Combined laser-induced breakdown spectroscopy and hyperspectral imaging with machine learning for the classification and identification of rice geographical origin.

With the events of fake and inferior rice and food products occurring frequently, how to establish a rapid and high accuracy monitoring method for rice food identification becomes an urgent problem. In this work, we investigate using combined laser-induced breakdown spectroscopy (LIBS) and hyperspectral imaging (HSI) with machine learning algorithms to identify the place of origin of rice production. Six geographical origin rice samples grown in different parts of China are selected and pretreated, and measured by the atomic emission spectra of LIBS and the reflection spectra of HSI, respectively. The principal component analysis (PCA) is utilized to realize data dimensionality and extract the data feat of LIBS, HSI and fusion data, and based on this, three models employing the partial least squares discriminant analysis (PLS-DA), the support vector machine (SVM) and the extreme learning machine (ELM) are used to identify the rice geographical origin. The results show that the accuracy of LIBS and HSI analysis with the SVM machine learning algorithm can reach 93.06% and 88.07%, respectively, and the accuracy of combined LIBS and HSI data fusion recognition can reach 99.85%. Besides, the classification accuracy of the three models measured after pretreatment is basically all above 95%, and up to 99.85%. This study proves the effectiveness of using the combined LIBS and HSI with the machine learning algorithm in rice geographical origin identification, which can achieve rapid and accurate rice quality and identity detection.

Botanical, Traditional Use, Phytochemical, and Toxicological of Arisaematis rhizoma.

MATERIALS AND METHODS: This review is a collection of all possible studies on AR, published in scientific journals, papers, and books. Using the papers related to Arisaematis, such as ScienceDirect, Wiley Online Library, Springer Link, Web of Science, CNKI, and WanFang Database. In this paper, the traditional uses, botany, phytochemistry, pharmacology, and toxicology of AR were reviewed. Finally, the existing problems and research directions of the research on AR are discussed. RESULTS: Ninety-eight chemical constituents were isolated from AR. AR has a wide range of pharmacological effects, such as the effects on the central nervous system and cardiovascular system. It also has anti-tumor, sedative, analgesic, anticonvulsant, anti-inflammatory, expectorant, antiarrhythmic, anticoagulant, and other effects. It is also considered an effective drug for in vitro and in vivo validation. CONCLUSIONS: AR is an excellent traditional medicinal plant in China. Pharmacological studies support the traditional use of AR and may verify the folk use of AR in the treatment of different diseases. The anti-tumor effect of AR has been widely concerned by scholars at home and abroad. It has become a hot spot in recent years and has made great contributions to the survival and development of human beings. Although it has a high value of comprehensive utilization, its development and utilization are far from enough. Therefore, the comprehensive development of AR is worthy of further analysis.

CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer.

OBJECTIVE: Precision immunotherapy in non-small cell lung cancer (NSCLC) have been the focus of tumor immunity research. The aim of this study is to identify novel candidate biomarkers predicting the response to immunotherapy in NSCLC. METHODS: GSE126044 was obtained from Gene Expression Omnibus (GEO). According to the response to anti-PD-1 antibody, 2 groups were divided: response group and non-response group. Differentially expressed genes (DEGs) were screened using R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. ROC curves and possible pathways of the seed genes were further analyzed. RESULTS: In total, 588 DEGs (487 upregulated DEGs and 101 downregulated) were identified. GO and KEGG analyses showed that upregulated DEGs were mainly enriched in immune response and cell adhesion pathways, while VEGF signaling pathway and metabolic pathways were mainly enriched in downregulated DEGs. In addition, CSF1 R and HCST showed more powerful predictive ability than PDL1. More importantly, these candidate genes were not only positively correlated with the expression of PDL1 and the infiltration of CD8+ T cells in the immune microenvironment, but also might improve the prognosis in lung squamous cell carcinoma. CONCLUSIONS: CSF1 R and HCST might be novel predictive markers for immunotherapy in NSCLC.

Immune-Stromal Score Signature: Novel Prognostic Tool of the Tumor Microenvironment in Lung Adenocarcinoma.

Background: Immune and stromal cells in the tumor microenvironment (TME) significantly contribute to the prognosis of lung adenocarcinoma; however, the TME-related immune prognostic signature is unknown. The aim of this study was to develop a novel immune prognostic model of the TME in lung adenocarcinoma. Methods: First, the immune and stromal scores among lung adenocarcinoma patients were determined using the ESTIMATE algorithm in accordance with The Cancer Genome Atlas (TCGA) database. Differentially expressed immune-related genes (IRGs) between high and low immune/stromal score groups were analyzed, and a univariate Cox regression analysis was performed to identify IRGs significantly correlated with overall survival (OS) among patients with lung adenocarcinoma. Furthermore, a least absolute shrinkage and selection operator (LASSO) regression analysis was performed to generate TME-related immune prognostic signatures. Gene set enrichment analysis was performed to analyze the mechanisms underlying these immune prognostic signatures. Finally, the functions of hub IRGs were further analyzed to delineate the potential prognostic mechanisms in comprehensive TCGA datasets. Results: In total, 702 intersecting differentially expressed IRGs (589 upregulated and 113 downregulated) were screened. Univariate Cox regression analysis revealed that 58 significant differentially expressed IRGs were correlated with patient prognosis in the training cohort, of which three IRGs (CLEC17A, INHA, and XIRP1) were identified through LASSO regression analysis. A robust prognostic model was generated on the basis of this three-IRG signature. Furthermore, functional enrichment analysis of the high-risk-score group was performed primarily on the basis of metabolic pathways, whereas analysis of the low-risk-score group was performed primarily on the basis of immunoregulation and immune cell activation. Finally, hub IRGs CLEC17A, INHA, and XIRP1 were considered novel prognostic biomarkers for lung adenocarcinoma. These hub genes had different mutation frequencies and forms in lung adenocarcinoma and participated in different signaling pathways. More importantly, these hub genes were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, B cells, and neutrophils. Conclusions: The robust novel TME-related immune prognostic signature effectively predicted the prognosis of patients with lung adenocarcinoma. Further studies are required to further elucidate the regulatory mechanisms of these hub IRGs in the TME and to develop new treatment strategies.

Identification of candidate genes and prognostic value analysis in patients with PDL1-positive and PDL1-negative lung adenocarcinoma.

BACKGROUND: Increasing bodies of evidence reveal that targeting a programmed cell death protein 1 (PD-1) monoclonal antibody is a promising immunotherapy for lung adenocarcinoma. Although PD receptor ligand 1 (PDL1) expression is widely recognized as the most powerful predictive biomarker for anti-PD-1 therapy, its regulatory mechanisms in lung adenocarcinoma remain unclear. Therefore, we conducted this study to explore differentially expressed genes (DEGs) and elucidate the regulatory mechanism of PDL1 in lung adenocarcinoma. METHODS: The GSE99995 data set was obtained from the Gene Expression Omnibus (GEO) database. Patients with and without PDL1 expression were divided into PDL1-positive and PDL1-negative groups, respectively. DEGs were screened using R. The Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks of DEGs was visualized using Cytoscape, and the MNC algorithm was applied to screen hub genes. A survival analysis involving Gene Expression Profiling Interactive Analysis was used to verify the GEO results. Mutation characteristics of the hub genes were further analyzed in a combined study of five datasets in The Cancer Genome Atlas (TCGA) database. RESULTS: In total, 869 DEGs were identified, 387 in the PDL1-positive group and 482 in the PDL1-negative group. GO and KEGG analysis results of the PDL1-positive group mainly exhibited enrichment of biological processes and pathways related to cell adhesion and the peroxisome proliferators-activated receptors (PPAR) signaling pathway, whereas biological process and pathways associated with cell division and repair were mainly enriched in the PDL1-negative group. The top 10 hub genes were screened during the PPI network analysis. Notably, survival analysis revealed BRCA1, mainly involved in cell cycle and DNA damage responses, to be a novel prognostic indicator in lung adenocarcinoma. Moreover, the prognosis of patients with different forms of lung adenocarcinoma was associated with differences in mutations and pathways in potential hub genes. CONCLUSIONS: PDL1-positive lung adenocarcinoma and PDL1-negative lung adenocarcinoma might be different subtypes of lung adenocarcinoma. The hub genes might play an important role in PDL1 regulatory pathways. Further studies on hub genes are warranted to reveal new mechanisms underlying the regulation of PDL1 expression. These results are crucial for understanding and applying precision immunotherapy for lung adenocarcinoma.

Early intervention with supplemental parenteral nutrition reduces the incidence of granulocytopenia-related infections in patients with lung cancer: a retrospective cohort study.

BACKGROUND AND OBJECTIVES: The optimal timing for initiating supplemental parenteral nutrition in chemotherapy- induced severe granulocytopenia in patients with lung cancer remains uncertain. METHODS AND STUDY DESIGN: A retrospective study was conducted among patients with lung cancer from February 2016 to June 2018. In total, 182 eligible patients were included and divided into 2 groups according to the time of supplemental parenteral nutrition intervention: early initiation (within 72 hours of development of granulocytopenia) and late initiation (over 72 hours). The primary outcomes of the study were bacterial infection and fungal infection, and the secondary outcomes were duration of absolute neutrophil count less than 1.0×109 cells/L, length of hospital stay, mortality rate, and rate of chemotherapy (4 cycles) completion. RESULTS: The incidence rates of bacterial infection and fungal infection were significantly lower among patients who received supplemental parenteral nutrition early than among patients who received it late. No significant difference in mortality was observed between the groups. In addition, compared with late supplemental parenteral nutrition, early supplemental parenteral nutrition was associated with a higher rate of completion of 4 chemotherapy cycles and shorter hospital stays and leukocyte recovery periods in our cohort. Univariate and multivariate logistic regression analyses revealed that the subgroup of patients with an NRS-2002 score of 2 benefited from early supplemental parenteral nutrition. CONCLUSIONS: Early supplemental parenteral nutrition after chemotherapy-induced severe granulocytopenia could reduce the risk of infection, improve the likelihood of chemotherapy completion, and shorten hospital stays and leukocyte recovery times.

Studies on the Bioactivities of ACE-inhibitory Peptides with Phenylalanine C-terminus Using 3D-QSAR, Molecular Docking and in vitro Evaluation.

3D-QSAR, molecular docking and activity evaluation were used to study the bioactivities of ACE-inhibitory peptides with phenylalanine C-terminus. Both CoMFA (Q2 =0.773, R2 =0.992) and CoMSIA (Q2 =0.664, R2 =0.990) models were constructed. According to the established models, four novel potent ACE-inhibitory tripeptides GEF, VEF, VRF, and VKF were synthesized. The IC50 values were respectively determined to be 13 µM, 23 µM, 5 µM, and 11 µM by in vitro evaluation. The results show good agreement with the predicted values. The established models play an important role in revealing the structure-activity relationship of ACE-inhibitory peptides and designing novel peptides with enhanced biological activity.

Phenylmethimazole and a thiazole derivative of phenylmethimazole inhibit IL-6 expression by triple negative breast cancer cells.

Inhibition of interleukin-6 (IL-6) holds significant promise as a therapeutic approach for triple negative breast cancer (TNBC). We previously reported that phenylmethimazole (C10) reduces IL-6 expression in several cancer cell lines. We have identified a more potent derivative of C10 termed COB-141. In the present work, we tested the hypothesis that C10 and COB-141 inhibit TNBC cell expressed IL-6 and investigated the potential for classical IL-6 pathway induced signaling within TNBC cells. A panel of TNBC cell lines (MDA-MB-231, Hs578T, MDA-MB-468) was used. Enzyme linked immunosorbent assays (ELISA) revealed that C10 and COB-141 inhibit MDA-MB-231 cell IL-6 secretion, with COB-141 being ~6.5 times more potent than C10. Therefore, the remainder of the study focused on COB-141 which inhibited IL-6 secretion, and was found, via quantitative real time polymerase chain reaction (QRT-PCR), to inhibit IL-6 mRNA in the TNBC panel. COB-141 had little, if any, effect on metabolic activity indicating that the IL-6 inhibition is not via a toxic effect. Flow cytometric analysis and QRT-PCR revealed that the TNBC cell lines do not express the IL-6 receptor (IL-6Rα). Trans-AM assays suggested that COB-141 exerts its inhibitory effect, at least in part, by reducing NF-κB (p65/p50) DNA binding. In summary, COB-141 is a potent inhibitor of TNBC cell expressed IL-6 and the inhibition does not appear to be due to non-specific toxicity. The TNBC cell lines do not have an intact classical IL-6 signaling pathway. COB-141's inhibitory effect may be due, at least in part, to reducing NF-κB (p65/p50) DNA binding.

Simple modifications to methimazole that enhance its inhibitory effect on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression by human endothelial cells.

The expression of vascular cell adhesion molecule-1 (VCAM-1) on the vascular endothelium can be increased by pro-inflammatory cytokines [e.g. tumor necrosis factor-α (TNF-α)]. VCAM-1 contributes to leukocyte adhesion to, and emigration from, the vasculature which is a key aspect of pathological inflammation. As such, a promising therapeutic approach for pathological inflammation is to inhibit the expression of VCAM-1. Methimazole [3-methyl-1, 3 imidazole-2 thione (MMI)] is routinely used for the treatment of Graves׳ disease and patients treated with MMI have decreased levels of circulating VCAM-1. In this study we used cultured human umbilical vein endothelial cells (HUVEC) to investigate the effect of MMI structural modifications on TNF-α induced VCAM-1 expression. We found that addition of a phenyl ring at the 4-nitrogen of MMI yields a compound that is significantly more potent than MMI at inhibiting 24h TNF-α-induced VCAM-1 protein expression. Addition of a para methoxy to the appended phenyl group increases the inhibition while substitution of a thiazole ring for an imidazole ring in the phenyl derivatives yields no clear difference in inhibition. Addition of the phenyl ring to MMI appears to increase toxicity as does substitution of a thiazole ring for an imidazole ring in the phenyl MMI derivatives. Each of the compounds reduced TNF-α-induced VCAM-1 mRNA expression and had a functional inhibitory effect, i.e. each inhibited monocytic cell adhesion to 24h TNF-α-activated HUVEC under fluid flow conditions. Combined, these studies provide important insights into the design of MMI-related anti-inflammatory compounds.

The potential toxic effects of cerium on organism: cerium prolonged the developmental time and induced the expression of Hsp70 and apoptosis in Drosophila melanogaster.

Due to the widespread application of cerium, a rare earth element, the risk of exposure to cerium has increased. Therefore, understanding the physiological effects of cerium is of great importance. Our previous work showed that cerium caused significant lifespan shortening accompanied by oxidative damage in Drosophila melanogaster, however, little is known about the detailed mechanism of cerium-induced cytotoxicity. Thus, we examined the developmental time during metamorphosis, and assessed the toxic effects of cerium by evaluating heat shock protein 70 (Hsp70), DNA damage markers and apoptosis in D. melanogaster. We found that cerium extended the developmental time of D. melanogaster and up-regulated the expression of Hsp70 when the concentration of cerium was increased (especially concentrations over 26.3 µg/g). Up-regulation of the cell cycle checkpoint p53 and cell signaling protein p38 were also observed when the concentration of cerium was over 104 µg/g. In addition, the activities of caspase-3 and caspase-9, markers of apoptosis, were significantly higher when the larvae were exposed to ceric sulfate. These results suggest that high concentrations of cerium may result in DNA damage and ultimately apoptosis in D. melanogaster, and strongly indicate that cerium should be applied with caution and the potential toxic effects in humans should also be taken into consideration.

Synthesis, structures and reactions of lithium complexes of [(o-RCHC6H4)PPh2=NSiMe3]-(R = H, SiMe3) ligands.

N-Trimethylsilyl o-methylphenyldiphenylphosphinimine, (o-MeC6H4)PPh2=NSiMe3 (1), was prepared by reaction of Ph2P(Br)=NSiMe3 with o-methylphenyllithium. Treatment of 1 with LiBun and then Me3SiCl afforded (o-Me3SiCH2C6H4)PPh2=NSiMe3 (2). Lithiations of both 1 and 2 with LiBu(n) in the presence of tmen gave crystalline lithium complexes [Li{CH(R)C6H4(PPh(2=NSiMe3)-.tmen](3, R = H; 4, R = SiMe3). From the mother liquor of 4, traces of the tmen-bridged complex [Li{CH(SiMe3)C6H4(PPh2=NSiMe3)-2}]2(mu-tmen) (5) were obtained. Reaction of 2 with LiBun in Et2O yielded complex [Li{CH(SiMe3)C6H4(PPh2=NSiMe3)-2}.OEt2] (6). Reaction of lithiated with Me2SiCl2 in a 2:1 molar ratio afforded dimethylsilyl-bridged compound Me2Si[CH2C6H4(PPh2=NSiMe3)-2]2 (7). Lithiation of 7 with two equivalents of LiBun in Et2O yielded [Li2{(CHC6H4(PPh2=NSiMe3)-2)2SiMe2}.0.5OEt2](8.0.5OEt2). Treatment of 4 with PhCN formed a lithium enamide complex [Li{N(SiMe3)C(Ph)CHC6H4(PPh2=NSiMe3)-2}.tmen] (9). Reaction of two equivalents of 5 with 1,4-dicyanobenzene gave a dilithium complex [{Li(OEt2)2}2(1,4-{C(N(SiMe3)CHC6H4(PPh2=NSiMe3)-2}2C6H4)] (10). All compounds were characterised by NMR spectroscopy and elemental analyses. The structures of compounds 2, 3, 5, 6 and 9 have been determined by single crystal X-ray diffraction techniques.