Cells employ signaling pathways to make decisions in response to changes in their immediate environment. Transforming growth factor beta (TGF-β) is an important growth factor that regulates many cellular functions in development and disease. Although the molecular mechanisms of TGF-β signaling have been well studied, our understanding of this pathway is limited by the lack of tools that allow the control of TGF-β signaling with high spatiotemporal resolution. Here, we developed an optogenetic system (optoTGFBRs) that enables the precise control of TGF-β signaling in time and space. Using the optoTGFBRs system, we show that TGF-β signaling can be selectively and sequentially activated in single cells through the modulation of the pattern of light stimulations. By simultaneously monitoring the subcellular localization of TGF-β receptor and Smad2 proteins, we characterized the dynamics of TGF-β signaling in response to different patterns of blue light stimulations. The spatial and temporal precision of light control will make the optoTGFBRs system as a powerful tool for quantitative analyses of TGF-β signaling at the single cell level.

Primary liver cancer (PLC) is one of the most common malignant tumours and has the third highest mortality rate worldwide. An active liver-targeting drug delivery system via the asialoglycoprotein receptors expressed in the hepatic parenchyma cells of mammals has become a research focus for the treatment of PLC. N-acetylaminogalactosyl-poly(lactide-co-glycolide)-succinyl-D-α-tocopherol polyethylene glycol 1000 succinate (GalNAc-PLGA-sTPGS) was synthesized to achieve active liver-targeting properties. Emodin (EMO)-loaded GalNAc-PLGA-sTPGS nanoparticles (EGPTN) were prepared with EMO which was selected for its potential antitumour efficacy. The in vitro cellular uptake, mechanism, cytotoxicity, and apoptosis of HepG2 cells were analyzed. The in vivo therapeutic effects of EGPTN were assessed in a PLC mouse model. The results showed that GalNAc-PLGA-sTPGS was successfully synthesized. The cellular uptake assay demonstrated that coumarin 6-loaded GalNAc-PLGA-sTPGS nanoparticles had superior active liver-targeting properties. The results of the cytotoxity and apoptosis studies indicated that EGPTN achieved the highest levels of cytotoxicity and cell apoptotic rate among the nanoparticles examined. Furthermore, EGPTN showed better in vivo therapeutic effects and anticancer efficacy in the PLC mice than did the other groups. Therefore, EGPTN enhanced the anticancer effect of EMO both in vitro and in vivo, making it a potential option for the treatment of PLC.

Summary Live cell imaging has been widely used to generate data for quantitative understanding of cellular dynamics. Various applications have been developed to perform automated imaging data analysis, which often requires tedious manual correction. It remains a challenge to develop an efficient curation method that can analyze massive imaging datasets with high accuracy. Here, we present eDetect, a fast error detection and correction tool that provides a powerful and convenient solution for the curation of live cell imaging analysis results. In eDetect, we propose a gating strategy to distinguish correct and incorrect image analysis results by visualizing image features based on principal component analysis. We demonstrate that this approach can substantially accelerate the data correction process and improve the accuracy of imaging data analysis. eDetect is well documented and designed to be user friendly for non-expert users. It is freely available at https://sites.google.com/view/edetect/ and https://github.com/Zi-Lab/eDetect .

Objective: To explore the efficacy comparison between epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) combined with traditional Chinese medicine (TCM) and single EGFR-TKIs for advanced non-small cell lung cancer (NSCLC).Methods: A total of 91 NSCLC patients with EGFR mutation were divided into an experimental group and a control group (in a ratio of 2:1) to receive TCM and EGFR-TKIs (61 cases) or single EGFR-TKIs (30 cases). Patients in the control group took EGFR-TKIs and those in the experimental group took EGFR-TKIs plus TCM. We analyzed the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events of two groups.Results: The mPFS of the experimental group and the control group was 12.3 and 8.9 months (P = 0.02), respectively, and the mOS of the experimental group and the control group was 28.2 and 24.2 months (P = 0.02), respectively. Subgroup analysis showed that for the patients with exon 19 deletion mutation (19DEL), mPFS between experimental group and control group was 12.7 and 10.1 months, respectively (P = 0.12). For exon 21 deletion mutation (L858R), the PFS of two groups was 10.8 vs. 8.2 months, respectively (P = 0.03). The subgroup analysis also showed that, for the patients with exon 19 deletion mutation, mOS between the experimental group and the control group was 30.3 and 28.7 months, respectively (P = 0.19). For exon 21 deletion mutation, the mOS of two groups was 25.5 vs. 21.3 months, respectively (P = 0.01). The DCR of the experimental group and the control group was 93.3% and 80.1%, respectively (P = 0.77). Grade 3–4 treatment-related adverse events were less common with the experimental group (11.48%) than the control group (26.67%).Conclusion: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM had a certain effect to prolong mPFS and mOS, compared with the use of EGFR-TKIs alone, especially for the patients with L858R. This conclusion has a significant effect on improving the survival of NSCLC patients after EGFR-TKIs resistance. It deserves further study.

Currently, both acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be the leading public health problems with gradually increasing incidence rates around the world. Rhein is a monomeric component of anthraquinone isolated from rhubarb, a traditional Chinese medicine. It has anti-inflammation, anti-oxidation, anti-apoptosis, anti-bacterial and other pharmacological activities, as well as a renal protective effects. Rhein exerts its nephroprotective effects mainly through decreasing hypoglycemic and hypolipidemic, playing anti-inflammatory, antioxidant and anti-fibrotic effects and regulating drug-transporters. However, the latest studies show that rhein also has potential kidney toxicity in case of large dosages and long use times. The present review highlights rhein’s molecular targets and its different effects on the kidney based on the available literature and clarifies that rhein regulates the function of the kidney in a positive and negative way. It will be helpful to conduct further studies on how to make full use of rhein in the kidney and to avoid kidney damage so as to make it an effective kidney protection drug.

Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has demonstrated that mitophagy is crucial to developing colorectal cancer. This study aims to examine the association between mitophagy-related genes and the prognosis of CRC patients. Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied to establish a prognostic signature using mitophagy related genes. Kaplan–Meier and receiver operating characteristic (ROC) curves were used to analyze patient survival and predictive accuracy. Meanwhile, we also used the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. ATG14 overexpression plasmid was used to regulate the ATG14 expression level in HCT116 and SW480 cell lines, and cell counting kit-8, colony formation and transwell migration assay were performed to validate the function of ATG14 in CRC cells. A total of 22 mitophagy-driven genes connected with CRC survival were identified, and then a novel prognostic signature was established based on 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter in both the training cohort and two independent cohorts. ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a Nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI 0.71–0.83) and more robust predictive accuracy. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more enriched in the high-risk group. Furthermore, patients in the high-risk group are more sensitive to targeted therapy or chemotherapy, including bosutinib, elesclomol, lenalidomide, midostaurin, pazopanib and sunitinib, while the low-risk group is more likely to benefit from immunotherapy. Finally, in vitro study confirmed the oncogenic significance of ATG14 in both HCT116 and SW480 cells, whose overexpression increased CRC cell proliferation, colony formation, and migration. In conclusion, we developed a novel mitophagy-related gene signature that can be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients, and we confirmed ATG14 as a novel oncogene in CRC.

Purpose: To explore a new therapeutic option for patients with hepatocellular carcinoma (HCC), the efficacy and safety of a group of traditional Chinese medicines (Banxia XieXin recipe) as monotherapy for patients with advanced HCC was studied. Materials and Methods: The study included 68 patients with advanced HCC from August 16,2016 to August 15,2019 for analysis. These eligible patients received treatment with Banxia XieXin recipe for at least 1 month. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR). In addition, safety was also assessed. Results: The median treatment duration of these 68 patients was 10.3 months (range = 1.6-33.5 months), and follow-up is still ongoing. The median PFS was 6.07 months (95% confidence interval [CI] = 3.748-8.392 months), and the median OS was 12.60 months (95% CI = 8.019-17.181 months). The ORR was 10.3% and the DCR was 41.2%. In the subgroup analysis, the median OS in the transcatheter arterial chemoembolization (TACE) group was not reached, and the median OS in the NO TACE group was 11.30 months (95% CI = 3.219-19.381 months). In addition, no drug-related serious adverse events were observed during the study. Conclusion: This is the first clinical analysis of traditional Chinese medicine as a single treatment for advanced HCC. The obtained results are encouraging as they suggest that this panel of Chinese herbs is safe and it may be effective for patients with advanced HCC in a real-world clinical setting.

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