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1.
Angew Chem Int Ed Engl ; : e202409763, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954763

RESUMEN

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

2.
Angew Chem Int Ed Engl ; : e202409948, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949953

RESUMEN

As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.

3.
Eur J Neurosci ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054660

RESUMEN

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

4.
Yi Chuan ; 46(7): 581-586, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39016091

RESUMEN

Biodiversity losses along with the exponential growth of global human population and human-provoked over-exploitation of natural resources. Genetic factors played an important role in the conservation of endangered species. Conservation genetics is a cross-field disciplinary of genetics and conservation biology. The course of conservation genetics is not available in colleges and universities, and the course of genetics does not directly reflect the content of biological conservation. We have taught genetics with integrative thoughts of conservation biology. In the form of case studies, we have integrated recent advances of research and technology in the relevant fields into the genetics classroom. As a result, we improved the undergraduates' motivation and interest in active learning, provoked the mutual promotion of "basic knowledge of genetics, awareness of ecological protection, and cultivate interdisciplinary thinking", and set up the groundwork for cultivating interdisciplinary talents who not only master solid basic knowledge, but also have the concept of ecological civilization.


Asunto(s)
Conservación de los Recursos Naturales , Genética , Conservación de los Recursos Naturales/métodos , Humanos , Genética/educación , Enseñanza , Biología/educación
5.
Huan Jing Ke Xue ; 45(6): 3433-3445, 2024 Jun 08.
Artículo en Chino | MEDLINE | ID: mdl-38897764

RESUMEN

This research was conducted using many spatial analysis approaches to dissect the spatiotemporal interactive characteristics of carbon emission intensity within the transportation sector from 2002 to 2020. An in-depth exploration of their transition mechanisms was conducted by nesting the obtained timewarp types with the panel quantile model. Finally, the geodetector model aligned with different transition mechanisms was employed to investigate and analyze the interaction effects among various factors influencing carbon intensity in the transportation sector. The results indicated that:① The carbon emission intensity of the transportation sector in 30 provinces and regions of China showed an overall downward trend with fluctuations, and the spatial clustering level was relatively stable. ② The spatiotemporal interactive features of ESTDA revealed that the relationship between the northwest region and its adjacent spatial units was unstable, with significant variations and fluctuations. In contrast, economically developed areas such as coastal cities in the eastern part had established mature transportation networks, resulting in a relatively stable local spatial pattern, though a few areas still exhibited spatiotemporal competitiveness. ③ The spatiotemporal transition of carbon intensity in the transportation sector could be categorized into four driving or constraining modes(the population economy urbanization constraint model, population economy urbanization facility constraint model, technology consumption industry-driven model, and technology industry regulation-driven model). Most provinces were influenced by the low quantile constraint and high quantile drive modes, with only a few affected by the high quantile constraint and low quantile drive modes, the majority of which were located in the northwest or southwest regions. ④ Further, we introduced the geographical detector model based on the identified mechanism of carbon emission intensity transition in the transportation sector, emphasizing the coordinated development of multiple factors and strengthening inter-regional collaborative governance.

6.
Front Pharmacol ; 15: 1409971, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38841374

RESUMEN

Background: Patrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine "Bai jiang cao (herba patriniae)," and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown. Method: UPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague-Dawley rats were categorized into five groups, and PV groups (125 and 375 mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serum level of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4. Results: A total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4. Conclusion: The results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent.

7.
Zhongguo Zhen Jiu ; 44(6): 732-4, 2024 Jun 12.
Artículo en Chino | MEDLINE | ID: mdl-38867638

RESUMEN

This paper introduces a moxa floss shaping and spreading device for governor vessel moxibustion. This device is consisted of a storage unit and a propulsion unit, capable of automatically shaping moxa sticks for governor vessel moxibustion. The device allows for the flexible adjustment of moxa stick length, better conforming to the physiological curvature of the spine, and avoiding potential burns associated with governor vessel moxibustion. It simplifies the operational procedures for healthcare professionals, offering the advantages of ease of use, safety, and efficiency.


Asunto(s)
Moxibustión , Humanos , Moxibustión/instrumentación , Moxibustión/métodos , Diseño de Equipo
8.
Ecotoxicol Environ Saf ; 280: 116534, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38823345

RESUMEN

The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 µM FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.


Asunto(s)
Asma , Formaldehído , Interferón gamma , Factor de Transcripción STAT1 , Proteínas de Dominio T Box , Asma/inducido químicamente , Animales , Factor de Transcripción STAT1/metabolismo , Interferón gamma/metabolismo , Ratones , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Formaldehído/toxicidad , Inflamación/inducido químicamente , Ratones Endogámicos BALB C , Humanos , Femenino , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/química , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Jurkat
9.
Nat Commun ; 15(1): 3961, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729932

RESUMEN

Mechanically interlocked molecules (MIMs) including famous catenanes show switchable physical properties and attract continuous research interest due to their potential application in molecular devices. The advantages of using spin crossover (SCO) materials here are enormous, allowing for control through diverse stimuli and highly specific functions, and enabling the transfer of the internal dynamics of MIMs from solution to solid state, leading to macroscopic applications. Herein, we report the efficient self-assembly of catenated metal-organic frameworks (termed catena-MOFs) induced by stacking interactions, through the combination of rationally selected flexible and conjugated naphthalene diimide-based bis-pyridyl ligand (BPND), [MI(CN)2]- (M = Ag or Au) and Fe2+ in a one-step strategy. The obtained bimetallic Hofmann-type SCO-MOFs [FeII(BPND){Ag(CN)2}2]·3CHCl3 (1Ag) and [FeII(BPND{Au(CN)2}2]·2CHCl3·2H2O (1Au) possess a unique three-dimensional (3D) catena-MOF constructed from the polycatenation of two-dimensional (2D) layers with hxl topology. Both complexes undergo thermal- and light-induced SCO. Significantly, abnormal increases in the maximum emission intensity and dielectric constant can be detected simultaneously with the switching of spin states. This research opens up SCO-actuated bistable MIMs that afford dual functionality of coupled fluorescence emission and dielectricity.

10.
Nano Lett ; 24(23): 6924-6930, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38820073

RESUMEN

We have experimentally investigated the mechanism of the exchange bias in 2D van der Waals (vdW) ferromagnets by means of the anomalous Hall effect (AHE) together with the dynamical magnetization property. The temperature dependence of the AC susceptibility with its frequency response indicates a glassy transition of the magnetic property for the Te-rich FeGeTe vdW ferromagnet. We also found that the irreversible temperature dependence in the anomalous Hall voltage follows the de Almeida-Thouless line. Moreover, the freezing temperature of the spin-glass-like phase is found to correlate with the disappearance temperature of the exchange bias. These important signatures suggest that the emergence of magnetic exchange bias in the 2D van der Waals ferromagnets is induced by the presence of the spin-glass-like state in FeGeTe. The unprecedented insights gained from these findings shed light on the underlying principles governing exchange bias in vdW ferromagnets, contributing to the advancement of our understanding.

11.
Nat Commun ; 15(1): 3901, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724505

RESUMEN

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Asunto(s)
Citoplasma , Inhibidor NF-kappaB alfa , FN-kappa B , Proteínas Tirosina Quinasas , Factor de Transcripción ReIA , Animales , Fosforilación , Inhibidor NF-kappaB alfa/metabolismo , Inhibidor NF-kappaB alfa/genética , Ratones , Factor de Transcripción ReIA/metabolismo , Humanos , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , FN-kappa B/metabolismo , Citoplasma/metabolismo , Proteolisis , Núcleo Celular/metabolismo , Replicación Viral , Células HEK293 , Transducción de Señal , Ratones Endogámicos C57BL , Citocinas/metabolismo , Transporte Activo de Núcleo Celular , Proteínas Serina-Treonina Quinasas
12.
PLoS One ; 19(5): e0302961, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38748691

RESUMEN

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Análisis Costo-Beneficio , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Años de Vida Ajustados por Calidad de Vida , Humanos , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , China , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/economía , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/economía , Neoplasias Esofágicas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Masculino , Femenino , Metástasis de la Neoplasia , Análisis de Costo-Efectividad
13.
Ecotoxicol Environ Saf ; 278: 116432, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38728947

RESUMEN

Cadmium (Cd) pollution is a serious global environmental problem, which requires a global concern and practical solutions. Microbial remediation has received widespread attention owing to advantages, such as environmental friendliness and soil amelioration. However, Cd toxicity also severely deteriorates the remediation performance of functional microorganisms. Analyzing the mechanism of bacterial resistance to Cd stress will be beneficial for the application of Cd remediation. In this study, the bacteria strain, up to 1400 mg/L Cd resistance, was employed and identified as Proteus mirabilis Ch8 (Ch8) through whole genome sequence analyses. The results indicated that the multiple pathways of immobilizing and detoxifying Cd maintained the growth of Ch8 under Cd stress, which also possessed high Cd extracellular adsorption. Firstly, the changes in surface morphology and functional groups of Ch8 cells were observed under different Cd conditions through SEM-EDS and FTIR analyses. Under 100 mg/L Cd, Ch8 cells exhibited aggregation and less flagella; the Cd biosorption of Ch8 was predominately by secreting exopolysaccharides (EPS) and no significant change of functional groups. Under 500 mg/L Cd, Ch8 were present irregular polymers on the cell surface, some cells with wrapping around; the Cd biosorption capacity exhibited outstanding effects (38.80 mg/g), which was mainly immobilizing Cd by secreting and interacting with EPS. Then, Ch8 also significantly enhanced the antioxidant enzyme activity and the antioxidant substance content under different Cd conditions. The activities of SOD and CAT, GSH content of Ch8 under 500 mg/L Cd were significantly increased by 245.47%, 179.52%, and 241.81%, compared to normal condition. Additionally, Ch8 significantly induced the expression of Acr A and Tol C (the resistance-nodulation-division (RND) efflux pump), and some antioxidant genes (SodB, SodC, and Tpx) to reduce Cd damage. In particular, the markedly higher expression levels of SodB under Cd stress. The mechanism of Ch8 lays a foundation for its application in solving soil remediation.


Asunto(s)
Cadmio , Proteus mirabilis , Contaminantes del Suelo , Cadmio/toxicidad , Contaminantes del Suelo/toxicidad , Biodegradación Ambiental
14.
World J Gastrointest Oncol ; 16(5): 1787-1795, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38764817

RESUMEN

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

15.
Comput Struct Biotechnol J ; 23: 1978-1989, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38765608

RESUMEN

With both the advancement of technology and the decline in costs, single-cell transcriptomics sequencing has become widespread in the biomedical area in recent years. It can facilitate the pathogenic characteristics at the single-cell level, which will assist clinical researchers in exploring the mechanism of diseases. As a result, single-cell transcriptome data based on clinical samples grew exponentially. However, there is still a lack of a comprehensive database about immunocytes in inflammatory-associated diseases. To address this deficiency, we propose a human inflammatory-associated disease-based single-cell transcriptome database, NTCdb (www.ntcdb.org.cn). NTCdb integrates the open-source data of 1,023,166 cells derived from 11 tissues of 17 inflammatory-associated diseases in a uniform pipeline. It provides a set of analyzing results, including cell communication analysis, enrichment analysis, and Pseudo-Time analysis, to obtain various characteristics of immune cells in inflammatory-associated disease. Taking COVID-19 as a case study, NTCdb displays important information including potentially significant functions of certain cells, genes, and signaling pathways, as well as the commonalities of specific immunocytes between different inflammatory-associated disease.

16.
Acta Pharmacol Sin ; 45(7): 1438-1450, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38565961

RESUMEN

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.


Asunto(s)
Movimiento Celular , Dinaminas , Células Endoteliales de la Vena Umbilical Humana , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Endogámicos C57BL , Dinámicas Mitocondriales , Quinazolinonas , Especies Reactivas de Oxígeno , Neovascularización Retiniana , Factor A de Crecimiento Endotelial Vascular , Dinámicas Mitocondriales/efectos de los fármacos , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Dinaminas/metabolismo , Dinaminas/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Quinazolinonas/farmacología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Neovascularización Retiniana/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Angiogénesis
17.
J Am Chem Soc ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38604977

RESUMEN

Polar compounds with switchable polarization properties are applicable in various devices such as ferroelectric memory and pyroelectric sensors. However, a strategy to prepare polar compounds has not been established. We report a rational synthesis of a polar CoGa crystal using chiral cth ligands (SS-cth and RR-cth, cth = 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane). Both the original homo metal Co crystal and Ga crystal exhibit a centrosymmetric isostructure, where the dipole moment of metal complexes with the SS-cth ligand and those with the RR-cth ligand are canceled out. To obtain a polar compound, the Co valence tautomeric complex with SS-cth in the homo metal Co crystal is replaced with the Ga complex with SS-cth by mixing Co valence tautomeric complexes with RR-cth and Ga complexes with SS-cth. The CoGa crystal exhibits polarization switching between the pseudononpolar state at a low temperature and the polar state at a high temperature because only Co complexes exhibit changes in electric dipole moment due to metal-to-ligand charge transfer. Following the same strategy, the polarization-switchable CoZn complex was synthesized. The CoZn crystal exhibits polarization switching between the polar state at a low temperature and the pseudononpolar state at a high temperature, which is the opposite temperature dependence to that of the CoGa crystal. These results revealed that the polar crystal can be synthesized by design, using a chiral ligand. Moreover, our method allows for the control of temperature-dependent polarization changes, which contrasts with typical ferroelectric compounds, in which the polar ferroelectric phase typically occurs at low temperatures.

18.
J Hazard Mater ; 470: 134180, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38569342

RESUMEN

Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.

20.
Chin Med ; 19(1): 43, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448912

RESUMEN

BACKGROUND: Myocardial ischemia-reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia-reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. METHODS: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. RESULTS: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. CONCLUSION: EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

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