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1.
Nat Chem Biol ; 20(6): 710-720, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38200110

RESUMO

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics.


Assuntos
Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Proteínas Supressoras de Tumor , Proteínas Serina-Treonina Quinases/metabolismo , Humanos , Proteínas Supressoras de Tumor/metabolismo , Células HEK293 , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linhagem Celular Tumoral , Camundongos , Proteínas de Sinalização YAP/metabolismo , Fatores de Transcrição/metabolismo
2.
Eur J Immunol ; : e2451342, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39479750

RESUMO

The major clinical challenge in lung cancer immunotherapy is drug resistance. Therefore, establishing efficient orthotopic lung cancer mouse models to explore the mechanisms of drug immunotherapy resistance is highly important. In this study, we generated multiple fluorescently labeled lung adenocarcinoma cell lines from a genetically engineered KPZ mice model. Orthotopic transplantation of the primary 1F3 cell line induced a strong immune response, causing many small tumors to disappear, but some tumors evaded the immune attack and eventually formed large tumors. Tumor microenvironment analysis demonstrated that M2 macrophages play key roles in the immune response. Further mechanistic studies revealed that the chemokine CCL7 promoted the infiltration of M2 macrophages to facilitate immune escape, thereby promoting tumor growth in the orthotopic mouse model. Moreover, CCL7 levels were elevated in human lung cancer biopsies and positively correlated with M2 macrophage infiltration, and high CCL7 levels predicted advanced pathological stage and poor survival in lung cancer patients. Overall, we established a visualized and orthotopic mouse model with fluorescently labeled cells to better dissect the tumor microenvironment of lung cancer and define the critical role of CCL7 in promoting M2 macrophage polarization and tumorigenesis, providing new preclinical tools and potential targets for lung cancer immunotherapy.

3.
BMC Cancer ; 24(1): 948, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095810

RESUMO

BACKGROUND: Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms. METHODS: This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes. RESULTS: The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis. CONCLUSION: Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Pessoa de Meia-Idade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Prognóstico , Programa de SEER , Adulto , Estimativa de Kaplan-Meier , Taxa de Sobrevida
4.
BMC Womens Health ; 24(1): 215, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570811

RESUMO

BACKGROUND: More than 2 billion women are experiencing the menopausal transition in China, and some of these women have hypertension. Limited studies has focused on perimenopausal syndrome and hypertension in a specific population, so we aimed to investigate the prevalence of perimenopausal syndrome and hypertension and to analyse their relationships and risk factors in perimenopausal women in South China. METHODS: This cross-sectional study included 3553 women aged 40 to 60 years from South China. We collected medical report, lifestyle, blood sample, general condition questionnaire, and modified Kupperman index (mKMI) data. Multivariate logistic regression analysis was performed to identify risk factors for perimenopausal syndrome and hypertension during perimenopause. RESULTS: The prevalence of hypertension in perimenopause patients was 16.58%, and the prevalence of perimenopausal syndrome was 9.9%. Compared with women without hypertension during perimenopause, women with HTN during perimenopause had an increased risk of perimenopausal syndrome (26.4% vs. 8.7%, P < 0.001). Lipid levels and urinary tract infections were risk factors for hypertension and perimenopausal syndrome, in addition to the presence of breast nodules, the intake of snacks at night, high-salt diets, red meat and sugar-sweetened beverages, and a history of smoking and drinking for perimenopausal syndrome and the presence of gestational hypertension and diabetes for hypertension. CONCLUSION: We concluded that perimenopausal syndrome and HTN are common in perimenopausal women in South China, and the associations between them are strong and positive. Perimenopausal syndrome shares some common risk factors with HTN during perimenopause, such as BMI and dyslipidaemia. Therefore, gynaecological endocrinologists in China should consider screening for perimenopausal syndrome in hypertensive perimenopausal women, and appropriate management of perimenopause is needed to alleviate these conditions.


Assuntos
Hipertensão , Perimenopausa , Feminino , Humanos , Prevalência , Estudos Transversais , Fatores de Risco , Hipertensão/epidemiologia , China/epidemiologia
5.
BMC Womens Health ; 24(1): 531, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334107

RESUMO

BACKGROUND: Uterine Fibroids (UFs) are common benign tumors in the female reproductive tract, but their progression to intravascular leiomyomatosis (IVL) is rare. Presently, there are few reports on single-stage resection of UFs and IVL. CASE PRESENTATION: A 47-year-old woman, G2P2, had been diagnosed multiple UFs four years ago and now developed heart failure. Imaging examinations revealed that UFs had invaded the right iliac vein and extended into the right atrium through the inferior vena cava. Through multidisciplinary collaboration and a single-stage resection, the patient has survived for over 24 months post-surgery, and her heart function has significantly improved compared to preoperative levels, with no recurrence of UFs observed. CONCLUSIONS: Single-stage resection of IVL and UF is feasible and advantageous for this case, and selecting the appropriate surgical approach is crucial.


Assuntos
Leiomioma , Leiomiomatose , Neoplasias Uterinas , Humanos , Feminino , Pessoa de Meia-Idade , Leiomiomatose/cirurgia , Leiomiomatose/patologia , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/patologia , Leiomioma/cirurgia , Leiomioma/patologia , Leiomioma/diagnóstico , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Neoplasias Vasculares/cirurgia , Neoplasias Vasculares/diagnóstico , Veia Ilíaca/cirurgia , Átrios do Coração/cirurgia , Átrios do Coração/patologia , Átrios do Coração/diagnóstico por imagem
6.
Int J Clin Pharmacol Ther ; 62(7): 311-318, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38660885

RESUMO

OBJECTIVE: To investigate the incidence of and risk factors for potential drug-drug interactions (DDIs) among elderly patients with corona virus disease 2019 (-COVID-19) in hospital and to explore management strategies to reduce the occurrence of potential DDIs and ensure patient medication safety. MATERIALS AND METHODS: This was a descriptive, retrospective cross-sectional study among patients aged 65 years and older who were hospitalized with COVID-19. Potential DDIs associated with prescriptions containing two or more medicines were analyzed with Lexicomp software, the incidence of DDIs was calculated, recommendations for medication adjustment were formulated, and the χ2-test and binary logistic regression were used to analyze related risk factors. RESULTS: A total of 772 prescriptions were analyzed, 527 (68.26) of which involved 5,732 potential DDIs. The results of this study showed that a total of 152 (28.84%) prescriptions had 270 X risk class potential DDIs (i.e., avoid combining), 313 (59.39%) prescriptions had 1,161 D risk class potential DDIs (i.e., consider therapy modification), and 476 (90.32%) prescriptions had 4,301 C risk class potential DDIs (i.e., monitor therapy). The study findings showed that the total number of drugs (p < 0.001), the length of hospital stay (p < 0.001), and the number of comorbidities (p < 0.001) were risk factors affecting the occurrence of potential DDIs. CONCLUSION: This study identified factors associated with potential DDIs, which can assist in changing medication strategies, preventing adverse drug reactions, and improving clinical efficacy.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Interações Medicamentosas , Humanos , Estudos Transversais , Idoso , Estudos Retrospectivos , Masculino , Feminino , Fatores de Risco , COVID-19/epidemiologia , COVID-19/prevenção & controle , Idoso de 80 Anos ou mais , Polimedicação , Hospitalização/estatística & dados numéricos , SARS-CoV-2 , Incidência
7.
BMC Pediatr ; 24(1): 5, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172693

RESUMO

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.


Assuntos
Corpos Estranhos , Trato Gastrointestinal , Humanos , Criança , Pré-Escolar , Trato Gastrointestinal/cirurgia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Corpos Estranhos/complicações , Vômito/etiologia , Ingestão de Alimentos , Fenômenos Magnéticos
8.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663731

RESUMO

The genetic origins of nanoscale extracellular vesicles in our body fluids remains unclear. Here, we perform a tracking analysis of urinary exosomes via RNA sequencing, revealing that urine exosomes mostly express tissue-specific genes for the bladder and have close cell-genetic relationships to the endothelial cell, basal cell, monocyte, and dendritic cell. Tracking the differentially expressed genes of cancers and corresponding enrichment analysis show urine exosomes are intensively involved in immune activities, indicating that they may be harnessed as reliable biomarkers of noninvasive liquid biopsy in cancer genomic diagnostics and precision medicine.


Assuntos
Exossomos/metabolismo , Neoplasias/patologia , Urina , Humanos , Biópsia Líquida , Neoplasias/metabolismo
9.
Perfusion ; : 2676591241297319, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39498735

RESUMO

BACKGROUND: Type A acute aortic dissection, an aggressive and highly fatal disease, is particularly common among pregnant women and foetuses. This disease often occurs during the third trimester of pregnancy and the postpartum period. CASE REPORT: This case involves a female who was 20 weeks pregnant with type A acute aortic dissection. While maintaining pregnancy, the patient underwent Bentall surgery and Sun's procedure. The duration of circulatory arrest was a brief 4 min. The patient fully recovered 40 days after surgery and remained pregnant post-discharge. At the 38th gestational week, she delivered a healthy male infant via caesarean section. CLINICAL DISCUSSION: Gestational morbidity can have a serious impact on the safety of mothers and children. Currently, the shortest time reported for hypothermic circulatory arrest is 5 min. In this case, the lower body circulatory arrest was controlled to approximately 4 min during cardiopulmonary bypass while simultaneously safeguarding both individuals. Ideal strategies for cardiopulmonary bypass to reduce foetal risk include shorter cardiopulmonary bypass times, higher flow rates, and higher perfusion pressures. A reduction in the duration of hypothermic circulatory arrest further increases foetal survival rates. CONCLUSIONS: The development of a rational cardiopulmonary bypass plan should be tailored to the physiological characteristics of the pregnant woman to ensure the safety of both the pregnant woman and the foetus, reduce complications, and improve the success rate of the operation.

10.
J Environ Manage ; 356: 120632, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38531129

RESUMO

To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.


Assuntos
Brassica , Microbiota , Fermentação , Caproatos , Saccharomyces cerevisiae , Anaerobiose , Ácidos Graxos Voláteis , Esgotos/química , Butiratos , Etanol , Concentração de Íons de Hidrogênio , Reatores Biológicos
11.
Angew Chem Int Ed Engl ; 63(46): e202412964, 2024 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-39048539

RESUMO

High efficiently photocatalytic CO2 reduction (CO2RR) into liquid fuels in pure water system remains challenged. Iron polyphthalocyanine (FePPc) with strong light harvesting, unique Fe-N4 structure, abundant pores, and good stability could serve as a promising catalyst for CO2 photoreduction. To further improve the catalytic efficiency, herein, symmetry-breaking Fe sites are constructed by coupling with atomically precise M1Ag24 (M=Ag, Au, Pt) series clusters. Especially, the introduction of Pt1Ag24 causes the most asymmetric charge distribution of Fe in FePPc (followed by Au1Ag24 and Ag25), leading to the favorable CO2 adsorption and activation. In addition, Pt1Ag24-FePPc exhibits the most effective photogenerated carriers transfer and separation. As a result, Pt1Ag24-FePPc shows the methanol/ethanol yield of 48.55/32.97 µmol ⋅ gcat -1 ⋅ h-1 in H2O-CO2 system under visible light irradiation, ~1.65/1.25-fold, 1.83/1.37-fold, and 3.60/1.61-fold higher than that of Au1Ag24-FePPc, Ag25-FePPc, and FePPc, respectively. This work provides a concept for precisely construction and regulation symmetry-breaking sites of cluster-based catalysts for effective CO2 conversion.

12.
Plant Cell Physiol ; 64(7): 771-785, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37098222

RESUMO

Artemisinin, a sesquiterpene lactone obtained from Artemisia annua, is an essential therapeutic against malaria. YABBY family transcription factor AaYABBY5 is an activator of AaCYP71AV1 (cytochrome P450-dependent hydroxylase) and AaDBR2 (double-bond reductase 2); however, the protein-protein interactions of AaYABBY5, as well as the mechanism of its regulation, have not yet been elucidated. AaWRKY9 protein is a positive regulator of artemisinin biosynthesis that activates AaGSW1 (glandular trichome-specific WRKY1) and AaDBR2 (double-bond reductase 2). In this study, YABBY-WRKY interactions are revealed to indirectly regulate artemisinin production. AaYABBY5 significantly increased the activity of the luciferase (LUC) gene fused to the promoter of AaGSW1. Toward the molecular basis of this regulation, AaYABBY5 interaction with AaWRKY9 protein was found. The combined effectors AaYABBY5 + AaWRKY9 showed synergistic effects toward the activities of AaGSW1 and AaDBR2 promoters, respectively. In AaYABBY5 overexpression plants, the expression of GSW1 was found to be significantly increased when compared to that of AaYABBY5 antisense or control plants. In addition, AaGSW1 was identified as an upstream activator of AaYABBY5. Further, it was found that AaJAZ8, a transcriptional repressor of jasmonate signaling, interacted with AaYABBY5 and attenuated its activity. Co-expression of AaYABBY5 and anti-AaJAZ8 in A. annua increased the activity of AaYABBY5 toward artemisinin biosynthesis. This current study provides the first indication of the molecular basis of regulation of artemisinin biosynthesis through YABBY-WRKY interactions, which are regulated through AaJAZ8. This knowledge presents AaYABBY5 overexpression plants as a powerful genetic resource for artemisinin biosynthesis.


Assuntos
Artemisia annua , Artemisininas , Artemisia annua/genética , Artemisia annua/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regiões Promotoras Genéticas/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Artemisininas/metabolismo
13.
Small ; 19(36): e2301357, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37127865

RESUMO

The precise self-assembly of building blocks at atomic level provides the opportunity to achieve clusters with advanced catalytic properties. However, most of the current self-assembled materials are fabricated by 1/2D assembly of blocks. High dimensional (that is, 3D) assembly is widely believed to improve the performance of cluster. Herein, the effect of 3D assembly on the activity for electrocatalytic CO2 reduction reaction (CO2 RR) is investigated by using a range of clusters (Au8 Ag55 , Au8 Ag57 , Au12 Ag60 ) based on 3D assembly of M13 unit as models. Although three clusters have almost the same sizes and geometric structures, Au8 Ag55 exhibits the best CO2 RR performance due to the strong CO2 adsorption capacity and effective inhibition of H2 evolution competition reaction. The deep insight into the superior activity of Au8 Ag55 is the unique electronic structure attributed to the charge segregation. This study not only demonstrates that the assembly mode greatly affects the catalytic activity, but also offers an idea for rational designing and precisely constructing catalysts with controllable activities.

14.
J Nanobiotechnology ; 21(1): 153, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37189121

RESUMO

Lung cancer is a prevalent cancer type worldwide that often remains asymptomatic in its early stages and is frequently diagnosed at an advanced stage with a poor prognosis due to the lack of effective diagnostic techniques and molecular biomarkers. However, emerging evidence suggests that extracellular vesicles (EVs) may promote lung cancer cell proliferation and metastasis, and modulate the anti-tumor immune response in lung cancer carcinogenesis, making them potential biomarkers for early cancer detection. To investigate the potential of urinary EVs for non-invasive detection and screening of patients at early stages, we studied metabolomic signatures of lung cancer. Specifically, we conducted metabolomic analysis of 102 EV samples and identified metabolome profiles of urinary EVs, including organic acids and derivatives, lipids and lipid-like molecules, organheterocyclic compounds, and benzenoids. Using machine learning with a random forest model, we screened for potential markers of lung cancer and identified a marker panel consisting of Kanzonol Z, Xanthosine, Nervonyl carnitine, and 3,4-Dihydroxybenzaldehyde, which exhibited a diagnostic potency of 96% for the testing cohort (AUC value). Importantly, this marker panel also demonstrated effective prediction for the validation set, with an AUC value of 84%, indicating the reliability of the marker screening process. Our findings suggest that the metabolomic analysis of urinary EVs provides a promising source of non-invasive markers for lung cancer diagnostics. We believe that the EV metabolic signatures could be used to develop clinical applications for the early detection and screening of lung cancer, potentially improving patient outcomes.


Assuntos
Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Reprodutibilidade dos Testes , Detecção Precoce de Câncer , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Vesículas Extracelulares/metabolismo
15.
Opt Express ; 30(15): 28142-28157, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236968

RESUMO

In off-axis digital holography, spatial filtering is a key problem limiting the quality of reconstructed image, especially in the case of spurious spectrum generated by coherent noise in the hologram spectrum. In this paper, a new spatial filtering method with spurious spectrum elimination is proposed. Side band centering judgment is firstly implemented to locate the center point of the +1 term in the hologram spectrum. Then by roughly recognizing the region of +1 term spectrum, most of the -1 term, 0 term and the spurious spectral components are eliminated. Finally, Butterworth filtering is performed to extract the +1 term spectrum as enough as possible without introducing the spurious spectrum. Simulated hologram of E-shaped specimen with the spurious spectrum is generated to evaluate the performance of the proposed method. Experimental data of USAF 1951 resolution target, ovarian slice and microlens array are adopted to verify the effectiveness of the proposed method. Simulation and experimental results demonstrated that the proposed method is able to accurately extract the +1 term spectrum with spurious spectrum elimination and achieve a relatively good balance between the structural detail characterization and noise suppression.

16.
FASEB J ; 35(1): e21138, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33184932

RESUMO

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8+ T cell mTORC1 activation, a link between Akt-mTORC1 signaling and CD8+ trafficking has been demonstrated. We have recently discovered that TCR-induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates TSC2 via its kinase domain to mediate mTORC1 activation in CD8+ T cells. However, whether DAPK1 regulates CD8+ trafficking into tumors remains unclear. Here, using pharmacological inhibitor and genetic approaches, we found that like rapamycin, inhibition of DAPK1 activity led to enhanced expression of the homing receptors CD62L and CCR7. Deletion of either kinase domain or death domain in the T cell compartment reduced the T cell activation and maintained the expression of CD62L and CCR7. DAPK1-DD-deficient mice were more susceptible to tumor growth and deficiency of DAPK1 activity significantly reduced the migratory ability of CD8+ into the tumors. These data revealed a crucial role of DAPK1-mTORC1 in mediating CD8+ trafficking and antitumor function.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Movimento Celular/imunologia , Proteínas Quinases Associadas com Morte Celular/imunologia , Imunidade Celular , Ativação Linfocitária , Neoplasias Experimentais/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , Linhagem Celular Tumoral , Proteínas Quinases Associadas com Morte Celular/genética , Camundongos , Camundongos Knockout , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia
17.
Int Urogynecol J ; 33(6): 1511-1520, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34132864

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the impact of different modes of delivery, especially forceps delivery (FD), on pelvic floor muscles (PFMs) through vaginal surface electromyography (sEMG) in primiparous women at early (6-8 weeks) postpartum. METHODS: A total of 1259 primiparous women with full-term singleton births were included in this cross-sectional study. Of these, 98 were delivered by forceps, 865 underwent spontaneous vaginal delivery (SD) and 296 underwent elective cesarean delivery (CD). Clinical demographic characteristics and vaginal sEMG variables of parturients 6-8 weeks after birth were collected and analyzed using SPSS software. One-way ANOVA with Bonferroni correction, Chi-square test or Student's t-test was used according to the variable type. Spearman correlation and binary logistic regression analyses were also used. P/α ≤ 0.05 was considered statistically significant. RESULTS: Amplitude of fast and sustained contractions on sEMG in the FD group was significantly lower compared with the CD and SD groups. The sEMG amplitude of all contractions was significantly higher in the CD group compared with the FD and SD groups (P < 0.01). According to binary logistic regression analysis, mode of delivery was a major influencing factor in sEMG. CONCLUSIONS: An early postpartum sEMG test appears to be helpful for the assessment of PFM activity. Mode of delivery was a major influencing factor on sEMG. Forceps delivery significantly inversely influenced PFM activity.


Assuntos
Distúrbios do Assoalho Pélvico , Diafragma da Pelve , Estudos Transversais , Eletromiografia , Feminino , Humanos , Contração Muscular/fisiologia , Diafragma da Pelve/fisiologia , Distúrbios do Assoalho Pélvico/diagnóstico , Distúrbios do Assoalho Pélvico/etiologia , Gravidez
18.
Appl Opt ; 61(14): 3945-3951, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36256065

RESUMO

Phase-shifting digital holography (PSDH) can effectively remove the zero-order term and twin image in on-axis holography, but the phase-shifting error deteriorates the quality of reconstructed object images. In this paper, accurate PSDH with an electro-optic modulator (EOM) is proposed. The EOM is used to generate the required phase shift of on-axis digital holography, and the required phase shift is precisely measured with orthogonal detection of a homodyne interferometer and controlled with proportional-integral-derivative feedback in real time. The merits of our method are that it can achieve fast and accurate phase shifting without mechanical motion or sacrificing the resolution and field of view. The optical configuration was designed, an experimental setup was constructed, and real-time phase shifting was realized. Experiments of the phase-shifting accuracy evaluation, suppression effectiveness of the zero-order and twin image terms, and the specimen measurement demonstrate that the proposed method has significant application for precision topography measurement.

19.
Environ Toxicol ; 37(9): 2214-2222, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35616142

RESUMO

Fucoxanthin is a natural pigment widely distributed in macroalgae and microalgae. An orange-colored xanthophyll, it has several bioactive effects, including anticancer, anti-obesity, oxidative stress reduction, and anti-inflammation. Acute lung injury (ALI) caused by acute infections or injurious stimuli to the lung tissues is a severe pulmonary inflammatory disease. To date, no evidence has shown ALI to be reduced by fucoxanthin through activation of Ras homolog family member A (RhoA) and the nuclear factor (NF)-κB pathway in lipopolysaccharide (LPS)-treated mice. Pretreatment with fucoxanthin inhibited histopathological changes in lung tissues and neutrophil infiltration into bronchoalveolar lavage fluid induced by LPS in ALI mice. Moreover, LPS-induced proinflammatory cytokine expression and neutrophil infiltration were inhibited by fucoxanthin in a concentration-dependent manner. Pretreatment of mice with fucoxanthin inhibited NF-κB phosphorylation and IκB degradation in the lungs of mice with LPS-induced ALI. We further found that phosphorylation of Akt and p38 mitogen-activated protein KINASE (MAPK) was inhibited by fucoxanthin. By contrast, the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase was not inhibited by fucoxanthin. Furthermore, we found that the activation of RhoA was inhibited by fucoxanthin in LPS-induced ALI. On the basis of these results, we propose that fucoxanthin disrupts the RhoA activation-mediated phosphorylation of Akt and p38 MAPK, leading to NF-κB activation in mice with LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Xantofilas , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Lipopolissacarídeos/toxicidade , Pulmão , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismo
20.
Cardiol Young ; 32(4): 589-596, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34247666

RESUMO

BACKGROUND: The safe closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim is a controversial issue. Few studies have been conducted on the closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim without fluoroscopy. This study evaluated the feasibility and safety of echocardiography-guided transcatheter closure of atrial septal defect with deficient posterior-inferior or inferior vena cava rim. METHODS: The data of 136 patients who underwent transcatheter atrial septal defect closure without fluoroscopy from March 2017 to March 2020 were retrospectively analysed. The patients were classified into the deficient (n = 45) and sufficient (n = 91) posterior-inferior or inferior vena cava rim groups. Procedure and the follow-up results were compared between the two groups. RESULTS: Atrial septal defect indexed diameter and the device indexed diameter in the deficient rim group were both larger than that in the sufficient rim group (22.12 versus 17.38 mm/m2, p < 0.001; 24.77 versus 21.21 mm/m2, p = 0.003, respectively). There was no significant difference in the success rate of occlusion between two groups (97.78% in the deficient rim group versus 98.90% in the sufficient rim group, p = 1.000). During follow-up, the incidence of severe adverse cardiac events was not statistically significant (p = 0.551). CONCLUSIONS: Atrial septal defect with deficient posterior-inferior or inferior vena cava rim can safely undergo transcatheter closure under echocardiography alone if precisely evaluated with transesophageal or transthoracic echocardiography and the size of the occluder is appropriate. The mid-term results after closure are similar to that for an atrial septal defect with sufficient rim.


Assuntos
Comunicação Interatrial , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/efeitos adversos , Ecocardiografia , Ecocardiografia Transesofagiana , Estudos de Viabilidade , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
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