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1.
Neural Regen Res ; 20(3): 779-793, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886942

RESUMEN

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood-brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

2.
Talanta ; 281: 126934, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39326116

RESUMEN

Combined the electrostatic interaction of the negatively charged gold nanorods (AuNRs) (as acceptor) and Ru(bpy)32+ (as donor), an electrochemiluminescence resonance energy transfer (ECL-RET) sensor was constructed and applied for the detection of organophosphorus pesticides (OPs). Negatively charged AuNRs were synthesized by modifying AuNRs with polystyrene sulfonate (PSS) firstly, which can bind to Ru(bpy)32+ through electrostatic interaction so that the luminophore was absorbed by the acceptor, the resonance energy transfer occurred and only low ECL signal had been detected. Thiocholine can be produced by the hydrolysis process of acetylthiocholine (ATCh) with the help of acetylcholinesterase (AChE), which can bond with PSS-modified AuNRs (PSS-AuNRs) through gold-sulfur interaction, this caused the releasing of the adsorbed Ru(bpy)32+ into the solution and resulting in the restoration of the ECL intensity. However, the activity of AChE was inhibited by OPs, and the recovery process of the ECL signal was thus suppressed as well. In this study, chlorpyrifos was chosen as model target, the results indicated that the correlation between the ECL intensity and the logarithm of chlorpyrifos concentration showed remarkable linearity across 1 ng/mL to 1 mg/mL, achieving a detection limit of 0.51 ng/mL. The proposed system has been utilized for detecting OPs in real samples with satisfied results.


Asunto(s)
Acetilcolinesterasa , Técnicas Electroquímicas , Oro , Mediciones Luminiscentes , Nanotubos , Plaguicidas , Nanotubos/química , Oro/química , Plaguicidas/análisis , Plaguicidas/química , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Límite de Detección , Compuestos Organofosforados/análisis , Compuestos Organofosforados/química , Transferencia de Energía , Técnicas Biosensibles/métodos , Poliestirenos/química , Compuestos Organometálicos/química
3.
Reprod Biol Endocrinol ; 22(1): 130, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39456075

RESUMEN

BACKGROUND: Females with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the "high-risk DOR" group. OBJECTIVE: The primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs). METHODS: A total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson's chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02). RESULTS: According to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332-0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558-2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM. CONCLUSION(S): Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.


Asunto(s)
Hormona Antimülleriana , Folículo Ovárico , Reserva Ovárica , Técnicas Reproductivas Asistidas , Humanos , Femenino , Hormona Antimülleriana/sangre , Reserva Ovárica/fisiología , Adulto , Embarazo , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/terapia , Infertilidad Femenina/sangre , Tasa de Natalidad , Índice de Embarazo , Estudios Retrospectivos , Nacimiento Vivo/epidemiología , Resultado del Embarazo/epidemiología , Recuperación del Oocito/métodos
4.
Bioorg Med Chem ; 114: 117940, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39442491

RESUMEN

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has triggered a protracted global pandemic from 2019 to 2022, and posed a significant threat to human health. One of the non-structural proteins 3CLpro of SARS-CoV-2 is considered as a validated target for the development of inhibitors against the virus. Disulfiram has been reported as a covalent inhibitor of 3CLpro; however, its structure lacks bonding site with active pockets of 3CLpro and its highly symmetric structure doesn't match well with the irregular cavity of the active center, limiting its therapeutic applications. To enhance their affinity for the 3CLpro target, in this study, two kinds of disulfiram derivatives, designed based on the reevaluation and optimization of disulfiram, have been synthesized through photoredox chemistry, and the novel carbamo(dithioperoxo)thioates 4g-m were found to display 5-17 folds potency against SARS-CoV-2 3CLpro compared to the parent disulfiram, with resulting half-maximal inhibitory concentration (IC50) values ranging from 0.14-0.47 µM. Carbamo(dithioperoxo)thioates 4i containing a 4-hydroxy piperidine and a 4-trifluoromethyl phenyl ring, was identified as the most potent inhibitor to both 3CLpro (IC50 = 0.14 µM) and PLpro (IC50 = 0.04 µM). Furthermore, molecular dynamics simulations, binding free energy analysis and mass analysis were performed and provided insights on the stability, conformational behavior, and interactions of 4g with 3CLpro. The green synthetic methodology, the privileged carbamo(dithioperoxo)thioate scaffold, and the molecular mechanisms presented might serve as a useful system for the further discovery of highly potent inhibitors targeting SARS-CoV-2 3CLpro.

5.
Nanomaterials (Basel) ; 14(20)2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39452983

RESUMEN

Since its discovery, the phenomenon of Surface Enhanced Raman Scattering (SERS) has gradually become an important tool for analyzing the composition and structure of substances. As a trace technique that can efficiently and nondestructively detect single molecules, the application of SERS has expanded from environmental and materials science to biomedical fields. In the past decade or so, the explosive development of nanotechnology and nanomaterials has further boosted the research of SERS technology, as nanomaterial-based SERS substrates have shown good signal enhancement properties. So far, it is widely recognized that the morphology, size, composition, and stacking mode of nanomaterials have a very great influence on the strength of the substrate SERS effect. Herein, an overview of methods for the preparation of surface-enhanced Raman scattering (SERS) substrates is provided. Specifically, this review describes a variety of common SERS substrate preparation methods and explores the potential and promise of these methods for applications in chemical analysis and biomedical fields. By detailing the influence of different nanomaterials (e.g., metallic nanoparticles, nanowires, and nanostars) and their structural features on the SERS effect, this article aims to provide a comprehensive understanding of SERS substrate preparation techniques.

6.
Radiol Imaging Cancer ; 6(6): e240050, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39400232

RESUMEN

Purpose To evaluate the performance of an artificial intelligence (AI) model in detecting overall and clinically significant prostate cancer (csPCa)-positive lesions on paired external and in-house biparametric MRI (bpMRI) scans and assess performance differences between each dataset. Materials and Methods This single-center retrospective study included patients who underwent prostate MRI at an external institution and were rescanned at the authors' institution between May 2015 and May 2022. A genitourinary radiologist performed prospective readouts on in-house MRI scans following the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 or 2.1 and retrospective image quality assessments for all scans. A subgroup of patients underwent an MRI/US fusion-guided biopsy. A bpMRI-based lesion detection AI model previously developed using a completely separate dataset was tested on both MRI datasets. Detection rates were compared between external and in-house datasets with use of the paired comparison permutation tests. Factors associated with AI detection performance were assessed using multivariable generalized mixed-effects models, incorporating features selected through forward stepwise regression based on the Akaike information criterion. Results The study included 201 male patients (median age, 66 years [IQR, 62-70 years]; prostate-specific antigen density, 0.14 ng/mL2 [IQR, 0.10-0.22 ng/mL2]) with a median interval between external and in-house MRI scans of 182 days (IQR, 97-383 days). For intraprostatic lesions, AI detected 39.7% (149 of 375) on external and 56.0% (210 of 375) on in-house MRI scans (P < .001). For csPCa-positive lesions, AI detected 61% (54 of 89) on external and 79% (70 of 89) on in-house MRI scans (P < .001). On external MRI scans, better overall lesion detection was associated with a higher PI-RADS score (odds ratio [OR] = 1.57; P = .005), larger lesion diameter (OR = 3.96; P < .001), better diffusion-weighted MRI quality (OR = 1.53; P = .02), and fewer lesions at MRI (OR = 0.78; P = .045). Better csPCa detection was associated with a shorter MRI interval between external and in-house scans (OR = 0.58; P = .03) and larger lesion size (OR = 10.19; P < .001). Conclusion The AI model exhibited modest performance in identifying both overall and csPCa-positive lesions on external bpMRI scans. Keywords: MR Imaging, Urinary, Prostate Supplemental material is available for this article. © RSNA, 2024.


Asunto(s)
Aprendizaje Profundo , Imagen por Resonancia Magnética , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Estudios Retrospectivos , Anciano , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Algoritmos , Próstata/diagnóstico por imagen , Próstata/patología , Interpretación de Imagen Asistida por Computador/métodos , Biopsia Guiada por Imagen/métodos
7.
Adv Mater ; : e2411012, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402778

RESUMEN

Mixed halide 3D perovskites are promising for bright, efficient, and wide-color gamut light-emitting diodes (LEDs) due to their excellent carrier transport, high luminescence, and easily tunable bandgaps. However, serious halide ion migration inside mixed halide 3D perovskite results in poor operational and spectral stability of the as-fabricated LEDs. Here, a hetero-nucleation crystallization strategy is reported to grow [111]-orientation preferred mixed halide 3D perovskite CsPbI3-xBrx thin films for stable pure red LEDs. This hetero-nucleation crystallization is enabled by the addition of phosphoric acid (H3PO4) complexation, which promotes the growth of small perovskite grains into large grains with uniform [111]-orientation. The obtained [111]-orientation preferred film exhibits excellent stability under light or electric field stimulus as revealed by model analysis and experimental results compared to that of [001]-orientation preferred film. Thus, based on the [111]-orientation preferred film, the fabricated LED exhibits an external quantum efficiency of 22.8%, a maximum brightness of 12 000 cd m-2, and a half-life time of 4080 min under 1.5 mA cm-2. More importantly, the electroluminescence spectrum of the device remains stable during the continuous operation of 4080 min, showcasing the significant spectral stability improvement enabled by the hetero-nucleation induced [111]-orientation strategy.

8.
Nano Lett ; 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39412214

RESUMEN

The specific capacity of Li- and Mn-rich layered oxide (LMROs) cathodes can be enhanced by the oxidation of lattice oxygen at high voltages. Nevertheless, an irreversible oxygen loss emerges with cycling, which triggers interlocking surface/interface issues and results in the fast deterioration of cycling performance. Herein, we prepare a surface modified LMRO electrode by one step doctor-blade casting and introducing a benzoquinone species DBBQ redox couple. The electrochemical test shows that the DBBQ-modified electrode has a high reversible capacity (>320 mAh g-1) and excellent rate performance, while the cyclic stability has been significantly improved as well. The capacity retention reaches as high as 93.3% after 500 cycles at 1 C. Mechanism analysis shows that DBBQ can not only play a redox couple in LMROs which achieves the adsorption and reduction of surface oxygen gas but also significantly enhance anionic redox in the bulk, thus realizing extraordinary capacity.

9.
Int Immunopharmacol ; 143(Pt 2): 113375, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39418730

RESUMEN

OBJECTIVE: Cognitive dysfunction is one of the major symptoms of chronic sleep deprivation (CSD). Abnormal autophagy and apoptosis are thought to be important mechanisms. S100 Calcium Binding Protein A8 (S100A8) plays a key role in autophagy and apoptosis of microglia. This study investigated whether S100A8 knockdown can effectively inhibit aberrant autophagy in microglia and improve cognitive function by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway under CSD conditions. METHODS: CSD mouse models and BV2 cell autophagy models were established in vivo and in vitro. Transcriptome sequencing was used to determine the key regulator related to autophagy. The Morris water maze test was used to evaluate the cognitive behavior of the mice. RT-qPCR and western blot were conducted to examine S100A8 expression and autophagy signalling. HE, TUNEL, transmission electron microscopy, immunofluorescence, and histochemistry were performed to detect pathological changes, neuronal autophagy, apoptosis, or positive cells in hippocampal tissues, respectively. RESULTS: Transcriptome sequencing showed that S100A8 was significantly elevated in CSD mice, and fluorescence colocalization results further suggested that S100A8 mainly colocalizes with microglia. In vivo studies revealed that knockdown of S100A8 alleviated CSD-induced cognitive impairment in mice. Through further mechanistic investigations employing both in vivo and in vitro models, we demonstrated that silencing S100A8 can activate the PI3K/AKT pathway, thereby reducing CSD-induced abnormal autophagy and apoptosis in microglia. Aberrant autophagy and apoptosis in microglia were reversed with the PI3K/AKT pathway inhibitor LY294002. CONCLUSION: The S100A8/PI3K/AKT axis plays a crucial role in chronic sleep deprivation-mediated autophagy and apoptosis in microglia.

10.
Int J Biol Macromol ; 281(Pt 2): 136209, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39383899

RESUMEN

Platelet-rich plasma (PRP) has been recognized as an effective therapy in regenerative medicine and surgery, which can reduce the risk of antibiotic abuse and promote the healing of infected wounds. Recent advances in PRP-based treatments have focused on the controlled release of growth factors in PRP with biocompatible hydrogels and antimicrobial promotion by introducing hydrogel components or antibiotics, while the inherent antimicrobial activity of PRP is mostly neglected or sacrificed. Here, we demonstrate the combination of an antimicrobial polysaccharide, carboxymethyl chitosan, and PRP to construct an antimicrobial hydrogel via dynamic bonding with oxidized chondroitin sulfate. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli (95 % of inhibition rate) are achieved through the synergistic contributions of the polysaccharide and PRP. Additionally, the resulting hydrogel promotes the migration of NIH-3T3 fibroblasts and collagen deposition by approximately 1.7 and 1.8 times, respectively, thereby accelerating the healing process of infected wounds. This work may bring new perspectives for potent applications of PRP-based hydrogel dressings for antibiotic-free management of infected wounds.

11.
Light Sci Appl ; 13(1): 286, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39389951

RESUMEN

Materials capable of dynamic persistent luminescence (PersL) within the visible spectrum are highly sought after for applications in display, biosensing, and information security. However, PersL materials with eye-detectable and excitation-wavelength-dependent characteristics are rarely achieved. Herein, a nonstoichiometric compound CaGaxO4:Bi (x < 2) is present, which demonstrates ultra-long, color-tunable PersL. The persistent emission wavelength can be tuned by varying the excitation wavelength, enabling dynamic color modulation from the green to the orange region within the visible spectrum. Theoretical calculations, in conjunction with experimental observations, are utilized to elucidate the thermodynamic charge transitions of various defect states, thereby providing insights into the relationship between Bi3+ emitters, traps, and multicolored PersL. Furthermore, the utility of color-tunable PersL materials and flexible devices is showcased for use in visual sensing of invisible ultraviolet light, multicolor display, information encryption, and anti-counterfeiting. These discoveries create new opportunities to develop smart photoelectric materials with dynamically controlled PersL for various applications.

12.
Sci Adv ; 10(42): eadr9602, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39423265

RESUMEN

All-solid-state batteries suffer from a loss of contact between the electrode and electrolyte particles, leading to poor cyclability. Here, a void-free ion-permeable interface between the solid-state polymer electrolyte and electrode is constructed in situ during cycling using charge/discharge voltage as the stimulus. During the charge-discharge, the permeation phase fills the voids at the interface and penetrates the electrode, forming strong bonds with the cathode and effectively mitigating the contact problem. Our all-solid-state potassium ion polymer batteries maintain high Coulombic efficiency more than 2000 cycles at a high operating voltage of 4.5 volt and stably cycle more than 500 cycles even at 4.6 volt. Our rational design for mitigating the contact problem is versatile, as demonstrated by the scalability of all-solid-state graphite-based polymer potassium-ion pouch cells and all-solid-state lithium-ion polymer batteries.

13.
Biomed Pharmacother ; 180: 117488, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39316974

RESUMEN

Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with hypercholesterolemia being a major risk factor. Although various lipid-lowering therapies exist, many patients fail to achieve optimal cholesterol control, highlighting the need for novel therapeutic approaches. ASGR1 (asialoglycoprotein receptor 1), predominantly expressed on hepatocytes, has emerged as a key regulator of cholesterol metabolism and low-density lipoprotein (LDL) clearance. This receptor's ability to regulate lipid homeostasis positions it as a promising target for therapeutic intervention in hypercholesterolemia and related cardiovascular diseases. This review critically examines the biological functions and regulatory mechanisms of ASGR1 in cholesterol metabolism, with a focus on its potential as a therapeutic target for hypercholesterolemia and related cardiovascular diseases. By analyzing recent advances in ASGR1 research, this article explores its role in liver-specific pathways, the implications of ASGR1 variants in CVD risk, and the prospects for developing ASGR1-targeted therapies. This review aims to provide a foundation for future research and clinical applications in hypercholesterolemia management.

14.
Polymers (Basel) ; 16(17)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39274100

RESUMEN

Conjugated polymers (CPs) are widely used as conductive materials in various applications, with their conductive properties adjustable through chemical doping. While doping enhances the thermoelectric properties of CPs due to improved main-chain transport, overdoping can distort the polymer structure, increasing energy disorder and impeding intrinsic electrical transport. This study explored how different dopants affect the structural integrity and electrical transport properties of CPs. We found that dopants vary in their impact on CP structure, consequently altering their electrical transport capabilities. Specifically, ferric chloride (FeCl3)-doped indacenodithiophene-co-benzothiadiazole (IDTBT) shows superior electrical transport properties to triethyloxonium hexachloroantimonate (OA)-doped IDTBT due to enhanced backbone planarity and rigidity, which facilitate carrier transport and lower energetic disorder. These results highlight the critical role of dopant selection in optimizing CPs for advanced applications, suggesting that strategic dopant choices can significantly refine the charge transport characteristics of CPs, paving the way for their industrialization.

15.
Natl Sci Rev ; 11(10): nwae252, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39301064

RESUMEN

While atomically precise metal nanoclusters (NCs) with unique structures and reactivity are very promising in catalysis, the spatial resistance caused by the surface ligands and structural instability poses significant challenges. In this work, Au25(Cys)18 NCs are encapsulated in multivariate metal-organic frameworks (MOFs) to afford Au25@M-MOF-74 (M = Zn, Ni, Co, Mg). By the MOF confinement, the Au25 NCs showcase highly enhanced activity and stability in the intramolecular cascade reaction of 2-nitrobenzonitrile. Notably, the interaction between the metal nodes in M-MOF-74 and Au25(Cys)18 is able to suppress the free vibration of the surface ligands on the Au25 NCs and thereby improve the accessibility of Au sites; meanwhile, the stronger interactions lead to higher electron density and core expansion within Au25(Cys)18. As a result, the activity exhibits the trend of Au25@Ni-MOF-74 > Au25@Co-MOF-74 > Au25@Zn-MOF-74 > Au25@Mg-MOF-74, highlighting the crucial roles of microenvironment modulation around the Au25 NCs by interaction between the surface ligands and MOF hosts.

16.
AAPS J ; 26(5): 90, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107477

RESUMEN

Changes to blood-brain barrier structure and function may affect the delivery of drugs into the brain. It is worthwhile to exploring more study on how the blood-brain barrier changes in structure and function and how that affects drug transport in high-altitude hypoxic environment. The DIA high-throughput sequencing technique indicate that the rats blood-brain barrier has been identified to have 7252 proteins overall and 8 tight junction proteins, among which Claudin-7 was a plateau-specific tight junction protein under high-altitude hypoxia, and based on the interaction network study, 2421 proteins are found to interact with one another, with ZO-1 being the primary target. The results of the projected gene function analysis demonstrated that changes in tight junction proteins are related to the control of TRP channels by inflammatory mediators, the wnt signaling pathway, the ABC transporter system, and drug metabolism-CYP450 enzyme regulation. Additionally, the electron microscopy, the Evans blue combination with confocal laser scanning microscopy, and the Western Blot and RT-qPCR revealed that high-altitude hypoxic environment induces blood-brain barrier tight junctions to open, blood-brain barrier permeability increases, ZO-1, Occludin, Claudin-5 protein and mRNA expression decreased. Our research implies that structural and functional alterations in the blood-brain barrier induced by high altitude hypoxia may impact drug transport inside the central nervous system, and that drug transporters and drug-metabolizing enzymes may be key players in this process.


Asunto(s)
Barrera Hematoencefálica , Proteínas de Uniones Estrechas , Animales , Barrera Hematoencefálica/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Proteínas de Uniones Estrechas/genética , Ratas , Hipoxia/metabolismo , Masculino , Altitud , Ratas Sprague-Dawley , Transporte Biológico , Permeabilidad , Uniones Estrechas/metabolismo
17.
Anal Chem ; 96(33): 13710-13718, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39115804

RESUMEN

Homogeneous electrochemiluminescence (ECL) has gained attention for its simplicity and stability. However, false positives due to solution background interference pose a challenge. To address this, magnetic ECL nanoparticles (Fe3O4@Ru@SiO2 NPs) were synthesized, offering easy modification, magnetic separation, and stable luminescence. These were utilized in an ECL sensor for miRNA-155 (miR-155) detection, with locked DNAzyme and substrate chain (mDNA) modified on their surface. The poor conductivity of long-chain DNA significantly impacts the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs, resulting in weaker ECL signals. Upon target presence, unlocked DNAzyme catalyzes mDNA cleavage, leading to shortened DNA chains and reduced density. In contrast, the presence of short-chain DNA has minimal impact on the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs. Simultaneously, the material surface's electronegativity decreases, weakening the electrostatic repulsion with the negatively charged electrode, resulting in the system detecting stronger ECL signals. This sensor enables homogeneous ECL detection while mitigating solution background interference through magnetic separation. Within a range of 100 fM to 10 nM, the sensor exhibits a linear relationship between ECL intensity and target concentration, with a 26.91 fM detection limit. It demonstrates high accuracy in clinical sample detection, holding significant potential for clinical diagnostics. Future integration with innovative detection strategies may further enhance sensitivity and specificity in biosensing applications.


Asunto(s)
ADN , Técnicas Electroquímicas , Mediciones Luminiscentes , MicroARNs , Dióxido de Silicio , MicroARNs/análisis , Técnicas Electroquímicas/métodos , ADN/química , Dióxido de Silicio/química , Humanos , Técnicas Biosensibles/métodos , Propiedades de Superficie , ADN Catalítico/química , ADN Catalítico/metabolismo , Nanopartículas de Magnetita/química , Límite de Detección , Rutenio/química
18.
J Hazard Mater ; 479: 135643, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39191019

RESUMEN

Water pollutions of heavy metal and metalloids (HMMs), typically including As, Cd, Cu, Cr, Mn, Ni, Pb, and Zn, are becoming a severe environmental problem to be controlled. Constructed wetlands (CWs) have been intensively investigated and applied for the removal of HMMs. By analyzing a mass of data from the existing literatures, this review found that the HMM removals in CWs varied from 12.35 % to 91.01 %, depending upon the HMM species and CW conditions. Nonetheless, 88.50 % of the influent HMMs were eventually immobilized in the CW sediments, while the common wetland plants are inefficient (i.e., accounting for 4.64 %) to uptake and accumulate the HMMs. It was also found that the concentrations of certain HMMs in the CW sediments have already exceeded up to 100 % of various environmental standards, indicating the urgency of introducing HMM hyperaccumulators in the systems. Through comparison, both the aboveground and belowground HMM accumulating capacities of reported hyperaccumulators were higher by magnitudes than common wetland plants. Following this, the efficacies and mechanisms of candidate hyperaccumulators were provided for the various scenarios of HMM control in CWs. Further, the selection principals, culture methods, and harvest strategies of hyperaccumulator in CWs were discussed. Finally, several perspectives were suggested for the future research. Overall, this review provided guiding information for the utilization of hyperaccumulators in CWs, which can improve the efficiency and sustainability of HMM removal in the CW systems.


Asunto(s)
Biodegradación Ambiental , Metaloides , Metales Pesados , Contaminantes Químicos del Agua , Humedales , Metales Pesados/metabolismo , Metaloides/metabolismo , Contaminantes Químicos del Agua/metabolismo , Plantas/metabolismo , Sedimentos Geológicos/química
19.
Front Mol Biosci ; 11: 1373754, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119476

RESUMEN

To investigate the genetic diversity of Triplophysa tenuis in the Shule River Basin of Gansu province, three populations were sequenced via RAD-seq technology. Twenty-nine microsatellite (SSR) markers with polymorphisms were finally screened to access the genetic diversity among the populations, of which 15 had high polymorphisms. The quantity of the alleles detected in the three populations of T. tenuis varied from 2 to 24. The locus with the most alleles was SSRC1, which had 24 alleles. Among the 29 SSRs, the range of effective allele number, observed heterozygosity, expected heterozygosity, and polymorphic information content were 1.246-16.615, 0.222-1, 0.198-0.940, and 0.178-0.937, respectively. Most of the identified loci were in the Hardy-Weinberg equilibrium. Analysis of the population structure revealed that the Yumen and Changma populations shared the same origin, while the Qiaowan population was different from them. The developed SSR markers discovered in this study will contribute to the conservation research on T. tenuis and the conservation of the fishery resources of the Shule River, providing scientific guidance for the development and utilization of T. tenuis resources and environmental protection.

20.
Adv Sci (Weinh) ; : e2309920, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175207

RESUMEN

Cytokines, crucial in immune modulation, impact disease progression when their secretion is dysregulated. Existing methods for profiling cytokine secretion suffer from time-consuming and labor-intensive processes and often fail to capture the dynamic nature of immune responses. Here, iSECRETE, an integrated platform that enables synchronous cell activation, wash-free, and target-responsive protein detection for single-cell IFN-γ cytokine secretion analysis within 30 min at room temperature is presented. By incorporating a DNA proximity assay (DPA) into a multifunctional microfluidic system, one-pot homogenous cytokine signal amplification, with a limit of detection of ≈50 secreted molecules per cell is achieved. iSECRETE can robustly handle various sample types that are shown. Two distinct immune activation assay modalities are demonstrated on iSECRETE. Finally, the detection of single-cell IFN-γ secretion as an activation hallmark of chimeric antigen receptor T cells within 6 h of exposure to cancer targets is shown. iSECRETE represents the fastest single-cell sample-to-result cytokine secretion assay to date, providing a powerful tool for advancing the understanding of biological phenotypes, functions, and pathways under in vivo-like conditions.

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