Insights into Genus Codonopsis: From past Achievements to Future Perspectives.

Codonopsis plants, as a kind of medicinal and edible herb, have a long history of application and have been widely concerned by pharmacists and biologists. In this article, the species diversity, taxonomy and distribution, ethnic medicinal records, chemical composition, pharmacological activity, and quality evaluation methods of Codonopsis species were systematically reviewed. In addition, the research progress of Codonopsis plants using biotechnology in recent years was summarized. The phytochemistry and biological activities of Codonopsis are widely evaluated. To date, more than 350 compounds have been isolated from Codonopsis. Codonopsis pilosula polysaccharides are important functional components and biomarkers. Lobetyolin, atractylenolide III, tangshenoside I, and oligosaccharide can be considered as characteristic index components to evaluate the quality of Codonopsis plants. Although recent experimental evidence has confirmed the pharmacological value of this genus, its quality control, resource development and utilization, and active ingredient synthesis mechanisms are not well studied. In particular, molecular biology research is still in its infancy, but its application prospects are broad, and it is a hot spot for future research on Codonopsis. Therefore, it is urgent to conduct a detailed study on the single level of phytochemistry, pharmacology, and molecular biology of Codonopsis to establish a scientific evaluation system and modern medication guidelines. The multi-angle, multi-level, and multi-aspect integrated association analysis is also an inevitable trend for the future in-depth study of Codonopsis plants. This research status was summarized in order to provide a broader scientific research idea and theoretical reference for the in-depth study of Codonopsis.

TGFß Antagonizes IFNγ-Mediated Adaptive Immune Evasion via Activation of the AKT-Smad3-SHP1 Axis in Lung Adenocarcinoma.

IFNγ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGFß promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGFß inhibits IFNγ signaling in immune cells. We thus sought to determine whether TGFß affects IFNγ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGFß stimulation of tumor cells increased SHP1 phosphatase activity in an AKT-Smad3-dependent manner, decreased IFNγ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion-related molecules, e.g., PD-L1, IDO1, herpes virus entry mediator (HVEM), and galectin-9 (Gal-9). In a lung cancer mouse model, dual blockade of TGFß and PD-L1 led to superior antitumor activity and prolonged survival compared with anti-PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti-PD-L1 monotherapy, dual TGFß and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared with that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti-PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFNγ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGFß on the development of IFNγ-mediated tumor resistance to immunotherapy. SIGNIFICANCE: Blocking TGFß facilitates IFNγ-mediated resistance to anti-PD-L1 therapy due to the role of TGFß in inhibiting IFNγ-induced immunoevasion by increasing SHP1 phosphatase activity in tumor cells.

Integrative genomic profiling reveals characteristics of lymph node metastasis in small cell lung cancer.

Background: Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, with more than 70% of patients having metastatic disease and a poor prognosis. However, no integrated multi-omics analysis has been performed to explore novel differentially expressed genes (DEGs) or significantly mutated genes (SMGs) associated with lymph node metastasis (LNM) in SCLC. Methods: In this study, whole-exome sequencing (WES) and RNA-sequencing were performed on tumor specimens to investigate the association between genomic and transcriptome alterations and LNM in SCLC patients with (N+, n=15) or without (N0, n=11) LNM. Results: The results of WES revealed that the most common mutations occurred in TTN (85%) and TP53 (81%). The SMGs, including ZNF521, CDH10, ZNF429, POLE, and FAM135B, were associated with LNM. Cosmic signature analysis showed that mutation signatures 2, 4, and 7 were associated with LNM. Meanwhile, DEGs, including MAGEA4, FOXI3, RXFP2, and TRHDE, were found to be associated with LNM. Furthermore, we found that the messenger RNA (mRNA) levels of RB1 (P=0.0087), AFF3 (P=0.058), TDG (P=0.05), and ANKRD28 (P=0.042) were significantly correlated with copy number variants (CNVs), and ANKRD28 expression was consistently lower in N+ tumors than in N0 tumors. Further validation in cBioPortal revealed a significant correlation between LNM and poor prognosis in SCLC (P=0.014), although there was no significant correlation between LNM and overall survival (OS) in our cohort (P=0.75). Conclusions: To our knowledge, this is the first integrative genomics profiling of LNM in SCLC. Our findings are particularly important for early detection and the provision of reliable therapeutic targets.

circCNN2 Accelerates Cell Proliferation and Invasion in Lung Squamous Cell Carcinoma via Regulating miR-184/E2F1 and Activating MAPK Signaling Pathway.

Circular RNAs (circRNAs) have been demonstrated as potential biomarkers for the diagnosis and treatment of human diseases. Previous studies have unveiled the carcinogenic role of circRNA_102399 (circCNN2) in lung cancer. Through the UALCAN database, it was found that CNN2, the parent gene of circCNN2, was specifically highly expressed in human lung squamous cell carcinoma (LUSC) cells, but the regulatory mechanism of circCNN2 in LUSC is unclear. In this study, circCNN2 expression in LUSC cells was examined via RT-qPCR, and its effects on LUSC progression was verified through functional assays. The subcellular localization of circCNN2 was identified via FISH assay, and the underlying mechanism of circCNN2 on the activation of MAPK signaling pathway was determined through mechanism experiments. Results demonstrated that circCNN2 was upregulated in LUSC cells, and it promoted LUSC cell proliferation and invasion. Besides, circCNN2 acted as a competing endogenous RNA (ceRNA) to sponge miR-184 to upregulate E2F transcription factor 1 (E2F1) expression. Furthermore, it was verified that circCNN2 activated the generic mitogen-activated protein kinases (MAPK) signaling pathway through E2F1 and thus promoting LUSC progression. In a word, this study indicated that circCNN2 activated MAPK signaling pathway through the miR-184/E2F1 axis to promote proliferation and invasion of LUSC cells.

Knockdown of hnRNPA1 Promotes NSCLC Metastasis and EMT by Regulating Alternative Splicing of LAS1L exon 9.

Tumor metastasis is still an insurmountable obstacle in tumor treatment. Lung cancer represents one of the most common malignancies with high morbidity worldwide. hnRNPA1 has been reported to be involved in the regulation of tumor metastasis, while its specific role in tumor metastasis seems to be controversial and its molecular mechanism in lung cancer metastasis remains to be further elucidated. In this study, we confirmed that knockdown of the hnRNPA1 led to enhanced migration, invasion and EMT transition in lung cancer cells. Bioinformatics analysis of the GSE34992 dataset revealed that hnRNPA1 may regulate the alternative splicing (AS) of LAS1L exon 9. Further AGE assays and RIP assays revealed that hnRNPA1 can directly bind to the LAS1L pre-mRNA to inhibit the splicing of LAS1L exon 9. The RNA pull-down assays showed that hnRNPA1 can specifically bind to the two sites (UAGGGU(WT1) and UGGGGU(WT3)) of LAS1L Intron 9. Further Transwell assays indicated that the expression ratio of LAS1L-L/LAS1L-S regulated by hnRNPA1 can further promote the migration, invasion and EMT transition in lung cancer cells. Moreover, hnRNPA1 expression showed significant heterogeneity in lung cancer tissues, which may contain new research directions and potential therapeutic targets. Our results indicate that hnRNPA1 can affect the metastasis of lung cancer cells by modulating the AS of LAS1L exon 9, highlighting the potential significance of hnRNPA1 in lung cancer metastasis.

Efficacy and safety of thoracoscopic resection for early-stage non-small cell lung cancer.

OBJECTIVE: To explore the efficacy and safety of thoracoscopic resection for early-stage non-small cell lung cancer (NSCLC). METHODS: A total of 110 patients with early-stage NSCLC admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2017 and December 2019 were enrolled and retrospectively analysed. Among them, 60 patients receiving thoracoscopic resection for lung cancer (LC) were assigned to the research group (Res group) and another 50 patients treated with routine open radical resection for LC were included in the control group (Con group). The following items of the two groups were evaluated and compared: treatment efficacy, operation indexes, VAS score, lung function, lung capacity, complications, 2-year tumour-free survival rate, 2-year survival rate, and quality of life (QoL). RESULTS: The Res group showed significantly better efficacy, and lower incidence of complications and VAS score than the Con group. In addition, patients in the Res group experienced less intraoperative blood loss, earlier anal exhaust, shorter hospital stay and indwelling time of drainage tube as well as less drainage volume. Furthermore, better recovery in pulmonary function and lung capacity, and significantly higher 2-year tumour-free survival rate, 2-year survival rate as well as postoperative QoL were noted in the Res group compared with the Con group. CONCLUSION: Thoracoscopic resection for LC is effective in the treatment of patients with early-stage NSCLC. It can substantially shorten the hospital stay and indwelling time of drainage tube and reduce drainage volume and blood loss, with high safety.

Evaluation of Ecological Suitability and Quality Suitability of Panax notoginseng Under Multi-Regionalization Modeling Theory.

Panax notoginseng is an important medicinal plant in China, but there are some limitations in the ecological suitability study, such as incomplete investigation of species distribution, single regionalization modeling, and lack of collaborative evaluation of ecological suitability, and quality suitability. In this study, the maximum entropy model was used to analyze the ecological suitability of P. notoginseng under current and future climates. The multi-source chemical information of samples was collected to evaluate the uniformity between quality and ecology. The results showed that the current suitable habitat was mainly in southwest China. In the future climate scenarios, the high suitable habitat will be severely degraded. Modeling based on different regionalization could predict larger suitable habitat areas. The samples in the high suitable habitat had both quality suitability and ecological suitability, and the accumulation of chemical components had different responses to different environmental factors. Two-dimensional correlation spectroscopy combined with deep learning could achieve rapid identification of samples from different suitable habitats. In conclusion, global warming is not conducive to the distribution and spread of P. notoginseng. The high suitable habitat was conducive to the cultivation of high-quality medicinal materials. Actual regionalization modeling had more guiding significance for the selection of suitable habitats in a small area. The multi-regionalization modeling theory proposed in this study could provide a new perspective for the ecological suitability study of similar medicinal plants. The results provided a reference for the introduction and cultivation, and lay the foundation for the scientific and standardized production of high-quality P. notoginseng.

Identification and Validation of 7-lncRNA Signature of Epigenetic Disorders by Comprehensive Epigenetic Analysis.

The survival rate of patients with lung adenocarcinoma (LUAD) is low. This study analyzed the correlation between the expression of long noncoding RNA (lncRNA) and epigenetic alterations along with the investigation of the prognostic value of these outcomes for LUAD. Differentially expressed lncRNAs were identified based on multiomic data and positively related genes using DESeq2 in R, differentially histone-modifying genes specific to LUAD based on histone modification data, gene enhancers from information collected from the FANTOM5 (Function Annotation Of The Mammalian Genome-5) (fantom.gsc.riken.jp/5) human enhancer database, gene promoters using the ChIPseeker and the human lincRNAs Transcripts database in R, and differentially methylated regions (DMRs) using Bumphunter in R. Overall survival was estimated by Kaplan-Meier, comparisons were performed among groups using log-rank tests to derive differences between sample subclasses, and epigenetic lncRNAs (epi-lncRNAs) potentially relevant to LUAD prognosis were identified. A total of seven dysregulated epi-lncRNAs in LUAD were identified by comparing histone modifications and alterations in histone methylation regions on lncRNA promoter and enhancer elements, including H3K4me2, H3K27me3, H3K4me1, H3K9me3, H4K20me1, H3K9ac, H3K79me2, H3K27ac, H3K4me3, and H3K36me3. Furthermore, 69 LUAD-specific dysregulated epi-lncRNAs were identified. Moreover, lncRNAs-based prognostic analysis of LUAD samples was performed and explored that seven of these lncRNAs, including A2M-AS1, AL161431.1, DDX11-AS1, FAM83A-AS1, MHENCR, MNX1-AS1, and NKILA (7-EpiLncRNA), showed the potential to serve as markers for LUAD prognosis. Additionally, patients having a high 7-EpiLncRNA score showed a generally more unfavorable prognosis compared with those which scored lower. Seven lncRNAs were identified as markers of prognosis in patients with LUAD. The outcomes of this research will help us understand epigenetically aberrant regulation of lncRNA expression in LUAD in a better way and have implications for research advances in the regulatory role of lncRNAs in LUAD.

Understanding the Critical Role of Glycolysis-Related lncRNAs in Lung Adenocarcinoma Based on Three Molecular Subtypes.

BACKGROUND: Glycolysis is closely associated with tumor progression, but the roles of lncRNAs in glycolysis have not been comprehensively investigated in lung adenocarcinoma (LUAD). This study is aimed at studying the possible mechanisms of glycolysis-related lncRNAs in tumor development and providing a guidance for targeted therapy. METHODS: Unsupervised consensus clustering was used to identify molecular subtypes. Gene enrichment analysis was applied to screen important pathways involved in tumor progression. A series of immune analysis was performed to assess immune infiltration. Critical transcription factors (TFs) interacting with lncRNAs were selected by Pearson correlation analysis. A first-order partial correlation analysis was implemented to identify critical lncRNAs with prognostic significance. RESULTS: Three molecular subtypes (C1, C2, and C3) were identified with distinct overall survival. Three subtypes showed differential immune infiltration, and C3 subtype was the optimal for immunotherapy treatment. Ten lncRNA-TF pairs among four glycolysis-related lncRNAs (FTX, LINC00472, PSMA3-AS1, and SNHG14) and six TFs (FOXP1, SP1, MYC, FOXM1, HIF1A, and FOS) were involved in tumor progression. We identified four critical glycolysis-related lncRNAs significantly associated with prognosis. CONCLUSIONS: This study identified three molecular subtypes that could guide personalized therapy. The four-lncRNA prognostic model can serve as an indicator for predicting prognosis or early screening of lung adenocarcinoma patients. The current results improve the understanding of the relation between lncRNAs and glycolysis.

Subxiphoid-subcostal thoracoscopic thymectomy for seropositive myasthenia offers equivalent remission rates and potentially faster recovery.

OBJECTIVES: To compare the perioperative and follow-up outcomes of patients with myasthenia gravis (MG) receiving subxiphoid-subcostal or unilateral thoracoscopic thymectomy and to identify the factors affecting MG prognosis. METHODS: From January 2013 to December 2019, a total of 137 consecutive MG patients received subxiphoid-subcostal thoracoscopic thymectomy (STT, n = 65) or conventional unilateral thoracoscopic thymectomy (UTT, n = 72). The primary outcomes of this study were perioperative complications, duration and expenses of hospitalization, VAS score and complete stable remission (CSR). RESULTS: The patients receiving STT had significantly shorter drainage duration and postoperative hospital stay and lower hospitalization expenses (P < 0.01). Pain scores on postoperative Days 1, 3, 7 and 14 were significantly lower in patients undergoing STT (P < 0.01). The average follow-up was 54.3 ± 24.18 months, with a CSR rate of 30.6% and an overall effective rate of 87.3%. Through uni- and multivariable analyses, shorter symptom duration and Myasthenia Gravis Foundation of America (MGFA) class I were independent predictors for CSR in MG patients receiving thymectomy. CONCLUSIONS: The present study not only showed that STT was a safe and feasible technique for MG, with a potentially faster postoperative recovery, lower hospitalization expenses, less postoperative pain and equivalent remission rate, but also revealed that shorter symptom duration and MGFA class I were favourable prognostic factors for CSR.

FILIP1L-mediated cell apoptosis, epithelial-mesenchymal transition and extracellular matrix synthesis aggravate posterior capsular opacification.

AIMS: The epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and cell migration of residual lens cells constitute the canonical mechanisms of posterior capsular opacification (PCO). Recently, myofibroblast cell apoptosis is also observed in the rabbit PCO model. However, whether cell apoptosis is a key factor affecting PCO and regulates EMT/ECM synthesis/cell migration remains obscure. MAIN METHODS: Flow cytometry was utilized to assess cell cycle and apoptosis. EMT marker α-smooth muscle actin (α-SMA), ECM markers fibronectin (Fn), type 1 collagen (COL-1) and apoptosis-associated proteins in the presence or absence of EMT/ECM inhibitor (LY2109761), apoptosis inhibitor (ZVAD) or apoptosis activator (BTSA1) were detected by Western blotting. Downstream effector genes in apoptosis-induced lens epithelial cell lines (LECs) were analyzed by RNA-seq. Gene silencing and overexpression in LECs were performed to validate the role of effector genes. We measured cell migration capability using Wound healing and Transwell assays. KEY FINDINGS: We found that TGF-ß2 induced cell apoptosis. ZVAD inhibited α-SMA expression in the ex vivo capsule model and decreased the expression of both EMT and ECM markers in TGF-ß2-treated LECs. RNA-seq revealed that FILIP1L was significantly decreased in apoptosis-activated cells. We further validated that the knockdown of FILIP1L could enhance EMT and ECM synthesis and promote cell migration and that FILIP1L overexpression could reverse these effects. Apoptosis might contribute to TGF-ß2-induced EMT and ECM synthesis during PCO, and these contributions are mediated by FILIP1L. SIGNIFICANCE: Our findings uncover the role of apoptosis in PCO development and provide new drug targets.

Superiority Verification of Deep Learning in the Identification of Medicinal Plants: Taking Paris polyphylla var. yunnanensis as an Example.

Medicinal plants have a variety of values and are an important source of new drugs and their lead compounds. They have played an important role in the treatment of cancer, AIDS, COVID-19 and other major and unconquered diseases. However, there are problems such as uneven quality and adulteration. Therefore, it is of great significance to find comprehensive, efficient and modern technology for its identification and evaluation to ensure quality and efficacy. In this study, deep learning, which is superior to conventional identification techniques, was extended to the identification of the part and region of the medicinal plant Paris polyphylla var. yunnanensis from the perspective of spectroscopy. Two pattern recognition models, partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM), were established, and the overall discrimination performance of the three types of models was compared. In addition, we also compared the effects of different sample sizes on the discriminant performance of the models for the first time to explore whether the three models had sample size dependence. The results showed that the deep learning model had absolute superiority in the identification of medicinal plant. It was almost unaffected by factors such as data type and sample size. The overall identification ability was significantly better than the PLS-DA and SVM models. This study verified the superiority of the deep learning from examples, and provided a practical reference for related research on other medicinal plants.

Signature identification of relapse-related overall survival of early lung adenocarcinoma after radical surgery.

BACKGROUND: The widespread use of low-dose chest CT screening has improved the detection of early lung adenocarcinoma. Radical surgery is the best treatment strategy for patients with early lung adenocarcinoma; however, some patients present with postoperative recurrence and poor prognosis. Through this study, we hope to establish a model that can identify patients that are prone to recurrence and have poor prognosis after surgery for early lung adenocarcinoma. MATERIALS AND METHODS: We screened prognostic and relapse-related genes using The Cancer Genome Atlas (TCGA) database and the GSE50081 dataset from the Gene Expression Omnibus (GEO) database. The GSE30219 dataset was used to further screen target genes and construct a risk prognosis signature. Time-dependent ROC analysis, calibration degree analysis, and DCA were used to evaluate the reliability of the model. We validated the TCGA dataset, GSE50081, and GSE30219 internally. External validation was conducted in the GSE31210 dataset. RESULTS: A novel four-gene signature (INPP5B, FOSL2, CDCA3, RASAL2) was established to predict relapse-related survival outcomes in patients with early lung adenocarcinoma after surgery. The discovery of these genes may reveal the molecular mechanism of recurrence and poor prognosis of early lung adenocarcinoma. In addition, ROC analysis, calibration analysis and DCA were used to verify the genetic signature internally and externally. Our results showed that our gene signature had a good predictive ability for recurrence and prognosis. CONCLUSIONS: We established a four-gene signature and predictive model to predict the recurrence and corresponding survival rates in patients with early lung adenocarcinoma after surgery. These may be helpful for reforumulating post-operative consolidation treatment strategies.

Study on the identification and evaluation of growth years for Paris polyphylla var. yunnanensis using deep learning combined with 2DCOS.

Paris polyphylla var. yunnanensis, as perennial plants, its quality is closely related to growth period. Different harvest years determine the dry matter accumulation of its medicinal parts and the dynamic accumulation of active ingredients, as well as its economic value and medicinal value. Therefore, it is necessary to establish a systematic evaluation method for the identification and evaluation of P. polyphylla var. yunnanensis with different growth years. Deep learning has a powerful ability in recognition. This study extends it to the identification analysis of medicinal plants from the perspective of spectrum. For the first time, two-dimensional correlation spectroscopy (2DCOS) based on the attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) combined with residual neural network (Resnet) was used to identify growth years. 525 samples were collected, 4725 2DCOS images were drawn, and the dry matter accumulation in rhizomes of different growth years and different sampling sites were briefly analyzed. The results show that the eight-year-old P. polyphylla var. yunnanensis in Dali has higher economic value and medicinal value. The synchronous 2DCOS models based on ATR-FTIR can realize the identification of growth years with accuracy of 100%. Synchronous 2DCOS are more suitable for the identification of medicinal plants with complex systems. 2DCOS images with different colors and second derivative processing cannot optimize the modeling results. In summary, the method we established is innovative and feasible. It not only solved the identification of growth years, expanded the application field of deep learning, but could also be extended to further research on other medicinal plants.

Genomic landscape of ground glass opacities (GGOs) in East Asians.

BACKGROUND: Understanding the genomic landscape of early-stage lung adenocarcinoma (LUAD) may provide new insights into the molecular evolution in the early stages of LUAD. METHODS: Through sequencing of 79 spatially distinct regions from 37 patients with ground glass opacities (GGOs), we provided a comprehensive mutational landscape of GGOs, highlighting the importance of ancestry differences. RESULTS: Our study had several interesting features. First, epidermal growth factor receptor (EGFR), BRAF (v-RAF murine sarcoma viral oncogene homologue B1), and ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, also known as HER2) were more frequently mutated in our study, which supports the notion that EGFR is considered to be a major driver and tends to drive the occurrence of LUAD. Second, Signature 1, Signature 3, and Signature 6 were identified in patients with GGOs. Our results further suggested that Signature 1 was more prominent among early mutations. Third, compared with LUADs, GGOs exhibited significantly lower levers of arm-level copy number variation (CNV)-which alter the diploid status of DNA, and lower focal CNVs. CONCLUSIONS: In our study, 79 samples of patients were included to analyze the GGO gene profile, revealing the genetic heterogeneity of GGO in East Asian population, and providing guidance for prognosis analysis of GGO patients by comparison with LUAD. Our study revealed that GGOs had fewer genomic alterations and simpler genomic profiles than LUADs. The most commonly altered processes were related to the receptor tyrosine kinase (RTK)/Ras/phosphatidylinositol-3-kinase (PI3K) signaling pathways in GGOs, and EGFR alterations were the dominant genetic changes across all targetable somatic changes.

Geographical traceability and multielement analysis of edible and medicinal fungi: Taking Wolfiporia cocos (F.A. Wolf) Ryvarden and Gilb. as an example.

Different geographical environment has a certain influence on the accumulation of fungi elements and chemical components. However, our knowledge is limited to elucidate the fungi elements in response to heterogeneous environmental and the quality differences among different habitats. Here, multielement analysis, FTIR spectrum, and feature-level fusion technique combined with chemometrics were used to study Wolfiporia cocos from different geographical areas, different sampling sites and different altitude sources. From the results, (1) there is significant difference in element content of samples from different sampling sites and no positive correlation with geographical ranges. (2) There is a correlation between elevation and elements, and relatively low elevation (<1,800 m) is conducive to the enrichment of elements. (3) From the perspective of elements, the W. cocos in Yuxi have relatively better quality. (4) FTIR and feature-level models can well realize origin identification. The SVM models are better than the PLS-DA models, and the feature-level model is better than the single FTIR models. In summary, this study demonstrated that the developed method was reliable and could realize the genuineness evaluation and origin identification of W. cocos. The results have implications for the establishment of the technology system of geographical traceability and the development of high-quality geographical indication products of W. cocos.

Application of Identification and Evaluation Techniques for Ethnobotanical Medicinal Plant of Genus Panax: A Review.

Genus Panax, as worldwide medicinal plants, has a medical history for thousands of years. Most of the entire genus are traditional ethnobotanical medicine in China, Myanmar, Thailand, Vietnam and Laos, which have given rise to international attention and use. This paper reviewed more than 210 articles and related books on the research of Panax medicinal plants and their Chinese patent medicines published in the last 30 years. The purpose was to review and summarize the species classification, geographical distribution, and ethnic minorities medicinal records of the genus Panax, and further to review the analytical tools and data analysis methods for the authentication and quality assessment of Panax medicinal materials and Chinese patent medicines. Five main technologies applied in the identification and evaluation of Panax have been introduced and summarized. Chromatography was the most widely used one. Further research and development of molecular identification technology had the potential to become a mainstream identification technology. In addition, some novel, controversial, and worthy methods including electronic noses, electronic eyes, and DNA barcoding were also introduced. At the same time, more than 80% of the researches were carried out by a combination of chemometric pattern-recognition technologies and multi-analysis technologies. All the technologies and methods applied can provide strong support and guarantee for the identification and evaluation of genus Panax, and also conduce to excellent reference value for the development and in-depth research of new technologies in Panax.

Interleukin-2 induces extracellular matrix synthesis and TGF-ß2 expression in retinal pigment epithelial cells.

Macular fibrosis is a vital obstacle of vision acuity improvement of age-related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL-2) on epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor ß2 (TGF-ß2) expression in retinal pigment epithelial (RPE) cells. 10 µg/L IL-2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α-smooth muscle actin (α-SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL-1), TGF-ß2, and the activation of the JAK/STAT3 and NF-κB signaling pathway. Furthermore, JAK/STAT3 and NF-κB signaling pathways were specifically blocked by WP1066 or BAY11-7082, respectively, and the expression of α-SMA, COL-1, Fn and TGF-ß2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL-2 with or without WP1066 or BAY11-7082. After induction of IL-2, the expressions of Fn, COL-1, TGF-ß2 protein were significantly increased, and this effect was correlated with IL-2 treatment duration, while α-SMA protein expression did not change significantly. Both WP1066 and BAY11-7082 could effectively downregulate the expression of Fn, COL-1 and TGF-ß2 induced by IL-2. What's more, both NF-κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF-κB inhibitor BAY 11-7082 could obviously decrease RPE cells migration capability induced by IL-2. IL-2 promotes cell migration, ECM synthesis and TGF-ß2 expression in RPE cells via JAK/STAT3 and NF-κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.

FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell.

Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery.

A novel Ni-WC/AC catalyst with enhanced electroactivity for glucose oxidation.

WC-doped Ni over an active carbon catalyst (Ni-WC/AC), prepared by incipient wetness impregnation, is proposed as an anode for the amplified electrochemical oxidation of glucose in 0.1 M KOH solution. Cyclic voltammetry and morphology characterizations were used to explore these electrocatalysts. It was found that Ni-WC/AC catalysts were nanoparticles with a diameter of 10 nm and the 20%wtNi-20%wtWC/AC catalyst showed superior electrocatalytic activity toward glucose oxidation. The extraordinary activity obtained at the 20%wtNi-20%wtWC/AC modified glass carbon electrode (GCE) is attributed to the synergistic effect between Ni and WC toward glucose electroxidation.