QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function

The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdel largely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting that QKI is associated with the pathogenesis of certain forms of cardiomyopathies

The effects of housing policies and macroeconomic factors on Singapore housing market : an ARDL approach

This study examines the impacts of several macroeconomic factors including the real GDP per capita, housing loan rate, housing supply and foreign population rate and the government housing policies on the Singapore public resale and condominium markets using the quarterly data from 1991 quarter 1 to 2011 quarter 1. The empirical study applies the Autoregressive Distributed Lag (ARDL) approach for estimating models of long run price determination and short run price dynamics. A new method is adopted to define the dummy variables for the government housing policies so that the initial and subsequent policy effects could be evaluated separately. The results show that there are long run relationships among the housing prices and the examined macroeconomic factors and housing policies in both markets. In particular, the public resale market is mainly affected by the housing policies, while the condominium market is influenced by both the macroeconomic factors and the housing policies. Furthermore, in both markets, the error correction models show that the short run price deviations can be corrected to the long run equilibriums through the negatively significant error correction terms.Bachelor of Art

The Anchoring Effect in Study Time Allocation: Labor-in-Vain versus Labor-and-Gain

How to allocate study time is an important decision-making problem learners face. Research on this problem can help improve the learning performance of learners and provide guidance for teaching activities. This research aimed to explore the potential of anchors (prior information that may influence individual decision-making and judgment under uncertainty) as clues for study time allocation and examine the effectiveness of study time allocation under the influence of anchors. Sixty-two Chinese university students (Mage = 21.21, SD = 1.74; 44 females) studied 20 word pairs under self-paced learning instructions. These instructions either set a high anchor (i.e., the typical participant spent 15 s learning each pair) or a low anchor (i.e., the typical participant spent 5 s learning each pair) for study time. After a brief distraction phase, participants took a cued recall test. The results showed that the higher the anchor value, the longer the corresponding study time, and the longer the study time, the better the memory performance. These results reveal that there is both an anchoring effect and a labor-and-gain effect in self-paced study time allocation. This study extends the range of observable anchoring effects and provides important information on allocating study time effectively

A novel graphene-based micro/nano architecture with high strength and conductivity inspired by multiple creatures

Abstract In the long history of development and elimination, the creatures have derived a variety of exquisite structures and unique properties, typically natural nacre, marine mussel and Glycera to adapt to the environment and resist the predation of the enemy. Hence, inspired by the combination of special structures and properties of multiple creatures, a novel type of graphene-based micro/nano architecture was proposed, and the related bioinspired nanocomposites were fabricated, Polydopamine coated Graphene oxide/Nanocellulose/Polydopamine (P-GCP). Apart from replicating the layered structure of natural nacre, P-GCP also introduced copper ions and polydopamine to simulate the hardening mechanism of the Glycera’s jaw and the composition of adhesive proteins in mussels to further improve the tensile strength and conductivity of nanocomposites, respectively. The test results showed that the tensile strength of P-GCP reached 712.9 MPa, which was 5.3 times that of natural nacre. The conductivity of artificial nacre was as high as 207.6 S/cm, which was equivalent to that of reduced graphene oxide (rGO). Furthermore, the material exhibited outstanding electrical conductivity when it connected as wires in a circuit, demonstrating the practical application prospects in aerospace, supercapacitors, biomaterials, artificial bones and tissue engineering

Mechanically Strong, Low Thermal Conductivity and Improved Thermal Stability Polyvinyl Alcohol–Graphene–Nanocellulose Aerogel

Porous aerogel materials have advantages of a low density, low thermal conductivity and high porosity, and they have broad application prospects in heat insulation and building energy conservation. However, aerogel materials usually exhibit poor mechanical properties. Single-component aerogels are less likely to possess a good thermal stability and mechanical properties. It is necessary to prepare multiple-composite aerogels by reinforcement to meet practical application needs. In this experiment, a simple preparation method for polyvinyl alcohol (PVA)–graphene (GA)–nanocellulose (CNF) ternary composite aerogels was proposed. This is also the first time to prepare ternary composite aerogels by mixing graphene, nanocellulose and polyvinyl alcohol. A GA–CNF hydrogel was prepared by a one-step hydrothermal method, and soaked in PVA solution for 48 h to obtain a PVA–GA–CNF hydrogel. PVA–GA–CNF aerogels were prepared by freeze drying. The ternary composite aerogel has advantages of excellent mechanical properties, a low thermal conductivity and an improved thermal stability, because strong hydrogen bonds form between the PVA, GA and CNF. The composite aerogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffractometry, Brunauer–Emmett–Teller analysis, dynamic thermal analysis, thermogravimetry and thermal constant analysis to characterize the properties of the ternary composite aerogels. The lightweight, low-density and porous PVA–GA–CNF composite aerogels withstood 628 times their mass. The thermal conductivity of the composite aerogels was 0.044 ± 0.005 W/mK at room temperature and 0.045 ± 0.005 W/mK at 70 °C. This solid, low thermal conductivity and good thermal stability PVA–GA–CNF ternary composite aerogel has potential application in thermal insulation

Mitochondrial GCN5L1 acts as a novel regulator for iron homeostasis to promote sorafenib sensitivity in hepatocellular carcinoma

Abstract Background Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. Methods We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. Results We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. Conclusions Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC

Neonatal Plasma Exosomes Contribute to Endothelial Cell-Mediated Angiogenesis and Cardiac Repair after Acute Myocardial Infarction

Acute myocardial infarction (AMI) accompanied by cardiac remodeling still lacks effective treatment to date. Accumulated evidences suggest that exosomes from various sources play a cardioprotective and regenerative role in heart repair, but their effects and mechanisms remain intricate. Here, we found that intramyocardial delivery of plasma exosomes from neonatal mice (npEXO) could help to repair the adult heart in structure and function after AMI. In-depth proteome and single-cell transcriptome analyses suggested that npEXO ligands were majorly received by cardiac endothelial cells (ECs), and npEXO-mediated angiogenesis might serve as a pivotal reason to ameliorate the infarcted adult heart. We then innovatively constructed systematical communication networks among exosomal ligands and cardiac ECs and the final 48 ligand–receptor pairs contained 28 npEXO ligands (including the angiogenic factors, Clu and Hspg2), which mainly mediated the pro-angiogenic effect of npEXO by recognizing five cardiac EC receptors (Kdr, Scarb1, Cd36, etc.). Together, the proposed ligand–receptor network in our study might provide inspiration for rebuilding the vascular network and cardiac regeneration post-MI

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study

Summary: Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020–2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436]

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020–2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436]