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1.
Biomed Pharmacother ; 179: 117397, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39232386

RESUMO

Celastrol, the primary constituent of Tripterygium wilfordii, has demonstrated neuroprotective properties in rats with dementia by reducing inflammation. A high-fat diet and streptozotocin injection were utilized to establish a diabetic rat model, which was then employed to investigate the possible protective effect of celastrol against the development of diabetes-induced learning and memory deficits. Afterwards, the experimental animals received a dose of celastrol by gavage (4 mg/kg/d). An animal study showed that celastrol enhanced insulin sensitivity and glucose tolerance in diabetic rats. In the Morris water maze test, rats with diabetes performed poorly in terms of spatial learning and memory; treatment with celastrol improved these outcomes. Additionally, administration of celastrol downregulated the expression of inflammatory-related proteins (NF-κB, IKKα, TNF-α, IL-1ß, and IL-6) and greatly reduced the generation of Aß in the diabetic hippocampus tissue. Moreover, the insulin signaling pathway-related proteins PI3K, AKT, and GSK-3ß were significantly upregulated in diabetic rats after celastrol was administered. Also, celastrol prevented damage to the brain structures and increased the synthesis of synaptic proteins like PSD-95 and SYT1. In conclusion, celastrol exerts a neuroprotective effect by modulating the insulin signaling system and reducing inflammatory responses, which helps to ameliorate the cognitive impairment associated with diabetes.

2.
J Colloid Interface Sci ; 677(Pt B): 365-376, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39151229

RESUMO

Developing effective photocatalysts to achieve stable and efficient solar-induced hydrogen production remains a significant challenge due to rapid photocarrier recombination and sluggish hydrogen evolution kinetics. Here, a multi-interfacial engineering strategy involving the decoration of metallic Ni3C onto CaTiO3/Mn0.5Cd0.5S was proposed to create an S-scheme/Schottky hybrid heterostructure with multiple carrier transport paths for effective photocatalytic H2 production. Exploiting the synergy between S-scheme heterojunction and Schottky barrier, the engineered ternary CaTiO3/Mn0.5Cd0.5S/Ni3C hybrid heterojunction exhibits outstanding photostability and significantly enhanced hydrogen evolution activity of 79.1 mmol g-1 h-1, which was about 4.55, 3.22 and 2.59 times greater than Mn0.5Cd0.5S, Mn0.5Cd0.5S/Ni3C, and CaTiO3/Mn0.5Cd0.5S, respectively. By creating an S-scheme heterojunction between CaTiO3 and Mn0.5Cd0.5S, accompanied by a robust internal electric field (IEF), spatial charge separation can be effectively accelerated while ensuring the simultaneous preservation of highly active electrons and holes. Meanwhile, Ni3C nanoparticles, acting as a Schottky-junction H2 generation cocatalyst, can efficiently trap the photoinduced electrons to establish multiple charge transfer channels and supply ample active sites for photoreduction reaction, thereby further optimizing the hydrogen generation kinetics. The integration of a Schottky barrier and S-scheme heterojunction in this research is expected to offer new perspectives for designing other highly effective hybrid catalysts for solar-to-hydrogen fuel conversion.

3.
Int Microbiol ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172273

RESUMO

The aquaculture sector, vital to global food security, grapples with bacterial pathogens compromising fish health and industry sustainability. This investigation probes mucosal immune responses and gut microbiota dynamics in snakehead (Channa argus) post-Aeromonas infection, a prevalent aquaculture challenge. Employing infection models, we delineated the integral role of immunoglobulin T (IgT) in mucosal immunity and its interaction with gut microbiota. Fish from a local farm, maintained under controlled conditions, were infected with Aeromonas veronii TH0426 and Aeromonas hydrophila TPS. Post-infection, daily monitoring and sample collection at specified intervals were conducted for comprehensive analysis. Histopathology, quantitative PCR, immunofluorescence, and microbiota profiling revealed significant immune and microbial changes, particularly at day 7. Intestinal IgT, IgM, and pIgR gene expression surged, indicative of a robust response. Immunofluorescence microscopy confirmed increased IgT+ and pIgR+ cell infiltration in the epithelium. Post-infection dysbiosis, with altered bacterial composition, was partially offset by elevated IgT levels. These insights underscore IgT's crucial function in mucosal defense and suggest potential for probiotic and vaccine strategies to enhance aquaculture disease resilience.

4.
ChemSusChem ; : e202401174, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183181

RESUMO

In response to carbon neutrality, photocatalytic reduction of CO2 has been the subject of growing interest for researchers over the past few years. Multi-carbon products (C2+) with higher energy density and larger market value produced from photocatalytic reduction of CO2 are still very limited owing to the low photocatalytic productivity and poor selectivity of products. This review focuses on the recent progress on photocatalytic reduction of CO2 towards C2+ products from the perspective of performance evaluation and mechanistic understanding. We first provide a systematic description of the entire fundamental procedures of photocatalytic reduction of CO2. An in-depth strategy analysis for improving the selectivity of photocatalytic reduction of CO2 to C2+ products is then addressed. Then the focus was on summarizing the ways to improve C2+ selectivity. The intrinsic mechanisms of photocatalytic reduction of CO2 to C2+ products are summarized in the final. Combining the foundation of photocatalysis with promising catalyst strategies, this review will offer valuable guidance for the development of efficient photocatalytic systems for the synthesis of C2+ products.

5.
ACS Appl Mater Interfaces ; 16(33): 43860-43868, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39105733

RESUMO

Due to the atomic asymmetry, Janus transition metal dichalcogenide monolayers possess spontaneous curling and can even form one-dimensional nanoscrolls. Unveiling this spontaneous formation mechanism of nanoscrolls is of great importance for precise structural control. In this paper, we successfully simulate the process of Janus MoSSe nanoscroll formation from flat nanoribbons, based on molecular dynamics (MD) simulations with hybrid potentials. The spontaneous scrolling is purely driven by the relaxation of intrinsic strain in Janus MoSSe. The final structure of nanoscroll is strongly affected by the length of nanoribbon with a nonmonotonous relation. To further understand the mechanism, we establish a thermodynamic model to determine the inner radius of MoSSe nanoscrolls, which is shown to be related to spontaneous curvature, bending stiffness, interlayer van der Waals interaction, interlayer distance, and length of initial nanoribbon. The results correspond well with MD simulations of nanoscrolls from flat nanoribbons and the molecular static simulations of directly built nanoscrolls. Moreover, the inner radii of MoSeTe and MoSTe nanoscrolls are predicted based on the model. Our results provide insights into the Janus TMD nanoscroll formation and a pathway for controllable fabrication of nanoscrolls.

6.
Mater Horiz ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39045671

RESUMO

Ultralong room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) materials provide exciting opportunities for the rational design of persistent luminescence owing to their long-lived excitons. However, conventional rare-earth-based all-inorganic emitters involve high cost and harsh synthesis conditions, and purely organic systems may require complicated synthesis routes and tedious purification. Therefore, it is highly desirable to develop a cost-effective and easily manufacturable method for achieving color-tunable RTP-TADF with a long afterglow. Herein, we demonstrate a rational strategy to introduce different anions (Cl-, Br- and OAc- ions) into a Zn-based metal-organic scaffold, which can improve the crystal rigidity and achieve a well-balanced RTP-TADF. Both theoretical and experimental studies have demonstrated that the adjustment of different anions can effectively modulate the spin-orbit coupling (SOC) and the energy gap of singlet-triplet states (ΔEST) and then tailor the afterglow lifetime. Moreover, we prepared dye-doped metal-organic hybrid glasses with remarkable potential for the color-tunable afterglow. Therefore, this work not only provides a new horizon for modulating crystal and glass states with color/lifetime-tunable persistent luminescence, but also contributes to optical information storage and anti-counterfeiting technology.

7.
Int J Biometeorol ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073612

RESUMO

Short-term exposure to air pollution has previously been studied in relation to certain neurological disorders, but there is still a lack of convincing data linking air pollution to epileptic seizures. The study's goal was to investigate how exposure to ambient nitrogen dioxide (NO2) affected the number of patients seeking assistance at the Wuhan Emergency Medical Center due to epileptic seizures. We gathered data on medical emergency calls (MECs), daily ambient air pollution concentrations (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables in Wuhan, China, spanning from January 1, 2017, to November 30, 2019. To investigate the potential influence of ambient nitrogen dioxide on MECs for epileptic seizures, we carried out a time-series investigation using the general additive model (GAM). Additionally, analyses stratified by season, age, and gender were performed. A total of 8989 records of MECs for epileptic seizures were enrolled in our study during the period. Statistical analysis indicates that a rise of 10 µg/m3 in NO2 concentration is linked to a 0.17% increase in daily MECs for epileptic seizures (95% confidence interval [CI]: 0.02%, 0.32%). Furthermore, people aged 14-59 years were more susceptible(2.25%, P < 0.05). The short-term effects of NO2 exposure on daily MECs for epileptic seizures were stronger in warm seasons than in cool seasons (0.55% vs. -0.10%, P < 0.0001). Our findings suggests that short-term exposure to ambient NO2 was positively correlated with daily MECs for epileptic seizures in Wuhan, China. Additionally, we observed that these associations were stronger in patients aged above 14 but under 60 years and the warmer seasons (from April to September).

8.
Biomed Pharmacother ; 176: 116870, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850658

RESUMO

Intracranial atherosclerotic stenosis (ICAS) is a pathological condition characterized by progressive narrowing or complete blockage of intracranial blood vessels caused by plaque formation. This condition leads to reduced blood flow to the brain, resulting in cerebral ischemia and hypoxia. Ischemic stroke (IS) resulting from ICAS poses a significant global public health challenge, especially among East Asian populations. However, the underlying causes of the notable variations in prevalence among diverse populations, as well as the most effective strategies for preventing and treating the rupture and blockage of intracranial plaques, remain incompletely comprehended. Rupture of plaques, bleeding, and thrombosis serve as precipitating factors in the pathogenesis of luminal obstruction in intracranial arteries. Pericytes play a crucial role in the structure and function of blood vessels and face significant challenges in regulating the Vasa Vasorum (VV)and preventing intraplaque hemorrhage (IPH). This review aims to explore innovative therapeutic strategies that target the pathophysiological mechanisms of vulnerable plaques by modulating pericyte biological function. It also discusses the potential applications of pericytes in central nervous system (CNS) diseases and their prospects as a therapeutic intervention in the field of biological tissue engineering regeneration.


Assuntos
Pericitos , Pericitos/patologia , Humanos , Animais , Arteriosclerose Intracraniana/patologia , Arteriosclerose Intracraniana/fisiopatologia , Vasa Vasorum/patologia , Vasa Vasorum/fisiopatologia , Artérias Cerebrais/patologia
9.
Autophagy ; 20(9): 2112-2113, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38744666

RESUMO

Hematopoietic stem cells (HSC) emerge from hemogenic endothelial cells (HEC) in the aorta-gonad-mesonephros (AGM) region of embryos, which go through the pre-HSC process. Various intrinsic and extrinsic factors are involved in this process. We recently discovered that the existence of distinct macroautophagic/autophagic statuses in hematopoietic precursors is related to the hematopoietic potential of pre-HSCs and the depletion of the Atg5 (autophagy related 5) gene specifically in endothelial cells impaired in the transition of endothelial to pre-HSCs, by hampering the autophagic process, likely via the NCL (nucleolin) pathway.Abbreviation: Atg5: autophagy related 5; EGFP: enhanced green fluorescent protein; EHT: endothelial-to-hematopoietic transition; HEC: hemogenic endothelial cell; HSC: hematopoietic stem cell; NCL: nucleolin; RFP: red fluorescent protein.


Assuntos
Autofagia , Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Autofagia/fisiologia , Animais , Humanos , Embrião de Mamíferos/citologia , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Hematopoese/fisiologia
10.
Eur J Pharmacol ; 975: 176642, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754538

RESUMO

The effective treatment of diabetes with comorbid depression is a big challenge so far. Honokiol, a bioactive compound from the dietary supplement Magnolia officinalis extract, possesses multiple health benefits. The present study aims to propose a network pharmacology-based method to elucidate potential targets of honokiol in treating diabetes with comorbid depression and related mechanisms. The antidepressant-like efficacy of honokiol was evaluated in high-fat diet (HFD) induced diabetic mice using animal behavior testing, immuno-staining and western blotting assay. Through network pharmacology analysis, retinoid X receptor alpha (RXRα) and vitamin D receptor (VDR) were identified as potential targets related to diabetes and depression. The stable binding conformation between honokiol and RXR/VDR was determined by molecular docking simulation. Moreover, hononkiol effectively alleviated depression-like behaviors in HFD diabetic mice, presented anti-diabetic and anti-neuroinflammatory functions, and protected the hippocampal neuroplasticity. Importantly, honokiol could activate RXR/VDR heterodimer in vivo. The beneficial effects of honokiol on HFD mice were significantly suppressed by UVI3003 (a RXR antagonist), while enhanced by calcitriol (a VDR agonist). Additionally, the disruption of autophagy in the hippocampus of HFD mice was ameliorated by honokiol, which was attenuated by UVI3003 but strengthened by calcitriol. Taken together, the data provide new evidence that honokiol exerts the antidepressant-like effect in HFD diabetic mice via activating RXR/VDR heterodimer to restore the balance of autophagy. Our findings indicate that the RXR/VDR-mediated signaling might be a potential target for treating diabetes with comorbid depression.


Assuntos
Compostos de Bifenilo , Depressão , Diabetes Mellitus Experimental , Lignanas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Receptores de Calcitriol , Animais , Lignanas/farmacologia , Lignanas/uso terapêutico , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Camundongos , Masculino , Depressão/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/agonistas , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Receptor X Retinoide alfa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Autofagia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Comorbidade , Compostos Alílicos , Fenóis
11.
Biomed Mater ; 19(4)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38772387

RESUMO

Single-cell analysis is an effective method for conducting comprehensive heterogeneity studies ranging from cell phenotype to gene expression. The ability to arrange different cells in a predetermined pattern at single-cell resolution has a wide range of applications in cell-based analysis and plays an important role in facilitating interdisciplinary research by researchers in various fields. Most existing microfluidic microwell chips is a simple and straightforward method, which typically use small-sized microwells to accommodate single cells. However, this method imposes certain limitations on cells of various sizes, and the single-cell capture efficiency is relatively low without the assistance of external forces. Moreover, the microwells limit the spatiotemporal resolution of reagent replacement, as well as cell-to-cell communication. In this study, we propose a new strategy to prepare a single-cell array on a planar microchannel based on microfluidic flip microwells chip platform with large apertures (50 µm), shallow channels (50 µm), and deep microwells (50 µm). The combination of three configuration characteristics contributes to multi-cell trapping and a single-cell array within microwells, while the subsequent chip flipping accomplishes the transfer of the single-cell array to the opposite planar microchannel for cells adherence and growth. Further assisted by protein coating of bovine serum albumin and fibronectin on different layers, the single-cell capture efficiency in microwells is achieved at 92.1% ± 1%, while ultimately 85% ± 3.4% on planar microchannel. To verify the microfluidic flip microwells chip platform, the real-time and heterogeneous study of calcium release and apoptosis behaviours of single cells is carried out. To our knowledge, this is the first time that high-efficiency single-cell acquisition has been accomplished using a circular-well chip design that combines shallow channel, large aperture and deep microwell together. The chip is effective in avoiding the shearing force of high flow rates on cells, and the large apertures better allows cells to sedimentation. Therefore, this strategy owns the advantages of easy preparation and user-friendliness, which is especially valuable for researchers from different fields.


Assuntos
Microfluídica , Análise de Célula Única , Análise de Célula Única/métodos , Humanos , Microfluídica/métodos , Adesão Celular , Animais , Desenho de Equipamento , Técnicas Analíticas Microfluídicas/instrumentação , Dispositivos Lab-On-A-Chip , Fibronectinas/química , Fibronectinas/metabolismo , Cálcio/metabolismo , Cálcio/química , Soroalbumina Bovina/química , Comunicação Celular
12.
EBioMedicine ; 104: 105161, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772282

RESUMO

BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric illness affecting ∼1% of the global adult population. Lithium (Li), is the most effective mood stabilizer for BD but works only for a subset of patients and its mechanism of action remains largely elusive. METHODS: In the present study, we used iPSC-derived neurons from patients with BD who are responsive (LR) or not (LNR) to lithium. Combined electrophysiology, calcium imaging, biochemistry, transcriptomics, and phosphoproteomics were employed to provide mechanistic insights into neuronal hyperactivity in BD, investigate Li's mode of action, and identify alternative treatment strategies. FINDINGS: We show a selective rescue of the neuronal hyperactivity phenotype by Li in LR neurons, correlated with changes to Na+ conductance. Whole transcriptome sequencing in BD neurons revealed altered gene expression pathways related to glutamate transmission, alterations in cell signalling and ion transport/channel activity. We found altered Akt signalling as a potential therapeutic effect of Li in LR neurons from patients with BD, and that Akt activation mimics Li effect in LR neurons. Furthermore, the increased neural network activity observed in both LR & LNR neurons from patients with BD were reversed by AMP-activated protein kinase (AMPK) activation. INTERPRETATION: These results suggest potential for new treatment strategies in BD, such as Akt activators in LR cases, and the use of AMPK activators for LNR patients with BD. FUNDING: Supported by funding from ERA PerMed, Bell Brain Canada Mental Research Program and Brain & Behavior Research Foundation.


Assuntos
Proteínas Quinases Ativadas por AMP , Transtorno Bipolar , Células-Tronco Pluripotentes Induzidas , Neurônios , Proteínas Proto-Oncogênicas c-akt , Transtorno Bipolar/metabolismo , Transtorno Bipolar/tratamento farmacológico , Humanos , Neurônios/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Lítio/farmacologia , Lítio/uso terapêutico , Transdução de Sinais , Perfilação da Expressão Gênica , Transcriptoma
13.
J Environ Manage ; 357: 120776, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579468

RESUMO

Hydro-Fluctuation Belt (HFB), a periodically exposed bank area formed by changes in water level fluctuations, is critical for damaging the reservoir wetland landscape and ecological balance. Thus, it is important to explore the mechanism of hydrological conditions on the plant-soil system of the HFB for protection of the reservoir wetland and landscape restoration. Here, we investigated the response of plant community characteristics and soil environment of the HFB of Tonghui River National Wetland Park (China), is a typical reservoir wetland, to the duration of inundation, as well as the correlation between the distribution of dominant plants and soil pH, nutrient contents, and enzyme activity by linear regression and canonical correlation analyses. The results show that as the duration of inundation decreases, the vegetation within the HFB is successional from annual or biennial herbs to perennial herbs and shrubs, with dominant plant species prominent and uneven distribution of species. Soil nutrient contents and enzyme activities of HFB decreased with increasing inundation duration. Dominant species of HFB plant community are related to soil environment, with water content, pH, urease, and available potassium being principle soil environmental factors affecting their distribution. When HFB was inundated for 0-30 days, soil pH was strongly acidic, with available potassium content above 150 mg kg-1 and higher urease activity, distributed with Arundo donax L., Polygonum perfoliatum L., Alternanthera philoxeroides (Mart.) Griseb., and Daucus carota L. communities. When inundated for 30-80 days, soil pH was acidic, with lower available potassium content (50-150 mg kg-1) and urease activity, distributed with Beckmannia syzigachne (Steud.) Fern.+ Polygonum lapathifolium L., Polygonum lapathifolium L., Medicago lupulina L. + Dysphania ambrosioides L. and Leptochloa panicea (Retz.) Ohwi communities. Using the constructed HFB plant-soil correlation model, changes in the wetland soil environment can be quickly judged by the succession of plant dominant species, which provides a simpler method for the monitoring of the soil environment in the reservoir wetland, and is of great significance for the scientific management and reasonable protection of the reservoir-type wetland ecosystem.


Assuntos
Ecossistema , Áreas Alagadas , Solo/química , Urease , Plantas , Água , Poaceae , China , Potássio
14.
Small ; 20(34): e2400796, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38607275

RESUMO

Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.

15.
EMBO J ; 43(9): 1722-1739, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580775

RESUMO

Understanding the regulatory mechanisms facilitating hematopoietic stem cell (HSC) specification during embryogenesis is important for the generation of HSCs in vitro. Megakaryocyte emerged from the yolk sac and produce platelets, which are involved in multiple biological processes, such as preventing hemorrhage. However, whether megakaryocytes regulate HSC development in the embryonic aorta-gonad-mesonephros (AGM) region is unclear. Here, we use platelet factor 4 (PF4)-Cre;Rosa-tdTomato+ cells to report presence of megakaryocytes in the HSC developmental niche. Further, we use the PF4-Cre;Rosa-DTA (DTA) depletion model to reveal that megakaryocytes control HSC specification in the mouse embryos. Megakaryocyte deficiency blocks the generation and maturation of pre-HSCs and alters HSC activity at the AGM. Furthermore, megakaryocytes promote endothelial-to-hematopoietic transition in a OP9-DL1 coculture system. Single-cell RNA-sequencing identifies megakaryocytes positive for the cell surface marker CD226 as the subpopulation with highest potential in promoting the hemogenic fate of endothelial cells by secreting TNFSF14. In line, TNFSF14 treatment rescues hematopoietic cell function in megakaryocyte-depleted cocultures. Taken together, megakaryocytes promote production and maturation of pre-HSCs, acting as a critical microenvironmental control factor during embryonic hematopoiesis.


Assuntos
Células-Tronco Hematopoéticas , Megacariócitos , Animais , Megacariócitos/citologia , Megacariócitos/metabolismo , Camundongos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular , Hematopoese/fisiologia , Mesonefro/embriologia , Mesonefro/metabolismo , Mesonefro/citologia , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Técnicas de Cocultura
16.
Cardiovasc Diabetol ; 23(1): 95, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486275

RESUMO

OBJECTIVE: The association of the triglyceride-glucose (TyG) index with intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) is unclear. This study aimed to investigate the relationship of TyG index with the distribution and severity of ICAS and ECAS. METHOD: Patients who underwent digital subtraction angiography (DSA) for evaluating ICAS/ECAS in Zhongnan Hospital of Wuhan University from January 2017 to October 2021 were retrospectively enrolled in our study. Clinical characteristics, DSA data, blood routine, lipid profile and fasting glucose were recorded. The association of TyG index and ICAS/ECAS status were investigated in four aspects: location and distribution of stenosis, stenosis severity and whether stenosis is symptomatic. Logistic regression models were used to evaluate the association. Restricted cubic splines were constructed to model the non-linear relationship between the TyG index and different arterial stenosis status. RESULTS: Among 1129 included patients, the median age was 62 (IQR 55-68) years, and 71.3% were male. The median TyG index was 8.81 (8.40, 9.21). Elevated TyG index was significantly associated with ICAS, combined ICAS/ECAS, anterior circulation stenosis, posterior circulation stenosis, combined anterior/posterior circulation stenosis, severe stenosis, both asymptomatic and symptomatic stenosis. This association was maintained after adjusting for age, sex, smoking, drinking, medical history of hypertension and stroke, platelet, total cholesterol, high-density lipoprotein, and low-density lipoprotein. Multivariable-adjusted spline regression models showed that a progressively increasing risk of arterial stenosis was related to an elevated TyG index. CONCLUSION: Elevated TyG index was associated with ICAS/ECAS. TyG index might be a useful indicator of ICAS and severe stenosis.


Assuntos
Glucose , Lipoproteínas HDL , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Triglicerídeos , Estudos Retrospectivos , Constrição Patológica
17.
Nat Commun ; 15(1): 2255, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490977

RESUMO

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.


Assuntos
Hemangioblastos , Células-Tronco Hematopoéticas , Animais , Camundongos , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular , Embrião de Mamíferos , Hematopoese/genética , Fatores de Transcrição/metabolismo , Autofagia/genética , Mesonefro
18.
Molecules ; 29(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38257381

RESUMO

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography-time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound-target-disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.


Assuntos
Ansiolíticos , Sesquiterpenos , Humanos , Ansiolíticos/farmacologia , Farmacologia em Rede , Microextração em Fase Sólida , Transtornos de Ansiedade , Cromatografia Gasosa-Espectrometria de Massas , Sesquiterpenos/farmacologia
19.
Heliyon ; 9(11): e22262, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38045129

RESUMO

Background: Cerebral venous sinus thrombosis (CVST) in pregnancy was common and endovascular treatment (EVT) could be an effective and safe treatment for patients with severe and refractory CVST. However, the efficacy and safety of hybrid EVT (craniotomy + endovascular treatment) for CVST were unknown. We represented a rare case of hybrid EVT through the incision of the superior sagittal sinus in a pregnant woman with CVST who failed to EVT through the femoral vein pathway. Case presentation: A 26-year-old woman, in her second month of pregnancy, complained of a headache for 5 days and aggravation with coma combined with convulsions for 2 days. She was diagnosed with CVST in the local hospital by digital subtraction angiography (DSA) and treated with anticoagulation. She had no history of illness and the biochemical tests were normal. Hybrid EVT (craniotomy + EVT) was attempted after failing to conduct EVT through the femoral vein pathway due to difficulty to reach the target cerebral venous sinus. Briefly, a small hole was made in the frontotemporal head to expose the superior sagittal sinus and a 6F sheath was inserted into 2cm of superior sagittal sinus incision and fixed on the scalp, after repeated aspiration by 5F intermediate catheter and balloon dilatation of stenosis in the right transverse sinus and right sigmoid sinus, the cerebral venous system got successful recanalization. No obvious complications were found and the patient recovered very well after the surgery. Conclusion: Anticoagulation was the standard treatment for CVST. EVT could rapidly restore venous flow and improve the prognosis for refractory and severe CVST. EVT by hybrid surgery through the superior sagittal sinus incision may be safe and effective for desperate patients with severe CVST.

20.
Plants (Basel) ; 12(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38140515

RESUMO

Toona ciliata M. Roem. is a valuable and fast-growing timber species which is found in subtropical regions; however, drought severely affects its growth and physiology. Although the exogenous application of salicylic acid (SA) has been proven to enhance plant drought tolerance by regulating the osmotic system and photosynthesis rate, the physiological processes involved in the regulation of drought tolerance by SA in various plants differ. Therefore, drought mitigation techniques tailored for T. ciliata should be explored or developed for the sustainable development of the timber industry. We selected 2-year-old T. ciliata seedlings for a potting experiment, set the soil moisture at 45%, and subjected some of the T. ciliata seedlings to a moderate drought (MD) treatment; to others, 0.5 mmol/L exogenous SA (MD + SA) was applied as a mitigation test, and we also conducted a control using a normal water supply at 70% soil moisture (CK). Our aim was to investigate the mitigating effects of exogenous SA on the growth condition, osmotic system, and photosynthesis rate of T. ciliata under drought stress conditions. OPLS-VIP was used to analyze the main physiological factors that enable exogenous SA to alleviate drought-induced injury in T. ciliata. The results indicated that exogenous SA application increased the growth of the ground diameter, plant height, and leaf blades and enhanced the drought tolerance of the T. ciliata seedlings by maintaining the balance of their osmotic systems, improving their gas exchange parameters, and restoring the activity of their PSII reaction centers. The seven major physiological factors that enabled exogenous SA to mitigate drought-induced injury in the T. ciliata seedlings were the soluble proteins (Sp), net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), stomatal opening window (Sow), activity of the photosystem II reaction center (ΦPSII), and electron transfer rate (ETR). Of these, Sp was the most dominant factor. There was a synergistic effect between the osmotic system and the photosynthetic regulation of drought injury in the T. ciliata seedlings. Overall, our study confirms that exogenous SA enhances the drought tolerance of T. ciliata by modulating the osmotic system and photosynthesis rate.

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