Optimization of Strategy for Modified mRNA Inducing Cardiac-Specific Expression in Mice.

Lipid nanoparticle (LNP)-coated-modified RNA(modRNA) has been developed for enhancing the stability of modRNA, but it tends to accumulate in liver. The current study aimed to optimize strategy for increasing cardiac expression efficiency of modRNA. We synthesized Luciferase (Luc)-modRNA, and also developed 122Luc modRNA, a liver silencing Luc modRNA. Intramyocardial injection of naked Luc modRNA induced high bioluminescence signal in heart, but very low in other organs including liver. Luc modRNA-LNP injection showed the signal was increased by 5 folds in the heart and by 15,000 folds in the liver, compared to naked Luc modRNA group. In comparison with Luc modRNA-LNP group, the liver signal was decreased to 0.17%, while cardiac signal showed a slight drop by intramyocardial injection of 122Luc-modRNA-LNP. Our data revealed that intramyocardial injection of naked modRNA could effectively induced cardiac-specific expression. For cardiac delivery of Luc modRNA-LNP, 122modRNA-LNP enhances specificity of cardiac expression by abolishing liver signal.

The impact of Helicobacter pylori infection on low skeletal muscle mass risk in Chinese women over 40: a cross-sectional analysis.

Background: Sarcopenia can lead to significant personal, social, and economic burdens. The diagnosis of sarcopenia heavily relies on the identification of Low Skeletal Muscle Mass (LSMM), which is an independent predictor of frailty, disability, and increased risk of death among seniors. Women have physiologically lower levels of skeletal muscle mass than men, and female sarcopenia appears to be more influenced by menopause. They also tend to have higher body fat levels than man, which increases the risk of sarcopenia obesity. On another front, it's also recognized that humans are largely prone to Helicobacter pylori (H. pylori) infection, with global prevalence rates often surpassing 50%. Nevertheless, the interconnection between H. pylori infection and LSMM remains relatively unexplored. Hence, our study specifically targeted women as the research population and sought to explore several risk factors for LSMM. Additionally, we delved into the potential correlation between LSMM and H. pylori infection in women, hoping to gain insights into potential preventative measures or treatment options that may enhance the quality of life for women affected by sarcopenia. Methods: We conducted a cross-sectional study among women aged over 18 years undergoing physical examination. We performed 13C-urea breath test (UBT) for diagnosis of H. pylori infection and Bioelectrical impedance analysis (BIA) for the assessment of LSMM. Logistic regression models were used to analyze the associations of H. pylori infection with LSMM. Results: This study enrolled 1984 Chinese women who were undergoing health check-ups. A univariate logistic regression analysis did not reveal a direct correlation between H. pylori infection and LSMM among this female population (OR=1.149, 95% CI 0.904-1.459, p=0.257). Yet, upon dividing the participants into age-based subgroups, an evident link was observed between H. pylori infection and LSMM in women aged 40 or above (OR=1.381, 95%CI 1.032-1.848, p= 0.030). After adjusting for variables including Age, BMI, TP, ALK, Cre, this relationship remained statistically relevant (OR=1.514, 95%CI 1.085-2.113, p= 0.015). Conclusions: Women who are over 40 years old and currently infected with H. pylori have an increased risk of developing LSMM. Therefore, timely treatment for H. pylori eradication is recommended for this group of women to reduce the occurrence of LSMM.

In situ assessment of statins' effect on autophagic activity in zebrafish larvae cardiomyocytes.

Improving the survival rate of cardiomyocytes is the key point to treat most of the heart diseases, and targeting autophagy is a potential advanced therapeutic approach. Monitoring autophagic activity in cardiomyocytes in situ will be useful for studying autophagy-related heart disease and screening autophagy-modulating drugs. Zebrafish, Danio rerio, has been proven as an animal model for studying heart diseases in situ. Taken the advantage of zebrafish, especially the imaging of intact animals, here we generated two stable transgenic zebrafish lines that specifically expressed EGFP-map1lc3b or mRFP-EGFP-map1lc3b in cardiomyocytes under the promoter of myosin light chain 7. We first used a few known autophagy-modulating drugs to confirm their usefulness. By quantifying the density of autophagosomes and autolysosomes, autophagy inducers and inhibitors showed their regulatory functions, which were consistent with previous studies. With the two lines, we then found a significant increase in the density of autophagosomes but not autolysosomes in zebrafish cardiomyocytes at the early developmental stages, indicating the involvement of autophagy in early heart development. To prove their applicability, we also tested five clinical statins by the two lines. And we found that statins did not change the density of autophagosomes but reduced the density of autolysosomes in cardiomyocytes, implying their regulation in autophagic flux. Our study provides novel animal models for monitoring autophagic activity in cardiomyocytes in situ, which could be used to study autophagy-related cardiomyopathy and drug screening.

Interaction of oil drops with surfaces of different interfacial energy and topography.

During a marine oil spill, the oil can interact with and potentially wet a variety of surfaces such as corals, skin/shells of marine animals, and bird feathers. We present both qualitative and quantitative data for the interaction of a dodecane droplet submerged in water with surfaces varying in both surface energy and roughness. Flat, unstructured silicon surfaces with water in air contact angles of 0°, 43°, 66°, 87°, 96°, and 108° were tested first to obtain base readings, after which photolithography was used to introduce structured surfaces representative of marine biological systems. We find that the more hydrophilic a surface, the less prone it is to oil contamination. Also, the Cassie-Baxter approximation holds up for submerged oil in water systems and can be used to predict contact angles of oil on solid rough surfaces submerged in an aqueous environment. Furthermore, the addition of surface structure, even on strongly hydrophobic (oleophilic) surfaces, greatly reduced (≈75% reduction in F(adhesion)) a surface's affinity for oil.

Origin of the contact angle hysteresis of water on chemisorbed and physisorbed self-assembled monolayers.

Self-assembled monolayers (SAMs) are known to form on a variety of substrates either via chemisorption (i.e., through chemical interactions such as a covalent bond) or physisorption (i.e., through physical interactions such as van der Waals forces or "ionic" bonds). We have studied the behavior and effects of water on the structures and surface energies of both chemisorbed octadecanethiol and physisorbed octadecylamine SAMs on GaAs using a number of complementary techniques including "dynamic" contact angle measurements (with important time and rate-dependent effects), AFM, and electron microscopy. We conclude that both molecular overturning and submolecular structural changes occur over different time scales when such SAMs are exposed to water. These results provide new insights into the time-dependent interactions between surfaces and colloids functionalized with SAMs when synthesized in or exposed to high humidity or bulk water or wetted by water. The study has implications for a wide array of phenomena and applications such as adhesion, friction/lubrication and wear (tribology), surfactant-solid surface interactions, the organization of surfactant-coated nanoparticles, etc.

Design and fabrication of gecko-inspired adhesives.

Recently, there has been significant interest in developing dry adhesives mimicking the gecko adhesive system, which offers several advantages compared to conventional pressure-sensitive adhesives. Specifically, gecko adhesive pads have anisotropic adhesion properties; the adhesive pads (spatulae) stick strongly when sheared in one direction but are non-adherent when sheared in the opposite direction. This anisotropy property is attributed to the complex topography of the array of fine tilted and curved columnar structures (setae) that bear the spatulae. In this study, we present an easy, scalable method, relying on conventional and unconventional techniques, to incorporate tilt in the fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive system, which provides anisotropic adhesion properties. We measured the anisotropic adhesion and friction properties of samples with various tilt angles to test the validity of a nanoscale tape-peeling model of spatular function. Consistent with the peel zone model, samples with lower tilt angles yielded larger adhesion forces. The tribological properties of the synthetic arrays were highly anisotropic, reminiscent of the frictional adhesion behavior of gecko setal arrays. When a 60° tilt sample was actuated in the gripping direction, a static adhesion strength of ~1.4 N/cm(2) and a static friction strength of ~5.4 N/cm(2) were obtained. In contrast, when the dry adhesive was actuated in the releasing direction, we measured an initial repulsive normal force and negligible friction.

Carbon microspheres as ball bearings in aqueous-based lubrication.

We present an exploratory study on a suspension of uniform carbon microspheres as a new class of aqueous-based lubricants. The surfactant-functionalized carbon microspheres (∼0.1 wt %) employ a rolling mechanism similar to ball bearings to provide low friction coefficients (µ ≈ 0.03) and minimize surface wear in shear experiments between various surfaces, even at high loads and high contact pressures. The size range, high monodispersity, and large yield stress of the C(µsphere), as well as the minimal environmental impact, are all desirable characteristics for the use of a C(µsphere)-SDS suspension as an alternative to oil-based lubricants in compatible devices and machinery.

Use of electrochemical deposition to create randomly rough surfaces and roughness gradients.

A novel approach to reproducibly generating randomly rough surfaces over large areas and generating surface roughness gradients is presented. By tuning the electrochemical deposition potential for silver onto an electrode, the island nucleation density can be systematically varied resulting in thin films of different roughness. We find that the potential range that significantly influences the surface roughness also corresponds to a reaction/mixed-controlled deposition regime. The roughness can be replicated onto other moldable materials, thus enabling future studies involving the effect of surface roughness.