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Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44–75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD.

В статье рассматриваются оценочные компоненты речей Си Цзиньпина и В. В. Путина на Всемирном экономическом форуме 2021 года в Давосе. The paper examines the evaluative components of the speeches of Xi Jinping and Vladimir Putin at the World Economic Forum 2021 in Davos.

OBJECTIVES: This study examined socioeconomic inequalities in compliance with precautions and health behavior changes during the coronavirus disease 2019 (COVID-19) outbreak using a representative Korean sample.METHODS: This exploratory study utilized around 210,000 participants aged ≥25 years in the Korean Community Health Survey 2020. Socioeconomic status was measured with educational attainment and household income. Outcomes included non-compliance with 8 precaution measures and deterioration in 6 health behaviors. The relative inequality index (RII) was calculated to quantify the degree of inequality by education and income level. RII values >1.0 indicate that deprived people have a higher frequency of health problems, and RII values

Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease.

Neurological disorders are listed as the second leading cause of death worldwide. Stroke and Alzheimer’s disease (AD) are the major contributors to neurological disorders of deaths. Every year, around 14 million new people are affected by stoke and nearly 10 million new cases of AD are diagonosed worldwide. The number of deaths and disabilities due to these disorders have increased considerably. Neuroinflammation is a major pathological feature appearing in the central nervous system (CNS) in these disorders. The central cellular components for neuroinflammation in CNS is microglia. The multifaceted roles of microglia under pathological conditions have been investigated by several research groups. Even if the knowledge about these cells is extensive, many aspects of their role in diseases have not been well elucidated. One of them is how microglia contribute to the pathology. Thus, I investigated how microglia communicate with other cells through extracellular vesicles (EVs) and how microglia cross-talk with the periphery under AD pathology. Firstly, upon LPS activation of microglia, we found that larger sizes of EVs were released and the levels of proinflammatory cytokines, TNF and IL-6, were increased in EVs. The proteomic profile was shifted to ribosomal assembly and translation. Complete ablation of TNF expression alleviated the inflammation and lead to reduced EVs secretion in a mouse model of stroke, as well as in vitro with LPS stimulation. Microglia are highly dynamic cells and can alter their phenotypes in response to diverse conditions. Therefore, we wanted to elucidate the activation profile of microglia under pathogenic conditions. In the early phase of AD pathogenesis, there is little known about how microglia contribute to the pathology. Thus, the 5xFAD mouse model of AD was used to investigate the effects before the formation of amyloid-β (Aβ) plaques in the CNS. Using a proteomic approach, early inflammatory activation of microglia was found before the formation of plaques.Last but not least, we studied the cross-talk between CNS and periphery under Aβ pathology. There are conflicting findings from animal studies on the contribution of peripheral inflammation on AD due to the variations in the degree of inflammation, timepoint of the stimulation, and the duration. Therefore, we designed our study to have two timepoints wherein we modulate the innate immunity, one was at the pre-plaque stage and the other was at the postnatal stage. Strikingly, a reduced number of plaques was found in hippocampus accompanied by less microglial activation in 5xFAD mice 4.5 months after the peripheral LPS challenge during the pre-plaque state. Subsequently, single-cell sequencing demonstrated that the early inflammation at the postnatal phase affected microglia and bone marrow resident monocytes (BM-Mo) similar to how AD affects these cell types. Interestingly, unique subpopulations of microglia were identified that were enriched in genes associated with lysosomal function (Lyz2) and a detrimental inflammatory marker (Galectin-3). These particular subsets carried a BM-Mo-like phenotype and appeared in response to acute peripheral inflammation and chronic inflammation caused by AD. We also observed that some subsets of myeloid cells were provoked by Aβ pathology but not systemic inflammation and vice versa.To summarize, microglia have multiple ways of contributing to the pathology of AD. Systemic inflammatory challenge can have pronounced effects on innate immunity in the CNS and the underlying mechanism remains to be elucidated. The findings of this thesis also provide potential candidates for use in early diagnostics and pharmacological targets to prevent the progression of AD.

В статье рассматривается состояние когнитивно-лингвистических исследований в Китае на фоне развития мировой когнитивной лингвистики., The article presents a review of the history and the current state of cognitive linguistic research in China on the background of development of the world cognitive linguistics., Политическая лингвистика, Issue № 4 (82), Pages 138-148

Nearly a quarter of the total number of deaths in the world are caused by unhealthy living or working environments. Therefore, we consider it significant to introduce the effect of a widely distributed component of air/water/food-source contaminants, polycyclic aromatic hydrocarbons (PAHs), on the human body, especially on immunity in this review. PAHs are a large class of organic compounds containing two or more benzene rings. PAH exposure could occur in most people through breath, smoke, food, and direct skin contact, resulting in both cellular immunosuppression and humoral immunosuppression. PAHs usually lead to the exacerbation of autoimmune diseases by regulating the balance of T helper cell 17 and regulatory T cells, and promoting type 2 immunity. However, the receptor of PAHs, aryl hydrocarbon receptor (AhR), appears to exhibit duality in the immune response, which seems to explain some seemingly opposite experimental results. In addition, PAH exposure was also able to exacerbate allergic reactions and regulate monocytes to a certain extent. The specific regulation mechanisms of immune system include the assistance of AhR, the activation of the CYP-ROS axis, the recruitment of intracellular calcium, and some epigenetic mechanisms. This review aims to summarize our current understanding on the impact of PAHs in the immune system and some related diseases such as cancer, autoimmune diseases (rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), and allergic diseases (asthma and atopic dermatitis). Finally, we also propose future research directions for the prevention or treatment on environmental induced diseases.

As one of the basic treatment modalities in the intensive care unit (ICU), mechanical ventilation can cause or aggravate acute lung injury or ventilator-induced lung injury (VILI). Resolvin D1 (RvD1) is an endogenous polyunsaturated fatty acid derivative with strong anti-inflammatory action. In this study, we explored if RvD1 possesses a protective effect on VILI. Mice were ventilated with high tidal volume (40 mL/kg, HVT) for 4 h and were then intraperitoneally administered RvD1 at the beginning of high tidal volume ventilation and given GW9662 (a PPAR-γ antagonist) intraperitoneally 30 min before ventilation. RvD1 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury, compared with HVT -induced lung injury. Similarly, it could ameliorate neutrophil accumulation and production of proinflammatory cytokines in lung tissue. In contrast, the protective effect of RvD1 on lung tissue could be reversed by GW9662. RvD1 mitigated VILI by activating peroxisome proliferator-activated receptor gamma (PPAR-γ) and inhibiting nuclear factor-kappa B (NF-κB) signaling pathways in mice. In conclusion, RvD1 could reduce the inflammatory response in VILI by activating PPAR-γ and inhibiting NF-κB signaling pathways.

As an avid advocator of education reform in the 1850s, Emerson was long neglected in the history of American educational thought. This paper, through the investigation from four aspects, namely the Transcendental Educational Thought, the Puritanical Educational Thought, the Romantic Educational Thought, and the Confucian’s Educational Thought, attempts to figure out the cultural background of Emerson’s education thought, tries to work out the connections between his ideas and his contemporaries, such as Thoreau, Fuller, and Alcott, and points out the significant role it plays in the history of American education thought up to day.

// Lihua Qiao 1, 2, * , Guoqing Ru 3, * , Zhuochao Mao 2, 4, * , Chenghui Wang 1, 2 , Zhipeng Nie 1, 2 , Qiang Li 1, 2 , Yiyi Huang-yang 2 , Ling Zhu 1, 2 , Xiaoyang Liang 1, 2 , Jialing Yu 2, 5 and Pingping Jiang 1, 2 1 Division of Medical Genetics and Genomics, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China 3 Department of Pathology, The Zhejiang Provincial People’s Hospital, Hangzhou, China 4 Department of Surgical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China 5 School of Public Health, Zhejiang University, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Pingping Jiang, email: ppjiang@zju.edu.cn Keywords: mitochondrion, hepatocellular carcinoma, somatic mutation, DNA copy number, TFAM Received: May 19, 2017 Accepted: August 17, 2017 Published: September 16, 2017 ABSTRACT We investigated the role of mitochondrial genetic alterations in hepatocellular carcinoma by directly comparing the mitochondrial genomes of 86 matched pairs of HCC and non-tumor liver samples. Substitutions in 637 mtDNA sites were detected, comprising 89.80% transitions and 6.60% transversions. Forty-six somatic variants, including 15 novel mutations, were identified in 40.70% of tumor tissues. Of those, 21 were located in the non-coding region and 25 in the protein-coding region. Twenty-two somatic nonsynonymous changes were identified as putative pathogenic variants, including 4 truncating mutations produced by three frameshifts ( MT-ATP6 8628 insC; MT-ND5 13475 T-del, and MT-CYB 14984 insA) and 1 nonsense mutation in MT-CO3 9253 G>A. Among the somatic variants, only m.13676 A>G ( MT-ND5 ), found in only 1 tumor, was heteroplasmic. Both inherited and somatic variants were predominately located in the D-loop region and the MT-ND5 gene. Tumor/non-tumor paired analysis showed that 69% of HCC samples contained significantly reduced mtDNA, compared with 49.0% of non-tumor counterparts. In 81.40% of HCC samples, mitochondrial transcription factor A (TFAM) was enriched in tumor cells but not in adjacent non-tumor cells. Neither mtDNA depletion nor TFAM overexpression correlated with the degree of cell differentiation, though TFAM expression correlated with tumor size.

Currently, the inefficient transport of liposomes in tumor tissue hinders their clinical application. Tumor-penetrating peptides (TPP) are a series of targeting peptides with the function of penetrating tumor blood vessels and tumor stroma. This work aimed to improve the penetration of liposomes in tumor tissues by TPP modification, thereby enhancing the antitumor effect. First, RPARPAR, a TPP, was modified to the surface of liposomes loaded with doxorubicin. The RPARPAR-modified liposomes (RPA-LP) and unmodified liposomes (LP) showed spherical morphology with average sizes about 90 nm. RPA-LP exhibited remarkably increased cellular accumulation by PC-3 tumor cells than LP as evidenced by the cellular uptake test. The in vivo imaging study confirmed that RPARPAR modification significantly increased the liposome accumulation in subcutaneous tumor tissues. RPA-LP could penetrate through tumor blood vessels and tumor stroma and into the deep tumor tissues as evidence by the immunofluorescence staining analysis. The cytotoxicity of RPARPAR-modified doxorubicin liposomes (RPA-LP-DXR) is considerably increased compared with that of doxorubicin liposomes (LP-DXR). The RPA-LP-DXR also showed significantly (p0.005) stronger growth-inhibiting effect on tumor than LP-DXR, possibly due to the tumor-penetrating ability of RPA-LP and targeted killing of tumor cells. This study proved that TPP mediation may be an effective strategy for improving the transport of liposomes in tumor tissue.

The targeted therapeutic effect of nano drug delivery system for glioblastoma has been hampered by the weak enhanced permeability and retention (EPR) effect of glioblastoma and the low delivering efficiency of NDDS in glioblastoma tissue. In this study, a tumor-penetrating peptide (RGERPPR), the specific ligand of neuropilin-1 overexpressed on glioblastoma and endothelial cells, was used as a targeting moiety to enhance the anti-glioblastoma effect of doxorubicin liposomes. Firstly, RGERPPR-PEG-DSPE was synthesized and used to prepare the RGERPPR peptide-functionalized liposomes (RGE-LS), which showed vesicle sizes of around 90 nm and narrow size distributions. The cellular uptake and in vivo near-infrared fluorescence imaging test displayed that RGE-LS exhibited increased uptake by glioblastoma cells and intracranial glioblastoma tissues. The cytotoxicity assay and anti-glioblastoma study proved that RGERPPR functionalization significantly enhanced the in vitro inhibitory effect of doxorubicin liposomes on glioblastoma cells and prolonged the median survival time of nude mice bearing intracranial glioblastoma. Finally, the immunofluorescence analysis evidenced that RGE-LS were able to penetrate through tumor vessels and stroma and deep into the whole tumor tissue. The results indicated that tumor-penetrating peptide functionalization is an effective strategy for enhancing the anti-glioblastoma effect of doxorubicin liposomes.