Absence of Nucks1 enhances mesenchymal stem cells mediated cardiac protection

Despite major advances in diagnosis and prevention of coronary artery disease (CAD), the development of therapies to regenerate functional cardiomyocytes after myocardial infarction (MI) is very challenging. Studies have demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) secrete a panel of growth factors and anti-inflammatory cytokines to activate resident cardiomyocytes and cardiac stem cells in myocardial repair after MI. However, the mechanisms of modulating BM-MSC secretions are not well understood. Recently, molecular candidates in regulating BM-MSCs paracrine secretion to improve cardiac protection have been explored. Amongst the molecular candidates, Nuclear casein kinase and cyclin-dependent kinase substrate 1 (Nucks1) is suggested as a regulatory protein in nuclear factor-kappa B (NF-κB) signaling pathway by interacting with TANK-binding kinase 1 (TBK1). TBK1 is a non-canonical I kappa B (IκB) kinase that can activate the NF-κB transcription factor and its transcriptional response. NF-κB signaling pathway controls many cellular responses such as cell survival, proliferation and cytokine productions. We hypothesizes Nucks1 may have potential roles in regulating mouse BM-MSCs secretion of growth factors and cytokine profiles in heart repairs after MI. To test our hypothesis, the cardiac protection efficacy of acute infarcted mouse myocardium was measured after the transplantation of WT versus Nucks1 KO BM-MSCs. To this end, we developed a mouse model of acute myocardial infarction (AMI) induced by ligation of left descendant coronary artery. Acute infarcted mouse myocardium receiving WT or Nuck1 KO BM-MSCs transplantation, demonstrated a significant improvement of left ventricular ejection fraction (LVEF), ESP, +dP/dt, ESPVR and vessel density, and reduced infarction size in comparison with PBS control group post-4 weeks of transplantation. Furthermore, acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs transplantation provided better cardioprotective effects than those receiving WT BM-MSCs transplantation. Immunostaining disclosed CD31 and smooth muscle actin (SMA) expression in acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs were relatively higher than those receiving WT BM-MSCs transplantation. Additionally, a distinct secretion profile of growth factors and cytokines between Nucks1 KO BM-MSCs versus WT BM-MSCs under in vitro ischemia was studied. Expression of vascular endothelial growth factor alpha (VEGFα) in Nucks1 KO BM-MSCs under hypoxia/ serum deprivation was significantly higher than that of WT BMMSCs. Taken together, our data suggested BM-MSCs provide cardiac protection in acute infarcted myocardium. Transplantation of Nucks1 KO BMMSCs may further enhance the cardiac repair of the acute infracted myocardium through an induction of VEGFα.published_or_final_versionMedicineMasterMaster of Philosoph

“And this one’s juuust right!”: Prosody Predicts Reading Comprehension in Hong Kong Chinese-English Bilingual Children

This study examined the development of prosodic reading and its within- and cross-language contributions to reading comprehension among 121 Cantonese-English bilingual second-graders (aged 7 years, 70 girls) in 2015, and 52 of them as third-graders in 2016. Spectrographic analysis of their reading of one Chinese and one English passage revealed both cross-language similarities and language-specific differences in the use of pitch and pause when producing syntactically complex sentences. Wh question pitch contours emerged as the most robust predictor of reading comprehension across Chinese (r = .359) and English (r = -.457). A crossover effect occurred from Cantonese pitch to English reading comprehension (r = -.169). These results support the prosodic catalysing hypothesis, indicating the role of pitch in reading comprehension

The roles of prosody in Chinese-English reading comprehension

Background: Despite being an essential component of children’s oral reading fluency, prosodic reading, which involves expressive changes in pitch patterns and pause durations, has not been explored in Cantonese-English bilingual children, whose first language (L1) is tonal, non-alphabetic, and whose second language (L2) is non-tonal, alphabetic. Aims: This study examined the development of prosodic reading and its within- and cross-language associations with reading comprehension among Cantonese-English bilingual children from second to third grade. Sample: One hundred and twenty-one 7-to 8-year-old Cantonese-English bilingual children completed initial testing in grade 2, with 52 tested in grade 3. Methods: Prosodic reading was assessed using one Chinese and one English passage, each comprising six types of syntactic structures: declaratives, clause-final commas, yes-no questions, wh- questions, complex adjectival phrases, and quotatives. Word-reading efficiency, oral passage-reading fluency, and reading comprehension in Chinese and English were also measured. Results: Spectrographic analyses revealed that these children were aware of language-independent functions and language-specific manifestations of pitch and pause cues within and across their L1 Chinese and L2 English. Wh question pitch contours emerged as the most robust link to reading comprehension across both languages, while a crossover effect occurred from Cantonese pitch to English reading comprehension. Shorter pauses for English declarative quotative sentences and phrase-final commas were concurrently associated with greater English reading comprehension. Conclusions: These findings are interpreted within a new reading framework, the Prosodic Catalysing Hypothesis (PCH), which proposes that pitch and pause production can bridge prosody and syntax to facilitate reading comprehension

Attenuation of fatty liver and prevention of hypercholesterolemia by extract of Curcuma longa through regulating the expression of CYP7A1, LDL-receptor, HO-1, and HMG-CoA reductase

The extract of Curcuma longa, better known as turmeric, was orally administered to experimental rats that were fed a high-cholesterol diet to investigate whether it could regulate plasma lipids and cholesterol levels and possibly improve hepatic conditions. With turmeric supplements, rats showed a significant decrease in total plasma cholesterol and low-density lipoprotein cholesterol but an increase in high-density lipoprotein cholesterol when compared with rats that were fed a high-cholesterol diet alone. Fatty liver developed in hypercholesterolemic rats with the high-cholesterol diet treatment, and this condition was markedly improved when rats were provided with turmeric supplements at 100 mg/kg or 300 mg/kg of body mass. The turmeric treatment resulted in a significant decrease in the total amount of hepatic lipid. Histological staining of liver tissues with Sudan III and hematoxylin showed that rats fed with a high-cholesterol diet alone had more and larger granular fat bodies than rats having turmeric extract supplementation in their high-cholesterol diet. Reverse-transcription polymerase chain reaction was used to assess the expression levels of enzymes involved in fat metabolism and cellular homeostasis in experimental rat livers. The results showed that rats fed a high-cholesterol diet supplemented with turmeric extract had a significant increase in the expression of cholesterol 7 α-hydroxylase, hemeoxygenase 1, and low-density lipoprotein receptors but a significant decrease in 3-hydroxy-3-methyl-glutaryl-CoA reductase level when compared with rats fed a normal or high-cholesterol diet, showing that turmeric prevents hypercholesterolemia and the formation of fatty liver by the modulation of expressions of enzymes that are important to cholesterol metabolism

Light enhanced direct Cu bonding for advanced electronic assembly

An innovative and efficient surface modification pre-treatment that enhances Cu–Cu direct bonding through electromagnetic irradiation, including pulsed Xenon flash and near infrared rays is proposed. Without vacuum, short but critical electromagnetic radiation exposure on faying faces prior to bonding can significantly improve the joint strength up to 50% or even more. Copper atom diffusion acceleration by increased compressive residual surface stresses resulting from sudden heating/cooling accounts for the joint reinforcement. A close relationship between the increase in joint strength and the change in surface physics properties due to electromagnetic irradiations can be found

Gelatin/Chitosan Bilayer Patches Loaded with Cortex Phellodendron amurense/Centella asiatica Extracts for Anti-Acne Application

Acne is a chronic inflammatory skin disease that often occurs with anaerobic Propionibacterium acnes (P. acnes). Anti-acne patches, made of hydrocolloid or hydrogel, have become a popular way of topical treatment. The outer water-impermeable layer of commercial patches might create hypoxic conditions and promote P. acnes growth. In this study, gelatin/chitosan (GC) bilayer patches were prepared at different temperatures that included room temperature (RT), −20 °C/RT, and −80 °C/RT. The most promising GC bilayer patch (−80 °C /RT) contained a dense upper layer for protection from bacteria and infection and a porous lower layer for absorbing pus and fluids from pimples. The anti-acne bilayer patch was loaded with Cortex Phellodendri amurensis (PA) and Centella asiatica (CA) extracts. PA extract could inhibit the growth of P. acnes and CA extract was reported to improve wound healing and reduce scar formation. Moreover, the water retention rate, weight loss rate, antibacterial activity, and in vitro cytotoxicity of the patches were investigated. The porous structure of the patches promoted water retention and contributed to absorbing the exudate when used on open acne wounds. The GC bilayer patches loaded with PA/CA extracts were demonstrated to inhibit the growth of P. acnes, and accelerate the skin fibroblast cell viability. Based on their activities and characteristics, the GC bilayer patches with PA/CA extract prepared at −80 °C/RT obtain the potential for the application of acne spot treatment

Enhanced Cu-to-Cu direct bonding by controlling surface physical properties

Cu-to-Cu direct bonding is one of the key technologies for three-dimensional (3D) chip stacking. This research proposes a new concept to enhance Cu-to-Cu direct bonding through the control of surface physical properties. A linear relationship between bonding strength and the $H/\sqrt{R}$ value of the bonding face (H: subsurface hardness, R: surface roughness) was found. Low vacuum air plasma and thermal annealing were adopted to adjust the surface physical conditions. Instead of surface activation, an acceleration in copper atom diffusion due to plasma-induced compressive stress accounts for the improvement in bonding strength