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Precise and spatiotemporally controllable analysis of microRNA-21 in living cells is crucial for accurate diagnosis and effective treatment of related diseases. Herein, a near-infrared (NIR)-photoactivatable DNA nanomachine (PUCNPs-NH2/PEG-ZL-DNA) was constructed for the precise analysis and diagnosis of microRNA-21 in tumor cells. Peanut-shaped upconversion nanoparticles (PUCNPs) were employed as the carriers and activators for the intelligent DNA probe, specifically enabling the cleavage of the photocleavable linker (PC-linker) from the hairpin DNA probe (Hp-Dzy) upon exposure to 808 nm irradiation. In the presence of the target microRNA-21, the locker DNA hybridized with microRNA-21 and the DNAzymes was freed to hybridize with the looped portion of the hairpin DNA (Hp-1). Mg2+ was employed as the cofactor, facilitating the precise cleavage of Hp-1, which triggered the restoration of fluorescence signals. Subsequently, DNAzymes exhibited the competency to selectively recognize and engage with additional Hp-1, and the fluorescence signals were effectively amplified by the recycling process. Consequently, the DNA nanomachine exhibited a linear response to microRNA-21 concentrations ranging from 0.5 nM to 1.0 µM, achieving a remarkable detection limit (LOD) of 1.19 nM under the optimal conditions. This strategy is realized through the integration of photocontrollable upconversion nanotechnology with the signal amplification approach, showing feasible prospects for spatiotemporally precise and highly sensitive monitoring of microRNA in tumor cells.

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Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that shows promise for the treatment of Parkinson's disease (PD). However, there is still limited understanding of the optimal stimulation frequencies and whether rTMS can alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. Methods: A PD mouse model was induced intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 1 Hz, 5 Hz, and 10 Hz rTMS. The neurological function, survival of dopaminergic neurons, and protein levels of Tyrosine hydroxylase (TH), α-synuclein(α-syn), and brain-derived neurotrophic factor (BDNF) in the striatum were measured to determine the optimal stimulation frequencies of rTMS treatment in PD mice. The levels of melatonin, cortisol, and the circadian rhythm of Brain and muscle ARNT-like 1 (BMAL1) in PD model mice were detected after optimal frequency rTMS treatment. Additionally, KN-93 and Bmal1siRNA interventions were used to verify that rTMS could alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. Results: Administration of 10 Hz rTMS significantly improved neurological function, increased the protein levels of TH and BDNF, and inhibited abnormal aggregation of a-syn. Furthermore, administration of 10 Hz rTMS regulated the secretion profile of cortisol and melatonin and reversed the circadian arrhythmia of BMAL1 expression. After the KN-93 intervention, the MPTP+rTMS+KN-93 group exhibited decreased levels of P- Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CaMKII, P-cAMP-response-element-binding protein (CREB)/CREB, BMALI, and TH. After Bmal1siRNA intervention, the protein levels of BMAL1 and TH were significantly reduced in the MPTP+10 Hz+ Bmal1siRNA group. At the same time, there were no significant changes in the proportions of P-CaMKIIα/CaMKIIα and P-CREB/CREB expression levels. Finally, immunohistochemical analysis showed that the number of TH-positive neurons was high in the MPTP+10 Hz group, but decreased significantly after KN-93 and Bmal1siRNA interventions. Conclusion: Treatment with 10 Hz rTMS alleviated MPTP-induced PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. This study provides a comprehensive perspective of the therapeutic mechanisms of rTMS in PD.

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Artemisia argyi Levl. et Vant. (A. argyi) is an important member of Asteraceae (Compositae) family, which has good medicinal potential and edible value. Phytochemical studies have shown that the A. argyi has a variety of bioactive components, mainly including polysaccharides, flavonoids, alkaloids, and volatile oil. More and more evidences show that A. argyi polysaccharide is a kind of representative pharmacological and biological active macromolecules, which has a variety of pharmacological activities in vitro and in vivo, such as estrogen-like effect, anti-bacterial, anti-tumor, anti-oxidant and immune regulation effect. As far as we know, there are few comprehensively reviews on A. argyi polysaccharide. This review aims to comprehensively and systematically review the research progress on the extractions and purifications, structural characteristics, pharmacological activities, structure-activity relationships, existing and potential applications of A. argyi polysaccharides in the past 12 years, in order to support their therapeutic potential and health functions. Finally, prospects were made for the further development and utilization of A. argyi polysaccharides in four fields: food, medicine, packaging materials, and daily chemicals.

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Metabolic syndrome (MetS) is a significant public health problem and presents an escalating clinical challenge globally. To combat this problem effectively, urgent measures including identify some modifiable environmental factors are necessary. Outdoor artificial light at night (LAN) exposure garnered much attention due to its impact on circadian rhythms and metabolic process. However, epidemiological evidence on the association between outdoor LAN exposure and MetS remains limited. To determine the relationship between outdoor LAN exposure and MetS, 15,477 adults participated the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. Annual levels of outdoor LAN exposure at participants' residential addresses were assessed using satellite data from the Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS). Generalized linear mixed effect models were utilized to assess the association of LAN exposure with MetS and its components, including elevated waist circumference (WC), triglycerides (TG), blood pressure (BP), fasting blood glucose (FBG), and reduced high-density lipoprotein cholesterol (HDL-C). Effect modification by various social demographic and behavior factors was also examined. Overall, 4701 (30.37 %) participants were defined as MetS. The LAN exposure ranged from 6.03 to 175.00 nW/cm2/sr. The adjusted odds ratio (OR) of MetS each quartile increment of LAN exposure were 1.43 (95 % CI: 1.21-1.69), 1.44 (95 % CI: 1.19-1.74) and 1.52 (95 % CI: 1.11-2.08), respectively from Q2-Q4. Similar adverse associations were also found for the components of MetS, especially for elevated BP, TG and FBG. Interaction analyses indicated that the above associations were stronger in participants without habitual exercise compared with those with habitual exercise (e.g. OR were 1.52 [95 % CI: 1.28-1.82] vs. 1.27 [95 % CI, 1.04-1.55], P-interaction = 0.042 for MetS). These findings suggested that long-term exposure to LAN can have a significant deleterious effect on MetS, potentially making LAN an important modifiable environmental factor to target in future preventive strategies.

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Lead (Pb) is an environmentally widespread bone toxic pollutant, contributes to the development of osteoporosis. Butyric acid, mainly produced by the fermentation of indigestible dietary fiber by gut microbiota, plays a pivotal role in the maintenance of bone homeostasis. However, the effects of butyric acids on the Pb induced osteoporosis have not yet been elucidated. In this study, our results showed that Pb exposure was negatively related to the abundance of butyric acid, in the Pb-exposed population and Pb-exposed mice. Pb exposure caused gut microbiota disorders, resulting in the decline of butyric acid-producing bacteria, such as Butyrivibrio_crossotus, Clostridium_sp._JN9, and the butyrate-producing enzymes through the acetyl-CoA pathway. Moreover, results from the NHANES data suggested that dietary intake of butyrate was associated with a reduced risk of osteoporosis in lead-burdened populations, particularly among men or participants aged 18-60 years. In addition, butyrate supplementation in mice with chronic Pb exposure improved the bone microarchitectures, repaired intestinal damage, upregulated the proportion of Treg cells. Taken together, these results demonstrated that chronic Pb exposure disturbs the gut-bone axis, which can be restored by butyric acid supplement. Our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced bone toxicity.

Asunto(s)

Butiratos , Microbioma Gastrointestinal , Plomo , Osteoporosis , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Osteoporosis/inducido químicamente , Ratones , Plomo/toxicidad , Masculino , Femenino , Butiratos/farmacología , Ácido Butírico/farmacología , Humanos , Adulto , Huesos/efectos de los fármacos , Persona de Mediana Edad , Adulto Joven , Adolescente , Ratones Endogámicos C57BL

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Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 min. The proposed detection platform offers portability, ease of use, and high sensitivity, which facilitates the monitoring of exercise-induced muscle injuries at the point of care. This feature is particularly advantageous for end users, enabling timely detection of sports-related injuries and ultimately enhancing prognosis and sports life.

Asunto(s)

Músculo Esquelético , Sistemas de Atención de Punto , Troponina I , Troponina I/sangre , Humanos , Inmunoensayo , Músculo Esquelético/lesiones , Biomarcadores/sangre , Técnicas Biosensibles , Límite de Detección

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Selenium (Se)-doped nanoparticles as novel Se fertilizers have a promising potential in the agricultural application. Here, the effects of two novel Se-doped carbon quantum dots (Se-CQDs1 and Se-CQDs2, prepared using co-cracking and adsorption-reduction methods, respectively) on the growth and Se enrichment of tomato plants were studied, where the promoting molecular mechanisms were explored in terms of the related genes expression and soil microbial composition. The results indicated that the soil application of 2.5 mg kg-1 Se-CQDs1 more significantly increased the root growth, plant biomass, and fruit yield than that of Se-CQDs2 and Na2SeO3 treatments (control). Specifically, Se-CQDs1 treatment was more effective to up-regulate the expressions of aquaporin gene (i.e., PIP) and growth hormone synthesis gene (i.e., NIT) than Se-CQDs1 and Na2SeO3 treatments. The expressions of Se methyltransferase gene (smt) and methionine methyltransferase gene (mmt) induced by Se-CQDs1 were 1.45 and 1.18 times higher than that by Se-CQDs2 as well as 1.82 and 2.17 times higher than that by Na2SeO3. Also, Se-CQDs1 more greatly increased the diversity and relative abundance of soil bacterial communities, especially the Actinobacteria phylum, which was beneficial to increase plant growth-promoting substances. These outstanding promoting effects of Se-CQDs1 were mainly ascribed to its higher hydrophilicity and content of the stable doped-Se. The overall results demonstrated that Se-CQDs would be a promising candidate for nano-fertilizer to increase crop growth and development (e.g., tomato plants), where the synthesis modes of Se-CQDs play a critical role in regulating the utilization efficiency of Se.

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Rationale: Autism spectrum disorder (ASD) represents a complex neurodevelopmental condition lacking specific pharmacological interventions. Given the multifaced etiology of ASD, there exist no effective treatment for ASD. Rapamycin (RAPA) can activate autophagy by inhibiting the mTOR pathway and has exhibited promising effects in treating central nervous system disorders; however, its limited ability to cross the blood-brain barrier (BBB) has hindered its clinical efficacy, leading to substantial side effects. Methods: To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism. Results: The fabricated SCM@RAPA nanoparticles, with an average diameter of 110 nm, exhibit rapid release of RAPA in a pathological environment characterized by oxidative stress. In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage. SS31 peptide modification significantly enhances the BBB penetration and rapid brain accumulation of SCM@RAPA. Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models. Conclusions: The therapeutic potential of SCM@RAPA in managing ASD signifies a paradigm shift in autism drug treatment, holding promise for clinical interventions in diverse neurological conditions.

Asunto(s)

Trastorno del Espectro Autista , Autofagia , Barrera Hematoencefálica , Nanopartículas , Estrés Oxidativo , Sirolimus , Sirolimus/administración & dosificación , Sirolimus/farmacología , Estrés Oxidativo/efectos de los fármacos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/metabolismo , Animales , Autofagia/efectos de los fármacos , Nanopartículas/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Ratones , Humanos , Sistemas de Liberación de Medicamentos/métodos , Modelos Animales de Enfermedad , Masculino , Materiales Biomiméticos/administración & dosificación , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Biomimética/métodos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología

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Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population.

Asunto(s)

Clopidogrel , Citocromo P-450 CYP2C19 , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Clorhidrato de Prasugrel , Medicina de Precisión , Sistema de Registros , Ticagrelor , Humanos , Intervención Coronaria Percutánea/efectos adversos , Citocromo P-450 CYP2C19/genética , Medicina de Precisión/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Ticagrelor/administración & dosificación , Ticagrelor/uso terapéutico , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/uso terapéutico , Clorhidrato de Prasugrel/efectos adversos , Terapia Antiplaquetaria Doble/métodos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control

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Anaplastic thyroid carcinoma (ATC) is a highly aggressive human malignancy without effective treatment. Yes-associated protein (YAP) is a critical effector of the Hippo pathway, which is essential in thyroid carcinogenesis. However, the underlying mechanisms of aberrant YAP expression in ATC are not completely understood. Ubiquitylation-related enzyme siRNA screening identified the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) as a stabilizer of YAP in ATC cells. UBR1 deficiency reduced YAP protein levels and its target gene expression. UBR1 directly interacted with YAP and promoted its monoubiquitylation, competitively suppressing its polyubiquitylation and resulting in extended protein half-life. UBR1 depletion reduced ATC cell proliferation and migration in vitro. Xenograft tumor studies also suggested that UBR1 knockdown suppressed ATC cell growth in vivo. Furthermore, exogenous YAP expression partially reversed the inhibitive effects of UBR1 depletion on ATC cell proliferation and migration. Our studies demonstrated that UBR1 directly interacts with YAP and stabilized it in a monoubiquitylation-dependent manner, consequently promoting ATC tumorigenesis, suggesting that UBR1 might be a potentially therapeutic target for ATC treatment.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales , Movimiento Celular , Proliferación Celular , Carcinoma Anaplásico de Tiroides , Factores de Transcripción , Ubiquitinación , Proteínas Señalizadoras YAP , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/genética , Proteínas Señalizadoras YAP/metabolismo , Proteínas Señalizadoras YAP/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Ratones , Estabilidad Proteica , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Progresión de la Enfermedad , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Fosfoproteínas/metabolismo , Fosfoproteínas/genética

RESUMEN

RESEARCH QUESTION: Does euploidy status differ among patients of different ages treated with progestin-primed ovarian stimulation (PPOS) or gonadotrophin releasing hormone antagonist (GnRH-a) protocols? DESIGN: Patients undergoing PGT-A (n = 418; 440 cycles) were enrolled and grouped according to female age (<35 years and ≥35 years). Protocols were as follows: PPOS: <35 years (n = 131; 137 cycles); ≥35 years (n = 72; 80 cycles); GnRH-a: <35 years (n = 149; 152 cycles); ≥35 years (n = 66; 71 cycles). RESULTS: For cycles treated with PPOS in the older group, rates of euploid blastocyst per metaphase Ⅱ oocyte (15.48% versus 10.47%) and per biopsied blastocyst (54.94% versus 40.88%) were significantly higher than those treated with GnRH-a (P < 0.05). The mosaic rate per biopsied blastocyst was significantly lower for cycles treated with PPOS than cycles treated with GnRH-a (8.64% versus 23.36%) (P < 0.001). In the younger group, no significant difference was found between treatments (P > 0.05). In older and younger groups, the drug to inhibit LH surge was cheaper for cycles treated with PPOS compared with GnRH-a (P < 0.001). Generalized estimation equations based on binomial distribution female age and euploidy rate was significantly negatively correlated for all participants (ß -0.109, 95% CI -0.183 to -0.035, P = 0.004), and between GnRH-a protocol (reference: PPOS) and the euploidy rate in the older group (ß -0.126, 95% CI -0.248 to -0.004, P = 0.042). Multiple logistic regression indicated that ovarian stimulation protocol was not associated with ongoing pregnancy rate (OR 0.652, 95% CI 0.358 to 1.177; P = 0.14). CONCLUSIONS: PPOS is suitable for patients undergoing PGT-A, particularly older patients for the higher euploid blastocyst rate attained by PPOS protocol.

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Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research. Material and methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references. Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends. Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.

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Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder affecting millions globally. It encompasses both motor and non-motor symptoms, with a notable impact on patients' quality of life. Electroencephalogram (EEG) is a non-invasive tool that is increasingly utilized to investigate neural mechanisms in PD, identify early diagnostic markers, and assess therapeutic responses. Methods: The data were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database, focusing on publications related to EEG research in PD from 2004 to 2023. A comprehensive bibliometric analysis was conducted using CiteSpace and VOSviewer software. The analysis began with an evaluation of the selected publications, identifying leading countries, institutions, authors, and journals, as well as co-cited references, to summarize the current state of EEG research in PD. Keywords are employed to identify research topics that are currently of interest in this field through the analysis of high-frequency keyword co-occurrence and cluster analysis. Finally, burst keywords were identified to uncover emerging trends and research frontiers in the field, highlighting shifts in interest and identifying future research directions. Results: A total of 1,559 publications on EEG research in PD were identified. The United States, Germany, and England have made notable contributions to the field. The University of London is the leading institution in terms of publication output, with the University of California closely following. The most prolific authors are Brown P, Fuhr P, and Stam C In terms of total citations and per-article citations, Stam C has the highest number of citations, while Brown P has the highest H-index. In terms of the total number of publications, Clinical Neurophysiology is the leading journal, while Brain is the most highly cited. The most frequently cited articles pertain to software toolboxes for EEG analysis, neural oscillations, and PD pathophysiology. Through analyzing the keywords, four research hotspots were identified: research on the neural oscillations and connectivity, research on the innovations in EEG Analysis, impact of therapies on EEG, and research on cognitive and emotional assessments. Conclusion: This bibliometric analysis demonstrates a growing global interest in EEG research in PD. The investigation of neural oscillations and connectivity remains a primary focus of research. The application of machine learning, deep learning, and task analysis techniques offers promising avenues for future research in EEG and PD, suggesting the potential for advancements in this field. This study offers valuable insights into the major research trends, influential contributors, and evolving themes in this field, providing a roadmap for future exploration.

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Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder with considerable heterogeneity, in which over-generated reactive oxygen species (ROS) induce a cascade of pathological changes, including cellular apoptosis and inflammatory responses. Given the complex etiology of ASD, no effective treatment is available for ASD. In this work, a specific catalytic nanoenzyme, calcium hexacyanoferrate (III) nanocatalysts (CaH NCs), is designed and engineered for efficient ASD treatment. CaH NCs can mimic the activities of natural enzymes including superoxide dismutase, peroxidase, catalase, and glutathione peroxidase, which mitigates intracellular excessive ROS and regulates redox equilibrium. These CaH NCs modulate mitochondrial membrane potential, elevate B-cell lymphoma-2 levels, and suppress pro-apoptotic proteins, including Caspase-3 and B-cell lymphoma-2-associated X, thus effectively reducing cellular apoptosis. Importantly, CaH NCs alleviate inflammation by upregulating anti-inflammatory cytokine interleukin-10 and downregulating pro-inflammatory factors, resulting in attenuated activation of microglial and astrocytic and subsequent reduction in neuroinflammation. Subsequently, CaH NCs enhance social abilities, decrease anxiety levels, ameliorate repetitive behaviors, and improve learning and memory in ASD animal models through inflammation regulation and apoptosis inhibition. The CaH NCs in managing and preventing ASD represents a paradigm shift in autism treatment, paving the alternative but efficient way for clinical interventions in neurological conditions.

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Lubricating base oils have been extensively employed for producing various industrial and consumer products. Therefore, their environmental and health impacts should be carefully evaluated. Although there have been many reports on pulmonary cytotoxicity and inflammatory responses of inhaled lubricating base oils, their potential influences on pulmonary surfactant (PS) films that play an essential role in maintaining respiratory mechanics and pulmonary immunity remains largely unknown. Here a systematic study on the interactions between an animal-derived natural PS and aerosols of water and representative mineral and vegetable base oils is performed using a novel biophysical assessing technique called constrained drop surfactometry capable of providing in vitro simulations of normal tidal breathing and physiologically relevant temperature and humidity in the lung. It was found that the mineral oil aerosols can impose strong inhibitions to the biophysical property of PS film, while the airborne vegetable oils and water show negligible adverse effects within the studied concentration range. The inhibitory effect is originated from the strong hydrophobicity of mineral oil, which makes it able to disrupt the interfacial molecular ordering of both phospholipid and protein compositions and consequently suppress the formation of condensed phase and multilayer scaffolds in a PS film. ENVIRONMENTAL IMPLICATION: Understanding the biophysical influence of airborne lubricating base oils on pulmonary surfactant (PS) films can provide new insights into the environmental impacts and health concerns of various industrial lubricant products. Here a comparative study on interactions between an animal-derived natural PS film and the aerosols of water and representative mineral and vegetable base oils under the true physiological conditions was conducted in situ using constrained drop surfactometry. We show that the most frequently used mineral base oil can cause strong inhibitions to the PS film by disrupting the molecular ordering of saturated phospholipids and surfactant-associated proteins at the interface.

Asunto(s)

Aerosoles , Lubricantes , Surfactantes Pulmonares , Aerosoles/química , Surfactantes Pulmonares/química , Lubricantes/química , Aceite Mineral/química , Animales , Aceites de Plantas/química , Fosfolípidos/química , Agua/química

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The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

Asunto(s)

Fármacos Anti-VIH , Coinfección , Infecciones por VIH , Lamivudine , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Polimorfismo de Nucleótido Simple , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Femenino , Masculino , Adulto , Lamivudine/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Tenofovir/uso terapéutico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Persona de Mediana Edad , Coinfección/tratamiento farmacológico , Coinfección/genética , Leucocitos Mononucleares/metabolismo , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/efectos de los fármacos , Organofosfatos/uso terapéutico , Organofosfatos/farmacocinética , Hepatitis B/tratamiento farmacológico , Hepatitis B/genética , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/farmacocinética , Polifosfatos/metabolismo , Farmacogenética/métodos

RESUMEN

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.

Asunto(s)

Enfermedades Cardiovasculares , MicroARN Circulante , Mieloma Múltiple , Oligopéptidos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/sangre , Masculino , Femenino , Oligopéptidos/efectos adversos , Anciano , Persona de Mediana Edad , MicroARN Circulante/sangre , MicroARN Circulante/genética , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/sangre , MicroARNs/genética , MicroARNs/sangre , Estudios Prospectivos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos

RESUMEN

A new species of the genus Hebius Thompson, 1913 is described from Yingjiang County, Dehong Dai and Jingpo Autonomous Prefecture, Yunnan Province, China, based on molecular and morphological evidence. It can be distinguished from its congeners by the following set of characters: (1) dorsal scale rows 19-17-17, feebly keeled; (2) ventrals 146-151; (3) nasal complete, nostril in the middle of the nasal; (4) supralabials 9, the fourth to sixth in contact with the eye; (5) infralabials 10-11, the first 5 touching the first pair of chin shields; (6) preoculars 2; (7) postoculars 3; (8) temporals 3, arranged in two rows (1+2); (9) maxillary teeth 31, the last 4 slightly enlarged, without diastema; (10) tail comparatively long, TAL/TL ratio 0.334 in the male; (11) dorsolateral series of irregular orange or ochre yellow blotches, extending from the neck to the posterior part of the tail; and (12) venter pale orange, tips of ventrals with subrectangular black blotches. All Hebius specimens were strongly recovered as monophyletic, in which Hebiustaronensis (Smith, 1940) and Hebiusvenningi (Wall, 1910) were monophyletic as sister to the Yingjiang County specimens. According to the p-distance of cytochrome b, the new species differs from its congeners by 9.7-15.4%.

RESUMEN

To improve the accuracy of the Hami melon discrete element model, the parameters of the Hami melon seed discrete element model were calibrated by combining practical experiments and simulation tests. The basic physical parameters of Hami melon seeds were obtained through physical experiments, including triaxial size, 100-grain mass, moisture content, density, Poisson's ratio, Young's modulus, shear modulus, angle of repose, suspension speed and various contact parameters. Taking the repose angle of seed simulation as an index, the parameters of each simulation model were significantly screened by the Plackett-Burman test. The results showed that the recovery coefficient, static friction coefficient and rolling friction coefficient of Hami melon seeds had significant effects on repose angle. Based on the steepest climbing test and quadratic regression orthogonal rotation combination test, it was determined that the significant order of the influence of various contact parameters on the angle of repose was static friction coefficient, collision recovery coefficient, and rolling friction coefficient. The optimal parameter combination was obtained through the mathematical regression model between the angle of repose and various contact parameters, namely, the collision recovery coefficient of Hami melon seeds was 0.518, the static friction coefficient of Hami melon seeds was 0.585 and the rolling friction coefficient of Hami melon seeds was 0.337. Under this condition, three static seed-dropping experiments and dynamic rolling accumulation experiments were carried out. The average simulated angle of repose was 31.93°, and the relative error with the actual value was only 1.71%. The average simulated rolling accumulation angle was 51.98°, and the relative error with the actual value was only 1.92%.

Asunto(s)

Cucurbitaceae , Semillas , Cucurbitaceae/fisiología , Semillas/fisiología , Calibración , Simulación por Computador , Módulo de Elasticidad , Modelos Teóricos , Fricción

RESUMEN

The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient-reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel-based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.

Asunto(s)

Antineoplásicos , Neoplasias , Pruebas de Farmacogenómica , Calidad de Vida , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Pruebas de Farmacogenómica/economía , Pruebas de Farmacogenómica/estadística & datos numéricos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Oncología Médica/métodos , Sistemas de Apoyo a Decisiones Clínicas , Farmacogenética