Synthesis and characterisation of hydrogels with controlled microstructure and enhanced mechanical properties

For the application of advanced hydrogel-based artificial muscle systems, conventional polymeric hydrogels usually suffer from various limitations such as structural inhomogeneity and poor mechanical strengths. Thus, improving the mechanical strength of a specific hydrogel system while maintaining its other useful properties become increasingly important. In this project, three different approaches were employed to improve the mechanical properties of hydrogels though microstructural control, including physical cross-links, copolymerisation, and interpenetrating systems. Analytical tools such as FTIR and XRD were used to confirm the success of sample preparation. Morphological SEM characterisations were applied to reveal direct graphic information on hydrogels microstructures. Equilibrium water swelling tests as well as uniaxial compression measurements were conducted to evaluate the influences of various experimental parameters on the hydrogels water-holding and mechanical properties. The physical cross-linker approach was proved to be successful since comparable swelling capacities and dramatically enhanced mechanical strength were achieved in nanocomposite systems in comparison with conventional chemically cross-linked gel systems, due to the presence of flexible cross-linking points and the multifunctional cross-linker role played by clay. The copolymerisation approach, both between two neutral monomers and between one neutral and the other ionic monomer, was unsuccessful in terms of mechanical property enhancement due to the low cross-linking density as a result of the dominate competition of copolymerisation rather than cross-lining kinetics. The interpenetrating approach was concluded as successful since hugely improved mechanical toughness and slightly reduced swelling capacities were observed in most IPN gel systems

Cheating off your neighbors: Improving activity recognition through corroboration

Understanding the complexity of human activities solely through an individual's data can be challenging. However, in many situations, surrounding individuals are likely performing similar activities, while existing human activity recognition approaches focus almost exclusively on individual measurements and largely ignore the context of the activity. Consider two activities: attending a small group meeting and working at an office desk. From solely an individual's perspective, it can be difficult to differentiate between these activities as they may appear very similar, even though they are markedly different. Yet, by observing others nearby, it can be possible to distinguish between these activities. In this paper, we propose an approach to enhance the prediction accuracy of an individual's activities by incorporating insights from surrounding individuals. We have collected a real-world dataset from 20 participants with over 58 hours of data including activities such as attending lectures, having meetings, working in the office, and eating together. Compared to observing a single person in isolation, our proposed approach significantly improves accuracy. We regard this work as a first step in collaborative activity recognition, opening new possibilities for understanding human activity in group settings

The association between serum total folic acid concentration and severe difficulty falling asleep in US adults: NHANES 2005–2008

ObjectiveThe present study aimed to explore the correlation of serum total folic acid concentration with severe difficulty falling asleep among US adults.MethodsCross-sectional data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006 and 2007 to 2008 cycles. Participants were divided into the severe difficulty falling asleep (SDFA) group and the control group according to the monthly frequency of having difficulty falling asleep. Serum total folic acid was taken as independent and dependent variables, respectively. The correlation of serum total folic acid concentration with severe difficulty falling asleep was examined using multivariable logistic regression models, where the adjusted odds ratio (OR) and 95% confidential intervals (CIs) were calculated.ResultsOverall, 8,926 individuals from the NHANES 2005 to 2006 and 2007 to 2008 waves were included in the analysis, of whom 683 participants had severe difficulty falling asleep. Higher serum total folic acid concentration (ng/ml) was associated with lower odds of severe difficulty falling asleep after adjusting for potentially confounding factors (OR = 0.98; 95% CI: 0.97–1.00), while participants at the highest quartile had the least odds of severe difficulty falling asleep (OR = 0.55; 95% CI: 0.40–0.74). The subgroup analysis based on gender, smoking history, and diabetes showed that this negative correlation was more significant in males, smokers, and nondiabetic population after adjusting for confounding factors.ConclusionHigh levels of serum folic acid were significantly related to less odds of severe difficulty in falling asleep among US adults, suggesting that folic acid supplementation may be beneficial to the prevention and even treatment of severe difficulty falling asleep

Curcumin Inhibits Polyethylene-Induced Osteolysis via Repressing NF-κB Signaling Pathway Activation

Background/Aims: Aseptic loosening is a common reason for failed artificial hip replacement after total hip arthroplasty. Aseptic loosening is mostly the result of wear debris that causes osteolysis and weakens the structures that support the prosthesis. Wear debris plays a crucial role in osteolysis during the loosening process, and polyethylene (PE) particles are found as wear debris more frequently than any other type of particle. In the absence of effective therapeutic agents, osteolysis has been hard to treat. Previous studies have demonstrated that curcumin influences signalosome-associated kinases and the proteasome-ubiquitin system during osteoclastogenesis. The aims of this study were to explore the anti-osteolysis effect of curcumin and if possible to identify the signaling pathway involved in a model of PE-induced osteolysis. Methods: Differentiation of osteoclasts was induced in vitro by PE particles in RAW264.7 (monocyte/macrophage) cells and in vivo by calvarial and air pouch models of osteolysis established by PE stimulation in mice. We performed a set of TRAP staining, realtime polymerase chain reaction (PCR), and Western blot experiments to evaluate the anti-osteolytic effect of curcumin by comparing specimens that were exposed and not exposed to curcumin. Results: Curcumin had a promising inhibitory effect on osteolysis induced by wear debris and suppressed the RANK/c-Fos/NFATc1 signaling pathway. Conclusion: Curcumin can prevent PE-induced osteolysis and bone loss. An inhibitory effect on the RANK/c-Fos/NFATc1 signaling pathway may explain the anti-osteolysis activity of curcumin

Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma

BackgroundMucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC.MethodsDifferential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry.ResultsWe constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p < 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p < 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated.ConclusionWe established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC

The transmembrane channel-like 6 (TMC6) in primary sensory neurons involving thermal sensation via modulating M channels

Introduction: The transmembrane channel-like (TMC) protein family contains eight members, TMC1–TMC8. Among these members, only TMC1 and TMC2 have been intensively studied. They are expressed in cochlear hair cells and are crucial for auditory sensations. TMC6 and TMC8 contribute to epidermodysplasia verruciformis, and predispose individuals to human papilloma virus. However, the impact of TMC on peripheral sensation pain has not been previously investigated.Methods: RNAscope was employed to detect the distribution of TMC6 mRNA in DRG neurons. Electrophysiological recordings were conducted to investigate the effects of TMC6 on neuronal characteristics and M channel activity. Zn2+ indicators were utilized to detect the zinc concentration in DRG tissues and dissociated neurons. A series of behavioural tests were performed to assess thermal and mechanical sensation in mice under both physiological and pathological conditions.Results and Discussion: We demonstrated that TMC6 is mainly expressed in small and medium dorsal root ganglion (DRG) neurons and is involved in peripheral heat nociception. Deletion of TMC6 in DRG neurons hyperpolarizes the resting membrane potential and inhibits neuronal excitability. Additionally, the function of the M channel is enhanced in TMC6 deletion DRG neurons owing to the increased quantity of free zinc in neurons. Indeed, heat and mechanical hyperalgesia in chronic pain are alleviated in TMC6 knockout mice, particularly in the case of heat hyperalgesia. This suggests that TMC6 in the small and medium DRG neurons may be a potential target for chronic pain treatment

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care