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1.
Cell ; 171(4): 836-848.e13, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-28988768

RESUMO

Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis. KCNK3 antagonizes norepinephrine-induced membrane depolarization by promoting potassium efflux in brown adipocytes. This limits calcium influx through voltage-dependent calcium channels and dampens adrenergic signaling, thereby attenuating lipolysis and thermogenic respiration. Adipose-specific Kcnk3 knockout mice display increased energy expenditure and are resistant to hypothermia and obesity. These findings uncover a critical K+-Ca2+-adrenergic signaling axis that acts to dampen thermogenesis, maintain tissue homeostasis, and reveal an electrophysiological regulatory mechanism of adipocyte function.


Assuntos
Tecido Adiposo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Obesidade/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Receptores Adrenérgicos/metabolismo , Transdução de Sinais , Termogênese , Adipócitos Marrons/metabolismo , Tecido Adiposo/patologia , Animais , Separação Celular , Células Cultivadas , Fenômenos Eletrofisiológicos , Feminino , Masculino , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Obesidade/patologia , Canais de Potássio de Domínios Poros em Tandem/genética
2.
Carcinogenesis ; 45(6): 363-377, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38459912

RESUMO

Long non-coding RNAs (lncRNAs) have been established as pivotal players in various cellular processes, encompassing the regulation of transcription, translation and post-translational modulation of proteins, thereby influencing cellular functions. Notably, lncRNAs exert a regulatory influence on diverse biological processes, particularly in the context of tumor development. Tumor-associated macrophages (TAMs) exhibit the M2 phenotype, exerting significant impact on crucial processes such as tumor initiation, angiogenesis, metastasis and immune evasion. Elevated infiltration of TAMs into the tumor microenvironment (TME) is closely associated with a poor prognosis in various cancers. LncRNAs within TAMs play a direct role in regulating cellular processes. Functioning as integral components of tumor-derived exosomes, lncRNAs prompt the M2-like polarization of macrophages. Concurrently, reports indicate that lncRNAs in tumor cells contribute to the expression and release of molecules that modulate TAMs within the TME. These actions of lncRNAs induce the recruitment, infiltration and M2 polarization of TAMs, thereby providing critical support for tumor development. In this review, we survey recent studies elucidating the impact of lncRNAs on macrophage recruitment, polarization and function across different types of cancers.


Assuntos
Macrófagos , Neoplasias , RNA Longo não Codificante , Microambiente Tumoral , Macrófagos Associados a Tumor , RNA Longo não Codificante/genética , Microambiente Tumoral/imunologia , Humanos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Exossomos/genética , Exossomos/metabolismo
3.
Carcinogenesis ; 45(5): 324-336, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38267812

RESUMO

Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration both in vitro and in vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reduced O-glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment of N-acetyl-d-glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Movimento Celular , Proliferação de Células , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante) , Hexosaminas , Neoplasias Pulmonares , Proteínas com Motivo Tripartido , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/metabolismo , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Hexosaminas/biossíntese , Hexosaminas/metabolismo , Animais , Camundongos , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Ubiquitinação , Linhagem Celular Tumoral , Masculino , Camundongos Nus , Feminino , Glicosilação , Camundongos Endogâmicos BALB C , Vias Biossintéticas , Peptídeos e Proteínas de Sinalização Intracelular
4.
J Cell Physiol ; 239(2): e31180, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219045

RESUMO

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment, and their different polarization states play multiple roles in tumors by secreting cytokines, chemokines, and so on, which are closely related to tumor development. In addition, the enrichment of TAMs is often associated with poor prognosis of tumors. Thus, targeting TAMs is a potential tumor treatment strategy, in which therapeutic approaches such as reducing TAMs numbers, remodeling TAMs phenotypes, and altering their functions are being extensively investigated. Meanwhile, the ubiquitin-proteasome system (UPS), an important mechanism of protein hydrolysis in eukaryotic cells, participates in cellular processes by regulating the activity and stability of key proteins. Interestingly, UPS plays a dual role in the process of tumor development, and its role in TAMs deserve to be investigated in depth. This review builds on this foundation to further explore the multiple roles of UPS on TAMs and identifies a promising approach to treat tumors by targeting TAMs with UPS.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Macrófagos/metabolismo , Neoplasias/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Animais
5.
BMC Genomics ; 25(1): 357, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600449

RESUMO

BACKGROUND: Broodiness significantly impacts poultry egg production, particularly notable in specific breeds such as the black-boned Silky, characterized by pronounced broodiness. An understanding of the alterations in ovarian signaling is essential for elucidating the mechanisms that influence broodiness. However, comparative research on the characteristics of long non-coding RNAs (lncRNAs) in the ovaries of broody chickens (BC) and high egg-laying chickens (GC) remains scant. In this investigation, we employed RNA sequencing to assess the ovarian transcriptomes, which include both lncRNAs and mRNAs, in eight Taihe Black-Bone Silky Fowls (TBsf), categorized into broody and high egg-laying groups. This study aims to provide a clearer understanding of the genetic underpinnings associated with broodiness and egg production. RESULTS: We have identified a total of 16,444 mRNAs and 18,756 lncRNAs, of which 349 mRNAs and 651 lncRNAs exhibited significantly different expression (DE) between the BC and GC groups. Furthermore, we have identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and have constructed an lncRNA-mRNA trans-regulated interaction network linked to ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses have revealed that DE mRNAs and the target genes of DE lncRNAs are associated with pathways including neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction, and ECM-receptor interaction. CONCLUSION: Our research presents a comprehensive compilation of lncRNAs and mRNAs linked to ovarian development. Additionally, it establishes a predictive interaction network involving differentially abundant lncRNAs and differentially expressed genes (DEGs) within TBsf. This significantly contributes to our understanding of the intricate interactions between lncRNAs and genes governing brooding behavior.


Assuntos
Galinhas , RNA Longo não Codificante , Feminino , Animais , Galinhas/genética , Galinhas/metabolismo , Ovário/metabolismo , RNA Longo não Codificante/metabolismo , Perfilação da Expressão Gênica , RNA Mensageiro/metabolismo , Redes Reguladoras de Genes
6.
Opt Lett ; 49(5): 1213-1216, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426976

RESUMO

In this Letter, the problems of achieving inter-CubeSat communication through radio frequency (RF) and lasers are explained, and the feasibility of using visible light communication to replace RF and lasers is investigated. On this basis, a novel, to the best of our knowledge, heterogeneous optical network with high flexibility is proposed, in which CubeSats are divided into clusters in pairs. CubeSats in each cluster utilize different optical modulation methods to achieve a compromise between optical power efficiency and spectral efficiency, as well as avoid inter-CubeSat interference. Furthermore, under the maximum power and minimum capacity constraints, a closed-form optical power allocation solution minimizing an overall bit error rate (BER) is investigated. Simulation results show that our proposed scheme is more preferred in practical systems and can achieve 3.8 dB gains compared to the conventional power allocation scheme at a BER of 10-4.

7.
Respir Res ; 25(1): 252, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902680

RESUMO

OBJECTIVES: To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD). METHODS: From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression. RESULTS: Over a median follow-up time of 31.6 months (interquartile range: 12.9-49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515). CONCLUSION: For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.


Assuntos
Dermatomiosite , Helicase IFIH1 Induzida por Interferon , Doenças Pulmonares Intersticiais , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pessoa de Meia-Idade , Dermatomiosite/mortalidade , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/diagnóstico , Helicase IFIH1 Induzida por Interferon/imunologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Valor Preditivo dos Testes , Idoso , Nomogramas , Autoanticorpos/sangue , Progressão da Doença , Medição de Risco/métodos , Seguimentos , Radiômica
8.
Arch Virol ; 169(4): 84, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38532129

RESUMO

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has prompted global concern due to its profound impact on public health and the economy. Effective treatment of COVID-19 patients in the acute phase or of those with long COVID is a major challenge. Using data-independent acquisition (DIA) technology, we performed proteomic profiling on plasma samples from 22 COVID-19 patients and six healthy controls at Dazhou Central Hospital. Random forest and least absolute shrinkage and selection operator algorithms were used for analysis at various COVID-19 treatment stages. We identified 79 proteins that were differentially expressed between COVID-19 patients and healthy controls, mainly involving pathways associated with cell processes and binding. Across different treatment stages of COVID-19, five proteins-PI16, GPLD1, IGFBP3, KRT19, and VCAM1-were identified as potential molecular markers for dynamic disease monitoring. Furthermore, the proteins BTD, APOM, IGKV2-28, VWF, C4BPA, and C7 were identified as candidate biomarkers for distinguishing between SARS-CoV-2 positivity and negativity. Analysis of protein change profiles between the follow-up and healthy control groups highlighted cardiovascular changes as a concern for patients recovering from COVID-19. Our study revealed the infection profiles of SARS-CoV-2 at the protein expression level comparing different phases of COVID-19. DIA mass spectrometry analysis of plasma samples from COVID-19 patients undergoing treatment identified key proteins involved in signaling pathways that might be used as markers of the recovery phase. These findings provide insight for the development of therapy options and suggest potential blood biomarkers for COVID-19.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Proteômica/métodos , Pandemias , Tratamento Farmacológico da COVID-19 , Biomarcadores
9.
Phys Chem Chem Phys ; 26(14): 10660-10672, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38511550

RESUMO

The cap-dependent mRNA translation is dysregulated in many kinds of cancers. The interaction between eIF4E and eIF4G through a canonical eIF4E-binding motif (CEBM) determines the efficacy of the cap-dependent mRNA translation. eIF4E-binding proteins (4E-BPs) share the CEBM and compete with eIF4G for the same binding surface of eIF4E and then inhibit the mRNA translation. 4E-BPs function as tumor repressors in nature. Hyperphosphorylation of 4E-BPs regulates the structure folding and causes the dissociation of 4E-BPs from eIF4E. However, until now, there has been no structure of the full-length 4E-BPs in complex with eIF4E. The regulation mechanism of phosphorylation is still unclear. In this work, we first investigate the interactions of human eIF4E with the CEBM and an auxiliary eIF4E-binding motif (AEBM) in eIF4G and 4E-BPs. The results unravel that the structure and interactions of the CEBM are highly conserved between eIF4G and 4E-BPs. However, the extended CEBM (ECEBM) in 4E-BPs forms a longer helix than that in eIF4G. The residue R62 in the ECEBM of 4E-BP2 forms salt bridges with E32 and E70 of eIF4E. The residue R63 of 4E-BP2 forms two special hydrogen bonds with N77 of eIF4E. Both of these interactions are missing in eIF4G. The AEBM of 4E-BPs folds into a ß-sheet conformation, which protects V81 inside a hydrophobic core in 4E-BP2. In eIF4G, the AEBM exists in a random coil state. The hydrophilic residues S637 and D638 of eIF4G open the hydrophobic core for solvents. The results show that the ECEBM and AEBM may be responsible for the competing advantage of 4E-BP2. Finally, based on our previous work (J. Zeng, F. Jiang and Y. D. Wu, J. Chem. Theory Comput., 2017, 13, 320), the human eIF4E:4E-BP2 complex (eIF4E:BP2P18-I88) including all reported phosphorylation sites is predicted. The eIF4E:BP2P18-I88 complex is different from the existing experimental eIF4E:eIF4G complex and provides an important structure for further studying the regulation mechanism of phosphorylation in 4E-BPs.


Assuntos
Fator de Iniciação 4E em Eucariotos , Fator de Iniciação Eucariótico 4G , Humanos , Proteínas de Transporte/metabolismo , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/química , Fator de Iniciação Eucariótico 4G/genética , Fator de Iniciação Eucariótico 4G/metabolismo , Ligação Proteica , Biossíntese de Proteínas
10.
Nucleic Acids Res ; 50(4): 1829-1848, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35166828

RESUMO

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.


Assuntos
Antineoplásicos/química , Neoplasias da Mama , Quadruplex G , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Desenho de Fármacos , Feminino , Genes myc , Humanos , Ligantes , Células MCF-7 , Camundongos , Regiões Promotoras Genéticas , Telômero
11.
Pestic Biochem Physiol ; 200: 105807, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582579

RESUMO

Recently, nanotechnology is among the most promising technologies used in all areas of research. The production of metal nanoparticles using plant parts has received significant attention for its environmental friendliness and effectiveness. Therefore, we investigated the possible applications of biological synthesized nickel oxide nanoparticles (NiONPs). In this study, NiONPs were synthesized through biological method using an aqueous extract of saffron stigmas (Crocus sativus L). The structure, morphology, purity, and physicochemical properties of the obtained NPs were confirmed through Scanning/Transmission Electron Microscopy attached with Energy Dispersive Spectrum, X-ray Diffraction, and Fourier transform infrared. The spherically shaped NiONPs were found by Debye Scherer's formula to have a mean dimension of 41.19 nm. The application of NiONPs in vitro at 50, 100, and 200 µg/mL, respectively, produced a clear region of 2.0, 2.2, and 2.5 cm. Treatment of Xoo cell with NiONPs reduced the growth and biofilm formation, respectively, by 88.68% and 83.69% at 200 µg/mL. Adding 200 µg/mL NiONPs into Xoo cells produced a significant amount of ROS in comparison with the control. Bacterial apoptosis increased dramatically from 1.05% (control) to 99.80% (200 µg/mL NiONPs). When compared to the control, rice plants treated with 200 µg/mL NiONPs significantly improved growth characteristics and biomass. Interestingly, the proportion of diseased leaf area in infected plants with Xoo treated with NiONPs reduced to 22% from 74% in diseased plants. Taken together, NiONPs demonstrates its effectiveness as a promising tool as a nano-bactericide in managing bacterial infection caused by Xoo.


Assuntos
Nanopartículas Metálicas , Níquel , Oryza , Xanthomonas , Oryza/microbiologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia
12.
J Environ Manage ; 362: 121308, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823301

RESUMO

Rural areas lacking essential sewage treatment facilities and collection systems often experience eutrophication due to elevated nutrient loads. Understanding nitrogen (N) sources and transport mechanisms in rural catchments is crucial for improving water quality and mitigating downstream export loads, particularly during storm events. To further elucidate the sources, pathways, and transport mechanisms of N from a rural catchment with intensive agricultural activities during storm events, we conducted an analysis of 21 events through continuous sampling over two rainy seasons in a small rural catchment from the lower reaches of the Yangtze River. The results revealed that ammonia-N (NH4+-N) and nitrate-N (NO3--N) exhibited distinct behaviors during rainstorm events, with NO3--N accounting for the primary nitrogen loss, its load being approximately forty times greater than that of NH4+-N. Through examinations of the concentration-discharge (c-Q) relationships, the findings revealed that, particularly in prolonged rainstorms, NH4+-N exhibited source limited pattern (b = -0.13, P < 0.01), while NO3--N displayed transport limited pattern (b = -0.21, P < 0.01). The figure-eight hysteresis pattern was prevalent for both NH4+-N and NO3--N (38.1% and 52.0%, respectively), arising from intricate interactions among diverse sources and pathways. For NO3--N, the hysteresis pattern shifted from clockwise under short-duration rainstorms to counter-clockwise under long-duration rainstorms, whereas hysteresis remained consistently clockwise for NH4+-N. The hysteresis analysis further suggests that the duration of rainstorms modifies hydrological connectivity, thereby influencing the transport processes of N. These insights provide valuable information for the development of targeted management strategies to reduce storm nutrient export in rural catchments.


Assuntos
Monitoramento Ambiental , Nitrogênio , Chuva , Nitrogênio/análise , Rios/química , Nitratos/análise , Qualidade da Água
13.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1397-1405, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621988

RESUMO

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional do Leste Asiático , Complexos Ventriculares Prematuros , Humanos , Complexos Ventriculares Prematuros/tratamento farmacológico , Medicamentos sem Prescrição/uso terapêutico , Reprodutibilidade dos Testes , Medicamentos de Ervas Chinesas/uso terapêutico , Cápsulas
14.
J Am Chem Soc ; 145(51): 28010-28021, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38095915

RESUMO

Phase regulation of noble metal-based nanomaterials provides a promising strategy for boosting the catalytic performance. However, realizing the continuous phase modulation in two-dimensional structures and unveiling the relevant structure-performance relationship remain significant challenges. In this work, we present the first example of continuous phase modulation in a library of Pd-Te hexagonal nanoplates (HNPs) from cubic-phase Pd4Te, rhombohedral-phase Pd20Te7, rhombohedral-phase Pd8Te3, and hexagonal-phase PdTe to hexagonal-phase PdTe2. Notably, the continuous phase regulation of the well-defined Pd-Te HNPs enables the successful modulation of the distance between adjacent Pd active sites, triggering an exciting way for tuning the relevant catalytic reactions intrinsically. The proof-of-concept oxygen reduction reaction (ORR) experiment shows a Pd-Pd distance-dependent ORR performance, where the hexagonal-phase PdTe HNPs present the best electrochemical performance in ORR (mass activity and specific activity of 1.02 A mg-1Pd and 1.83 mA cm-2Pd at 0.9 V vs RHE). Theoretical investigation reveals that the increased Pd-Pd distance relates to the weak *OH adsorption over Pd-Te HNPs, thus contributing to the remarkable ORR activity of PdTe HNPs. This work advances the phase-controlled synthesis of noble metal-based nanostructures, which gives huge impetus to the design of high-efficiency nanomaterials for diverse applications.

15.
Biol Reprod ; 109(6): 965-981, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37694817

RESUMO

The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier protection. Proper placenta development and function are critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown. We hypothesized that mapping sites of transcriptional enhancer activity and associated changes in gene expression across gestation in human placenta tissue would identify genomic loci and predicted transcription factor activity related to critical placenta functions. We used a suite of genomic assays [i.e., RNA-sequencing (RNA-seq), Precision run-on-sequencing (PRO-seq), and Chromatin immunoprecipitation-sequencing (ChIP-seq)] and computational pipelines to identify a set of >20 000 enhancers that are active at various time points in gestation. Changes in the activity of these enhancers correlate with changes in gene expression. In addition, some of these enhancers encode risk for adverse pregnancy outcomes. We further show that integrating enhancer activity, transcription factor motif analysis, and transcription factor expression can identify distinct sets of transcription factors predicted to be more active either in early pregnancy or at term. Knockdown of selected identified transcription factors in a trophoblast stem cell culture model altered the expression of key placental marker genes. These observations provide a framework for future mechanistic studies of individual enhancer-transcription factor-target gene interactions and have the potential to inform genetic risk prediction for adverse pregnancy outcomes.


Assuntos
Placenta , Placentação , Humanos , Feminino , Gravidez , Placentação/genética , Placenta/metabolismo , Elementos Facilitadores Genéticos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica
16.
Mol Cell Biochem ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38129626

RESUMO

The neutrophil-to-platelet ratio (NPR) is considered to be an indicator of inflammatory status. The value of the NPR in predicting in-hospital adverse events (AEs) and long-term prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients has not yet been reported. Meanwhile, the mechanisms behind its predictive value for long-term prognosis remain unreported as well. The study retrospectively enrolled 7284 consecutive patients with CAD undergoing PCI from January 2012 to December 2018. Multivariable logistic regression analysis, multivariable Cox regression analysis, Kaplan‒Meier (KM) curve analysis, restricted cubic spline (RCS) curve analysis, and sensitivity analysis were used in the study. All-cause death was the endpoint of the study. According to the median value of the NPR, the patients were divided into two groups: the high group (NPR ≥ 0.02, n = 3736) and the low group (NPR < 0.02, n = 3548). Multivariate logistic regression analysis demonstrated that a high NPR was a risk factor for in-hospital AEs [odds ratio (OR) = 1.602, 95% CI 1.347-1.909, p = 0.001]. During a mean follow-up period of 3.01 ± 1.49 years, the multivariate Cox regression analysis showed that a high NPR affected the long-term prognosis of patients (HR 1.22, 95% CI 1.03-1.45, p = 0.025) and cardiac death (HR 1.49, 95% CI 1.14-1.95, p = 0.003). The subgroup analysis showed that the NPR was affected by age and sex. The mediation analysis identified that the effect of the NPR on long-term outcomes is partially mediated by serum creatinine (Scr) and triglycerides. The NPR may be a convenient indicator of in-hospital AEs and poor long-term and cardiac outcomes in CAD patients. It might have impacted prognosis through effects on kidney function and lipid metabolism.

17.
J Cardiovasc Pharmacol ; 82(2): 93-103, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37314134

RESUMO

ABSTRACT: Ubiquitin E3 ligases are a structurally conserved family of enzymes that exert a variety of regulatory functions in immunity, cell death, and tumorigenesis through the ubiquitination of target proteins. Emerging evidence has shown that E3 ubiquitin ligases play crucial roles in the pathogenesis of endothelial dysfunction and related vascular diseases. Here, we reviewed the new findings of E3 ubiquitin ligases in regulating endothelial dysfunction, including endothelial junctions and vascular integrity, endothelial activation, and endothelial apoptosis. The critical role and potential mechanism of E3 ubiquitin ligases in vascular diseases, such as atherosclerosis, diabetes, hypertension, pulmonary hypertension, and acute lung injury, were summarized. Finally, the clinical significance and potential therapeutic strategies associated with the regulation of E3 ubiquitin ligases were also proposed.


Assuntos
Ubiquitina-Proteína Ligases , Doenças Vasculares , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ubiquitina/metabolismo , Proteínas , Doenças Vasculares/tratamento farmacológico
18.
BMC Pregnancy Childbirth ; 23(1): 747, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872490

RESUMO

OBJECTIVES: To compare the clinical outcomes of different multifetal pregnancy reduction (MFPR) programs in dichorionic (DC) triplets, and explore the association between early ultrasound characteristics and co-twin death after potassium chloride (KCl) injection into one monochorionic (MC) twin. METHODS: We retrospectively reviewed the data of DC triplets who underwent MFPR at our center during 2012-2021. Patients were grouped as follows: intracardiac KCl injection into one MC twin (group A), intracardiac KCl injection into both MC twins simultaneously (group B), and reduction of the singleton fetus (group C) and pregnancy outcomes were compared. Logistic regression was used to determine whether ultrasound measurements at 11-13+6 weeks predicted co-twin death and the receiver operator characteristic (ROC) analysis was conducted to assess the predictive performance. RESULTS: Finally, we enrolled 184 patients. 153 cases were in group A, and 18, 13 cases were in group B and C respectively. Gestational age at the time of MFPR did not differ among the 3 groups (median: [Formula: see text] weeks). The survival rate was 89.6%, 88.9%, and 92.3% in group A, B, and C respectively, which was comparable among groups. Preterm birth was more common in group C (10/12, 83.3%). After KCl injection into one MC twin, co-twin death occurred in 86.3% cases (132/153) within 1 day; however, 3 patients had 2 live births each, with normal postnatal development. Intertwin nuchal translucency (NT) difference/discordance significantly predicted co-twin death within 1 day after MFPR, and the areas under the ROC curve were 0.694 and 0.689, respectively. CONCLUSIONS: For MFPR in DC triplet pregnancies, reduction of the MC twins results in less preterm birth, and women with KCl injection into either one or both MC twins had similar outcomes. Large intertwin NT difference/discordance was associated with co-twin death within 1 day after KCl injection into one of the MC twins.


Assuntos
Gravidez de Trigêmeos , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Gravidez , Idade Gestacional , Medição da Translucência Nucal , Resultado da Gravidez , Redução de Gravidez Multifetal/métodos , Gravidez de Gêmeos , Estudos Retrospectivos , Ultrassonografia Pré-Natal
19.
BMC Urol ; 23(1): 193, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980490

RESUMO

BACKGROUND: Urinary incontinence is a common complication among patients with prostate cancer who have undergone radical prostatectomy. Guided by social cognitive theory and a framework for the recovery of health and well-being, we propose to develop and test a self-management intervention for patients with prostate cancer who experience urinary incontinence after undergoing radical prostatectomy. METHODS: In this study, a self-management intervention for urinary incontinence (SMI-UI) is developed, comprising a mobile self-management application, a self-management handbook, and professional support. The feasibility, acceptability, and effectiveness of this intervention will be assessed. Patient data from the urology departments of two hospitals will be collected through convenience sampling by adopting an experimental, parallel, and random assignment research design. Patients experiencing urinary incontinence after undergoing radical prostatectomy will be invited to participate. After completing the pretest questionnaire, patients will be randomly divided into the experimental and attention control groups. The experimental group will undergo a 12-week SMI-UI, whereas the attention control group will receive an intervention consisting of a single dietetic education information package. The two groups will be tested 12 and 16 weeks after the pretest. In this study, we recorded the sociodemographic and clinical variables; recruitment rate; retention rate; satisfaction with the intervention; cancer-related self-efficacy; urination symptoms and disturbance; social participation and satisfaction; resilience; and demoralization. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05335967 [date of registration 04-04-2022].


Assuntos
Neoplasias da Próstata , Autogestão , Incontinência Urinária , Masculino , Humanos , Estudos de Viabilidade , Terapia por Exercício/métodos , Incontinência Urinária/terapia , Incontinência Urinária/cirurgia , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
BMC Anesthesiol ; 23(1): 83, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932318

RESUMO

BACKGROUND: To develop prediction models for extubation time and midterm recovery time estimation in ophthalmic patients who underwent general anesthesia. METHODS: Totally 1824 ophthalmic patients who received general anesthesia at Joint Shantou International Eye Center were included. They were divided into a training dataset of 1276 samples, a validation dataset of 274 samples and a check dataset of 274 samples. Up to 85 to 87 related factors were collected for extubation time and midterm recovery time analysis, respectively, including patient factors, anesthetic factors, surgery factors and laboratory examination results. First, multiple linear regression was used for predictor selection. Second, different methods were used to develop predictive models for extubation time and midterm recovery time respectively. Finally, the models' generalization abilities were evaluated using a same check dataset with MSE, RMSE, MAE, MAPE, R-Squared and CCC. RESULTS: The fuzzy neural network achieved the highest R-Squared of 0.956 for extubation time prediction and 0.885 for midterm recovery time, and the RMSE value was 6.637 and 9.285, respectively. CONCLUSION: The fuzzy neural network developed in this study had good generalization performance in predicting both extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia. TRIAL REGISTRATION: This study is prospectively registered in the Chinese Clinical Trial Registry, registration number: CHiCRT2000036416, registration date: August 23, 2020.


Assuntos
Extubação , Anestesia Geral , Humanos , Estudos Transversais , Extubação/métodos , Anestesia Geral/métodos , Cabeça , Período de Recuperação da Anestesia
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