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1.
Artigo em Inglês | MEDLINE | ID: mdl-36337583

RESUMO

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attention deficit, hyperactivity, and impulsivity. Jing-Ning Granules (JNG) is a traditional Chinese medicine (TCM) that can alleviate ADHD. Although JNG is commonly used for the effective treatment of ADHD and has obtained the national invention patent, the exact mechanism of action remains unclear. Objective: In this study, we examined the effect and mechanism of JNG in spontaneously hypertensive rats (SHRs). We hypothesized that JNG affects dopaminergic D2/D1-like receptors and related pathways. Materials and Methods: Six rat groups were used in the experiment: Wistar-Kyoto rats (WKY, control group) and five SHR groups, including a model group; atomoxetine (ATX, positive control) group; and low, medium, and high-dose JNG groups. The corresponding treatments were daily administered to each group for 6 weeks. A behavioral test, including a step-down test and open field test (OFT), was carried out at the end of treatment. After the behavioral test, all animals were sacrificed, and the brain tissue was collected and analyzed ex vivo; histopathological analysis was performed to assess the pathological changes of the hippocampus; expression of D1-like and D2-like receptors, sensor protein calmodulin (CaM), protein kinase A (PKA), and calcium/calmodulin-dependent serine/threonine protein kinase (CaMKII) in the striatum and hippocampus was measured by western blot and real-time quantitative PCR (RT-PCR); cyclic adenosine monophosphate (cAMP) levels in the striatum were analyzed using an enzyme-linked immunosorbent assay (ELISA), while the level of Ca2+ in the striatum was analyzed by a calcium kit. Results: Our results showed that ATX or JNG could ameliorate the hyperactive/impulsive behavior and cognitive function of ADHD by promoting neuroprotection. Mechanistically, ATX or JNG could prompt the expressions of Dl-like and D2-like receptors and improve the mRNA and protein levels of cAMP/PKA and Ca2+/CAM/CAMKII signaling pathways. Conclusion: These results indicate that JNG can produce therapeutic effects by regulating the balance of D2/D1-like receptor-mediated cAMP/PKA and Ca2+/CaM/CaMKII signaling pathways.

2.
JAMA Netw Open ; 5(11): e2243457, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36416825

RESUMO

Importance: Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). Objective: To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. Design, Setting, and Participants: From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. Main Outcomes and Measures: The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. Results: A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)-based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. Conclusions and Relevance: In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.


Assuntos
Neoplasias Colorretais , Neoplasias Primárias Múltiplas , Masculino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Tipagem Molecular , Neoplasias Primárias Múltiplas/genética
3.
NPJ Parkinsons Dis ; 8(1): 151, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351910

RESUMO

This study aimed to investigate the cortical microstructural/macrostructural degenerative patterns in Parkinson's disease (PD) patients with mild cognitive impairment (MCI). Overall, 38 PD patients with normal cognition (PD-NC), 38 PD-MCI, and 32 healthy controls (HC) were included. PD-MCI was diagnosed according to the MDS Task Force level II criteria. Cortical microstructural alterations were evaluated with Neurite Orientation Dispersion and Density Imaging. Cortical thickness analyses were derived from T1-weighted imaging using the FreeSurfer software. For cortical microstructural analyses, compared with HC, PD-NC showed lower orientation dispersion index (ODI) in bilateral cingulate and paracingulate gyri, supplementary motor area, right paracentral lobule, and precuneus (PFWE < 0.05); while PD-MCI showed lower ODI in widespread regions covering bilateral frontal, parietal, occipital, and right temporal areas and lower neurite density index in left frontal area, left cingulate, and paracingulate gyri (PFWE < 0.05). Furthermore, compared with PD-NC, PD-MCI showed reduced ODI in right frontal area and bilateral caudate nuclei (voxel P < 0.01 and cluster >100 voxels) and the ODI values were associated with the Montreal Cognitive Assessment scores (r = 0.440, P < 0.001) and the memory performance (r = 0.333, P = 0.004) in the PD patients. However, for cortical thickness analyses, there was no difference in the between-group comparisons. In conclusion, cortical microstructural alterations may precede macrostructural changes in PD-MCI. This study provides insightful evidence for the degenerative patterns in PD-MCI and contributes to our understanding of the latent biological basis of cortical neurite changes for early cognitive impairment in PD.

4.
Front Psychol ; 13: 1014972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405133

RESUMO

Chinese e-commerce platforms have long helped to sell agricultural products through farmer-assisting marketing activities, effectively alleviating the problem of stagnant agricultural products in some areas, and have become a valuable cause-related marketing strategy. The ethical attributes of farmer-assisting agricultural products have unique value compared with other agricultural products. However, the existing research rarely pays attention to the influence of the ethical attributes of farmer-assisting agricultural products on consumers' willingness to buy farmer-assisting agricultural products online. Based on collective efficacy theory and risk perception theory, this study systematically explores the influence mechanism of ethical attributes (symbolic ethical attribute and functional ethical attribute) on consumers' willingness to buy farmer-assisting agricultural products online through three situational experiments. The results show that compared with functional ethical attributes, symbolic ethical attributes have a more positive impact on consumers' willingness to buy farmer-assisting agricultural products online. In addition, it further reveals two mediating pathways of ethical effects (collective efficacy and risk perception) and boundaries (emergency of farmer-assisting events). This study helps to understand the ethical attributes of farmer-assisting agricultural products, and provides some practical suggestions for e-commerce enterprises implementing farmer-assisting marketing communication activities or marketers developing and promoting farmer-assisting agricultural products.

5.
J Parkinsons Dis ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36336939

RESUMO

BACKGROUND: In Parkinson's disease (PD), excessive iron deposition in the substantia nigra may exacerbate α-synuclein aggregation, facilitating the degeneration of dopaminergic neurons and their neural projection. OBJECTIVE: To investigate the interaction effect between nigral iron deposition and PD status on brain networks. METHODS: Eighty-five PD patients and 140 normal controls (NC) were included. Network function and nigral iron were measured using multi-modality magnetic resonance imaging. According to the median of nigral magnetic susceptibility of NC (0.095 ppm), PD and NC were respectively divided into high and low nigral iron group. The main and interaction effects were investigated by mixed effect analysis. RESULTS: The main effect of disease was observed in basal ganglia network (BGN) and visual network (VN). The interaction effect between nigral iron and PD status was observed in left inferior frontal gyrus and left insular lobe in BGN, as well as right middle occipital gyrus, right superior temporal gyrus, and bilateral cuneus in VN. Furthermore, multiple mediation analysis revealed that the functional connectivity of interaction effect clusters in BGN and medial VN partially mediated the relationship between nigral iron and Unified Parkinson's Disease Rating Scale II score. CONCLUSION: Our study demonstrates an interaction of nigral iron deposition and PD status on brain networks, that is, nigral iron deposition is associated with the change of brain network configuration exclusively when in PD. We identified a potential causal mediation pathway for iron to affect disease severity that was mediated by both BGN dysfunction and VN hyperfunction in PD.

6.
Phytother Res ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331006

RESUMO

This study aimed to investigate the potential nephrotoxicity of icaritin and the underlying mechanism by in vitro-in vivo experiment technology combined with proteomics technology. First, icaritin showed a significant cytotoxic effect on HK-2 cells, which was accompanied by increased LDH and TNF-α in the supernatant, decreased protein expressions of Bcl-2 and increased Bax and enhanced apoptosis of HK-2 cells as measured by TUNEL staining. Moreover, icaritin induced obvious tubular damage and up-regulation of BUN and CRE levels in plasma in mice. Second, intracellular uptake of icaritin was considerably higher in hOAT1-HEK293 cells than in mock-HEK293 cells, suggesting that icaritin might accumulate in renal cells via OAT1 uptake. Importantly, icaritin caused significant changes in the PPAR signaling pathway in HK2 cells through proteomic analysis. Then, in vitro and in vivo results verified that icaritin significantly downregulated the protein expression of PPAR-α as well as downregulated APOB, ACSL3, ACSL4, and upregulated 5/12/15-HETE, implying that a lipid metabolism disorder was involved in the icaritin-induced nephrotoxicity. Finally, icaritin was found to increase the accumulation of iron and LPO levels while reducing the activity of GPX4, suggesting that ferroptosis was involved in the nephrotoxicity induced by icaritin.

7.
J Appl Stat ; 49(15): 3976-4002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324487

RESUMO

It is well known that financial data frequently contain outlying observations. Almost all methods and techniques used to estimate GARCH models are likelihood-based and thus generally non-robust against outliers. Minimum distance method, as an important tool for statistical inferences and a competitive alternative for achieving robustness, has surprisingly not been well explored for GARCH models. In this paper, we proposed a minimum Hellinger distance estimator (MHDE) and a minimum profile Hellinger distance estimator (MPHDE), depending on whether the innovation distribution is specified or not, for estimating the parameters in GARCH models. The construction and investigation of the two estimators are quite involved due to the non-i.i.d. nature of data. We proved that the MHDE is a consistent estimator and derived its bias in explicit expression. For both of the proposed estimators, we demonstrated their finite-sample performance through simulation studies and compared with the well-established methods including MLE, Gaussian Quasi-MLE, Non-Gaussian Quasi-MLE and Least Absolute Deviation estimator. Our numerical results showed that MHDE and MPHDE have much better performance than MLE-based methods when data are contaminated while simultaneously they are very competitive when data is clean, which testified to the robustness and efficiency of the two proposed MHD-type estimations.

8.
Opt Express ; 30(13): 23828-23839, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225056

RESUMO

The bound state in the continuum (BIC) is widely applied to metamaterial study in order to obtain robust resonance and high quality (Q) factor. In this paper, we propose a metallic metasurface structure that can support double types of BICs, and acquire quasi-BIC state by restructuring each type with a specific approach. Electric field distribution is investigated to explore the physic mechanism behind the evolution of BICs. Moreover, we substitute structured graphene with corresponding metal counterparts. The promoted design is able to switch freely between BIC and quasi-BIC state even after the fabrication, as the graphene would convert from semiconductor-like to metal-like when increasing the Fermi level. Further exploration on electric field distribution demonstrates the metallicity difference between graphene and gold, which leads to the exotic phenomenon emerge on the proposed metal-graphene structure. Finally, the proposed metal-graphene structure is applied to a digital coding display through Fermi level regulating. Therefore, our work provides deep insights to the BIC metasurface investigation, and introduces a desirable improvement for current BIC metasurface design to achieve the free conversion between BIC and quasi-BIC states.

9.
Transl Oncol ; 27: 101564, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36252282

RESUMO

CD3+CD4-CD8- double-negative T (DNT) cells are new weapons in cancer immunotherapy. Here, we explored DNT cells in malignant pleural effusions (MPEs) from lung cancer patients. DNT cells, especially TCRαß+CD56- DNT cells, were increased in MPE from lung cancer patients. DNT cells highly expressed PD-1, TRAIL, NKG2D and DNAM-1. In contrast, FasL was barely detected in DNT cells. Compared with non-MPE cells, MPE-derived DNT cells expressed much higher levels of PD-1 and TRAIL. DNT cells from healthy peripheral blood donors potentially killed lung cancers, which was decreased by MPE supernatant. Exosomes from MPE supernatant expressed PD-1 and CEACAM1 and impaired the cytotoxicity of DNT cells. Blocking PD-1 and TIM3 rescued the cytotoxicity of DNT cells treated with MPE-derived exosomes. Overall, we demonstrated that the frequency of DNT cells in MPE from lung cancer patients was increased and that MPE-derived exosomes impaired the cytotoxicity of DNT cells via the PD-1/PD-L1 and CEACAM1/TIM3 pathways.

10.
Front Plant Sci ; 13: 917755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186057

RESUMO

Environmental heterogeneity in temperature, moisture, and soil fertility caused by elevation gradients can affect the trade-offs in the survival strategies of tree species. There is uncertainty about the allocation of resources to different tissues of trees in response to the elevation gradient with respect to carbon (C), nitrogen (N), and phosphorus (P). Here, the C, N, and P content of leaves, branches, trunks, and thick and fine roots of Picea crassifolia (Qinghai spruce) and their stoichiometric changes across three different elevations were investigated in the Qilian Mountains. We found that N:P of Qinghai spruce was <14 in all tissues at most elevations, indicating that Qinghai spruce was more susceptible to N limitation. Meanwhile, the N content and N:P of Qinghai spruce each were significantly negatively correlated with temperature (p < 0.05), and its P content was lower at high elevation. The contribution of soil-climate interactions on the elevation gradient to each tissue type was 34.02% (leaves), 16.84% (branches), 67.78% (trunks), 34.74% (thick roots), and 49.84% (fine roots), indicating that interacting climate and soil factors on the elevation gradient predominately drove the C, N, and P content and stoichiometry variation in each tissue type of Qinghai spruce trees. The results of this study clarify that the elevation gradient regulates the elemental content and resource allocation in Qinghai spruce, providing basic data and an important timely reference for future forest management in the regions where coniferous trees grows. These findings also help improve our understanding of elevational patterns of forest ecosystem stoichiometry in arid and semiarid regions.

11.
Cancers (Basel) ; 14(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36230676

RESUMO

The colorectal-cancer (CRC) incidence rate and mortality have remained high for several years. In recent years, immune-checkpoint-inhibitor (ICI) therapy has rapidly developed. However, it is only effective in a few CRC patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) CRC. How to improve the efficiency of ICI therapy in CRC patients with microsatellite stability (MSS) remains a huge obstacle. Tumor-associated neutrophils (TANs), which are similar to macrophages, also have N1 and N2 phenotypes. They can be recruited and polarized through different cytokines or chemokines, and then play an antitumor or tumor-promoting role. In CRC, we find that the prognostic significance of TANs is still controversial. In this review, we describe the antitumor regulation of TANs, and their mechanism of promoting tumor progression by boosting the transformation of inflammation into tumors, facilitating tumor-cell proliferation, metastasis and angiogenesis. The targeting of TANs combined with ICIs may be a new treatment model for CRC. Relevant animal experiments have shown good responses, and clinical trials have also been carried out in succession. TANs, as "assistants" of ICI treatment, may become the key to the success of CRC immunotherapy, although no significant results have been obtained.

12.
Neuroimage ; 264: 119683, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36243270

RESUMO

Brain iron deposition is a promising marker for human brain health, providing insightful information for understanding aging as well as neurodegenerations, e.g., Parkinson's disease (PD) and Alzheimer's disease (AD). To comprehensively evaluate brain iron deposition along with aging, PD-related neurodegeneration, from prodromal PD (pPD) to clinical PD (cPD), and AD-related neurodegeneration, from mild cognitive impairment (MCI) to AD, a total of 726 participants from July 2013 to December 2020, including 100 young adults, 189 old adults, 184 pPD, 171 cPD, 31 MCI and 51 AD patients, were included. Quantitative susceptibility mapping data were acquired and used to quantify regional magnetic susceptibility, and the resulting spatial standard deviations were recorded. A general linear model was applied to perform the inter-group comparison. As a result, relative to young adults, old adults showed significantly higher iron deposition with higher spatial variation in all of the subcortical nuclei (p < 0.01). pPD showed a high spatial variation of iron distribution in the subcortical nuclei except for substantia nigra (SN); and iron deposition in SN and red nucleus (RN) were progressively increased from pPD to cPD (p < 0.01). AD showed significantly higher iron deposition in caudate and putamen with higher spatial variation compared with old adults, pPD and cPD (p < 0.01), and significant iron deposition in SN compared with old adults (p < 0.01). Also, linear regression models had significances in predicting motor score in pPD and cPD (Rmean = 0.443, Ppermutation = 0.001) and cognition score in MCI and AD (Rmean = 0.243, Ppermutation = 0.037). In conclusion, progressive iron deposition in the SN and RN may characterize PD-related neurodegeneration, namely aging to cPD through pPD. On the other hand, extreme iron deposition in the caudate and putamen may characterize AD-related neurodegeneration.

13.
Front Genet ; 13: 998846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246636

RESUMO

Background: The study aimed to report a boy with familial exudative vitreoretinopathy and amblyopia harboring a new mutation of the LRP5 and OPA1 gene abnormality. Case presentation: A 9-year-old boy presented with a 2-year history of deteriorating visual acuity in the right eye. His best-corrected visual acuity was -7.00/-1.75 × 100 = 0.3 in the right eye and -2.50/-1.50 × 170 = 0.8 in the left eye. Two autosomal dominant gene mutation sites were identified in the patient: LRP5 (c.2551C > T, p.His851Tyr) from his father and OPA1 (c.565G > A, p.Glu189Lys) from his mother. Interestingly, his fraternal twin brother harbored no abnormal gene mutations, and his eye tests were normal. Conclusion: This case expands the spectrum of LRP5 gene mutations among Chinese patients with familial exudative vitreoretinopathy, and it is the first time to report a patient harboring both LRP5 and OPA1 gene mutations having anisometropic amblyopia and strabismus as the primary manifestations. These four family members exhibited individual heterogeneity of phenotypes and genotypes associated with hereditary ophthalmopathy. A comprehensive analysis of clinical phenotypes and genotypes provides clinical clues for improving the level of clinical and genetic diagnoses and a deeper understanding of the disease.

14.
iScience ; 25(11): 105287, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36304123

RESUMO

Central and peripheral sensory neurons tightly regulate nociception and avoidance behavior. The peripheral modulation of nociception provides more veridical and instantaneous information for animals to achieve rapid, more fine-tuned and concentrated behavioral responses. In this study, we find that positive interaction between ASH and ASK sensory neurons is essential for the fast-rising phase of ASH Ca2+ responses to noxious copper ions and inhibits the adaption of avoiding Cu2+. We reveal the underlying neuronal circuit mechanism. ASK accelerates the ASH Ca2+ responses by transferring cGMP through gap junctions. ASH excites ASK via a disinhibitory neuronal circuit composed of ASH, AIA, and ASK. Avoidance adaptation depends on the slope rate of the rising phase of ASH Ca2+ responses. Thus, in addition to amplitude, sensory kinetics is significant for sensations and behaviors, especially for sensory and behavioral adaptations.

15.
Front Microbiol ; 13: 993285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312959

RESUMO

Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) exhibit heterogeneous tumor characteristics, distinct responses to immunotherapy, and different survival outcomes. However, it is unclear whether gut microbiota is distinct between CRCs with different MMR status. In this study, we used immunohistochemistry for four major MMR proteins to determine the MMR status in 230 CRC patients. The gut microbiota was profiled in cancerous and adjacent normal tissues by using bacterial 16S rRNA sequencing. The differences in microbiota diversity, composition and related metabolic pathways between patients with dMMR and pMMR CRCs were explored. Linear discriminant analysis effect size (LEfSe) analysis was further applied to validate the significant taxonomic differences at the genus level. In our study cohort, dMMR status was identified in 29 of 230 (12.61%) tumors. The richness (alpha-diversity) of gut microbiome in dMMR tumor tissue was higher compared with pMMR tumor tissues. The microbial community composition (beta-diversity) between the two groups was significantly different. The dMMR group was enriched considerably for some microbiota, including Fusobacteria, Firmicutes, Verrucomicrobia, and Actinobacteria at the phylum level and Fusobacterium, Akkermansia, Bifidobacterium, Faecalibacterium, Streptococcus, and Prevotella bacteria at the genus level. However, the pMMR group was dominated by Proteobacteria at the phylum level and Serratia, Cupriavidus and Sphingobium at the genus level. Moreover, a wide variety of microbiota associated functional pathways were observed with different MMR status. KEGG pathway analysis indicated a higher abundance of the biosynthesis and metabolic pathways of glycan and nucleotide, cell growth and death pathways, genetic replication and repair pathways in dMMR samples compared with the pMMR group. These findings demonstrate that CRC patients with different MMR status have distinct gut bacterial community richness, compositions and related metabolic pathways, suggesting basis that may explain the effectiveness of immunotherapy in dMMR tumors.

16.
Opt Express ; 30(22): 40231-40242, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36298959

RESUMO

Optical vortex beam carrying orbit angular momentum has been extensively researched and applied recently. Among which a perfect vortex beam (PVB) has attracted much attention owing to its topological charge (TC)-irrelevant intensity profile. However, the morphology singularity, as well as implementation complexity of the PVB tie the degree of freedom for multiplexing. Herein, by introducing the concept of a composite vortex beam, we originally propose a novel kind of PVB - perfect composite vortex beam (PCVB) - which possesses a rosette-like intensity pattern that is exactly correlated with the TC and can be directly generated using a single all-dielectric geometric metasurface rather than bulky optical systems. We numerically simulate the broadband generation of the proposed PCVB with various TCs, sizes, and rotation angles. To further explore the potential of our design in practical applications, we demonstrated the coaxial array of the PCVBs and detected their optical angular force for manipulating nanoparticles. We believe that our fruitage may pave a desirable avenue for optical communication, information processing, and optical manipulation.

17.
Planta Med ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064115

RESUMO

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic enzyme overexpressed in many tumors and associated with angiogenesis. Ginkgetin, isoginkgetin, sciadopitysin and amentoflavone, the primary biflavones found in Ginkgo biloba, have excellent anti-inflammatory and anti-tumor effects. However, the effect of biflavones on CYP1B1 activities remains unknown. In this study, 7-ethoxyresorufin O-deethylation (EROD) was used to characterize the activities of CYP1 families. The impacts of four ginkgo biflavones on CYP1B1 activity and the cellular protein expression of CYP1B1 were systematically investigated. The results showed that amentoflavone with six hydroxyl substituents exhibited the most potent selective inhibitory effect on CYP1B1 activity with IC50 of 0.054 µM in four biflavones. Sciadopitysin with three hydroxyl and three methoxy substituents had the weakest inhibitory activity against CYP1B1. Ginkgetin and isoginkgetin, both with four hydroxyl and two methoxy substituents, showed similar inhibitory intensity towards CYP1B1 with IC50 values of 0.289 and 0.211 µM, respectively. Kinetic analysis showed that ginkgetin and amentoflavone inhibited CYP1B1 in a non-competitive mode, whereas sciadopitysin and isoginkgetin induced competitive or mixed types of inhibition. Notably, four ginkgo biflavones were also confirmed to suppress the protein expressions of CYP1B1 and AhR in MCF-7. Furthermore, molecular docking studies indicated more hydrogen bonds formed between amentoflavone and CYP1B1, which might explain the strongest inhibitory action towards CYP1B1. In summary, these findings suggested that biflavones remarkably inhibited both the activity and protein expression of CYP1B1 and the inhibitory activities enhanced with the increasing hydroxyl substitution, providing new insights into the anti-tumor potentials of biflavones.

18.
Nanoscale Res Lett ; 17(1): 81, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053435

RESUMO

Metasurface can use artificial microstructures to manipulate electromagnetic waves more accurately and flexibly. All-dielectric metalens have a wide range of materials and low cost so it has a wide application prospect. Herein, we propose a all-dielectric achromatic metalens built with Si as the structural unit that can operate over a broadband of wavelengths in the visible region. It controls the wavefront of light through the Pancharatnam-Berry phase and propagation phase to eliminate the chromatic aberration. Meanwhile, we also use Gerchberg-Saxton algorithm and its improved algorithm to iterate over multiple design wavelengths and obtain holographic phases suitable for broadband. Thus, both the metalenses and holographic metasurfaces can achieve achromatic broadband in the visible light range, which provides a new method for the development of meta-optical imaging devices.

19.
Front Cell Dev Biol ; 10: 876071, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120557

RESUMO

Objective: To find potential diagnostic biomarkers for ovarian cancer (OC), a prospective analysis of the expression of five biomarkers in patients with intermediate-risk and their correlation with the occurrence of OC was conducted. Method: A prospective observational study was carried out, patients who underwent surgical treatment with benign or malignant ovarian tumors in our hospital from January 2020 to February 2021 were included in this study, and a total of 263 patients were enrolled. Based on the postoperative pathological results, enrolled patients were divided into ovarian cancer group and benign tumor group (n = 135). The ovarian cancer group was further divided into a mid-stage group (n = 46) and an advanced-stage group (n = 82). The basic information of the three groups of patients was collected, the preoperative imaging data of the patients were collected to assess the lymph node metastasis, the preoperative blood samples were collected to examine cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and the postoperative pathological data were sorted and summarized. Result: The average during of disease in the advanced ovarian cancer group was 0.55 ± 0.18 years higher than the benign tumor group (0.43 ± 0.14 years), p < 0.001. In the advanced ovarian cancer group, the ratio of patients with the tumor, node, metastasis (TNM) stage IV (64.63%), with tumor Grade stage II and III (93.90%), and without lymph node metastasis (64.63%) was respectively more than that in the mid-stage group (accordingly 0.00, 36.96, 23.91%) (p < 0.001); The ratio of patients with TNM grade III in the mid-stage group (73.91%) was more than that in the advanced group (35.37%) (p < 0.001). The levels of the five biomarkers: CA19-9, CA125, NLR, PLR, and BDNF were different among the three groups (p < 0.001). Conclusion: CA19-9, CA125, NLR, PLR, BDNF are five biomarkers related to the occurrence of ovarian cancer and are risk factors for it. These five biomarkers and their Combined-Value may be suitable to apply in the diagnosis and the identification of ovarian cancer in patients with intermediate-risk.

20.
Front Psychol ; 13: 979059, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092114

RESUMO

With changing trends and technology, the education system has evolved from a traditional to a modernized, qualitative, and innovatively sustained education system. Many factors contribute to process innovation and quality management benchmarks. This study has two primary goals: (1) determining the causal relationship between TQM and innovation capability, and (2) determining whether the exam, admission, and placement process have any effect on TQM and identifying whether TQM can act as a mediator between the admission, exam, and placement process and innovation capabilities. Furthermore, the study used TQM in multiple dimensions (quality management and leadership, staff interaction, institute productivity, and control and measurement of processes). As a result, the current study is the only one to look at TQM with its specific dimensions as a mediator, specifically in higher education. The survey and correlational methods were chosen to test the theoretical framework established using resource-based theory and explicitly based on structural equation modeling using Partial Least Square. A structured questionnaire based on a five-point Likert scale was also distributed to 350 professors (faculty members) from Chinese universities to assess the research constructs. The findings revealed that TQM positively and significantly impacts innovation capabilities. Besides, the admission, exam, and placement process is inextricably linked to TQM's dimensions and innovation capabilities. TQM also mediated significantly, and all hypotheses tested supported the findings. Future researchers should look into collaborative innovation capabilities and compare teachers' innovation capabilities in higher education, according to the study.

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