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Protein therapy targeting the intracellular machinery holds great potentials for disease treatment, and therefore, effective cytosolic protein delivery technologies are highly demanded. Herein, we developed reactive oxygen species (ROS)-degradable, branched poly(β-amino ester) (PBAE) with built-in phenylboronic acid (PBA) in the backbone and terminal-pendent arginine for the efficient cytosolic protein delivery. The PBAE could form stable and cell-ingestible nanocomplexes (NCs) with proteins via electrostatic interaction, nitrogen-boronate (N-B) coordination, and hydrogen bonding, while it can be degraded into small segments by the over-produced H

Inflammation mediates the neurological deficits caused by fluoride. Thus, whether inflammation is the underlying mechanism of dental fluorosis (DF) in school-aged children is worth exploring. A cross-sectional study was conducted to investigate the association between inflammation and the prevalence and severity of DF with low-to-moderate fluoride exposure. Fasting morning urine and venous blood samples were collected from 593 children aged 7-14 years. The fluoride content in the water and urine samples was measured using a fluoride ion-selective electrode assay. The levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were detected using an enzyme-linked immunosorbent assay. The Dean's index was used when performing dental examinations. Regression, stratified, and mediation analyses were performed to analyze the association between fluoride exposure, inflammation, and DF prevalence. In the adjusted regression models, the prevalence of mild DF was 1.723-fold (95% confidence interval [CI]:1.612, 1.841) and 1.594-fold (1.479, 1.717) greater than that of normal DF for each 1 mg/L increase in water and urinary fluoride content, respectively. The prevalence of mild DF increased by 3.3% for each 1 pg/mL increase in the IL-1β level and by 26.0% for each 1 mg/L increase in the CRP level. Stratified analysis indicated a weaker association between fluoride concentration and DF prevalence in boys than in girls, and susceptibility in the boys was reflected by the association of IL-1β with very mild and moderate DF prevalence. For every 1 mg/L increase in water and urinary fluoride levels, the proportion of IL-1β-mediated effects on the prevalence of mild DF was 10.0% (6.1%, 15.8%) and 8.7% (4.8%, 15.2%), respectively, and the proportion of CRP-mediated effects was 9.2% (5.5%, 14.9%) and 6.1% (3.3%, 11.0%), respectively. This study indicates that the DF prevalence may be sex-specific. Inflammatory factors may partially mediate the increased prevalence of mild DF in school-aged children with low-to-moderate fluoride exposure.

The n-back task is widely used in working memory (WM) research. However, it remains unclear how the electrophysiological correlates of WM processes, the P2, N2, P300, and negative slow wave (NSW), are affected by differences in load. Specifically, while previous work has examined the P300, less attention has been paid to the other components assessing the load of the n-back paradigm. The present study aims to investigate whether other sub-processes in WM (such as inhibitory control) are as sensitive to n-back load changes as the update process by observing changes in the above event-related potential (ERP) components. The results showed poorer behavioral performance with increasing WM load. Greater NSW and smaller P300 amplitudes were elicited by n-back task with a higher load compared to that with lower load. In contrast, there was no significant effect of the n-back load on the amplitudes of P2 and N2. These findings suggest that the updating process and the maintenance process are sensitive to the n-back load change. Therefore, changes in the updating and maintenance processes should be considered when using the n-back task to manipulate the WM load in experiments. The present study may contribute to the understanding of the complexity of WM loads. Additionally, a theoretical basis for follow-up research to explore ways of improving WM performance with high load is provided.

The development of effective targeted therapies for triple negative breast cancer (TNBC) remains a challenge. This targeted drug delivery system used a near-infrared fluorescence dye cyanine 5.5 (Cy5.5) and an ICAM-1 antibody on thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The ICAM-1 antibody and cyanine 5.5-engineered PMOs (PMO-Cy5.5-ICAM) offer excellent in vivo and in vitro biocompatibility. The PMO-Cy5.5-ICAM shows a loading capacity up to 400 mg/g of doxorubicin (DOX). The drug release profile of the DOX-loaded targeted delivery system (DOX@PMO-Cy5.5-ICAM) is pH-sensitive. Confocal microscopy showed that the PMO-Cy5.5-ICAM efficiently targets and enters TNBC cells. In in vivo experiments, the DOX@PMO-Cy5.5-ICAM accumulates more in TNBCs than in the control groups and exhibits better therapeutic effects on TNBC; thus, it is a promising treatment strategy for TNBC.

The Black Sea receives increasing amounts of microplastics from rivers. In this study, we explore options to reduce future river export of microplastics to the Black Sea. We develop five scenarios with different reduction options and implement them to a Model to Assess River Inputs of pollutaNts to seA (MARINA-Global) for 107 sub-basins. Today, European rivers draining into the Black Sea export over half of the total microplastics. In 2050, Asian rivers draining into the sea will be responsible for 34–46% of microplastic pollution. Implemented advanced treatment will reduce point-source pollution. Reduced consumption or more collection of plastics will reduce 40% of microplastics in the sea by 2050. In the optimistic future, sea pollution is 84% lower than today when the abovementioned reduction options are combined. Reduction options affect the share of pollution sources. Our insights could support environmental policies for a zero pollution future of the Black Sea.

Food production in China has been changing fast as a result of socio-economic development. This resulted in an increased use of nitrogen (N) in food production, and also to increased reactive nitrogen (Nr) losses to the environment, causing nitrogen pollution. Our study is the first to quantify future Nr losses from China's food system for the Shared Socio-economic Pathways (SSPs). We show that Nr losses differ largely among SSPs. We first qualitatively described the five SSP storylines for China with a focus on food production and consumption. Next, we interpreted these SSP scenarios quantitatively for 2030 and 2050, using the NUFER (NUtrient Flows in Food chains, Environment and Resources use) model to project the Nr losses from China's food system. The results indicate that Nr losses from future food system in China are relatively low for SSP1 and SSP2, and relatively high for SSP3 and SSP4. In SSP5 Nr losses from China's food system are projected to be slightly lower than the level of today.

Type 1 astrocytes (A1), which are highly proinflammatory and neurotoxic, are prevalent in multiple sclerosis (MS). In addition, in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), immune cells must cross the blood-brain barrier (BBB) and infiltrate into the parenchyma of the central nervous system (CNS) in order to induce neurological deficits. We have previously reported that treatment of EAE with matrine (MAT), a quinazine alkaloid derived from Sophorae Flavescens, effectively inhibited CNS inflammation and promoted neuroregeneration. However, the impact of MAT treatment on astrocyte phenotype is not known. In the present study, we showed that MAT treatment inhibited the generation of neurotoxic A1 astrocytes and promoted neuroprotective A2 astrocytes in the CNS of EAE, most likely by inhibiting production of the A1-inducing cytokine cocktail. MAT also downregulated the expression of vascular endothelial growth factor-A (VEGF-A) and upregulated tight junction proteins Claudin 5 and Occludin, thus protecting the BBB from CNS inflammation-induced damage. Moreover, MAT treatment promotes the formation of astrocyte tight junctions at glia limitans, thereby limiting parenchymal invasion of the CNS by immune cells. Taken together, the inhibition of A1 astrogliogenesis, and the dual effects on the BBB and astrocytic glia limitans, may be the mechanisms whereby MAT significantly improves EAE clinical scores and neuroprotection.

In this study, a polyethylene (PE) film contained tert-butyl hydroquinone (TBHQ) was immersed into an aqueous solution containing dehydrogenated ascorbic acid (DHA) as a separable system for verifying the regenerative effect between the two antioxidants with different solubilities. It was confirmed that DHA was regenerated to either ascorbic acid (AA) with the presence of TBHQ; and the regeneration rate of AA was significantly increased compared with the control without using the TBHQ-contained PE film. The extent of regeneration from DHA to AA was influenced by the following factors, including surface area of PE film, content of TBHQ, reaction time, and temperature. The regenerative mechanism of DHA to AA by TBHQ was proposed accordingly in which DHA was regenerated to AA by TBHQ, and the TBHQ was reacted to 2-tert-butyl-1,4-benzoquinone (TQ) as one of the oxidation products. A further application of the two antioxidants to liqueur chocolate was adopted. Results showed that the TBHQ added into chocolate shell significantly improved the antioxidant capacity of AA when added into the liquor filling. Therefore, such an established antioxidant combination would expect to extend the shelf-life of liqueur chocolate.

In this study, the polyphenol oxidase (PPO) activity of whole potatoes was inhibited by ultrasound. A 17-run Box-Behnken Design was used to optimize the ultrasound conditions for inhibiting the PPO activity. Three factors of ultrasound treatment including power, time, and temperature were investigated. Moreover, the effects of ultrasound treatment on the PPO activity of ultrasound-treated bruising damaged whole potatoes as well as on the micro-structure of the ultrasound-treated whole potatoes were evaluated. The adjusted coefficients of determination for models of Y1 and Y2 were 0.9980 and 0.9991, respectively. The p-values of two models for the responses were below 0.05, implying that the models can well represent PPO activities. The optimal ultrasound conditions were determined to be: ultrasound power 540 W, ultrasound time 15 min, and temperature 20 °C. Under these conditions, the mean PPO activities of the whole potatoes were 44.948 U/g, in accordance with the values predicted by the model. Besides, the PPO activity increases in the damaged whole potatoes. Nevertheless, the PPO activity of the ultrasound-treated whole potatoes was lower than that of untreated whole potatoes. Moreover, the power and time of ultrasound have a large impact on the micro-structures of the whole potatoes.

International audience; BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52*8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24*9% of deaths worldwide in 2010, down from 15*9 million (34*1%) of 46*5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2*5 to 1*4 million), lower respiratory infections (from 3*4 to 2*8 million), neonatal disorders (from 3*1 to 2*2 million), measles (from 0*63 to 0*13 million), and tetanus (from 0*27 to 0*06 million). Deaths from HIV/AIDS increased from 0*30 million in 1990 to 1*5 million in 2010, reaching a peak of 1*7 million in 2006. Malaria mortality also rose by an estimated 19*9% since 1990 to 1*17 million deaths in 2010. Tuberculosis killed 1*2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34*5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1*5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12*9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1*3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5*1 million deaths) was marginally higher in 2010 (9*6%) compared with two decades earlier (8*8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1*3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

For the earthquake disaster frequently happened in china, it is necessary to do some research about risk analysis of earthquake. The paper analyzed major factors of earthquake disaster firstly, established earthquake disaster risk assessment model with data of earthquake disaster between 1966 to 2010 and determinated the value of three factors quantitatively. Finally, taking Wenchuan earthquake region as an example, used the spatial analyst function of ArcMap system, analyzed the risk of population in earthquake disaster and created the population risk distribution map with a division of population high risk areas.