Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
Foods ; 13(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38731776

RESUMO

This paper reports the preparation of margarine fat using Lipozyme TL IM as a catalyst and peony seed oil (PSO), palm stearin (PS) and coconut oil (CO) as raw materials. The results indicate that there were no significant changes in fatty acid composition before or after interesterification of the oil samples. However, the total amount of medium- and long-chain triglycerides (MLCTs) increased from 2.92% to 11.38% in sample E1 after interesterification, mainly including LaLaO, LaMO, LaPM, LaOO, LaPO and LaPP. Moreover, the slip melting point (SMP) of sample E1 decreased from 45.9 °C (B1) to 33.5 °C. The solid fat content (SFC) of all the samples at 20 °C was greater than 10%, indicating that they could effectively prevent oil exudation. After interesterification, the samples exhibited a ß' crystal form and could be used to prepare functional margarine.

2.
Angew Chem Int Ed Engl ; : e202405746, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666518

RESUMO

Developing stable electrocatalysts with accessible isolated sites is desirable but highly challenging due to metal agglomeration and low surface stability of host materials. Here we report a general approach for synthesis of single-site Fe electrocatalysts by integrating a solvated Fe complex in conductive macroporous organic networks through redox-active coordination linkages. Electrochemical activation of the electrode exposes high-density coordinately unsaturated Fe sites for efficient adsorption and conversion of reaction substrates such as NO3- and H2O. Using the electrode with isolated active Fe sites, electrocatalytic NO3- reduction and H2O oxidation can be coupled in a single cell to produce NH3 and O2 at Faradaic efficiencies of 97% and 100%, respectively. The electrode exhibits excellent robustness in electrocatalysis for 200 hours with small decrease in catalytic efficiencies. Both the maximized Fe-site efficiency and the microscopic localization effect of the conductive organic matrix contribute to the high catalytic performances, which provides new understandings in tuning the efficiencies of metal catalysts for high-performance electrocatalytic cells.

3.
J Clin Sleep Med ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38557475

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is common in children with Syndromic Craniosynostosis (SC). The efficacy of Fort III procedure in managing OSA in children with SC remains a subject of ongoing debate. This study aimed to explore the efficacy of Le Fort III procedure in the management of OSA in children with SC. METHODS: A retrospective study was performed in children with SC and OSA diagnosed by polysomnography (PSG), which was defined as an apnea and hypopnea index (AHI) ≥ 1. Patients meeting the inclusion criteria were those who underwent Le Fort III surgery and had both baseline PSG and follow-up sleep studies. Relevant clinical and demographic data were collected from all subjects who participated in the study. RESULTS: Overall, forty-five OSA children with SC were identified, with a mean age of 6.8 ± 4.7 years. Twenty-five received the Le Fort III procedure and follow-up sleep studies. The Le Fort III procedure resulted in a significant reduction in AHI (6.0 [2.6, 10.1] versus 37.6 [20.9, 48.0] events/h; P < 0.001). However, normalization of OSA was only achieved in one patient (4%). CONCLUSIONS: The Le Fort III procedure is efficacious in the treatment of OSA in children with SC. However, despite the observed improvement, residual OSA following treatment remains common.

4.
Foods ; 13(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38672849

RESUMO

Gallic acid-Antarctic krill peptides (GA-AKP) nanocapsules (GA-AKP-Ns) were prepared using a dual delivery system with complex emulsion as the technical method, a high-pressure microjet as the technical means, polylactic acid-hydroxyacetic acid (PLGA) as the drug delivery vehicle, and GA-AKP as the raw material for delivery. This study aimed to investigate the effects of microjet treatment and the concentration of PLGA on the physicochemical properties and stability of the emulsion. Under optimal conditions, the physicochemical properties and hypoglycemic function of nano-microcapsules prepared after lyophilization by the solvent evaporation method were analyzed. Through the microjet treatment, the particle size of the emulsion was reduced, the stability of the emulsion was improved, and the encapsulation rate of GA-AKP was increased. The PLGA at low concentrations decreased the particle size of the emulsion, while PLGA at high concentrations enhanced the encapsulation efficiency of the emulsion. Additionally, favorable results were obtained for emulsion preparation through high-pressure microjet treatment. After three treatment cycles with a PLGA concentration of 20 mg/mL and a microjet pressure of 150 MPa (manometric pressure), the emulsion displayed the smallest particle size (285.1 ± 3.0 nm), the highest encapsulation rates of GA (71.5%) and AKP (85.2%), and optimal physical stability. GA-AKP was uniformly embedded in capsules, which can be slowly released in in vitro environments, and effectively inhibited α-amylase, α-glucosidase, and DPP-IV at different storage temperatures. This study demonstrated that PLGA as a carrier combined with microjet technology can produce excellent microcapsules, especially nano-microcapsules, and these microcapsules effectively improve the bioavailability and effectiveness of bioactive ingredients.

5.
Neural Regen Res ; 19(12): 2708-2722, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38595289

RESUMO

JOURNAL/nrgr/04.03/01300535-202412000-00027/figure1/v/2024-04-08T165401Z/r/image-tiff Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.

6.
BMC Genomics ; 25(1): 425, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684983

RESUMO

BACKGROUND: Purple non-heading Chinese cabbage [Brassica campestris (syn. Brassica rapa) ssp. chinensis] has become popular because of its richness in anthocyanin. However, anthocyanin only accumulates in the upper epidermis of leaves. Further studies are needed to investigate the molecular mechanisms underlying the specific accumulation of it. RESULTS: In this study, we used the laser capture frozen section method (LCM) to divide purple (ZBC) and green (LBC) non-heading Chinese cabbage leaves into upper and lower epidermis parts (Pup represents the purple upper epidermis, Plow represents the purple lower epidermis, Gup represents the green upper epidermis, Glow represents the green lower epidermis). Through transcriptome sequencing, we found that the DIHYDROFLAVONOL 4-REDUCTASE-encoding gene BcDFR, is strongly expressed in Pup but hardly in others (Plow, Gup, Glow). Further, a deletion and insertion in the promoter of BcDFR in LBC were found, which may interfere with BcDFR expression. Subsequent analysis of gene structure and conserved structural domains showed that BcDFR is highly conserved in Brassica species. The predicted protein-protein interaction network of BcDFR suggests that it interacts with almost all functional proteins in the anthocyanin biosynthesis pathway. Finally, the results of the tobacco transient expression also demonstrated that BcDFR promotes the synthesis and accumulation of anthocyanin. CONCLUSIONS: BcDFR is specifically highly expressed on the upper epidermis of purple non-heading Chinese cabbage leaves and regulates anthocyanin biosynthesis and accumulation. Our study provides new insights into the functional analysis and transcriptional regulatory network of anthocyanin-related genes in purple non-heading Chinese cabbage.


Assuntos
Antocianinas , Brassica , Proteínas de Plantas , Antocianinas/biossíntese , Brassica/genética , Brassica/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma , Microdissecção e Captura a Laser , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , RNA-Seq , Regiões Promotoras Genéticas
7.
Adv Sci (Weinh) ; 11(12): e2304342, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38229183

RESUMO

Immunotherapy targeting PD-L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine-threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD-L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN-γ-mediated PD-L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti-PD-1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD-L1/PD-1 signaling and is a promising target for combined immunotherapy.


Assuntos
Antígeno B7-H1 , Linfócitos T CD8-Positivos , Humanos , Animais , Camundongos , Antígeno B7-H1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Evasão Tumoral , Linhagem Celular Tumoral
8.
Biochem Pharmacol ; 220: 115993, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38151075

RESUMO

Phosphatidylinositol 4-kinases (PI4Ks) could phosphorylate phosphatidylinositol (PI) to produce phosphatidylinositol 4-phosphate (PI4P) and maintain its metabolic balance and location. PI4P, the most abundant monophosphate inositol in eukaryotic cells, is a precursor of higher phosphoinositols and an essential substrate for the PLC/PKC and PI3K/Akt signaling pathways. PI4Ks regulate vesicle transport, signal transduction, cytokinesis, and cell unity, and are involved in various physiological and pathological processes, including infection and growth of parasites such as Plasmodium and Cryptosporidium, replication and survival of RNA viruses, and the development of tumors and nervous system diseases. The development of novel drugs targeting PI4Ks and PI4P has been the focus of the research and clinical application of drugs, especially in recent years. In particular, PI4K inhibitors have made great progress in the treatment of malaria and cryptosporidiosis. We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.


Assuntos
Criptosporidiose , Cryptosporidium , Humanos , 1-Fosfatidilinositol 4-Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Cryptosporidium/metabolismo , Fosfatos de Fosfatidilinositol , Fosfatidilinositóis/metabolismo
9.
Cancer Manag Res ; 15: 1343-1347, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38046891

RESUMO

Schwannomas are benign slow-growing tumors arising from the embryonic neural crest cells of the nerve sheaths of peripheral and cranial nerves, and they are a rare type of soft tissue mass that is usually always solitary. Generally, it grows in the head, neck, and flexor portions of the limbs, where many nerves are located. Schwannomas of the lung are extremely rare. Fewer than ten cases of schwannomas in this organ region have been reported in the existing literature. In this case report, a 40-year-old male non-smoker was hospitalized with occasional chest pain. His chest computed tomographic scan revealed a 3.8 cm space occupying lesion in the upper lobe of the right lung. This lesion has clear boundaries and uneven internal density. And it was concluded as a benign lesion possibility, it is preferred to be considered as a haematoma. This space occupying lesion was eventually confirmed as a schwannoma by needle biopsy tissues. Due to the presence in rare locations, such as the lung, the clinical presentation of this space occupying lesion is non-specific, making diagnosis difficult. The data presented in this case report can help clinicians to obtain information on the identification of this disease, which highlighted lung schwannoma as a differential diagnosis for patients with intermittent pain. It can also alert clinicians and radiologists to observe every detail of the radiology imaging findings.

10.
Sarcoidosis Vasc Diffuse Lung Dis ; 40(4): e2023051, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38126503

RESUMO

We present a rare case of a 55-year-old female patient with quadruple overlapping autoimmune diseases, including vitiligo, autoimmune hypothyroidism, ulcerative colitis, and sarcoidosis with mediastinal lymphadenopathy. The patient had been suffering from vitiligo since 2003 and was diagnosed with autoimmune hypothyroidism and ulcerative colitis through thyroid ultrasound and colonoscopy, respectively. After physical examination, mediastinal lymph nodes enlargement was detected, and sarcoidosis was diagnosed through ultrasound bronchoscope-guided transbronchial needle aspiration (EBUS-TBNA), which is a quadruple overlapping sign of autoimmune disease of sarcoidosis that has not been reported previously. The patient was treated with oral Chinese medicine for leukoplakia, oral levothyroxine sodium tablets to control thyroid function, and Chinese medicine enema for colitis, with intermittent treatment for 2 years. Prednisone acetate was administered for 1 month to reduce the size of the enlarged lymph nodes. Our case highlights the importance of considering sarcoidosis as a potential diagnosis in patients with autoimmune diseases who present with mediastinal lymphadenopathy.

11.
Transl Lung Cancer Res ; 12(9): 1949-1958, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37854153

RESUMO

Background: The ARROW study demonstrated favorable clinical efficacy and safety of pralsetinib (PRL) in treating rearranged during transfection (RET) fusion positive non-small cell lung cancer (NSCLC) in clinical trials. However, due to the high cost of PRL, evaluating its cost-effective characteristics is crucial. Currently, there has been no cost-effectiveness analysis specifically for PRL. Therefore, the aim of this study was to assess the cost-effectiveness characteristics of using PRL as a first-line therapy versus reserving it until the second-line versus solely relying on chemotherapy from the perspective of payers in the United States. Methods: A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies. Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year. To ensure the robustness of the model, both probabilistic and univariate sensitivity analyses were performed. The primary endpoints included quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY. Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY. The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY. Univariable sensitivity analyses revealed that the cost of PRL and the utility of progressed disease had the most significant impact on the ICER. To be considered cost-effective at a WTP threshold of $150,000 per QALY, the cost of PRL would need to be reduced by 71.34% in first-line treatment or 84.49% in second-line treatment. Conclusions: Based on current pricing, neither PRL as first-line nor second-line therapy was found to be cost-effective for patients with RET fusion-positive advanced NSCLC compared to chemotherapy. Reserving PRL until second-line therapy may be a compromise approach to maintaining control over healthcare expenses yet still achieving favorable clinical outcomes.

12.
Eur J Med Res ; 28(1): 187, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37291613

RESUMO

OBJECTIVES: Endoscopic diagnosis of invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by white-light imaging (WLI) modality remains difficult. This study aims to clarify WLI-based features which are predictive for invasion depth of SESCC. METHODS: A two-phase study was performed by enrolling 1288 patients with 1396 SESCC lesions. Endoscopic appearances, clinical characteristics and post-operative pathological outcomes were collected and reviewed. The association between lesion features and invasion depth were analyzed. A predictive nomogram was constructed for prediction of invasion depth. RESULTS: Among 1396 lesions in derivation and validation cohort, 1139 (81.6%), 194 (13.9%) and 63 (4.5%) lesions were diagnosed as lesions confined into the intraepithelium or the lamina propria mucosa (T1a-EP/LPM), lesions invading the muscularis mucosa (T1a-MM) or superficial submucosa (T1b-SM1) and tumor with moderate invasion into the submucosa or deeper submucosal invasion (≥ T1b-SM2), respectively. Lesion length > 2 cm (p < 0.001), wider circumferential extension (p < 0.001, 0.002 and 0.048 for > 3/4, 1/2-3/4 and 1/4-1/2 circumferential extension, respectively), surface unevenness (p < 0.001 for both type 0-IIa/0-IIc lesions and mixed type lesions), spontaneous bleeding (p < 0.001), granularity (p < 0.001) and nodules (p < 0.001) were identified as significant factors predictive for lesion depth. A nomogram based on these factors was constructed and the values of area under the Receiver Operating Characteristics curve were 0.89 and 0.90 in the internal and external patient cohort. CONCLUSIONS: Our study provides six WLI-based morphological features predicting for lesion depth of SESCC. Our findings will make endoscopic evaluation of invasion depth for SESCC more convenient by assessing these profiles.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Invasividade Neoplásica/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos
13.
Mol Nutr Food Res ; 67(14): e2200665, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37143286

RESUMO

SCOPE: Excellent health-promoting effects of cedrol (CED), including anti-inflammatory, anti-arthritic, and antinociceptive effects, have been reported. The present study aims to investigate the preventive effects of CED on high-fat diet (HFD)-induced obesity and the related metabolic syndrome, and to delineate the underlying mechanism. METHODS AND RESULTS: Ten-week-old C57BL/6J mice are fed chow, HFD, or HFD supplemented with CED (0.2% w/w) for 19 weeks. Results demonstrate that CED effectively reduces HFD-induced body weight gain, decreases visceral fat pad weight, and significantly prevents adipocyte hypertrophy in mice. HFD-induced hepatic steatosis, glucose intolerance, insulin resistance, and gluconeogenesis are ameliorated by CED supplementation. 16S rRNA analysis reveals that CED does not change gut microbiota composition at the phylum and genus levels, indicating that CED may have limited effects on gut microbiota in HFD-fed mice. Further transcriptome analysis of epididymal white adipose tissue reveals reprogrammed RNA profiles by CED. CONCLUSION: These results demonstrate that incorporating CED in the diet can prevent HFD-induced obesity and related metabolic syndrome, and highlight that CED can be a promising dietary component for obesity therapeutic intervention.


Assuntos
Dieta Hiperlipídica , Síndrome Metabólica , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , RNA Ribossômico 16S , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/prevenção & controle , Obesidade/tratamento farmacológico
14.
Discov Oncol ; 14(1): 73, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208546

RESUMO

BACKGROUND: The use of artificial intelligence (AI) assisted white light imaging (WLI) detection systems for superficial esophageal squamous cell carcinoma (SESCC) is limited by training with images from one specific endoscopy platform. METHODS: In this study, we developed an AI system with a convolutional neural network (CNN) model using WLI images from Olympus and Fujifilm endoscopy platforms. The training dataset consisted of 5892 WLI images from 1283 patients, and the validation dataset included 4529 images from 1224 patients. We assessed the diagnostic performance of the AI system and compared it with that of endoscopists. We analyzed the system's ability to identify cancerous imaging characteristics and investigated the efficacy of the AI system as an assistant in diagnosis. RESULTS: In the internal validation set, the AI system's per-image analysis had a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 96.64%, 95.35%, 91.75%, 90.91%, and 98.33%, respectively. In patient-based analysis, these values were 90.17%, 94.34%, 88.38%, 89.50%, and 94.72%, respectively. The diagnostic results in the external validation set were also favorable. The CNN model's diagnostic performance in recognizing cancerous imaging characteristics was comparable to that of expert endoscopists and significantly higher than that of mid-level and junior endoscopists. This model was competent in localizing SESCC lesions. Manual diagnostic performances were significantly improved with the assistance by AI system, especially in terms of accuracy (75.12% vs. 84.95%, p = 0.008), specificity (63.29% vs. 76.59%, p = 0.017) and PPV (64.95% vs. 75.23%, p = 0.006). CONCLUSIONS: The results of this study demonstrate that the developed AI system is highly effective in automatically recognizing SESCC, displaying impressive diagnostic performance, and exhibiting strong generalizability. Furthermore, when used as an assistant in the diagnosis process, the system improved manual diagnostic performance.

17.
Nanomaterials (Basel) ; 13(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36903676

RESUMO

Ir-based perovskite oxides are efficient electrocatalysts for anodic oxygen evolution. This work presents a systematic study of the doping effects of Fe on the OER activity of monoclinic SrIrO3 to reduce the consumption of Ir. The monoclinic structure of SrIrO3 was retained when the Fe/Ir ratio was less than 0.1/0.9. Upon further increases in the Fe/Ir ratio, the structure of SrIrO3 changed from a 6H to 3C phase. The SrFe0.1Ir0.9O3 had the highest activity among the investigated catalysts with the lowest overpotential of 238 mV at 10 mA cm-2 in 0.1 M HClO4 solution, which could be attributed to the oxygen vacancies induced by the Fe dopant and the IrOx formed upon the dissolution of Sr and Fe. The formation of oxygen vacancies and uncoordinated sites at the molecular level may be responsible for the improved performance. This work explored the effect of Fe dopants in boosting the OER activity of SrIrO3, thus providing a detailed reference to tune perovskite-based electrocatalyst by Fe for other applications.

18.
Nutrients ; 15(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36771494

RESUMO

Methyl cedryl ether (MCE) is a derivative of cedrol and is widely used as a fragrance compound. The aim of this study was to evaluate the preventative effects of MCE on obesity and related metabolic syndromes and to delineate the mechanisms from the perspective of gut microbiota and white adipose tissues (WAT) transcriptomic profiles. Five-week-old male C57BL/6J mice were randomly assigned into 3 groups and fed with chow diet, high-fat diet (HFD), or HFD supplemented with 0.2% (w/w) MCE for 13 weeks. We found that MCE significantly reduced body weight, inhibited adipocyte hypertrophy, and ameliorated hepatic steatosis under HFD conditions. MCE dietary supplementation downregulated the expression of adipogenesis genes (FAS and C/EBPα) and upregulated the mRNA levels of thermogenesis genes (PGC-1α, PRDM16, UCP1, Cidea, Cytc, and COX4) in epididymal WAT. 16S rRNA sequencing revealed that MCE improved gut microbiota dysbiosis in HFD-fed mice, as manifested by the alteration of strains associated with obesity. Further transcriptome analysis of WAT indicated that MCE dramatically changed the gene expression profiles. Our results demonstrate the anti-obesity effect of MCE under HFD conditions, highlighting the nutraceutical potential of MCE for preventing obesity.


Assuntos
Adiposidade , Dieta Hiperlipídica , Masculino , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , RNA Ribossômico 16S/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle , Obesidade/metabolismo , Suplementos Nutricionais , Éteres
19.
Nat Biotechnol ; 41(10): 1457-1464, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36747096

RESUMO

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine.

20.
Cancer Med ; 12(2): 1228-1236, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35766144

RESUMO

BACKGROUND: Manual cytological diagnosis for early esophageal squamous cell carcinoma (early ESCC) and high-grade intraepithelial neoplasia (HGIN) is unsatisfactory. Herein, we have introduced an artificial intelligence (AI)-assisted cytological diagnosis for such lesions. METHODS: Low-grade squamous intraepithelial lesion or worse was set as the diagnostic threshold for AI-assisted diagnosis. The performance of AI-assisted diagnosis was evaluated and compared to that of manual diagnosis. Feasibility in large-scale screening was also assessed. RESULTS: AI-assisted diagnosis for abnormal cells was superior to manual reading by presenting a higher efficiency for each slide (50.9 ± 0.8 s vs 236.8 ± 3.9 s, p = 1.52 × 10-76 ) and a better interobserver agreement (93.27% [95% CI, 92.76%-93.74%] vs 65.29% [95% CI, 64.35%-66.22%], p = 1.03 × 10-84 ). AI-assisted detection showed a higher diagnostic accuracy (96.89% [92.38%-98.57%] vs 72.54% [65.85%-78.35%], p = 1.42 × 10-14 ), sensitivity (99.35% [95.92%-99.97%] vs 68.39% [60.36%-75.48%], p = 7.11 × 10-15 ), and negative predictive value (NPV) (97.06% [82.95%-99.85%] vs 40.96% [30.46%-52.31%], p = 1.42 × 10-14 ). Specificity and positive predictive value (PPV) were not significantly differed. AI-assisted diagnosis demonstrated a smaller proportion of participants of interest (3.73%, [79/2117] vs.12.84% [272/2117], p = 1.59 × 10-58 ), a higher consistence between cytology and endoscopy (40.51% [32/79] vs. 12.13% [33/272], p = 1.54 × 10- 8), specificity (97.74% [96.98%-98.32%] vs 88.52% [87.05%-89.84%], p = 3.19 × 10-58 ), and PPV (40.51% [29.79%-52.15%] vs 12.13% [8.61%-16.75%], p = 1.54 × 10-8 ) in community-based screening. Sensitivity and NPV were not significantly differed. AI-assisted diagnosis as primary screening significantly reduced average cost for detecting positive cases. CONCLUSION: Our study provides a novel cytological method for detecting and screening early ESCC and HGIN.


Assuntos
Carcinoma in Situ , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Intraepiteliais Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Neoplasias Esofágicas/diagnóstico , Inteligência Artificial , Lesões Intraepiteliais Escamosas/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA