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1.
J Card Fail ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38614444

RESUMO

BACKGROUND: Prognosis of individuals with and without an established heart failure (HF) diagnosis and similarly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels is not well known. METHODS: CANVAS (Canagliflozin Cardiovascular Assessment Study) trial participants were stratified according to baseline NT-proBNP quartiles and history of HF at baseline. Adjusted event rates per 1000 patient-years follow-up for hospitalizations for HF (HHF), cardiovascular mortality, and kidney events were assessed, and hazard ratios (HR) were calculated using Cox proportional hazard models. RESULTS: Of the 3507 participants with available NT-proBNP concentrations, 471 (13.4%) had history of HF. Incidence rate per 1000 patient-years for HHF increased across the NT-proBNP quartiles in patients with (0, 2.8, 13.4 and 40.1; P<0.001) and without (1.8, 3.1, 6.0 and 19.1; P<0.001) HF, with significantly higher risk in patients with HF compared to those without (with HF: quartile 3 HR 9.28 [1.15, 75.05]; P=0.04; without HF: quartile-4 HR 4.86, [2.08, 11.35]; P<0.001). Similar higher risk for kidney events was seen in HF patients (with HF: quartile-4 HR 6.94, [2.66, 18.08]; P=0.001; without HF: quartile-4th HR 4.85 [3.02, 7.80]; P=0.001). Similar trends were seen for cardiovascular mortality. CONCLUSIONS: Among patients with type 2 diabetes and cardiovascular risk, an elevated NT-proBNP level was associated with worse HF and kidney outcomes in general regardless of history of HF, however presence of a clinical diagnosis of HF at baseline was associated with incrementally higher risk particularly in higher NT-proBNP quartiles.

2.
Front Neurosci ; 18: 1341986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533445

RESUMO

Introduction: In studies on consciousness detection for patients with disorders of consciousness, difference comparison of EEG responses based on active and passive task modes is difficult to sensitively detect patients' consciousness, while a single potential analysis of EEG responses cannot comprehensively and accurately determine patients' consciousness status. Therefore, in this paper, we designed a new consciousness detection paradigm based on a multi-stage cognitive task that could induce a series of event-related potentials and ERD/ERS phenomena reflecting different consciousness contents. A simple and direct task of paying attention to breathing was designed, and a comprehensive evaluation of consciousness level was conducted using multi-feature joint analysis. Methods: We recorded the EEG responses of 20 healthy subjects in three modes and reported the consciousness-related mean event-related potential amplitude, ERD/ERS phenomena, and the classification accuracy, sensitivity, and specificity of the EEG responses under different conditions. Results: The results showed that the EEG responses of the subjects under different conditions were significantly different in the time domain and time-frequency domain. Compared with the passive mode, the amplitudes of the event-related potentials in the breathing mode were further reduced, and the theta-ERS and alpha-ERD phenomena in the frontal region were further weakened. The breathing mode showed greater distinguishability from the active mode in machine learning-based classification. Discussion: By analyzing multiple features of EEG responses in different modes and stimuli, it is expected to achieve more sensitive and accurate consciousness detection. This study can provide a new idea for the design of consciousness detection methods.

3.
J Prosthet Dent ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493065

RESUMO

STATEMENT OF PROBLEM: A defective socket is common after tooth extraction in the esthetic zone, but whether an implant can be immediately placed in a defective socket is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to summarize relevant studies within the last 20 years on implant survival and changes in soft and hard tissues after immediate implant placement in esthetic areas with socket defects. MATERIAL AND METHODS: A search was conducted for the relevant studies in the PubMed/Medline, the Cochrane Library, Web of Science, and Embase databases from January 2000 to March 2022. The literature review, data retrieval, and judgment whether the included studies had a risk of bias were handled independently by 2 reviewers, and a single-arm meta-analysis was performed using a statistical software program. RESULTS: A total of 23 studies evaluating the immediate implant placement of 630 implants (9 studies without a flap and 14 studies with a flap) were included. A 98.1% implant survival rate (95% confidence interval (CI): 96.2%, 100.0%) was determined. Marginal bone loss (MBL) at 6, 12, and ≥24 months were 1.03 mm (95%CI: 1.02, 1.03), 0.72 mm (0.72, 0.73), and 1.15 mm (1.14, 1.16). Gingival recession at 12 months was 0.25 mm (95%CI: 0.17, 0.33). The pink esthetic score (PES) were 12.34 (95%CI: 12.16, 12.52) at 12 months and 12.58 (12.39, 12.76) at ≥24 months. CONCLUSIONS: Current evidence shows that immediate implant placement into defective sockets in esthetic areas is feasible. Immediate implant placement can have a relatively good therapeutic effect in terms of implant survival rate, MBL, gingival recession, and PES.

4.
BMC Ophthalmol ; 24(1): 126, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504225

RESUMO

BACKGROUND: This study evaluates the impact of corneal power on the accuracy of 14 newer intraocular lens (IOL) calculation formulas in cataract surgery. The aim is to assess how these formulas perform across different corneal curvature ranges, thereby guiding more precise IOL selection. METHODS: In this retrospective case series, 336 eyes from 336 patients who underwent cataract surgery were studied. The cohort was divided into three groups according to preoperative corneal power. Key metrics analyzed included mean prediction error (PE), standard deviation of PE (SD), mean absolute prediction error (MAE), median absolute error (MedAE), and the percentage of eyes with PE within ± 0.25 D, 0.50 D, ± 0.75 D, ± 1.00 D and ± 2.00 D. RESULTS: In the flat K group (Km < 43 D), VRF-G, Emmetropia Verifying Optical Version 2.0 (EVO2.0), Kane, and Hoffer QST demonstrated lower SDs (± 0.373D, ± 0.379D, ± 0.380D, ± 0.418D, respectively) compared to the VRF formula (all P < 0.05). EVO2.0 and K6 showed significantly different SDs compared to Barrett Universal II (BUII) (all P < 0.02). In the medium K group (43 D ≤ Km < 46 D), VRF-G, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS recorded lower MAEs (0.307D to 0.320D) than Olsen (OLCR) and Castrop (all P < 0.03), with RBF3.0 having the second lowest MAE (0.309D), significantly lower than VRF and Olsen (OLCR) (all P < 0.05). In the steep K group (Km ≥ 46D), RBF3.0, K6, and Kane achieved significantly lower MAEs (0.279D, 0.290D, 0.291D, respectively) than Castrop (all P < 0.001). CONCLUSIONS: The study highlights the varying accuracy of newer IOL formulas based on corneal power. VRF-G, EVO2.0, Kane, K6, and Hoffer QST are highly accurate for flat corneas, while VRF-G, RBF3.0, BUII, Karmona, K6, EVO2.0, Kane, and Pearl-DGS are recommended for medium K corneas. In steep corneas, RBF3.0, K6, and Kane show superior performance.


Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Facoemulsificação , Humanos , Estudos Retrospectivos , Córnea , Olho Artificial , Biometria , Refração Ocular , Óptica e Fotônica , Comprimento Axial do Olho
5.
NPJ Precis Oncol ; 8(1): 22, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287113

RESUMO

Triple-negative breast cancer (TNBC) is a highly aggressive cancer with distant metastasis. Accumulated evidence has demonstrated that exosomes are involved in TNBC metastasis. Elucidating the mechanism underlying TNBC metastasis has important clinical significance. In the present study, exosomes were isolated from clinical specimens and TNBC cell lines. Colony formation, EdU incorporation, wound healing, and transwell assays were performed to examine TNBC cell proliferation, migration, and metastasis. Macrophage polarization was evaluated by flow cytometry and RT-qPCR analysis of polarization markers. A mouse model of subcutaneous tumor was established for assessment of tumor growth and metastasis. RNA pull-down, RIP and Co-IP assays were used for analyzing molecular interactions. Here, we proved that high abundance of circRHCG was observed in exosomes derived from TNBC patients, and increased exosomal circRHCG indicated poor prognosis. Silencing of circRHCG suppressed TNBC cell proliferation, migration, and metastasis. TNBC cell-derived exosomes promoted M2 polarization via delivering circRHCG. Exosomal circRHCG stabilized BTRC mRNA via binding FUS and naturally enhanced BTRC expression, thus promoting the ubiquitination and degradation of TFEB in THP-1 cells. In addition, knockdown of BTRC or overexpression of TFEB counteracted exosomal circRHCG-mediated facilitation of M2 polarization. Furthermore, exosomal circRHCG promoted TNBC cell proliferation and metastasis by facilitating M2 polarization. Knockdown of circRHCG reduced tumor growth, metastasis, and M2 polarization through the BTRC/TFEB axis in vivo. In summary, exosomal circRHCG promotes M2 polarization by stabilizing BTRC and promoting TFEB degradation, thereby accelerating TNBC metastasis and growth. Our study provides promising therapeutic strategies against TNBC.

6.
Eye (Lond) ; 38(3): 594-599, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752342

RESUMO

OBJECTIVES: To identify factors associated with progressive anisometropia after bilateral intraocular lens (IOL) implantation in patients with pediatric cataract. METHODS: Clinical and standardized questionnaire data were collected for Sixty-eight patients with pediatric cataract (136 eyes) who underwent bilateral IOL implantation and at least 1 year of follow-up. Univariate and multivariate linear regression models were used to identify factors associated with postoperative anisometropia. RESULTS: The median age at IOL implantation was 3.2 years (range: 1-12.4 years), and median follow-up time was 5.7 years (range: 1.1-14 years). At 1 month postoperatively and at the last follow-up, there were 19 (27%) and 31 (46%) cases of anisometropia ≥1 D, 9 (13%) and 15 (22%) cases of anisometropia ≥2 D, and 2 (3%) and 9 (13%) cases of anisometropia ≥3 D, respectively. Compared with 1 month postoperatively, the amount of anisometropia increased in 45 (67%) patients. Greater anisometropia one year or more after bilateral IOL implantation was associated with larger intereye difference in IOL power (P = 0.032, 95%CI 0.013 to 0.285), intereye difference in preoperative axial length (P = 0.018, 95%CI -1.247 to -0.123), presence of strabismus (P = 0.017, 95%CI 0.063-0.601), anisometropia at 1 month postoperatively (P = 0.001, 95%CI 0.126-0.478), and intereye difference in axial length at the last follow-up (P = 0.047, 95%CI 0.005-0.627). CONCLUSION: Anisometropia might progress after bilateral IOL implantation in patients with pediatric cataract. Greater intereye difference in IOL power, presence of strabismus might increase the potential of progressive anisometropia.


Assuntos
Anisometropia , Extração de Catarata , Catarata , Lentes Intraoculares , Estrabismo , Humanos , Criança , Lactente , Pré-Escolar , Extração de Catarata/efeitos adversos , Implante de Lente Intraocular , Anisometropia/etiologia , Acuidade Visual , Catarata/complicações , Seguimentos
7.
Nanomaterials (Basel) ; 13(23)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38063762

RESUMO

Environmental pollution has been decreased by using photocatalytic technology in conjunction with solar energy. An efficient method to obtain highly efficient photocatalysts is to build heterojunction photocatalysts by combining graphitic carbon nitride (g-C3N4) with layered double hydroxides (LDHs). In this review, recent developments in LDH/g-C3N4 heterojunctions and their applications for organic pollutant removal are systematically exhibited. The advantages of LDH/g-C3N4 heterojunction are first summarized to provide some overall understanding of them. Then, a variety of approaches to successfully assembling LDH and g-C3N4 are simply illustrated. Last but not least, certain unmet research needs for the LDH/g-C3N4 heterojunction are suggested. This review can provide some new insights for the development of high-performance LDH/g-C3N4 heterojunction photocatalysts. It is indisputable that the LDH/g-C3N4 heterojunctions can serve as high-performance photocatalysts to make new progress in organic pollutant removal.

8.
Materials (Basel) ; 16(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38138811

RESUMO

The indirect tensile test plays a crucial role in experimental investigations of brittle material properties. In this study, a mechanical analysis model of the rectangular test block is established based on the theory of elastic mechanics for the characteristics of the indirect tensile test. The theoretical solution of the triangular series is derived for the rectangular test block under the locally distributed load. The finite element simulation results and splitting test results were compared with the theoretical results. The results of the study verify the accuracy of the theoretical solutions. Based on the proposed analytical solution, the effects of loading width and length-to-height ratio (h/l) of local loading on the measured tensile strength of test block are discussed. The results demonstrate that the tensile strength of the test block increases as the loading width expands, and the rate of growth in the recorded tensile strength gradually stabilizes. The variation in loading width affects the location of crack initiation points during the concrete test block splitting tests. When the loading width exceeds 6% of the side length of test block, the cracking point is positioned at the center of test block, ensuring the effectiveness of the splitting test. As the length-to-height ratio of the test block increases, there is a general upward trend in the measured tensile strength. When h/l < 0.6, the measured tensile strength initially increases before decreasing. However, when h/l > 0.6, the measured tensile strength consistently increases, with the rate of increase gradually diminishing until it stabilizes. The length-to-height ratio also significantly influences the location of the cracking point in the test block. As the length-to-height ratio increases, the cracking point initially shifts from around the center to the central point and then further from the center toward the edge. To ensure that the location of the crack initiation point is in the center of the specimen and that the tensile strength is close to the measured result, the length to height ratio can be chosen at around 0.85.

9.
Nanomaterials (Basel) ; 13(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37999317

RESUMO

Carbon nanomaterial is widely used in structural health monitoring due to the advantage of sensitivity and good mechanical properties. This study presents a novel approach employing carbon nanocomposite materials (CNMs) to characterize deformation and damage evolution in physical modelling. As the primary measurement method, the CNM is used to investigate the deformation characteristics of a 200-400 m thick sandstone bed at a 1 km deep longwall mine. The sandstone unit is identified as an ultra-thick key stratum (UTKS), with its thicknesses varying across different mining panels of the UTKS. The results of CNM monitoring show that the UTKS remains stable even after a consecutive excavation of 900 m in width. This stability impedes the upward propagation of overlying strata failure, leading to minimal surface subsidence. The study demonstrates the huge potential of CNM in the mining area, which can be useful for investigating material damage in physical modelling studies. The findings suggest that the cumulative extraction width in individual mining areas of the mine should be controlled to avoid a sudden collapse of the UTKS, and that special attention should be paid to where the UTKS's thickness changes substantially. The substantial variation in UTKS thickness significantly impacts the pattern of overburden subsidence.

10.
Int J Mol Sci ; 24(19)2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37833951

RESUMO

The protein tyrosine phosphatase PTPN22 inhibits T cell activation by dephosphorylating some essential proteins in the T cell receptor (TCR)-mediated signaling pathway, such as the lymphocyte-specific protein tyrosine kinase (Lck), Src family tyrosine kinases Fyn, and the phosphorylation levels of Zeta-chain-associated protein kinase-70 (ZAP70). For the first time, we have successfully produced PTPN22 CS transgenic mice in which the tyrosine phosphatase activity of PTPN22 is suppressed. Notably, the number of thymocytes in the PTPN22 CS mice was significantly reduced, and the expression of cytokines in the spleen and lymph nodes was changed significantly. Furthermore, PTPN22 CS facilitated the positive and negative selection of developing thymocytes, increased the expression of the TCRαß-CD3 complex on the thymus cell surface, and regulated their internalization and recycling. ZAP70, Lck, Phospholipase C gamma1(PLCγ1), and other proteins were observed to be reduced in PTPN22 CS mouse thymocytes. In summary, PTPN22 regulates TCR internalization and recycling via the modulation of the TCR signaling pathway and affects TCR expression on the T cell surface to regulate negative and positive selection. PTPN22 affected the development of the thymus, spleen, lymph nodes, and other peripheral immune organs in mice. Our study demonstrated that PTPN22 plays a crucial role in T cell development and provides a theoretical basis for immune system construction.


Assuntos
Receptores de Antígenos de Linfócitos T , Quinases da Família src , Animais , Camundongos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Camundongos Transgênicos , Fosforilação , Proteínas Tirosina Fosfatases/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Quinases da Família src/metabolismo
11.
J Agric Food Chem ; 71(42): 15855-15862, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37831971

RESUMO

In this paper, a high-performance ion exclusion chromatographic (ICE) method was developed and applied for monitoring maleic hydrazide (MH) translocation in complex potato plant tissue and tuber matrices. After middle leaf uptake, most MH was trapped and dissipated in the middle leaf, and the rest was transported to other parts mainly through the phloem. Soil absorption significantly reduced the uptake efficiency of the root system, in which MH was partitioned to dissipate in root protoplasts or transfer through the xylem and persisted in the plant. Tuber uptake enabled MH to remain in the flesh and maintain stable levels under storage conditions, but during germination, MH was translocated from the flesh to the growing buds, where it dissipated through the short-day photoperiodic regime. The results demonstrated successful application of the ICE method and provided necessary insights for real-time monitoring of MH translocation behavior to effectively improve potato edible safety.


Assuntos
Hidrazida Maleica , Solanum tuberosum , Hidrazida Maleica/análise , Tubérculos/química , Plantas , Cromatografia em Gel
12.
Neoplasia ; 45: 100942, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37839160

RESUMO

BACKGROUND: Tumor antigenicity and efficiency of antigen presentation jointly influence tumor immunogenicity, which largely determines the effectiveness of immune checkpoint blockade (ICB). However, the role of altered antigen processing and presentation machinery (APM) in breast cancer (BRCA) has not been fully elucidated. METHODS: A series of bioinformatic analyses and machine learning strategies were performed to construct APM-related gene signatures to guide personalized treatment for BRCA patients. A single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) were combined to screen for BRCA-specific APM-related genes. The non-negative matrix factorization (NMF) algorithm was used to divide the cohort into different clusters and the fgsea algorithm was applied to investigate the altered signaling pathways. Random survival forest (RSF) and the least absolute shrinkage and selection operator (Lasso) Cox regression analysis were combined to construct an APM-related risk score (APMrs) signature to predict overall survival. Furthermore, a nomogram and decision tree were generated to improve predictive accuracy and risk stratification for individual patients. Based on Tumor Immune Dysfunction and Exclusion (TIDE) method, random forest (RF) and Lasso logistic regression model were combined to establish an APM-related immunotherapeutic response score (APMis). Finally, immune infiltration, immunomodulators, mutational patterns, and potentially applicable drugs were comprehensively analyzed in different APM-related risk groups. IHC staining was used to assess the expression of APM-related genes in clinical samples. RESULTS: In this study, APMrs and APMis showed favorable performances in risk stratification and therapeutic prediction for BRCA patients. APMrs exhibited more powerful prognostic capacity and accurate survival prediction compared to conventional clinicopathological features. APMrs was closely associated with distinct mutational patterns, immune cell infiltration and immunomodulators expression. Furthermore, the two APM-related gene signatures were independently validated in external cohorts with prognosis or immunotherapeutic responses. Potential applicable drugs and targets were mined in the APMrs-high group. APM-related genes were further validated in our in-house samples. CONCLUSION: The APM-related gene signatures established in our study could improve the personalized assessment of survival risk and guide ICB decision-making for BRCA patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Oncogenes , Mama , Biologia Computacional , Fatores Imunológicos , Prognóstico
13.
Herz ; 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37721628

RESUMO

BACKGROUND: This study aimed to screen out the potential diagnostic biomarkers for atherosclerosis (AS). METHODS: We downloaded the gene expression profiles GSE66360, GSE28829, GSE41571, GSE71226, and GSE100927 from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the "limma" package in R. Weighted gene co-expression network analysis (WGCNA) was applied to reveal the correlation between genes in different samples. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The interaction pairs of proteins were retained by the STRING database, and the protein-protein interaction (PPI) network was visualized with the hub genes. Finally, the R packages "ggpubr" and "preprocessCore" were used to analyze immune cell infiltration. RESULTS: In total, 40 overlapping genes both in GSE66360 and GSE28829 were found to be related to the occurrence of AS. Further, the top 10 network hub genes including TYROBP, CSF1R, TLR2, CD14, CCL4, FCER1G, CD163, TREM1, PLEK, and C5AR1 were identified as significant key genes. Moreover, four genes (TYROBP, CSF1R, FCGR1B, and CD14) were verified that could efficiently diagnose AS. Finally, the gene TYROBP was found to have a strong correlation with immune-infiltrating cells. CONCLUSION: Our study identified four genes (TYROBP, CSF1R, FCGR1B, and CD14) that may be effective biomarkers for AS, with the potential to guide the clinical diagnosis of AS.

14.
Small ; 19(52): e2304989, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37626453

RESUMO

The calixarenes are ideal building blocks for constructing photocatalytic covalent organic frameworks (COFs), owing to their electron-rich and bowl-shaped π cavities that endow them with electron-donating and adsorption properties. However, the synthesis and structural confirmation of COFs based on calixarenes are still challenging due to their structural flexibility and conformational diversity. In this study, a calix[4]arene-derived 2D COF is synthesized using 5,11,17,23-tetrakis(p-formyl)-25,26,27,28-tetrahydroxycalix[4]arene (CHO-C4A) as the electron donor and 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) as the acceptor. The powder X-ray diffraction data and theoretical simulation of crystal structure indicate that COF-C4A-BTD exhibits high crystallinity and features a non-interpenetrating undulating 2D layered structure with AA-stacking. The density functional theory theoretical calculation, transient-state photocurrent tests, and electrochemical impedance spectroscopy confirm the intramolecular charge transfer behavior of COF-C4A-BTD with a donor-acceptor structure, leading to its superior visible-light-driven photocatalytic activity. COF-C4A-BTD exhibits a narrow band gap of 1.99 eV and a conduction band energy of -0.37 V versus normal hydrogen electrode. The appropriate energy band structure can facilitate the participation of ·O2- and h+ . COF-C4A-BTD demonstrates high efficacy in removing organic pollutants, such as bisphenol A, rhodamine B, and methylene blue, with removal rates of 66%, 85%, and 99% respectively.

15.
Environ Sci Pollut Res Int ; 30(43): 96689-96700, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37578585

RESUMO

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. Metal exposure is an emerging factor affecting the risk of GDM. However, the effects of metal mixture on GDM and key metals within the mixture remain unclear. This study was aimed at investigating the association between metal mixture during early pregnancy and the risk of GDM using four statistical methods and further at identifying the key metals within the mixture associated with GDM. A nested case-control study including 128 GDM cases and 318 controls was conducted in Beijing, China. Urine samples were collected before 13 gestational weeks and the concentrations of 13 metals were measured. Single-metal analysis (unconditional logistic regression) and mixture analyses (Bayesian kernel machine regression (BKMR), quantile g-computation, and elastic-net regression (ENET) models) were applied to estimate the associations between exposure to multiple metals and GDM. Single-metal analysis showed that Ni was associated with lower risk of GDM, while positive associations of Sr and Sb with GDM were observed. Compared with the lowest quartile of Ni, the ORs of GDM in the highest quartiles were 0.49 (95% CI 0.24, 0.98). In mixture analyses, Ni and Mg showed negative associations with GDM, while Co and Sb were positively associated with GDM in BKMR and quantile g-computation models. No significant joint effect of metal mixture on GDM was observed. However, interestingly, Ni was identified as a key metal within the mixture associated with decreased risk of GDM by all three mixture methods. Our study emphasized that metal exposure during early pregnancy was associated with GDM, and Ni might have important association with decreased GDM risk.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/epidemiologia , Estudos de Casos e Controles , Teorema de Bayes , Metais , Modelos Logísticos
16.
Drug Resist Updat ; 69: 100974, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37230023

RESUMO

AIMS: Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. METHODS: Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. RESULTS: Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. CONCLUSIONS: GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Apoptose , Ferro/metabolismo , Ferro/uso terapêutico , Catálise , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/uso terapêutico
17.
Front Neurosci ; 17: 1145051, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250401

RESUMO

Rhythmic visual cues can affect the allocation of cognitive resources during gait initiation (GI) and motor preparation. However, it is unclear how the input of rhythmic visual information modulates the allocation of cognitive resources and affects GI. The purpose of this study was to explore the effect of rhythmic visual cues on the dynamic allocation of cognitive resources by recording electroencephalographic (EEG) activity during exposure to visual stimuli. This study assessed event-related potentials (ERPs), event-related synchronization/desynchronization (ERS/ERD), and EEG microstates at 32 electrodes during presentation of non-rhythmic and rhythmic visual stimuli in 20 healthy participants. The ERP results showed that the amplitude of the C1 component was positive under exposure to rhythmic visual stimuli, while the amplitude of the N1 component was higher under exposure to rhythmic visual stimuli compared to their non-rhythmic counterparts. Within the first 200 ms of the onset of rhythmic visual stimuli, ERS in the theta band was highly pronounced in all brain regions analyzed. The results of microstate analysis showed that rhythmic visual stimuli were associated with an increase in cognitive processing over time, while non-rhythmic visual stimuli were associated with a decrease. Overall, these findings indicated that, under exposure to rhythmic visual stimuli, consumption of cognitive resources is lower during the first 200 ms of visual cognitive processing, but the consumption of cognitive resources gradually increases over time. After approximately 300 ms, cognitive processing of rhythmic visual stimuli consumes more cognitive resources than processing of stimuli in the non-rhythmic condition. This indicates that the former is more conducive to the completion of gait-related motor preparation activities, based on processing of rhythmic visual information during the later stages. This finding indicates that the dynamic allocation of cognitive resources is the key to improving gait-related movement based on rhythmic visual cues.

18.
Int J Biol Sci ; 19(6): 1713-1730, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063427

RESUMO

BAP31 expression was robustly decreased in obese white adipose tissue (WAT). To investigate the roles of BAP31 in lipid metabolism, adipocyte-specific conditional knockout mice (BAP31-ASKO) were generated. BAP31-ASKO mice grow normally as controls, but exhibited reduced lipid accumulation in WAT. Histomorphometric analysis reported increased adipocyte size in BAP31-ASKO mice. Mouse embryonic fibroblasts (MEFs) were induced to differentiation to adipocytes, showed reduced induction of adipogenic markers and attenuated adipogenesis in BAP31-deficient MEFs. BAP31-deficiency inhibited fasting-induced PKA signaling activation and the fasting response. ß3-adrenergic receptor agonist-induced lipolysis also was reduced, accompanied by reduced free-fatty acids and glycerol release, and impaired agonist-induced lipolysis from primary adipocytes and adipose explants. BAP31 interacts with Perilipin1 via C-terminal cytoplasmic portion on lipid droplets (LDs) surface. Depletion of BAP31 repressed Perilipin1 proteasomal degradation, enhanced Perilipin1 expression and blocked LDs degradation, which promoted LDs abnormal growth and supersized LDs formation, resulted in adipocyte expansion, thus impaired insulin signaling and aggravated pro-inflammation in WAT. BAP31-deficiency increased phosphatidylcholine/phosphatidylethanolamine ratio, long chain triglycerides and most phospholipids contents. Overall, BAP31-deficiency inhibited adipogenesis and lipid accumulation in WAT, decreased LDs degradation and promoted LDs abnormal growth, pointing the critical roles in modulating LDs dynamics and homeostasis via proteasomal degradation system in adipocytes.


Assuntos
Adipogenia , Lipólise , Animais , Camundongos , Adipogenia/genética , Fibroblastos/metabolismo , Gotículas Lipídicas/metabolismo , Lipólise/genética , Obesidade/metabolismo , Triglicerídeos/metabolismo , Perilipina-1/metabolismo
19.
Cell Prolif ; 56(11): e13477, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37057399

RESUMO

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4+ cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation.


Assuntos
Cristalino , Humanos , Cristalino/metabolismo , Epitélio , Células Epiteliais/metabolismo , Olho , Diferenciação Celular , Análise de Sequência de RNA
20.
Brain Sci ; 13(3)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36979243

RESUMO

Visuospatial selective attention can focus attention on a certain spatial area and rationally allocate attentional resources during visual target perception. Previous studies investigated the behavioral advantages of subjects when the target appeared in the upper and lower visual fields. However, the neurophysiological characteristics of the brain are not clear, and there is a lack of comprehensive analysis of the external behavior and the internal neurophysiological characteristics. We designed two task paradigms containing a spatial location orientation task and a visual search task. We used event-related potentials (ERP) components (P1 and P2) and electroencephalogram (EEG) rhythms (theta and alpha) to analyze the attention level and allocation of attention resources of the brain. The results showed that when the target appeared in the lower visual field in the spatial location orientation task, subjects consumed fewer attention resources and demonstrated better behavioral performance. In the visual search task, when the target appeared in the upper left visual field, subjects could better mobilize attention resources and behaved more advantageously. The study provides a basis for the design of the target in the upper and lower visual fields in the rehabilitation task, especially for stroke patients with low attention levels due to attention disorders such as spatial attention deficit.

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