Computational Thinking (CT) is seen as an important competence that is required in order to adapt to the future. However, educators, especially K-12 teachers and researchers, have not clearly ...identified how to teach it. In this study, a meta-review of the studies published in academic journals from 2006 to 2017 was conducted to analyze application courses, adopted learning strategies, participants, teaching tools, programming languages, and course categories of CT education. From the review results, it was found that the promotion of CT in education has made great progress in the last decade. In addition to the increasing number of CT studies in different countries, the subjects, research issues, and teaching tools have also become more diverse in recent years. It was also found that CT has mainly been applied to the activities of program design and computer science, while some studies are related to other subjects. Meanwhile, most of the studies adopted Project-Based Learning, Problem-Based Learning, Cooperative Learning, and Game-based Learning in the CT activities. In other words, such activities as aesthetic experience, design-based learning, and storytelling have been relatively less frequently adopted. Most of the studies focused on programming skills training and mathematical computing, while some adopted a cross-domain teaching mode to enable students to manage and analyze materials of various domains by computing. In addition, since the cognitive ability of students of different ages varies, the CT ability cultivation methods and content criteria should vary accordingly. Moreover, most studies reported the learners' CT performance and perspectives, while their information society ability was seldom trained. Accordingly, the research trends and potential research issues of CT are proposed as a reference for researchers, instructors, and policy makers.
•A meta-review of selected SSCI/SCI journal CT studies for 2006–2017 is reported.•The number of CT studies shows an obviously increasing trend in recent years.•Program design was the most common subject used to convey CT instruction.•Visual programming languages were the most common instruments of CT instruction.•PBL, CL, and GBL were the top strategies used for CT instruction.
The development of in‐memory computing has opened up possibilities to build next‐generation non‐von‐Neumann computing architecture. Implementation of logic functions within the memristors can ...significantly improve the energy efficiency and alleviate the bandwidth congestion issue. In this work, the demonstration of arithmetic logic unit functions is presented in a memristive crossbar with implemented non‐volatile Boolean logic and arithmetic computing. For logic implementation, a standard operating voltage mode is proposed for executing reconfigurable stateful IMP, destructive OR, NOR, and non‐destructive OR logic on both the word and bit lines. No additional voltages are needed beyond “VP” and its negative component. With these basic logic functions, other Boolean functions are constructed within five devices in at most five steps. For arithmetic computing, the fundamental functions including an n‐bit full adder with high parallelism as well as efficient increment, decrement, and shift operations are demonstrated. Other arithmetic blocks, such as subtraction, multiplication, and division are further designed. This work provides solid evidence that memristors can be used as the building block for in‐memory computing, targeting various low‐power edge computing applications.
In‐memory computation tasks of a memristive arithmetic logic unit are demonstrated based on stateful logic in a memristive crossbar. Highly reconfigurable and parallel operations are designed with simplified instructions, including Boolean logic, addition, subtraction, multiplication, division, increment, decrement, and shift operations. The energy efficiency and short latency prove its advance for future in‐memory computing applications.
Photoluminescent gold nanodots (Au NDs) are prepared via etching and codeposition of hybridized ligands, an antimicrobial peptide (surfactin; SFT), and 1‐dodecanethiol (DT), on gold nanoparticles ...(≈3.2 nm). As‐prepared ultrasmall SFT/DT–Au NDs (size ≈2.5 nm) are a highly efficient antimicrobial agent. The photoluminescence properties and stability as well as the antimicrobial activity of SFT/DT–Au NDs are highly dependent on the density of SFT on Au NDs. Relative to SFT, SFT/DT–Au NDs exhibit greater antimicrobial activity, not only to nonmultidrug‐resistant bacteria but also to the multidrug‐resistant bacteria. The minimal inhibitory concentration values of SFT/DT–Au NDs are much lower (>80‐fold) than that of SFT. The antimicrobial activity of SFT/DT–Au NDs is mainly due to the synergistic effect of SFT and DT–Au NDs on the disruption of the bacterial membrane. In vitro cytotoxicity and hemolysis analyses have revealed superior biocompatibility of SFT/DT–Au NDs than that of SFT. Moreover, in vivo methicillin‐resistant S. aureus–infected wound healing studies in rats show faster healing, better epithelialization, and are more efficient in the production of collagen fibers when SFT/DT–Au NDs are used as a dressing material. This study suggests that the SFT/DT–Au NDs are a promising antimicrobial candidate for preclinical applications in treating wounds and skin infections.
Surfactin, an antimicrobial lipopeptide, when self‐assembled on photoluminescent gold nanodots (Au NDs) exhibits an >80‐fold improvement in its antimicrobial activity against multidrug‐resistant bacteria. Antibacterial wound‐healing assays further reveal that the surfactin–Au ND hybrid material is superior to that of surfactin alone on a bacteria‐infected flesh wound in rats.
Golgi apparatus (GA) is assembled as a crescent-like ribbon in mammalian cells under immunofluorescence microscope without knowing the shaping mechanisms. It is estimated that roughly 1/5 of the ...genes encoding kinases or phosphatases in human genome participate in the assembly of Golgi ribbon, reflecting protein modifications play major roles in building Golgi ribbon.
To explore how Golgi ribbon is shaped as a crescent-like structure under the guidance of protein modifications, we identified a protein complex containing the scaffold proteins Ajuba, two known GA regulators including the protein kinase Aurora-A and the protein arginine methyltransferase PRMT5, and the common substrate of Aurora-A and PRMT5, HURP. Mutual modifications and activation of PRMT5 and Aurora-A in the complex leads to methylation and in turn phosphorylation of HURP, thereby producing HURP p725. The HURP p725 localizes to GA vicinity and its distribution pattern looks like GA morphology. Correlation study of the HURP p725 statuses and GA structure, site-directed mutagenesis and knockdown-rescue experiments were employed to identify the modified HURP as a key regulator assembling GA as a crescent ribbon.
The cells containing no or extended distribution of HURP p725 have dispersed GA membranes or longer GA. Knockdown of HURP fragmentized GA and HURP wild type could, while its phosphorylation deficiency mutant 725A could not, restore crescent Golgi ribbon in HURP depleted cells, collectively indicating a crescent GA-constructing activity of HURP p725. HURP p725 is transported, by GA membrane-associated ARF1, Dynein and its cargo adaptor Golgin-160, to cell center where HURP p725 forms crescent fibers, binds and stabilizes Golgi assembly factors (GAFs) including TRIP11, GRASP65 and GM130, thereby dictating the formation of crescent Golgi ribbon at nuclear periphery.
The Ajuba/PRMT5/Aurora-A complex integrates the signals of protein methylation and phosphorylation to HURP, and the HURP p725 organizes GA by stabilizing and recruiting GAFs to its crescent-like structure, therefore shaping GA as a crescent ribbon. Therefore, the HURP p725 fiber serves a template to construct GA according to its shape. Video Abstract.
The Golgi apparatus (GA) translocates to the cell leading end during directional migration, thereby determining cell polarity and transporting essential factors to the migration apparatus. The study ...provides mechanistic insights into how GA repositioning (GR) is regulated. We show that the methyltransferase PRMT5 methylates the microtubule regulator HURP at R122. The HURP methylation mimicking mutant 122F impairs GR and cell migration. Mechanistic studies revealed that HURP 122F or endogenous methylated HURP, that is, HURP m122, interacts with acetyl‐tubulin. Overexpression of HURP 122F stabilizes the bundling pattern of acetyl‐tubulin by decreasing the sensitivity of the latter to a microtubule disrupting agent nocodazole. HURP 122F also rigidifies GA via desensitizing the organelle to several GA disrupting chemicals. Similarly, the acetyl‐tubulin mimicking mutant 40Q or tubulin acetyltransferase αTAT1 can rigidify GA, impair GR, and retard cell migration. Reversal of HURP 122F‐induced GA rigidification, by knocking down GA assembly factors such as GRASP65 or GM130, attenuates 122F‐triggered GR and cell migration. Remarkably, PRMT5 is found downregulated and the level of HURP m122 is decreased during the early hours of wound healing‐based cell migration, collectively implying that the PRMT5‐HURP‐acetyl‐tubulin axis plays the role of brake, preventing GR and cell migration before cells reach empty space.
TDP-43 inclusions are found in many Alzheimer's disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical ...oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ's ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.
Background and Purpose
Increasing evidence suggests systemic inflammation‐caused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook ...F possesses potent anti‐inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation‐induced skeletal muscle atrophy.
Experimental Approach
The effects of triptolide on skeletal muscle atrophy were investigated in LPS‐treated C2C12 myotubes and C57BL/6 mice. Protein expressions and mRNA levels were analysed by western blot and qPCR, respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro‐CT and grip strength, respectively. Locomotor activity was measured using the open field test.
KEY RESULTS
Triptolide (10–100 fM) up‐regulated protein synthesis signals (IGF‐1/p‐IGF‐1R/IRS‐1/p‐Akt/p‐mTOR) and down‐regulated protein degradation signal atrogin‐1 in C2C12 myotubes. In LPS (100 ng·ml−1)‐treated C2C12 myotubes, triptolide up‐regulated MyHC, IGF‐1, p‐IGF‐1R, IRS‐1 and p‐Akt. Triptolide also down‐regulated ubiquitin‐proteasome molecules (n‐FoxO3a/atrogin‐1/MuRF1), proteasome activity, autophagy‐lysosomal molecules (LC3‐II/LC3‐I and Bnip3) and inflammatory mediators (NF‐κB, Cox‐2, NLRP3, IL‐1β and TNF‐α). However, AG1024, an IGF‐1R inhibitor, suppressed triptolide‐mediated effects on MyHC, myotube diameter, MuRF1 and p62 in LPS‐treated C2C12 myotubes. In LPS (1 mg·kg−1, i.p.)‐challenged mice, triptolide (5 and 20 μg·kg−1·day−1, i.p.) decreased plasma TNF‐α levels and it increased skeletal muscle volume, cross‐sectional area of myofibers, weights of the gastrocnemius and tibialis anterior muscles, forelimb grip strength and locomotion.
Conclusions and Implications
These findings reveal that triptolide prevented LPS‐induced inflammation and skeletal muscle atrophy and have implications for the discovery of novel agents for preventing muscle wasting.
The policy enforcing visiting restriction during the COVID-19 pandemic may cause feelings of social isolation among residents in long-term care facilities. This study aimed to explore family members' ...concerns for their relatives during the lockdown period, assess their level of acceptance of the visiting restriction policy and determine the associated factors.
From the 156 family members interviewed, demographic data, satisfaction with overall care quality, worry and concerns for their relatives, acceptance of the visiting restriction and arrangement for the residents if cluster infections occur in the facility were recorded.
Among the members interviewed, 83 (53.2%) were men; mean age of members was 56.3 ± 9.8; most were offspring of residents in the facility (n = 121, 77.6%), most visited the residents at least once a week (n = 113, 72.4%) before the lockdown. The most common concerns of the family members for their relatives were psychological stress (38.5%), followed by nursing care (26.9%) and daily activity (21.1%). Nearly 84.6% of those interviewed accepted the visiting restriction policy, and a higher satisfaction rating independently associated with acceptance of the visiting restriction policy (odds ratio 2.15).
During the lockdown period, staff members should provide more psychological information about residents to their family members. Higher satisfaction rating was found to be independent of the acceptance of the visiting restriction policy. Therefore, good quality of care of the facility wins the trust of family members, and this might mitigate the tension between the family members and staff during a major crisis. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; 20: 938-942.
Social media marketing is an influential marketing method. Liking or sharing social media messages can increase the effects of popular cohesion and message diffusion. This research investigates how ...persuasive messages (i.e., argument quality, post popularity, and post attractiveness) can lead internet users to click like and share messages in social media marketing activities. This research develops hypotheses on the basis of elaboration likelihood model and a 392 fans survey from a fan page on Facebook. Structural equation modeling analyzes questionnaire data. Results show that the three types of persuasive messages are important to click like and to share post messages. Post popularity is essential and works through both central route and peripheral according to research model. In addition, different message characteristics and user groups have different communicating behaviors. This research provides valuable recommendations for social media marketing activities.
Background and Purpose
Heparanase is the only confirmed endoglycosidase that cleaves heparan sulfate (HS), a ubiquitous glycosaminoglycan with various essential roles in multiple pathological ...processes. Thus, the development of heparanase inhibitors has become an attractive strategy for drug discovery, especially in tumour therapy, in which HS mimetics are the most promising compounds. The various biological effects of heparanase also suggest a role for HS mimetics in many non‐cancer indications, such as type 1 diabetes. However, the potential benefits of HS mimetics in obesity‐related type 2 diabetes have not been elucidated.
Experimental Approach
In this study, we investigated muparfostat (PI‐88), a developed HS mimetic currently enrolled in Phase III clinical trials, in obese mouse models and in vitro cultured murine hepatocytes.
Key Results
Daily administration of muparfostat for 4 weeks caused hyperlipidaemia and aggravated hepatic steatosis in obese mice models, but not in lean animals. In cultured hepatocytes, muparfostat did not alter lipid accumulation. Acute tests suggested that muparfostat binds to lipoprotein lipase in competition with HS on vascular endothelial cell surfaces, thereby reducing the degradation of circulating triglycerides by lipoprotein lipase and subsequent uptake of fatty acids into vascular endothelial cells and causing hyperlipidaemia. This hyperlipidaemia aggravates hepatic steatosis and causes liver injury in muparfostat‐treated obese mice.
Conclusions and Implications
The binding activity of HS mimetics to lipoprotein lipase should be investigated as an additional pharmacological effect during heparanase inhibitor drug discovery. This study also provides novel evidence for an increased risk of drug‐induced liver injury in obese individuals.
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