Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD).
We performed ...a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization.
We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network.
Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression.
Modular steel construction (MSC) comprises off-site manufactured volumetric modules and on-site assembly, leading to reduced construction periods, improved quality, and reduced waste of resources. ...This environmentally friendly solution has been extensively used for low-rise buildings as an alternative to traditional on-site construction. The popularity of MSC has now spread to mid-to-high rise applications in seismic regions to meet the increasing urban construction demand, owing to its significant technical advantages. The influence of earthquake becomes critical as the height of the building increases. Hence, this paper presents a state-of-the-art review of the seismic performance of mid-to-high MSC and articulates the key technical issues. The module classification is presented as a brief introduction of MSC, followed by discussion of the structural system. Afterwards, the seismic performance of the lateral force resisting system and recent innovations on the connection system are reviewed in detail, on which the seismic performance of MSC highly depend. The global seismic response analysis methodology, characteristics, failure mode as well as the current design criteria are evaluated, providing a more comprehensive understanding of the seismic performance of MSC. Finally, the recently developed isolation systems for MSC are introduced. As a currently developing area, there is great potential for innovation in mid-to-high rise MSC. Despite progressively increasing research exploring the seismic performance of MSC, a comprehensive understanding of this topic has not been achieved, hindering the further prevalence of mid-to-high rise MSC in areas with potential seismic hazards. Given this situation, several key research areas are suggested thereupon at last, aiming to promote the further extended application of MSC in seismic regions.
•Module classification and structural form of modular steel construction (MSC).•State-of-the-art review on the seismic performance of mid-to-high rise MSC.•Research progress on the lateral force resisting system and connection system.•Currently available seismic design criteria are summarized and evaluated.•Key research areas are identified for extended seismic application of MSC.
Upland forests are traditionally thought to be net sinks for atmospheric methane (CH4). In such forests, in situ CH4 fluxes on tree trunks have been neglected relative to soil and canopy fluxes.
We ...measured in situ CH4 fluxes from the trunks of living trees and other surfaces, such as twigs and soils, using a static closed-chamber method, and estimated the CH4 budget in a temperate upland forest in Beijing.
We found that the trunks of Populus davidiana emitted large quantities of CH4 during July 2014–July 2015, amounting to mean annual emissions of 85.3 and 103.1 μg m−2 h−1 on a trunk surface area basis on two replicate plots. The emission rates were similar in magnitude to those from tree trunks in wetland forests. The emitted CH4 was derived from the heartwood of trunks. On a plot or ecosystem scale, trunk CH4 emissions were equivalent to c. 30–90% of the amount of CH4 consumed by soils throughout the year, with an annual average of 63%.
Our findings suggest that wet heartwoods, regardless of rot or not, occur widely in living trees on various habitats, where CH4 can be produced.
Alzheimer disease (AD) is the most common neurodegenerative disease. An imbalance between the production and clearance of Aβ (amyloid beta) is considered to be actively involved in AD pathogenesis. ...Macroautophagy/autophagy is a major cellular pathway leading to the removal of aggregated proteins, and upregulation of autophagy represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aβ. PPARA/PPARα (peroxisome proliferator activated receptor alpha) is a transcription factor that regulates genes involved in fatty acid metabolism and activates hepatic autophagy. We hypothesized that PPARA regulates autophagy in the nervous system and PPARA-mediated autophagy affects AD. We found that pharmacological activation of PPARA by the PPARA agonists gemfibrozil and Wy14643 induces autophagy in human microglia (HM) cells and U251 human glioma cells stably expressing the human APP (amyloid beta precursor protein) mutant (APP-p.M671L) and this effect is PPARA-dependent. Administration of PPARA agonists decreases amyloid pathology and reverses memory deficits and anxiety symptoms in APP-PSEN1ΔE9 mice. There is a reduced level of soluble Aβ and insoluble Aβ in hippocampus and cortex tissues from APP-PSEN1ΔE9 mice after treatment with either gemfibrozil or Wy14643, which promoted the recruitment of microglia and astrocytes to the vicinity of Aβ plaques and enhanced autophagosome biogenesis. These results indicated that PPARA is an important factor regulating autophagy in the clearance of Aβ and suggested gemfibrozil be assessed as a possible treatment for AD.
Abbreviation: Aβ: amyloid beta; ACTB: actin beta; ADAM10: ADAM metallopeptidase domain 10; AD: Alzheimer disease; AIF1/IBA1: allograft inflammatory factor 1; ANOVA: analysis of variance; APOE: apolipoprotein E; APP: amyloid beta precursor protein; APP-PSEN1ΔE9: APPswe/PSEN1dE9; BAFA1: bafilomycin A
1
; BDNF: brain derived neurotrophic factor; BECN1: beclin 1; CD68: CD68 molecule; CREB1: cAMP responsive element binding protein 1; DAPI: 4',6-diamidino-2-phenylindole; DLG4/PSD-95: discs large MAGUK scaffold protein 4; DMSO: dimethyl sulfoxide; ELISA: enzyme linked immunosorbent assay; FDA: U.S. Food and Drug Administration; FKBP5: FK506 binding protein 5; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; gemfibrozil: 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid; GFAP: glial fibrillary acidic protein; GLI2/THP1: GLI family zinc finger 2; HM: human microglia; IL6: interleukin 6; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NC: negative control; OQ: opposite quadrant; PPARA/PPARα, peroxisome proliferator activated receptor alpha; PSEN1/PS1: presenilin 1; SEM: standard error of the mean; SQSTM1: sequestosome 1; SYP: synaptophysin; TFEB: transcription factor EB; TNF/TNF-α: tumor necrosis factor; TQ: target quadrant; WT: wild type; Wy14643: 2-4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-ylsulfanylacetic acid
Systematic review with meta-analysis.
To evaluate the effects of enhanced recovery after surgery (ERAS) on the postoperative recovery of patients who underwent total hip arthroplasty (THA) or total ...knee arthroplasty (TKA).
The PubMed, Embase, Cochrane and ISI Web of Science databases were searched to identify literature including randomised controlled trials (RCTs), cohort studies and case-control studies through 2 May 2018. The analysed outcomes were mortality rate, transfusion rate, range of motion (ROM), 30-day readmission rate, postoperative complication rate and in-hospital length of stay (LOS).
A total of 25 studies involving 16 699 patients met the inclusion criteria and were included in the meta-analysis. Compared with conventional care, ERAS was associated with a significant decrease in mortality rate (relative risk (RR) 0.48, 95% CI 0.27 to 0.85), transfusion rate (RR 0.43, 95% CI 0.37 to 0.51), complication rate (RR 0.74, 95% CI 0.62 to 0.87) and LOS (mean difference (MD) -2.03, 95% CI -2.64 to -1.42) among all included trials. However, no significant difference was found in ROM (MD 7.53, 95% CI -2.16 to 17.23) and 30-day readmission rate (RR 0.86, 95% CI 0.56 to 1.30). There was no significant difference in complications of TKA (RR 0.84, 95% CI 0.34 to 2.06) and transfusion rate in RCTs (RR 0.66, 95% CI 0.15 to 2.88) between the ERAS group and the control group.
This meta-analysis showed that ERAS significantly reduced the mortality rate, transfusion rate, incidence of complications and LOS of patients undergoing TKA or THA. However, ERAS did not show a significant impact on ROM and 30-day readmission rate. Complications after hip replacement are less than those of knee replacement, and the young patients recover better.
Level 1.
Currently, the synthesis of pure silica zeolites always requires the presence of organic structure‐directing agents (OSDAs), which direct the assembly pathway and ultimately fill the pore space. A ...sustainable route is now reported for synthesizing pure silica zeolites in the absence of OSDAs from a combined strategy of zeolite seeding and alcohol filling, where the zeolite seeds direct crystallization of zeolite crystals from amorphous silica, while the alcohol is served as pore filling in the zeolites. Very importantly, the alcohol could be fully washed out from zeolite pores by water at room temperature, which completely avoids calcination at high temperature for removal of OSDAs in the synthesis of pure silica zeolites.
A sustainable route for synthesizing pure silica zeolites in the absence of organic structure‐directing agents from a combined strategy of zeolite seeding and alcohol filling is presented. The zeolite seeds direct crystallization of zeolite crystals from amorphous silica, while the alcohol is served as pore filling in the zeolite.
A highly diastereo‐ and enantioselective dearomative 3+2 cycloaddition reaction of 3‐nitrobenzothiophenes and 3‐nitrothieno2,3‐bwith 3‐isothiocyanato oxindoles is developed. The reaction is catalyzed ...by the chiral Zn(OTf)2/bis(oxazoline, and is the second example of a catalytic asymmetric dearomative cycloaddition reaction of 3‐nitrobenzothiophene derivatives. A range of complex heterocyclic compounds containing three contiguous stereocenters, one of which is spirocyclic center, can be obtained in quantitative yields with excellent stereoselectivities.
Cassava (Manihot esculenta) is a major staple food, animal feed and energy crop in the tropics and subtropics. It is one of the most drought-tolerant crops, however, the mechanisms of cassava drought ...tolerance remain unclear. Abscisic acid (ABA)-responsive element (ABRE)-binding factors (ABFs) are transcription factors that regulate expression of target genes involved in plant tolerance to drought, high salinity, and osmotic stress by binding ABRE cis-elements in the promoter regions of these genes. However, there is little information about ABF genes in cassava. A comprehensive analysis of Manihot esculenta ABFs (MeABFs) described the phylogeny, genome location, cis-acting elements, expression profiles, and regulatory relationship between these factors and Manihot esculenta betaine aldehyde dehydrogenase genes (MeBADHs). Here we conducted genome-wide searches and subsequent molecular cloning to identify seven MeABFs that are distributed unevenly across six chromosomes in cassava. These MeABFs can be clustered into three groups according to their phylogenetic relationships to their Arabidopsis (Arabidopsis thaliana) counterparts. Analysis of the 5'-upstream region of MeABFs revealed putative cis-acting elements related to hormone signaling, stress, light, and circadian clock. MeABF expression profiles displayed clear differences among leaf, stem, root, and tuberous root tissues under non-stress and drought, osmotic, or salt stress conditions. Drought stress in cassava leaves and roots, osmotic stress in tuberous roots, and salt stress in stems induced expression of the highest number of MeABFs showing significantly elevated expression. The glycine betaine (GB) content of cassava leaves also was elevated after drought, osmotic, or salt stress treatments. BADH1 is involved in GB synthesis. We show that MeBADH1 promoter sequences contained ABREs and that MeBADH1 expression correlated with MeABF expression profiles in cassava leaves after the three stress treatments. Taken together, these results suggest that in response to various dehydration stresses, MeABFs in cassava may activate transcriptional expression of MeBADH1 by binding the MeBADH1 promoter that in turn promotes GB biosynthesis and accumulation via an increase in MeBADH1 gene expression levels and MeBADH1 enzymatic activity. These responses protect cells against dehydration stresses by preserving an osmotic balance that enhances cassava tolerance to dehydration stresses.
Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We ...retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs.
This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost.
A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure.
Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.
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