RESUMO

Phoxim, extensively utilized in agriculture as an organothiophosphate insecticide, has the potential to cause neurotoxicity and pose human health hazards. In this study, an electrochemical enzyme biosensor based on Ti3C2 MXene/MoS2@AuNPs/AChE was constructed for the sensitive detection of phoxim. The two-dimensional multilayer structure of Ti3C2 MXene provides a robust framework for MoS2, leading to an expansion of the specific surface area and effectively preventing re-stacking of Ti3C2 MXene. Additionally, the synergistic effect of self-reduced grown AuNPs with MoS2 further improves the electrical conductivity of the composites, while the robust framework provides a favorable microenvironment for immobilization of enzyme molecules. Ti3C2 MXene/MoS2@AuNPs electrochemical enzyme sensor showed a significant response to phoxim in the range of 1 × 10-13 M to 1 × 10-7 M with a detection limit of 5.29 × 10-15 M. Moreover, the sensor demonstrated excellent repeatability, reproducibility, and stability, thereby showing its promising potential for real sample detection.

Assuntos

Técnicas Biossensoriais , Técnicas Eletroquímicas , Frutas , Ouro , Nanopartículas Metálicas , Nanocompostos , Compostos Organotiofosforados , Titânio , Ouro/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Nanocompostos/química , Frutas/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/instrumentação , Compostos Organotiofosforados/análise , Titânio/química , Limite de Detecção , Contaminação de Alimentos/análise , Molibdênio/química , Inseticidas/análise , Inseticidas/química , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/química

RESUMO

The rapid detection of fertilizer nutrient information is a crucial element in enabling intelligent and precise variable fertilizer application. However, traditional detection methods possess limitations, such as the difficulty in quantifying multiple components and cross-contamination. In this study, a rapid detection method was proposed, leveraging Raman spectroscopy combined with machine learning, to identify five types of fertilizers: K2SO4, (CO(NH2)2, KH2PO4, KNO3, and N:P:K (15-15-15), along with their concentrations. Qualitative and quantitative models of fertilizers were constructed using three machine learning algorithms combined with five spectral preprocessing methods. Two variable selection methods were used to optimize the quantitative model. The results showed that the classification accuracy of the five fertilizer solutions obtained by random forest (RF) was 100 %. Moreover, in terms of regression, partial least squares regression (PLSR) outperformed extreme learning machine (ELM) and least squares support vector machine (LSSVM), yielding prediction Rp2 within the range of 0.9843-0.9990 and a root mean square error in the range of 0.0486-0.1691. In addition, this study evaluated the impact of different water types (deionized water, well water, and industrial transition water) on the detection of fertilizer information via Raman spectroscopy. The results showed that while different water types did not notably affect the identification of fertilizer nutrients, they did exert a pronounced effect on the quantification of concentrations. This study highlights the efficacy of combining Raman spectroscopy with machine learning in detecting fertilizer nutrients and their concentration information effectively.

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Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) are therapeutic agents for advanced and metastatic non-small cell lung cancer (NSCLC) with high clinical antitumor efficacy. However, immune-related adverse events occur in 20% of these patients and often requiring treatment with immunosuppressive agents, such as corticosteroids. Consequently, this may increase the risk of patients to opportunistic infections. Pneumocystis jirovecii pneumonia (PJP), a rare but serious opportunistic infection typically observed in patients with human immunodeficiency virus, can also occur in cancer patients undergoing long-term glucocorticoid treatment. CASE SUMMARY: We report a case of a 56-year-old male with squamous NSCLC treated with triplimab combined with paclitaxel, carboplatin, and radical thoracic radiation therapy. Following this regimen, he developed acute kidney injury (AKI) with elevated creatinine levels. After concurrent radical chemoradiotherapy ended, he developed a grade 3 immune-related AKI. High-dose corticosteroids were administered to treat AKI, and renal function gradually recovered. Corticosteroids were reduced to a dose of 10 mg prednisone equivalent daily eight weeks later; however, he developed severe pneumonia with spontaneous pneumothorax. Next-generation sequencing of the bronchoscopic lavage revealed PJP co-infection with herpes simplex virus 1 and cytomegalovirus. The inflammation was more severe in areas exposed to radiation. Piperacillin-tazobactam, acyclovir, sulfamethoxazole, and trimethoprim were used to control the infection. The patient recovered, and immunotherapy was terminated. CONCLUSION: PJP is rare but can occur in patients with ICI adverse events and should be differentiated from tumor progression or immune-related adverse events. Thoracic radiation may increase risk, necessitating careful monitoring and prevention.

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Cadmium (Cd) has garnered significant attention due to reproductive toxicity in inducing ferroptosis. However, the specific mechanisms underlying Cd-induced germ cell ferroptosis remain poorly understood. This study aimed to systematically explore the molecular mechanisms of germ cell ferroptosis by investigating differential changes in transcription factors and proteins in male mice treated orally with CdCl2 (0.5 g/L) reaching postnatal day 60, alongside Leydig cell (TM3) and Sertoli cell (TM4) lines. Results demonstrated that Cd exposure led to increased iron overload and oxidative stress in mouse testes, disrupted intracellular mitochondrial morphology characteristic of ferroptosis. RNA sequencing revealed significant upregulation of Atf3 and Hmox1 in Cd-exposed germ cells, along with increased expression of ATF3 and HO-1. Intervention in ferroptosis or HO-1 effectively rescued cells from Cd-induced mortality by breaking the detrimental cycle between lipid peroxidation and HO-1 activation. Further findings showed that NRF2 and HO-1 expression was notably elevated upon ATF3 overexpression in TM3 and TM4 cells, activating the Keap1-Nrf2 pathway and triggering ferroptosis in testes, whereas NRF2 and HO-1 expression levels were reversed when ATF3 was silenced. This study provides novel insights into ATF3-mediated NRF2/HO-1 signaling in Cd-induced mitochondrial ferroptosis in testes, shedding light on the mechanisms underlying Cd-induced ferroptosis and testicular injury.

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Background: The HALP score, comprising hemoglobin, albumin, lymphocyte, and platelet levels, serves as an indicator of both nutritional and inflammatory status. However, its correlation with all-cause and cause-specific mortality among cancer survivors remains unclear. Therefore, this study aims to investigate the relationship between HALP scores and mortality outcomes in this population. Method: We extracted cohort data spanning ten cycles (1999-2018) from the U.S. National Health and Nutrition Examination Survey (NHANES). Mortality rates, determined using the National Death Index (NDI) as of December 31, 2019, were assessed. Weighted multivariate logistic regression analyzed the association between HALP scores and cancer prevalence. Kaplan-Meier analyses and weighted multivariate-adjusted Cox analyses investigated the link between HALP scores and all-cause and cause-specific mortality in cancer survivors. Restricted cubic spline (RCS) analysis was employed to assess nonlinear relationships. Furthermore, multi-parametric subgroup analyses were conducted to ensure the robustness of the results. Results: Our study included 41,231 participants, of whom 3,786 were cancer survivors (prevalence: 9.5%). Over a median follow-up of 91 months (range: 51-136), we observed 1,339 deaths, including 397 from cancer, 368 from cardio-cerebrovascular disease, and 105 from respiratory disease. Elevated HALP scores showed a consistent association with reduced cancer incidence (P for trend <0.001). In multivariable-adjusted Cox regression analyses, HALP scores were significantly inversely associated with all-cause mortality, cancer mortality, cardio-cerebrovascular disease mortality, and respiratory disease mortality in cancer survivors (P for trend < 0.05). Nonlinear relationships between HALP scores and all-cause and cause-specific mortality in cancer survivors were evident through RCS regression modeling (P for nonlinearity < 0.01). Kaplan-Meier analyses demonstrated that higher HALP scores were indicative of a poorer prognosis. Conclusion: Our findings indicate a notable inverse correlation between HALP scores and both all-cause and cause-specific mortality among cancer survivors.

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BACKGROUND: Metabolic disorder, malnutrition and inflammation are involved and interplayed in the mechanisms of heart failure with preserved ejection fraction (HFpEF). We aimed to construct a Metabolism-malnutrition-inflammation score (MIS) to predict the risk of death in patients with HFpEF. METHODS: We included patients diagnosed with HFpEF and without infective or systemic disease. 20 biomarkers were filtered by the Least absolute shrinkage and selection operator (Lasso)-Cox regression. 1000 times bootstrapping datasets were generated to select biomarkers that appeared above 95% frequency in repetitions to construct the MIS. RESULTS: Among 1083 patients diagnosed with HFpEF, 342 patients (31.6%) died during a median follow-up period of 2.5 years. The MIS was finally constructed based on 6 biomarkers, they were albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), high-sensitivity C-reactive protein (hs-CRP), lymphocytes, triiodothyronine (T3) and uric acid (UA). Incorporating MIS into the basic predictive model significantly increased both discrimination (∆C-index = 0.034, 95% CI 0.013-0.050) and reclassification (IDI, 6.6%, 95% CI 4.0%-9.5%; NRI, 22.2% 95% CI 14.4%-30.2%) in predicting all-cause mortality. In the time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) for the MIS was 0.778, 0.782 and 0.772 at 1, 3, and 5 years after discharge in the cross-validation sets. The MIS was independently associated with all-cause mortality (hazard ratio: 1.98, 95% CI [1.70-2.31], P < 0.001). CONCLUSIONS: A risk score derived from 6 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF, providing potential individualized management strategies for patients with HFpEF.

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BACKGROUND: Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM: To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS: Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS: From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION: Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

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Introduction: Premature ovarian insufficiency (POI) has affected about 3.7% of women of reproductive age and is a major factor contributing to infertility. Bushen Huoxue formula (BHF), a traditional Chinese medicine prescription, is clinically used to treat POI in China. This study aims to investigate the potential mechanisms of BHF in combating POI using corticosterone-induced rats and palmitic acid (PA)-challenged human ovarian granulosa cells (GCs). Methods: Initially, ultra performance liquid chromatography tandem mass spectrometry was employed to analyze the components of BHF. The pharmacodynamic parameters evaluated included body weight, ovaries index, and serum hormone in rats. Follicle numbers were observed using H&E staining. Additionally, PCNA and TUNEL staining were used to assess GCs proliferation and apoptosis, respectively. Lipid accumulation and ROS levels were examined using Oil Red O and ROS staining. Protein expressions were determined by western blot. To probe mechanisms, cell viability and E2 levels in BHF-treated, PA-stimulated GCs were determined using MTT and ELISA, respectively. Cell apoptosis and ROS levels were assessed using TUNEL and ROS staining. Proteins related to lipid metabolism and autophagy in PA-stimulated GCs were studied using agonists. Results: Our results shown that BHF effectively normalized serum hormone levels, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH). Concurrently, BHF also significantly reduced follicular atresia and promoted cell proliferation while inhibiting apoptosis in POI rats. Furthermore, BHF mitigated ovarian lipid accumulation by modulating lipid metabolism, which included reducing lipid synthesis (expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α), increasing lipid catabolism (expression of adipose triglyceride lipase), and enhancing lipid oxidation (expression of carnitine palmitoyl transferase 1A). Mechanistically, the therapeutic effects of BHF on POI were linked with alleviation of lipid deposition-induced reactive oxygen species (ROS) accumulation and excessive autophagy, corroborating the results in PA-challenged GCs. After treatment with elesclomol (a ROS inducer) and rapamycin (an autophagy inducer) in GCs, the effects of BHF were almost counteracted under model conditions. Conclusion: These findings suggest that BHF alleviates the symptoms of POI by altering lipid metabolism and reducing lipid accumulation-induced ROS and autophagy, offering evidence for BHF's efficacy in treating POI clinically.

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Tin-oxo clusters are increasingly recognized as promising materials for nanolithography technology due to their unique properties, yet their structural impacts on lithography performance remain underexplored. This work explores the structural impacts of heterometal strategies on the performance of tin-oxo clusters in nanolithography, focusing on various metal dopants and their coordination geometries. Specifically, SnOC-1(In), SnOC-1(Al), SnOC-1(Fe), and SnOC-2 were synthesized and characterized. These clusters demonstrate excellent solubility, dispersibility, and stability, facilitating the preparation of high-quality films via spin-coating for lithographic applications. Notably, this work innovatively employs nano-infrared (nano-IR), neutron reflectivity (NR), and X-ray reflectivity (XRR) measurements to confirm film homogeneity. Upon electron beam lithography (EBL), all four materials achieve 50 nm line patterns, with SnOC-1(In) demonstrating the highest lithography sensitivity. This enhanced sensitivity is attributed to indium dopants, which possess superior EUV absorption capabilities and unsaturated coordination environments. Further studies on exposure mechanisms indicated that Sn-C bond cleavage generates butyl free radicals, promoting network formations that induce solubility-switching behaviors for lithography. These findings underscore the efficacy of tailored structural design and modulation of cluster materials through heterometal strategies in enhancing lithography performance, offering valuable insights for future material design and applications.

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OBJECTIVE: To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. METHODS: 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. RESULTS: 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0-0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256-25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. CONCLUSION: A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

Assuntos

Fibrilação Atrial , Criocirurgia , Átrios do Coração , Veias Pulmonares , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Criocirurgia/métodos , Criocirurgia/efeitos adversos , Átrios do Coração/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Veias Pulmonares/cirurgia , Idoso , Ablação por Cateter/métodos , Ablação por Cateter/efeitos adversos , Resultado do Tratamento

RESUMO

OBJECTIVES: This study aimed to evaluate the impact of different collagen membran fixation protocols on the volume stability in horizontal ridge augmentation in the aesthetic area. METHODS: A total of 48 patients with 65 augmented sites were included in this study. Implants were placed in the aesthetic region, and simultaneous guided bone regeneration (GBR) surgery was performed for horizontal ridge augmentation. Participants were divided into four groups, each comprising 12 patients, based on different absorbable collagen membrane fixation protocols. Group 1: without fixation; Group 2: fixation with absorbable sutures; Group 3: fixation with titanium pins; Group 4: fixation with titanium pins and absorbable sutures. Cone beam computed tomography (CBCT) was performed immediately after surgery and at 6 months post-surgery, respectively. The horizontal thickness of the augmented region was analyzed for volume stability at the implant shoulder (H0) and 1-5 mm apical to the implant shoulder (H1-H5). Changes in labial thickness during bone healing were calculated as absolute values (mm) and relative values (%). RESULTS: After 6 months of bone healing, horizontal thickness was significantly reduced at all levels (H0-H5) in all groups compared to immediate post-surgery results (p < 0.05). At H1-H5, horizontal bone loss in group 1 was significantly higher than in the other three groups (p < 0.05). Group 4 exhibited significantly less horizontal bone loss compared to group 2 at H0-H2 (p < 0.05) and group 4 compared to group 3 at H0-H1 (p < 0.05). No significant difference in horizontal bone loss between groups 2 and 3 was detected at H0-H5 (p > 0.05). CONCLUSION: Guided bone regeneration in the aesthetic area with additional membrane fixation demonstrated superior volume stability of the augmented region compared to cases without fixation. There was no significant difference in bone volume stability between membrane fixation with titanium pins and fixation with absorbable sutures. However, the combined use of pins and absorbable sutures yielded superior volume stability.

RESUMO

BACKGROUND AND AIMS: Evidence is increasingly suggesting that shift work is a risk factor for cardiometabolic disease. However, the causal relationship between shift work and cardiometabolic disease is not yet fully understood. In this study, we employed two-sample Mendelian randomization (MR) to investigate the causal relationship between shift work and the risk of cardiometabolic outcomes. METHODS AND RESULTS: Genome-wide association study (GWAS) statistics for shift work were obtained from the UK Biobank. Mendelian randomization analyses were conducted to explore the causal effects of shift work on cardiometabolic outcomes, using single-nucleotide polymorphisms (SNPs) as instrumental variables. The results suggested a causal effect between shift work and body mass index, body fat percentage, triglycerides, high-density lipoprotein, type 2 diabetes, hypertension, and cardiorespiratory fitness. After correcting for multiple tests, only body mass index and high-density lipoprotein showed significant associations. No causal effects were found between shift work and overweight, obesity, total cholesterol, low-density lipoprotein, fasting glucose, 2-h glucose, fasting insulin, coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, or ischemic stroke. CONCLUSION: This MR study provides genetic evidence for a suggestive causal link between shift work and certain cardiometabolic outcomes. Our research may have the significance of providing insight into public hygiene to improve the understanding of shift work and cardiometabolic disease risk. Further experimental studies are needed to confirm our findings.

RESUMO

OBJECTIVE: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. PATIENTS AND METHODS: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. RESULTS: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470-21.569), PR (OR = 7.690, 95%CI: 3.974-16.129, Her-2 (OR = 10.489, 95%CI: 2.779-23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031-0.377 were significant independent risk factors affecting AR expression. CONCLUSIONS: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

Assuntos

Biomarcadores Tumorais , Neoplasias da Mama , Recidiva Local de Neoplasia , Receptor ErbB-2 , Receptores Androgênicos , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Receptores Androgênicos/metabolismo , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Prognóstico , Adulto , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/metabolismo , Seguimentos , Idoso , Estudos Retrospectivos , Metástase Linfática , Estadiamento de Neoplasias , Gradação de Tumores , Idoso de 80 Anos ou mais

RESUMO

BACKGROUND: In recent years, research on the apolipoprotein E (APOE) gene has gradually proven that many diseases, including atherosclerosis, coronary heart disease, and neurological diseases, are closely related to ApoE gene diversity. However, the relationship between the APOE gene and the prediction and prognosis evaluation of ischemic stroke has not been determined or unified so far. The purpose of this study was to investigate the application value of APOE allele-4 combined with high-resolution vascular wall imaging in predicting the occurrence and prognosis of acute ischemic stroke. METHODS: A total of 511 patients with acute ischemic stroke (AIS), who were admitted from January 2022 to December 2023, were included in the study, including 317 patients with intracranial artery stenosis. Blood lipids, lipoproteins, apolipoprotein E (including allelic typing), and lipoproteins (a) were measured in all cases, and high-resolution magnetic resonance imaging of the vascular walls was performed. At 6 months, the functional outcomes of the AIS patients were followed up, assessed by using the modified Rankin Scale (mRS) (a score of 2 - 6 was rated as poor prognosis), and the high-definition vascular wall imaging results were followed up as well. High-definition vascular wall imaging ensures the accurate location of vascular stenosis and the accurate diagnosis of acute stroke. RESULTS: There were no significant differences in the total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or lipoprotein (a) in patients with and without intracranial artery stenosis, but the plasma apolipoprotein E (APOE) levels were significantly reduced in patients with intracranial artery stenosis (ICAS). At the 6-month follow-up, 230 patients with the APOE-ε4 gene were enrolled, out of which 104 had a poor prognosis (mRS score ≥ 2), accounting for 45.22%. Among 281 patients without the APOE-ε4 gene, 45 had a poor prognosis (mRS score ≥ 2), accounting for 16.01%. Patients with the APOE-ε4 gene had a worse functional prognosis after 6 months. CONCLUSIONS: It is suggested that low plasma APOE levels may be a high risk factor for ICAS in patients with acute ischemic stroke, and carrying the APOE-ε4 gene may be a high risk factor for a poor functional prognosis in AIS patients. The APOE-ε4 genotype, combined with high-resolution vascular wall imaging, has certain clinical application value in predicting the occurrence of acute ischemic death and evaluating the functional outcome.

Assuntos

AVC Isquêmico , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Prognóstico , Idoso , Apolipoproteínas E/genética , Apolipoproteínas E/sangue , Imageamento por Ressonância Magnética/métodos , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/genética , Fatores de Risco

RESUMO

The establishment of an early pro-regenerative niche is crucial for tissue regeneration1,2. Gasdermin D (GSDMD)-dependent pyroptosis accounts for the release of inflammatory cytokines upon various insults3-5. However, little is known about its role in tissue regeneration followed by homeostatic maintenance. Here, we show that macrophage GSDMD deficiency delayed tissue recovery, with little impact on the local inflammatory milieu or the lytic pyroptosis process. Metabolite secretome profiling of hyperactivated macrophages unveiled the non-canonical metabolite-secreting function of GSDMD. And we further identified 11,12-epoxyeicosatrienoic acid (11,12-EET) as a bioactive pro-healing oxylipin, secreted from hyperactive macrophages in a GSDMD-dependent manner. Indeed, accumulation of 11,12-EET by direct supplementation or deletion of its hydrolytic enzyme Ephx2 accelerated muscle regeneration. We further demonstrated that the Ephx2 level accumulated within aged muscle. And consecutive 11,12-EET treatment rejuvenated aged muscle. Mechanistically, 11,12-EET amplifies FGF-FGFR signaling by modulating FGF liquid-liquid phase separation, hence boosting the activation and proliferation of muscle stem cells (MuSCs). These data depict a GSDMD-guided metabolite crosstalk between macrophages and MuSCs that governs the repair process, which offers new therapeutic insights for the regeneration of injured or aged tissues.

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The design and synthesis of hybrid borates by the organic ligand modification method are urgent and undeveloped areas of research. It is difficult to directly integrate organoboronic acids within inorganic borate chemistry by adopting the traditional preparation approaches. This work reports a facile synthetic method to synthesize a large family of pyrazole molecule-protected borates in a rapid and precise manner under mild conditions. A unique cyclic eight-membered B4O4-ring has been identified as the cluster core for all these hybrid borates with two different conformations (boat and crown). This strategy can be applied to a system of pyrazolyl molecules to generate such hybrid borates in two independent routes from organoboronic or inorganic boric acids. Furtherly, the mechanism of 'click reaction' between boric acid and pyrazole induced by copper ions has been proposed based on the synthetic conditions and the structure of intermediate. Due to the bimetallic Cu sites and the functional surfaces, these materials can be used as electrocatalysts for CO2 reduction reaction and efficiently enhance the selectivity of HCOOH and C2H4. Our strategy can be regarded as a typical template technique for organic molecule-protected borates.