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Induction of the pluripotent cell mass termed callus from detached organs or tissues is an initial step in typical in vitro plant regeneration, during which auxin-induced ectopic activation of root stem cell factors is required for subsequent de novo shoot regeneration. While Arabidopsis (Arabidopsis thaliana) AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 and their downstream transcription factors LATERAL ORGAN BOUNDARIES DOMAIN (LBD) are known to play key roles in directing callus formation, the molecules responsible for activation of root stem cell factors and thus establishment of callus pluripotency are unclear. Here, we identified Arabidopsis WRKY23 and BASIC HELIX-LOOP-HELIX 041 (bHLH041) as a transcriptional activator and repressor, respectively, of root stem cell factors during establishment of auxin-induced callus pluripotency. We show that auxin-induced WRKY23 downstream of ARF7 and ARF19 directly activates the transcription of PLETHORA 3 (PLT3) and PLT7 and thus that of the downstream genes PLT1, PLT2, and WUSCHEL-RELATED HOMEOBOX 5 (WOX5), while LBD-induced removal of bHLH041 derepresses the transcription of PLT1, PLT2, and WOX5. We provide evidence that transcriptional activation by WRKY23 and loss of bHLH041-imposed repression act synergistically in conferring shoot-regenerating capability on callus cells. Our findings thus disclose a transcriptional mechanism underlying auxin-induced cellular reprogramming, which, together with previous studies, outlines the molecular framework of auxin-induced pluripotent callus formation for in vitro plant regeneration programs.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Ativação Transcricional , Fatores de Transcrição/metabolismo , Ácidos Indolacéticos , Regulação da Expressão Gênica de Plantas/genética , Raízes de Plantas/metabolismoRESUMO
Toll-like receptors (TLRs), especially TLR7, play an important role in systemic lupus erythematosus (SLE) pathogenesis. However, the regulatory mechanism underlying the abnormal activation of TLR pathways in patients with SLE has not been elucidated. Notably, accumulating evidence indicates that myeloid-derived suppressor cells (MDSCs) are important regulators of inflammation and autoimmune diseases. Compared with healthy control subjects, patients with SLE have a greater proportion of MDSCs among peripheral blood mononuclear cells (PBMCs); however, the effect of MDSCs on TLR7 pathway activation has not been determined. In the present study, lupus MDSCs significantly promoted TLR7 pathway activation in macrophages and dendritic cells (DCs), exacerbating the imiquimod-induced lupus model. RNA-sequencing analysis revealed significant overexpression of S100 calcium-binding protein A8 (S100A8) and S100A9 in MDSCs from diseased MRL/lpr mice. In vitro and in vivo studies demonstrated that S100A8/9 effectively promoted TLR7 pathway activation and that S100A8/9 deficiency reversed the promoting effect of MDSCs on TLR7 pathway activation in lupus. Mechanistically, MDSC-derived S100A8/9 upregulated interferon gamma (IFN-γ) secretion by macrophages and IFN-γ subsequently promoted TLR7 pathway activation in an autocrine manner. Taken together, these findings suggest that lupus MDSCs promote TLR7 pathway activation and lupus pathogenesis through the S100A8/9-IFN-γ axis. Our study identified an important target for SLE therapy.
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Calgranulina A , Calgranulina B , Lúpus Eritematoso Sistêmico , Células Supressoras Mieloides , Animais , Camundongos , Células Dendríticas/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Macrófagos/metabolismo , Camundongos Endogâmicos MRL lpr , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Calgranulina A/metabolismo , Calgranulina B/metabolismoRESUMO
Induction of a pluripotent cell mass, called callus, from detached organs is an initial step in in vitro plant regeneration, during which phytohormone auxin-induced ectopic activation of a root developmental program has been shown to be required for subsequent de novo regeneration of shoots and roots. However, whether other signals are involved in governing callus formation, and thus plant regeneration capability, remains largely unclear. Here, we report that the Arabidopsis calcium (Ca2+) signaling module CALMODULIN IQ-MOTIF CONTAINING PROTEIN (CaM-IQM) interacts with auxin signaling to regulate callus and lateral root formation. We show that disruption of IQMs or CaMs retards auxin-induced callus and lateral root formation by dampening auxin responsiveness, and that CaM-IQM complexes physically interact with the auxin signaling repressors INDOLE-3-ACETIC ACID INDUCIBLE (IAA) proteins in a Ca2+-dependent manner. We further provide evidence that the physical interaction of CaM6 with IAA19 destabilizes the repressive interaction of IAA19 with AUXIN RESPONSE FACTOR 7 (ARF7), and thus regulates auxin-induced callus formation. These findings not only define a critical role of CaM-IQM-mediated Ca2+ signaling in callus and lateral root formation, but also provide insight into the interplay of Ca2+ signaling and auxin actions during plant regeneration and development.
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Proteínas de Arabidopsis , Arabidopsis , Sinalização do Cálcio , Organogênese Vegetal , Raízes de Plantas , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Calmodulina/metabolismo , Ácidos Indolacéticos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: Fluorescence imaging-guided surgery has been used in oncology. However, for tiny tumors, the current imaging probes are still difficult to achieve high-contrast imaging, leading to incomplete resection. In this study, we achieved precise surgical resection of tiny metastatic cancers by constructing an engineering erythrocyte membrane-camouflaged bioprobe (AR-M@HMSN@P). METHODS: AR-M@HMSN@P combined the properties of aggregation-induced emission luminogens (AIEgens) named PF3-PPh3 (P), with functional erythrocyte membrane modified by a modular peptide (AR). Interestingly, AR was composed of an asymmetric tripodal pentapeptide scaffold (GGKGG) with three appended modulars: KPSSPPEE (A6) peptide, RRRR (R4) peptide and cholesterol. To verify the specificity of the probe in vitro, SKOV3 cells with overexpression of CD44 were used as the positive group, and HLF cells with low expression of CD44 were devoted as the control group. The AR-M@HMSN@P fluorescence imaging was utilized to provide surgical guidance for the removal of micro-metastatic lesions. RESULTS: In vivo, the clearance of AR-M@HMSN@P by the immune system was reduced due to the natural properties inherited from erythrocytes. Meanwhile, the A6 peptide on AR-M@HMSN@P was able to specifically target CD44 on ovarian cancer cells, and the electrostatic attraction between the R4 peptide and the cell membrane enhanced the firmness of this targeting. Benefiting from these multiple effects, AR-M@HMSN@P achieved ultra-precise tumor imaging with a signal-to-noise ratio (SNR) of 15.2, making it possible to surgical resection of tumors < 1 mm by imaging guidance. CONCLUSION: We have successfully designed an engineered fluorescent imaging bioprobe (AR-M@HMSN@P), which can target CD44-overexpressing ovarian cancers for precise imaging and guide the resection of minor tumors. Notably, this work holds significant promise for developing biomimetic probes for clinical imaging-guided precision cancer surgery by exploiting their externally specified functional modifications.
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Maternal inflammation can lead to premature birth and fetal brain damage. CircRNA_19038 and lncRNA-AK016022 have been shown to be significantly reduced in brain tissues of preterm mice, while whether they are involved in the regulation of preterm white matter injury remains to be explored. Pregnant mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish a preterm brain injury model. Healthy mice born at term served as controls. Lentivirus-mediated circ_19038 overexpression vector (LV-circ_19038), LV-lnc-AK016022, LV-Sirt1 and LV-sh-Sirt1 were administered to preterm mice through the ventricles. The expression levels of circ_19038, lnc-AK016022 and Sirt1 in the brain tissues of preterm mice were significantly lower than those of full-term healthy mice, and circ_19038 and lnc-AK016022 were co-localized in the brain tissues. Upregulation of circ_19038 or/and lnc-AK016022 promoted remyelination and alleviated white matter structural damage, neuroinflammation, and long-term cognitive and motor deficits in preterm mice, and the combined effect of circ_19038 and lnc-AK016022 showed better results. Primary mouse neuronal cells were isolated to investigate the regulatory effects of circ_19038 and lnc-AK016022 on Sirt1. Circ_19038 and lnc-AK016022 jointly promoted the expression of Sirt1 by adsorbing miR-1b and miR-328, respectively. Moreover, silencing Sirt1 antagonized the beneficial effects of circ_19038 or/and lnc-AK016022 on brain white matter injury in preterm mice. In conclusion, circ_19038 and lnc-AK016022 synergistically regulated Sirt1 expression to promote remyelination and alleviate white matter injury in preterm mice.
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Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl is a widely distributed secreted protein in the body, involved in regulating glucose and lipid metabolism and maintaining cardiovascular system homeostasis. In this review, we present the predictive and therapeutic roles of Metrnl in various cardiovascular and metabolic diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, heart failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, and obesity.
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Biomarcadores , Doenças Cardiovasculares , Doenças Metabólicas , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Biomarcadores/metabolismo , AnimaisRESUMO
BACKGROUND: Recent clinical trials have evaluated the efficacy of vonoprazan-amoxicillin (VA) dual therapy as the first-line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta-analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. MATERIALS AND METHODS: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium-competitive acid blocker" OR "P-CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention-to-treat and per-protocol analysis. The secondary outcomes were adverse events and compliance. RESULTS: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention-to-treat and per-protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors-based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan-containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7-day VA dual therapy showed lower eradication rates than 10-day (χ2 = 24.09, p < 0.01) and 14-day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth-containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. CONCLUSION: VA dual therapy, a novel regimen, showed high efficacy as the first-line treatment for H. pylori eradication, which should be optimized before application in different regions.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Inibidores da Bomba de Prótons , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to explore obesity phenotypes and investigate their association with dietary patterns. METHODS: Data were obtained from the baseline survey conducted in the China Multi-Ethnic Cohort Study from July 2018 to August 2019. All participants with a body mass index of at least 24 kg/m2 were enrolled and underwent a questionnaire survey, physical examination, and clinical laboratory tests. A two-step cluster analysis was employed to classify the participants into phenotypes. Dietary information was collected using the food frequency questionnaire, and principal component analysis was conducted to identify distinct dietary patterns. RESULTS: We analyzed the data of 8757 participants. They were categorized based on demographic characteristics, biochemical indicators, and anthropometric measurements into two distinct clusters identified as metabolically healthy obesity and metabolically unhealthy obesity (MUO). Key predictors included serum uric acid, sex, and diastolic blood pressure. Subgroup analysis by sex identified three distinct clusters within both male and female participants. The MUO group had the highest prevalence of a range of chronic noncommunicable diseases. The analysis uncovered three unique dietary patterns among participants classified as the premium protein, rice-oil-red meat, and oil-salt patterns. Notably, the MUO subgroup demonstrated significantly higher factor scores for both the rice-oil-red meat and oil-salt patterns. CONCLUSIONS: Obesity phenotypes are closely related to metabolic and demographic characteristics, with serum uric acid being a significant factor in categorizing the metabolic states of obesity. The rice-oil-red meat and oil-salt patterns may be related to the metabolic status of individuals with obesity.
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Chronic arsenic exposure is considered to increase the risk of breast cancer. p62 is a multifunctional adaptor protein that controls myriad cellular processes and is overexpressed in breast cancer tissues. Although previous studies have indicated the involvement of p62 accumulation in arsenic tumorigenesis, the underlying mechanism remains obscure. Here, we found that 0.1 µM or 0.5 µM arsenite exposure for 24 weeks induced oncogenic phenotypes in human mammary epithelial cells. Elevated aerobic glycolysis, cell proliferation capacity, and activation of p62-mTOR pathway, as indicated by increased protein levels of p62, phosphorylated-mTOR (p-mTOR) and hypoxia-inducible factor 1α (HIF1α), were observed in chronically arsenite-exposed cells, and of note in advance of the onset of oncogenic phenotypes. Moreover, p62 silencing inhibited acquisition of oncogenic phenotypes in arsenite-exposed cells. The protein levels of p-mTOR and HIF1α, as well as aerobic glycolysis and cell proliferation, were suppressed by p62 knockdown. In addition, re-activation of pmTOR reversed the inhibitory effects of p62 knockdown. Collectively, our data suggest that p62 exerts an oncogenic role via mTORC1 activation and acts as a key player in glucose metabolism during arsenite-induced malignant transformation, which provides a new mechanistic clue for the arsenite carcinogenesis.
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Arsênio , Arsenitos , Neoplasias da Mama , Humanos , Feminino , Arsênio/toxicidade , Arsenitos/toxicidade , Glicólise , Serina-Treonina Quinases TOR/metabolismo , Carcinogênese , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Células Epiteliais/metabolismo , Linhagem Celular TumoralRESUMO
OBJECT: To review recent advances of artificial intelligence (AI) in enhancing the efficiency and throughput of the MRI acquisition workflow in neuroimaging, including planning, sequence design, and correction of acquisition artifacts. MATERIALS AND METHODS: A comprehensive analysis was conducted on recent AI-based methods in neuro MRI acquisition. The study focused on key technological advances, their impact on clinical practice, and potential risks associated with these methods. RESULTS: The findings indicate that AI-based algorithms have a substantial positive impact on the MRI acquisition process, improving both efficiency and throughput. Specific algorithms were identified as particularly effective in optimizing acquisition steps, with reported improvements in workflow efficiency. DISCUSSION: The review highlights the transformative potential of AI in neuro MRI acquisition, emphasizing the technological advances and clinical benefits. However, it also discusses potential risks and challenges, suggesting areas for future research to mitigate these concerns and further enhance AI integration in MRI acquisition.
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Algoritmos , Inteligência Artificial , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Artefatos , Encéfalo/diagnóstico por imagem , Fluxo de Trabalho , Interpretação de Imagem Assistida por Computador/métodosRESUMO
The prevalence of dyslipidemia is increasing, and it has become a significant global public health concern. Some studies have demonstrated contradictory relationships between urinary metals and dyslipidemia, and the combined effects of mixed urinary metal exposure on dyslipidemia remain ambiguous. In this study, we examined how individual and combined urinary metal exposure are associated with the occurrence of dyslipidemia. According to the data from the 2018-2019 baseline survey database of the China Multi-Ethnic Cohort (CMEC) Study, a population of 9348 individuals was studied. Inductively coupled plasmamass spectrometry (ICP-MS) was used to measure 21 urinary metal concentrations in the collected adult urinary samples. The associations between urinary metals and dyslipidemia were analyzed by logistic regression, weighted quantile sum regression (WQS), and quantile-based g-computation (qgcomp), controlled for potential confounders to examine single and combined effects. Dyslipidemia was detected in 3231 individuals, which represented approximately 34.6â¯% of the total population. According to the single-exposure model, Al and Na were inversely associated with the risk of dyslipidemia (OR = 0.95, 95â¯% CI: 0.93, 0.98; OR = 0.89, 95â¯% CI: 0.83, 0.95, respectively), whereas Zn, Ca, and P were positively associated (OR = 1.69, 95â¯% CI: 1.42, 2.01; OR = 1.12, 95â¯% CI: 1.06, 1.18; OR = 1.21, 95â¯% CI: 1.09, 1.34, respectively). Moreover, Zn and P were significantly positively associated even after adjusting for these metals, whereas Al and Cr were negatively associated with the risk of dyslipidemia. The results of the WQS and qgcomp analyses showed that urinary metal mixtures were positively associated with the risk of dyslipidemia (OR = 1.26, 95â¯% CI: 1.15, 1.38; OR = 1.09, 95â¯% CI: 1.01, 1.19). This positive association was primarily driven by Zn, P, and Ca. In the sensitivity analyses with collinearity diagnosis, interaction, and stratified analysis, the results remained, confirming the reliability of the study findings. In this study, the individual and combined effects of urinary Zn, P, and Ca on dyslipidemia were determined, which provided novel insights into the link between exposure to metals and dyslipidemia.
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Dislipidemias , Metais , Humanos , Dislipidemias/epidemiologia , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Adulto , Metais/urina , Poluentes Ambientais/urina , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Idoso , Etnicidade/estatística & dados numéricos , População do Leste AsiáticoRESUMO
Constituents of cigarette smoke are known to be carcinogens. Additionally, there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Nicotine, the primary constituent of tobacco, plays a role in cancer progression. In our previous study, it was found that nicotine enhances the proliferation of a human normal fetal hepatic (WRL68) cell due to the activation of p53 mutation at Ser249 (p53-RS)/STAT1/CCND1 signaling pathway. Here, we further elucidated the mechanism of regulating this pathway. Firstly, dose-dependent increase of SETDB1 protein level in WRL68 cells upon exposure to nicotine (1.25, 2.5, and 5⯵M), significantly enhanced cellular proliferation. In addition, the upregulation of SETDB1 protein was necessary for the nuclear translocation of p53-RS to establish a ternary complex with STAT1 and SETDB1, which facilitated p53-RS di-methylation at K370 (p53-RS/K370me2). After that, the activation of CCND1/PI3K/AKT pathway was initiated when STAT1 stability was enhanced by p53-RS/K370me2, ultimately resulting in cell proliferation. Altogether, the study revealed that the increase in SETDB1 expression could potentially have a significant impact on the activation of CCND1/PI3K/AKT pathway through p53-RS/K370me2, leading to the proliferation of WRL68 cells induced by nicotine, which could contribute to hepatocellular carcinoma for smokers. Besides, the results of this study provided a foundation for the development of anticancer therapies for cancers associated with tobacco use.
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Proliferação de Células , Ciclina D1 , Histona-Lisina N-Metiltransferase , Nicotina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Proteína Supressora de Tumor p53 , Humanos , Nicotina/toxicidade , Ciclina D1/metabolismo , Ciclina D1/genética , Histona-Lisina N-Metiltransferase/genética , Proliferação de Células/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Metilação/efeitos dos fármacos , Linhagem Celular , Fator de Transcrição STAT1/metabolismoRESUMO
OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Nomogramas , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Fatores de RiscoRESUMO
Nanochannel technology has emerged as a powerful tool for label-free and highly sensitive detection of protein folding/unfolding status. However, utilizing the inner walls of a nanochannel array may cause multiple events even for proteins with the same conformation, posing challenges for accurate identification. Herein, we present a platform to detect unfolded proteins through electrical and optical signals using nanochannel arrays with outer-surface probes. The detection principle relies on the specific binding between the maleimide groups in outer-surface probes and the protein cysteine thiols that induce changes in the ionic current and fluorescence intensity responses of the nanochannel array. By taking advantage of this mechanism, the platform has the ability to differentiate folded and unfolded state of proteins based on the exposure of a single cysteine thiol group. The integration of these two signals enhances the reliability and sensitivity of the identification of unfolded protein states and enables the distinction between normal cells and Huntington's disease mutant cells. This study provides an effective approach for the precise analysis of proteins with distinct conformations and holds promise for facilitating the diagnoses of protein conformation-related diseases.
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The INDETERMINATE DOMAIN (IDD) transcription factors mediate various aspects of plant growth and development. We previously reported that an Arabidopsis IDD subfamily regulates spatial auxin accumulation, and thus organ morphogenesis and gravitropic responses. However, its functions in stress responses are not well defined. Here, we use a combination of physiological, biochemical, molecular, and genetic approaches to provide evidence that the IDD14 cooperates with basic leucine zipper-type binding factors/ABA-responsive element (ABRE)-binding proteins (ABRE-binding factors (ABFs)/AREBs) in ABA-mediated drought tolerance. idd14-1D, a gain-of-function mutant of IDD14, exhibits decreased leaf water loss and improved drought tolerance, whereas inactivation of IDD14 in idd14-1 results in increased transpiration and reduced drought tolerance. Altered IDD14 expression affects ABA sensitivity and ABA-mediated stomatal closure. IDD14 can physically interact with ABF1-4 and subsequently promote their transcriptional activities. Moreover, ectopic expression and mutation of ABFs could, respectively, suppress and enhance plant sensitivity to drought stress in the idd14-1 mutant. Our results demonstrate that IDD14 forms a functional complex with ABFs and positively regulates drought-stress responses, thus revealing a previously unidentified role of IDD14 in ABA signaling and drought responses.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Água/metabolismoRESUMO
Arsenic is a notorious environmental pollutant. Of note, developmental arsenic exposure has been found to increase the risk of developing a variety of ailments later in life, but the underlying mechanism is not well understood. Many elements of host health have been connected to the gut microbiota. It is still unclear whether and how developmental arsenic exposure affects the gut microbiota. In the present study, we found that developmental arsenic exposure changed intestinal morphology and increased intestinal permeability and inflammation in mouse pups at weaning. These alterations were accompanied by a significant change in gut microbiota, as evidenced by considerably reduced gut microbial richness and diversity. In developmentally arsenic-exposed pups, the relative abundance of Muribaculaceae was significantly decreased, while the relative abundance of Akkermansia and Bacteroides was significantly enhanced at the genus level. Metabolome and pathway enrichment analyses indicated that amino acid and purine metabolism was promoted, while glycerophospholipid metabolism was inhibited. Interestingly, the relative abundance of Muribaculaceae and Akkermansia showed a strong correlation with most plasma metabolites significantly altered by developmental arsenic exposure. These data indicate that gut microbiota dysbiosis may be a critical link between developmental arsenic exposure and metabolic disorders and shed light on the mechanisms underlying increased susceptibility to diseases due to developmental arsenic exposure.
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Arsênio , Microbioma Gastrointestinal , Animais , Arsênio/toxicidade , Disbiose/induzido quimicamente , Metabolismo dos Lipídeos , Metaboloma , CamundongosRESUMO
Accurate and automated reconstruction of the in vivo human cerebral cortical surface from anatomical magnetic resonance (MR) images facilitates the quantitative analysis of cortical structure. Anatomical MR images with sub-millimeter isotropic spatial resolution improve the accuracy of cortical surface and thickness estimation compared to the standard 1-millimeter isotropic resolution. Nonetheless, sub-millimeter resolution acquisitions require averaging multiple repetitions to achieve sufficient signal-to-noise ratio and are therefore long and potentially vulnerable to subject motion. We address this challenge by synthesizing sub-millimeter resolution images from standard 1-millimeter isotropic resolution images using a data-driven supervised machine learning-based super-resolution approach achieved via a deep convolutional neural network. We systematically characterize our approach using a large-scale simulated dataset and demonstrate its efficacy in empirical data. The super-resolution data provide improved cortical surfaces similar to those obtained from native sub-millimeter resolution data. The whole-brain mean absolute discrepancy in cortical surface positioning and thickness estimation is below 100 µm at the single-subject level and below 50 µm at the group level for the simulated data, and below 200 µm at the single-subject level and below 100 µm at the group level for the empirical data, making the accuracy of cortical surfaces derived from super-resolution sufficient for most applications.
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Córtex Cerebral/patologia , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Encéfalo/patologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Razão Sinal-RuídoRESUMO
BACKGROUND: Early identification of risk factors for cognition decline may contribute to the interventions for Alzheimer's disease. Obesity is a common modifiable risk factor for chronic diseases. The association between obesity and cognition in older adults is limited, and sex differences in this area have not been well recognized. OBJECTIVE: The aim of the study was to observe the sex differences in the relationship between obesity and cognition in a rural community-dwelling older population of Guizhou, China. METHODS: Data were gathered from the baseline survey of a cohort study of older people in rural areas of Guizhou, China. Demographic and behavioral data (sex, age, education, household income, smoking history, drinking history, history of head injury, diet, and level of physical exercise time) were collected. The Mini-Mental State Examination (MMSE) was used to assess cognitive function. Body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were used as different measures of obesity. Comparisons between the groups were made by the Wilcoxon rank-sum test or Kruskal-Wallis H test. Restricted cubic spline regression was used to examine a dose-response relationship between obesity indicators and cognitive function. Linear relationships were performed by the multivariable linear regression model. RESULTS: A total of 1,654 participants including 964 women and 690 men were enrolled in this study. After adjustment, BMI showed a nonlinear relationship with MMSE scores in women. There was a significant trend toward increasing MMSE scores at the low end of BMI (13.52-20.10 kg/m2, p = 0.014). The multivariable linear regression model showed that MMSE increased by 0.631 (p < 0.001) for every one standard deviation increase in HC in women. No association was found between obesity parameters and cognitive function in men. CONCLUSION: Our results suggest that there are significant sex differences in some obesity parameters and cognition in an older Chinese population. BMI and HC are positively associated with cognitive function in women. No association was found between obesity measures and cognitive function in men.
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Obesidade , Caracteres Sexuais , Idoso , Índice de Massa Corporal , China/epidemiologia , Cognição/fisiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Fatores de Risco , Circunferência da CinturaRESUMO
Chronic exposure to arsenic has been associated with a variety of cancers with the mechanisms undefined. Arsenic exposure causes alterations in metabolites in bio-samples. Recent research progress on cancer biology suggests that metabolic reprogramming contributes to tumorigenesis. Therefore, metabolic reprogramming provides a new clue for the mechanisms of arsenic carcinogenesis. In the present manuscript, we review the latest findings in reprogramming of glucose, lipids, and amino acids in response to arsenic exposure. Most studies focused on glucose reprogramming and found that arsenic exposure enhanced glycolysis. However, in vivo studies observed "reverse Warburg effect" in some cases due to the complexity of the disease evolution and microenvironment. Arsenic exposure has been reported to disturb lipid deposition by inhibiting lipolysis, and induce serine-glycine one-carbon pathway. As a dominant mechanism for arsenic toxicity, oxidative stress is considered to link with metabolism reprogramming. Few studies analyzed the causal relationship between metabolic reprogramming and arsenic-induced cancers. Metabolic alterations may vary with exposure doses and periods. Identifying metabolic alterations common among humans and experiment models with human-relevant exposure characteristics may guide future investigations.
Assuntos
Arsênio , Neoplasias , Arsênio/toxicidade , Carcinogênese , Transformação Celular Neoplásica , Glicólise , Humanos , Neoplasias/induzido quimicamente , Microambiente TumoralRESUMO
Chronic arsenic exposure is associated with the increased risk of several types of cancer, among which, lung cancer is the most deadly one. Nuclear factor erythroid 2 like 1 (NFE2L1), a transcription factor belonging to CNC-bZIP family, regulates multiple important cellular functions in response to acute arsenite exposure. However, the role of NFE2L1 in lung cancer induced by chronic arsenite exposure is unknown. In this study, we firstly showed that chronic arsenite exposure (36 weeks) led to epithelial-mesenchymal transition (EMT) and malignant transformation in human bronchial epithelial cells (BEAS-2B). During the process of malignant transformation, the expression of long isoforms of NFE2L1 (NFE2L1-L) was elevated. Thereafter, BEAS-2B cells with NFE2L1-L stable knockdown (NFE2L1-L-KD) was chronically exposed to arsenite. As expected, silencing of NFE2L1-L gene strikingly inhibited the arsenite-induced EMT and the subsequent malignant transformation. Additionally, NFE2L1-L silencing suppressed the transcription of EMT-inducer SNAIL1 and increased the expression of E-cadherin. Conversely, NFE2L1-L overexpression increased SNAIL1 transcription but decreased E-cadherin expression. Collectively, our data suggest that NFE2L1-L promotes EMT by positively regulating SNAIL1 transcription, and is involved in malignant transformation induced by arsenite.