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1.
BMC Med Imaging ; 24(1): 167, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969972

RESUMEN

PURPOSE: To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC). METHODS: The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve. RESULTS: Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort. CONCLUSION: The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Invasividad Neoplásica , Nomogramas , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Femenino , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Invasividad Neoplásica/diagnóstico por imagen , Adulto , Metástasis Linfática/diagnóstico por imagen , Anciano , Radiómica
2.
Am J Cancer Res ; 14(6): 2852-2867, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005692

RESUMEN

Cholangiocarcinoma (CCA) is a common malignancy of the digestive system, and its treatment is greatly challenged by rising chemoresistance. Long non-coding RNAs (lncRNAs) have been shown to play critical roles in the development of drug resistance in tumors. However, the role of the lncRNA CCAT1 in erlotinib resistance in CCA remains unclear. In this investigation, we identified CCAT1 as a pivotal factor contributing to erlotinib resistance in CCA. Furthermore, we uncovered that lncRNA CCAT1 modulated epithelial-mesenchymal transition (EMT) through Rho-associated coiled-coil-forming protein kinase 2 (ROCK2), thereby conferring erlotinib resistance upon CCA cells. Mechanistically, we demonstrated that miR-181a-5p interacted with CCAT1 to modulate the expression of ROCK2. Collectively, these findings shed light on the significant role of CCAT1 in the development of erlotinib resistance in CCA. The functional suppression of CCAT1 holds promise in enhancing the sensitivity to erlotinib by reversing EMT through the miR-181a-5p/ROCK2 signaling pathway. These findings provide valuable insights into the mechanisms underlying erlotinib resistance in CCA and the potential strategies for its treatment.

3.
Front Pharmacol ; 15: 1281095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011501

RESUMEN

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

5.
Int J Hyperthermia ; 41(1): 2370969, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38945548

RESUMEN

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.


Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación , Humanos , Femenino , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Enfermedades de los Genitales Femeninos
6.
J Biotechnol ; 391: 106-116, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38871028

RESUMEN

Icaritin, a hydrolysate from total flavonoids of Epimedii (TFE), which has better anti-hepatoma activity than its glycosylated form. In this work, immobilized enzymes 4LP-Tpebgl3@Na-Y and DtRha@ES-107 were used to hydrolyze TFE to prepare icaritin. Five different hydrophobic deep eutectic solvents (HDES) were prepared and the most ideal HDES was successfully selected, which was composed of dodecyl alcohol and thymol with the molar ratio of 2:1. The relative enzyme activity of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 was about 102.4 % and 112.5 %, respectively. In addition, the thermal and binding stability of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 in HDES was not affected negatively. In the biphasic system composed of 50 % (v/v) HDES and Na2HPO4-citric acid buffer (50 mM, pH 5.5), 4LP-Tpebgl3@Na-Y (1.0 U/mL) and TFE (1 g/L) were reacted at 80 °C for 1 h, and then reacted with DtRha@ES-107 (20 U/mL) at 80 °C for 2 h. Finally, TFE was completely converted to 301.8 mg/L icaritin (0.82 mM). After 10 cycles, 4LP-Tpebgl3@Na-Y/DtRha@ES-107 still maintained 84.1 % original activity. In this study, we developed an efficient methodology for icaritin preparation through the integration of enzymatic catalysis and adsorption separation, presenting a viable approach for large-scale, cost-effective production of icaritin.


Asunto(s)
Biotransformación , Enzimas Inmovilizadas , Flavonoides , Interacciones Hidrofóbicas e Hidrofílicas , Flavonoides/metabolismo , Flavonoides/química , Enzimas Inmovilizadas/metabolismo , Enzimas Inmovilizadas/química , Disolventes Eutécticos Profundos/química , Disolventes Eutécticos Profundos/metabolismo , Epimedium/química , Epimedium/metabolismo , Hidrólisis , Solventes/química
7.
Commun Chem ; 7(1): 133, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862828

RESUMEN

Molecular representation is critical in chemical machine learning. It governs the complexity of model development and the fulfillment of training data to avoid either over- or under-fitting. As electronic structures and associated attributes are the root cause for molecular interactions and their manifested properties, we have sought to examine the local electron information on a molecular manifold to understand and predict molecular interactions. Our efforts led to the development of a lower-dimensional representation of a molecular manifold, Manifold Embedding of Molecular Surface (MEMS), to embody surface electronic quantities. By treating a molecular surface as a manifold and computing its embeddings, the embedded electronic attributes retain the chemical intuition of molecular interactions. MEMS can be further featurized as input for chemical learning. Our solubility prediction with MEMS demonstrated the feasibility of both shallow and deep learning by neural networks, suggesting that MEMS is expressive and robust against dimensionality reduction.

8.
BMC Cardiovasc Disord ; 24(1): 300, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867152

RESUMEN

BACKGROUND: Diabetes is a common chronic metabolic disease. The progression of the disease promotes vascular inflammation and the formation of atherosclerosis, leading to cardiovascular disease. The coronary artery perivascular adipose tissue attenuation index based on CCTA is a new noninvasive imaging biomarker that reflects the spatial changes in perivascular adipose tissue attenuation in CCTA images and the inflammation around the coronary arteries. In this study, a radiomics approach is proposed to extract a large number of image features from CCTA in a high-throughput manner and combined with clinical diagnostic data to explore the predictive ability of vascular perivascular adipose imaging data based on CCTA for coronary heart disease in diabetic patients. METHODS: R language was used for statistical analysis to screen the variables with significant differences. A presegmentation model was used for CCTA vessel segmentation, and the pericoronary adipose region was screened out. PyRadiomics was used to calculate the radiomics features of pericoronary adipose tissue, and SVM, DT and RF were used to model and analyze the clinical data and radiomics data. Model performance was evaluated using indicators such as PPV, FPR, AAC, and ROC. RESULTS: The results indicate that there are significant differences in age, blood pressure, and some biochemical indicators between diabetes patients with and without coronary heart disease. Among 1037 calculated radiomic parameters, 18.3% showed significant differences in imaging omics features. Three modeling methods were used to analyze different combinations of clinical information, internal vascular radiomics information and pericoronary vascular fat radiomics information. The results showed that the dataset of full data had the highest ACC values under different machine learning models. The support vector machine method showed the best specificity, sensitivity, and accuracy for this dataset. CONCLUSIONS: In this study, the clinical data and pericoronary radiomics data of CCTA were fused to predict the occurrence of coronary heart disease in diabetic patients. This provides information for the early detection of coronary heart disease in patients with diabetes and allows for timely intervention and treatment.


Asunto(s)
Tejido Adiposo , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Diabetes Mellitus Tipo 2 , Valor Predictivo de las Pruebas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Persona de Mediana Edad , Tejido Adiposo/diagnóstico por imagen , Masculino , Femenino , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Anciano , Vasos Coronarios/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador , Máquina de Vectores de Soporte , Adiposidad , Pronóstico , Tejido Adiposo Epicárdico , Radiómica
9.
Artículo en Inglés | MEDLINE | ID: mdl-38861441

RESUMEN

The medical literature and records on diabetes provide crucial resources for diabetes prevention and treatment. However, extracting entities from these textual diabetes data is crucial but challenging. Named entity recognition (NER) - an important corner-stone technology of natural language processing - has been studied well in the general medical field. However, there is still a lack of effective NER methods to handle diabetes data. Briefly, there are three challenges in the real world, including 1) the large volume of diabetes-related data to be processed, 2) the lack of labeled data, and 3) the high costs of manual labeling. To mitigate those challenges, this paper proposes a novel NER method based on semi-supervised learning, namely SNER, for diabetes data processing. It utilizes large amounts of unlabeled data to solve the problem of lack of labeled data. Specifically, it filters the predicted labels based on their confidence and uncertainty scores to reduce the noise entering the model and divide them into positive pseudo-labels and negative pseudo-labels. Also, it utilizes negative pseudo-labels reasonably to improve the training effect of pseudo-labels. Experiments on two public diabetes datasets show that SNER achieves the best performance compared with existing state-of-the-art models.

10.
Br J Radiol ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38885406

RESUMEN

OBJECTIVES: To find the optimal acceleration factor (AF) of the compressed SENSE (CS) technique for uterine isotropic high-resolution 3D T2-weighted imaging (3D-ISO-T2WI). METHODS: A total of 91 female volunteers from the XXX, XXX and XXX were recruited. A total of 44 volunteers received uterus sagittal 3D-ISO-T2WI scans on 3.0 T MRI device with different CS AFs (including SENSE3, CS3, CS4, CS5, CS6, and CS7), 51 received 3D-ISO-T2WI scans with different degrees of fat suppression (none, light, moderate, and severe), while 4 volunteers received both series of scans. Image quality was subjectively evaluated with a three-point scoring system. Junction zone signal-to-noise ratio (SNR) and contrast to noise ratio (CNR) and myometrial SNR were also calculated. Intraclass correlation coefficients (ICC) were used to analyze the consistency of the measurement results by two observers. ANOVA test or Friedman rank sum test was used to compare the differences in subjective scores, SNR and CNR under different AFs/different degrees of fat suppression. RESULTS: Images by AFs of CS3, CS4, and CS5 had the highest SNR and CNR. Among them, CS5 had the shortest scan time. CS5 also had one of the highest subjective scores. There was no significant difference in SNR and CNR among images acquired with different degrees of fat suppression. Also, images with moderate fat suppression had the highest subjective scores. CONCLUSION: The CS5 combined with moderate fat suppression is recommended for routine female pelvic 3D-ISO-T2WI scan. ADVANCES IN KNOWLEDGE: The CS5 has the highest images quality and has the shortest scan time, which is the best AF. Moderate fat suppression has the highest subjective scores. The CS5 and moderate fat suppression are the best combination for female pelvic 3D-ISO-T2WI scan.

11.
Eur Radiol ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842691
12.
Langmuir ; 40(24): 12443-12453, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38833582

RESUMEN

The nature always offers amazing inspiration, where it is highly desirable to endow coatings on marine equipment with powerful functions. An excellent example is slippery zone of Nepenthes pitcher, which possesses novel liquid-repellent and self-cleaning performance. Therefore, this study presents an efficient fabrication method to prepare a novel coating. The coatings were fabricated by designing biomimetic textures extracted from the lunate bodies of slippery zone on polydimethylsiloxane (PDMS) and then grafting Dictyophora indusiata polysaccharide (DIP) modifier. The as-prepared slippery coatings exhibited outstanding antifouling properties against kinds of daily life pollutants such as Chlorella and coffee. This synergistic strategy was proposed combined with environmentally friendly modifier grafting and heterogeneous microstructure on the surface to broaden new probabilities for manufacturing slippery coatings with incredible protective functionality.

13.
Lancet HIV ; 11(5): e285-e299, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38692824

RESUMEN

BACKGROUND: An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA-protein HIV vaccine with matching envelope (Env) immunogens. METHODS: HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18-50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one gag p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime-boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA-protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT03409276) and is closed to new participants. FINDINGS: Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime-boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime-boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime-boost and coadministration groups (eg, 20 [95%] of 21 in the prime-boost group vs 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] vs nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime-boost group vs 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] vs 12 [57%]), and myalgia (four [40%] and 13 [62%] vs ten [48%]), mostly of mild or moderate severity. INTERPRETATION: Both vaccine regimens were safe, warranting evaluation in larger trials. FUNDING: US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.


Asunto(s)
Vacunas contra el SIDA , Anticuerpos Anti-VIH , Infecciones por VIH , VIH-1 , Vacunas de ADN , Humanos , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/efectos adversos , Adulto , Masculino , Femenino , Método Doble Ciego , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Vacunas de ADN/efectos adversos , Infecciones por VIH/prevención & control , Infecciones por VIH/inmunología , Persona de Mediana Edad , Adulto Joven , Anticuerpos Anti-VIH/sangre , Adolescente , VIH-1/inmunología , Estados Unidos , Inmunización Secundaria , Inmunogenicidad Vacunal , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/genética , Anticuerpos Neutralizantes/sangre
14.
Exp Cell Res ; 439(1): 114090, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38740167

RESUMEN

Dopamine D2 receptors (D2Rs) play crucial roles in regulating diverse physiological functions of the central nervous system and peripheral organs. D2Rs are also expressed in mammary glands. However, which cell types express D2Rs and whether they are involved in milk production remains unclear. The present findings revealed that D2Rs are expressed in the apical regions of the lateral membranes of mammary epithelial cells (MECs) in lactating mice. We also investigated the effects of the D2R agonist bromocriptine and/or antagonist domperidone on intracellular cAMP levels, milk protein production, and apoptosis in a lactation culture model of MECs that produce major milk components like lactating MECs in vivo. We found that bromocriptine decreased intracellular cAMP levels, whereas domperidone dose-dependently neutralized this effect. Bromocriptine also inhibited casein and lactoferrin production and suppressed activities of STAT5 and glucocorticoid receptors (GRs). Domperidone neutralized the inhibition of casein production as well as STAT5 and GR inactivation induced by bromocriptine. Furthermore, D2R activation by bromocriptine induced apoptosis and inactivated ERK, a signaling molecule responsible for promoting cell proliferation and survival. Domperidone attenuated ERK inactivation and apoptosis induced by bromocriptine. These findings suggest that D2Rs play regulatory roles in milk protein production and apoptosis in MECs.


Asunto(s)
Apoptosis , Bromocriptina , Domperidona , Células Epiteliales , Lactancia , Glándulas Mamarias Animales , Proteínas de la Leche , Receptores de Dopamina D2 , Animales , Femenino , Ratones , Apoptosis/efectos de los fármacos , Bromocriptina/farmacología , Células Cultivadas , AMP Cíclico/metabolismo , Domperidona/farmacología , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Lactancia/metabolismo , Glándulas Mamarias Animales/citología , Glándulas Mamarias Animales/metabolismo , Proteínas de la Leche/metabolismo , Proteínas de la Leche/genética , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Factor de Transcripción STAT5/metabolismo
15.
J Affect Disord ; 359: 78-85, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772506

RESUMEN

BACKGROUND: While many studies have established a positive correlation between adolescents' internet addiction and mental health problems, most of these studies have overlooked the internal heterogeneity of Internet addiction. This study aims to identify latent profiles among adolescents based on their Internet addiction and to examine the differences in aggression, depression, and anxiety across these profiles. METHODS: We conducted a survey involving 7422 adolescents and administered the Young's Internet Addiction Test, Aggression Behavior Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder Scale. Latent profile analysis was utilized to categorize Internet addiction profiles among adolescents. Associations between Internet addiction profiles and related factors were examined using the Bolck-Croon-Hagenaars method. RESULTS: Latent profile analysis suggested four profiles of Internet addiction, which were labeled: Regular, Risk, Low Internet addiction, and Internet addiction. The Internet addiction profile showed higher levels of aggression, depression, and anxiety than the Low Internet addiction profile. The Low Internet addiction profile had higher levels of aggression, depression, and anxiety than the Risk profile. The Risk profile demonstrated higher levels of aggression, depression, and anxiety when compared to the Regular profile. LIMITATIONS: Limitations include the cross-sectional design and the self-report measures. CONCLUSIONS: The identified Internet addiction profiles offer differential predictions for aggression, depression, and anxiety. These results underscore the significance of employing latent profile analysis when exploring the associations between Internet addiction and mental health issues.


Asunto(s)
Agresión , Ansiedad , Depresión , Trastorno de Adicción a Internet , Humanos , Adolescente , Agresión/psicología , Masculino , Trastorno de Adicción a Internet/epidemiología , Trastorno de Adicción a Internet/psicología , Femenino , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Estudios Transversales , Encuestas y Cuestionarios , Conducta Adictiva/psicología , Conducta Adictiva/epidemiología , Conducta del Adolescente/psicología , Internet , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Análisis de Clases Latentes
16.
Nat Commun ; 15(1): 4301, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773089

RESUMEN

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.


Asunto(s)
Vacunas contra el SIDA , Anticuerpos Neutralizantes , Antígenos CD4 , Anticuerpos Anti-VIH , VIH-1 , Humanos , Vacunas contra el SIDA/inmunología , VIH-1/inmunología , Anticuerpos Anti-VIH/inmunología , Anticuerpos Neutralizantes/inmunología , Antígenos CD4/inmunología , Antígenos CD4/metabolismo , Vacunas de ADN/inmunología , Anticuerpos Monoclonales/inmunología , Infecciones por VIH/prevención & control , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Microscopía por Crioelectrón , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/química , Sitios de Unión , Regiones Determinantes de Complementariedad/inmunología , Regiones Determinantes de Complementariedad/química
17.
J Antibiot (Tokyo) ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789532

RESUMEN

Saccharothriolide L (1), a derivative of saccharothriolides (STLs) produced by the rare actinomycete Saccharotrix sp. A1506, was synthesized through the precursor-directed in situ synthesis (PDSS) method. The structure of 1 was determined by 1D and 2D NMR and HR-ESI-MS data analyses. A comparison of the rate of the retro-aza-Michael reaction between saccharothriolide L (1) and saccharothriolide B (2) indicated that the 2-amino-4-methylphenol group in 1 might be an effective masking tool for highly reactive, bioactive α, ß-unsaturated carbonyl compounds.

18.
Regen Ther ; 27: 419-433, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38694444

RESUMEN

Regarded as the most promising treatment modality for retinal degenerative diseases, retinal pigment epithelium cell replacement therapy holds significant potential. Common retinal degenerative diseases, including Age-related Macular Degeneration, are frequently characterized by damage to the unit comprising photoreceptors, retinal pigment epithelium, and Bruch's membrane. The selection of appropriate tissue engineering materials, in conjunction with retinal pigment epithelial cells, for graft preparation, can offer an effective treatment for retinal degenerative diseases. This article presents an overview of the research conducted on retinal pigment epithelial cell tissue engineering, outlining the challenges and future prospects.

19.
Biochem Biophys Res Commun ; 716: 150011, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38704890

RESUMEN

Methionine adenosyltransferase 2 A (MAT2A) mediates the synthesis of methyl donor S-Adenosylmethionine (SAM), providing raw materials for methylation reactions in cells. MAT2A inhibitors are currently used for the treatment of tumors with methylthioadenosine phosphorylase (MTAP) deficiency in clinical research. Methyltransferase like 3 (METTL3) catalyzes N6-methyladenosine (m6A) modification of mRNA in mammalian cells using SAM as the substrate which has been shown to affect the tumorigenesis of non-small cell lung cancer (NSCLC) from multiple perspectives. MAT2A-induced SAM depletion may have the potential to inhibit the methyl transfer function of METTL3. Therefore, in order to expand the applicability of inhibitors, improve anti-tumor effects and reduce toxicity, the combinational effect of MAT2A inhibitor AG-270 and METTL3 inhibitor STM2457 was evaluated in NSCLC. The results showed that this combination induced cell apoptosis rather than cell cycle arrest, which was non-tissue-specific and was independent of MTAP expression status, resulting in a significant synergistic anti-tumor effect. We further elucidated that the combination-induced enhanced apoptosis was associated with the decreased m6A level, leading to downregulation of PI3K/AKT protein, ultimately activating the apoptosis-related proteins. Unexpectedly, although combination therapy resulted in metabolic recombination, no significant change in methionine metabolic metabolites was found. More importantly, the combination also exerted synergistic effects in vivo. In summary, the combination of MAT2A inhibitor and METTL3 inhibitor showed synergistic effects both in vivo and in vitro, which laid a theoretical foundation for expanding the clinical application research of the two types of drugs.


Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Sinergismo Farmacológico , Neoplasias Pulmonares , Metionina Adenosiltransferasa , Metiltransferasas , Metionina Adenosiltransferasa/metabolismo , Metionina Adenosiltransferasa/antagonistas & inhibidores , Metionina Adenosiltransferasa/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , Metiltransferasas/metabolismo , Metiltransferasas/antagonistas & inhibidores , Línea Celular Tumoral , Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Ratones , Ratones Desnudos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto
20.
J Chem Phys ; 160(20)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804487

RESUMEN

Lanthanide-doped upconversion (UC) luminescent materials display multicolor emissions, making them ideal for a variety of applications, such as multi-channel biological imaging, fluorescence encryption, anti-counterfeiting, and 3D display. Manipulating the UC emissions of the luminescent materials with a fixed composition is crucial for their applications. Herein, we propose a facile strategy to achieve pulse-width-dependent multicolor UC emissions in NaYF4:Yb/Er/Tm nanocrystals. Upon excitation with a 980 nm continuous-wave laser diode, Er3+ ions in NaYF4:20%Yb,15%Er,1%Tm nanocrystals exhibited UC emissions with a red-to-green (R/G) ratio of 11.3. Nevertheless, by employing a 980 nm pulse laser with pulse widths from 0.1 to 10 ms, the UC R/G ratio can be easily adjusted from 0.9 to 11.3, resulting in continuous and remarkable color transformation from green, yellow, orange, to red. By virtue of the dynamic luminescence color variation of these NaYF4:20%Yb,15%Er,1%Tm nanocrystals, we demonstrated their potential applications in the areas of anti-counterfeiting and information encryption. These findings provide deep insights into the excited-state dynamics and energy transfer of Er3+ in NaYF4:Yb/Er/Tm nanocrystals upon 980 nm pulse excitation, which may pave the way for designing multicolor UC materials toward versatile applications.

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