Amyloid precursor protein (APP) is a transmembrane precursor protein that is widely expressed in the central nervous system and peripheral tissues in the liver and pancreas, adipose tissue, and ...myotubes. APP can be cleaved by proteases in two different ways to produce a variety of short peptides, each with different physiological properties and functions. APP peptides generated by non-amyloidogenic processing can positively influence metabolism, while the peptides produced by amyloidogenic processing have the opposite effects. Here, we summarize the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues. In addition, abnormal expression and function of APP and APP-derived peptides are associated with metabolic diseases, such as type 2 diabetes, obesity, non-alcoholic fatty liver disease, and cardiovascular disease, and cancers. Pharmacological intervention of APP function or reduction of the production of peptides derived from amyloidogenic processing may be effective strategies for the prevention and treatment of Alzheimer's disease, and they may also provide new guidance for the treatment of metabolic diseases.
•APP is a transmembrane precursor protein that plays an important role in metabolism of the central nervous system and peripheral tissues.•Peptides produced by APP through non-amyloidogenic pathway have protective effects on metabolism, while peptides produced by the amyloidogenic pathway have detrimental effects.•Pharmacological intervention of APP or reduction of the peptides derived from amyloidogenic processing has benefical effects on AD and metabolic diseases.
As the first large-scale free trade arrangement in the Asia-Pacific region, the Regional Comprehensive Economic Partnership (RCEP) will play an important role in economic and trade cooperation, and ...regional governance in the region. Since the signing on 15 November 2020, RCEP has encountered internal and external risks and challenges. Effectively avoiding risks and coping with challenges are important for RCEP to play its due role. To China, RCEP presents a new opportunity and platform to expand its opening up.
This paper establishes a fully automatic real-time image segmentation and recognition system for breast ultrasound intervention robots. It adopts the basic architecture of a U-shaped convolutional ...network (U-Net), analyses the actual application scenarios of semantic segmentation of breast ultrasound images, and adds dropout layers to the U-Net architecture to reduce the redundancy in texture details and prevent overfitting. The main innovation of this paper is proposing an expanded training approach to obtain an expanded of U-Net. The output map of the expanded U-Net can retain texture details and edge features of breast tumours. Using the grey-level probability labels to train the U-Net is faster than using ordinary labels. The average Dice coefficient (standard deviation) and the average IOU coefficient (standard deviation) are 90.5% (±0.02) and 82.7% (±0.02), respectively, when using the expanded training approach. The Dice coefficient of the expanded U-Net is 7.6 larger than that of a general U-Net, and the IOU coefficient of the expanded U-Net is 11 larger than that of the general U-Net. The context of breast ultrasound images can be extracted, and texture details and edge features of tumours can be retained by the expanded U-Net. Using an expanded U-Net can quickly and automatically achieve precise segmentation and multi-class recognition of breast ultrasound images.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2D hierarchically porous carbon (2D-HPC) nanosheets with unique advantages are highly desired as host materials for lithium sulfur (Li–S) batteries and other energy storage devices. Herein, we ...propose a self-template and organic solvent-free approach to synthesize nanosheets of monoclinic ZIF-8 at room temperature from which 2D-HPC nanosheets (ZIF-8 nanosheets carbon denoted as ZIF-8-NS-C) are derived to be an efficient sulfur immobilizer for Li–S batteries for the first time. The anisotropic nanosheets are believed to relate to the symmetry of the monoclinic structure. The 2D ZIF-8-NS-C nanosheets with embedded hierarchical pores construct an effective conductive network through “plane-to-plane” modes to endow superior electron transfer and fast electrochemical kinetics. Moreover, the nitrogen-rich feature of ZIF-8-NS-C can increase the affinity/interaction of carbon host with lithium polysulfides, favoring the cyclic performance. The sulfur/ZIF-8-NS-C (S/ZIF-8-NS-C) cathode shows a superior rate capability with high capacities of 1226 mA h g–1 at 0.2 C and 785 mA h g–1 at 2 C, and a sustainable cycling stability with a capacity attenuation of 0.12% per cycle at 0.5 C for 300 cycles. The approach proposed here pioneers the controllable design of MOF-based structures to inspire the exploration of more variable MOF-derived porous materials for energy storage applications.
It remains unclear how many hours of sleep are associated with the lowest risk of type 2 diabetes. This meta-analysis was performed to assess the dose-response relationship between sleep duration and ...risk of type 2 diabetes.
PubMed and Embase were searched up to 20 March 2014 for prospective observational studies that assessed the relationship of sleep duration and risk of type 2 diabetes. Both semiparametric and parametric methods were used.
Ten articles with 11 reports were eligible for inclusion in the meta-analysis. A total of 18,443 incident cases of type 2 diabetes were ascertained among 482,502 participants with follow-up periods ranging from 2.5 to 16 years. A U-shaped dose-response relationship was observed between sleep duration and risk of type 2 diabetes, with the lowest risk observed at a sleep duration category of 7-8 h per day. Compared with 7-h sleep duration per day, the pooled relative risks for type 2 diabetes were 1.09 (95% CI 1.04-1.15) for each 1-h shorter sleep duration among individuals who slept <7 h per day and 1.14 (1.03-1.26) for each 1-h increment of sleep duration among individuals with longer sleep duration.
Our dose-response meta-analysis of prospective studies shows a U-shaped relationship between sleep duration and risk of type 2 diabetes, with the lowest type 2 diabetes risk at 7-8 h per day of sleep duration. Both short and long sleep duration are associated with a significantly increased risk of type 2 diabetes, underscoring the importance of appropriate sleep duration in the delay or prevention of type 2 diabetes.
To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint ...association to rotating night shift work only, to lifestyle only, and to their interaction.
Prospective cohort study.
Nurses' Health Study (1988-2012) and Nurses' Health Study II (1991-2013).
143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline.
Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above.
Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire.
During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction <0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction.
Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.
Clinical and epidemiologic studies have shown that obesity is associated with asthma and that these associations differ by asthma subtype. Little is known about the shared genetic components between ...obesity and asthma.
We sought to identify shared genetic associations between obesity-related traits and asthma subtypes in adults.
A cross-trait genome-wide association study (GWAS) was performed using 457,822 subjects of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma through a GWAS was sought by using results from obese versus lean mouse RNA sequencing and RT-PCR experiments.
We found a substantial positive genetic correlation between body mass index and later-onset asthma defined by asthma age of onset at 16 years or greater (Rg = 0.25, P = 9.56 × 10−22). Mendelian randomization analysis provided strong evidence in support of body mass index causally increasing asthma risk. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and Genotype-Tissue Expression (GTEx) quantitative trait loci and shared immune- and cell differentiation–related pathways between obesity and asthma. Finally, RNA sequencing data from lungs of obese versus control mice found that 2 genes (acyl-coenzyme A oxidase-like ACOXL and myosin light chain 6 MYL6) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by using RT-PCR in an independent set of mice.
Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma and identifying molecular pathways that might underlie both obesity and asthma.
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Although hybrid maize seed production is one of the most important agriculture systems worldwide, its greenhouse gas (GHG) emissions and potential mitigation measures have not been studied. In this ...study, we used life cycle assessment (LCA) to quantify the GHG emissions of 150 farmers run by 6 companies in an area of northwest China known for hybrid maize seed production. The results indicated that the average reactive nitrogen (Nr) losses and GHG emissions from hybrid maize seed production were 53 kg N ha
−1
and 8077 kg CO
2
eq ha
−1
, respectively. Furthermore, the average nitrogen and carbon footprints of the process were 12.2 kg N Mg
−1
and 1495 kg CO
2
eq Mg
−1
, respectively. Nitrogen fertilizer and electricity consumption for irrigation were the main contributors to high GHG emissions, accounting for 60% and 30% of the total, respectively. The GHG emissions from seed production for different companies varied greatly with their resource input. There was also a large variation in environmental burdens among the 150 farmers. Based on an analysis of the yield group, we found that the carbon footprint of the first group (the one with the highest yield) was 27% lower than the overall average. Scenario analysis suggests that a combined reduction of N input rate, optimizing irrigation, and increasing yield can eventually mitigate the carbon footprint of hybrid maize seed production by 37%. An integrated systematic approach (e.g., ISSM: integrated soil-crop system management) can reduce the GHG emissions involved in producing hybrid maize seeds. This study provides quantitative evidence and a potential strategy for GHG emissions reduction of hybrid maize seed production.
Runaway stars are OB-type stars ejected from their birthplace with large peculiar velocities. The leading hypothesis addressed in their formation includes the supernova ejection mechanism and the ...dynamic ejection scenario. Identification of runaway populations is the first step to investigating their formation and evolution. Here we present our work of searching for Galactic runaway candidate stars from the Large sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) Medium Resolution Survey Data Release 8 (DR8) database. After studying the kinematic properties for a collection of 4432 early-type stars, predominantly B-type stars, using radial velocity measurements from LAMOST DR8 and astrometric solutions made by Gaia Data Release 3, we identified 229 runaway candidate stars. They span a wide distribution in projected rotational velocities. We investigated the Galactic spatial distribution of the runaway population and noticed that most of them likely reside within the Galactic thin disk. Based upon analyzing the Doppler shifts of the candidate stars, we found two binary runaway candidates displaying velocity variations with estimated orbital periods of 40 and 61 days.
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