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1.
Cereb Cortex ; 34(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436464

RESUMO

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Conectoma , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Medo
2.
Inorg Chem ; 62(13): 5145-5157, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36959749

RESUMO

Hexachlorocyclotriphosphazene is one of the most representative phosphazene compounds which have been proved to have broad application prospects in many fields. However, it is an emerging research perspective to combine cyclotriphosphazene-derived polycarboxylic acid compounds with lanthanides for the construction of Tb-DPCP metal-organic framework (MOF) materials. Herein, a Tb-DPCP MOF, (CH3)2NH2[Tb3(HDPCP)(DMF)(H2O)3]·6DMF (1), was successfully prepared via the reaction of H12HDPCP [hexa(4-carboxyphenoxy) cyclotriphosphazene] and Tb(NO3)3·6H2O under the solvothermal condition. Through fluorescence sensing experiments, it was found that both nitrophenols and chlorophenols could cause the fluorescence quenching of compound 1. At the same time, the compound also exhibited nice trace detection ability for small-molecule drugs (moxifloxacin hydrochloride, balsalazide disodium, and colchicine); the limits of detection were all lower than 0.2 µM. These experimental results fully demonstrated the potential application value of 1 as a multifunctional fluorescent sensor.

3.
Angew Chem Int Ed Engl ; 62(36): e202306509, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37417837

RESUMO

Acepleiadylene (APD), a nonbenzenoid isomer of pyrene, exhibits a unique charge-separated character with a large molecular dipole and a small optical gap. However, APD has never been explored in optoelectronic materials to take advantage of these appealing properties. Here, we employ APD as a building block in organic semiconducting materials for the first time, and unravel the superiority of nonbenzenoid APD in electronic applications. We have synthesized an APD derivative (APD-IID) with APD as the terminal donor moieties and isoindigo (IID) as the acceptor core. Theoretical and experimental investigations reveal that APD-IID has an obvious charge-separated structure and enhanced intermolecular interactions as compared with its pyrene-based isomers. As a result, APD-IID displays significantly higher hole mobilities than those of the pyrene-based counterparts. These results imply the advantages of employing APD in semiconducting materials and great potential of nonbenzenoid polycyclic arenes for optoelectronic applications.

4.
Phytother Res ; 35(2): 1033-1047, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33006176

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Dieta Hiperlipídica/métodos , Células Endoteliais/metabolismo , Glucosídeos/uso terapêutico , Interleucina-17/metabolismo , Monoterpenos/uso terapêutico , Vasculite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Glucosídeos/farmacologia , Humanos , Masculino , Monoterpenos/farmacologia , Ratos , Transdução de Sinais
5.
Acta Pharmacol Sin ; 41(6): 800-812, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31937932

RESUMO

IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1(CD4+IFN-γ+), and Th17(CD4+IL-17+) were significantly increased, whereas the Treg (CD4+CD25+Foxp3+) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1 (CD4+IFN-γ+), and Th17(CD4+IL-17+); increased Treg (CD4+CD25+Foxp3+) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 µg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 µg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling.


Assuntos
Artrite Experimental/imunologia , Imunoglobulina D/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , NF-kappa B/metabolismo , Receptores de IgG/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Ácido Acético , Animais , Artrite Experimental/induzido quimicamente , Imunoglobulina D/química , Fragmentos Fc das Imunoglobulinas/química , Masculino , Ratos , Ratos Wistar , Receptores de IgG/metabolismo
6.
Acta Pharmacol Sin ; 40(6): 801-813, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30446734

RESUMO

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19+TRAF2+ cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger anti-inflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Glucosídeos/uso terapêutico , Monoterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/induzido quimicamente , Fator Ativador de Células B/metabolismo , Linfócitos B/metabolismo , Proliferação de Células/efeitos dos fármacos , Colágeno , Etanercepte/uso terapêutico , Células HEK293 , Humanos , Articulações/patologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos Endogâmicos DBA , Subunidade p50 de NF-kappa B/metabolismo , Rituximab/uso terapêutico , Baço/patologia , Linfócitos T/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo
7.
Sensors (Basel) ; 19(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146459

RESUMO

This work reports a new simulated inductor which is suitable for a Contactless Electrical Tomography (CET) system and can effectively overcome the unfavorable influence of coupling capacitance on the measurement results. By detailed analysis and comparison, it is found that the grounded simulated inductor has a simple circuit construction but its output current is not equal to its input current, while the floating simulated inductor can be used as an independent inductor module but its circuit structure is relatively complex. A new simulated inductor is designed by compensating the currents from the common node of an introduced independent power source to the main circuit. The new simulated inductor combines the advantages of the grounded simulated inductor and the floating simulated inductor. It has the simple construction similar to that of the grounded simulated inductor and its input current is equal to the output current, which means it can be used as an independent module. The impedance measurement and practical image reconstruction experiments were carried out to verify the effectiveness of the new simulated inductor. The experimental results show that the design of the new simulated inductor is successful, and the performance of the impedance measurement is satisfactory. The signal-to-noise ratio of the CET system is improved. Meanwhile, the research work also indicates that in the case when the independent power source is not available, the new simulated inductor is also an effective alternative method. But the phase difference between input signal and output signal is approximately 90° when the elimination principle is realized.

8.
Rev Esp Enferm Dig ; 111(9): 710-711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368327

RESUMO

A 50-year-old female came to our hospital with a 6-month history of upper abdominal discomfort. An upper endoscopy detected a protruding lesion that measured 3.0×2.0 cm at around 35-38 cm from the incisors located on the posterior wall. Endoscopic ultrasonography revealed a homogeneous hyperechoic mass located in the muscularis propria, with no malignant features. Contrast-enhanced CT was also performed. A submucosal tunneling endoscopic resection (STER) was performed. A longitudinal mucosal incision was made and a submucosal tunnel created, which uncovered an irregularly giant tumor. The size of the resected tumor was 3.0×4.0×1.5cm and the histopathological analysis identified leiomyomas. The patient was discharged 7 days after the procedure and 3 months after the surgery there was no recurrence on the CT scan. Meanwhile, the discomfort of the patient was relieved after STER and there were no severe complications during the 6-month follow-up. DISCUSSION Esophageal leiomyoma is a benign submucosal tumor derived from the muscularis propria layer of the esophagus [1]. STER has been demonstrated to be safe and effective for treating small (≤3.5 cm) and solitary esophageal leiomyoma with low complication rates [2-3]. Most esophageal leiomyoma grow into the lumen and their positions in the tunnel are relatively superficial and the entire surgery is comparatively safe. In this case, the tumor was very large and was close to the mediastinum, which greatly increases the difficulty of surgery. However, STER is recommended according to our experience, even in rare cases.


Assuntos
Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Leiomioma/cirurgia , Endossonografia/métodos , Mucosa Esofágica/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Esofagoscopia/métodos , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
9.
Appl Microbiol Biotechnol ; 99(13): 5739-48, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25935346

RESUMO

Furfural and acetic acid from lignocellulosic hydrolysates are the prevalent inhibitors to Zymomonas mobilis during cellulosic ethanol production. Developing a strain tolerant to furfural or acetic acid inhibitors is difficul by using rational engineering strategies due to poor understanding of their underlying molecular mechanisms. In this study, strategy of adaptive laboratory evolution (ALE) was used for development of a furfural and acetic acid-tolerant strain. After three round evolution, four evolved mutants (ZMA7-2, ZMA7-3, ZMF3-2, and ZMF3-3) that showed higher growth capacity were successfully obtained via ALE method. Based on the results of profiling of cell growth, glucose utilization, ethanol yield, and activity of key enzymes, two desired strains, ZMA7-2 and ZMF3-3, were achieved, which showed higher tolerance under 7 g/l acetic acid and 3 g/l furfural stress condition. Especially, it is the first report of Z. mobilis strain that could tolerate higher furfural. The best strain, Z. mobilis ZMF3-3, has showed 94.84% theoretical ethanol yield under 3-g/l furfural stress condition, and the theoretical ethanol yield of ZM4 is only 9.89%. Our study also demonstrated that ALE method might also be used as a powerful metabolic engineering tool for metabolic engineering in Z. mobilis. Furthermore, the two best strains could be used as novel host for further metabolic engineering in cellulosic ethanol or future biorefinery. Importantly, the two strains may also be used as novel-tolerant model organisms for the genetic mechanism on the "omics" level, which will provide some useful information for inverse metabolic engineering.


Assuntos
Ácido Acético/metabolismo , Adaptação Biológica , Tolerância a Medicamentos , Etanol/metabolismo , Furaldeído/metabolismo , Zymomonas/genética , Zymomonas/metabolismo , Antibacterianos/metabolismo , Lignina/metabolismo , Engenharia Metabólica , Zymomonas/efeitos dos fármacos
10.
Biosci Biotechnol Biochem ; 78(4): 708-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25036971

RESUMO

In the current study, three native signal peptides (SPs) from PhoC, PhoD, and ZMO0331were investigated and compared to construct novel secretion expression systems in Zymomonas mobilis. The secretion expression of target protein, α-amylase from Bacillus amyloliquefaciens (BAA), guided by PhoD's SP resulted in more hydrolysis of starch than that by the other two SPs. Extracellular and intracellular α-amylase activities of the strain containing PhoD's SP were also higher than the other two strains containing PhoC or ZMO0331's SP. In addition, the evidence by alcohol dehydrogenase activity assay further confirmed that the starch hydrolysis was resulted from the secretion expression of BAA rather than the breakage of cells. Our results indicated that the SP of PhoD is able to serve as a promising candidate to assist secretion expression of heterogeneous genes in Z. mobilis. This will contribute to development of engineered Z. mobilis strains converting starch into ethanol.


Assuntos
Fosfatase Alcalina/química , Fosfatase Alcalina/metabolismo , Engenharia Genética/métodos , Sinais Direcionadores de Proteínas/genética , Zymomonas/genética , Álcool Desidrogenase/metabolismo , Fosfatase Alcalina/genética , Bacillus/enzimologia , Clonagem Molecular , Fermentação , Expressão Gênica , Hidrólise , Ipomoea batatas/química , Análise de Sequência , Amido/metabolismo , Zymomonas/metabolismo , alfa-Amilases/genética
11.
Sci Rep ; 13(1): 8361, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37225746

RESUMO

For some new mines, the utilization rate of tailings is not satisfactory when using unclassified tailings as backfill aggregate for cemented backfill. At the same time, with the progress of mineral processing technology, the tailings discharged by the concentrator gradually become finer. Therefore, cemented filling with fine-grained tailings as aggregate will become the development direction of filling technology in the future. In this paper, the feasibility of fine particle tailings backfill is studied by taking the particle tailings of-200 mesh as aggregate in Shaling gold mine. The calculation shows that the utilization rate of tailings is increased from 45.1% to 90.3% by using-200 mesh tailings as filling aggregate. The response surface central composite design method (RSM-CCD) was used to study the strength of backfill with alkali-activated cementitious material as binder by taking the mass concentration of backfill slurry and sand-binder ratio as input factors. The results show that the 28-day strength of the backfill with graded fine-grained tailings as filling aggregate can reach 5.41 MPa when the sand-binder ratio is 4, which can fully meet the needs of the mine for the strength of the backfill. The thickening test of-200 mesh fine particle tailings was carried out by static limit concentration test and dynamic thickening test. In the case of adding 35 g/t BASF 6920 non-ionic flocculant, the concentration of 64.74% tail mortar can reach 67.71% after 2 h of static thickening, and the concentration can reach 69.62% after 2 h of static thickening. The feeding speed of thickener should be controlled between 0.4 and 0.59 t/(m2 h). In this case, the underflow concentration of thickener is relatively high, which is 64.92-65.78%, and the solid content of overflow water is less than 164 ppm. The conventional full tailings thickening process was improved by using the design of high-efficiency deep cone thickener and vertical sand silo. The feasibility of fine-grained tailings as filling aggregate was demonstrated by combining the filling ratio test of fine-grained tailings, the data of thickening test and the improved thickening process. The research results can provide reference for other mines to use fine-grained tailings as filling aggregate to design filling system.

12.
J Neurosurg Sci ; 67(6): 727-732, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35416452

RESUMO

BACKGROUND: Unruptured intracranial vertebral artery dissecting aneurysms (IVADAs) with mass effect have an extremely poor natural course, and treatment of these aneurysms remains a challenge for endovascular and surgical strategies. The aim of this study was to analyze the role of double-stent-assisted coil embolization in preventing rupture and bleeding of intracranial vertebral artery dissecting aneurysm with brainstem compression by reducing mass effect and preventing the recurrence of the aneurysm. METHODS: A total of 25 patients (mean age, 56.04±13.0 years) with unruptured IVADAs with mass effect received dual-stent-assisted coil embolization. The baseline characteristics, the change of aneurysm size on MR, the rate of retreatment, and the improvement rate of clinical symptoms and signs were analyzed retrospectively. RESULTS: All patients completed the surgical procedures successfully. No aneurysm bleeding or perforating artery occlusion occurred during the perioperative and follow-up periods. The initial maximum diameter of the aneurysm on MR was 17.5±3.6 mm. One year after treatment, the maximum diameter of the aneurysm on MR was 15.8±4.9 mm. The reduction rate of the maximum diameter of the aneurysm was 10.7±12.7%. The change of the maximum diameter before and after treatment of aneurysm was statistically significant (P<0.001). In terms of the improvement rate of clinical symptoms, 15 cases were completely improved (60.0%), 6 cases were partially improved (24.0%), and the total clinical improvement rate was 84%. Four cases (16.0%) showed no improvement or even had aggravation of clinical symptoms. In 5 cases (20.0%), aneurysms recurred. Among 4 cases involving posterior inferior cerebellar artery origin, 3 cases had the recurrence (75%). 5 recurred cases were treated with single-stent-assisted coil embolization. No residual aneurysm and recurrence were found on the follow-up angiography. CONCLUSIONS: The double-stent-assisted coil embolization procedure is very safe and reliable. It can effectively prevent the aneurysm from continuing to grow and rupture and thereby reduce the clinical symptoms caused by the mass effect.


Assuntos
Dissecção Aórtica , Embolização Terapêutica , Aneurisma Intracraniano , Dissecação da Artéria Vertebral , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Artéria Vertebral/cirurgia , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Embolização Terapêutica/métodos , Resultado do Tratamento , Dissecação da Artéria Vertebral/cirurgia , Stents , Angiografia Cerebral/métodos
13.
Appl Microbiol Biotechnol ; 95(1): 189-99, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22592554

RESUMO

Furfural from lignocellulosic hydrolysates is the prevalent inhibitor to microorganisms during cellulosic ethanol production, but the molecular mechanisms of tolerance to this inhibitor in Zymomonas mobilis are still unclear. In this study, genome-wide transcriptional responses to furfural were investigated in Z. mobilis using microarray analysis. We found that 433 genes were differentially expressed in response to furfural. Furfural up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. However, furfural has a subtle negative effect on Entner-Doudoroff pathway mRNAs. Our results revealed that furfural had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to furfural. This research has provided insights into the molecular response to furfural in Z. mobilis, and it will be helpful to construct more furfural-resistant strains for cellulosic ethanol production.


Assuntos
Furaldeído/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Estresse Fisiológico , Zymomonas/fisiologia , Biotecnologia , Etanol/metabolismo , Furaldeído/metabolismo , Genoma Bacteriano , Hidrólise , Lignina/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Zymomonas/genética , Zymomonas/crescimento & desenvolvimento
14.
Front Immunol ; 13: 994594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466869

RESUMO

Background: T-cell-T-cell interactions play important roles in the regulation of T-cells' cytotoxic function, further impacting the anti-tumor efficacy of immunotherapy. There is a lack of comprehensive studies of T-cell types in bladder urothelial carcinoma (BLCA) and T-cell-related signatures for predicting prognosis and monitoring immunotherapy efficacy. Methods: More than 3,400 BLCA patients were collected and used in the present study. The ssGSEA algorithm was applied to calculate the infiltration level of 19 T-cell types. A cell pair algorithm was applied to construct a T-cell-related prognostic index (TCRPI). Survival analysis was performed to measure the survival difference across TCRPI-risk groups. Spearman's correlation analysis was used for relevance assessment. The Wilcox test was used to measure the expression level difference. Results: Nineteen T-cell types were collected; 171 T-cell pairs (TCPs) were established, of which 26 were picked out by the least absolute shrinkage and selection operator (LASSO) analysis. Based on these TCPs, the TCRPI was constructed and validated to play crucial roles in survival stratification and the dynamic monitoring of immunotherapy effects. We also explored several candidate drugs targeting TCRPI. A composite TCRPI and clinical prognostic index (CTCPI) was then constructed, which achieved a more accurate estimation of BLCA's survival and was therefore a better choice for prognosis prediction in BLCA. Conclusions: All in all, we constructed and validated TCRPI based on cell pair algorithms in this study, which might put forward some new insights to increase the survival estimation and clinical response to immune therapy for individual BLCA patients and contribute to the personalized precision immunotherapy strategy of BLCA.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Algoritmos , Carcinoma de Células de Transição/terapia , Fatores Imunológicos , Imunoterapia , Linfócitos T , Bexiga Urinária , Neoplasias da Bexiga Urinária/terapia
15.
Front Immunol ; 13: 845956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371006

RESUMO

Skin fibrosis is a common pathological feature of various diseases, and few treatment strategies are available because of the molecular pathogenesis is poorly understood. The urokinase-type plasminogen activator (uPA) system is the major serine protease system, and its components uPA, urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) are widely upregulated in fibrotic diseases, including hypertrophic scars, keloids, and scleroderma. Here, we found that the successful binding of uPA and uPAR activates the downstream peroxisome proliferator-activated receptor (PPAR) signalling pathway to reduce the proliferation, migration, and contraction of disease-derived fibroblasts, contributing to the alleviation of skin fibrosis. However, increased or robust upregulation of the inhibitor PAI-1 inhibits these effects, suggesting of the involvement of PAI-1 in skin fibrosis. Subsequent in vivo studies showed that uPAR inhibitors increased skin fibrosis in mouse models, while uPA agonists and PAI-1 inhibitors reversed these effects. Our findings demonstrate a novel role for the uPA system and highlights its relationships with skin fibrosis, thereby suggesting new therapeutic approaches targeting the uPA system.


Assuntos
Inibidor 1 de Ativador de Plasminogênio , Ativador de Plasminogênio Tipo Uroquinase , Animais , Células Cultivadas , Fibroblastos/metabolismo , Fibrose , Camundongos , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
16.
Rev Sci Instrum ; 92(10): 105006, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717397

RESUMO

The flow parameter measurement of the gas-liquid two-phase flow in small channels is very crucial and challenging in both academia and industry. Conventional techniques based on radiations, optics, acoustics, or electrics most lose their superiorities in the scenario with small channels due to the spatial limitation and the online and contactless measurement requirements. In addition, the conductive characteristic of the two-phase flow is equivalent to an impedance rather than a resistance due to the existence of multi-phases. The equivalent impedance information of the two-phase flow, especially the imaginary part, is promising to provide more flowing details but has seldom been detected or analyzed. In this paper, a method for the void fraction measurement of bubble/slug flow in small channels is proposed. The method implements void fraction measurement in a contactless way, based on the acquisition of the total impedance information of the gas-liquid two-phase flow. First, a new contactless impedance detection sensor is designed, based on the simulated inductor technique and the analog phase sensitive demodulation technique, to obtain the complete equivalent impedance information of the two-phase fluid. Then, based on the flow pattern identification result, the void fraction measurement model is developed, which is a fusion of the relationships between the void fraction and the real part/the imaginary part of the equivalent impedance information, respectively. Experimental results on prototypes with different inner diameters (2.48, 3.64, and 4.52 mm, respectively) validate the effectiveness of the proposed void fraction method. The maximum void fraction measurement biases are within 5.0%.

17.
Front Cell Dev Biol ; 9: 713605, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354997

RESUMO

In recent years, research on wound healing has become increasingly in-depth, but therapeutic effects are still not satisfactory. Occasionally, pathological tissue repair occurs. Influencing factors have been proposed, but finding the turning point between normal and pathological tissue repair is difficult. Therefore, we focused our attention on the most basic level of tissue repair: fibroblasts. Fibroblasts were once considered terminally differentiated cells that represent a single cell type, and their heterogeneity was not studied until recently. We believe that subpopulations of fibroblasts play different roles in tissue repair, resulting in different repair results, such as the formation of normal scars in physiological tissue repair and fibrosis or ulcers in pathological tissue repair. It is also proposed that scarless healing can be achieved by regulating fibroblast subpopulations.

18.
Rev Sci Instrum ; 91(5): 055001, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32486734

RESUMO

Based on the C4D technique and cross correlation velocity measurement technique, a new method for bubble/slug velocity measurement of the gas-liquid two-phase flow in small channels is proposed. A new C4D sensor, which is suitable for the parameter measurement of the gas-liquid two-phase flow in small channels, is developed by introducing the principle of capacitive reactance elimination. With two new C4D sensors, a bubble/slug velocity measurement system is developed, and the bubble/slug velocity is determined by the cross correlation velocity measurement technique. To verify the effectiveness of the proposed bubble/slug velocity measurement method, three prototypes of bubble/slug velocity measurement systems with different diameters (1.82 mm, 2.65 mm, and 2.96 mm, respectively) were established, and the bubble/slug measurement experiments were carried out. The research results show that the capacitive reactance elimination is an effective way to overcome the unfavorable influence of the coupled capacitances on measurement results. The experimental results indicate that the proposed method can successfully realize the bubble/slug velocity measurement in small channels, and the velocity measurement accuracy is satisfactory. For the three prototypes of the bubble/slug velocity measurement system, the maximum relative errors of the bubble/slug velocity measurement are all less than 5%.

19.
Front Pharmacol ; 11: 676, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477138

RESUMO

OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19-CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19-CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

20.
Artigo em Zh | MEDLINE | ID: mdl-20232625

RESUMO

OBJECTIVE: To make an epidemiological investigation on clonorchiasis sinensis and relevant factors in the south of Hunan Province. METHODS: One village from each of Lengshuitan District and Qiyang County was selected for the survey from November to December in 2006. Stool samples from villagers were collected and examined by modified Kato-Katz method. Questionnairing was performed for relevant knowledge and attitude among residents. The infection rate in animal reservoirs and intermediate hosts were detected. RESULTS: A total of 586 cases with Clonorchis sinensis infection were found from 777 people with a prevalence of 75.4%. The average egg density was 451 eggs per gram (EPG) feces. Light, moderate and heavy infections occupied 85.5% (501/586), 14.0% (82/586), and 0.5% (3/586) respectively. Prevalence in males and females was 76.9% (316/411) and 73.8% (270/366) respectively with no significant difference (chi2 = 1.013, P > 0.05). Infections were found in all age groups, with the highest prevalence in the group of 70 to 79 years (85.7%, 30/35). By occupations, the prevalence was 82.5% (447/542) in peasants, 79.3% (42/53) in doctors, 73.7% (28/38) in teachers, and 73.5% (25/34) in local cadres. The infection rate was 17.4% (29/167) and 7.4% (2/27) in Parafossarulus seriatulus and Alocinma longicornis, and 69.2% (9/13) and 5.3% (1/19) in Carassius auratus and Cyprinus carpios respectively. Adult worms were found in all 3 dogs dissected. Over 80% inhabitants did not know that this disease can be acquired by eating raw fish. 95.6% (153/160) of the farmers and 56.7% (349/616) of the students had a history of eating raw fish. The water was contaminated with C. sinensis eggs by using untreated feces as fertilizer for farming and by scrubbing pail latrines in the ponds. CONCLUSION: The prevalence of clonorchiasis in human population is high in Lengshuitan District and Qiyang County of Hunan Province. Eating raw fish and using untreated feces as fertilizer are the most important epidemiological factors of the disease.


Assuntos
Clonorquíase/epidemiologia , Clonorquíase/parasitologia , Clonorchis sinensis , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , China/epidemiologia , Cães , Fezes/parasitologia , Comportamento Alimentar , Feminino , Interações Hospedeiro-Parasita , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Inquéritos e Questionários , Adulto Jovem
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