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The biogenesis and differentiation (B&D) of amyloplasts contributes to fruit flavor and color. Here, remodeling of starch granules, thylakoids and plastoglobules was observed during development and ripening in two kiwifruit (Actinidia spp.) cultivars - yellow-fleshed 'Hort16A' and green-fleshed 'Hayward'. A protocol was developed to purify starch-containing plastids with a high degree of intactness, and amyloplast B&D was studied using label-free-based quantitative proteomic analyses in both cultivars. Over 3000 amyloplast-localized proteins were identified, of which >98% were quantified and defined as the kfALP (kiwifruit amyloplast proteome). The kfALP data were validated by Tandem-Mass-Tag (TMT) labeled proteomics in 'Hort16A'. Analysis of the proteomic data across development and ripening revealed: 1) a conserved increase in the abundance of proteins participating in starch synthesis/degradation during both amyloplast B&D; 2) up-regulation of proteins for chlorophyll degradation and of plastoglobule-localized proteins associated with chloroplast breakdown and plastoglobule formation during amyloplast differentiation; 3) constitutive expression of proteins involved in ATP supply and protein import during amyloplast B&D. Interestingly, two different pathways of amyloplast B&D were observed in the two cultivars. In 'Hayward', significant increases in abundance of photosynthetic- and tetrapyrrole metabolism-related proteins were observed, but the opposite trend was observed in 'Hort16A'. In conclusion, analysis of the kfALP provides new insights into the potential mechanisms underlying amyloplast B&D with relevance to key fruit quality traits in contrasting kiwifruit cultivars.
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Actinidia , Proteoma , Proteoma/metabolismo , Actinidia/genética , Actinidia/metabolismo , Proteômica/métodos , Frutas/metabolismo , Plastídeos/metabolismo , Amido/metabolismoRESUMO
Chromoplasts act as a metabolic sink for carotenoids, in which plastoglobules serve as versatile lipoprotein particles. PGs in chloroplasts have been characterized. However, the features of PGs from non-photosynthetic plastids are poorly understood. We found that the development of chromoplast plastoglobules (CPGs) in globular and crystalloid chromoplasts of citrus is associated with alterations in carotenoid storage. Using Nycodenz density gradient ultracentrifugation, an efficient protocol for isolating highly purified CPGs from sweet orange (Citrus sinensis) pulp was established. Forty-four proteins were defined as likely comprise the core proteome of CPGs using comparative proteomics analysis. Lipidome analysis of different chromoplast microcompartments revealed that the nonpolar microenvironment within CPGs was modified by 35 triacylglycerides, two sitosterol esters, and one stigmasterol ester. Manipulation of the CPG-localized gene CsELT1 (esterase/lipase/thioesterase) in citrus calli resulted in increased lipids and carotenoids, which is further evidence that the nonpolar microenvironment of CPGs contributes to carotenoid accumulation and storage in the chromoplasts. This multi-feature analysis of CPGs sheds new light on the role of chromoplasts in carotenoid metabolism, paving the way for manipulating carotenoid content in citrus fruit and other crops.
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Citrus sinensis , Citrus , Citrus/genética , Citrus/metabolismo , Multiômica , Carotenoides/metabolismo , Plastídeos/metabolismo , Citrus sinensis/genética , Frutas/genética , Frutas/metabolismoRESUMO
Whole blood, as one of the most significant biological fluids, provides critical information for health management and disease monitoring. Over the past 10 years, advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems for whole blood testing toward the goal of disease monitoring and treatment. Among the techniques employed for whole-blood diagnostics, electrochemical biosensors, as known to be rapid, sensitive, capable of miniaturization, reagentless and washing free, become a class of emerging technology to achieve the target detection specifically and directly in complex media, e.g., whole blood or even in the living body. Here we are aiming to provide a comprehensive review to summarize advances over the past decade in the development of electrochemical sensors for whole blood analysis. Further, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Nanotecnologia/métodos , Biomarcadores , MicrofluídicaRESUMO
Herein, the vitamin K2 (VK2)/maleimide (MA) coloaded mesoporous silica nanoparticles (MSNs), functional molecules including folic acid (FA)/triphenylphosphine (TPP)/tetrapotassium hexacyanoferrate trihydrate (THT), as well as CaCO3 are explored to fabricate a core-shell-corona nanoparticle (VMMFTTC) for on-demand anti-tumor immunotherapy. After application, the tumor-specific acidic environment first decomposed CaCO3 corona, which significantly levitates the pH value of tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMMFTT would then internalize in both tumor cells and macrophages via FA-assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMMFTT in above two cells followed by 1) TPP-induced accumulation in the mitochondria, 2) THT-mediated effective capture of various signal ions to cut off signal transmission and further inhibit glutathione (GSH) generation, 3) ions catalyzed reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of tumor cells and additional M2-to-M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Nanopartículas/química , Estresse Oxidativo , Neoplasias/terapia , Imunoterapia , Mitocôndrias/metabolismo , Íons , Linhagem Celular TumoralRESUMO
The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMAEF) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMAEF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (AEF). During therapy, the BMAEF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and AEF with exposed EGTA. The EGTA further captures Ca2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes AEF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.
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Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E. coli expressing strain BL21(DE3) was engineered by deleting the IpxM gene and inserting the GROEL/S and Trigger factor genes. The engineered E. coli strain BL21(TG)/pT-MYDGF accumulated 3557.3 ± 185.6 µg/g and 45.7 ± 6.7 mg/L of soluble hMYDGF in shake flask fermentation, representing a 15.6-fold increase compared to the control strain BL21(DE3)/pT-MYDGF. Furthermore, the yield of hMYDGF was significantly enhanced by optimizing the fermentation conditions. Under optimized conditions, the 5L bioreactor yielded up to 2665.8 ± 164.3 µg/g and 407.6 ± 42.9 mg/L of soluble hMYDGF. The results indicate that the implementation of these optimization strategies could enhance the ratio and yield of soluble proteins expressed by E.coli, thereby meeting the demands of industrial production. This study employed sophisticated strategies to lay a solid foundation for the industrial application of hMYDGF.
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OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. CONCLUSION: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.
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Creatina Quinase , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pacientes Internados , Rabdomiólise , Humanos , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Incidência , Adulto , Creatina Quinase/sangue , Rabdomiólise/induzido quimicamente , Rabdomiólise/epidemiologia , Pacientes Internados/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adolescente , Idoso de 80 Anos ou mais , Adulto Jovem , Hospitalização/estatística & dados numéricos , Criança , Doenças Musculares/induzido quimicamente , Doenças Musculares/epidemiologiaRESUMO
A novel Gram-stain-positive, oval-shaped, and non-flagellated bacterial strain YIM S02556T was isolated from forest soil in Xiongbi Town, Shizong County, Qujing City, Yunnan Province, southwestern China. The strain exhibited high pairwise 16 S rRNA gene sequence similarity with Psychromicrobium lacuslunae (97.3%) and Psychromicrobium silvestre (96.3%). Strain YIM S02556T exhibited an average nucleotide identity (ANI) of 72.5% with P. lacuslunae IHBB 11,108T and 72.8% ANI with P. silvestre AK 20-18T. The digital DNA-DNA hybridization (dDDH) value between strain YIM S02556T and P. lacuslunae IHBB 11,108T was 20.2%, while with P. silvestre AK 20-18T, the dDDH value was 20.8%. Strain YIM S02556T exhibited optimal growth at 28 °C, pH 7.0, without NaCl. Growth occurred within 10-37 â, pH 5.0-8.0, and in the presence of up to 5% w/v NaCl concentration. The genome size was 3.1 Mbp with 64.2% G + C content. The predominant menaquinone was MK-8(H4). The major cellular fatty acid was anteiso-C15:0. Based on the polyphasic analysis, strain YIM S02556T (= KCTC 49,805T = CCTCC AB2020166T) represents a novel Psychromicrobium species in which the name Psychromicrobium xiongbiense sp.nov. was proposed.
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Florestas , Cloreto de Sódio , China , Solo , DNARESUMO
Tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT-PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2-like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2-like MΦ and consequently inhibiting the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2-type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.
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BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.
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Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/genética , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Prognóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Imageamento por Ressonância Magnética/métodosRESUMO
Bridged isoxazolidines were synthesized via Rh(III)-catalyzed C-H allylation of α-aryl nitrones with 5-methylene-1,3-dioxan-2-one. The nitrone group serves as a directing group and 1,3-dipole in the C-H activation/[3 + 2] cycloaddition cascade, exhibiting excellent chemo- and stereoselectivity along with good functional group compatibility. The resulting skeletal structure was conveniently modified to produce a range of important chemical frameworks, and the protocol was applied to biologically active molecules.
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Amomum villosum Lour. is a medicinal and edible plant, whose medicinal parts are dried and mature fruits, and its stems and leaves are always treated as waste. HPLC-MS/MS analysis showed that the chemical components contained in the stems/leaves of A. villosum and those in fruits are quite different. To discover potential active ingredients from the stems/leaves of A. villosum, phytochemical evaluation of the stems/leaves of A. villosum was conducted to isolate and identify-four undescribed compounds (1, 2a, 2b, and 3) along with 41 known ones (4a, 4b, 5a, 5b, and 6-42). All isolated compounds were assessed for their anti-inflammatory and antioxidant activities. Among them, compounds 5b, 33, 34, and 38 exhibited anti-inflammatory activity, and compounds 1, 4a, 4b, 6, 7, 15, 33, 35, 37, and 41 showed antioxidant effects. Among them, the new compound 1 showed a significant antioxidant effect via activation of NRF2/HO-1 pathways. Therefore, the leaves and stems of A. villosum may be served as a potential medicine or dietary supplement for preventing and treating diseases resulting from inflammation and oxidative stress.
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Amomum , Zingiberaceae , Antioxidantes/farmacologia , Amomum/química , Espectrometria de Massas em Tandem , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: Spatial epidemiology plays an important role in public health. Yet, it is unclear whether the current university education in spatial epidemiology in China could meet the competency-oriented professional demands. This study aimed to understand the current situation of education and training, practical application, and potential demands in spatial epidemiology among public health postgraduates in China, and to assess the critical gaps in a future emerging infectious diseases (EID) pandemic preparedness and response. METHODS: This study was divided into three parts. The first part was a comparative study on spatial epidemiology education in international public health postgraduate training. The second part was a cross-sectional survey conducted among public health professionals. The third part was a nationwide cross-sectional survey conducted among public health postgraduates at Chinese universities from October 2020 to February 2021. Data was collected by the WeChat-based questionnaire star survey system and analyzed using the SPSS software. RESULTS: International education institutions had required public health postgraduates to master the essential knowledge and capacity of spatial epidemiology. A total of 198 public health professionals were surveyed, and they had a median of 4.00 (IQR 3.13-4.53) in demand degree of spatial epidemiology. A total of 1354 public health postgraduates were surveyed from 51 universities. Only 29.41% (15/51) of universities offered spatial epidemiology course. Around 8.05% (109/1354) of postgraduates had learned spatial epidemiology, and had a median of 1.05 (IQR 1.00-1.29) in learning degree and a median of 1.91 (IQR 1.05-2.78) in practical application degree of spatial epidemiology. To enhance professional capacity, 65.95% (893/1354) of postgraduates hoped that universities would deliver a credit-course of spatial epidemiology. CONCLUSIONS: A huge unmet education and training demand in spatial epidemiology existed in the current education system of public health postgraduates in China. To enhance the competency-oriented professional capacity in preparedness and response to a future pandemic, it is urgent to incorporate the teaching and training of spatial epidemiology into the compulsory curriculum system of public health postgraduates in China.
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Pandemias , Humanos , Universidades , Estudos Transversais , Autorrelato , China/epidemiologiaRESUMO
As a member of the silent information regulators (sirtuins) family, SIRT6 can regulate a variety of biological processes, including DNA repair, glucose and lipid metabolism, oxidative stress and lifespan, and so forth. SIRT6 maintains organism homeostasis in a variety of phenotypes by mediating epigenetic regulation and posttranslational modification of functional proteins. In this review, we outline the structural basis of SIRT6 enzyme activity and its mechanism of maintaining organism homeostasis in a variety of phenotypes, with an emphasis on the upstream that regulates SIRT6 expression and the downstream substrates. And how SIRT6 achieves multidimensional coordination to maintain organism homeostasis and even extend lifespan. We try to understand the regulatory mechanism of SIRT6 in different phenotypes from the perspective of protein interaction.
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Epigênese Genética , Sirtuínas , Epigênese Genética/genética , Glucose/metabolismo , Homeostase/genética , Longevidade/fisiologia , Sirtuínas/genética , Sirtuínas/metabolismoRESUMO
Thirteen undescribed diterpenoids, including an ent-isopimarane (1), ten ent-atisanes (2-8 and 15-17), and two ingenanes (20 and 21) and ten known compounds, were separated from the whole plant of E. wallichii. The structures and absolute stereochemistry of these compounds were delineated by 1D and 2D NMR, mass spectrometry, pyridine-induced solvent shifts, and X-ray diffraction analyses. Euphwanoid A (1) is elucidated as an ent-16norisopimarane type diterpenoid featuring a C-8-O-C-15 lactone fragment. And euphwanoid B (2) represents a rare ent-atisane type tetranorditerpene possessing a tetrahydrofuran moiety. In addition, all these isolated compounds were assayed for their protective effects on H2O2-induced BV-2 microglial cells damage. And representative compound 1 could protect BV-2 cells against oxidative damage via the NRF2/HO-1 signaling pathway.
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Diterpenos , Euphorbia , Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Peróxido de Hidrogênio/farmacologia , Microglia , Estrutura MolecularRESUMO
INTRODUCTION AND HYPOTHESIS: In the present study, we aimed to compare the efficacy and safety of quinolones with trimethoprim-sulfamethoxazole (TMP/SMX), nitrofurantoin, fosfomycin, and ß-lactams for the treatment of uncomplicated urinary tract infections (UTIs) in adults. METHODS: All controlled clinical trials assessing quinolones for uncomplicated UTIs in adults were searched from PubMed, Embase, and Cochrane Library databases. Meta-analyses were used to evaluate the efficacy and safety in randomized controlled trials (RCTs). RESULTS: A total of 47 RCTs consisting of 8992 patients were included in the present analysis. The clinical and bacteriological remission rates of quinolones were significantly higher (P < 0.01) compared with ß-lactams and nitrofurantoin, while quinolones showed similar clinical and bacteriological remission rates compared with TMP/SMX and fosfomycin. Moreover, the bacterial resistance and relapse rates of quinolones were significantly lower (P < 0.01) compared with TMP/SMX, ß-lactams, and nitrofurantoin. Regarding the adverse drug reactions (ADRs), quinolones did not bring higher risks, while the incidence of ADRs in the quinolone group was also even significantly lower (P < 0.01) compared with the TMP/SMX and nitrofurantoin groups, including the most reported ADRs associated with the gastrointestinal tract. CONCLUSIONS: Compared with other anti-UTI drugs, quinolones exerted an excellent effect on clinical remission and bacteriological eradication, and the application of quinolones did not bring a higher risk of ADRs.
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Anti-Infecciosos , Fosfomicina , Quinolonas , Infecções Urinárias , Adulto , Anti-Infecciosos/uso terapêutico , Fosfomicina/uso terapêutico , Humanos , Nitrofurantoína/uso terapêutico , Quinolonas/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Infecções Urinárias/epidemiologia , beta-Lactamas/uso terapêuticoRESUMO
BACKGROUND: To verify the accuracy and stability of the prediction formula based on the ciliary sulcus diameter and lens thickness and to analyse factors influencing the prediction results. METHODS: In total, 925 eyes from 506 subjects were enrolled in this prospective study between July 1, 2020, and June 30, 2021. Subjects were divided into four seasons, each spanning three months. The target vault was set to be between 300 µm and 700 µm according the prediction formula. The actual vault was measured one month postoperatively. The Bland-Altman test, 95% confidence intervals (95% CI) and 95% limits of agreement (95% LoA) were used to evaluate the agreement between the predicted vault and the actual vault. Eyes with absolute prediction errors greater than 300 µm were further analysed. RESULTS: The mean predicted vaults for the four seasons were 503 ± 99, 494 ± 96, 481 ± 92 and 502 ± 93 µm, while the mean actual vaults were 531 ± 189, 491 ± 179, 464 ± 179 and 529 ± 162 µm, respectively. The predicted and actual vaults of the overall subjects were 493 ± 95 and 500 ± 180 µm, respectively. Of the 925 eyes, 861 eyes (93.08%), 42 eyes (4.54%), and 22 eyes (2.38%) showed a normal vault, high vault, and low vault, respectively. Bland-Altman plots showed that the mean difference between the actual vault and predicted vault overall (± 95% LoA) was 6.43 ± 176.2 µm (-339 to 352 µm). Three UBM features may lead to large prediction errors (more than 300 µm): wide iris-ciliary angle (ICA), iris concavity and anteriorly positioned ciliary body. CONCLUSIONS: This study demonstrated the accuracy and stability of the prediction formula through the validation of a large sample size and a long time span. Wide ICA, iris concavity and anteriorly positioned ciliary body may have an effect on vault.
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Corpo Ciliar , Humanos , Estudos Prospectivos , Estações do AnoRESUMO
Bisphenol A (BPA) is a ubiquitous environmental pollutant that can specifically induce estrogen receptor ß (ERß) expression, and the latter plays a crucial role during wound healing. However, no study has investigated the association between BPA exposure and skin regeneration. This study aimed to explore the impacts of BPA on wound repair using mice models. C57BL/6 mice were administrated with BPA in two different ways during the process of wound healing-dietary intake (5 and 50 mg/kg) and wound application (1 and 100 nM). Mice primary fibroblasts were exposed to BPA to verify the role of BPA on the function of fibroblasts. We also applied BPA in diabetic mice to evaluate its therapy value. BPA showed dual effects on wound healing, which were dependent on the application routes. Dietary intake of BPA delayed wound healing by suppressing ovarian estrogen secretion, whereas wound application of BPA accelerated skin regeneration via up-regulating wound localized ERß expression. Highly expressed ERß enhanced the function of fibroblasts and promoted the transformation from fibroblasts to myofibroblasts. Impacts of BPA on wound healing were dismissed when ERß was blocked. Moreover, wound application of BPA significantly accelerated wound repair in diabetic mice, but has no significant adverse effect on ovarian hormones levels. The current study indicates that although BPA disrupts the function of the endocrine system when administrated by diet, local application of BPA on wounds shows a superior role in promoting wound repair, and this may provide a novel approach for the therapy of pathologic wound healing.
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Diabetes Mellitus Experimental , Receptor beta de Estrogênio , Animais , Compostos Benzidrílicos/toxicidade , Receptor alfa de Estrogênio , Camundongos , Camundongos Endogâmicos C57BL , Fenóis , CicatrizaçãoRESUMO
Hybridization chain reaction (HCR) amplification strategy has been extensively explored for the application of electrochemical DNA-based sensors. Despite the enhancement in its sensitivity using the HCR, such sensor platform exhibited significant sensor-to-sensor variations in current due to variations in probe counts and lengths. To circumvent this, we are developing here a calibration-free "O-N" approach to generate a ratiometric, unitless value that is independent of these variations. Specifically, this approach employs two types of redox reporters, denoted as "One reporter" and "N reporters", with the former attached on the capture DNA and the latter on H1 and H2 strands. By optimizing the attachment sites of these reporters onto DNA strands, we demonstrate a significantly enhanced sensitivity of such sensor platform by four orders of magnitude, achieving accurate, calibration-free measurement of nucleic acids including ctDNA directly in undiluted whole blood without the requirement to calibrate each individual sensor.
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Técnicas Biossensoriais , Ácidos Nucleicos , Calibragem , DNA/genética , Técnicas Eletroquímicas , Hibridização de Ácido NucleicoRESUMO
BACKGROUND: Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer. METHODS: Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared. RESULTS: CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872-0.920; test set, AUC, 0.904, 95% CI, 0.869-0.939) than did CA15-3, CEA, or CA125. CONCLUSION: CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.