Single-cell analysis reveals the COL11A1+ fibroblasts are cancer-specific fibroblasts that promote tumor progression

Background: Cancer-associated fibroblasts (CAFs) promote tumor progression through extracellular matrix (ECM) remodeling and extensive communication with other cells in tumor microenvironment. However, most CAF-targeting strategies failed in clinical trials due to the heterogeneity of CAFs. Hence, we aimed to identify the cluster of tumor-promoting CAFs, elucidate their function and determine their specific membrane markers to ensure precise targeting.Methods: We integrated multiple single-cell RNA sequencing (scRNA-seq) datasets across different tumors and adjacent normal tissues to identify the tumor-promoting CAF cluster. We analyzed the origin of these CAFs by pseudotime analysis, and tried to elucidate the function of these CAFs by gene regulatory network analysis and cell-cell communication analysis. We also performed cell-type deconvolution analysis to examine the association between the proportion of these CAFs and patients’ prognosis in TCGA cancer cohorts, and validated that through IHC staining in clinical tumor tissues. In addition, we analyzed the membrane molecules in different fibroblast clusters, trying to identify the membrane molecules that were specifically expressed on these CAFs.Results: We found that COL11A1+ fibroblasts specifically exist in tumor tissues but not in normal tissues and named them cancer-specific fibroblasts (CSFs). We revealed that these CSFs were transformed from normal fibroblasts. CSFs represented a more activated CAF cluster and may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. High CSF proportion was associated with poor prognosis in bladder cancer (BCa) and lung adenocarcinoma (LUAD), and IHC staining of COL11A1 confirmed their specific expression in tumor stroma in clinical BCa samples. We also identified that CSFs specifically express the membrane molecules LRRC15, ITGA11, SPHK1 and FAP, which could distinguish CSFs from other fibroblasts.Conclusion: We identified that CSFs is a tumor specific cluster of fibroblasts, which are in active state, may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. Membrane molecules LRRC15, ITGA11, SPHK1 and FAP could be used as therapeutic targets for CSF-targeting cancer treatment

Robot Calibration for Cooperative Process under Typical Installation

A method with easy operation procedure and simple calibration condition is presented in this paper to solve the base frame calibration problem for cooperative robots. It is carried out through constructing a series of handclasp configurations and recording coordinates of the contact points, respectively, in base frame of each robot. Then the rotation matrix and translation matrix between base frame of cooperative robots can be calculated which is just the calibration result for cooperative robots. Based on typical installation mode for industrial robot, the floor mounted, wall mounted and ceiling mounted, constraints between base frames of these robots are further explored. These constraints are used to improve the calibration results for base frame calibration problem. In order to validate the correctness and effectiveness of our method, experiments on two industrial robots (Motoman VA1400 and HP20) are carried out at the end of the paper. The calibration errors are less than 8 mm in most cases, which satisfies the requirement of positioning accuracy for most industrial process, such as arc welding, transporting, and cutting. These experiment results assert the correctness of our method which can be used effectively to solve the base frame calibration problem for cooperative robots in manufacturing process

Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo

Background/Aims: Acute myeloid leukemia (AML) remains a hematologic malignancy with poor survival and a high risk of relapse, which is mainly caused by the emergence of multidrug resistance (MDR). The identification of novel agents to improve therapeutic strategies becomes important priority for AML treatment. It has been shown that emodin has therapeutic effects on many kinds of human malignant tumors. In this study, we investigated the anti-leukemia effects of emodin alone or in combination with cytarabine (Ara-C) on multidrug-resistant AML HL-60/ADR cells and in a mouse xenograft model of human highly tumorigenic AML HL-60/H3 cells. The underlying mechanism was also addressed. Methods: Cell viability after treatment was measured by MTT assay. The DNA fragmentation assay, Annexin V-PE/7-AAD, AO/EB staining, and electron microscopy were introduced to assess the apoptotic induction effects. Changes in protein expression in the Akt and ERK signaling pathways were determined by western blotting. In vivo antileukemia effects on HL-60/H3 xenograft model and overall mouse survival outcomes were further analyzed in this study. Results: Emodin dose-dependently induced growth inhibition and apoptotic effects in resistant HL-60/ADR cells in vitro as well as in the HL-60/H3 xenograft models in vivo. Moreover, emodin significantly enhanced chemosensitivity of AML cells to Ara-C, inhibited leukemic cell growth, and improved survival in the mouse xenograft model of AML. Dual targeting of Akt and ERK signaling pathways might contribute to the anti-leukemia effects on AML cells in vitro and in vivo. Conclusion: Emodin and its combination with Ara-C may be considered a promising therapeutic approach in AML and worthy of further investigation

Present Situation and Development Measures of Beef Cattle Industry in Xuanhan County

This paper analyzes the actual situation and bottleneck problems in the development of beef cattle industry in Xuanhan County. In view of the existing problems, this paper puts forward reasonable suggestions, with a view to better exploring the development model of characteristic beef cattle industry in Xuanhan County based on the unique cattle resources of Xuanhan County, and effectively promoting the implementation of the strategy of rural revitalization

Genome-wide SNP discovery and evaluation of genetic diversity among six Chinese indigenous cattle breeds in Sichuan

<div><p>Indigenous cattle in Sichuan Province, southwestern China, provide abundant genetic resources. However, their genetic diversity and population structure remain largely unknown, especially on the genome-wide scale. In the present study, we successfully employed the restriction site-associated DNA sequencing approach (RADseq) to explore genome-wide SNPs among six breeds of Sichuan cattle. A total of 238,725 high-confidence SNPs were finally obtained with a mean distance of 11,140 bp between two adjacent sites, and 43.4% were revealed to be novel in comparison with a public reference database of genetic variants. The mean nucleotide diversity and polymorphism information content (PIC) among all six breeds were 0.1878 and 0.1555, respectively. Pingwu and Ganzi cattle showed the highest and lowest genetic diversity, respectively. The inter-breed comparisons revealed that Ganzi and Ebian cattle were obviously separate from the others. Our reference set of genome-wide SNPs specific to indigenous cattle in Sichuan is the first of its kind. Moreover, our set can be used to investigate the genetic diversity and population structure and for genome-wide association studies.</p></div

Development Status and Strategies of Xieka

In this paper, the present situation of Xieka cattle was investigated, and the body size of Xieka cattle was measured. It was found that there were some problems in Xieka cattle, such as backward feeding and management, and degradation of breeds. The corresponding strategies were put forward in order to promote the resource protection, development and utilization of Xieka cattle

Genetic structure among the six populations.

<p>The matrix (A) shows the pairwise Wright’s F_ST values in the lower triangular area and F_IS values in diagonal cells. The IBS distance-based multidimensional scaling plot of 55 samples is shown in (B).</p

Overview of genetic diversity within each breed.

<p>Overview of genetic diversity within each breed.</p