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1.
Sci Adv ; 10(19): eadn6642, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38718123

RESUMEN

Existing grippers for unmanned aerial vehicle (UAV) manipulation have persistent challenges, highlighting a need for grippers that are soft, self-adaptive, self-contained, easy to control, and lightweight. Inspired by tendril plants, we propose a class of soft grippers that are voltage driven and based on winding deformation for self-adaptive grasping. We design two types of U-shaped soft eccentric circular tube actuators (UCTAs) and propose using the liquid-gas phase-transition mechanism to actuate UCTAs. Two types of UCTAs are separately cross-arranged to construct two types of soft grippers, forming self-contained systems that can be directly driven by voltage. One gripper inspired by tendril climbers can be used for delicate grasping, and the other gripper inspired by hook climbers can be used for strong grasping. These grippers are ideal for deployment in UAVs because of their self-adaptability, ease of control, and light weight, paving the way for UAVs to achieve powerful manipulation with low positioning accuracy, no complex grasping planning, self-adaptability, and multiple environments.

2.
Foods ; 13(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38731731

RESUMEN

Hydroponic cultivation of lettuce is an increasingly popular sustainable agricultural technique. However, Escherichia coli, a prevalent bacterium, poses significant concerns for the quality and safety of hydroponically grown lettuce. This study aimed to develop a growth model for E. coli and background microflora in hydroponically grown lettuce. The experiment involved inoculating hydroponically grown lettuce with E. coli and incubated at 4, 10, 15, 25, 30, 36 °C. Growth models for E. coli and background microflora were then developed using Origin 2022 (9.9) and IPMP 2013 software and validated at 5 °C and 20 °C by calculating root mean square errors (RMSEs). The result showed that E. coli was unable to grow at 4 °C and the SGompertz model was determined as the most appropriate primary model. From this primary model, the Ratkowsky square root model and polynomial model were derived as secondary models for E. coli-R168 and background microflora, respectively. These secondary models determined that the minimum temperature (Tmin) required for the growth of E. coli and background microflora in hydroponically grown lettuce was 6.1 °C and 8.7 °C, respectively. Moreover, the RMSE values ranged from 0.11 to 0.24 CFU/g, indicating that the models and their associated kinetic parameters accurately represented the proliferation of E. coli and background microflora in hydroponically grown lettuce.

3.
Nat Commun ; 15(1): 3966, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729935

RESUMEN

Rhenium (Re) and uranium (U) are essential proxies in reconstructing past oceanic oxygenation evolution. However, their removal in continental shelf sediments, hotspots of early diagenesis, were previously treated as quantitatively unimportant sinks in the ocean. Here we examine the sedimentary reductive removal of Re and U and their coupling with organic carbon decomposition, utilizing the 224Ra/228Th disequilibria within the East China Sea shelf. We identified positive correlations between their removal fluxes and the rates of sediment oxygen consumption or organic carbon decomposition. These correlations enable an evaluation of global shelf reductive sinks that are comparable to (for Re) or higher than (~4-fold for U) previously established suboxic/anoxic sinks. These findings suggest potential imbalances in the modern budgets of Re and U, or perhaps a substantial underestimation of their sources. Our study thus highlights shelf sedimentary reductive removal as critical yet overlooked sinks for Re and U in the modern ocean.

4.
CNS Neurosci Ther ; 30(5): e14748, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38727518

RESUMEN

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.


Asunto(s)
Homeostasis , Accidente Cerebrovascular Isquémico , Terapia Trombolítica , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Terapia Trombolítica/métodos , Homeostasis/fisiología , Homeostasis/efectos de los fármacos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Circulación Cerebrovascular/fisiología , Circulación Cerebrovascular/efectos de los fármacos , Estudios Prospectivos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Administración Intravenosa , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Nomogramas , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/fisiopatología
5.
J Ethnopharmacol ; : 118291, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705427

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana radix (GR) and wine-processed Gentiana radix (WGR) are commonly used in folk medicine for the treatment of bile or liver disorders, including jaundice, hepatitis, swelling or inflammation for thousands of years. However, the therapeutic effects of gentian root (GR) and wine-made gentian root (WGR) treatment on damp-heat jaundice syndrome (DHJS) have not been studied in animal experiments. AIM OF THE STUDY: This study aimed to investigate the protective effects and mechanisms of GR and WGR on DHJS in rats. MATERIALS AND METHODS: In a high-fat and high-sugar diet in a humidified hot environment, hepatic injury induced by giving of alpha-naphthalene isothiocyanate (ANIT) in rats were used as a DHJS model. Histological analysis, enzyme-linked immunosorbent assay (ELISA), PCR analysis, and metabolomics were used to elucidate the mechanism of GR and WGR for DHJS. RESULTS: The results indicated that GR and WGR affected DHJS by inhibiting the release of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (D-BIL), total bilirubin (TBIL), total bile acid (TBA), malondialdehyde (MDA), glutathione S-transferase (GST) (P < 0.05). In addition, they significantly reduced the gene expression levels of Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BESP), multidrug resistance-associated protein 2 (MRP2) and multidrug resistance-associated protein 3 (MRP3) (P < 0.05). The WGR group improved the above function indicators better than the GR group. GR and WGR could restore 11 potential biomarkers in rats with DHJS tended to return to normal levels, these biomarkers were involved in arachidonic acid metabolism, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, porphyrin and chlorophyll metabolism, retinol metabolism, arginine biosynthesis. The results of the metabolic pathway showed that WGR was significantly better than GR in the improvement of porphyrin and chlorophyll metabolism. CONCLUSIONS: These findings suggest that treatment with GR and WGR has a beneficial effect on DHJS in rats, the major mechanisms may be involved in improving functional indicators of the body and endogenous metabolism, and WGR is more effective than GR. It provides important evidence for the clinical application of GR and WGR in the treatment of DHJS.

7.
J Res Adolesc ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717122

RESUMEN

In past decades, the positive role of self-control in students' academic success has attracted plenty of scholarly attention. However, fewer studies have examined the link between adolescents' neural development of the inhibitory control system and their academic achievement, especially using a longitudinal approach. Moreover, less is known about the role of parents in this link. Using large-scale longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (N = 9574; mean age = 9.94 years at baseline, SD = .63; 50% girls), the current study took an integrative biopsychosocial approach to explore the longitudinal link between early adolescents' fronto-striatal connectivity and their academic achievement, with attention to the moderating role of parental warmth. Results showed that weaker intrinsic connectivity between the frontoparietal network and the striatum was associated with early adolescents' worse academic achievement over 2 years during early adolescence. Notably, parental warmth moderated the association between fronto-striatal connectivity and academic achievement, such that weaker fronto-striatal connectivity was only predictive of worse academic achievement among early adolescents who experienced low levels of parental warmth. Taken together, the findings demonstrate weaker fronto-striatal connectivity as a risk factor for early adolescents' academic development and highlight parental warmth as a protective factor for academic development among those with weaker connectivity within the inhibitory control system.

8.
Nanoscale ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38721638

RESUMEN

The photocatalytic water-mediated CO2 reduction reaction, which holds great promise for the conversion of CO2 into valuable chemicals, is often hindered by inefficient separation of photogenerated charges and a lack of suitable catalytic sites. Herein, we have developed a glycerol coordination assembly approach to precisely control the distribution of atomically dispersed Cu species by occupying Ti-defects and adjusting the ratio between Cu species and Ti-defects in a hierarchical TiO2. The optimal sample demonstrates a ∼4-fold improvement in CO2-to-CO conversion compared to normal TiO2 nanoparticles. The high activity could be attributed to the Ti defects, which enhance the photogenerated charge separation and simultaneously facilitate the adsorption of water molecules, thereby promoting the water oxidation reaction. Moreover, by means of in situ EPR and FTIR spectra, we have demonstrated that Cu species can effectively capture photogenerated electrons and facilitate the adsorption of CO2, so as to catalyze the reduction of CO2. This work provides a strategy for the construction of atomic-level synergistic catalytic sites and the utilization of in situ techniques to reveal the underlying mechanism.

9.
J Virol ; 98(5): e0001624, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38563732

RESUMEN

Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca2+) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca2+ signaling in the regulation of IFN-I, the relationship between Ca2+ and TBK1 in different infection models requires further elucidation. Here, we examined the effects of the Newcastle disease virus (NDV)-induced increase in intracellular Ca2+ levels on the suppression of host antiviral responses. We demonstrated that intracellular Ca2+ increased significantly during NDV infection, leading to impaired IFN-I production and antiviral immunity through the activation of calcineurin (CaN). Depletion of Ca²+ was found to lead to a significant increase in virus-induced IFN-I production resulting in the inhibition of viral replication. Mechanistically, the accumulation of Ca2+ in response to viral infection increases the phosphatase activity of CaN, which in turn dephosphorylates and inactivates TBK1 in a Ca2+-dependent manner. Furthermore, the inhibition of CaN on viral replication was counteracted in TBK1 knockout cells. Together, our data demonstrate that NDV hijacks Ca2+ signaling networks to negatively regulate innate immunity via the CaN-TBK1 signaling axis. Thus, our findings not only identify the mechanism by which viruses exploit Ca2+ signaling to evade the host antiviral response but also, more importantly, highlight the potential role of Ca2+ homeostasis in the viral innate immune response.IMPORTANCEViral infections disrupt intracellular Ca2+ homeostasis, which affects the regulation of various host processes to create conditions that are conducive for their own proliferation, including the host immune response. The mechanism by which viruses trigger TBK1 activation and IFN-I induction through viral pathogen-associated molecular patterns has been well defined. However, the effects of virus-mediated Ca2+ imbalance on the IFN-I pathway requires further elucidation, especially with respect to TBK1 activation. Herein, we report that NDV infection causes an increase in intracellular free Ca2+ that leads to activation of the serine/threonine phosphatase CaN, which subsequently dephosphorylates TBK1 and negatively regulates IFN-I production. Furthermore, depletion of Ca2+ or inhibition of CaN activity exerts antiviral effects by promoting the production of IFN-I and inhibiting viral replication. Thus, our results reveal the potential role of Ca2+ in the innate immune response to viruses and provide a theoretical reference for the treatment of viral infectious diseases.


Asunto(s)
Calcineurina , Calcio , Inmunidad Innata , Interferón Tipo I , Virus de la Enfermedad de Newcastle , Proteínas Serina-Treonina Quinasas , Replicación Viral , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Virus de la Enfermedad de Newcastle/inmunología , Animales , Calcineurina/metabolismo , Humanos , Calcio/metabolismo , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Fosforilación , Enfermedad de Newcastle/inmunología , Enfermedad de Newcastle/virología , Enfermedad de Newcastle/metabolismo , Señalización del Calcio , Línea Celular , Células HEK293
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 450-457, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38660851

RESUMEN

OBJECTIVE: To investigate the expression and clinical significance of CD30 in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on 124 cases of primary DLBCL diagnosed at Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2018 to July 2020. The expression of CD30 in patients with DLBCL was detected by immunohistochemical method, and the clinicopathological characteristics were analyzed and compared between CD30+ and CD30- groups. Kaplan-Meier analysis was used for survival analysis. The relationship between CD30 expression and clinical features and prognosis were analyzed. RESULTS: Among the 124 patients with DLBCL, 19 patients expressed CD30, and the positive rate is 15.32%. The clinico-pathological characteristics of CD30+ in patients with DLBCL were characterized by low age, more common in males, fewer extranodal lesions, lower international prognostic index (IPI), GCB type being more common in Hans subtype, and achieving better therapeutic effects (P < 0.05). However, there were no significant statistical differences in B-symptoms (P =0.323), Ann Arbor staging (P =0.197), Eastern Cooperative Oncology Group (ECOG) score (P =0.479), lactate dehydrogenase (LDH) (P =0.477), and the involvement of bone marrow (P =0.222). There were significant differences in OS and PFS between the CD30+ and CD30- groups (χ2=5.653, P =0.017; χ2=4.109,P =0.043), the CD30+ group had a better prognosis than that of the CD30- group. The results of subgroup analysis showed that the CD30+ group in the IPI score=1-2, LDH elevated group had a better prognosis (P < 0.05). In the subgroups of Ann Arbor staging III-IV (P =0.055) and non GCB type (P =0.053), the CD30+ group had a good prognosis trend, but the difference was not statistically significant. The results of univariate analysis showed that the good prognosis of DLBCL patients was closely related to CD30+ expression, no B-symptoms, early Ann Arbor staging, low ECOG score, normal LDH, low IPI score, fewer extranodal involvement, and obtaining the best therapeutic effect as CR (all P <0.05). COX multivariate regression analysis showed that the presence of B-symptoms and achieving the best therapeutic effect as Non-CR were independent risk factors affecting the prognosis of DLBCL patients (P < 0.05). CONCLUSION: The CD30+ expression in DLBCL patients indicates a good prognosis and has certain diagnostic value in evaluating the prognosis of DLBCL patients.


Asunto(s)
Antígeno Ki-1 , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Antígeno Ki-1/metabolismo , Estudios Retrospectivos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Estimación de Kaplan-Meier , Relevancia Clínica
11.
Dev Cogn Neurosci ; 67: 101380, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38626612

RESUMEN

Research on social determinants of health has highlighted the influence of neighborhood characteristics (e.g., neighborhood safety) on adolescents' health. However, it is less clear how changes in neighborhood environments play a role in adolescent development, and who are more sensitive to such changes. Utilizing the first three waves of data from the Adolescent Brain Cognitive Development (ABCD) project (N = 7932, M (SD) age = 9.93 (.63) years at T1; 51% boys), the present study found that increases in neighborhood safety were associated with decreased adolescent externalizing symptoms, internalizing symptoms, but not sleep disturbance over time, controlling for baseline neighborhood safety. Further, adolescents' insula and anterior cingulate cortex (ACC) reactivity to positive emotional stimuli moderated the association between changes in neighborhood safety and adolescent adjustment. Among youth who showed higher, but not lower, insula and ACC reactivity to positive emotion, increases in neighborhood safety were linked with better adjustment. The current study contributes to the differential susceptibility literature by identifying affective neural sensitivity as a marker of youth's susceptibility to changes in neighborhood environment. The findings highlight the importance of neighborhood safety for youth during the transition to adolescence, particularly for those with heightened affective neural sensitivity.

12.
Neural Regen Res ; 19(11): 2430-2443, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38526280

RESUMEN

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

13.
PLoS Med ; 21(3): e1004362, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38489391

RESUMEN

BACKGROUND: The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. METHODS AND FINDINGS: We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian-Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. CONCLUSIONS: In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.


Asunto(s)
Análisis de la Aleatorización Mendeliana , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Factores de Riesgo , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Fumar/efectos adversos , Fumar Tabaco , Estudios Observacionales como Asunto
14.
J Res Adolesc ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38480475

RESUMEN

Adolescents' family obligation is a cultural strength that shows enduring prevalence in China. Given that the meaning of family obligation has undergone rapid changes in recent decades, it is crucial to examine the role of family obligation in adolescent adjustment in contemporary China. More importantly, although past research has investigated the consequences of family obligation on adolescents' adjustment, little is known about the antecedents of Chinese adolescents' family obligation. Using a two-wave longitudinal sample of 450 Chinese adolescents (mean age = 13.78 years, SD = .71 years; 49% female) and their parents, the current research explored two questions. First, this study examined the role of family obligation in adolescents' academic achievement, externalizing problems, and internalizing problems over early adolescence. Second, this study explored the role of parents in predicting Chinese adolescents' family obligation, specifically whether parental expectations or parental acceptance was predictive of adolescents' family obligation over time. Third, this study investigated whether family obligation is an underlying mechanism between parenting and Chinese adolescents' adjustment. Results showed that Chinese adolescents' family obligation was longitudinally associated with increased academic achievement and reduced externalizing problems. Moreover, perceived parental acceptance, but not parental expectations, was longitudinally associated with Chinese adolescents' greater family obligation. Notably, family obligation mediated the longitudinal effect of parental acceptance on Chinese adolescents' externalizing problems. By studying both the consequences and antecedents of Chinese adolescents' family obligation, this study helps provide a comprehensive understanding of this cultural strength.

15.
J Tissue Eng ; 15: 20417314241237052, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481708

RESUMEN

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

16.
Biomed Mater ; 19(3)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38471163

RESUMEN

Exosomes, typically 30-150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g. proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.


Asunto(s)
Exosomas , MicroARNs , Exosomas/química , MicroARNs/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Proteínas/metabolismo , ARN Interferente Pequeño
17.
J Transl Med ; 22(1): 314, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532419

RESUMEN

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Curva ROC , Detección Precoz del Cáncer/métodos , Neoplasias de la Vejiga Urinaria/patología , Biomarcadores de Tumor
18.
Sci Total Environ ; 924: 171634, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38471585

RESUMEN

In recent years, the escalating attention on Pharmaceutical and Personal Care Products (PPCPs) and Heavy Metals in urban stormwater runoff highlights the critical role of Road-deposited sediments (RDS) as a significant carrier for pollutant occurrence and transport in runoff. However, existing research has overlooked the composite characteristics of PPCPs and Heavy Metals, hampering a holistic understanding of their transformation in diverse forms within runoff. This limitation impedes the exploration of their subsequent migration and conversion properties, thereby obstructing coordinated strategies for the control of co-pollution in runoff. This study focuses on the typical PPCP sulfamethoxazole (SMX) and heavy metal Cu(II) to analyze their occurrence characteristics in the Runoff-RDS system. Kinetics and isotherm studies reveal that RDS effectively accumulates SMX and Cu(II), with both exhibiting rapid association with RDS in the early stages of runoff. The accumulation of SMX and Cu(II) accounts for over 80 % and 70 % of the total accumulation within the first 240 min and 60 min, respectively. Moreover, as runoff pH values decrease, the initially synergistic effect between the co-pollutant transforms into an antagonistic effect. In the composite system, varying pH values from 2.0 to 6.0 lead to an increase in SMX accumulation from 4.01 mg/kg to 6.19 mg/kg and Cu(II) accumulation from 0.43 mg/g to 3.39 mg/g. Compared to the single system, the composite system capacity for SMX and Cu(II) increases by 0.04 mg/kg and 0.33 mg/g at pH 4.0. However, at pH 3.0, the composite system capacity for SMX and Cu(II) decreases by 0.21 mg/kg and 0.36 mg/g, respectively. Protonation/deprotonation of SMX under different pH conditions influences electrostatic repulsion/attraction between SMX and RDS. The mechanism of RDS accumulation of SMX involves Electron Donor-Acceptor (EDA) interaction, hydrogen bond interaction, and Lewis acid-base interaction. Cu(II) enrichment on RDS includes surface complexation reaction, electrostatic interaction, and surface precipitation. Complex formation enhances the accumulation of both SMX and Cu(II) on RDS in runoff. This study elucidates the co-occurrence characteristics and mechanisms of SMX and Cu(II) co-pollution in runoff systems. The findings contribute valuable insights to understanding the existence patterns and mechanisms of co-pollution, providing a reference for investigating the migration and fate of co-pollutant in runoff. Moreover, these insights could offer guidance for the development of effective strategies to mitigate co-pollution in rainwater.

19.
J Am Heart Assoc ; 13(7): e033407, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38533986

RESUMEN

BACKGROUND: The study aimed to investigate the relationship between uric acid (UA) levels and functional outcomes at 3 months in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT). METHODS AND RESULTS: This prospective cohort study included 1001 consecutive patients with AIS who underwent IVT. The correlation between UA levels and post-IVT AIS outcomes was examined. Any nonlinear relationship was assessed using a restricted cubic spline function. The nonlinear P value for the association of UA levels with favorable (modified Rankin Scale [mRS] score ≤2) and excellent (mRS score ≤1) outcomes at 3 months post-IVT were <0.001 and 0.001, respectively. However, for patients with and without hyperuricemia, no evident nonlinear relationship was observed between UA levels and favorable 3-month post-IVT outcomes, with nonlinear P values of 0.299 and 0.207, respectively. The corresponding interaction analysis yielded a P value of 0.001, indicating significant heterogeneity. Similar results were obtained for excellent outcomes at 3 months post-IVT. In the hyperuricemia group, increased UA levels by 50 µmol/L reduced the odds of a favorable 3-month post-AIS outcome (odds ratio [OR], 0.75 [95% CI, 0.57-0.97]). Conversely, in the nonhyperuricemia group, a similar UA increase was linked to higher favorable outcome odds (OR, 1.31 [95% CI, 1.15-1.50]). CONCLUSIONS: An inverted U-shaped nonlinear relationship was observed between UA levels and favorable and excellent outcomes at 3 months in patients with AIS who underwent IVT. Higher UA levels predict favorable outcomes in patients without hyperuricemia but unfavorable outcomes in those with hyperuricemia.


Asunto(s)
Isquemia Encefálica , Hiperuricemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/complicaciones , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Ácido Úrico , Resultado del Tratamiento , Hiperuricemia/diagnóstico , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Estudios Prospectivos , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Fibrinolíticos/uso terapéutico
20.
EClinicalMedicine ; 69: 102484, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38389712

RESUMEN

Background: Ultra-processed food (UPF) consumption continues to increase worldwide. However, evidences from meta-analyses are limited regarding the effects on cardiovascular events (CVEs). Methods: A meta-analysis was performed to assess the dose-response relationship of UPF consumption and CVEs risk (including the morbidity and mortality of cardiovascular causes, and myocardial infarction, stroke, transient ischemic attack, coronary intervention). Databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched for observational studies published in English language up to October 24, 2023. Generalized least squares regression and restricted cubic splines were used to estimate the linear/nonlinear relationship. PROSPERO CRD 42023391122. Findings: Twenty studies with 1,101,073 participants and 58,201 CVEs cases with a median follow-up of 12.2 years were included. A positive linear relationship between UPF intake and CVEs risk was identified. In addition, positive correlation between coronary heart disease and UPF consumption in terms of daily serving and daily energy proportion. No significant association of UPF consumption with the risk of cerebrovascular disease was observed. Briefly, 10% increase of UPF by daily weight proportion was associated with a 1.9% increase of CVEs risk (RR = 1.019; 95% CI, 1.007-1.031; P = 0.002), an additional daily serving corresponding to 2.2% CVEs risk increase (RR = 1.022; 95% CI, 1.013-1.031; P < 0.001), and 10% increase by daily energy proportion corresponding to 1.6% CVEs risk increase (RR = 1.016; 95% CI, 1.002-1.030; P = 0.022). Interpretation: UPF consumption were associated with a higher risk of CVEs in the positive linear relationship. Our findings highlight the importance of minimizing UPF consumption for cardiovascular health and might be help to pursue public health policies in control of UPF consumption. Funding: This work was supported by the Key Research and Development Program of Shaanxi Province (2023-ZDLSF-22), the Innovative Talent Support Program of Shaanxi Province (2022KJXX-106), and the Key Research and Development Program of Shaanxi Province (2023-YBSF-424).

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