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1.
Plant Cell ; 35(3): 1092-1109, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36512471

RESUMO

Tight control of lateral root (LR) initiation is vital for root system architecture and function. Regulation of cortical microtubule reorganization is involved in the asymmetric radial expansion of founder cells during LR initiation in Arabidopsis (Arabidopsis thaliana). However, critical genetic evidence on the role of microtubules in LR initiation is lacking and the mechanisms underlying this regulation are poorly understood. Here, we found that the previously uncharacterized microtubule-stabilizing protein TPX2-LIKE5 (TPXL5) participates in LR initiation, which is finely regulated by the transcription factor ELONGATED HYPOCOTYL5 (HY5). In tpxl5 mutants, LR density was decreased and more LR primordia (LRPs) remained in stage I, indicating delayed LR initiation. In particular, the cell width in the peripheral domain of LR founder cells after the first asymmetric cell division was larger in tpxl5 mutants than in the wild-type. Consistently, ordered transverse cortical microtubule arrays were not well generated in tpxl5 mutants. In addition, HY5 directly targeted the promoter of TPXL5 and downregulated TPXL5 expression. The hy5 mutant exhibited higher LR density and fewer stage I LRPs, indicating accelerated LR initiation. Such phenotypes were partially suppressed by TPXL5 knockout. Taken together, our data provide genetic evidence supporting the notion that cortical microtubules are essential for LR initiation and unravel a molecular mechanism underlying HY5 regulation of TPXL5-mediated microtubule reorganization and cell remodeling during LR initiation.


Assuntos
Proteínas de Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Proteínas do Citoesqueleto , Raízes de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Divisão Celular Assimétrica , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Regulação da Expressão Gênica de Plantas , Microtúbulos/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
BMC Gastroenterol ; 24(1): 146, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689244

RESUMO

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.


Assuntos
Neoplasias da Vesícula Biliar , Pólipos , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores Etários , Idoso , Fatores de Risco , Colecistectomia , China/epidemiologia , Período Pré-Operatório , Adulto Jovem , Cuidados Pré-Operatórios
3.
Endocr Pract ; 30(3): 239-245, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38122932

RESUMO

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.


Assuntos
Hiperparatireoidismo Primário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada Quadridimensional/métodos , Hiperparatireoidismo Primário/diagnóstico por imagem , Colina , Tecnécio Tc 99m Sestamibi , Glândulas Paratireoides/diagnóstico por imagem , Compostos Radiofarmacêuticos
4.
Physiol Genomics ; 55(10): 427-439, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37575065

RESUMO

Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (m7G) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea. These modifications promote the turnover and stability of some mRNAs to prevent mRNA decay, improve translation efficiency, and reduce ribosomal pausing but are associated with poor survival in human cancer cells. However, expression of m7G-related genes in LUSC and their association with prognosis remain unclear. In the present study, we identified nine differentially expressed genes related to prognosis by comparing the expression profiles of tumor tissues (502 LUSC reports) with normal tissues (49 adjacent nontumor lung tissue reports). The genes included six upregulated genes (KLK7, LCE3E, AREG, KLK6, ZBED2, and MAPK4) and three downregulated genes (ADH1C, NTS, and ERLIN2). Based on these nine genes, patients with LUSC were classified into low- and high-risk groups to analyze the trends in prognosis. We found that the nine m7G-related genes play important roles in immune regulation, hormone regulation, and drug sensitivity through pathways including antigen processing and presentation, adherent plaques, extracellular matrix receptor interactions, drug metabolism of cytochrome P-450, and metabolism of cytochrome P-450 to xenobiotics; the functions of these genes are likely accomplished in part by m6A modifications. The effect of m7G-related genes on the diagnosis and prognosis of LUSC was further indicated by population analysis.NEW & NOTEWORTHY Based on the differential expression of 7-methylguanosine (m7G) modification-associated genes between normal and lung squamous cell carcinoma (LUSC) tissues, and considering the performance of our m7G-related gene risk profiles as independent risk factors in predicting overall survival, we conclude that m7G modification is closely linked to the development of LUSC. In addition, this study offers a new genetic marker for predicting the prognosis of patients with LUSC and presents a crucial theoretical foundation for future investigations on the relationship between m7G modification-related genes, immunity, and drug sensitivity in LUSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Pulmão/patologia , Regulação Neoplásica da Expressão Gênica
5.
Cancer Sci ; 114(6): 2534-2543, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36788727

RESUMO

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Reirradiação , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/efeitos adversos , Neoplasias Nasofaríngeas/patologia , Estudos Prospectivos , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/patologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
6.
Opt Express ; 31(16): 25781-25796, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710455

RESUMO

Infrared polarization image fusion integrates intensity and polarization information, producing a fused image that enhances visibility and captures crucial details. However, in complex environments, polarization imaging is susceptible to noise interference. Existing fusion methods typically use the infrared intensity (S0) and degree of linear polarization (DoLP) images for fusion but fail to consider the noise interference, leading to reduced performance. To cope with this problem, we propose a fusion method based on polarization salient prior, which extends DoLP by angle of polarization (AoP) and introduces polarization distance (PD) to obtain salient target features. Moreover, according to the distribution difference between S0 and DoLP features, we construct a fusion network based on attention-guided filtering, utilizing cross-attention to generate filter kernels for fusion. The quantitative and qualitative experimental results validate the effectiveness of our approach. Compared with other fusion methods, our method can effectively suppress noise interference and preserve salient target features.

7.
Phys Rev Lett ; 131(6): 066601, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37625050

RESUMO

The Su-Schrieffer-Heeger (SSH) model is an important cornerstone in modern condensed-matter topology, yet it is the simplest one-dimensional (1D) tight binding approach to dwell into the characteristics of spinless electrons in chains of staggered bonds. Moreover, the chiral symmetry assures that its surface-confining states pin to zero energy, i.e., they reside midgap in the energy dispersion. Symmetry is also an attribute related to artificial media that are subject to parity P and time-reversal T operations. This non-Hermitian family has been thoroughly nourished in a wave-based context, where anti-PT (APT) symmetric systems are the youngest belonging members, permitting refractionless optics, inverse PT-symmetry breaking transition, and asymmetric mode switching. Here, we report the first extension of APT symmetry in an acoustic setting by endowing a SSH lattice with gain and loss components. We show that the in-gap topological defect state hinges on the non-Hermitian phase, in that the broken symmetry suppresses it, yet when PT or APT symmetry is intact, it is observed with either damped or evanescent decay, respectively. Our experiments showcase how the non-Hermitian SSH lattice serves as a utile platform to investigate topological properties across various PT symmetric phases using sound.

8.
Nanotechnology ; 35(3)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37848017

RESUMO

Cobalt carbides are emerging as promising materials for various magnetic and catalytic applications. However, exploring dedicated cobalt carbides with optimal catalytic properties via adjusting phase compositions remains a significant challenge. Herein, three different cobalt carbides, CoxC (Co2C-Co3C), Co2C-Co, and Co3C, were successfully prepared using a facile one-pot green method. The phase compositions of cobalt carbides could be easily controlled by varying the cobalt-based precursors and carbon sources. More remarkably, three different cobalt carbides could serve as reduction cocatalysts decorated CdS for improved hydrogen production under visible light. Intriguingly, the obtained Co3C/CdS nanocomposite displayed the highest photocatalytic hydrogen evolution activity among the three composites and superior photocatalytic stability. This work provides a fundamental approach to tuning the photocatalytic properties of cobalt carbides for energy conversion fields.

9.
Surg Endosc ; 37(1): 518-527, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36002683

RESUMO

BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.


Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Teorema de Bayes , Doenças da Vesícula Biliar/cirurgia , Colecistectomia , Ultrassonografia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Pólipos/patologia , Estudos Retrospectivos
10.
Surg Endosc ; 37(7): 5453-5463, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37041283

RESUMO

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.


Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Teorema de Bayes , Doenças da Vesícula Biliar/cirurgia , Ultrassonografia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Pólipos/patologia , Estudos Retrospectivos
11.
Inj Prev ; 29(2): 173-179, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600524

RESUMO

BACKGROUND: This study aimed to examine the association between mild cognitive impairment (MCI) and the follow-up risk of falls among Chinese older adults, exploring the mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. METHODS: A total of 5482 adults aged 60 years and above from waves 2015 and 2018 of the China Health and Retirement Longitudinal Study were included for analysis. Cognition was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status. Depressive symptoms were assessed with the Centre for Epidemiological Studies Depression Scale. Logistic regression models were used to estimate the association between MCI and falls. Mediation analysis was employed to explore the potential mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. RESULTS: MCI was significantly associated with the risk of falls (OR 1.259, 95% CI 1.080 to 1.467). Balance capacity and depressive symptoms played parallel mediating roles in the association between MCI and falls, and the mediating effects were 0.004 (95% CI 0.003 to 0.024) and 0.010 (95% CI 0.004 to 0.016), respectively. CONCLUSIONS: It is necessary to screen for and recognise MCI in order to prevent falls among older adults. More efforts should be made to improve balance capacity and relieve depressive symptoms to reduce the risk of falls among older adults with MCI.


Assuntos
Acidentes por Quedas , Disfunção Cognitiva , Depressão , Idoso , Humanos , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Depressão/epidemiologia , População do Leste Asiático , Estudos Longitudinais
12.
Arch Gynecol Obstet ; 307(3): 891-901, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35708782

RESUMO

PURPOSE: To evaluate the effects of adjuvant chemotherapy (CT) and radiotherapy (RT) on the survival of uterine carcinosarcoma (UCS) patients. METHODS: We analyzed 3207 patients with uterine carcinosarcoma without distant metastasis after surgery from 2004 to 2015 by utilizing data from the Surveillance, Epidemiology, and End Results database. Generally, cancer-specific survival (CSS) and overall survival (OS) outcomes were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Further subgroup survival analysis was performed for those receiving RT and chemoradiotherapy (CRT). RESULTS: In general, both univariate and multivariate analyses showed that age, race, marital status, stage, lymph node metastasis, lymphadenectomy (LND), RT, and chemotherapy (CT) were associated with improved CSS and OS (P < 0.05). Further subgroup analysis showed that CRT exhibited a survival advantage over RT or CT alone in different groups. Various RT modalities, including brachytherapy (BT), external radiotherapy (EBRT), and EBRT + BT, were correlated with improved survival for patients aged 60-69 years with stage III-IV disease and lymph node metastasis. Patients with stage I-II disease aged > 70 years seemed to gain survival benefits from brachytherapy (BT) alone. BT with or without external radiotherapy was associated with improved survival for those who did not undergo lymphadenectomy. CONCLUSION: For UCS without distant metastasis after surgery, CRT should be considered. Regarding RT, BT alone is efficient in improving survival, especially for patients with stage I-II disease aged > 70 years old. EBRT alone does not show results in survival improvement for patients who did not undergo LND and those with lymph node metastasis. However, considering the limitation of SEER database, further studies with more large sample size and strict study design are needed to confirm it.


Assuntos
Carcinossarcoma , Neoplasias Uterinas , Feminino , Humanos , Idoso , Metástase Linfática , Radioterapia Adjuvante/métodos , Estadiamento de Neoplasias , Neoplasias Uterinas/patologia , Quimioterapia Adjuvante , Carcinossarcoma/patologia , Estudos Retrospectivos
13.
Sensors (Basel) ; 23(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37837005

RESUMO

The inverse finite element method (iFEM) based on fiber grating sensors has been demonstrated as a shape sensing method for health monitoring of large and complex engineering structures. However, the existing optimization algorithms cause the local optima and low computational efficiency for high-dimensional strain sensor layout optimization problems of complex antenna truss models. This paper proposes the improved adaptive large-scale cooperative coevolution (IALSCC) algorithm to obtain the strain sensors deployment on iFEM, and the method includes the initialization strategy, adaptive region partitioning strategy, and gbest selection and particle updating strategies, enhancing the reconstruction accuracy of iFEM for antenna truss structure and algorithm efficiency. The strain sensors optimization deployment on the antenna truss model for different postures is achieved, and the numerical results show that the optimization algorithm IALSCC proposed in this paper can well handle the high-dimensional sensor layout optimization problem.

14.
J Transl Med ; 20(1): 463, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221084

RESUMO

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.


Assuntos
Embolização Terapêutica , Lidocaína , Carragenina , Hemólise , Humanos , Inflamação , Interleucina-10 , Interleucina-6 , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Fator de Crescimento Transformador beta
15.
J Org Chem ; 87(15): 9576-9592, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35820108

RESUMO

A simple and efficient two-step method for the construction of novel 2,4,9a-trisubstituted-4a,9a-dihydroindeno[2,1-d][1,3]oxazin-9-ones has been developed. The NHC-catalyzed aza-benzoin reaction of o-alkenyl benzaldehydes with N-acylarylimines afforded 1-(o-alkenylaryl)-2-amido-2-aryl-1-ethanones, which underwent regioselective 5-exo-trig radical cyclization to furnish the three-ring-fused heterocyclic products, generally in good yields. The synthetic method displayed good tolerance toward the nature of substituents, substitution pattern, and steric hindrance of o-alkenyl benzaldehydes. Based on this method, the synthesis of unprecedented dihydrobenzo[6,7]indeno[2,1-d][1,3]oxazin-7-ones and dihydropyrido[2',3':3,4]cyclopenta[1,2-d][1,3]oxazin-9-ones has been achieved by employing o-alkenylnaphthaldehyde and o-alkenylnicotinaldehyde as substrates. The regioselectivity between 5-exo-trig and 6-endo-trig radical cyclization reactions of different 1-(o-alkenylaryl)-2-amido-2-aryl-1-ethanones were elucidated with DFT calculations.


Assuntos
Benzaldeídos , Cetonas , Ciclização , Modelos Teóricos , Estrutura Molecular
16.
J Nanobiotechnology ; 20(1): 114, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248071

RESUMO

Cancer-associated fibroblasts (CAFs) deteriorate tumor microenvironment (TME) and hinder intra-tumoral drug delivery. Direct depleting CAFs exists unpredictable risks of tumor metastasis. Epithelial-mesenchymal transition (EMT) is a critical process of CAFs converted from hepatic stellate cells during hepatocellular tumorigenesis; however, until now the feasibility of reversing EMT to battle hepatocellular carcinoma has not been comprehensively explored. In this study, we report a CFH peptide (CFHKHKSPALSPVGGG)-decorated liposomal oxymatrine (CFH/OM-L) with a high affinity to Tenascin-C for targeted inactivating CAFs through reversing EMT, which is verified by the upregulation of E-cadherin and downregulation of vimentin, N-cadherin, and snail protein in vivo and in vitro. After the combination with icaritin-loaded lipid complex, CFH/OM-L obviously boosts the comprehensive anticancer efficacy in both 3D tumor spheroids and stromal-rich tumor xenograft nude mouse models. The combinational therapy not only effectively reversed the in vivo EMT process but also significantly lowered the collagen, creating favorable conditions for deep penetration of nanoparticles. More importantly, CFH/OM-L does not kill but inactivates CAFs, resulting in not only a low risk of tumor metastasis but also a reprogramming TME, such as M1 tumor-associated macrophages polarization and natural killer cells activation. Such strategy paves a moderate way to remold TME without depleting CAFs and provides a powerful tool to design strategies of combinational hepatocellular carcinoma therapy.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Alcaloides , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/fisiologia , Fibroblastos/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Peptídeos/metabolismo , Peptídeos/farmacologia , Quinolizinas , Microambiente Tumoral
17.
BMC Public Health ; 22(1): 1493, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931976

RESUMO

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.


Assuntos
Dor Lombar , Doenças Profissionais , China/epidemiologia , Estudos Transversais , Humanos , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Doenças Profissionais/etiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários
18.
BMC Musculoskelet Disord ; 23(1): 952, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329459

RESUMO

BACKGROUND: Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. METHODS: A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. RESULTS: Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. CONCLUSION: Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.


Assuntos
Doenças Musculoesqueléticas , Doenças Profissionais , Humanos , Estudos Transversais , Ombro , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia , Prevalência , Inquéritos e Questionários , China/epidemiologia , Fatores de Risco
19.
J Hum Genet ; 66(5): 475-489, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33106546

RESUMO

In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10-9). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10-10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina , Estudo de Associação Genômica Ampla , Síndrome de Linfonodos Mucocutâneos/genética , Adulto , Alelos , Linfócitos B/metabolismo , Simulação por Computador , Conjuntos de Dados como Assunto , Seguimentos , Regulação da Expressão Gênica , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão/epidemiologia , Leucócitos/metabolismo , Desequilíbrio de Ligação , Modelos Genéticos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia , Taiwan/epidemiologia , Transcrição Gênica
20.
BMC Cancer ; 21(1): 180, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607955

RESUMO

BACKGROUND: Aberrant activation of the Wnt/ß-catenin signaling pathway is one of the most frequent abnormalities in human cancer, including colorectal cancer (CRC). Previous studies revealed pivotal functions of WNT family members in colorectal cancer, as well as their prognostic values. Nevertheless, the prognostic role and mechanisms underlying WNT7b in colorectal cancer development remains unclear. METHODS: In this study, WNT7b expression was measured by immunohistochemical staining of 100 cases of surgically resected human colorectal cancerous tissues as well as matched adjacent normal tissues constructed as tissue microarrays. In vitro studies, we attempted to substantiate the WNT7b expressional pattern previously found in immunohistochemistry staining. We used the colorectal cancer cell-line HCT116 and normal colorectal cell-line FHC for immunofluorescence staining and nuclear/cytoplasmic separated western blotting. We measured epithelial-mesenchymal transition (EMT) markers and migration capacity of HCT116 in the context of WNT7b knocked-down using short interfering RNA. Finally, clinical and prognostic values of WNT7b activation levels were examined. RESULTS: WNT7b was expressed in the nucleus in adjacent normal tissues. In CRC tissues, nuclear expression of WNT7b was similar; however, membrane and cytoplasmic expression was strikingly enhanced. Consistently, in vitro analysis confirmed the same expression pattern of WNT7b. Compared with FHC cells, HCT116 cells displayed higher levels of WNT7b membrane and cytoplasmic enrichment, as well as higher migration capacity with a sensitized EMT process. Either partial knockdown of WNT7b or blockade of the Wnt/ß-catenin signaling pathway reversed EMT process and inhibited the migration of HCT116 cells. Finally, elevated secretion levels of WNT7b were significantly associated with lymphatic and remote metastasis and predicted worse prognosis in the CRC cohort. CONCLUSION: In summary, we demonstrated that the activation of WNT7b autocrine probably contributes to CRC metastasis by triggering EMT process through the Wnt/ß-catenin signaling pathway. High levels of WNT7b autocrine secretion predicts poor outcome in patients with CRC. This molecule is a promising candidate for clinical CRC treatments.


Assuntos
Neoplasias Colorretais/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida
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