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Kawasaki disease (KD) is a disease characterized by systemic immune vasculitis that often involves coronary arteries and can result in long-term cardiovascular sequelae. Different strategies for treatment of KD-and KD-induced coronary artery lesions are currently under investigation, including passive immunization with anti-TNFα monoclonal antibodies (mAbs). Herein, we examine the potential therapeutic capabilities of a novel type of TNFα-targeting agent based on an affibody molecule possessing fundamentally different properties than mAbs. Using phage display technology, we successfully screened and obtained three TNF-α binding affibody molecules and confirmed their high binding affinity and specificity for recombinant and native TNF-α by surface plasmon resonance (SPR), confocal double immunofluorescence and coimmunoprecipitation assays. Moreover, by binding to TNF-α, the affibody molecules could effectively neutralize TNFα-induced L929 cytotoxicity. To increase the targeting properties and serum half-life, one preferred affibody molecule ZTNF-α263 was redesigned to assemble drugs with bivalent TNFα binding with added specificity for serum albumin (ZTNF-α263-ABD035-ZTNF-α263, hereinafter denoted ZTAT). We further determined its binding ability, TNF-α signal blocking and neutralizing capacity, serum half-life and immunogenicity. Most importantly, our study provides strong evidence that the engineered ZTAT protein was therapeutically effective against KD induced-endothelial injury, as judged by both in vitro and in vivo assessments. These data suggested that because of the flexibility inherent, low-molecular weight anti-TNFα affibody construct ZTAT, can be developed into a potent therapeutic agent that can be produced and purified cost-effectively.
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The challenging synthesis of thermodynamic-unfavored cis-olefins through catalytic cross-coupling reactions requires the synergistic interaction of substrate-activating units and configuration-regulating catalysts. Successfully hitting these two birds with one stone, we herein develop a convenient photoredox access to Z-alkenes from alkynes and light alkanes with a bifunctional iron-catalyzed system possessing both C(sp3)-H activation and configuration-controlling abilities. The protocol exhibits 100% atom utilization, mild conditions, a broad substrate scope, and compatibility with multitudinous functional groups. The detailed reaction mechanism and the origin of geometry regulation are well investigated by experimental and computational studies. Progressively, a catalytic amount of diaryl disulfides is introduced for consecutive photoinduced Z-E isomerization via reversible radical addition and flipping. Big steric hindrance substituents assembled on the disulfide emerge necessity for suppressing double-bond migration. This tandem strategy paves a promising way for stereoselective alkene construction and will bring significant inspiration for the development of transition metal photocatalysis.
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OBJECTIVE: Insufficient or prolonged sleep each day may contribute to the onset of cardiovascular disease and diabetes, and there may be some variability between genders; however, current research evidence is limited. We aimed to investigate the effects of gender on self-reported sleep duration and the prevalence of cardiovascular disease and diabetes. RESEARCH DESIGN AND METHODS: This study is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults obtained from the National Health and Nutrition Examination Survey (NHANES) (2005-2020), and 13,002 participants, including 6,774men and 6,228women, were obtained by excluding the missing values for each variable self-reported sleep duration data obtained by using a habitual baseline questionnaire. Logistic regression models investigated the associations between gender-specific self-reported sleep duration, CVDs, and diabetes events. RESULT: In all participants, respectively, compared with sleep 7-8 h/day, the multivariable-adjusted odds ratios significantly associated with < 7 h /day and > 8 h /day were (1.43[1.15, 1.78]) and (1.34[1.01, 1.76]) for CHF, (1.62[1.28, 2.06]) for Angina, (1.42[1.17, 1.71]) for heart attack, (1.38[1.13, 1.70]) and (1.54[1.20, 1.97]) for Stroke, (1.21[1.09, 1.35]) and (1.28[1.11, 1.48]) for diabetes. In men, CHF (1.67[1.21, 2.14]), Angina (1.66[1.18, 2.15]), Stroke (1.55[1.13,1.97]), and diabetes (1.15[1.00, 1.32]) were significantly associated with < 7 h /day, and stroke (1.73[1.16, 2.32]) and diabetes (1.32[1.06, 1.52]) were significantly associated with > 8 h /day. In women, angina(1.83[1.16, 2.50]), heart attack(1.63[1.11, 2.15]), and diabetes (1.32[1.11, 1.54]) were significantly associated with < 7 h /day, while diabetes (1.31[1.03, 1.59]) was significantly associated with > 8 h /day. CONCLUSION: Self-reported long and short sleep duration was independently associated with partial CVDs and diabetes risk. However, sleep duration and gender did not have multiplicative or additive interactions with the onset of diabetes and CVDs.
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Maladies cardiovasculaires , Diabète , Enquêtes nutritionnelles , Autorapport , Sommeil , Humains , Mâle , Femelle , Études transversales , Adulte d'âge moyen , Maladies cardiovasculaires/épidémiologie , Diabète/épidémiologie , Adulte , Facteurs sexuels , États-Unis/épidémiologie , Sommeil/physiologie , Facteurs temps , Sujet âgé , Facteurs de risque , Temps de sommeilRÉSUMÉ
BACKGROUND: To investigate the values of apparent diffusion coefficient (ADC) for the treatment response evaluation in pancreatic cancer (PC) patients receiving neoadjuvant therapy (NAT). METHODS: This study included 103 NAT patients with histologically proven PC. ADC maps were generated using monoexponential diffusion-weighted imaging (b values: 50, 800 s/mm2). Tumors' minimum, maximum, and mean ADCs were measured and compared pre- and post-NAT. Variations in ADC values measured between pre- and post-NAT completion for NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0-2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analyzed. RESULTS: The minimum, maximum, and mean ADC values all increased dramatically after NAT, rising from 23.4 to 25.4% (all p < 0.001): mean (average: 1.626 × 10- 3 mm2/s vs. 1.315 × 10- 3 mm2/s), minimum (median: 1.274 × 10- 3 mm2/s vs. 1.034 × 10- 3 mm2/s), and maximum (average: 1.981 × 10- 3 mm2/s vs. 1.580 × 10- 3 mm2/s). The ADCs between the subgroups of all the criteria under investigation did not differ significantly for the minimum, maximum, or mean values pre- or post-NAT (P = 0.08 to 1.00). In the patients with borderline resectable PC (n = 47), the rate of tumor size changes after NAT was correlated with the pre-NAT mean ADC values (Spearman's coefficient: 0.288, P = 0.049). CONCLUSIONS: The ADC values of PC increased significantly following NAT; however, the percentage increases failed to provide any predictive value for the resection margin status or TRG levels.
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Imagerie par résonance magnétique de diffusion , Traitement néoadjuvant , Tumeurs du pancréas , Humains , Tumeurs du pancréas/anatomopathologie , Tumeurs du pancréas/thérapie , Tumeurs du pancréas/imagerie diagnostique , Tumeurs du pancréas/traitement médicamenteux , Traitement néoadjuvant/méthodes , Mâle , Femelle , Imagerie par résonance magnétique de diffusion/méthodes , Adulte d'âge moyen , Sujet âgé , Adulte , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Études rétrospectives , Résultat thérapeutique , Sujet âgé de 80 ans ou plus , Stadification tumoraleRÉSUMÉ
Thoracic aortic aneurysm and dissection (TAAD) is a devastating macrovascular disease, and its pathogenic mechanisms have not been well clarified. This study aimed to investigate the role of PANoptosis, which is newly defined programmed cell death (PCD) and characterized by pyroptosis, apoptosis, and necroptosis, in the pathogenesis of TAAD. We found that the expression of initiator factor Z-DNA binding protein 1 (ZBP1) and PANoptosis-related genes were upregulated in the ß-aminopropionitrile (BAPN) + Angiotensin II (Ang II)-induced TAAD mice. Ang II stimuli enhanced the expression of ZBP1, promoted the generation of bioactive GSDMD (Gasdermin D) fragments, the cleavage of Caspase 3, and increased the phosphorylation of mixed lineage kinase domain-like pseudokinase (MLKL) in human aortic vascular smooth muscle cells (HASMCs), indicating the activation of hallmarks for PANoptosis. Moreover, ZBP1-mediated PANoptosis occurs in the aortic tissues of TAAD patients. These results highlight the significant role of PANoptosis in TAAD pathogenesis, suggesting ZBP1 and other PANoptosis-related genes as potential therapeutic targets for this condition.
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BACKGROUND AND OBJECTIVE: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients. METHODS: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI). KEY FINDINGS AND LIMITATIONS: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023). CONCLUSIONS AND CLINICAL IMPLICATIONS: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma. PATIENT SUMMARY: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used.
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Soft-bodied aquatic organisms exhibit extraordinary navigation and mobility in liquid environments which inspiring the development of biomimetic actuators with complex movements. Stimulus-responsive soft materials including hydrogels and shape-memory polymers are replacing traditional rigid parts that leading to dynamic and responsive soft actuators. In this study, we took inspiration from water strider to develop a biomimetic actuator for targeted stimulation and pH sensing in the gastrointestinal tract. We designed a soft and water-based Janus adhesive hydrogel patch that attaches to specific parts of the intestine and responds to pH changes through external stimulation. The hydrogel patch that forms the belly of the water strider driver incorporates an inverse opal microstructure that enables pH responsive behavior. The hydrogel patch on the water strider's leg uses a sandwich structure of Cu particles to convert light into heat and bend under infrared light to mimic the water strider's leg simulating the efficient and steady movement of the water strider's leg which transporting the biological fluid in one direction. This miniature bionic actuator demonstrates controlled adhesion and unidirectional biofluid delivery capabilities, proving its potential for targeted stimulus response and pH sensing in the gastrointestinal tract, thus opening up new possibilities for medical applications in the growing field of soft actuators.
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Diffusion Magnetic Resonance Imaging (dMRI) is a noninvasive method for depicting brain microstructure in vivo. Fiber orientation distributions (FODs) are mathematical representations extensively used to map white matter fiber configurations. Recently, FOD estimation with deep neural networks has seen growing success, in particular, those of neonates estimated with fewer diffusion measurements. These methods are mostly trained on target FODs reconstructed with multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD), which might not be the ideal ground truth for developing brains. Here, we investigate this hypothesis by training a state-of-the-art model based on the U-Net architecture on both MSMT-CSD and single-shell three-tissue constrained spherical deconvolution (SS3T-CSD). Our results suggest that SS3T-CSD might be more suited for neonatal brains, given that the ratio between single and multiple fiber-estimated voxels with SS3T-CSD is more realistic compared to MSMT-CSD. Additionally, increasing the number of input gradient directions significantly improves performance with SS3T-CSD over MSMT-CSD. Finally, in an age domain-shift setting, SS3T-CSD maintains robust performance across age groups, indicating its potential for more accurate neonatal brain imaging.
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BACKGROUND: The cell development atlas of transition stage from late Carnegie to fetal development (7-9 weeks) remain unclear. It can be seen that the early period of human embryos (7-9 weeks) is a critical research gap. Therefore, we employed singlecell RNA sequencing to identify cell types and elucidate differentiation relationships. RESULTS: The singlecell RNA sequencing analysis determines eighteen cell clusters in human embryos during the 7-9 weeks period. We uncover two distinct pathways of cellular development and differentiation. Initially, mesenchymal progenitor cells differentiated into osteoblast progenitor cells and neural stem cells, respectively. Neural stem cells further differentiated into neurons. Alternatively, multipotential stem cells differentiated into adipocyte, hematopoietic stem cells and neutrophil, respectively. Additionally, COL1A2-(ITGA1 + ITGB1) mediated the cell communication between mesenchymal progenitor cells and osteoblast progenitor cells. NCAM1-FGFR1 facilitated the cell communication between mesenchymal progenitor cells and neural stem cells. Notably, NCAM1-NCAM1 as a major contributor mediated the cell communication between neural stem cells and neurons. Moreover, CGA-FSHR simultaneously mediated the communication between multipotential stem cells, adipocyte, hematopoietic stem cells and neutrophil. Distinct cell clusters activated specific transcription factors such as HIC1, LMX1B, TWIST1, and et al., which were responsible for their specific functions. These coregulators, such as HOXB13, VSX2, PAX5, and et al., may mediate cell development and differentiation in human embryos. CONCLUSIONS: We provide the cell development atlas for human embryos (7-9 weeks). Two distinct cell development and differentiation pathways are revealed.
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Depending on the intrinsic photoactivity of nitroarenes, we herein developed a practical Brønsted acid-catalyzed decarbonylative amide synthesis from alkynes and photoexcited nitroarenes without any metal or photocatalyst. This method exhibited compatibility with water and air, broad substrate applicability, marvelous functional group tolerance, and wide applications in scale-up synthesis, late-stage functionalization, and total synthesis. Mechanism studies and DFT calculations supported that a 1,3,2-dioxazole intermediate was involved, and gaseous carbon monoxide was the only byproduct during amide construction.
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Recent studies have provided promising evidence that neuroimaging data can predict treatment outcomes for patients with major depressive disorder (MDD). As most of these studies had small sample sizes, a meta-analysis is warranted to identify the most robust findings and imaging modalities, and to compare predictive outcomes obtained in magnetic resonance imaging (MRI) and studies using clinical and demographic features. We conducted a literature search from database inception to July 22, 2023, to identify studies using pretreatment clinical or brain MRI features to predict treatment outcomes in patients with MDD. Two meta-analyses were conducted on clinical and MRI studies, respectively. The meta-regression was employed to explore the effects of covariates and compare the predictive performance between clinical and MRI groups, as well as across MRI modalities and intervention subgroups. Meta-analysis of 13 clinical studies yielded an area under the curve (AUC) of 0.73, while in 44 MRI studies, the AUC was 0.89. MRI studies showed a higher sensitivity than clinical studies (0.78 vs. 0.62, Z = 3.42, P = 0.001). In MRI studies, resting-state functional MRI (rsfMRI) exhibited a higher specificity than task-based fMRI (tbfMRI) (0.79 vs. 0.69, Z = -2.86, P = 0.004). No significant differences in predictive performance were found between structural and functional MRI, nor between different interventions. Of note, predictive MRI features for treatment outcomes in studies using antidepressants were predominantly located in the limbic and default mode networks, while studies of electroconvulsive therapy (ECT) were restricted mainly to the limbic network. Our findings suggest a promise for pretreatment brain MRI features to predict MDD treatment outcomes, outperforming clinical features. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. Overlapping but distinct network-level measures predicted antidepressants and ECT outcomes. Future studies are needed to predict outcomes using multiple MRI features, and to clarify whether imaging features predict outcomes generally or differ depending on treatments.
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Background: The cholinergic hypothesis is one of the main theories that describe the pathogenesis of Alzheimer's disease (AD). Cholinergic neurons degenerate early and are severely damaged in AD. Despite extensive research, the causes of cholinergic neuron damage and the underlying molecular changes remain unclear. Objective: This study aimed to explore the characteristics and transcriptomic changes in cholinergic neurons derived from human induced pluripotent stem cells (iPSCs) with APP mutation. Methods: Peripheral blood mononuclear cells from patients with AD and healthy individuals were reprogrammed into iPSCs. The iPSCs were differentiated into cholinergic neurons. Cholinergic neurons were stained, neurotoxically tested, and electrophysiologically and transcriptomically analyzed. Results: The iPSCs-derived cholinergic neurons from a patient with AD carrying a mutation in APP displayed enhanced susceptibility to Aß1-42-induced neurotoxicity, characterized by severe neurotoxic effects, such as cell body coagulation and neurite fragmentation. Cholinergic neurons exhibited electrophysiological impairments and neuronal death after 21 days of culture in the AD group. Transcriptome analysis disclosed 883 differentially expressed genes (DEGs, 420 upregulated and 463 downregulated) participating in several signaling pathways implicated in AD pathogenesis. To assess the reliability of RNA sequencing, the expression of 16 target DEGs was validated using qPCR. Finally, the expression of the 8 core genes in different cell types of brain was analyzed by the AlzData database. Conclusions: In this study, iPSCs-derived cholinergic neurons from AD patients with APP mutations exhibit characteristics reminiscent of neurodegenerative disease. Transcriptome analysis revealed the corresponding DEGs and pathways, providing potential biomarkers and therapeutic targets for advancing AD research.
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Maladie d'Alzheimer , Précurseur de la protéine bêta-amyloïde , Neurones cholinergiques , Cellules souches pluripotentes induites , Mutation , Humains , Cellules souches pluripotentes induites/métabolisme , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/anatomopathologie , Précurseur de la protéine bêta-amyloïde/génétique , Neurones cholinergiques/métabolisme , Neurones cholinergiques/anatomopathologie , Mutation/génétique , Analyse de profil d'expression de gènes , Transcriptome , Peptides bêta-amyloïdes/métabolisme , Différenciation cellulaire/génétique , Mâle , Fragments peptidiques/génétique , Fragments peptidiques/métabolisme , FemelleRÉSUMÉ
Polymyxin B (PB) and Polymyxin E (PE, also called colistin) are used as the last treatment resort for multidrug-resistant Gram-negative bacterial infections. The nephrotoxicity and neurotoxicity of polymyxins limit their clinical use, and guidelines recommend therapeutic drug monitoring (TDM) to optimize efficacy and reduce toxicity. However, there are limited analytical methods available for the determination of PB and PE. This study aimed to develop a simple and robust liquid chromatography with tandem mass spectrometry (LC-MS/MS) analytical method for determining the main compounds of PB and PE, namely PB1, PB2, ile-PB1, PE1, and PE2, in human plasma and to investigate of their pharmacokinetics in critically ill patients with the use of PB and PE, respectively. Plasma PB1, PB2, ile-PB1, PE1, and PE2 were chromatographically separated on a Welch LP-C18 column and detected using electrospray ionization mode coupled with multiple reaction monitoring. The calibration curve showed acceptable linearity over 20-10,000â¯ng/mL for PB1, PE1, and PE2 and 10-5000â¯ng/mL for PB2 and ile-PB1 in the plasma, respectively. After validation following approved guidelines, this method was successfully applied for PB and PE pharmacokinetic analysis and TDM in critically ill patients. Additionally, the composition of PB1, PB2, ile-PB1, PE1, and PE2 remains unchanged from 0 to 12â¯h after entering the patient's body.
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Antibactériens , Surveillance des médicaments , Polymyxine B , Spectrométrie de masse en tandem , Femelle , Humains , Mâle , Adulte d'âge moyen , Antibactériens/pharmacocinétique , Antibactériens/sang , Calibrage , Chromatographie en phase liquide à haute performance/méthodes , Chromatographie en phase liquide/méthodes , Colistine/pharmacocinétique , Colistine/sang , Colistine/analogues et dérivés , Maladie grave , Surveillance des médicaments/méthodes , Limite de détection , Polymyxine B/pharmacocinétique , Polymyxine B/sang , Polymyxines/pharmacocinétique , Polymyxines/sang , Polymyxines/analogues et dérivés , Reproductibilité des résultats , Spectrométrie de masse en tandem/méthodesRÉSUMÉ
The pursuit of flexible, sensitive, and cost-effective pressure sensors plays a pivotal role in medical diagnostics, particularly in the domain of cervical health monitoring. However, significant challenges remain in the economical production of flexible piezoresistive materials and the integration of microstructures aimed at enhancing sensor sensitivity. This urge highlights the use of innovative, stable hydrogel films that demonstrate robust adherence to soft biological tissues, thereby enabling prolonged bio-signal monitoring. In this study, we introduce an innovative integration of a flexible pressure electrical signal sensor with structural color hydrogel scaffolds. This integration leverages the tunability of the inverse opal structure to fine-tune the scaffold's adherence to the endocervical wall under varying environmental conditions and to amplify the sensitivity of pressure measurements. Our findings indicate that this novel approach holds promise for substantial enhancements in the manufacturing and functional capabilities of cervical pressure sensors, potentially revolutionizing personalized medical treatments and improving patient monitoring.
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Col de l'utérus , Hydrogels , Pression , Mouillabilité , Femelle , Hydrogels/composition chimique , Humains , Colloïdes/composition chimique , Propriétés de surfaceRÉSUMÉ
Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of three commonly used TKIs (imatinib, dasatinib, and nilotinib) and three commonly used triazoles (voriconazole, itraconazole, and posaconazole) in human plasma. The analytes were eluted on a Welch XB-C18 analytical column (50 × 2.1 mm, 5 µm) at 0.7 mL/min, using a gradient elution of 10 mM ammonium formate (A) and methanol-acetonitrile-isopropanol (80:10:10, v/v/v) containing 0.2 % formic acid (B) with a total analysis time of 3.5 min. The calibration curves were linear over the range from 20 to 4000 ng/mL for imatinib and nilotinib, from 2 to 400 ng/mL for dasatinib, and from 50 to 10,000 ng/mL for voriconazole, itraconazole, and posaconazole. Selectivity, accuracy, precision, recovery, matrix effect, and stability all met the validation requirements. The method was successfully used for TDM in CML patients who co-treated with both TKIs and triazoles. Drug-drug interaction analysis between TKIs and triazoles showed that a significant positive correlation was observed between imatinib and voriconazole, as well as dasatinib and voriconazole. Therefore, this method can be well applied in clinical TDM for patients receiving TKIs, triazoles, or both simultaneously.
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Interactions médicamenteuses , Surveillance des médicaments , Inhibiteurs de protéines kinases , Spectrométrie de masse en tandem , Triazoles , Humains , Spectrométrie de masse en tandem/méthodes , Triazoles/sang , Triazoles/usage thérapeutique , Surveillance des médicaments/méthodes , Inhibiteurs de protéines kinases/sang , Inhibiteurs de protéines kinases/usage thérapeutique , Inhibiteurs de protéines kinases/pharmacocinétique , Inhibiteurs de protéines kinases/composition chimique , Reproductibilité des résultats , Chromatographie en phase liquide/méthodes , Modèles linéaires , Limite de détection , Liquid Chromatography-Mass SpectrometryRÉSUMÉ
PURPOSE: To investigate the prevalence of insomnia among nurses with long COVID-19, analyze the potential risk factors and establish a nomogram model. METHODS: Nurses in Ningbo, China, were recruited for this study. General demographic information and insomnia, burnout, and stress assessment scores were collected through a face-to face questionnaire survey administered at a single center from March to May 2023. We used LASSO regression to identify potential factors contributing to insomnia. Then, a nomogram was plotted based on the model chosen to visualize the results and evaluated by receiver operating characteristic curves and calibration curves. RESULTS: A total of 437 nurses were recruited. 54% of the nurses had insomnia according to the Insomnia Severity Index (ISI) score. Eleven variables, including family structure, years of work experience, relaxation time, respiratory system sequelae, nervous system sequelae, others sequelae, attitudes toward COVID-19, sleep duration before infection, previous sleep problems, stress, and job burnout, were independently associated with insomnia. The R-squared value was 0.464, and the area under the curve was 0.866. The derived nomogram showed that neurological sequelae, stress, job burnout, sleep duration before infection, and previous sleep problems contributed the most to insomnia. The calibration curves showed significant agreement between the nomogram models and actual observations. CONCLUSION: This study focused on insomnia among nurses with long COVID-19 and identified eleven risk factors related to nurses' insomnia. A nomogram model was established to illustrate and visualize these factors, which will be instrumental in future research for identifying nurses with insomnia amid pandemic normalization and may increase awareness of the health status of healthcare workers with long COVID-19.
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BACKGROUND: Auxin, a plant hormone, plays diverse roles in the modulation of plant growth and development. The transport and signal transduction of auxin are regulated by various factors involved in shaping plant morphology and responding to external environmental conditions. The auxin signal transduction is primarily governed by the following two gene families: the auxin response factor (ARF) and auxin/indole-3-acetic acid (AUX/IAA). However, a comprehensive genomic analysis involving the expression profiles, structures, and functional features of the ARF and AUX/IAA gene families in Vaccinium bracteatum has not been carried out to date. RESULTS: Through the acquisition of genomic and expression data, coupled with an analysis using online tools, two gene family members were identified. This groundwork provides a distinguishing characterization of the chosen gene families in terms of expression, interaction, and response in the growth and development of plant fruits. In our genome-wide search of the VaARF and VaIAA genes in Vaccinium bracteatum, we identified 26 VaARF and 17 VaIAA genes. We analyzed the sequence and structural characteristics of these VaARF and VaIAA genes. We found that 26 VaARF and 17 VaIAA genes were divided into six subfamilies. Based on protein interaction predictions, VaIAA1 and VaIAA20 were designated core members of VaIAA gene families. Moreover, an analysis of expression patterns showed that 14 ARF genes and 12 IAA genes exhibited significantly varied expressions during fruit development. CONCLUSION: Two key genes, namely, VaIAA1 and VaIAA20, belonging to a gene family, play a potentially crucial role in fruit development through 26 VaARF-IAAs. This study provides a valuable reference for investigating the molecular mechanism of fruit development and lays the foundation for further research on Vaccinium bracteatum.
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Régulation de l'expression des gènes végétaux , Acides indolacétiques , Famille multigénique , Protéines végétales , Acides indolacétiques/métabolisme , Protéines végétales/génétique , Protéines végétales/métabolisme , Phylogenèse , Génome végétal , Facteur de croissance végétal/métabolisme , Facteur de croissance végétal/génétique , Vaccinium/génétique , Vaccinium/métabolisme , Fruit/génétique , Fruit/métabolisme , Fruit/croissance et développement , Facteurs de transcription/génétique , Facteurs de transcription/métabolismeRÉSUMÉ
Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.
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Apolipoprotéines E , Cellules souches pluripotentes induites , Mutation , Humains , Cellules souches pluripotentes induites/métabolisme , Cellules souches pluripotentes induites/cytologie , Femelle , Apolipoprotéines E/génétique , Apolipoprotéines E/métabolisme , Lignée cellulaire , Différenciation cellulaire , Caryotype , Agranulocytes/métabolisme , Agranulocytes/cytologieRÉSUMÉ
INTRODUCTION: The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer's disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail. METHODS AND ANALYSIS: This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events. ETHICS AND DISSEMINATION: This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences. PROTOCOL VERSION: V 3.0, 3 September 2022. TRIAL REGISTRATION NUMBER: ChiCTR1800018362.
Sujet(s)
Benzofuranes , Dysfonctionnement cognitif , Neuroprotecteurs , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Benzofuranes/usage thérapeutique , Benzofuranes/effets indésirables , Cognition/effets des médicaments et des substances chimiques , Dysfonctionnement cognitif/traitement médicamenteux , Méthode en double aveugle , Études multicentriques comme sujet , Neuroprotecteurs/usage thérapeutique , Neuroprotecteurs/effets indésirables , Tests neuropsychologiques , Essais contrôlés randomisés comme sujet , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Controllability analysis is an approach developed for evaluating the ability of a brain region to modulate function in other regions, which has been found to be altered in major depressive disorder (MDD). Both depressive symptoms and cognitive impairments are prominent features of MDD, but the case-control differences of controllability between MDD and controls can not fully interpret the contribution of both clinical symptoms and cognition to brain controllability and linked patterns among them in MDD. METHODS: Sparse canonical correlation analysis was used to investigate the associations between resting-state functional brain controllability at the network level and clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. FINDINGS: Average controllability was significantly correlated with clinical features. The average controllability of the dorsal attention network (DAN) and visual network had the highest correlations with clinical variables. Among clinical variables, depressed mood, suicidal ideation and behaviour, impaired work and activities, and gastrointestinal symptoms were significantly negatively associated with average controllability, and reduced cognitive flexibility was associated with reduced average controllability. INTERPRETATION: These findings highlight the importance of brain regions in modulating activity across brain networks in MDD, given their associations with symptoms and cognitive impairments observed in our study. Disrupted control of brain reconfiguration of DAN and visual network during their state transitions may represent a core brain mechanism for the behavioural impairments observed in MDD. FUNDING: National Natural Science Foundation of China (82001795 and 82027808), National Key R&D Program (2022YFC2009900), and Sichuan Science and Technology Program (2024NSFSC0653).