Role of collagen VI in peripheral nerves and wound-induced hair regrowth

Collagen VI is an extracellular matrix (ECM) molecule dynamically expressed in a variety of tissues, including peripheral nerves and skin. However, the role of collagen VI in the peripheral nervous system (PNS) and hair follicle growth is yet unknown. The main focus of my PhD study was to investigate the role and the underlying mechanisms of collagen VI in peripheral nerve myelination and function, in PNS regeneration, as well as in wound-induced hair growth. During the first year of my PhD, I focused on investigating the phenotype of peripheral nerve myelination and function in collagen VI null (Col6a1–/–) mice. The data shows that Schwann cells, but not axons, contribute to collagen VI deposition in peripheral nerves. Lack of collagen VI in Col6a1–/– mice leads to hypermyelination via multiple signaling pathways, disorganized C-fibers in the PNS, impaired nerve conduction velocity, and sensorimotor dysfunction. These findings indicate that that collagen VI is a critical component of PNS contributing to the structural integrity and proper function of peripheral nerves. The second part of my PhD work focused on investigating the role of collagen VI in PNS under pathological conditions using nerve crush injury models, and revealed a novel mechanism of this ECM protein in modulating macrophage function. The results show that collagen VI is critical for macrophage migration and polarization during peripheral nerve regeneration. Nerve injury induces a robust upregulation of collagen VI, whereas lack of collagen VI in Col6a1–/– mice delays peripheral nerve regeneration. In vitro studies demonstrated that collagen VI promotes macrophage migration and polarization via AKT and PKA pathways. Col6a1–/– macrophages exhibit impaired migration abilities and reduced anti-inflammatory (M2) phenotype polarization, but are prone to skewing towards pro-inflammatory (M1) phenotype. In vivo, macrophage recruitment and M2 polarization are impaired in Col6a1–/– mice after nerve injury. The delayed nerve regeneration of Col6a1–/– mice is induced by macrophage deficits and rejuvenated by transplantation of wild-type bone marrow cells. These results identify collagen VI as a novel regulator for peripheral nerve regeneration by modulating macrophage function. In the last year of my PhD I moved my focus to skin homeostasis and investigated the role of collagen VI in wound-induced hair regrowth. The data shows that collagen VI is strongly deposited in hair follicles, and it is dramatically upregulated by skin wounding. Lack of collagen VI in Col6a1–/– mice promotes wound-induced hair regrowth, but does not affect skin regeneration. Conversely, addition of purified collagen VI rescues the abnormal wound-induced hair regrowth in Col6a1–/– mice. Mechanistic studies revealed that the increased wound-induced hair regrowth of Col6a1–/– mice is triggered by upregulation of Keratin 79 and activation of the Wnt/beta-catenin signaling pathway, and is abolished by inhibition of the Wnt/beta-catenin pathway. These findings highlight the essential relationships between ECM and hair follicle regeneration, and point at collagen VI as a potential therapeutic target for hair loss. Altogether, the data I obtained during my PhD studies strongly support a key role of collagen VI in peripheral nerves and wound-induced hair follicle growth, thus paving the way for future studies on ECM molecules in PNS and skin under physiological and pathological conditions

Revisiting the anomalous bending elasticity of sharply bent DNA

Several recent experiments suggest that sharply bent DNA has a surprisingly high bending flexibility, but the cause of this flexibility is poorly understood. Although excitation of flexible defects can explain these results, whether such excitation can occur with the level of DNA bending in these experiments remains unclear. Intriguingly, the DNA contained preexisting nicks in most of these experiments but whether nicks might play a role in flexibility has never been considered in the interpretation of experimental results. Here, using full-atom molecular dynamics simulations, we show that nicks promote DNA basepair disruption at the nicked sites, which drastically reduces DNA bending energy. In addition, lower temperatures suppress the nick-dependent basepair disruption. In the absence of nicks, basepair disruption can also occur but requires a higher level of DNA bending. Therefore, basepair disruption inside B-form DNA can be suppressed if the DNA contains preexisting nicks. Overall, our results suggest that the reported mechanical anomaly of sharply bent DNA is likely dependent on preexisting nicks, therefore the intrinsic mechanisms of sharply bent nick-free DNA remain an open question.Comment: 39 pages, 11 figures, 1 supporting materia

QDR-Tree: An Efcient Index Scheme for Complex Spatial Keyword Query

With the popularity of mobile devices and the development of geo-positioning technology, location-based services (LBS) attract much attention and top-k spatial keyword queries become increasingly complex. It is common to see that clients issue a query to find a restaurant serving pizza and steak, low in price and noise level particularly. However, most of prior works focused only on the spatial keyword while ignoring these independent numerical attributes. In this paper we demonstrate, for the first time, the Attributes-Aware Spatial Keyword Query (ASKQ), and devise a two-layer hybrid index structure called Quad-cluster Dual-filtering R-Tree (QDR-Tree). In the keyword cluster layer, a Quad-Cluster Tree (QC-Tree) is built based on the hierarchical clustering algorithm using kernel k-means to classify keywords. In the spatial layer, for each leaf node of the QC-Tree, we attach a Dual-Filtering R-Tree (DR-Tree) with two filtering algorithms, namely, keyword bitmap-based and attributes skyline-based filtering. Accordingly, efficient query processing algorithms are proposed. Through theoretical analysis, we have verified the optimization both in processing time and space consumption. Finally, massive experiments with real-data demonstrate the efficiency and effectiveness of QDR-Tree

Clinicopathological and prognostic value of epithelial cell adhesion molecule in solid tumours: a meta-analysis

BackgroundMalignant tumors, mainly solid tumors, are a significant obstacle to the improvement of life expectancy at present. Epithelial cell adhesion molecule (EpCAM), a cancer stem cell biomarker, showed widespread expression in most normal epithelial cells and most cancers. Although the clinical significance of EpCAM in various malignant solid tumors has been studied extensively, the latent relationships between EpCAM and pathological and clinical characteristics in solid tumors and differences in the roles of EpCAM among tumors have not been clearly determined. The destination point of this study was to analyze the value of EpCAM in solid tumors in clinicopathological and prognostic dimension using a meta-analysis approach.Method and materialsA comprehensive and systematic search of the researches published up to March 7th, 2022, in PubMed, EMBASE, Web of Science, Cochrane library and PMC databases was performed. The relationships between EpCAM overexpression, clinicopathological characteristics, and survival outcomes were analyzed. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) were estimated as indicators of the degree of correlation. This research was registered on PROSPERO (International prospective register of systematic reviews), ID: CRD42022315070.ResultsIn total, 57 articles and 14184 cases were included in this study. High EpCAM expression had a significant coherence with a poorer overall survival (OS) (HR: 1.30, 95% CI: 1.08–1.58, P < 0.01) and a worse disease-free survival (DFS) (HR: 1.58, 95% CI: 1.28–1.95, P < 0.01), especially of gastrointestinal tumors’ OS (HR: 1.50, 95% CI: 1.15–1.95, P < 0.01), and DFS (HR: 1.84, 95% CI: 1.52–2.33, P < 0.01). The DFS of head and neck tumors (HR: 2.33, 95% CI: 1.51–3.61, P < 0.01) was also associated with the overexpression of EpCAM. There were no positive relationships between the overexpression of EpCAM and sex (RR: 1.03, 95% CI: 0.99–1.07, P = 0.141), T classification (RR: 0.93, 95% CI: 0.82–1.06, P = 0.293), lymph node metastasis (RR: 0.85, 95% CI: 0.54–1.32, P = 0.461), distant metastasis (RR: 0.97, 95% CI: 0.84–1.10, P = 0.606), vascular infiltration (RR: 1.05, 95% CI: 0.85–1.29, P = 0.611), and TNM stage (RR: 0.93, 95% CI: 0.83–1.04, P = 0.187). However, the overexpression of EpCAM exhibited a significant association with the histological grades (RR: 0.88, 95% CI: 0.80–0.97, P < 0.01).ConclusionBased on pooled HRs, the positive expression of EpCAM was totally correlated to a worse OS and DFS in solid tumors. The expression of EpCAM was related to a worse OS in gastrointestinal tumors and a worse DFS in gastrointestinal tumors and head and neck tumors. Moreover, EpCAM expression was correlated with the histological grade. The results presented pointed out that EpCAM could serve as a prognostic biomarker for gastrointestinal and head and neck tumors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022315070

In-situ Thermophysical Measurement of Flowing Molten Chloride Salt Using Modulated Photothermal Radiometry

Molten salts are a leading candidate for high-temperature heat transfer fluids (HTFs) for thermal energy storage and conversion systems in concentrated solar power (CSP) and nuclear energy power plants. The ability to probe molten salt thermal transport properties in both stationary and flowing status is important for the evaluation of their heat transfer performance under realistic operational conditions, including the temperature range and potential degradation due to corrosion and contamination. However, accurate thermal transport properties are usually challenging to obtain even for stagnant molten salts due to different sources of errors from convection, radiation, and corrosion, let alone flowing ones. To the best of authors' knowledge, there is no available in-situ technique for measuring flowing molten salt thermal conductivity. Here, we report the first in-situ flowing molten salt thermal conductivity measurement using modulated photothermal radiometry (MPR). We could successfully perform the first in-situ thermal conductivity measurement of flowing molten $NaCl-KCl-MgCl_2$ in the typical operating temperature (520 and 580 $^oC$) with flow velocities ranging from around 0.3 to 1.0 $m$$s^-1$. The relative change of the molten salt thermal conductivity was measured. Gnielinski's correlation was also used to estimate the heat transfer coefficient h of the flowing $NaCl-KCl-MgCl_2$ in the given experimental condition. The work showed the potential of the MPR technique serving as an in-situ diagnostics tool to evaluate the heat transfer performance of flowing molten salts and other high-temperature HTFs

The role of 245 phase in alkaline iron selenide superconductors revealed by high pressure studies

Here we show that a pressure of about 8 GPa suppresses both the vacancy order and the insulating phase, and a further increase of the pressure to about 18 GPa induces a second transition or crossover. No superconductivity has been found in compressed insulating 245 phase. The metallic phase in the intermediate pressure range has a distinct behavior in the transport property, which is also observed in the superconducting sample. We interpret this intermediate metal as an orbital selective Mott phase (OSMP). Our results suggest that the OSMP provides the physical pathway connecting the insulating and superconducting phases of these iron selenide materials.Comment: 32 pages, 4 figure