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1.
Langmuir ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833582

RESUMO

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.

2.
Eur Radiol ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842691
3.
BMC Cardiovasc Disord ; 24(1): 300, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867152

RESUMO

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.


Assuntos
Tecido Adiposo , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Diabetes Mellitus Tipo 2 , Valor Preditivo dos Testes , Humanos , Diabetes Mellitus Tipo 2/complicações , Pessoa de Meia-Idade , Tecido Adiposo/diagnóstico por imagem , Masculino , Feminino , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Vasos Coronários/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador , Máquina de Vetores de Suporte , Adiposidade , Prognóstico , Tecido Adiposo Epicárdico , Radiômica
4.
J Biotechnol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871028

RESUMO

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 (50mM, pH 5.5), 4LP-Tpebgl3@Na-Y (1.0U/mL) and TFE (1g/L) were reacted at 80oC for 1h, and then reacted with DtRha@ES-107 (20U/mL) at 80oC for 2h. Finally, TFE was completely converted to 301.8mg/L icaritin (0.82mM). 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.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38861441

RESUMO

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.

6.
Commun Chem ; 7(1): 133, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862828

RESUMO

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.

7.
J Chem Phys ; 160(20)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804487

RESUMO

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.

8.
J Antibiot (Tokyo) ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789532

RESUMO

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.

9.
Sci Rep ; 14(1): 11897, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789483

RESUMO

The aim of this study was to create and validate a ten-item Domain-specific Grit Scale for College Athletic Students (DGSCAS) to assess the level of grit among college athletic students. College athletic students from a single independent college located in a northern city in China (526 participants at time 1 and 589 participants at time 2) were assessed according to the scale. Various analyses were conducted in this study, including exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and measurement invariance analysis across different sex and birthplaces. The results of the EFA revealed two factors: consistency of interests and perseverance of effort. The CFA results demonstrated acceptable fit indices (x2 = 160.048, df = 34, x2/df = 4.707, CFI = 0.983, TLI = 0.978, SRMR = 0.021, and RMSEA = 0.079). The scale exhibited satisfactory convergent validity and discriminant validity. The significant correlation of these factors with the Grit scale provided strong evidence of criterion-related validity. Measurement invariance analysis indicated that the scale performed consistently across different sex and birthplaces. Three limitations and corresponding recommendations were discussed, including sample heterogeneity, the lack of a unified test result as a criterion for predictive validity, and the cross-sectional design of the study. In conclusion, the DGSCAS is a practical and validated instrument that can be used to assess the level of grit among college athletic students in an educational context.


Assuntos
Estudantes , Humanos , Masculino , Feminino , Estudantes/psicologia , Universidades , Adulto Jovem , China , Atletas/psicologia , Psicometria/métodos , Inquéritos e Questionários , Análise Fatorial , Estudos Transversais , Adolescente , Adulto , Reprodutibilidade dos Testes , Esportes/psicologia
10.
Reprod Sci ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769248

RESUMO

Endometrial elasticity is a potential new marker for assessing endometrial receptivity and pregnancy outcomes based on endometrial thickness and type. Currently, little research has been conducted on the elasticity of the endometrium using shear wave elasticity imaging (SWEI). This study aimed to explore whether endometrial elasticity is an ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer. A total of 245 infertile women underwent ultrasonography before embryo transfer at the Peking University Third Hospital. We compared the endometrial elasticity and sub-endometrial blood flow rate using SWEI in the groups with different pregnancy outcomes. Trends in clinical pregnancy outcomes across the quartiles of endometrial elasticity in the fundus of the uterus (E1) were assessed. Logistic regression analysis was performed to obtain odds ratios for clinical pregnancy outcomes based on the quartiles of E1, with or without adjusting for potential confounding variables. Women in the clinical pregnancy group had higher E1 values and sub-endometrial blood flow rates in the uterine fundus than those in the non-pregnancy group. Women in the highest quartile of E1 had the most favorable clinical pregnancy rates. Endometrial elasticity measured using SWEI is a promising ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer.

11.
Nat Commun ; 15(1): 4301, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773089

RESUMO

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.


Assuntos
Vacinas contra a AIDS , Anticorpos Neutralizantes , Antígenos CD4 , Anticorpos Anti-HIV , HIV-1 , Humanos , Vacinas contra a AIDS/imunologia , HIV-1/imunologia , Anticorpos Anti-HIV/imunologia , Anticorpos Neutralizantes/imunologia , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Vacinas de DNA/imunologia , Anticorpos Monoclonais/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/imunologia , Infecções por HIV/virologia , Microscopia Crioeletrônica , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/química , Sítios de Ligação , Regiões Determinantes de Complementaridade/imunologia , Regiões Determinantes de Complementaridade/química
12.
Exp Cell Res ; 439(1): 114090, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38740167

RESUMO

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.


Assuntos
Apoptose , Bromocriptina , Domperidona , Células Epiteliais , Lactação , Glândulas Mamárias Animais , Proteínas do Leite , Receptores de Dopamina D2 , Animais , Feminino , Camundongos , Apoptose/efeitos dos fármacos , Bromocriptina/farmacologia , Células Cultivadas , AMP Cíclico/metabolismo , Domperidona/farmacologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Lactação/metabolismo , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/metabolismo , Proteínas do Leite/metabolismo , Proteínas do Leite/genética , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Fator de Transcrição STAT5/metabolismo
13.
J Affect Disord ; 359: 78-85, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38772506

RESUMO

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.


Assuntos
Agressão , Ansiedade , Depressão , Transtorno de Adição à Internet , Humanos , Adolescente , Agressão/psicologia , Masculino , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , Feminino , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Inquéritos e Questionários , Comportamento Aditivo/psicologia , Comportamento Aditivo/epidemiologia , Comportamento do Adolescente/psicologia , Internet , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Análise de Classes Latentes
14.
Lancet HIV ; 11(5): e285-e299, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692824

RESUMO

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.


Assuntos
Vacinas contra a AIDS , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Vacinas de DNA , Humanos , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/efeitos adversos , Adulto , Masculino , Feminino , Método Duplo-Cego , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Vacinas de DNA/efeitos adversos , Infecções por HIV/prevenção & controle , Infecções por HIV/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Anti-HIV/sangue , Adolescente , HIV-1/imunologia , Estados Unidos , Imunização Secundária , Imunogenicidade da Vacina , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/genética , Anticorpos Neutralizantes/sangue
15.
Regen Ther ; 27: 419-433, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38694444

RESUMO

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.

16.
Neuropsychiatr Dis Treat ; 20: 979-987, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741580

RESUMO

Background: Postoperative delirium (POD) significantly impacts patient outcomes after acute type A aortic dissection (ATAAD) surgeries. This study investigates the role of Neuronal Pentraxin 2 (NPTX2) as a potential biomarker for POD in ATAAD patients. Methods: This secondary analysis involved ATAAD patients from a prospective observational study. Serum NPTX2 levels were measured preoperatively and immediately postoperatively using Enzyme-Linked Immunosorbent Assay (ELISA). Delirium was assessed using the Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU). Statistical analyses included the Pearson Correlation Coefficient and multivariate logistic regression to evaluate the association between NPTX2 levels and POD. Results: Among the 62 patients included, 46.77% developed POD. Patients with POD had significantly lower preoperative and postoperative serum NPTX2 levels. The Receiver Operating Characteristic (ROC) curve analysis showed that postoperative NPTX2 had a strong predictive capability for POD (AUC = 0.895). The optimal cutoff for postoperative NPTX2 in predicting POD was less than 421.4 pg/mL. Preoperative NPTX2 also demonstrated predictive value, albeit weaker (AUC = 0.683). Conclusion: Serum NPTX2 levels, both preoperatively and postoperatively, are promising biomarkers for predicting POD in ATAAD patients. These findings suggest that NPTX2 could be instrumental in early POD detection and intervention strategies.

17.
Biochem Biophys Res Commun ; 716: 150011, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704890

RESUMO

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.


Assuntos
Apoptose , Carcinoma Pulmonar de Células não Pequenas , Sinergismo Farmacológico , Neoplasias Pulmonares , Metionina Adenosiltransferase , Metiltransferases , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Animais , Metiltransferases/metabolismo , Metiltransferases/antagonistas & inibidores , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Vis Exp ; (207)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767359

RESUMO

Chronic pelvic pain caused by the sequelae of inflammatory pelvic disease is a common clinical condition of pelvic pain in women. At present, the main challenges in its treatment are the limited effectiveness of pain relief and the frequent recurrence of symptoms, which significantly impact patients' quality of life and impose a considerable psychological burden on them. It is a clinically challenging disease. After summarizing years of treatment experience, the author's team discovered that acupoint catgut embedding demonstrated notable clinical efficacy in managing chronic pelvic pain stemming from pelvic inflammatory disease sequelae. Compared to existing Western medicine treatment methods, acupoint catgut embedding offers advantages such as a good analgesic effect, lower recurrence rate, economic benefits, and a relatively straightforward procedure. This article provides a comprehensive guide on embedding absorbable catgut into patients' acupoints for the treatment of chronic pelvic pain in females resulting from the sequelae of pelvic inflammatory disease.


Assuntos
Pontos de Acupuntura , Categute , Dor Crônica , Doença Inflamatória Pélvica , Dor Pélvica , Humanos , Dor Pélvica/terapia , Dor Pélvica/etiologia , Feminino , Dor Crônica/terapia , Dor Crônica/etiologia , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/terapia , Terapia por Acupuntura/métodos
19.
ACS Nano ; 18(18): 11837-11848, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38654614

RESUMO

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.


Assuntos
Biofilmes , Elementos da Série dos Lantanídeos , Pseudomonas aeruginosa , Nanomedicina Teranóstica , Biofilmes/efeitos dos fármacos , Animais , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Terapia Fototérmica , Camundongos Endogâmicos BALB C
20.
Cell Death Discov ; 10(1): 159, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561330

RESUMO

Non-SMC condensin II complex subunit D3 (NCAPD3) is a subunit of the non-structural maintenance of chromosomes condensin II complex, which involves chromosome condensation and segregation during mitosis. NCAPD3 has recently been demonstrated as a crucial oncogenic factor. However, the underlying mechanism of NCAPD3 in prostate cancer (PCa) remains not completely clear. In this study, we confirmed that lncRNA MALAT1 was induced by NCAPD3-STAT3, and the expression of miR-30a-5p was controlled by NCAPD3 in PCa cells by miRNA-seq. Through quantitative real-time PCR, fluorescence in situ hybridization, western blotting, and immunohistochemistry assay, we demonstrated that miR-30a-5p was lowly expressed in PCa cells and tissues compared to the controls, which was contrary to NCAPD3 expression and markedly downregulated by NCAPD3. Then, MALAT1 was analyzed for the complementary sequence in the potential interaction with miR-30a-5p by using the predicted target module of public databases. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to verify that MALAT1 functioned as a sponge for miR-30a-5p to reduce miR-30a-5p expression. Meanwhile, MYC acted as a transcriptional repressor to directly bind the promoter of the miR-30a-5p located gene and repress the miR-30a-5p expression. Furthermore, the upregulation of NCAPD3 on cell viability and migration was significantly attenuated in PC-3 cells when miR-30a-5p was overexpressed. NCAPD3 overexpression also accelerated tumor growth in the xenograft mouse model and repressed miR-30-5p. In summary, this work elucidates NCAPD3 inhibits miR-30a-5p through two pathways: increasing STAT3-MALAT1 to sponge miR-30a-5p and increasing MYC to directly inhibit miR-30a-5p transcription, which could serve as potential therapeutic targets for prostate cancer.

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