Sonic Hedgehog Pathway Is Essential for Maintenance of Cancer Stem-Like Cells in Human Gastric Cancer

Abnormal activation of the Sonic hedgehog (SHH) pathway has been described in a wide variety of human cancers and in cancer stem cells (CSCs), however, the role of SHH pathway in gastric CSCs has not been reported. In this study, we investigated the possibility that abnormal activation of the SHH pathway maintained the characteristics of gastric CSCs. First, we identified cancer stem-like cells (CSLCs) from human gastric cancer cell lines (HGC-27, MGC-803 and MKN-45) using tumorsphere culture. Compared with adherent cells, the floating tumorsphere cells had more self-renewing capacity and chemoresistance. The cells expressing CSCs markers (CD44, CD24 and CD133) were also significantly more in tumorsphere cells than in adherent cells. More importantly, in vivo xenograft studies showed that tumors could be generated with 2×104 tumorsphere cells, which was 100-fold less than those required for tumors seeding by adherent cells. Next, RT-PCR and Western blot showed that the expression levels of Ptch and Gli1 (SHH pathway target genes) were significantly higher in tumorsphere cells than in adherent cells. The results of quantitative real-time PCR were similar to those of RT-PCR and Western blot. Further analysis revealed that SHH pathway blocked by cyclopamine or 5E1 caused a higher reduction in self-renewing capacity of HGC-27 tumorsphere cells than that of adherent cells. We also found that SHH pathway blocking strongly enhanced the efficacy of chemotherapeutic drugs in HGC-27 tumorsphere cells in vitro and in vivo but had no significant effect in adherent cells. Finally, we isolated the tumorspheres from gastric cancer specimen, these cells also had chemoresistance and tumorigenic capacity, and SHH pathway maintained the gastric CSLCs characteristics of tumorsphere cells from primary tumor samples. In conclusion, our data suggested that SHH pathway was essential for maintenance of CSLCs in human gastric cancer

Measuring thermoelectric transport properties of materials

In this review we discuss considerations regarding the common techniques used for measuring thermoelectric transport properties necessary for calculating the thermoelectric figure of merit, zT. Advice for improving the data quality in Seebeck coefficient, electrical resistivity, and thermal conductivity (from flash diffusivity and heat capacity) measurements are given together with methods for identifying possible erroneous data. Measurement of the Hall coefficient and calculation of the charge carrier concentration and mobility is also included due to its importance for understanding materials. It is not intended to be a complete record or comparison of all the different techniques employed in thermoelectrics. Rather, by providing an overview of common techniques and their inherent difficulties it is an aid to new researchers or students in the field. The focus is mainly on high temperature measurements but low temperature techniques are also briefly discussed

Microbial community composition in urban riverbank sediments: response to municipal effluents over spatial gradient

Municipal effluents have adverse impacts on the aquatic ecosystem and especially the microbial community. This study described the compositions of sediment bacterial communities in the urban riverbank over the spatial gradient. Sediments were collected from seven sampling sites of the Macha River. The physicochemical parameters of sediment samples were determined. The bacterial communities in sediments were analyzed by 16S rRNA gene sequencing. The results showed that these sites were affected by different types of effluents, leading to regional variations in the bacterial community. The higher microbial richness and biodiversity at SM2 and SD1 sites were correlated with the levels of NH4+-N, organic matter, effective sulphur, electrical conductivity, and total dissolved solids (p < 0.01). Organic matter, total nitrogen, NH4+-N, NO3-N, pH, and effective sulphur were identified to be important drivers for bacterial community distribution. At the phylum level, Proteobacteria (32.8–71.7%) was predominant in sediments, and at the genus level, Serratia appeared at all sampling sites and accounted for the dominant genus. Sulphate-reducing bacteria, nitrifiers, and denitrifiers were detected and closely related to contaminants. This study expanded our understanding of municipal effluents on microbial communities in riverbank sediments, and also provided valuable information for further exploration of microbial community functions. HIGHLIGHTS This study described the compositions of sediment bacterial communities in the municipal effluent-affected urban riverbank over the spatial gradient.; This study showed that different types of effluents led to regional variations in the bacterial community. Downstream effluents were more affected by effluents, accompanied by higher abundance and biodiversity of bacteria.

Integrated bioinformatics analysis for the identification of idiopathic pulmonary fibrosis–related genes and potential therapeutic drugs

Abstract Objective The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. We sought to identify IPF-related genes that may participate in the pathogenesis and predict potential targeted traditional Chinese medicines (TCMs). Methods Using IPF gene-expression data, Wilcoxon rank-sum tests were performed to identify differentially expressed genes (DEGs). Protein–protein interaction (PPI) networks, hub genes, and competitive endogenous RNA (ceRNA) networks were constructed or identified by Cytoscape. Quantitative polymerase chain reaction (qPCR) experiments in TGF-β1-induced human fetal lung (HFL) fibroblast cells and a pulmonary fibrosis mouse model verified gene reliability. The SymMap database predicted potential TCMs targeting IPF. The reliability of TCMs was verified in TGF-β1-induced MRC-5 cells. Materials Multiple gene-expression profile data of normal lung and IPF tissues were downloaded from the Gene Expression Omnibus database. HFL fibroblast cells and MRC-5 cells were purchased from Wuhan Procell Life Science and Technology Co., Ltd. (Wuhan, China). C57BL/12 mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Results In datasets GSE134692 and GSE15197, DEGs were identified using Wilcoxon rank-sum tests (both p < 0.05). Among them, 1885 DEGs were commonly identified, and 87% (1640 genes) had identical dysregulation directions (binomial test, p < 1.00E-16). A PPI network with 1623 nodes and 8159 edges was constructed, and 18 hub genes were identified using the Analyze Network plugin in Cytoscape. Of 18 genes, CAV1, PECAM1, BMP4, VEGFA, FYN, SPP1, and COL1A1 were further validated in the GeneCards database and independent dataset GSE24206. ceRNA networks of VEGFA, SPP1, and COL1A1 were constructed. The genes were verified by qPCR in samples of TGF-β1-induced HFL fibroblast cells and pulmonary fibrosis mice. Finally, Sea Buckthorn and Gnaphalium Affine were predicted as potential TCMs for IPF. The TCMs were verified by qPCR in TGF-β1-induced MRC-5 cells. Conclusion This analysis strategy may be useful for elucidating novel mechanisms underlying IPF at the transcriptome level. The identified hub genes may play key roles in IPF pathogenesis and therapy

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

Abstract Background MYO15A variants are responsible for human non-syndromic autosomal recessive deafness (DFNB3). The majority of MYO15A variants are associated with a congenital severe-to-profound hearing loss phenotype, except for MYO15A variants in exon 2, which cause a milder auditory phenotype, suggesting a genotype-phenotype correlation of MYO15A. However, MYO15A variants not in exon 2 related to a milder phenotype have also been reported, indicating that the genotype-phenotype correlation of MYO15A is complicated. This study aimed to provide more cases of MYO15A variation with diverse phenotypes to analyse this complex correlation. Methods Fifteen Chinese autosomal recessive non-syndromic hearing loss (ARNSHL) individuals with MYO15A variants (8 males and 7 females) from 14 unrelated families, identified by targeted gene capture of 127 known candidate deafness genes, were recruited. Additionally, we conducted a review of the literature to further analyses all reported MYO15A genotype-phenotype relationships worldwide. Results We identified 16 novel variants and 12 reported pathogenic MYO15A variants in 15 patients, two of which presented with a milder phenotype. Interestingly, one of these cases carried two reported pathogenic variants in exon 2, while the other carried two novel variants not in exon 2. Based on our literature review, MYO15A genotype-phenotype correlation analysis showed that almost all domains were reported to be correlated with a milder phenotype. However, variants in the N-terminal domain were more likely to cause a milder phenotype. Using next-generation sequencing (NGS), we also found that the number of known MYO15A variants with milder phenotypes in Southeast Asia has increased in recent years. Conclusion Our work extended the MYO15A variant spectrum, enriched our knowledge of auditory phenotypes, and tried to explore the genotype-phenotype correlation in different populations in order to investigate the cause of the complex MYO15A genotype-phenotype correlation

Research on variable universe fuzzy PID control for semi-active suspension with CDC dampers based on dynamic adjustment functions

Abstract The vehicle suspension system is a complex system with multiple variables, nonlinearity and time-varying characteristics, and the traditional variable universe fuzzy PID control algorithm has the problems of over-reliance on expert experience and non-adaptive adjustment of the contracting-expanding factor parameters, which make it difficult to achieve a better control effect. In this paper, the system error e(t) and its change rate ec(t) are introduced into the contracting-expanding factor as dynamic parameters to realize the adaptive adjustment of the contracting-expanding factor parameters, and propose a variable universe fuzzy PID control based on dynamic adjustment functions (VUFP-DAF), which uses the real-time contracting-expanding factor to realize the adaptive adjustment of the fuzzy universe, so as to improve the ride comfort of vehicles. The research results show that the proposed VUFP-DAF has strong adaptability and can effectively improve the ride comfort and handling stability of vehicles under different speeds and road excitations, providing a certain technical basis for the development of the semi-active suspension system

Effect of Drilling Parameters on Machining Performance in Drilling Polytetrafluoroethylene

Polytetrafluoroethylene (PTFE) plays an important role in semiconductor manufacturing. It is an important processing material for the key sealing components in the field of immersion lithography. The lack of research related to the mechanical processing of PTFE leads to many challenges in producing complex parts. This paper conducted a drilling experiment on PTFE. The effect of cutting parameters on the drilling performance was investigated. Thrust, torque, surface roughness, and drilling temperature were used to evaluate the influence of cutting parameters on drilling performance. In addition, the empirical mathematical models of thrust and torque were developed using analysis of variance (ANOVA). The results indicated that the spindle speed had the most important effect on the thrust and the feed rate had the most significant effect on the torque. The lowest values of thrust and torque were, respectively, 22.64 N and 0.12 Nm, achieved in the case of spindle speed of 5000 rev/min, and feed rate of 50 mm/min. The surface quality is also best at this cutting parameter. Studies have shown that higher spindle speeds with lower feed rates are ideal parameters for improving the drilling performance and machining quality of PTFE. In addition, it was found that the temperature differences due to different drilling depths were related to chip accumulation. Surface roughness inconsistencies at various locations in the inner wall of the hole were influenced by chip adhesion during machining. This paper provides a suggestion for optimizing cutting parameters and hole quality

Are Cu2Te‐Based Compounds Excellent Thermoelectric Materials?

Most of the state‐of‐the‐art thermoelectric (TE) materials exhibit high crystal symmetry, multiple valleys near the Fermi level, heavy constituent elements with small electronegativity differences, or complex crystal structure. Typically, such general features have been well observed in those well‐known TE materials such as Bi2X3‐, SnX‐, and PbX‐based compounds (X = S, Se, and Te). The performance is usually high in the materials with heavy constituent elements such as Te and Se, but it is low for light constituent elements such as S. However, there is a great abnormality in Cu2X‐based compounds in which Cu2Te has much lower TE figure of merit (zT) than Cu2S and Cu2Se. It is demonstrated that the Cu2Te‐based compounds are also excellent TE materials if Cu deficiency is sufficiently suppressed. By introducing Ag2Te into Cu2Te, the carrier concentration is substantially reduced to significantly improve the zT with a record‐high value of 1.8, 323% improvement over Cu2Te and outperforms any other Cu2Te‐based materials. The single parabolic band model is used to further prove that all Cu2X‐based compounds are excellent TE materials. Such finding makes Cu2X‐based compounds the only type of material composed of three sequent main group elements that all possess very high zT  s above 1.5.By introducing Ag2Te into Cu2Te, the phase‐transition features are well tuned and the high carrier concentration is substantially reduced, leading to a record‐high zT of 1.8. It is demonstrated that Cu2Te, Cu2S, and Cu2Se are all excellent thermoelectric (TE) materials that are beyond all other state‐of‐the‐art TE materials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152745/1/adma201903480-sup-0001-SupMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152745/2/adma201903480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152745/3/adma201903480.pd