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1.
Micromachines (Basel) ; 15(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38675328

RESUMO

This study demonstrates a particular composited barrier structure of high-electron-mobility transistors (HEMTs) with an enhancement mode composed of p-GaN/GaN/AlN/AlGaN/GaN. The purpose of the composite barrier structure device is to increase the maximum drain current, reduce gate leakage, and achieve lower on-resistance (Ron) performance. A comparison was made between the conventional device without the composited barrier and the device with the composited barrier structure. The maximum drain current is significantly increased by 37%, and Ron is significantly reduced by 23%, highlighting the synergistic impact of the composite barrier structure on device performance improvement. This reason can be attributed to the undoped GaN (u-GaN) barrier layer beneath p-GaN, which was introduced to mitigate Mg diffusion in the capping layer, thus addressing its negative effects. Furthermore, the AlN barrier layer exhibits enhanced electrical properties, which can be attributed to the critical role of high-energy-gap properties that increase the 2DEG carrier density and block leakage pathways. These traps impact the device behavior mechanism, and the simulation for a more in-depth analysis of how the composited barrier structure brings improvement is introduced using Synopsys Sentaurus TCAD.

2.
Integr Cancer Ther ; 23: 15347354241236205, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38462929

RESUMO

BACKGROUND: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. OBJECTIVE: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. MATERIALS AND METHODS: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein-protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. RESULTS: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. CONCLUSION: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Espectrometria de Massas em Tandem , Fator A de Crescimento do Endotélio Vascular , Neoplasias Hepáticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microambiente Tumoral
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005928

RESUMO

Objective To understand the epidemiological characteristics of new occupational pneumoconiosis in Zigong City from 2018 to 2022, and to provide the basis for further prevention and treatment of local pneumoconiosis. Methods The information of newly diagnosed and reported cases of pneumoconiosis in Zigong City from 2018 to 2022 was collected through the occupational disease and occupational health information monitoring system, and the characteristics of the distribution of pneumoconiosis in three regions, the composition of diseases and the length of service of exposure to dust were analyzed. Results From 2018 to 2022, the top 3 newly diagnosed pneumoconiosis diseases in Zigong City were silicosis, coal workers' pneumoconiosis and asbestosis. Silicosis cases were mainly distributed in small and medium-sized employers, accounting for 81.41%. Coal workers' pneumoconiosis was mainly distributed in large and medium-sized employers, accounting for 97.24%. Asbestosis mainly distributed in large scale employers, accounting for 96.36%. There was significant difference in dust handling age of different scale employers (H=11.453, P<0.05). The median ages of silicosis, coal workers' pneumoconiosis and other pneumoconiosis were 47.0 years, 52.0 years and 48.2 years, respectively. The median age of dust handling was 3.3 years, 22.0 years and 23.2 years, respectively. The age of onset of coal workers' pneumoconiosis was higher than that of silicosis and other pneumoconiosis (H=72.547, P<0.05), and the age of dust exposure of silicosis was shorter than that of coal workers' pneumoconiosis and other pneumoconiosis (H=10.453, P<0.05). Conclusion The current situation of pneumoconiosis in Zigong City is still severe, with obvious clustering in disease types and industries. Prevention and treatment of pneumoconiosis in key industries should be further strengthened to protect the health rights and interests of workers.

4.
Neural Comput ; 36(1): 107-127, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38052079

RESUMO

This letter considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study used functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was then parcellated into 246 regions of interest (ROIs) using the Brainnetome atlas. After data preprocessing, the data sets were transformed into tensor form. We developed a tensor-based unsupervised machine learning algorithm to reduce the size of the data tensor from 275 (individuals) × 2 (fMRI and dMRI) × 246 (ROIs) × 246 (ROIs) to 275 (individuals) × 2 (fMRI and dMRI) × 6 (clusters) × 6 (clusters). This was achieved by applying the high-order Lloyd algorithm to group the ROI data into six clusters. Features were extracted from the reduced tensor and combined with demographic features (age, gender, race, and HIV status). The resulting data set was used to train a Catboost model using subsampling and nested cross-validation techniques, which achieved a prediction accuracy of 0.857 for identifying cocaine users. The model was also compared with other models, and the feature importance of the model was presented. Overall, this study highlights the potential for using tensor-based machine learning algorithms to predict cocaine use based on MRI connectomic data and presents a promising approach for identifying individuals at risk of substance abuse.


Assuntos
Cocaína , Conectoma , Humanos , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal , Aprendizado de Máquina
5.
Biomedicines ; 11(10)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37893141

RESUMO

Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma.

6.
Micromachines (Basel) ; 14(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37893374

RESUMO

Gallium nitride (GaN) possesses remarkable characteristics such as a wide bandgap, high critical electric field, robust antiradiation properties, and a high saturation velocity for high-power devices. These attributes position GaN as a pivotal material for the development of power devices. Among the various GaN-based devices, vertical GaN MOSFETs stand out for their numerous advantages over their silicon MOSFET counterparts. These advantages encompass high-power device applications. This review provides a concise overview of their significance and explores their distinctive architectures. Additionally, it delves into the advantages of vertical GaN MOSFETs and highlights their recent advancements. In conclusion, the review addresses methods to enhance the breakdown voltage of vertical GaN devices. This comprehensive perspective underscores the pivotal role of vertical GaN MOSFETs in the realm of power electronics and their continual progress.

7.
Anim Biosci ; 36(12): 1918-1925, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641836

RESUMO

OBJECTIVE: The objective of this study was to evaluate the effect of biogas slurry application on biomass production and the silage quality of corn. METHODS: A field experiment was conducted in which corn was grown using different biogas slurry application rates. The effect of 25% to 500% biogas slurry nitrogen replacement (T1 to T14) on the yield and quality indices of corn were studied by field plot experiments. RESULTS: The results revealed that biogas slurry application improved the stem diameter and relative feed value of corn silage in treatments T13 and T11. Moreover, the fermentation quality of corn silage was improved due to an increase in lactic acid content; in comparison with the chemical synthetic fertilizer (CF) group. The crude protein contents of corn silage had no obvious change with increasing biogas slurry application. However, the forage quality index of acid detergent fiber was decreased (p<0.05) in the T11 group compared with the CF group. In addition, higher (p<0.05) 30 h in vitro dry matter digestibility and 30 h in vitro neutral detergent fiber digestibility were observed in the T11 and T13 groups than in the CF group. CONCLUSION: Based on these results, it was concluded that the optimum biogas slurry application rate for corn was approximately 350% to 450% biogas slurry nitrogen replacement under the present experimental conditions.

8.
Micromachines (Basel) ; 14(8)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37630118

RESUMO

A typical method for normally-off operation, the metal-insulator-semiconductor-high electron mobility transistor (MIS-HEMT) has been investigated. Among various approaches, gate recessed MIS-HEMT have demonstrated a high gate voltage sweep and low leakage current characteristics. Despite their high performance, obtaining low-damage techniques in gate recess processing has so far proven too challenging. In this letter, we demonstrate a high current density and high breakdown down voltage of a MIS-HEMT with a recessed gate by the low damage gate recessed etching of atomic layer etching (ALE) technology. After the remaining 3.7 nm of the AlGaN recessed gate was formed, the surface roughness (Ra of 0.40 nm) was almost the same as the surface without ALE (no etching) as measured by atomic force microscopy (AFM). Furthermore, the devices demonstrate state-of-the-art characteristics with a competitive maximum drain current of 608 mA/mm at a VG of 6 V and a threshold voltage of +2.0 V. The devices also show an on/off current ratio of 109 and an off-state hard breakdown voltage of 1190 V. The low damage of ALE technology was introduced into the MIS-HEMT with the recessed gate, which effectively reduced trapping states at the interface to obtain the low on-resistance (Ron) of 6.8 Ω·mm and high breakdown voltage performance.

9.
Micromachines (Basel) ; 14(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37420998

RESUMO

In this paper, we will discuss the rapid progress of third-generation semiconductors with wide bandgap, with a special focus on the gallium nitride (GaN) on silicon (Si). This architecture has high mass-production potential due to its low cost, larger size, and compatibility with CMOS-fab processes. As a result, several improvements have been proposed in terms of epitaxy structure and high electron mobility transistor (HEMT) process, particularly in the enhancement mode (E-mode). IMEC has made significant strides using a 200 mm 8-inch Qromis Substrate Technology (QST®) substrate for breakdown voltage to achieve 650 V in 2020, which was further improved to 1200 V by superlattice and carbon-doped in 2022. In 2016, IMEC adopted VEECO metal-organic chemical vapor deposition (MOCVD) for GaN on Si HEMT epitaxy structure and the process by implementing a three-layer field plate to improve dynamic on-resistance (RON). In 2019, Panasonic HD-GITs plus field version was utilized to effectively improve dynamic RON. Both reliability and dynamic RON have been enhanced by these improvements.

10.
J Clin Oncol ; 41(22): 3772-3781, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499357

RESUMO

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

11.
Int J Oncol ; 62(5)2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37083075

RESUMO

Bladder cancer (BC) cells exhibit a high basal level of autophagy activity, which contributes to the development of a protective mechanism for cellular survival against current treatments. Hsa­microRNA­34a (miR­34a) presents anti­tumor function in several types of cancer. However, the functional mechanism of miR­34a in regulating tumor aggressiveness and protective autophagy of BC remains largely unknown. First, transfected BC cells with miR­34a mimic exhibited LC3­II and p62 accumulation through immunofluorescence staining. It was demonstrated that syntaxin 17 (STX17), which is required for autophagosome­lysosome fusion, was downregulated upon miR­34a mimic treatment. Mechanistically, miR­34a reduced the expression of STX17 proteins that directly bind on STX17 3'­untranslated regions and thus suppressed STX17 mRNA translation to eventually inhibit protective autophagy in BC. Cell viability and colony formation assays revealed that overexpression of miR­34a in BC cells enhances the chemosensitivity of cisplatin, doxorubicin, epirubicin and mitomycin C. Furthermore, miR­34a inhibited cell proliferation and triggered G0/G1 cell cycle arrest by inhibiting cyclin D1 and cyclin E2 protein expression. Moreover, miR­34a suppressed cell motility through the downregulation of epithelial­mesenchymal transition. In summary, miR­34a inhibits cell proliferation, motility and autophagy activity in BC, which can benefit BC treatment.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proliferação de Células/genética , Ciclo Celular/genética , Autofagia/genética , Linhagem Celular Tumoral , Apoptose/genética
12.
Biochem Pharmacol ; 211: 115540, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37028462

RESUMO

Bone metastases during lung cancer are common. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, plays important functions in bone mineralization processes and in integrin-mediated cell-matrix interactions. Importantly, BSP induces bone metastasis in lung cancer, but the underlying mechanisms remain unclear. This study therefore sought to determine the intracellular signaling pathways responsible for BSP-induced migration and invasion of lung cancer cells to bone. Analyses of the Kaplan-Meier, TCGA, GEPIA and GENT2 databases revealed that high levels of BSP expression in lung tissue samples were associated with significantly decreased overall survival (hazard ratio = 1.17; p = 0.014) and with a more advanced clinical disease stage (F-value = 2.38, p < 0.05). We also observed that BSP-induced stimulation of matrix metalloproteinase (MMP)-14 promoted lung cancer cell migration and invasion via the PI3K/AKT/AP-1 signaling pathway. Notably, BSP promoted osteoclastogenesis in RAW 264.7 cells exposed to RANKL and BSP neutralizing antibody reduced osteoclast formation in conditioned medium (CM) from lung cancer cell lines. Finally, at 8 weeks after mice were injected with A549 cells or A549 BSP shRNA cells, the findings revealed that the knockdown of BSP expression significantly reduced metastasis to bone. These findings suggest that BSP signaling promotes lung bone metastasis via its direct downstream target gene MMP14, which reveals a novel potential therapeutic target for lung cancer bone metastases.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Camundongos , Animais , Sialoproteína de Ligação à Integrina/genética , Sialoproteína de Ligação à Integrina/metabolismo , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Metaloproteinase 14 da Matriz , Fosfatidilinositol 3-Quinases , Linhagem Celular Tumoral , Neoplasias Ósseas/metabolismo
13.
Materials (Basel) ; 16(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36903177

RESUMO

Surface roughness quality is still a significant problem in the laser powder bed fusion (LPBF) process. This study proposes a wobble-based scanning strategy to improve the insufficiencies of the traditional scanning strategy with regard to surface roughness. A laboratory LPBF system with a self-developed controller was used to fabricate Permalloy (Fe-79Ni-4Mo) with two scanning methods: traditional line scanning (LS) and the proposed wobble-based scanning (WBS). This study investigates the influences of these two scanning strategies on porosity and surface roughness. The results imply that WBS can maintain higher surface accuracy than LS, and the surface roughness can be reduced by about 45%. Furthermore, WBS can produce periodic surface structures arranged in fish scales or parallelograms with appropriate parameters.

14.
Micromachines (Basel) ; 14(3)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36984983

RESUMO

In this study, we report a low ohmic contact resistance process on a 650 V E-mode p-GaN gate HEMT structure. An amorphous silicon (a-Si) assisted layer was inserted in between the ohmic contact and GaN. The fabricated device exhibits a lower contact resistance of about 0.6 Ω-mm after annealing at 550 °C. In addition, the threshold voltage shifting of the device was reduced from -0.85 V to -0.74 V after applying a high gate bias stress at 150 °C for 10-2 s. The measured time to failure (TTF) of the device shows that a low thermal budget process can improve the device's reliability. A 100-fold improvement in HTGB TTF was clearly demonstrated. The study shows a viable method for CMOS-compatible GaN power device fabrication.

15.
Aging (Albany NY) ; 15(5): 1652-1667, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36917086

RESUMO

Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressive disease and lymph node metastasis. ANGPTL2 enhanced VEGF-A-dependent lymphatic endothelial cell (LEC) tube formation and migration. Integrin α5ß1, p38 and nuclear factor (NF)-κB signaling mediated ANGPTL2-regulated lymphangiogenesis. Importantly, overexpression ANGPTL2 facilitated tumor growth and lymphangiogenesis in vivo. Thus, ANGPTL2 is a promising therapeutic object for treating lung cancer.


Assuntos
Neoplasias Pulmonares , Linfangiogênese , Humanos , Proteína 2 Semelhante a Angiopoietina , Fator A de Crescimento do Endotélio Vascular , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Transdução de Sinais , NF-kappa B/metabolismo , Linhagem Celular Tumoral
16.
Oncol Ther ; 11(2): 231-244, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36800099

RESUMO

INTRODUCTION: Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves. METHODS: This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit. RESULTS: Concept elicitation interview data from 26 participants with SCLC were used to develop a conceptual model of clinical treatment benefit that organized 28 patient-reported concepts into two domains: disease-related symptoms (organ-specific and systemic) and impacts. Organ-specific symptoms included cough, chest pain, and difficulty breathing. Systemic symptoms included pain, fatigue, appetite loss, and dizziness. Impacts included physical functioning, role functioning, reduced movement, impact on sleep, and weight loss. CONCLUSION: As evidenced by this study, people with SCLC experience considerable and significant symptoms and impacts, including physical and role functioning challenges, that affect their quality of life. This conceptual model will inform the design of a patient-reported outcome (PRO) questionnaire for a future SCLC clinical trial, helping to establish the content validity of the items and questionnaires used in the trial and ensuring that the questionnaires and items selected are appropriately targeted to the population. This conceptual model could also be used to inform future SCLC clinical trials.

17.
Int J Biol Sci ; 19(3): 760-771, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778124

RESUMO

Background: Metastatic prostate cancer (PCa) predicts a poor prognosis and lower likelihood of survival. Osteoblasts (OBs) are known to be responsible for the synthesis and mineralization of bone, although it is unclear as to whether PCa in the prostate gland cooperates with OBs in bone to promote PCa malignant transformation. We aimed to elucidate how primary PCa cells cooperate with distal OBs and contribute to the vicious cycle that leads to metastatic PCa. Methods: N-cadherin, E-cadherin, and Twist protein expression were measured by Western blot. Twist translocation into the nucleus was detected by the immunofluorescence (IF) assay. Enzyme-linked immunosorbent assay (ELISA) detected protein levels in human serum samples. Levels of candidate protein expression were examined by the human cytokine array. Prostate tumor growth and metastasis were analyzed by orthotopic and metastatic prostate cancer models, respectively. Immunohistochemistry (IHC) staining was used to observe ADAM metallopeptidase domain 9 (ADAM9) and WNT1 inducible signaling pathway protein 1 (WISP-1) expression in tissue. Results: Our in vitro and in vivo analyses have now discovered that primary PCa expressing ADAM9 protein enables the transformation of OBs into PCa-associated osteoblasts (PCa-OBs), inducing WISP-1 secretion from PCa-OBs in the bone microenvironment. The upregulation of WISP-1 in bone provided feedback to primary PCa and promoted PCa cell aggressiveness via epithelial-mesenchymal transition (EMT) activity. Elevated levels of WISP-1 expression were detected in the serum of patients with PCa. ADAM9 levels were overexpressed in tumor tissue from PCa patients; ADAM9 blockade interrupted OB-induced release of WISP-1 and also suppressed primary tumor growth and distal metastasis in orthotopic PCa mouse models. Conclusion: Our study suggests that the ADAM9/WISP-1 axis assists with metastatic PCa progression. Thus, targeting the ADAM9/WISP-1 axis may help to prevent the malignant phenotypes of PCa cells.


Assuntos
Proteínas ADAM , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Proteínas ADAM/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Osteoblastos/metabolismo , Neoplasias da Próstata/metabolismo , Microambiente Tumoral , Regulação para Cima
18.
J Integr Plant Biol ; 65(4): 1012-1025, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36479821

RESUMO

Ghd7 is an important gene involved in the photoperiod flowering pathway in rice. A Ghd7-involved transcriptional regulatory network has been established, but its translational regulatory pathway is poorly understood. The mutant suppressor of overexpression of Ghd7 (sog7) was identified from EMS-induced mutagenesis on the background of ZH11 overexpressing Ghd7. MutMap analysis revealed that SOG7 is allelic to Ghd8 and delayed flowering under long-day (LD) conditions. Biochemical assays showed that Ghd8 interacts with OsHAP5C and Ghd7 both in vivo and in vitro. Surprisingly, a point mutation E96K in the α2 helix of the Ghd8 histone fold domain (HFD) destroyed its ability to interact with Ghd7. The prediction of the structure shows that mutated amino acid is located in the interaction region of CCT/NF-YB/YC complexes, which alter the structure of α4 of Ghd8. This structural difference prevents the formation of complex NF-YB/YC. The triple complex of Ghd8-OsHAP5C-Ghd7 directly bound to the promotor of Hd3a and downregulated the expression of Ehd1, Hd3a and RFT1, and finally resulted in a delayed heading. These findings are helpful in deeply understanding the Ghd7-involved photoperiod flowering pathway and promote the elucidation of rice heading.


Assuntos
Flores , Oryza , Flores/genética , Flores/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Aminoácidos/metabolismo , Regiões Promotoras Genéticas , Regulação da Expressão Gênica de Plantas , Fotoperíodo
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996121

RESUMO

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-995087

RESUMO

Objective:To analyze the prevalence of parturiophobia and its association with preferred mode of delivery in pregnant women in Changning District, Shanghai.Methods:A cross- sectional study was conducted among 1 560 pregnant women in the third trimester who had their antenatal examination in Changning Maternity and Infant Health Hospital from September 2020 to March 2021. Fear of childbirth was measured with a validated Chinese version of Wijma Delivery Expectancy/Experience Questionnaire version A (W-DEQ-A). Based on the W-DEQ-A scores, the participants were divided into two groups: non-clinical parturiophobia group [<85 scores, including mild (≤37 scores), moderate (38-65 scores) and severe (66-84 scores) parturiophobia] and clinical parturiophobia group (≥85 scores). Rank-sum test, Chi-square test and t-test were used for univariate analysis. Multivariate binary logistic regression was used to analyze the factors associated with fear of childbirth and its relationship with preferred mode of delivery. Results:The detection rates of mild, moderate, severe and clinical parturiophobia were 18.8% (294/1 560), 44.9% (700/1 560), 31.1% (485/1 560) and 5.2% (81/1 560), respectively. Multivariate binary logistic regression showed that the participants who were supported by relatives and friends to have cesarean section ( OR=3.45, 95% CI: 1.29-9.22) or had antenatal anxiety ( OR=4.73, 95% CI: 2.49-8.97) were more likely to have clinical parturiophobia, while those with planned pregnancy ( OR=0.49, 95% CI: 0.29-0.82), high intensity physical activity ( OR=0.36, 95% CI: 0.18-0.72) or better/well understanding of the delivery process ( OR=0.42, 95% CI: 0.19-0.97) were less likely to develop clinical parturiophobia (all P<0.05). Compared with the non-clinical parturiophobia women, those with clinical parturiophobia were more likely to choose cesarean section ( OR=2.15, 95% CI: 1.22-3.78, P=0.008). Conclusions:The detection rates of severe and clinical parturiophobia are 31.1% and 5.2% in Changning District, Shanghai. The associated factors mainly include the attitudes of relatives and friends towards the mode of delivery, antenatal anxiety, planned pregnancy or not, physical activity level and the understanding of delivery process. Clinical parturiophobia might be an important factor for cesarean section on maternal request.

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