Summary In October, 2015, China's one-child policy was replaced by a universal two-child policy. The effects of the new policy are inevitably speculative, but predictions can be made based on recent ...trends. The population increase will be relatively small, peaking at 1·45 billion in 2029 (compared with a peak of 1·4 billion in 2023 if the one-child policy continued). The new policy will allow almost all Chinese people to have their preferred number of children. The benefits of the new policy include: a large reduction in abortions of unapproved pregnancies, virtual elimination of the problem of unregistered children, and a more normal sex ratio. All of these effects should improve health outcomes. Effects of the new policy on the shrinking workforce and rapid population ageing will not be evident for two decades. In the meantime, more sound policy actions are needed to meet the social, health, and care needs of the elderly population.
Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a ...difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and β-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, β-elemene liposome and cabazitaxel-β-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and β-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and β-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and β-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and β-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that β-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.
Summary Background The oldest-old (those aged ≥80 years) are the most rapidly growing age group globally, and are most in need of health care and assistance. We aimed to assess changes in mortality, ...disability in activities of daily living, and physical and cognitive functioning among oldest-old individuals between 1998 and 2008. Methods We used data from the Chinese Longitudinal Healthy Longevity Study. Three pairs of cohorts aged 80–89 years, 90–99 years, and 100–105 years (in total, 19 528 oldest-old participants) were examined; the two cohorts in each pair were born 10 years apart, with the same age at the time of the assessment in the 1998 and 2008 surveys. Four health outcomes were investigated: annual death rate, Activities of Daily Living (ADL), physical performance in three tests and cognitive function measured by Mini-Mental State Examination (MMSE). We used different tests and multivariate regression analyses to examine the cohort differences. Findings Controlling for various confounding factors, we noted that annual mortality among oldest-old individuals was substantially reduced between 0·2% and 1·3% in 1998–2008 compared with individuals of the same age born 10 years previously, and that disability according to activities of daily living had significantly reduced annually between 0·8% and 2·8%. However, cognitive impairment in the later cohorts increased annually between 0·7% and 2·2% and objective physical performance capacity (standing up from a chair, picking up a book from the floor, and turning around 360°) decreased anually between 0·4% and 3·8%. We also noted that female mortality was substantially lower than male mortality among the oldest-old, but that women's functional capacities in activities of daily living, cognition, and physical performance were worse than their male counterparts. Interpretation Advances in medications, lifestyle, and socioeconomics might compress activities of daily living disability, that is, benefits of success, but lifespan extension might expand disability of physical and cognitive functioning as more frail, elderly individuals survive with health problems, that is, costs of success. Funding National Natural Science Foundation of China, National Institute on Aging/National Institutes of Health, United Nations Funds for Population Activities.
Abstract
Glucose transporter GLUT1 is a transmembrane protein responsible for the uptake of glucose into the cells of many tissues through facilitative diffusion. Plasma membrane (PM) localization is ...essential for glucose uptake by GLUT1. However, the mechanism underlying GLUT1 PM localization remains enigmatic. We find that GLUT1 is palmitoylated at Cys207, and S-palmitoylation is required for maintaining GLUT1 PM localization. Furthermore, we identify DHHC9 as the palmitoyl transferase responsible for this critical posttranslational modification. Knockout of DHHC9 or mutation of GLUT1 Cys207 to serine abrogates palmitoylation and PM distribution of GLUT1, and impairs glycolysis, cell proliferation, and glioblastoma (GBM) tumorigenesis. In addition, DHHC9 expression positively correlates with GLUT1 PM localization in GBM specimens and indicates a poor prognosis in GBM patients. These findings underscore that DHHC9-mediated GLUT1 S-palmitoylation is critical for glucose supply during GBM tumorigenesis.
Sequence-derived structural and physiochemical features have been frequently used for analysing and predicting structural, functional, expression and interaction profiles of proteins and peptides. To ...facilitate extensive studies of proteins and peptides, we developed a freely available, open source python package called protein in python (propy) for calculating the widely used structural and physicochemical features of proteins and peptides from amino acid sequence. It computes five feature groups composed of 13 features, including amino acid composition, dipeptide composition, tripeptide composition, normalized Moreau-Broto autocorrelation, Moran autocorrelation, Geary autocorrelation, sequence-order-coupling number, quasi-sequence-order descriptors, composition, transition and distribution of various structural and physicochemical properties and two types of pseudo amino acid composition (PseAAC) descriptors. These features could be generally regarded as different Chou's PseAAC modes. In addition, it can also easily compute the previous descriptors based on user-defined properties, which are automatically available from the AAindex database.
The python package, propy, is freely available via http://code.google.com/p/protpy/downloads/list, and it runs on Linux and MS-Windows.
Supplementary data are available at Bioinformatics online.
The objectives of this article are to facilitate deeper research and promote better policy analysis for healthy aging with sound policy and intervention programs. Toward these objectives, we ...introduce the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which has been conducted by Center for Healthy Aging and Development Studies, National School of Development of Peking University since 1998. We cover the CLHLS study design, sample distributions, contents, general quality assessment and availability of the CLHLS data collected. Such an introduction would be helpful to our colleagues who may be interested in using this unique and more-than-14-year longitudinal survey data resource for deeper interdisciplinary research and better policy analysis on healthy aging. To illustrate how the unique data resources of CLHLS may be useful, we also summarize and discuss ten selected healthy aging policy related researches based on data from the CLHLS. Finally, we discussed the future prospects using the unique and rich CLHLS datasets.
A large nonlinear optical (NLO) coefficient and a wide band gap are two crucial but contradictory parameters that are difficult to achieve simultaneously in a single infrared (IR) NLO compound. A ...salt‐inclusion chalcogenide (SIC), LiLiCs2ClGa3S6 (1), was prepared that presents a nanosized tunnel framework constructed from monotype chalcogenide tetrahedra. Highly oriented covalent GaS4 tetrahedra in the host lead to a moderate second harmonic generation response (0.7 AgGaS2), and ionic guests effectively broaden the band gap to the widest value (4.18 eV) among all IR NLO chalcogenides, thereby achieving a remarkable balance between NLO efficiency and band gap.
The salt‐inclusion chalcogenide LiLiCs2ClGa3S6 is presented, which features a 3D framework composed of Ga3S6 nanosized tunnels. Introduction of an ionic guest to the covalent chalcogenide host produces a material with a moderate nonlinear optical (NLO) coefficient and an ultrawide band gap (Eg). These characteristics are promising for the development of infrared (IR) NLO materials.
Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related ...malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.
The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the oncogenic Epstein-Barr virus ...(EBV), the unique association with intake of Chinese-style salt-preserved fish, and etiologic heterogeneity by histologic subtype.
This review summarizes the current epidemiologic literature on NPC, highlighting recent results from our population-based case-control study in southern China.
Findings from our case-control study provide new insight into the epidemiology of NPC, including a diminished role of Chinese-style salt-preserved fish, a profound impact of EBV genetic sequence variation, modest positive associations with passive smoking and household air pollution, and possible effects of oral health and the oral microbiome. Recent findings from other studies include a protective association with infectious mononucleosis, suggesting a causal role of early EBV infection; familial risk conferred by shared genetic variation in the host antibody-mediated immune response to EBV infection; and an unclear association with occupational exposure to formaldehyde.
To shed further light on the interplay of environmental, genetic, and viral causes of NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.
New epidemiologic findings have reshaped the causal model for NPC.
Osteosarcoma, an aggressive malignant cancer, has a high lung metastasis rate and lacks therapeutic target. Here, we reported that chromobox homolog 4 (CBX4) was overexpressed in osteosarcoma cell ...lines and tissues. CBX4 promoted metastasis by transcriptionally up-regulating Runx2 via the recruitment of GCN5 to the Runx2 promoter. The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα. Consistently, CK1α suppressed cell migration and invasion through inhibition of CBX4. There was a reverse correlation between CK1α and CBX4 in osteosarcoma tissues, and CK1α was a valuable marker to predict clinical outcomes in osteosarcoma patients with metastasis. Pyrvinium pamoate (PP) as a selective activator of CK1α could inhibit osteosarcoma metastasis via the CK1α/CBX4 axis. Our findings indicate that targeting the CK1α/CBX4 axis may benefit osteosarcoma patients with metastasis.
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