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1.
Fish Shellfish Immunol ; 150: 109635, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38754648

RESUMO

The present study explored the effects of different lipid sources on growth performance, lipid deposition, antioxidant capacity, inflammatory response and disease resistance of largemouth bass (Micropterus salmoides). Four isonitrogenous (crude protein 50.46 %) and isolipidic (crude lipid 11.12 %) diets were formulated to contain 7 % of different oil sources including fish oil (FO) (control), soybean oil (SO), linseed oil (LO) and coconut oil (CO). Largemouth bass with initial body weight of 36.0 ± 0.2 g were randomly distributed into 12 tanks, with 30 fish per tank and 3 tanks per treatment. The fish were fed with the experiment diets twice daily for 8 weeks. The results indicated that the weight gain of largemouth bass fed the FO diet was significantly higher than that of fish fed the LO and CO diets. The liver crude lipid content in FO group was significantly higher than other groups, while the highest liver triglyceride content was showed in SO group and the lowest was detected in LO group. At transcriptional level, expression of lipogenesis related genes (pparγ, srebp1, fas, acc, dgat1 and dgat2) in the SO and CO group were significantly higher than the FO group. However, the expression of lipolysis and fatty acids oxidation related genes (pparα, cpt1, and aco) in vegetable oils groups were significantly higher than the FO group. As to the antioxidant capacity, vegetable oils significantly reduced the malondialdehyde content of largemouth bass. Total antioxidant capacity in the SO and LO groups were significantly increased compared with the FO group. Catalase in the LO group was significantly increased compared with the FO group. Furthermore, the ER stress related genes, such as grp78, atf6α, atf6ß, chop and xbp1 were significantly enhanced in the vegetable oil groups compared with the FO group. The activity of serum lysozyme in vegetable oil groups were significantly higher than in FO group. Additionally, the relative expression of non-specific immune related genes, including tlr2, mapk11, mapk13, mapk14, rela, tgf-ß1, tnfα, 5lox, il-1ß and il10, were all significantly increased in SO and CO groups compared to the other groups. In conclusion, based on the indexes including growth performance, lipid deposition, antioxidant capacity and inflammatory response, SO and LO could be alternative oil sources for largemouth bass.

2.
Anim Biotechnol ; 35(1): 2334725, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38623994

RESUMO

The lactation character of dairy goats is the most important characteristic, and milk protein is an important index to evaluate milk quality. Casein accounts for more than 80% of the total milk protein in goat milk and is the main component of milk protein. Using GMECs (goat mammary epithelial cells) as the research object, the CHECK2 vector of the CSN1S1 gene and the overexpression vector of pcDNA 3.1 were constructed, and the mimics of miR-2284b and the interfering RNA of CSN1S1 were synthesized. Using PCR, RT-qPCR, a dual luciferase activity detection system, EdU, CCK8, cell apoptosis detection and ELISA detection, we explored the regulatory mechanism and molecular mechanism of miR-2284b regulation of αs1-casein synthesis in GMECs. miR-2284b negatively regulates proliferation and apoptosis of GMECs and αs1-casein synthesis. Two new gene sequences of CSN1S1 were discovered. CSN1S1-1/-2 promoted the proliferation of GMECs and inhibited cell apoptosis. However, it had no effect on αs1-casein synthesis. MiR-2284b negatively regulates αs1-casein synthesis in GMECs by inhibiting the CSN1S1 gene. These results all indicated that miR-2284b could regulate αs1-casein synthesis, thus playing a theoretical guiding role in the future breeding process of dairy goats and accelerating the development of dairy goat breeding.


Assuntos
Caseínas , MicroRNAs , Feminino , Animais , Caseínas/genética , Caseínas/metabolismo , Proteínas do Leite , Cabras/fisiologia , Células Epiteliais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Glândulas Mamárias Animais/metabolismo
3.
J Psychiatr Res ; 174: 297-303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678687

RESUMO

BACKGROUND: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments. METHODS: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet. RESULTS: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms. CONCLUSION: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety.


Assuntos
Ansiedade , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Ritmo Circadiano/fisiologia , Transtorno Depressivo/fisiopatologia , Adulto Jovem , Transtornos Cronobiológicos/fisiopatologia
4.
Nano Lett ; 24(12): 3647-3653, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488282

RESUMO

With exceptional quantum confinement, 2D monolayer semiconductors support a strong excitonic effect, making them an ideal platform for exploring light-matter interactions and as building blocks for novel optoelectronic devices. Different from the well-known in-plane excitons in transition metal dichalcogenides (TMD), the out-of-plane excitons in indium selenide (InSe) usually show weak emission, which limits their applications as light sources. Here, by embedding InSe in an anisotropic gap plasmon nanocavity, we have realized plasmon-enhanced linearly polarized photoluminescence with an anisotropic ratio up to ∼140, corresponding to degree of polarization (DoP) of ∼98.6%. Such polarization selectivity, originating from the polarization-dependent plasmonic enhancement supported by the "nanowire-on-mirror" nanocavity, can be well tuned by the InSe thickness. Moreover, we have also realized an InSe-based light-emitting diode with polarized electroluminescence. Our research highlights the role of excitonic dipole orientation in designing nanophotonic devices and paves the way for developing InSe-based optoelectronic devices with polarization control.

5.
Diabetes ; 73(5): 713-727, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38320300

RESUMO

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that the obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration and expression of proinflammatory and fibrosis genes in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity-related disorders.


Assuntos
Quimiocina CCL2 , Ribonucleoproteína Nuclear Heterogênea A1 , Resistência à Insulina , Obesidade , Animais , Camundongos , Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Glucose/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/genética , Inflamação/genética , Inflamação/metabolismo , Resistência à Insulina/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Regulação para Cima
6.
J Cancer ; 15(2): 456-465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169541

RESUMO

Objective: To investigate the patterns of local failure and prognosis in patients with locally recurrent nasopharyngeal carcinoma (rNPC) after primary intensity-modulated radiotherapy (IMRT). Methods: The data of 298 patients with locally rNPC after IMRT were retrospectively analyzed. Magnetic resonance images of the initial and recurrent tumors were reviewed and, for patients with extra-nasopharyngeal local recurrence, the gross tumor volume of local recurrence was transferred to the original IMRT plan for dosimetry analysis. Significant prognostic factors for overall survival (OS) were selected by multivariate Cox regression analysis. Results: The commonest recurrence sites were the nasopharynx (93%, 277/298) and skull base (53.7%, 160/298). Of the 21 patients with extra-nasopharyngeal recurrence (19 cases valid), 12 had in-field failures, 4 had marginal failures, and 3 had out-field failures. The ethmoid sinus (57.1%, 4/7) and nasal cavity (28.6%, 2/7) were the most frequent sites of marginal and out-field failures. After median follow-up of 37 months, the 3-year and estimated 5-year OS rates were 57.3% and 41.7%, respectively. Multivariate analysis showed that age, recurrence interval, plasma Epstein-Barr virus (EBV) DNA level, and recurrent T stage were independent prognostic factors for OS. Conclusions: Local failure after IMRT occurs most commonly in the nasopharynx and skull base. In patients with extra-nasopharyngeal recurrence, in-field failure remains the main failure pattern, and marginal and out-field failures mainly occur in the ethmoid sinus and nasal cavity. Elder age, shorter recurrence interval, detectable plasma EBV DNA, and advanced recurrent T stage are negative predictors of OS in patients with rNPC.

7.
Cancer Cell ; 42(3): 464-473.e3, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38242125

RESUMO

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Estadiamento de Neoplasias , Herpesvirus Humano 4 , Prognóstico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Infecções por Vírus Epstein-Barr/patologia , Carcinoma/patologia , Estudos Retrospectivos
8.
Br J Nutr ; 131(8): 1308-1325, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38073302

RESUMO

A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3-4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.


Assuntos
Bass , Clostridium butyricum , Humanos , Animais , Antioxidantes/metabolismo , Bass/metabolismo , Clostridium butyricum/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , RNA Ribossômico 16S/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Dieta/veterinária , Carboidratos
9.
Nat Methods ; 21(1): 92-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749214

RESUMO

Natural proteins are composed of 20 proteinogenic amino acids and their post-translational modifications (PTMs). However, due to the lack of a suitable nanopore sensor that can simultaneously discriminate between all 20 amino acids and their PTMs, direct sequencing of protein with nanopores has not yet been realized. Here, we present an engineered hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore containing a sole Ni2+ modification. It enables full discrimination of all 20 proteinogenic amino acids and 4 representative modified amino acids, Nω,N'ω-dimethyl-arginine (Me-R), O-acetyl-threonine (Ac-T), N4-(ß-N-acetyl-D-glucosaminyl)-asparagine (GlcNAc-N) and O-phosphoserine (P-S). Assisted by machine learning, an accuracy of 98.6% was achieved. Amino acid supplement tablets and peptidase-digested amino acids from peptides were also analyzed using this strategy. This capacity for simultaneous discrimination of all 20 proteinogenic amino acids and their PTMs suggests the potential to achieve protein sequencing using this nanopore-based strategy.


Assuntos
Nanoporos , Aminoácidos/química , Proteínas/metabolismo , Porinas/química , Porinas/metabolismo , Peptídeos/química
10.
iScience ; 26(12): 108467, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38089590

RESUMO

Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

11.
Nat Commun ; 14(1): 6701, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872139

RESUMO

Excitons in monolayer semiconductors, benefitting from their large binding energies, hold great potential towards excitonic circuits bridging nano-electronics and photonics. However, achieving room-temperature ultrafast on-chip electrical modulation of excitonic distribution and flow in monolayer semiconductors is nontrivial. Here, utilizing lateral bias, we report high-speed electrical modulation of the excitonic distribution in a monolayer semiconductor junction at room temperature. The alternating charge trapping/detrapping at the two monolayer/electrode interfaces induces a non-uniform carrier distribution, leading to controlled in-plane spatial variations of excitonic populations, and mimicking a bias-driven excitonic flow. This modulation increases with the bias amplitude and eventually saturates, relating to the energetic distribution of trap density of states. The switching time of the modulation is down to 5 ns, enabling high-speed excitonic devices. Our findings reveal the trap-assisted exciton engineering in monolayer semiconductors and offer great opportunities for future two-dimensional excitonic devices and circuits.

12.
Clin Nucl Med ; 48(10): 910-912, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37682610

RESUMO

ABSTRACT: Primary sarcomatoid carcinoma of the esophagus is a rare and highly malignant neoplasm with a poor prognosis. A 51-year-old man presented with difficulty in swallowing for 2 weeks. Thoracic CT revealed a huge mass in the middle-lower thoracic esophagus. 18F-FDG PET/CT showed intense 18F-FDG uptake of the esophageal tumor. Histopathology and immunohistochemistry of the esophageal lesion tissue confirmed the diagnosis of sarcomatoid carcinoma after postoperative pathological biopsy.


Assuntos
Carcinoma , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Humanos , Pessoa de Meia-Idade , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Esofágicas/diagnóstico por imagem
13.
World Neurosurg ; 180: e149-e157, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37696435

RESUMO

OBJECTIVE: To explore the clinical value of constructing a nomogram model based on apparent diffusion coefficient values within 1 cm of the residual tumor cavity to predict the postoperative progression of gliomas. METHODS: Clinical data of patients with glioma who underwent surgery were retrospectively retrieved from the First Hospital of Qinhuangdao. The mean apparent diffusion coefficient (mADC) was measured using a picture archiving and communication system. The Kaplan-Meier survival curve was constructed with the optimal mADC threshold determined by the X-tile. A nomogram was developed based on the independent risk factors determined using the Cox proportional hazards model (Cox regression model) to predict the progression of postoperative glioma. A receiver operating characteristic curve was drawn to evaluate the prediction accuracy of the model, and decision curve analysis was performed to assess the clinical value of the nomogram. RESULTS: There was good agreement between the mADC values of the 2 repeated measurements before and after, with a consistency correlation coefficient of 0.83. Multivariate Cox regression analysis showed that peritumoral mADC values, degree of peritumoral enhancement, age, pathological grading, and degree of tumor resection were independent risk factors for predicting postoperative progression of glioma (all P < 0.05). The receiver operating characteristic curves of the nomogram predicting 1, 2, and 3 years postoperative progression were 0.86, 0.82, and 0.91, respectively. The calibration curve showed good consistency between the observed and predicted values in the model. The curve showed that the nomogram model has a good clinical application value. CONCLUSIONS: The peritumoral mADC values, degree of peritumoral enhancement, age, pathological grade, and degree of tumor resection were independent factors affecting the postoperative progression of glioma. The nomogram model established for the first time based on mADC values within 1 cm of the tumor can predict the postoperative condition of patients with glioma intuitively and comprehensively. It can provide a relatively accurate prediction tool for neurosurgeons to individualize the evaluation of survival and prognosis, and formulate treatment plans for patients.


Assuntos
Glioma , Nomogramas , Humanos , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Imagem de Difusão por Ressonância Magnética , Prognóstico
14.
J Chem Phys ; 159(7)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37602804

RESUMO

Kohn-Sham density functional theory (DFT) is nowadays widely used for electronic structure theory simulations, and the accuracy and efficiency of DFT rely on approximations of the exchange-correlation functional. By including the kinetic energy density τ, the meta-generalized-gradient approximation (meta-GGA) family of functionals achieves better accuracy and flexibility while retaining the efficiency of semi-local functionals. For example, the strongly constrained and appropriately normed (SCAN) meta-GGA functional has been proven to yield accurate results for solid and molecular systems. We implement meta-GGA functionals with both numerical atomic orbitals and plane wave bases in the ABACUS package. Apart from the exchange-correlation potential, we also discuss the evaluation of force and stress. To validate our implementation, we perform finite-difference tests and convergence tests with the SCAN, rSCAN, and r2SCAN meta-GGA functionals. We further test water hexamers, weakly interacting molecules from the S22 dataset, as well as 13 semiconductors using the three functionals. The results show satisfactory agreement with previous calculations and available experimental values.

15.
J Vasc Res ; 60(3): 160-171, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37499638

RESUMO

BACKGROUND: Atherosclerotic plaque locations in the carotid bulb increasingly have been found to be associated with patterns of ischemic lesions and plaque progression. However, the occurrence of carotid bulb plaque is a complex process. We aimed to investigate plaque characteristics and geometric and hemodynamic parameters among patients with body and apical plaques of the carotid bulb and to identify the mechanism of bulb plaque formation and location. METHODS: Consecutive patients with single carotid bulb stenosis (50-99%) were enrolled retrospectively. Patients were divided into body and apical plaque groups based on plaque location. Plaque location and characteristics were identified and measured on high-resolution vessel wall magnetic resonance imaging. Geometric parameters were derived from time-of-flight magnetic resonance imaging. Computational fluid dynamics simulations were performed to quantify wall shear stress (WSS) and four associated WSS-based metrics on the plaque side, on the non-plaque side, and in different parts of the lesion. Plaque characteristics and geometric and hemodynamic parameters were compared, and their associations with the plaque location were determined. RESULTS: Seventy patients were recruited (41 body plaques and 29 apical plaques). WSSplaque values were lower than WSSnon-plaque values for all plaques (median [interquartile range], 12.59 [9.83-22.14] vs. 17.27 [11.63-27.63] Pa, p = 0.001). In a multivariate binary logistic regression, the tortuosity of the stenosed region, the magnitudes of the mean relative residence time, and the minimum transverse WSS in the proximal part of the lesion were the key factors independently associated with plaque location (p = 0.022, 0.013, and 0.012, respectively). CONCLUSIONS: Plaque formation was associated with the local flow pattern, and the tortuosity and proximal-specific hemodynamics were significantly associated with plaque location in the carotid bulb.


Assuntos
Estenose das Carótidas , Placa Aterosclerótica , Humanos , Constrição Patológica/complicações , Constrição Patológica/patologia , Estudos Retrospectivos , Hemodinâmica , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Estresse Mecânico
16.
Nat Med ; 29(6): 1424-1436, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37280275

RESUMO

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.


Assuntos
Cisplatino , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Cisplatino/uso terapêutico , Gencitabina , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/uso terapêutico , Microambiente Tumoral
17.
Lancet Oncol ; 24(6): 611-623, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37269842

RESUMO

BACKGROUND: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. METHODS: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. FINDINGS: The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). INTERPRETATION: The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. FUNDING: Institut National du Cancer and Ligue Nationale Contre le Cancer.


Assuntos
Quimiorradioterapia , Neoplasias Nasofaríngeas , Masculino , Humanos , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Metanálise em Rede , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Taxoides/uso terapêutico , Nasofaringe
18.
Small ; 19(43): e2301949, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357166

RESUMO

Transition metal dichalcogenide (TMD)-based 2D monolayer semiconductors, with the direct bandgap and the large exciton binding energy, are widely studied to develop miniaturized optoelectronic devices, e.g., nanoscale light-emitting diodes (LEDs). However, in terms of polarization control, it is still quite challenging to realize polarized electroluminescence (EL) from TMD monolayers, especially at room temperature. Here, by using Ag nanowire top electrode, polarized LEDs are demonstrated based on 2D monolayer semiconductors (WSe2 , MoSe2 , and WS2 ) at room temperature with a degree of polarization (DoP) ranging from 50% to 63%. The highly anisotropic EL emission comes from the 2D/Ag interface via the electron/hole injection and recombination process, where the EL emission is also enhanced by the polarization-dependent plasmonic resonance of the Ag nanowire. These findings introduce new insights into the design of polarized 2D LED devices at room temperature and may promote the development of miniaturized 2D optoelectronic devices.

19.
BMJ ; 380: e072133, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36746459

RESUMO

OBJECTIVES: To address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma. DESIGN: Open-label, non-inferiority, multicentre, randomised, phase 3 trial. SETTING: Three Chinese hospitals between 20 November 2017 and 3 December 2018. PARTICIPANTS: Adults (18-65 years) with newly diagnosed, non-keratinising, non-distant metastatic nasopharyngeal carcinoma without MRLN involvement. INTERVENTIONS: Randomisation was done centrally by the Clinical Trials Centre at Sun Yat-sen University Cancer Center. Eligible patients were randomly assigned (1:1; block size of four) to receive MRLN sparing radiotherapy or standard radiotherapy (both medial and lateral retropharyngeal lymph node groups), and stratified by institution and treatment modality as follows: radiotherapy alone; concurrent chemoradiotherapy; induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy. MAIN OUTCOME MEASURES: Non-inferiority was met if the lower limit of the one sided 97.5% confidence interval of the absolute difference in three year local relapse-free survival (MRLN sparing radiotherapy minus standard radiotherapy) was greater than -8%. RESULTS: 568 patients were recruited: 285 in the MRLN sparing radiotherapy group; 283 in the standard radiotherapy group. Median follow-up was 42 months (interquartile range 39-45), intention-to-treat analysis showed that the three year local relapse-free survival of the MRLN sparing radiotherapy group was non-inferior to that of the standard radiotherapy group (95.3% v 95.5%, stratified hazard ratio 1.04 (95% confidence interval 0.51 to 2.12), P=0.95) with a difference of -0.2% ((one sided 97.5% confidence interval -3.6 to ∞), Pnon-inferiority<0.001). In the safety set (n=564), the sparing group had a lower incidence of grade ≥1 acute dysphagia (25.5% v 35.1%, P=0.01) and late dysphagia (24.0% v 34.3%, P=0.008). Patient reported outcomes at three years after MRLN sparing radiotherapy were better in multiple domains after adjusting for the baseline values: global health status (mean difference -5.6 (95% confidence interval -9.1 to -2.0), P=0.002), role functioning (-5.5 (-7.4 to -3.6), P<0.001), social functioning (-6.2 (-8.9 to -3.6), P<0.001), fatigue (7.9 (4.0 to 11.8), P<0.001), and swallowing (11.0 (8.4 to 13.6), P<0.001). The difference in swallowing scores reached clinical significance (>10 points difference). CONCLUSION: Compared with standard radiotherapy, MRLN sparing radiotherapy showed non-inferiority in terms of risk of local relapse with fewer radiation related toxicity and improved patient reported outcomes in patients with non-metastatic nasopharyngeal carcinoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT03346109.


Assuntos
Transtornos de Deglutição , Neoplasias Nasofaríngeas , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfonodos/patologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/radioterapia
20.
Int J Womens Health ; 15: 51-57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643713

RESUMO

Early pregnancy complications, including miscarriage, ectopic pregnancies, and hyperemesis gravidarum, are common discomforts accounting for about 15% to 20% of all pregnancies. A proportion of women with early pregnancy complications will experience short- and long-term psychologic sequelae in the aftermath of pregnancy complications, including anxiety, depression, and post-traumatic stress disorder (PTSD) which are the most commonly reported psychologic reactions. This review will focus on the course and impact of these psychologic sequelae in early pregnancy complications, and the noninvasive interventions to improve mental health are also briefly discussed.

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