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1.
Artigo em Inglês | MEDLINE | ID: mdl-38622370

RESUMO

Type A acute aortic dissection (TA-AAD) patients are prone to life-threatening complications and death. This study aimed to analyze the association between eosinophil (EOS) recovery and clinical outcomes in TA-AAD. A total of 274 patients with TA-AAD were eligible for inclusion, and 54 patients died within 1 month. The patients with poor clinical outcomes showed significantly lower EOS count within 8 days after surgery. The time-dependent ROC analysis showed that EOS recovery days predicted 1-month death with an AUC of 0.886 and a cutoff of 6 days. EOS recovery within 6 days was associated with a lower incidence of postoperative infection, a poorer prognosis, and a lower risk of 1-month and 6-month mortality than those requiring more recovery days. Collectively, postoperative early recovery of EOS predicted lower mortality and better prognosis and may be applied as an effective, rapid, and simple tool for the risk stratification and prognostic prediction of patients with TA-AAD.Clinical trial registration number: NCT05409677.

3.
Front Pharmacol ; 15: 1361371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633608

RESUMO

The lymphoma incidence rate is on the rise, with invasive forms particularly prone to relapse following conventional treatment, posing a significant threat to human life and wellbeing. Numerous studies have shown that traditional Chinese botanical drug medicine offers promising therapeutic benefits for various malignancies, with previous experimental findings indicating that Celastrus orbiculatus extract effectively combats digestive tract tumors. However, its impact on lymphoma remains unexplored. This study aims to investigate the impact and underlying mechanisms of COE on the proliferation and apoptosis of Burkitt lymphoma cells. We diluted COE in RPMI-1640 medium to create various working concentrations and introduced it to human Burkitt lymphoma Raji and Ramos cells. To evaluate cell viability, we used the CCK-8 assay, and we observed morphological changes using HE staining. We also conducted Annexin V-PI and JC-1 staining experiments to assess apoptosis. By combining the cell cycle experiment with the EDU assay, we gained insights into the effects of COE on DNA replication in lymphoma cells. Using Western blotting, we detected alterations in apoptosis-related proteins. In vivo experiments revealed that following COE intervention, tumor volume decreased, survival time was prolonged, spleen size reduced, and the expression of tumor apoptosis-related proteins changed. Our findings indicate that COE effectively inhibits lymphoma cell proliferation and promotes apoptosis by regulating these apoptosis-related proteins.

4.
ACS Omega ; 9(8): 8885-8892, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38434857

RESUMO

In this work, unusual potentiometric hydrogen sensing of mixed conducting Ba0.5Sr0.5Co0.8Fe0.2O3-δ was reported. Inspired by the unusual polarity, a dual sensing electrode (SE) potentiometric hydrogen sensor was fabricated by pairing Ba0.5Sr0.5Co0.8Fe0.2O3-δ with electronic conducting ZnO to enhance the hydrogen response. Hydrogen sensing measurements suggested that significantly higher response, larger sensitivity, and lower limit of detection (LOD) were achieved by the dual SE sensor when compared with the single SE sensor based on Ba0.5Sr0.5Co0.8Fe0.2O3-δ or ZnO. A high response of 97.3 mV for 500 ppm hydrogen and a low LOD of 2.5 ppm were obtained by the dual SE sensor at 450 °C. Furthermore, the effect of the Fe doping concentration in Ba0.5Sr0.5Co1-yFeyO3-δ (y = 0.2, 0.5, and 0.8) on hydrogen sensing response was investigated. The potentiometric response values to hydrogen increased monotonically with increasing Fe doping concentration. With the Fe/Co atomic ratio increased from 0.25 to 4, the responses to 500 ppm hydrogen raised by 69.6 and 94% at 350 and 450 °C, respectively. The sensing behaviors of unusual Ba0.5Sr0.5Co1-yFeyO3-δ may be ascribed to the predominant surface electrostatic effect. These results show that mixed conducting Ba0.5Sr0.5Co1-yFeyO3-δ is desirable for developing high-performance dual SE hydrogen sensors.

5.
Front Endocrinol (Lausanne) ; 15: 1344058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501104

RESUMO

Background: PANoptosis is a newly discovered cell death type, and tightly associated with immune system activities. To date, the mechanism, regulation and application of PANoptosis in tumor is largely unknown. Our aim is to explore the prognostic value of PANoptosis-related genes in colon adenocarcinoma (COAD). Methods: Analyzing data from The Cancer Genome Atlas-COAD (TCGA-COAD) involving 458 COAD cases, we concentrated on five PANoptosis pathways from the Molecular Signatures Database (MSigDB) and a comprehensive set of immune-related genes. Our approach involved identifying distinct genetic COAD subtype clusters and developing a prognostic model based on these parameters. Results: The research successfully identified two genetic subtype clusters in COAD, marked by distinct profiles in PANoptosis pathways and immune-related gene expression. A prognostic model, incorporating these findings, demonstrated significant predictive power for survival outcomes, underscoring the interplay between PANoptosis and immune responses in COAD. Conclusion: This study enhances our understanding of COAD's genetic framework, emphasizing the synergy between cell death pathways and the immune system. The development of a prognostic model based on these insights offers a promising tool for personalized treatment strategies. Future research should focus on validating and refining this model in clinical settings to optimize therapeutic interventions in COAD.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/genética , Adenocarcinoma/genética , Prognóstico , Família Multigênica , Biomarcadores
6.
Comput Biol Med ; 173: 108366, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554661

RESUMO

BACKGROUND: Gender carries important information related to male and female characteristics, and a large number of studies have attempted to use physiological measurement methods for gender classification. Although previous studies have shown that there exist statistical differences in some Electroencephalographic (EEG) microstate parameters between males and females, it is still unknown that whether these microstate parameters can be used as potential biomarkers for gender classification based on machine learning. METHODS: We used two independent resting-state EEG datasets: the first dataset included 74 females and matched 74 males, and the second one included 42 males and matched 42 females. EEG microstate analysis based on modified k-means clustering method was applied, and temporal parameter and nonlinear characteristics (sample entropy and Lempel-Ziv complexity) of EEG microstate sequences were extracted to compare between males and females. More importantly, these microstate temporal parameters and complexity were tried to train six machine learning methods for gender classification. RESULTS: We obtained five common microstates for each dataset and each group. Compared with the male group, the female group has significantly higher temporal parameters of microstate B, C, E and lower temporal parameters of microstate A and D, and higher complexity of microstate sequence. When using combination of microstate temporal parameters and complexity or only microstate temporal parameters as classification features in an independent test set (the second dataset), we achieved 95.2% classification accuracy. CONCLUSION: Our research findings indicate that the dynamics of microstate have considerable Gender-specific alteration. EEG microstates can be used as neurophysiological biomarkers for gender classification.


Assuntos
Mapeamento Encefálico , Encéfalo , Masculino , Humanos , Feminino , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Análise por Conglomerados , Biomarcadores
7.
Nat Commun ; 15(1): 2531, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514704

RESUMO

YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).


Assuntos
Ferroptose , Histonas , Histonas/metabolismo , Cromatina/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ferroptose/genética , Oncogenes
8.
Drug Des Devel Ther ; 18: 909-917, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545432

RESUMO

Aim: Approximately 50% of patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) are estimated to develop brain metastases (BMs). This study was aimed to assess the intracranial efficacy and survival benefits of pyrotinib and capecitabine combination therapy in the treatment of BMs in patients with HER2-positive BC. Methods: A total of 56 HER2-positive BC patients with BMs were treated with 400 mg pyrotinib once daily along with 1000 mg/m2 capecitabine twice daily for 14 days in 21-day cycles. The patients were allocated into three cohorts: (1) Cohort A composed of patients with newly diagnosed BMs without prior local radiotherapy, (2) Cohort B included patients with stable post-local radiotherapy, and (3) Cohort C composed of patients with progression following local radiotherapy. The primary endpoint was the intracranial objective response rate (CNS-ORR), while secondary endpoints included intracranial disease control rate (CNS-DCR), progression-free survival (PFS), overall survival (OS), safety, as well as QoL. Results: The observed CNS-ORR CNS-ORR of 72.73% (95% CI 51.85-86.85%) in cohort A, 55% (95% CI 34.21-74.18%) in cohort B, and 42.86% (95% CI 21.38-67.41%) in cohort C. The mPFS was 11 months, 8.4 months, and 5.2 months in cohorts A, B, and C, respectively. Diarrhea, accounting for 23.21% of all the patients, was the most common grade 3/4 adverse event related with treatments (6/22 [27.3%] in cohort A, 4/20 [20.0%] in cohort B, and 3/14 [21.4%] in cohort C). However, there were no deaths related with treatments observed. Importantly, the QoL was efficiently maintained throughout the treatment duration. Conclusion: Pyrotinib and capecitabine combination therapy proved significant effectiveness as well as tolerability in treating HER2-positive BC with BMs, yielding satisfactory results, especially in radiotherapy-naive population.


Assuntos
Acrilamidas , Aminoquinolinas , Neoplasias Encefálicas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Capecitabina , Qualidade de Vida , Receptor ErbB-2/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
9.
Sci Adv ; 10(13): eadk4423, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38536911

RESUMO

DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)-dependent repressive modification limits DNMTi efficacy. Here, we show that low-dose DNMTi treatment sensitizes colon cancer cells to select EZH2 inhibitors (EZH2is). Integrative epigenomic analysis reveals that DNMTi-induced H3K27me3 accumulates at genomic regions poised with EZH2. Notably, combined EZH2i and DNMTi alters the epigenomic landscape to transcriptionally up-regulate the calcium-induced nuclear factor of activated T cells (NFAT):activating protein 1 (AP-1) signaling pathway. Blocking this pathway limits transcriptional activating effects of these drugs, including transposable element and innate immune response gene expression involved in viral defense. Analysis of primary human colon cancer specimens reveals positive correlations between DNMTi-, innate immune response-, and calcium signaling-associated transcription profiles. Collectively, we show that compensatory EZH2 activity limits DNMTi efficacy in colon cancer and link NFAT:AP-1 signaling to epigenetic therapy-induced viral mimicry.


Assuntos
Neoplasias do Colo , Proteína Potenciadora do Homólogo 2 de Zeste , Histonas , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Histonas/metabolismo , Metilação , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo
10.
J Pain Res ; 17: 953-963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476873

RESUMO

Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.

11.
Entropy (Basel) ; 26(3)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38539690

RESUMO

The celebrated Blahut-Arimoto algorithm computes the capacity of a discrete memoryless point-to-point channel by alternately maximizing the objective function of a maximization problem. This algorithm has been applied to degraded broadcast channels, in which the supporting hyperplanes of the capacity region are again cast as maximization problems. In this work, we consider general broadcast channels and extend this algorithm to compute inner and outer bounds on the capacity regions. Our main contributions are as follows: first, we show that the optimization problems are max-min problems and that the exchange of minimum and maximum holds; second, we design Blahut-Arimoto algorithms for the maximization part and gradient descent algorithms for the minimization part; third, we provide convergence analysis for both parts. Numerical experiments validate the effectiveness of our algorithms.

12.
J Pharm Pharmacol ; 76(3): 257-268, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38334432

RESUMO

OBJECTIVES: Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms. METHODS: The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment. KEY FINDINGS: COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4. CONCLUSIONS: The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC.


Assuntos
Celastrus , Extratos Vegetais , Lesões Pré-Cancerosas , Neoplasias Gástricas , Animais , Ratos , Proteínas Reguladoras de Apoptose , Autofagia , Celastrus/química , Linhagem Celular Tumoral , Metilnitronitrosoguanidina , Lesões Pré-Cancerosas/tratamento farmacológico , Transdução de Sinais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Extratos Vegetais/uso terapêutico
13.
Signal Transduct Target Ther ; 9(1): 50, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424050

RESUMO

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1ß, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.


Assuntos
Neoplasias , PPAR gama , Humanos , Estresse Oxidativo , Neoplasias/genética , Inflamação , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
14.
J Pediatr Urol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38378373

RESUMO

BACKGROUND: Hypospadias is a congenital genitourinary malformation, with the etiology remaining complex and poorly understood. Despite several genes have been identified to be associated with the risk of hypospadias, current understanding of the susceptibility loci for hypospadias yet remained largely improved. The CACNA1D gene encodes calcium voltage-gated channel subunit alpha 1d and may be involved in androgen signaling. However, the genetic susceptibility of CACNA1D associated with hypospadias has yet been addressed. OBJECTIVE: To evaluate the association between CACNA1D polymorphisms and the susceptibility to hypospadias. METHODS: In this study, we accessed the association between two potential regulatory SNPs (rs3774491 and rs898415) within CACNA1D and hypospadias in a cohort of southern Chinese population which comprised of 740 cases and 948 healthy individuals. Both SNP and haplotypic associations were evaluated. Bioinformatic analysis of the regulatory abilities of the CACNA1D SNPs were carried out by utilizing public ChIP-seq and DNase-seq data. The expression of Cacna1d in mouse external genitalia and testis was evaluated by qPCR. RESULTS: We found that the allele C in rs3774491 and allele G in rs898415 were significantly associated with an increased risk of hypospadias, especially for proximal hypospadias. Further model-based genotypic analyses showed that these association were prominent in additive model and recessive models. Bioinformatic analyses indicated that both SNPs were colocalized with DNase and multiple histone marker across multiple tissues, suggesting the regulatory potentials for these variants. Cacna1d is detectable in both testis and external genitalia of mouse, but the expression level was more prominent in testis than that in external genitalia, suggesting tissue-specific differences in its expression. CONCLUSION: Our findings provide evidence for CACNA1D as a novel predisposing gene for hypospadias, shedding new light on the genetic basis of malformation of urinary tract. Further investigations are warranted to elucidate the functional implication of CACNA1D underlying the development of hypospadias. LEVEL OF EVIDENCE: N/A.

15.
J Mater Chem B ; 12(7): 1892-1904, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305086

RESUMO

In recent years, a number of initially approved magnetic iron oxide nanoparticle (IONP)-based nano-medicines have been withdrawn due to the obscure nano-bio effects. Therefore, there is an urgent need to study the cellular effects triggered by IONPs on cells. In this study, we investigate the time-course cellular effects on the response of RAW 264.7 cells caused by Si-IONPs via pharmacological and mass spectrometry-based proteomics techniques. Our results revealed that Si-IONPs were internalized by clathrin-mediated endocytosis within 1 hour, and gradually degraded in endolysosomes over time, which might influence autophagy, oxidative stress, innate immune response, and inflammatory response after 12 hours. Our research provides a necessary assessment of Si-IONPs for further clinical treatment.


Assuntos
Endocitose , Proteômica , Lisossomos/metabolismo , Endossomos , Nanopartículas Magnéticas de Óxido de Ferro
16.
Nucl Med Commun ; 45(5): 396-405, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372033

RESUMO

PURPOSE: The objective of this study was to investigate the value of delayed 18F fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) images in patients with small colorectal cancer liver metastases (CRLMs) with hypothyroidism. METHOD: We performed a retrospective analysis of 66 small-CRLM patients with hypothyroidism and 66 small-CRLM patients with euthyroidism, all of whom underwent dual-time-point 18 F-FDG PET/CT imaging. First, the diagnostic accuracy of PET/CT early imaging and PET/CT delayed imaging on lesions was analyzed. Next, the correlation of metabolic parameters between PET/CT early imaging and PET/CT delayed imaging was analyzed according to the grouping of all lesions. Finally, PET/CT parameters were analyzed for correlation with thyroid hormones. RESULTS: The diagnostic accuracy of delayed imaging in small-CRLM patients with hypothyroidism is not as good as that in small-CRLM patients with euthyroidism; PET/CT metabolic parameters are also unfavorable for the diagnosis of small-CRLM. For small-CRLM patients with hypothyroidism, the greater the thyroid-stimulating hormone level, the greater the uptake of 18 F-FDG in normal liver tissue, and the smaller the ratio of tumor lesion uptake to normal liver tissue uptake. CONCLUSION: PET/CT-delayed imaging has better performance than early imaging in small-CRLM patients with euthyroidism. However, the more severe the hypothyroidism, the worse the diagnostic delayed imaging performance. The scan time can be extended appropriately to optimize the imaging efficacy.


Assuntos
Neoplasias Colorretais , Hipotireoidismo , Neoplasias Hepáticas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Estudos Retrospectivos , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico por imagem
17.
Artigo em Inglês | MEDLINE | ID: mdl-38241115

RESUMO

Text-to-speech (TTS) has made rapid progress in both academia and industry in recent years. Some questions naturally arise that whether a TTS system can achieve human-level quality, how to define/judge that quality, and how to achieve it. In this paper, we answer these questions by first defining the human-level quality based on the statistical significance of subjective measure and introducing appropriate guidelines to judge it, and then developing a TTS system called NaturalSpeech that achieves human-level quality on benchmark datasets. Specifically, we leverage a variational auto-encoder (VAE) for end-to-end text-to-waveform generation, with several key modules to enhance the capacity of the prior from text and reduce the complexity of the posterior from speech, including phoneme pre-training, differentiable duration modeling, bidirectional prior/posterior modeling, and a memory mechanism in VAE. Experimental evaluations on the popular LJSpeech dataset show that our proposed NaturalSpeech achieves -0.01 CMOS (comparative mean opinion score) to human recordings at the sentence level, with Wilcoxon signed rank test at p-level p >> 0.05, which demonstrates no statistically significant difference from human recordings for the first time.

18.
RSC Adv ; 14(4): 2850-2861, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38234868

RESUMO

A series of Ru-Sn/γ-Al2O3 catalysts were prepared by the immersion method for tetramethylcyclobutane-1,3-dione (TMCB) hydrogenation to prepare 2,2,4,4-tetramethyl-1,3-cyclobutanediol (CBDO). The effect of the preparation method and reaction technology on TMCB hydrogenation activity was discussed. The catalysts were analyzed by means of XRD, BET, H2-TPR, XPS, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), and it was found that the synthesized Ru was distributed on the surface of the carrier in the form of nanoparticles, showing a good catalytic effect. The results showed that when Ru loading was fixed at 5%, Sn was used as an auxiliary agent, and Ru/Sn = 1 : 1 as the catalyst, the reaction conditions were 120 °C, 4 MPa, and 1 h, and the catalytic hydrogenation effect of TMCB on CBDO was the best. The selectivity was as high as 73.5%, and the cis-trans ratio was 1.11. It may be the strong interaction between Ru and Sn under this ratio condition, which leads to the largest number of nano-active centers of elemental Ru. Finally, the reaction mechanism of TMCB hydrogenation to CBDO is discussed.

19.
J Hazard Mater ; 466: 133479, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244451

RESUMO

In order to clarify the emission characteristics of VOCs during the initial degradation of kitchen waste, a year-long sampling campaign of kitchen waste in residential household municipal solid waste (HMSW) bins was conducted. A total of 93 VOCs with an average annual concentration of 2271 µg/m3 were detected. Alkanes and oxygenated compounds were the dominant released from the initial degradation of kitchen waste. Seasonal and daily variations were observed, with VOC concentrations generally higher in spring (1413 µg/m3) and summer (5882 µg/m3) and lower in autumn (505 µg/m3) and winter (1258 µg/m3). In addition, peak releases occurred earlier in the spring and summer (at 6 h) than in autumn and winter (at 24 h). Correlation analysis showed that ambient temperature correlated significantly with alkanes and oxygenated compounds (P < 0.01). 67 substances have been found to cause odor pollution. Based on the odor index, oxygenated compounds were the most significant odor pollutants. Acetaldehyde and 2-ketone required particular concern because of its high concentration and high odor index. This study not only enriched the understanding of emissions of VOCs from MSW front-end facilities but will also provide a scientific and theoretical basis for holistic management and odor control of MSW.

20.
Vet Microbiol ; 290: 109974, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262115

RESUMO

Pseudorabies virus (PRV) is a neurotropic virus, which infects a wide range of mammals. The activity of PRV is gradually suppressed in hosts that have tolerated the primary infection. Increased glucocorticoid levels resulting from stressful stimuli overcome repression of PRV activity. However, the host cell mechanism involved in the activation processes under stressful conditions remains unclear. In this study, infection of rat PC-12 pheochromocytoma cells with neuronal properties using PRV at a multiplicity of infection (MOI) = 1 for 24 h made the activity of PRV be the relatively repressed state, and then incubation with 0.5 µM of the corticosteroid dexamethasone (DEX) for 4 h overcomes the relative repression of PRV activity. RNA-seq deep sequencing and bioinformatics analyses revealed different microRNA and mRNA profiles of PC-12 cells with/without PRV and/or DEX treatment. qRT-PCR and western blot analyses confirmed the negative regulatory relationship of miRNA-194-5p and its target heparin-binding EGF-like growth factor (Hbegf); a dual-luciferase reporter assay revealed that Hbegf is directly targeted by miRNA-194-5p. Further, miRNA-194-5p mock transfection contributed to PRV activation, Hbegf was downregulated in DEX-treated PRV infection cells, and Hbegf overexpression contributed to returning activated PRV to the repression state. Moreover, miRNA-194-5p overexpression resulted in reduced levels of HBEGF, c-JUN, and p-EGFR, whereas Hbegf overexpression suppressed the reduction caused by miRNA-194-5p overexpression. Overall, this study is the first to report that changes in the miR-194-5p-HBEGF/EGFR pathway in neurons are involved in DEX-induced activation of PRV, laying a foundation for the clinical prevention of stress-induced PRV activation.


Assuntos
Neoplasias das Glândulas Suprarrenais , Herpesvirus Suídeo 1 , MicroRNAs , Feocromocitoma , Pseudorraiva , Doenças dos Roedores , Ratos , Animais , Herpesvirus Suídeo 1/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Feocromocitoma/veterinária , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores ErbB/metabolismo , Neoplasias das Glândulas Suprarrenais/veterinária , Dexametasona/farmacologia , Mamíferos
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