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1.
World J Gastrointest Oncol ; 16(9): 3887-3897, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39350993

RESUMEN

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

2.
MedComm (2020) ; 5(10): e764, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39376737

RESUMEN

This study investigated alterations in functional connectivity (FC) within cortico-basal ganglia-thalamo-cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single-target stimulation. We delineated individual-specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles-based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas-based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome-based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual-specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual-specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl-Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas-based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual-specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease-related circuits is essential for understanding poststroke brain reorganization.

3.
Philos Trans A Math Phys Eng Sci ; 382(2283): 20240014, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39370796

RESUMEN

Recent advances in origami science and engineering have particularly focused on the challenges of dynamics. While research has primarily focused on statics and kinematics, the need for effective and processable dynamic models has become apparent. This paper evaluates various dynamic modelling techniques for rigid-foldable origami, particularly focusing on their ability to capture nonlinear dynamic behaviours. Two primary methods, the lumped mass-spring-damper approach and the energy-based method, are examined using a bistable stacked Miura-origami (SMO) structure as a case study. Through systematic dynamic experiments, we analyse the effectiveness of these models in predicting bistable dynamic responses, including intra- and interwell oscillations, in different loading conditions. Our findings reveal that the energy-based approach, which considers the structure's inertia and utilizes dynamic experimental data for parameter identification, outperforms other models in terms of validity and accuracy. This model effectively predicts the dynamic response types, the rich and complex nonlinear characteristics and the critical frequency where interwell oscillations occur. Despite its relatively increased complexity in model derivation, it maintains computational efficiency and shows promise for broader applications in origami dynamics. By comparing model predictions with experimental results, this study enhances our understanding of origami dynamics and contributes valuable insights for future research and applications. This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

4.
Magn Reson Med ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39370883

RESUMEN

PURPOSE: To develop a 3D free-breathing cardiac multi-parametric mapping framework that is robust to confounders of respiratory motion, fat, and B1+ inhomogeneities and validate it for joint myocardial T1 and T1ρ mapping at 3T. METHODS: An electrocardiogram-triggered sequence with dual-echo Dixon readout was developed, where nine cardiac cycles were repeatedly acquired with inversion recovery and T1ρ preparation pulses for T1 and T1ρ sensitization. A subject-specific respiratory motion model relating the 1D diaphragmatic navigator to the respiration-induced 3D translational motion of the heart was constructed followed by respiratory motion binning and intra-bin 3D translational and inter-bin non-rigid motion correction. Spin history B1+ inhomogeneities were corrected with optimized dual flip angle strategy. After water-fat separation, the water images were matched to the simulated dictionary for T1 and T1ρ quantification. Phantoms and 10 heathy subjects were imaged to validate the proposed technique. RESULTS: The proposed technique achieved strong correlation (T1: R2 = 0.99; T1ρ: R2 = 0.98) with the reference measurements in phantoms. 3D cardiac T1 and T1ρ maps with spatial resolution of 2 × 2 × 4 mm were obtained with scan time of 5.4 ± 0.5 min, demonstrating comparable T1 (1236 ± 59 ms) and T1ρ (50.2 ± 2.4 ms) measurements to 2D separate breath-hold mapping techniques. The estimated B1+ maps showed spatial variations across the left ventricle with the septal and inferior regions being 10%-25% lower than the anterior and septal regions. CONCLUSION: The proposed technique achieved efficient 3D joint myocardial T1 and T1ρ mapping at 3T with respiratory motion correction, spin history B1+ correction and water-fat separation.

5.
Front Pediatr ; 12: 1417818, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39363969

RESUMEN

Background: Patients with distant metastases from neuroblastoma (NB) usually have a poorer prognosis, and early diagnosis is essential to prevent distant metastases. The aim was to develop a machine-learning model for predicting the risk of distant metastasis in patients with neuroblastoma to aid clinical diagnosis and treatment decisions. Methods: We built a predictive model using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 on 1,542 patients with neuroblastoma. Seven machine-learning methods were employed to forecast the likelihood of neuroblastoma distant metastases. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for building machine learning models. Secondly, the subject operating characteristic area under the curve (AUC), Precision-Recall (PR) curves, decision curve analysis (DCA), and calibration curves were used to assess model performance. To further explain the optimal model, the Shapley summation interpretation method (SHAP) was applied. Ultimately, the best model was used to create an online calculator that estimates the likelihood of neuroblastoma distant metastases. Results: The study included 1,542 patients with neuroblastoma, multifactorial logistic regression analysis showed that age, histology, tumor size, tumor grade, primary site, surgery, chemotherapy, and radiotherapy were independent risk factors for distant metastasis of neuroblastoma (P < 0.05). Logistic regression (LR) was found to be the optimal algorithm among the seven constructed, with the highest AUC values of 0.835 and 0.850 in the training and validation sets, respectively. Finally, we used the logistic regression model to build a network calculator for distant metastasis of neuroblastoma. Conclusion: The study developed and validated a machine learning model based on clinical and pathological information for predicting the risk of distant metastasis in patients with neuroblastoma, which may help physicians make clinical decisions.

6.
Front Pharmacol ; 15: 1418609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39364050

RESUMEN

Background: Epilepsy is a chronic neurological condition requiring effective management with minimal adverse effects. Lacosamide (LCM) and Perampanel (PER), two promising treatments, have distinct profiles that merit comparative analysis to guide clinical decision-making. Methods: This study utilizes a pharmacovigilance analysis of adverse events reported in the FDA Adverse Event Reporting System database from Q1 2009 to Q3 2023. Employing disproportionality and Bayesian analyses, we assessed and compared the AE signals associated with LCM and PER to elucidate their safety profiles in epilepsy treatment. Results: The analysis included 12,576 AE reports for LCM and 2,703 for PER, highlighting a higher incidence of psychiatric disorders, including aggression with LCM, and a notable association of PER with psychiatric disorders such as psychotic disorders and dizziness. LCM showed a relatively safe profile during pregnancy, whereas PER's data suggested caution due to reported cases of suicidal ideation and attempts. Conclusion: This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of LCM and PER in clinical practice, providing valuable insights for personalized epilepsy management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events.

7.
Eur J Pediatr ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382648

RESUMEN

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5 mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known • Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. • There are few reports on aAVP-D, most of which focus on adult patients. • The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New • Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. • Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. • Early recognition and structured management of ADI lowered the risk of complications.

8.
Health Commun ; : 1-12, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39466127

RESUMEN

Numerous universities nationwide announced urgent implementation of closed campus management due to the epidemics of COVID-19 in Chinese universities since March 2022, and a large number of students were under quarantine. This study aims to explore how embodied experiences (i.e., centralized quarantine and self-quarantine) and mediated experiences (i.e., exposure to media sources, pandemic information overload, and online help seeking) influence the acquisition of learned helplessness during the campus epidemics among the Chinese university students, besides, how do these two types of experiences interact with each other to elicit learned helplessness is another interested research question. The data was collected nationwide via an online survey platform from March 22nd to April 16 2022 immediately after the outbreak of campus epidemics. A total of 1267 valid student samples were retained. Hierarchical regression analysis showed that embodied experience of centralized quarantine is positively related to learned helplessness. Mediated experience of information access from friends on social media and government official media as well as online help seeking are negatively related to learned helplessness. Information access from overseas media and pandemic information overload are positively related to learned helplessness. Besides, the interaction between self-quarantine and pandemic information overload is positively related to learned helplessness. Theoretical contributions and intervention strategies aimed at enhancing authoritative communication and managing information overload during public health crisis were discussed.

9.
J Med Chem ; 67(20): 18247-18264, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39388374

RESUMEN

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of ZLC491 as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader. The compound effectively degraded CDK12 and CDK13 with DC50 values of 32 and 28 nM, respectively, in TNBC MDA-MB-231 cells. Global proteomic assessment and mechanistic studies revealed that ZLC491 selectively induced CDK12/13 degradation in a cereblon- and proteasome-dependent manner. Furthermore, the molecule efficiently suppressed transcription and expression of long genes, predominantly a subset of genes associated with DNA damage response, and significantly inhibited proliferation of multiple TNBC cell lines. Importantly, ZLC491 achieved an oral bioavailability of 46.8% in rats and demonstrated potent in vivo degradative effects on CDK12/13 in an MDA-MB-231 xenografted mouse model.


Asunto(s)
Antineoplásicos , Disponibilidad Biológica , Quinasas Ciclina-Dependientes , Proteolisis , Humanos , Animales , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Ratas , Proteolisis/efectos de los fármacos , Administración Oral , Proliferación Celular/efectos de los fármacos , Ratones , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Descubrimiento de Drogas , Ensayos Antitumor por Modelo de Xenoinjerto , Ratas Sprague-Dawley , Ratones Desnudos , Relación Estructura-Actividad , Proteína Quinasa CDC2
10.
Sci Total Environ ; 955: 177033, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39447894

RESUMEN

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

11.
Ren Fail ; 46(2): 2417743, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39444286

RESUMEN

BACKGROUND: Primary hyperoxaluria type 2 (PH2) is a rare disorder caused by GRHPR mutations. Research on the mutation spectrum and pedigree of PH2 helps in comprehending its pathogenesis and clinical outcomes, guiding clinical diagnosis and treatment. METHODS: We report a case of PH2 with a three-generational pedigree. The GRHPR genotypes of the family members were confirmed by Sanger sequencing. Urine and blood samples were collected for biochemical analysis. Computational analysis was performed to assess the pathogenicity of the mutations. Cellular experiments based on site-directed mutagenesis were conducted to confirm the effect of mutations on GRHPR expression, activity, and subcellular localization. RESULTS: The proband underwent her first kidney transplantation in 2015, and experienced recurrent urinary tract infections and urolithiasis postoperatively. Graft failure occurred in 2018. Whole exome sequencing identified compound heterozygous GRHPR mutations p.G160E/p.P203Rfs*7. The patient underwent a second kidney transplantation in 2019 and maintained good graft function with urine dilution measures. Notably, her brother and sister carried the same mutations; however, only the proband progressed to renal failure. Computational analysis suggested that p.G160E reduced the affinity of GRHPR for coenzymes. Cellular experiments indicated that p.G160E reduced GRHPR activity (p < 0.001), whereas p.P203Rfs*7 not only suppressed expression (p < 0.001) and reduced activity (p < 0.001), but also facilitated protein aggregation. Based on our results, the variant p.G160E was classified as 'pathogenic' according to ACMG guidelines. CONCLUSIONS: Our findings suggest that treatment strategies for the long-term prevention of oxalate nephropathy should be developed for patients with PH2 receiving isolated kidney transplantation. Moreover, the pathogenicity of the compound heterozygous GRHPR mutations p.G160E/p.P203Rfs*7 was also validated.


Asunto(s)
Hiperoxaluria Primaria , Trasplante de Riñón , Mutación , Linaje , Humanos , Trasplante de Riñón/efectos adversos , Hiperoxaluria Primaria/genética , Hiperoxaluria Primaria/cirugía , Femenino , Adulto , Oxidorreductasas de Alcohol/genética , Masculino , Análisis Mutacional de ADN , Reoperación
12.
Org Lett ; 26(42): 9097-9102, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39413030

RESUMEN

Gem-borylsilylalkanes are versatile intermediates in organic synthesis, and the traditional synthesis methods have mainly focused on metal reagents, the insertion reactions of diazo compounds, and hydrosilylation/hydroborylation reactions of unsaturated bonds. Herein, a novel, efficient gem-borylsilylalkanes synthesis via a radical approach is reported. This method introduced a ß-gem-borylsilyl NHPI ester as the precursor of the ß-borylsilyl radical that, coupling with radical acceptors under photo conditions, and the corresponding gem-borylsilylalkanes bearing unsaturated bonds, facilitate subsequent transformations.

13.
Sci Rep ; 14(1): 24907, 2024 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-39438524

RESUMEN

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient's complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (ß = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and ß-C-terminal telopeptide of type I collagen (ß-CTX) (ß = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (ß = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and ß-CTX (ß = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (ß = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and ß-CTX (ß = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, ß-CTX. In addition, the stratified analysis validated the result's stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with ß-CTX, whereas PLR demonstrates a positive correlation with ß-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism.


Asunto(s)
Biomarcadores , Remodelación Ósea , Fracturas Osteoporóticas , Humanos , Femenino , Anciano , Masculino , Biomarcadores/sangre , Fracturas Osteoporóticas/sangre , Estudios Transversales , Estudios Retrospectivos , Neutrófilos/metabolismo , Anciano de 80 o más Años , Procolágeno/sangre , Inflamación/sangre , Fragmentos de Péptidos/sangre , Colágeno Tipo I/sangre , Linfocitos/metabolismo , Persona de Mediana Edad , Monocitos/metabolismo , Osteoporosis/sangre , Plaquetas/metabolismo , Péptidos
14.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(5): 903-910, 2024 Oct 25.
Artículo en Chino | MEDLINE | ID: mdl-39462657

RESUMEN

To assist grassroots sonographers in accurately and rapidly detecting intussusception lesions from children's abdominal ultrasound images, this paper proposes an improved YOLOv8n children's intussusception detection algorithm, called EMC-YOLOv8n. Firstly, the EfficientViT network with a cascaded group attention module was used as the backbone network to enhance the speed of target detection. Secondly, the improved C2fMBC module was used to replace the C2f module in the neck network to reduce network complexity, and the coordinate attention (CA) module was introduced after each C2fMBC module to enhance attention to positional information. Finally, experiments were conducted on the self-built dataset of intussusception in children. The results showed that the recall rate, average detection accuracy (mAP@0.5) and precision of the EMC-YOLOv8n algorithm improved by 3.9%, 2.1% and 0.9%, respectively, compared to the baseline algorithm. Despite slightly increased network parameters and computational load, significant improvements in detection accuracy enable efficient completion of detection tasks, demonstrating substantial economic and social value.


Asunto(s)
Algoritmos , Intususcepción , Ultrasonografía , Humanos , Intususcepción/diagnóstico por imagen , Ultrasonografía/métodos , Niño , Procesamiento de Imagen Asistido por Computador/métodos
15.
Chembiochem ; : e202400410, 2024 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-39462891

RESUMEN

(+)-Bicyclogermacrene is a sesquiterpene compound found in various plant essential oils and serves as a crucial precursor for multiple biologically active compounds. Many derivatives of (+)-bicyclogermacrene have been shown to exhibit valuable bioactivities. Cytochrome P450 BM3 from Bacillus megaterium can catalyze a variety of substrates and different types of oxidation reactions, making it become a powerful tool for oxidizing terpenes. In this study, we employed P450 BM3-139-3 variant for in vitro enzymatic oxidation of (+)-bicyclogermacrene, identifying a novel oxidized derivative of (+)-bicyclogermacrene, named (+)-3,6-epoxymaaliane, and an unknown sesquiterpenoid in a ratio of 70 : 30 (by GC peak area). (+)-3,6-Epoxymaaliane showed demonstrated antibacterial activities toward Escherichia coli and Staphylococcus aureus. To obtain a better variant of the monooxygenase with a high selectivity to form (+)-3,6-epoxymaaliane, we combined alanine scanning with the "Focused Rational Iterative Site-Specific Mutagenesis" (FRISM) strategy to modify the closest residues within 5 Šradius surrounding the substrate to create a small-but-smart library of mutants. Consequently, it gave an optimal variant with 1.6-fold improvement, in a turnover number (TON) of up to 964 toward (+)-3,6-epoxymaaliane production with a higher product selectivity.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39384367

RESUMEN

BACKGROUND: The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) of the CYP1A1 gene and the gene-environment interaction on the susceptibility to endometrial cancer in Chinese women. METHOD: Logistic regression was performed to investigate the association between the four SNPs of the CYP1A1 gene and the risk of endometrial cancer. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the gene-environmental interaction. RESULTS: A total of 934 women with a mean age of 61.7 ± 10.5 years were selected, including 310 endometrial cancer patients and 624 normal controls. The frequency of rs4646421- T allele was higher in endometrial cancer patients than normal controls, the T allele of rs4646421 was 28.1% in endometrial cancer patients and 21.0% in normal controls (p < 0.001). Logistic regression analysis showed that the rs4646421 - T allele was associated with increased risk of endometrial cancer, OR (95% CI) were 1.52 (1.11-1.97) and 1.91 (1.35-2.52), respectively. GMDR analysis found a significant two-locus model (p = 0.0107) involving rs4646421 and abdominal obesity (defined by waist circumference), indicating a potential gene-environment interaction between rs4646421 and abdominal obesity. Abdominal obese subjects with rs4646421- CT or TT genotype have the highest risk of endometrial cancer, compared to non-abdominal obese subjects with the rs4646421- CC genotype, the OR (95%CI) was 2.23 (1.62-2.91). CONCLUSIONS: Both the rs4646421- T allele and the interaction between rs4646421 and abdominal obesity were associated with increased risk of endometrial cancer.


Asunto(s)
Citocromo P-450 CYP1A1 , Neoplasias Endometriales , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias Endometriales/genética , Neoplasias Endometriales/epidemiología , Femenino , Persona de Mediana Edad , Anciano , Citocromo P-450 CYP1A1/genética , China/epidemiología , Factores de Riesgo , Estudios de Casos y Controles
17.
Front Endocrinol (Lausanne) ; 15: 1418271, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39359411

RESUMEN

Objective: To evaluate the correlation between the triglyceride-glucose (TyG) index and bone turnover markers (BTMs) in osteoporotic fractures (OPFs) patients hospitalized for surgical intervention. Methods: A retrospective cross-sectional study was conducted on 3558 OPFs patients hospitalized for surgical intervention between January 2017 and July 2022. The study obtained baseline values for various biomarkers and covariates, including fasting blood glucose, ß-C-terminal telopeptide of type I collagen (ß-CTX), procollagen type 1 N-terminal propeptide (P1NP), triglycerides, age, sex, body mass index, smoking, drinking, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, uric acid, the score of American society of anesthesiologists, homocysteine, parathyroid hormone, apolipoprotein B, apolipoprotein A, magnesium, phosphorus and calcium. Multiple linear regression, curve fitting, threshold effects, and subgroup analyses were also applied. Results: After adjusting for covariates in the regression analysis, the results revealed a negative correlation between ß-CTX and P1NP levels and the baseline TyG index. Specifically, a one-unit increase in the TyG index was associated with a reduction in ß-CTX levels of -0.06 (95% CI: -0.10, -0.01; P-value = 0.012) and a reduction in P1NP levels of -4.70 (95% CI: -9.30, -0.09; P-value = 0.046). Additionally, the inflection points for the nonlinear correlation between the TyG index and ß-CTX and P1NP were found to be K = 6.31 and K = 6.63, respectively. Conclusion: The study demonstrated a negative, non-linear relationship among the TyG index, ß-CTX and P1NP in OPFs patients hospitalized for surgical intervention. These findings suggest that elevated TyG index levels may adversely affect bone turnover, potentially contributing to the progression of OP.


Asunto(s)
Biomarcadores , Glucemia , Remodelación Ósea , Fracturas Osteoporóticas , Triglicéridos , Humanos , Estudios Transversales , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Remodelación Ósea/fisiología , Biomarcadores/sangre , Fracturas Osteoporóticas/sangre , Fracturas Osteoporóticas/cirugía , Triglicéridos/sangre , Glucemia/metabolismo , Hospitalización , Anciano de 80 o más Años , Colágeno Tipo I/sangre , Procolágeno/sangre , Fragmentos de Péptidos/sangre , Péptidos
18.
Artículo en Inglés | MEDLINE | ID: mdl-39364552

RESUMEN

As a novel approach to pursue high-performance multifunctional materials, the structural design of cutting-edge two-dimensional (2D) materials has ignited substantial interests. Borophene, an emerging member in the realm of 2D materials, exhibits crucial attributes, including high theoretical carrier density, electrical conductivity, magnetism, and high aspect ratio, rendering it highly promising for diverse applications. Yet, the exploration of porous structural configurations of borophene remains untapped. Addressing this gap, our study focuses on the fabrication of a multifunctional borophene hybrid foam (CMB-foam). This hybridization leverages the exceptional multifunctionality of MXene alongside borophene within a three-dimensional porous framework, facilitating reflection and absorption of electromagnetic waves, thereby demonstrating remarkable electromagnetic interference (EMI) shielding capabilities. Moreover, this structural configuration exposes an enlarged surface area, thus shortening the transport pathway for electrolyte ions, leading to an excellent energy storage performance. Additionally, CMB-foam performs well in thermal management and thermal insulation. These findings underscore the potential of borophene-based materials in multifunctional applications and offer valuable insights into further performance explorations in this domain.

19.
Adv Mater ; : e2406891, 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39394784

RESUMEN

Suspension bath-based 3D bioprinting (SUB3BP) is effective in creating engineered vascular structures. The transfer of oxygen and nutrients via engineered vascular networks is necessary for tissue or organ survival and integration following transplantation. Existing SUB3BP techniques face challenges in fabricating hierarchical structures with multicellular organization, including issues related to suspension bath removal, restricted material choices, and low accuracy. A next-generation SUB3BP technique that is removal-free and multicellular is presented. A simple, storable, stable, and scalable starch hydrogel design leverages the diverse spectrum of hydrogels available for use in SUB3BP. Starch granules (8.1 µm) create vascular structures with minimal surface roughness (2.5 µm) that simulate more natural vessel walls compared to prior research. The development of cells and organoids, as well as the bioprinting of multicellular skin models with vasculature, demonstrates that starch suspension baths eliminate the removal process and have the potential for fabricating artificial tissue with a hierarchical structure and multicellular distribution.

20.
bioRxiv ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39416128

RESUMEN

The patho-mechanism of apolipoprotein variant, APOE4, the strongest genetic risk for late-onset Alzheimer's disease (AD) and longevity, remains unclear. APOE's neighboring gene, TOMM40 (mitochondria protein transport channel), is associated with brain trauma outcome and aging-related cognitive decline, however its role in AD APOE4-independently is controversial. We report that TOMM40 is prone to transcription readthrough into APOE that can generate spliced TOMM40-APOE mRNA chimera (termed T9A2) detected in human neurons and other cells and tissues. T9A2 translation tethers APOE (normal APOE3 or APOE4) to near-full-length TOM40 that is targeted to mitochondria. Importantly, T9A2-APOE3 boosts mitochondrial bioenergetic capacity and decreases oxidative stress significantly more than T9A2-APOE4 and APOE3, and lacking in APOE4. We describe detailed interactomes of these actors that may inform about the activities and roles in pathogenesis. T9A2 uncovers a new candidate pathway for mitochondria regulation and oxidative stress-protection that are impaired in APOE4 genotypes and could initiate neurodegeneration.

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