify the protein level of these four key nodes mentioned above, which showed the same trend as quantified by isobaric tags for relative and absolute quantitation (iTRAQ) and confirmed the reliability of our Proteome Profiling analysis. Our results indicated that IR related dysregulation of protein expression might participated in tumorigenesis and malignant phenotype of hepatocarcinoma cells.

19.
Front Cell Infect Microbiol ; 12: 827129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223549

RESUMO

As a life-threatening disease, stroke is the leading cause of death and also induces adult disability worldwide. To investigate the efficacy of the integrated traditional Chinese medicine (ITCM) on the therapeutic effects of acute ischemic stroke (AIS) patients, we enrolled 26 patients in the ITCM [Tanhuo decoction (THD) + Western medicine (WM)] group and 23 in the WM group. Thirty healthy people were also included in the healthy control (HC) group. ITCM achieved better functional outcomes than WM, including significant reduction of the phlegm-heat syndrome and neurological impairment, and improvement of ability. These facts were observed in different pretreatment gut enterotypes. In this paper, we collected the stool samples of all participants and analyzed the 16S rRNA sequence data of the gut microbiota. We identified two enterotypes (Type-A and Type-B) of the gut microbial community in AIS samples before treatment. Compared to Type-B, Type-A was characterized by a high proportion of Bacteroides, relatively high diversity, and severe functional damage. In the ITCM treatment group, we observed better clinical efficacy and positive alterations in microbial diversity and beneficial bacterial abundance, and the effect of approaching healthy people's gut microbiota, regardless of gut enterotypes identified in pretreatment. Furthermore, we detected several gut microbiota as potential therapeutic targets of ITCM treatment by analyzing the correlations between bacterial abundance alterations and functional outcomes, where Dorea with the strongest correlation was known to produce anti-inflammatory metabolite and negatively linked to trimethylamine-N-oxide (TMAO), a biomarker of AIS. This study analyzed clinical and gut microbial data and revealed the possibility of a broad application independent of the enterotypes, as well as the therapeutic targets of the ITCM in treating AIS patients with phlegm-heat syndrome.


Assuntos
Microbioma Gastrointestinal , AVC Isquêmico , Microbiota , Adulto , Humanos , AVC Isquêmico/tratamento farmacológico , Medicina Tradicional Chinesa , RNA Ribossômico 16S/genética
20.
Folia Histochem Cytobiol ; 60(1): 66-73, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35037695

RESUMO

INTRODUCTION: This study is to detect the expression of inflammatory factor or neutrophil-activating factor IL-8 and Wnt2 in gastric cancer (GC) and investigate the involvement of IL-8 and Wnt2 expressions in the clinicopathological indexes and prognosis. MATERIAL AND METHODS: We detected the expression of IL-8 and Wnt2 in 100 GC tissues and 40 normal gastric mucosae using immunohistochemistry. The relationships between the IL-8 and Wnt2 expression and the clinicopathological characteristics were explored. The relationship between IL-8 expression, Wnt2 expression, and prognosis of GC was analyzed by survival curve and survival regression. RESULTS: The expression of IL-8 and Wnt2 in GC tissue was 64% and 75% respectively, which was significantly higher than that in adjacent normal gastric mucosa tissues, moreover, expressions of IL-8 and Wnt2 were positively correlated. The positive rate of IL-8 and Wnt2 expressions were correlated with lymph node metastasis and TNM staging (P < 0.01, and Wnt2 was also correlated with infiltration depth (P = 0.021), but there was no difference with age, sex, and differentiation (P > 0.05). The 3-year survival analysis showed that the survival rates of IL-8- and Wnt2-positive patients were 20% and 24%, respectively, which were significantly lower than those of negative patients. Cox regression analysis showed that IL-8 and Wnt2 may be independent factors affecting the prognosis of GC. CONCLUSIONS: Our data demonstrated that the overexpression of IL-8 and Wnt2 could be isolated prognostic factors in patients with GC and, possibly, may present new targets for the treatment of GC.


Assuntos
Interleucina-8/metabolismo , Neoplasias Gástricas/patologia , Proteína Wnt2/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Imuno-Histoquímica , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Proteína Wnt2/genética
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