Since radiotherapy is widely used in managing thoracic tumors, physicians have begun to realize that radiation-induced lung injury (RILI) seriously limits the effects of radiotherapy. Unfortunately, there are still no effective methods for controlling RILI. Over the last few decades numerous studies have reported the beneficial effects of mesenchymal stem cells (MSCs) on tissue repair and regeneration. MSCs can not only differentiate into lung alveolar epithelial cells and secrete anti-inflammatory factors, but they also deliver some vehicles for gene therapy in repairing the injured lung, which provides new ideas for managing RILI. Thus, many scientists have attempted to manage RILI using MSC-based therapy. However, as a novel therapy MSCs still face various limitations. Herein, we shed light on the current understanding of MSC-based therapy for RILI, including the feasibility, molecular mechanisms, animal studies, and clinical research of MSC-based therapy for RILI. We also present an overview of RILI and MSCs.

Clustering of the load patterns from distribution network customers is of vital importance for several applications. However, the growing number of Advanced Metering Infrastructure (AMI) and a variety of customer behaviors make the clustering task quite challenging due to the increasing amount of load data. K-means is a widely used clustering algorithm in processing large dataset with acceptable computational efficiency, but suffers from local optimal solutions. To address this issue, this paper presents a hierarchical K-means (H-K-means) method for better clustering performance for big data problems. The proposed method is applied to a large-scale AMI dataset and its effectiveness is evaluated by benchmarking with several existing clustering methods in terms of five common adequacy indices, outliers detection, and computation time.Index Terms-Advanced Metering Infrastructure (AMI), big data problems, clustering, hierarchical K-means (H-K-means), load patterns.

Lung adenocarcinomas exhibit various patterns of genomic alterations. During the development of this cancer, KRAS serves as a driver oncogene with a relatively high mutational frequency. Emerging data suggest that lung adenocarcinomas with KRAS mutations can show enhanced PD-L1 expression and additional somatic mutations, thus linking the prospect of applying immune checkpoint blockade therapy to this disease. However, the responses of KRAS-mutant lung adenocarcinomas to this therapy are distinct, which is largely attributed to the heterogeneity in the tumoral immune milieus. Recently, it was revealed that KRAS-mutant lung adenocarcinomas simultaneously expressing either a LKB1 or TP53 mutation typically have different immune profiles of their tumours: tumours with a KRAS/TP53 co-mutation generally present with a significant upregulation of PD-L1 expression and tumoricidal T-cell accumulation, and those with a KRAS/LKB1 co-mutation are frequently negative for PD-L1 expression and have few tumoricidal immune infiltrates. In this regard, interrogating TP53 or LKB1 mutation in addition to PD-L1 expression will be promising in guiding clinical use of immune checkpoint blockade therapy for KRAS-mutant lung adenocarcinomas.

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The chemokine C–X–C motif chemokine 12 (CXCL12) greatly impacts various biological processes in mammals, including cell survival, growth and migration. Mesenchymal stem cells (MSCs) are promising tools for carrying foreign genes to treat radiation-induced injuries in the intestinal epithelium. In this study, human adipose-derived MSCs were constructed to over-express the mouse cxcl12 gene to treat such injuries. In vitro, because of the high levels of mouse CXCL12 in conditioned medium produced by mouse cxcl12 gene-modified cells, phosphorylation of Akt at Ser473 and Erk1/2 at Thr202/Thr204 was increased within crypt cells of irradiated organoids compared with unmodified controls. Moreover, intracellular stabilization of β-catenin was achieved after treatment of mouse cxcl12 gene-modified cells with conditioned medium. As a result, survival of crypt cells was maintained and their proliferation was promoted. When delivering mouse cxcl12 gene-modified cells into irradiated BALB/c nude mice, mice were rescued despite the clearance of cells from the host within 1 week. Irradiated mice that received mouse cxcl12 gene-modified MSCs exhibited reduced serum levels of interleukin-1α (IL-1α) and IL-6 as well as elevated levels of CXCL12. Additionally, epithelial recovery from radiation stress was accelerated compared with the irradiated-alone controls. Moreover, mouse cxcl12 gene-modified MSCs were superior to unmodified cells at strengthening host repair responses to radiation stress as well as presenting increased serum CXCL12 levels and decreased serum IL-1α levels. Furthermore, the number of crypt cells that were positive for phosphorylated Akt at Ser473 and phosphorylated Erk1/2 at Thr202/Thr204 increased following treatment with mouse cxcl12 gene-modified MSCs. Thus, cxcl12 gene-modified MSCs confer radioresistance to the intestinal epithelium.