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Immune checkpoint inhibitors (ICIs) offer promise in breaking through the treatment and survival dilemma of triple-negative breast cancer (TNBC), yet only immunomodulatory subtype and ≈5% TNBC patients respond as monotherapy due to lack of effector immune cells (internal problem) and physical barrier (external limitation) formed by cancer-associated fibroblasts (CAFs). A hydrogel drug-delivery platform, ALG@TBP-2/Pt(0)/nintedanib (ALG@TPN), is designed to induce strong immune functions and the dual elimination of the internal and external tumor microenvironment (TME). Activated by white light, through type I and II photodynamic therapy (PDT), TBP-2 generates large amounts of reactive oxygen species (ROS) intracellularly, oxidizing mitochondrial DNA (mtDNA). The unique catalase activity of Pt(0) converts endogenous H2O2 to O2, reducing the anoxia-limiting PDT and enhancing ROS generation efficacy. Abundant ROS can oxidize Pt(0) to cytotoxic Pt(II), damaging the nuclear DNA (nDNA). Dual damage to mtDNA and nDNA might bi-directionally activate the cGAS/STING pathway and enhance the immune cell response. Besides, nintedanib demonstrates a significant inhibitory effect on CAFs, weakening the immune barrier and deepening immune cell infiltration. Overall, the study provides a self-oxygenating hydrogel with the "PDT/chemotherapy/anti-CAFs" effect, triggering the cGAS/STING pathway to reshape the TME. Both internal and external interventions increase anti-TNBC immune responses.
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Scars are fibrous tissues that replace normal tissue during the wound healing process. Scarring can lead to low self-esteem, social impairment, depression, anxiety, and other psychiatric and psychological distress, necessitating a comprehensive understanding of the latest perspectives, topical research, and directions in scarring-mental health. This is a biblioshiny and VOSviewer based bibliometric analysis study. All data were obtained from the Web of Science, and a total of 664 articles from 2003 to 2022 met the criteria. The last 7 years have been a period of rapid growth in the field, with 2022 having the highest number of articles. The United States is the core country with the highest production and citation rate. The most cited literature was written in 2003 by Van Loey NE et al. Van Loey NE is the most prolific and influential author in this field. The top five popular keywords include "quality of life", "depression", "management", "anxiety", and "prevalence". The paper concludes that the current focus of scholars in the field is on the treatment of scars and that multidisciplinary treatment of such patients is worth exploring. These findings provide relevant researchers with the current state of research and possible future directions in this field.
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Ansiedade , Cicatriz , Humanos , Transtornos de Ansiedade , Cicatrização , BibliometriaRESUMO
This study aimed to compare the blood metabolic status of neonates with idiopathic polyhydramnios (IPH) and those with normal amniotic fluid, and to explore the relationship between IPH and fetal health. Blood metabolites of 32 patients with IPH and 32 normal controls admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between January 2017 and December 2022 were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) and metabolite enrichment analyses were performed to identify the differential metabolites and metabolic pathways. There was a significant difference in the blood metabolism between newborns with IPH and those with normal amniotic fluid. Six discriminant metabolites were identified: glutamate, serine, asparagine, aspartic acid, homocysteine, and phenylalanine. Differential metabolites were mainly enriched in two pathways: aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism. CONCLUSIONS: This study is the first to investigate metabolomic profiles in newborns with IPH and examine the correlation between IPH and fetal health. Differential metabolites and pathways may affect amino acid synthesis and the nervous system. Continuous attention to the development of the nervous system in children with IPH is necessary. WHAT IS KNOWN: ⢠There is an increased risk of adverse pregnancy outcomes with IPH, such as perinatal death, neonatal asphyxia, neonatal intensive care admission, cesarean section rates, and postpartum hemorrhage. ⢠Children with a history of IPH have a higher proportion of defects than the general population, particularly central nervous system problems, neuromuscular disorders, and other malformations. WHAT IS NEW: ⢠In neonates with IPH, six differential metabolites were identified with significant differences and good AUC values using LC-MS/MS analysis: glutamic acid, serine, asparagine, aspartic acid, homocysteine, and phenylalanine, which were mainly enriched in two metabolic pathways: aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. ⢠These differential metabolites and pathways may affect amino acid synthesis and development of the nervous system in neonates with IPH.
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Ácido Aspártico , Poli-Hidrâmnios , Criança , Humanos , Recém-Nascido , Gravidez , Feminino , Cromatografia Líquida , Poli-Hidrâmnios/diagnóstico , Asparagina , Cesárea , Espectrometria de Massas em Tandem , Alanina , Fenilalanina , Serina , Glutamatos , Homocisteína , RNA de TransferênciaRESUMO
OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. CONCLUSIONS: Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.
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Retinopatia da Prematuridade , Espectrometria de Massas em Tandem , Recém-Nascido , Lactente , Humanos , Recém-Nascido Prematuro , Cromatografia Líquida , Retinopatia da Prematuridade/diagnóstico , Ácido Glutâmico , OrnitinaRESUMO
BACKGROUND: State-of-the-art renewal has indicated the improvement of diagnostics of patients with metabolic associated fatty liver disease (MAFLD) and/or type II diabetes mellitus (T2DM) by dissecting the clinical characteristics as well as genomic analysis. However, the deficiency of the characterization of microbial and metabolite signatures largely impedes the symptomatic treatment. METHODS: For the purpose, we retrospectively analyzed the clinical data of 20 patients with MAFLD (short for "M"), 20 cases with MAFLD and T2DM (short for "MD"), together with 19 healthy donors (short for "Ctr"). Microbial and metabolite analyses were further conducted to explore the similarities and differences among the aforementioned populations based on feces and blood samples, respectively. RESULTS: Compared with those in the Ctr group, patients with M or MD revealed multifaceted similarities (e.g., Age, ALP, LDL, BUN) and distinctions in clinical indicators of liver (e.g., BMI, ALT, PCHE, CAP). With the aid of microbial and metabolite analyses as well as bioinformatic analyses, we found that the characteristics of gut microbiota (e.g., abundance, hierarchical clustering, cladogram, species) and lipid metabolism (e.g., metabolite, correlation coefficient and scatter plot) were distinct among the indicated groups. CONCLUSIONS: The patients with MD revealed multifaceted similarities and distinctions in characteristics of microbiome and metabolites with those in the M and HD groups, and in particular, the significantly expressed microbes (e.g., Elusimicrobiota, Berkelbacteria, Cyanobacteria, Peregrinibacteria) and lipid metabolites (e.g., Lipid-Q-P-0765, Lipid-Q-P-0216, Lipid-Q-P-0034, Lipid-Q-P-0800), which would collectively benefit the clinical diagnosis of MAFLD and T2DM.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Bactérias/genética , Diabetes Mellitus Tipo 2/complicações , Microbioma Gastrointestinal/genética , Humanos , Lipídeos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estudos RetrospectivosRESUMO
Fluorine chemistry was demonstrated to show the importance of stretching the limits of chemical synthesis, oxidation state, and chemical bonding at ambient conditions. Thus far, the highest fluorine stoichiometry of a neutral first-row transition-metal fluoride is five, in VF5 and CrF5. Pressure can stabilize new stoichiometric compounds that are inaccessible at ambient conditions. Here, we attempted to delineate the fluorination limits of first-row transition metals at a high pressure through first-principles swarm-intelligence structure searching simulations. Besides reproducing the known compounds, our extensive search has resulted in a plethora of unreported compounds: CrF6, MnF6, FeF4, FeF5, FeF6, and CoF4, indicating that the application of pressure achieves not only the fluorination limit (e.g., hexafluoride) but also the long-sought bulky tetrafluorides. Our current results provide a significant step forward towards a comprehensive understanding of the fluorination limit of first-row transition metals.
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OBJECTIVE: To carry out genetic testing for a child featuring global developmental delay, abnormal liver function, congenital heart disease, and brain malformation. METHODS: Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored a heterozygous c.2002G>T (p.Glu668Ter) variant of the SMARCA2 gene, which was predicted to be likely pathogenic by bioinformatic analysis. His mother was found to be a low-percentage mosaic for the same variant, with a ratio of 0.054 (246/4549). CONCLUSION: The child was diagnosed with Nicolaides-Baraitser syndrome resulting from maternal mosaicism for the SMARCA2 gene variant.
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Mosaicismo , Pais , Criança , Feminino , Humanos , Deficiências do Desenvolvimento , MãesRESUMO
Metal phosphides have triggered growing interest for their exotic structures and striking properties. Hence, within advanced structure search and first-principle calculations, several unprecedented Y-P compounds (e. g., Y3 P, Y2 P, Y3 P2 , Y2 P3 , YP2 , and YP3 ) were identified under compression. Interestingly, as phosphorus content increases, P atoms exhibit diverse behaviors corresponding to standalone anion, dumbbell, zigzag chain, planar sheet, crossing chain-like network, buckled layer, three-dimensional framework, and wrinkled layer. Particularly, Fd-3m YP2 can be viewed as assemblage of diamond-like Y structure and rare vertex-sharing tetrahedral P4 â units. Impressively, electron-phonon coupling (EPC) calculations elucidate that Pm-3m Y3 P possesses the highest superconducting critical temperature Tc of 10.2â K among binary transition metal phosphides. Remarkably, the EPC of Pm-3m Y3 P mainly arises from the contribution of low-frequency soft phonon modes, whereas mid-frequency phonon modes of Fd-3m YP2 dominate. These results strengthen knowledge of metal phosphides and pave a way for seeking superconductive transition metal phosphides.
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The investigations on gold science have been capturing research interest due to its diverse physical and chemical properties. Gold hydrides in the solid state, as a member of the Au compound family, are rare since the reaction of Au with H is hindered in terms of their similar electronegativity. It is expected that Li and F can provide electrons and holes, respectively, to help stabilize gold hydrides under high pressure. Herein, by means of a crystal structural search based on particle swarm optimization methodology accompanied by first-principles calculations, four hitherto unknown Li-Au-H compounds (i.e., LiAuH, LiAu2H, Li2Au2H, and Li6AuH) are predicted to be stable under compression. Intriguingly, Au-H bonding is found in LiAuH, LiAu2H, and Li2Au2H. As the gold content increases, Au atom arrangements exhibit diverse forms, from the chain in Li6AuH, the square layer in LiAuH, the network in Li2Au2H, and eventually to the coexistence of square and pyramid layers in LiAu2H. Additionally, Li6AuH has a unique cage-type lithium structure. Furthermore, electron-phonon coupling calculations show that these Li-Au-H phases are phonon-modulated superconductors with a superconducting critical temperature of 1.3, 0.06, and 0.02 K at 25 GPa and 2.79 K at 100 GPa. In contrast, we also identified two solid F4AuH and F6AuH phases with unexpected semiconductivity. They have structural configurations of H-bridged AuF4 quasi-square components and distorted AuF6 octahedrons, respectively, and have no gold-to-hydrogen bonds. Our current results indicate that electron doping at suitable concentrations under pressure can stabilize unique gold hydrides, and provide deep insights into the structures, electron properties, bonding behavior, and stability mechanism of ternary Li-Au-H and F-Au-H compounds.
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Transition metal nitrides have attracted great interest due to their unique crystal structures and applications. Here, we predict two N-rich iridium nitrides (IrN4 and IrN7) under moderate pressure through first-principles swarm-intelligence structural searches. The two new compounds are composed of stable IrN6 octahedrons and interlinked with high energy polynitrogens (planar N4 or cyclo-N5). Balanced structural robustness and energy content result in IrN4 and IrN7 being dynamically stable under ambient conditions and potentially as high energy density materials. The calculated energy densities for IrN4 and IrN7 are 1.3 kJ/g and 1.4 kJ/g, respectively, comparable to other transition metal nitrides. In addition, IrN4 is predicted to have good tensile (40.2 GPa) and shear strengths (33.2 GPa), as well as adequate hardness (20 GPa). Moderate pressure for synthesis and ambient pressure recoverability encourage experimental realization of these two compounds in near future.
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Diabetic kidney disease (DKD) is a serious disease that presents a major health problem worldwide. There is a desperate need to explore novel biomarkers to further facilitate the early diagnosis and effective treatment in DKD patients, thus preventing them from developing end-stage renal disease (ESRD). However, most regulation mechanisms at the genetic level in DKD still remain unclear. In this paper, we describe our innovative methodologies that integrate biological, computational, and statistical approaches to investigate important roles performed by regulations among microRNAs (miRs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) in DKD. We conducted fully transparent, rigorously designed experiments. Our robust and reproducible results identified hsa-miR-223-3p as a candidate novel biomarker performing important roles in DKD disease process.
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Nefropatias Diabéticas/genética , Falência Renal Crônica/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Idoso , Biomarcadores/metabolismo , Glicemia/metabolismo , Estudos de Casos e Controles , Biologia Computacional/métodos , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Masculino , MicroRNAs/metabolismo , Análise em Microsséries , Pessoa de Meia-Idade , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Reprodutibilidade dos TestesRESUMO
Against the backdrop of continuous socio-economic development, there is a growing concern among people about food quality and safety. Individuals are increasingly realizing the critical importance of healthy eating for bodily health; hence the continuous rise in demand for detecting food pollution. Simultaneously, the rapid expansion of global food trade has made people's pursuit of high-quality food more urgent. However, traditional methods of food analysis have certain limitations, mainly manifested in the high degree of reliance on personal subjective judgment for assessing food quality. In this context, the emergence of artificial intelligence and biosensors has provided new possibilities for the evaluation of food quality. This paper proposes a comprehensive approach that involves aggregating data relevant to food quality indices and developing corresponding evaluation models to highlight the effectiveness and comprehensiveness of artificial intelligence and biosensors in food quality evaluation. The potential prospects and challenges of this method in the field of food safety are comprehensively discussed, aiming to provide valuable references for future research and practice.
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OBJECTIVE: The PAOLA-1 trial (NCT02477644) reported final survival benefit associated with olaparib plus bevacizumab maintenance treatment of patients with advanced ovarian cancer (AOC) based on molecular status. Our aimed to compare the cost-effectiveness of olaparib plus bevacizumab for overall patients, patients with a breast cancer susceptibility genes (BRCA) mutation, homologous recombination deficiency (HRD), or HRD without BRCA mutations AOC from the context of the American healthcare system. METHODS: Analysis of health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) in various molecular status-based AOC patient at a $150,000/QALY of willingness-to-pay was performed using a state-transitioned Markov model with a 20-year time horizon. Meanwhile, sensitivity analyses assessments were also used to gauge the model's stability. RESULTS: The ICERs of olaparib plus bevacizumab versus bevacizumab alone were $487,428 ($374,758), $249,579 ($191,649), $258,859 ($198,739), and $270,736 ($206,640) per QALY (LY) in the overall patients, patients with BRCA mutations, patients with HRD, and patients with HRD without BRCA mutations AOC, respectively, which indicated that The ICERs was higher than $150,000/QALY in the US. Progression-free survival (PFS) value and olaparib cost emerged as the primary influencing factors of these findings in the sensitivity analysis. CONCLUSION: At current cost levels, olaparib plus bevacizumab treatment is not a cost-effective treatment for patients with AOC regardless of their molecular status in the US. However, this maintenance treatment may be more favorable health advantages for patients with BRAC mutations AOC.
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Neoplasias Ovarianas , Ftalazinas , Piperazinas , Humanos , Feminino , Bevacizumab/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Análise de Custo-Efetividade , Análise Custo-Benefício , Carcinoma Epitelial do OvárioRESUMO
INTRODUCTION: Diabetic peripheral neuropathy (DPN) impacts patient quality of life. In such patients, increased expression of mer tyrosine kinase (MerTK) has been demonstrated; however, its mechanism of action remains unclear. In this study, type 2 diabetes mellitus (T2DM) and DPN models were established in Sprague Dawley rats via low-dose streptozotocin and a high-fat diet and the mode of action of MerTK was examined. METHODS: MerTK-specific inhibitors were administered by gavage once daily for 2 weeks. Sciatic nerve conduction velocity and nerve structure were measured. The levels of MerTK, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and relevant biochemical indexes were detected. RESULTS: The study revealed upregulation of MerTK expression in T2DM and more so in DPN groups. Inhibiting MerTK led to reduced nerve conduction velocity and further deterioration of sciatic nerve structure, as evidenced by structural morphology. Concurrently, serum levels of total cholesterol, glycated hemoglobin, and triglyceride significantly increased. Moreover, levels of NF-κB increased in both serum and nerve tissue, alongside a significant rise in TNF-α and IL-1ß expressions. MerTK could bind to the inhibitor of kappa B kinase beta (Ikbkb) in Schwann cells, establishing Ikbkb as a precursor to NF-κB activation. DISCUSSION: Inhibition of MerTK exacerbates neuropathy, indicating its protective role in DPN by suppressing the NF-κB pathway, highlighting a potential new target for its diagnosis and treatment.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , NF-kappa B , Ratos Sprague-Dawley , Transdução de Sinais , c-Mer Tirosina Quinase , Animais , Masculino , Ratos , c-Mer Tirosina Quinase/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The prevalence of autism spectrum disorders (ASD) has been steadily increasing, and growing evidence suggests a link between high-fat diet (HFD), obesity, and ASD; however, the mechanism underlying this association remains elusive. Herein, BTBR T + tf/J (BTBR) inbred mice (a mouse ASD model) and C57Bl/6J (C57) mice were fed an HFD and normal diet (ND) for 8 weeks (groups: C57 + ND, C57 + HFD, BTBR + ND, and BTBR + HFD). Subsequently, mice underwent behavioral assessments, followed by intestinal tissues harvesting to detect expression of intestinal barrier proteins and inflammatory factors and immune cell numbers, and a correlation analysis. HFD-fed BTBR mice developed obesity, elevated blood sugar, significantly aggravated anxiety-like behaviors, impaired intestinal barrier function, intestinal inflammation with elevated CD4+IL17+ T (Th17) cells and reduced CD4+Foxp3+ T (Treg) cells, exhibiting reduced expression of proteins related to AMPK regulatory pathway (AMPK, p-AMPK, SIRT1). Correlation analysis revealed that the degree of behavioral anxiety, the degree of intestinal barrier damage, the severity of intestinal inflammation, and the degree of immune cell imbalance positively correlated with each other. Accordingly, HFD-induced obesity may cause intestinal Th17/Treg imbalance via the AMPK-SIRT1 pathway, leading to an inflammatory environment in the intestine, impairing intestinal barrier function, and ultimately aggravating anxiety-like behaviors in mice.
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Sirtuína 1 , Linfócitos T Reguladores , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Proteínas Quinases Ativadas por AMP , Intestinos , Obesidade , Camundongos Endogâmicos , Camundongos Endogâmicos C57BL , Inflamação , Ansiedade/etiologia , Modelos Animais de DoençasRESUMO
Intimal hyperplasia is one of the common pathophysiological foundations of vascular remodeling including restenosis and atherosclerosis. The Rho GTPase activating protein 24 (ARHGAP24) has been reported as a tumor suppressor in multiple cancers. Nevertheless, the role of ARHGAP24 in intimal hyperplasia is unclear. Interestingly, our results showed that ARHGAP24 was significantly up-regulated in dedifferentiated VSMC in vitro and vivo, which suggested that ARHGAP24 could promote VSMC dedifferentiation and proliferation. Knockdown of ARHGAP24 effectively inhibited VSMC dedifferentiation and proliferation in the absence and present of PDGF-BB, which might inactivate both ATK and ERK1/2 signaling pathways. Moreover, AAV9-mediated silencing of Arhgap24 also alleviates VSMC dedifferentiation and proliferation in the wire-injured mouse femoral arteries, contributing to reducing neointima formation. AAV9-mediated overexpression of Arhgap24 exacerbates intimal hyperplasia. We demonstrate that decreased ARHGAP24 expression restrained VSMC proliferation and dedifferentiation possibly by inactivating both AKT and ERK1/2 signaling pathways, which may provide a potential therapeutic strategy for diseases associated with intimal hyperplasia including restenosis and atherosclerosis.
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Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.
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Lead poisoning in children is a non-negligible and ongoing threat to children's health and optimal development worldwide. There is no sufficient scientometric analysis available on this subject, though. Aiming to uncover the research development, hotspots, and possible future orientation, we performed a scientometric analysis of related publications from 2012 to 2022. Initial information was accessed using the "Analysis Results" and "Create Citation Report" sections of the Web of Science core collection database, which were utilized to find original publications in this field of research. Biblioshiny and VOSviewer software were applied to further analyze and visualize the data. The research addressed a range of topics, including yearly publications, highly cited articles, co-cited references, journals, authors, nations, organizations, and keywords. A total of 883 articles were retrieved. From 2018 to 2021, the annual publication output was abundant and peaked in 2019. Among 111 countries, the USA obtained the highest number of documents issued, total citations, and total link strength. Meanwhile, most of the top 15 institutions, including the top four, are located in the USA. Further, we spotted greater scopes with development potential, including enhancing records to lessen exposure to harmful risks, improving methods for observing lead sources, and elucidating the gradient link between lead poisoning symptoms and concentrations. We anticipate that our research will assist researchers in summarizing previous research and providing perspectives for workable prospective study topics.
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Saúde da Criança , Intoxicação por Chumbo , Criança , Humanos , Estudos Prospectivos , Chumbo , Bibliometria , Bases de Dados FactuaisRESUMO
Introduction: Pregnancy outcomes of patients with systemic lupus erythematosus (SLE) have improved over the past four decades, leading to an increased desire for pregnancy among this cohort. However, the offspring of patients with SLE still face the risks of preterm birth, low birth weight, learning disabilities, and neurological disorders, while the causes underlying these risks remain unclear. Methods: In this study, we analyzed the blood metabolic features of neonates born to 30 SLE patients and 52 healthy control mothers by employing tandem mass spectrometry with the dual aims of identifying the etiology of metabolic features specific to infants born from mothers with SLE and providing new insights into the clinical management of such infants. Results: We found significant differences in serum metabolite levels between infants born from mothers with SLE and those born from mothers without SLE, including 15 metabolites with reduced serum levels. Further analysis revealed a disrupted tyrosine metabolism pathway in the offspring of mothers with SLE. Discussion: By constructing a composite model incorporating various factors, such as serum tyrosine levels, gestational age, and birth weight, we were able to accurately differentiate between newborns of SLE and non-SLE pregnancies. Our data reveal significant differences in serum concentrations of amino acids and acylcarnitines in newborns born to mothers with SLE. We conclude that the reduction of blood L-tyrosine levels is a feature that is characteristic of adverse neurological outcomes in infants born from mothers with SLE.
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Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Lactente , Feminino , Recém-Nascido , Humanos , Tirosina , Lúpus Eritematoso Sistêmico/diagnóstico , Recém-Nascido de Baixo PesoRESUMO
Introduction: Cancer represents a significant global public health concern. In recent years, the incidence of cancer has been on the rise worldwide due to various factors, including diet, environment, and an aging population. Simultaneously, advancements in tumor molecular biology and genomics have led to a shift from systemic chemotherapy focused on disease sites and morphopathology towards precise targeted therapy for driver gene mutations. Therefore, we propose a comprehensive review aimed at exploring the research hotspots and directions in the field of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers over the past decade, providing valuable insights for cancer treatment strategies. Specifically, we aim to present an intellectual landscape using data obtained from the Web of Science (WoS) regarding KRAS mutation. Methods: Bibliometrix, VOSviewer, CiteSpace, and HistCite were employed to conduct scientometric analyses on national publications, influential authors, highly cited articles, frequent keywords, etc. Results: A total of 16,609 publications met the screening criteria and exhibited a consistent annual growth trend overall. Among 102 countries/regions, the United States occupied the vast majority share of the published volume. The journal Oncotarget had the highest circulation among all scientific publications. Moreover, the most seminal articles in this field primarily focus on biology and targeted therapies, with overcoming drug resistance being identified as a future research direction. Conclusion: The findings of the thematic analysis indicate that KRAS mutation in lung cancer, the prognosis following B-Raf proto-oncogene, serine/threonine kinase (BRAF) or rat sarcoma (RAS) mutations, and anti-epidermal growth factor receptor (EGFR)-related lung cancer are the significant hotspots in the given field. Considering the significant advancements made in direct targeting drugs like sotorasib, it is anticipated that interest in cancers associated with KRAS mutations will remain steadfast.