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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.
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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/genéticaRESUMO
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.
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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/metabolismoRESUMO
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.
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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 IntracelularRESUMO
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.
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Neoplasias , Microambiente Tumoral , Humanos , Macrófagos/metabolismo , Neoplasias/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , AnimaisRESUMO
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.
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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 GenesRESUMO
PURPOSE: To evaluate the application effects of The-Optimal-Lymph-Flow IT System in Chinese patients at high risk of developing breast cancer-related lymphedema. METHODS: A total of 104 breast cancer patients were randomly assigned to either the control group or the intervention group. The intervention group was provided with the The-Optimal-Lymph-Flow program, while the control group received the usual care. Trial outcomes including symptom experience, quality of life, and limb volume were evaluated at baseline, and at end of the 1- and 3-month trials. RESULTS: After controlling for covariates, the incidence of eight symptoms was significantly higher in the control group than in the intervention group. There were significant differences in the changes in the severity of symptoms and arm volume between the two groups from baseline to 3 months after the intervention. CONCLUSIONS: The application of TOLF in patients at high risk of developing lymphedema following breast cancer treatment significantly improved the lymphedema-related symptoms experienced in the early stage after surgery. Trial registration ChiCTR1800016713.
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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.
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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.
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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 , RadiômicaRESUMO
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, KaplanâMeier (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.
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Plaquetas , Doença da Artéria Coronariana , Neutrófilos , Intervenção Coronária Percutânea , Humanos , Masculino , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Plaquetas/metabolismo , Plaquetas/patologia , Estudos Retrospectivos , Fatores de Risco , Valor Preditivo dos TestesRESUMO
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.
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COVID-19 , Humanos , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Proteômica/métodos , Pandemias , Tratamento Farmacológico da COVID-19 , BiomarcadoresRESUMO
Avian leukosis virus subgroup J (ALV-J) is an alpharetrovirus that infects chickens, causing immunosuppression and a decrease in production performance, leading to substantial economic losses in the poultry industry. ALV-J is also well-known for its oncogenic properties, inducing tumors such as myelomas and hemangiomas in infected chickens. TRIM45 has been identified as a potential tumor suppressor, however, the relationship between TRIM45 expression and ALV-J infection remains to be elucidated.This study aimed to dissect the molecular characteristics of the chicken TRIM45 gene and its modulation during ALV-J infection, as well as its influence on viral replication. We found that the chicken TRIM45 RING domain is significantly different from that of humans and other mammals. TRIM45 is expressed in all chicken tissues, with the highest levels in the heart. Subcellular localization studies indicated a cytoplasmic distribution of TRIM45, forming aggregates within cells. Our findings demonstrate that ALV-J infection significantly upregulates TRIM45 expression in DF-1 cells. To assess the functional role of TRIM45 in ALV-J replication, we employed both gene silencing and overexpression strategies. Strikingly, the overexpression of TRIM45, including a mutant lacking the RING domain, was found to markedly suppress ALV-J replication. In contrast, TRIM45 knockdown via siRNA resulted in an enhanced viral replication, highlighting the importance of TRIM45 limiting ALV-J replication. Mechanistically, overexpression of TRIM45 induces apoptosis in infected cells, independent of its RING domain function. In conclusion, our study demonstrates that chicken TRIM45 acts as a negative regulator of ALV-J replication in vitro by promoting apoptosis in infected cells.
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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.
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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 ProteínasRESUMO
Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.
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Perfilação da Expressão Gênica , Neoplasias Bucais , Análise de Célula Única , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Metástase Linfática/patologia , Metástase Linfática/genética , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Microambiente Tumoral/imunologia , Masculino , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologiaRESUMO
BACKGROUND: Non-invasive chromosome screening (NICS) and trophectoderm biopsy preimplantation genetic testing for aneuploidy (TE-PGT) were both applied for embryo ploidy detection, However, the cumulative live birth rates (CLBR) of NICS and TE-PGT in older age groups have yet to be reported. This study aimed to ascertain whether NICS and TE-PGT could enhance the cumulative live birth rates among patients of advanced maternal age. METHODS: A total of 384 couples aged 35-40 years were recruited. The patients were assigned to three groups: NICS, TE-PGT, and intracytoplasmic sperm injection (ICSI). All patients received frozen single blastocyst transfer. Patients in the NICS and TE-PGT groups underwent aneuploidy screening. RESULTS: When compared to the ICSI group, the CLBR was significantly higher in the NICS and TE-PGT groups (27.9% vs. 44.9% vs. 51.0%, p = 0.003 for NICS vs. ICSI, p < 0.001 for TE-PGT vs. ICSI). There were no significant differences in the clinical outcomes between the NICS and TE-PGT groups. Adjusting for confounding factors, the NICS and TE-PGT groups still showed a higher CLBR than the ICSI group (adjusted odds ratio (OR) 3.847, 95% confidence interval (CI) 1.939 to 7.634; adjusted OR 3.795, 95% CI 1.981 to 7.270). Additionally, the cumulative pregnancy loss rates of the NICS and TE-PGT groups were significantly lower than that of the ICSI group (adjusted OR 0.277, 95% CI 0.087 to 0.885; adjusted OR 0.182, 95% CI 0.048 to 0.693). There was no significant difference in the birth weights of the three groups (p = 0.108). CONCLUSIONS: In women 35-40 years old, the CLBR can be increased by selecting euploid embryos using NICS and TE-PGT. For elderly women at high risk of embryonic aneuploidy, NICS, characterized by its safety and non-invasive nature, may emerge as an alternative option for preimplantation genetic testing.
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Aneuploidia , Testes Genéticos , Idade Materna , Diagnóstico Pré-Implantação , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Diagnóstico Pré-Implantação/métodos , Adulto , Gravidez , Estudos Prospectivos , Testes Genéticos/métodos , Nascido Vivo , Coeficiente de Natalidade , Taxa de Gravidez , Masculino , Transferência Embrionária/métodosRESUMO
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.
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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 , TelômeroRESUMO
The synchronous meshing of the gear pair and the screw pair is a typical feature of the planetary roller screw mechanism. In order to fully derive and analyze the nonlinear dynamic characteristics of the system, this paper creatively incorporates the time-varying meshing stiffness of gear pair and the comprehensive transmission error into the research content. Combined with the thread contact force and friction force between the roller and the screw and between the roller and the nut, the nonlinear dynamic model of the planetary roller screw mechanism considering the meshing excitation of the gear pair is established. According to the time domain diagram, frequency domain diagram, phase plane diagram, Poincaré section diagram, three-dimensional spectrum diagram, and spatial phase diagram, the nonlinear behavior of the system is described in detail, and the bifurcation evolution process of the system under the excitation frequency parameters of the external load is revealed. In addition, based on the theory of multi-scale method and considering the variables such as meshing stiffness, meshing damping, and load fluctuation, the stability equation of the primary resonance of the system is derived. The analysis of the stability of the system under different working conditions shows that the parameters are selected within a reasonable range, which effectively reduces the primary common amplitude value and enhances the overall stability of the system. The research content improves the previous system dynamics modeling method and provides a theoretical basis for the nonlinear dynamics modeling method and parameter optimization design of the planetary roller screw mechanism.
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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/microbiologiaRESUMO
The Taihe Black-Bone Silky Fowl (Gallus gallus domesticus Brisson) possesses significant value in terms of consumption, medicinal applications, and ornamental appeal, representing a precious genetic resource and traditional Chinese medicinal material. However, considerable variation exists within populations regarding egg-laying performance. This study integrates a whole-genome selection signal analysis (SSA) with a transcriptome analysis to identify genes associated with egg-laying traits in Taihe Black-Bone Silky Fowls. We identified 31 candidate genes under selection from the high-yield chicken (HC) and low-yield chicken (LC) groups. Additionally, through RNA-seq analysis, 257 common differentially expressed genes (DEGs) were identified from four comparative groups. Two overlapping genes-LPL and SETBP1-were found in both the selected gene and DEG lists. These selected genes and DEGs were enriched in pathways related to ovarian development, including the lysosome pathway, the ECM-receptor interaction pathway, the TGF-beta signaling pathway, the Wnt signaling pathway, the PPAR signaling pathway, and the glycerolipid metabolism pathway. These research findings contribute to the breeding of Taihe Black-Bone Silky Fowls with high egg production traits and provide a theoretical foundation for exploring the regulatory mechanisms of avian reproduction.
Assuntos
Galinhas , Perfilação da Expressão Gênica , Genômica , Transcriptoma , Animais , Galinhas/genética , Genômica/métodos , Perfilação da Expressão Gênica/métodos , Feminino , Oviposição/genéticaRESUMO
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 ÁguaRESUMO
The denitrification process in aquaculture systems plays a crucial role in nitrogen (N) cycle and N budget estimation. Reliable models are needed to rapidly quantify denitrification rates and assess nitrogen losses. This study conducted a comparative analysis of denitrification rates in fish, crabs, and natural ponds in the Taihu region from March to November 2021, covering a complete aquaculture cycle. The results revealed that aquaculture ponds exhibited higher denitrification rates compared to natural ponds. Key variables influencing denitrification rates were Nitrate nitrogen (NO3--N), Suspended particles (SPS), and chlorophyll a (Chla). There was a significant positive correlation between SPS concentration and denitrification rates. However, we observed that the denitrification rate initially rose with increasing Chla concentration, followed by a subsequent decline. To develop parsimonious models for denitrification rates in aquaculture ponds, we constructed five different statistical models to predict denitrification rates, among which the improved quadratic polynomial regression model (SQPR) that incorporated the three key parameters accounted for 80.7% of the variability in denitrification rates. Additionally, a remote sensing model (RSM) utilizing SPS and Chla explained 43.8% of the variability. The RSM model is particularly valuable for rapid estimation in large regions where remote sensing data are the only available source. This study enhances the understanding of denitrification processes in aquaculture systems, introduces a new model for estimating denitrification in aquaculture ponds, and offers valuable insights for environmental management.