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1.
Entropy (Basel) ; 25(10)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37895522

RESUMO

The past few years have witnessed a surge of interest in non-Hermitian Floquet topological matter due to its exotic properties resulting from the interplay between driving fields and non-Hermiticity. The present review sums up our studies on non-Hermitian Floquet topological matter in one and two spatial dimensions. We first give a bird's-eye view of the literature for clarifying the physical significance of non-Hermitian Floquet systems. We then introduce, in a pedagogical manner, a number of useful tools tailored for the study of non-Hermitian Floquet systems and their topological properties. With the aid of these tools, we present typical examples of non-Hermitian Floquet topological insulators, superconductors, and quasicrystals, with a focus on their topological invariants, bulk-edge correspondences, non-Hermitian skin effects, dynamical properties, and localization transitions. We conclude this review by summarizing our main findings and presenting our vision of future directions.

2.
Opt Express ; 31(10): 16054-16066, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37157692

RESUMO

Single-photon light detection and ranging (LiDAR) has emerged as a strong candidate technology for active imaging applications. In particular, the single-photon sensitivity and picosecond timing resolution permits high-precision three-dimensional (3D) imaging capability through atmospheric obscurants including fog, haze and smoke. Here we demonstrate an array-based single-photon LiDAR system, which is capable of performing 3D imaging in atmospheric obscurant over long ranges. By adopting the optical optimization of system and the photon-efficient imaging algorithm, we acquire depth and intensity images through dense fog equivalent to 2.74 attenuation lengths at distances of 13.4 km and 20.0 km. Furthermore, we demonstrate real-time 3D imaging for moving targets at 20 frames per second in mist weather conditions over 10.5 km. The results indicate great potential for practical applications of vehicle navigation and target recognition in challenging weather.

3.
Food Chem ; 405(Pt A): 134551, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36371390

RESUMO

Lutein is a carotenoid that is beneficial to human health. However, its low stability and bioavailability have limited its application in the pharmaceutical and food industries. Herein, lutein has been successfully modified with carbon-dots (CDs) via a simple and mild solvent-ultrasonic method at room temperature. The synthesized lutein/CDs composites (LCs) showed 3.4 times higher photostability than the pristine lutein under UV irradiation, and 3.5 times higher than that under visible light, and the retention rate of lutein in the air rose from 3.6 % to 68 % over 25 days. Meanwhile, the antioxidant capacity of lutein has been improved by 6.4 times. Based on the photoluminescence (PL) measurements, a possible mechanism for the enhanced photostability and antioxidant ability of LCs has been proposed. The work provides a simple but effective approach to enhancing the stability and antioxidant capacity of lutein, and is expected to extend its application in food and biomedical fields.


Assuntos
Antioxidantes , Luteína , Humanos , Carbono , Disponibilidade Biológica , Raios Ultravioleta
5.
J Acoust Soc Am ; 151(4): 2649, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35461489

RESUMO

Core-shell nanostructures are widely used, and their photoacoustic (PA) properties are important for applications. However, the relations between their structural parameters and the properties of the PA spectrum are indirect because most theoretical models have been reported for them in the time domain. In this study, we develop a complete model in the frequency domain to analyze the PA response of core-shell particles. As in the case of solid spheres, the core-shell particles have pronounced resonant modes. The PA mode varies with the thickness of the shell and the radius of the core. Under single-pulse irradiation, PA signals of gold-silica nanospheres obtained by our theory agreed with those of the theory in the time domain and experiments. Under multi-pulse irradiation, the magnitude of the PA signals peaked whether the repeated excitation itself or its harmonic was equal to the PA mode. The structure could thus be monitored by the PA signals. These findings enrich PA theory and may inspire new techniques for the noninvasive characterization of nanoparticles.

6.
Int J Med Sci ; 19(1): 175-185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975311

RESUMO

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both in vitro and in vivo experiments showed that HF or HF-ATS induces apoptosis via activation of caspase-9 and caspase-8 while only caspase-9 is involved in ATS-induced apoptosis. Furthermore, we found HF or HF-ATS induces autophagy; ATS can't induce autophagy until caspase-9 is blocked. Further analyzing the crosstalk between autophagic and caspase activation in CRC cells, we found autophagy is essential for activation of caspase-8, and ATS switches to activate capase-8 via induction of autophagy when caspase-9 is inhibited. When apoptosis is totally blocked, HF-ATS switches to induce autophagic cell death. This scenario was then confirmed in studies of chemoresistance CRC cells with defective apoptosis. Our results indicate that HF-ATS induces cell death via interaction between apoptosis and autophagy in CRC cells. These results highlight the value of continued investigation into the potential use of this combination in cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Artemisininas/farmacologia , Neoplasias Colorretais/patologia , Piperidinas/farmacologia , Quinazolinonas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Artemisininas/uso terapêutico , Autofagia/efeitos dos fármacos , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Sinergismo Farmacológico , Ativação Enzimática , Humanos , Piperidinas/uso terapêutico , Quinazolinonas/uso terapêutico , Receptor Cross-Talk
7.
Zhonghua Nan Ke Xue ; 28(4): 314-320, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37477452

RESUMO

OBJECTIVE: To study the changes in the erectile function of the male patients with renal failure after hemodialysis (HD) or kidney transplantation (KT) and explore the causes of these changes. METHODS: From January 2015 to January 2021, 160 male patients with renal failure complaining of ED underwent HD (n = 80) or KT (n = 80) in the General Hospital of Eastern Theater Command. The patients were aged 25-45 (31.7 ± 4.8) years, 32 ± 4.5 years in the HD group and 31.4 ± 5.1 years in the KT group. We recorded the levels of serum T, E2, FSH and LH and the scores on IIEF-5, Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) of the patients, and compared them between the two groups. RESULTS: Compared with the patients in the HD group, those in the KT group showed a significantly higher T level (ï¼»7.45 ± 3.54ï¼½ vs ï¼»17.75 ± 7.32ï¼½ nmol/L, P < 0.01) and a lower E2 level (ï¼»151.37 ± 20.89ï¼½ vs ï¼»94.17 ± 40.79ï¼½ pmol/L, P < 0.01), but no statistically significant difference from the former group in the levels of FSH (ï¼»8.12 ± 5.12ï¼½ vs ï¼»8.97 ± 2.36ï¼½ IU/L, P > 0.05) and LH (ï¼»5.16 ± 3.87ï¼½ vs ï¼»4.69 ± 2.18ï¼½ IU/L, P > 0.05). There were fewer cases of severe ED in the KT than in the HD group (3.75% vs 16.25%, P < 0.05). Different degrees of anxiety and depression were observed in both groups, with fewer severe cases of anxiety (6.25% vs 30.00%, P < 0.05) and depression (6.25% vs 31.25%, P < 0.05) and more mild cases of anxiety (68.75% vs 47.50%, P < 0.05) and depression (70.00% vs 48.75%, P < 0.05) in the KT than in the HD group, but no statistically significant difference in the incidence of moderate anxiety (25.00% vs 22.50%, P > 0.05) and depression (23.75% vs 20.00%, P > 0.05) between the KT and HD groups. CONCLUSION: For male patients with renal failure, kidney transplantation can evidently improve erectile function, while hemodialysis has a poorer effect. The altered hormone levels, anxiety and depression of the patients are important causes of the changes in their erectile function.

8.
Front Med (Lausanne) ; 8: 774487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881268

RESUMO

Background: To address the worldwide dramatically increased Cesarean section (CS) rate in the past decades, WHO has recommended the CS rate should not be higher than 10-15%. Whether it is achievable remains unknown. Methods: We collected the data of delivery from 2008 to 2017 in two typical regional hospitals in China: Longhua Hospital (national policies rigorously implemented) and Dongguan Hospital (national policies not rigorously implemented). We compared between the two hospitals the 10 years trend in annual rate of CS, standardized by age, education level, parity, and CS history, against the time of issuing relevant national, local, and hospital policies. Results: In 10 years, 42,441 women in Longhua and 36,935 women in Dongguan have given birth. China's first national policy on CS reduction was issued in 2010 and the formal relaxation of one-child policy was issued in 2015-2016. In Longhua, the standardized annual CS rate was around 35% in 2008-2009, which declined sharply since 2010 down to 13.1% in 2016 (p < 0.001) and then leveled off. In contrast, in Dongguan, the rate stayed around 25% at the beginning, increased to 36% in 2011, decreased sharply to 27% in 2012, and leveled off until 2015 (p < 0.001), and then bounced back to 35% in 2017. The proportion of women with the history of CS increased significantly in the two hospitals (both roughly from 6% before 2010 to 20% after 2015). Analyses stratified by modified Robson classification showed that CS rates reduced in all risk classes of delivery women in Longhua but only in the Robson class 2 group in Dongguan. Major complications did not differ by hospital. Conclusion: With vigorously implementing national policies at micro levels, the WHO-recommended CS rate could be achieved without increase in major complications.

9.
Nanoscale Adv ; 3(14): 4089-4097, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-36132837

RESUMO

Dye degradation via photocatalysis technology has been investigated intensively to tackle environmental issues and energy crisis concerns. In this study, a newly designed ternary photocatalyst was facilely prepared by a simple one-pot hydrothermal process by directly mixing TiO2 nanoparticles with carbon dots (C-dots) and graphitic carbon nitride (g-C3N4). The optimized precursor treatments and heterostructure components show significantly enhanced photodegradation activity towards organic dyes Rhodamine B (RhB) and methylene blue (MB). Excellent photocatalytic activities were achieved owing to the better attachment of anatase-type TiO2 nanoparticle-aggregations to the C-dots/g-C3N4 (CC) nanocomposite, which impressively displays superhydrophilicity by employing the hydrothermal activation process. FT-IR spectra revealed that the hydrothermal treatment could remarkably increase the coupling interactions between TiO2 nanoparticles and the CC nanosheets within the ternary catalyst, enhancing the photocatalytic activity. Thus, it was concluded that this ternary photocatalyst is highly suitable for the remediation of dye-contaminated wastewater.

10.
Zookeys ; 1008: 17-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33505186

RESUMO

From a biodiversity survey of a subterranean habitat near Sinan County, Guizhou Province, southwestern China, a new atyid shrimp of the genus Caridina H. Milne Edwards, 1837, C. sinanensis sp. nov. was discovered. The new species can be separated from other congeners based on a combination of characters including depigmentation in body and reduction of eyes, small pigment spot at the centre of the cornea, the shape of rostrum and the endopod of the 1st male pleopod, and the relatively longer appendix interna on the appendix masculina of the 2nd pleopod. Mitochondrial COI and 16S rRNA gene sequences also support the establishment of the new species. Information on the habitat, and the levels of threat are discussed to guide the conservation of C. sinanensis sp. nov.

11.
Rice (N Y) ; 12(1): 99, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31883029

RESUMO

BACKGROUND: Salt stress is an important factor that limits rice yield. We identified a novel, strongly salt tolerant rice landrace called Changmaogu (CMG) collected from a coastal beach of Zhanjiang, Guangdong Province, China. The salt tolerance of CMG was much better than that of the international recognized salt tolerant rice cultivar Pokkali in the germination and seedling stages. RESULTS: To understand the molecular basis of salt tolerance in CMG, we performed BSA-seq for two extreme bulks derived from the cross between CMG and a cultivar sensitive to salt, Zhefu802. Transcriptomic sequencing was conducted for CMG at the germination and young seedling stages. Six candidate regions for salt tolerance were mapped on Chromosome 1 by BSA-seq using the extreme populations. Based on the polymorphisms identified between both parents, we detected 32 genes containing nonsynonymous coding single nucleotide polymorphisms (SNPs) and frameshift mutations in the open reading frame (ORF) regions. With transcriptomic sequencing, we detected a large number of differentially expressed genes (DEGs) at the germination and seedling stages under salt stress. KEGG analysis indicated two of 69 DEGs shared at the germination and seedling stages were significantly enriched in the pathway of carotenoid biosynthesis. Of the 169 overlapping DEGs among three sample points at the seedling stage, 13 and six DEGs were clustered into the pathways of ABA signal transduction and carotenoid biosynthesis, respectively. Of the 32 genes carrying sequence variation, only OsPP2C8 (Os01g0656200) was differentially expressed in the young seedling stage under salt stress and also showed sequence polymorphism in the ORFs between CMG and Zhefu802. CONCLUSION: OsPP2C8 was identified as the target candidate gene for salinity tolerance in the seedling stage. This provides an important genetic resource for the breeding of novel salt tolerant rice cultivars.

12.
Chemistry ; 25(51): 11933-11939, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31310395

RESUMO

Electrochemical reduction of N2 to NH3 is a promising method for artificial N2 fixation, but it requires efficient and robust electrocatalysts to boost the N2 reduction reaction (NRR). Herein, a combination of experimental measurements and theoretical calculations revealed that a hybrid material in which ZnO quantum dots (QDs) are supported on reduced graphene oxide (ZnO/RGO) is a highly active and stable catalyst for NRR under ambient conditions. Experimentally, ZnO/RGO was confirmed to favor N2 adsorption due to the largely exposed active sites of ultrafine ZnO QDs. DFT calculations disclosed that the electronic coupling of ZnO with RGO resulted in a considerably reduced activation-energy barrier for stabilization of *N2 H, which is the rate-limiting step of the NRR. Consequently, ZnO/RGO delivered an NH3 yield of 17.7 µg h-1 mg-1 and a Faradaic efficiency of 6.4 % in 0.1 m Na2 SO4 at -0.65 V (vs. RHE), which compare favorably to those of most of the reported NRR catalysts and thus demonstrate the feasibility of ZnO/RGO for electrocatalytic N2 fixation.

13.
J Acoust Soc Am ; 145(3): 1331, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31067931

RESUMO

Drug delivery by acoustic waves is a crucial technology for targeted therapy. Recently, a three-layered drug micro-particle was proposed and fabricated, the second shell of which greatly improves both the encapsulation of the drug and the flexibility in its release rate. In this work, the acoustic radiation force (ARF) of an acoustic focused Gaussian beam on a three-layered particle comprising an inner drug core (D), a middle layer of poly(lactide-co-glycolide) (PLGA), and an outer chitosan shell (CS) is investigated. A three-layered elastic shell (TES) mimics the D-PLGA-CS structure, and the acoustic scattering from and ARF of the D-PLGA-CS are studied using Mie theory. This paper focuses on how the geometry and acoustic parameters of the outer shell influence the ARF, finding that the Poisson's ratio of the outer shell affects the ARF more than does the density or Young's modulus. In addition, this paper finds that the choice of the inner drug has little effect on the ARF acting on the D-PLGA-CS particle. The present work may benefit the acoustic manipulation of both TESs and three-layered drugs.

14.
Medicine (Baltimore) ; 98(19): e15512, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083194

RESUMO

At present, the precise role of human menopausal gonadotropin (HMG) and recombinant luteinizing hormone (rLH) supplementation at an early time of follicular phase on in vitro fertilization (IVF)/intra cytoplasmatic sperm injection (ICSI) outcomes remains uncertain.Here infertile women of normal ovarian function undergoing their first cycle of IVF/ICSI were studied and were randomly allocated into 3 groups. Group 1, ovarian stimulation with 150IU recombinant follicle-stimulating hormone (FSH) alone. Group 2, patients received 75IU rFSH and 75IU HMG. Group 3 patients were given 150IU rFSH and 75IU rLH.There were no significant differences in the clinical characteristics, ovarian response, the biochemical, clinical and ongoing pregnancy rates among the 3 groups. No significant differences were found in biochemical, clinical and ongoing pregnancy rates between the patients whose LH levels were lower than 0.75 mIU/ml and those above this threshold in group 1. Furthermore, there were also no significant differences in biochemical, clinical and ongoing pregnancy rates among the 3 group patients whose LH level lower than 0.75 mIU/ml.The results showed that either the addition of HMG or rLH supplementation at an early time of follicular phase produce no significant benefit on IVF outcome in patients with normal ovarian function.


Assuntos
Fármacos para a Fertilidade Feminina/administração & dosagem , Hormônio Luteinizante/administração & dosagem , Menotropinas/administração & dosagem , Indução da Ovulação/métodos , Adulto , Feminino , Fertilização in vitro , Fase Folicular , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Adulto Jovem
15.
BMJ Open ; 9(5): e027807, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31129593

RESUMO

OBJECTIVES: To develop a nomogram to predict the likelihood of vaginal birth after caesarean section (VBAC) among women after a previous caesarean section (CS). DESIGN: A retrospective cohort study. SETTING: Two secondary hospitals in Guangdong Province, China. PARTICIPANTS: Inclusion criteria were as follows: pregnant women with singleton fetus, age ≥18 years, had a history of previous CS and scheduled for trial of labour after caesarean delivery (TOLAC). Patients with any of the following were excluded from the study: preterm labour (gestational age <37 weeks), two or more CSs, contradictions for vaginal birth, history of other uterine incision such as myomectomy, and incomplete medical records. PRIMARY OUTCOME MEASURE: The primary outcome was VBAC, which was retrospectively abstracted from computerised medical records by clinical staff. RESULTS: Of the women who planned for TOLAC, 84.0% (1686/2006) had VBAC. Gestational age, history of vaginal delivery, estimated birth weight, body mass index, spontaneous onset of labour, cervix Bishop score and rupture of membranes were independently associated with VBAC. An area under the receiver operating characteristic curve (AUC) in the prediction model was 0.77 (95% CI 0.73 to 0.81) in the training cohort. The validation set showed good discrimination with an AUC of 0.70 (95% CI 0.60 to 0.79). CONCLUSIONS: TOLAC may be a potential strategy for decreasing the CS rate in China. The validated nomogram to predict success of VBAC could be a potential tool for VBAC counselling.


Assuntos
Nascimento Vaginal Após Cesárea/estatística & dados numéricos , Adulto , Índice de Massa Corporal , China , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Prova de Trabalho de Parto
16.
Oncogenesis ; 7(9): 77, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30275459

RESUMO

Colorectal cancer stem cells (CSCs), characterized by self-renewal ability and high expression of proliferative genes, contribute to the chemoresistance of colorectal cancer (CRC). We aimed to identify the molecular mechanisms underlying CRC chemoresistance through comprehensive bioinformatics screenings and experimental confirmation of gene functions. We found that high expression of FGF1 intracellular binding protein (FIBP) was correlated with chemoresistance and poor prognosis in CRC patients. Therefore, the chemoresistant CRC cell line HCT116-CSC with high expression of the stem cell markers CD44 and CD133 was established for further phenotypic tests. FIBP knockdown inhibited proliferation, enhanced chemotherapy effects, and attenuated the stemness markers of CRC cells in vivo and in vitro. Through RNA-seq and gene set enrichment analysis, we identified cyclin D1 as a key downstream target in FIBP-regulated cell cycle progression and proliferation. Moreover, FIBP bound to GSK3ß, inhibited its phosphorylation at Tyr216, and activated ß-catenin/TCF/cyclin D1 signaling in HCT116-CSCs. Additional GSK3ß knockdown reversed the FIBP silencing-induced inhibition of proliferation and decreased stemness marker expression in HCT116-CSCs. Furthermore, DNA methylation profiling suggested that FIBP regulated the stemness of CRC cells via methylation activity that was dependent on GSK3ß but independent of ß-catenin signaling. Our data illuminate the potential of FIBP as a novel therapeutic target for treating chemoresistant CRC through inhibition of GSK3ß-related signaling.

17.
Sci Rep ; 8(1): 12682, 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30139974

RESUMO

Acoustic bottle-beams have been realized by acoustic metasurfaces (AMs) composed of space-coiling subunits. By manipulating the transmitted acoustical phase, the special AM can generate two intersecting accelerating beams along the designed convex trajectories, forming the acoustic bottle-beam. The transmitted acoustic bottle-beams are investigated theoretically and demonstrated numerically. We find that the shape and area of the acoustic bottle-beam could be statically controlled by designing the AM as well as dynamically modulated by the incident angles. In addition, the highly efficient acoustic focusing could be obtained at the convergence point of the bottle-beams, which also could be adjusted dynamically by the incident angles. It is further found that this focusing is robust against the obstacle scattering. The realization and manipulation of acoustic bottle-beams may have potential applications in biomedical imaging/therapy and non-destructive evaluation.

18.
Zool Res ; 39(6): 387-395, 2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-29955025

RESUMO

DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase(RAD51)focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA/genética , Oócitos/metabolismo , Proteínas de Ligação a RNA/fisiologia , Envelhecimento , Animais , Feminino , Meiose/genética , Camundongos/genética , Camundongos Endogâmicos C57BL/genética , Recombinação Genética/genética
19.
Phys Rev Lett ; 120(17): 170501, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29756821

RESUMO

Quantifying coherence has received increasing attention, and considerable work has been directed towards finding coherence measures. While various coherence measures have been proposed in theory, an important issue following is how to estimate these coherence measures in experiments. This is a challenging task, since the state of a system is often unknown in practical applications and the accessible measurements in a real experiment are typically limited. In this Letter, we put forward an approach to estimate coherence measures of an unknown state from any limited experimental data available. Our approach is not only applicable to coherence measures but can be extended to other resource measures.

20.
Chin Med ; 13: 14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29560022

RESUMO

BACKGROUND: Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model. METHODS: One week after surgery, PF was intraperitoneally administered at a dose of 40 mg/kg once a day for 28 successive days. The effects of PF on memory deficit were investigated by a Morris water maze test, and the effects of PF on hippocampal neuronal damage were evaluated by light microscope and electron microscope. The mRNA and protein expression levels of key molecules related to the M1/M2 polarization of microglia/macrophages were assessed by RT-qPCR and Western blotting, respectively. RESULTS: Administration of PF could significantly attenuate cerebral hypoperfusion-induced impairment of learning and memory and reduce the morphological and ultrastructural changes in the hippocampal CA1 region of rats. Moreover, PF promoted an M1 to M2 phenotype transition in microglia/macrophages in the hippocampus of rats. In addition to its inhibitory property against proinflammatory M1 mediator expression, such as IL-1ß, IL-6, TNF-α and NO, PF dramatically up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-ß1. Importantly, CB2R antagonist AM630 abolished these beneficial effects produced by PF on learning, memory and hippocampus structure in rats, as well as the polarization of microglia/macrophages to the M2 phenotype. Additionally, PF treatment significantly inhibited cerebral hypoperfusion-induced mTOR/NF-κB proinflammatory pathway and enhanced PI3K/Akt anti-inflammatory pathway. Effects of PF on these signaling pathways were effectively attenuated when rats were co-treated with PF and AM630, indicating that the mTOR/NF-κB and PI3K/Akt signaling pathways were involved in the PF effects through CB2R activation. CONCLUSION: These findings demonstrated PF exerts its neuroprotective effect and shifts the inflammatory milieu toward resolution by modulation of microglia/macrophage polarization via CB2R activation.

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