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This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA., (© 2024 John Wiley & Sons Ltd.)

Background: Lung adenocarcinoma is one of the leading causes of cancer-related deaths because of the lack of early specific clinical indicators. MicroRNAs (miRNAs) have become the focus in lung cancer diagnosis. Further studies are required to explore miRNA expression in the serum of lung adenocarcinoma patients and their correlation with therapy and analyse specific messenger RNA targets to improve the specificity and sensitivity of early diagnosis., Methods: The Toray 3D-Gene miRNA array was used to compare the expression levels of various miRNAs in the sera of patients with lung adenocarcinoma and healthy volunteers. Highly expressed miRNAs were selected for further analysis. To verify the screening results, serum and pleural fluid samples were analysed using qRT-PCR. Serum levels of the miRNAs and their correlation with the clinical information of patients with lung adenocarcinoma were analysed. The functions of miRNAs were further analysed using the Kyoto Encyclopedia of Gene and Genomes and Gene Ontology databases., Results: Microarray analysis identified 60 and 50 miRNAs with upregulated and downregulated expressions, respectively, in the serum of patients with lung adenocarcinoma compared to those in healthy individuals. Using qRT-qPCR to detection of miRNAs expression in the serum or pleural effusion of patients with early and advanced lung adenocarcinoma, we found that miR-4433a-3p could be used as a diagnostic marker and therapeutic evaluation indicator for lung adenocarcinoma. Serum of miR-4433a-3p levels significantly correlated with the clinical stage. miR-4433a-3p may be more suitable than other tumour markers for the early diagnosis and evaluation of therapeutic effects in lung adenocarcinoma. miR-4433a-3p may affect tumour growth and metastasis by acting on target genes ( PIK3CD, UBE2J2, ICMT, PRDM16 and others) and regulating tumour-related signalling pathways (MAPK signal pathway, Ras signalling pathway and others)., Conclusion: miR-4433a-3p may serve as a biomarker for the early diagnosis of lung adenocarcinoma and monitoring of therapeutic effects., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zhongxiang Liu reports financial support was provided by the Elderly Health Research Project of 10.13039/501100002949Jiangsu Province. Zhongxiang Liu has patent pending to Guan Sun. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Cancer cell resistance presents a significant clinical challenge. The mechanisms underlying drug resistance in cancer cells are intricate and remain incompletely understood. Notably, tumor cell resistance often coincides with the epithelial-mesenchymal transition (EMT). In this study, we observed an elevation in autophagy levels following the development of drug resistance in oesophageal cancer cells. Inhibition of autophagy led to a reduction in drug-resistant cell migration and the inhibition of EMT. Furthermore, we identified an upregulation of SIRT1 expression in drug-resistant oesophageal cancer cells. Subsequent inhibition of SIRT1 expression in drug-resistant cells resulted in the suppression of autophagy levels, migration ability, and the EMT process. Our additional investigations revealed that a SIRT1 inhibitor effectively curbed tumor growth in human oesophageal cancer xenograft model mice (TE-1, TE-1/PTX) without evident toxic effects. This mechanism appears to be associated with the autophagy levels within the tumor tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored., Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP., Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis., Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration., Competing Interests: The authors declare that they have no competing interests to declare in this work., (© 2024 Liu et al.)

Background: Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. However, the underlying molecular mechanism of anlotinib mediates cisplatin (DDP) resistance in NSCLC remains unclear., Methods: Cell viability was assessed by the cell counting kit 8 assay. Cell proliferation, migration, and invasion were determined using the colony formation assay and transwell assay. The mRNA expression levels of mesenchymal-epithelial transition factor (MET) and myeloid cell leukemia-1 (MCL-1) were measured by quantitative real-time PCR. Protein expression levels of MET, MCL-1, and STAT3/Akt pathway-related markers were examined using western blot analysis., Results: Our data showed that anlotinib inhibited the DDP resistance of NSCLC cells by regulating cell proliferation and metastasis. Moreover, MET and MCL-1 expression could be decreased by anlotinib treatment. Silencing of MET suppressed the activity of the STAT3/Akt pathway and MCL-1 expression. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway)., Conclusion: Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Lile Wang et al.)

With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a common problem in the clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients. BALF was obtained, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. We found that FGF14 was the binding target of miR-1246b by luciferase assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further leading to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion., (© 2023. The Author(s).)

The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2'-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu 2+ based on enol-keto excited-state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calculations to investigate the detailed primary photodynamics of the BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of the HBI halves with a time constant of 300 fs; after that, the rotation of the dihedral angle between the two HBI halves generated a planarized BBM-keto* isomer in 3 ps, leading to a dynamic redshift of BBM-keto* emission.

The reliable predictive markers to identify which patients with advanced non-small cell lung cancer tumors (NSCLC) will achieve durable clinical benefit (DCB) for chemo-immunotherapy are needed. In this retrospective study, we collected radiomics and clinical signatures from 94 patients with advanced NSCLC treated with anti-PD-1/PD-L1 combined with chemotherapy from January 1, 2018 to May 31, 2022. Radiomics variables were extracted from pretreatment CT and selected by Spearman correlation coefficients and clinical features by Logistics regression analysis. We performed effective diagnostic algorithms principal components analysis (PCA) and support vector machine (SVM) to develop an early classification model among DCB and non-durable benefit (NDB) groups. A total of 26 radiomics features and 6 clinical features were selected, and then principal component analysis was used to obtain 6 principal components for SVM building. RC-SVM achieved prediction accuracy with AUC of 0.91 (95% CI 0.87-0.94) in the training set, 0.73 (95% CI 0.61-0.85) in the cross-validation set, 0.84 (95% CI 0.80-0.89) in the external validation set. The new method of RC-SVM model based on radiomics-clinical signatures provides a significant additive value on response prediction in patients with NSCLC preceding chemo-immunotherapy., (© 2023. The Author(s).)

Seminaphthorhodafluor (SNARF) Schiff base (SNARF-SB) bridged periodic mesoporous organosilicas (SSPMOs) with "turn-on" fluorescence enhancement for sensing Cu 2+ were synthesized via a template-directed co-condensation method. Small-angle x-ray scattering (SAXS) patterns, high resolution transmission electron microscope (HRTEM) images, and N 2 adsorption-desorption isotherms indicated the presence of mesoporous structure in the SSPMOs. FT-IR spectra and 29 Si MAS NMR data confirmed the successful incorporation of bridged organic groups in the framework of SSPMOs. The luminous properties that SSPMOs had a selective response to Cu 2+ were investigated by UV-Vis absorption spectroscopy and fluorescence spectroscopy. The limit of detection (LOD) was 5.1 × 10 -7  M and binding stoichiometry was determined 1:1 between SNARF-SB and Cu 2+ . The fluorescence enhancement of SSPMOs towards Cu 2+ was induced by ring-opening of the spirolactam in SNARF-SB in framework of SSPMOs, which was confirmed by FT-IR spectra of SNARF-SB with Cu 2+ . Moreover, SSPMOs have improved fluorescence lifetimes compared with that of SNARF-SB. Therefore, SSPMOs can be a progressive chemical sensor for Cu 2+ due to its high selectivity, recyclability, and stability., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The optimal systemic treatment of advanced large cell neuroendocrine carcinoma (LCNEC) is still controversial. We intend to explore advanced LCNEC through SEER database, construct nomogram model of advanced LCNEC, and understand the effect of different treatment regimens on LCNEC. We collected 909 patients, divided them into a training set validation set, constructed nomograms using Cox proportional hazards regression models, and evaluated nomogram discrimination and calibration by C-index and calibration curves. Kaplan-Meier will also be used to compare OS in different groups of patients and to explore the impact of different treatment regimens on advanced LCNEC. On the nomogram plotted, the nomogram predicted AUC values over time were always greater than 0.7, the C-index was 0.681 (95% CI 0.656-0.706) and 0.663 (95% CI 0.628-0.698) in the training and validation sets, respectively, and patients were divided into two groups according to risk, and a significant difference in OS was observed between the high-risk and low-risk groups in the training and validation cohorts. Different treatment analyses showed that chemotherapy is still the best treatment for advanced LCNEC. This nomogram provides a convenient and reliable tool for individual assessment and clinical decision-making of patients with advanced LCNEC., (© 2022. The Author(s).)

A novel type of organic-inorganic hybrid periodic mesoporous materials based on 1,8-dihydroxyanthraquinone (DHAQ-PMOs) was synthesized in a ternary deep eutectic solvent (DES). In the process of the material synthesis, an organosiloxane precursor (DHAQ-Si) and tetraethylorthosilicate (TEOS) were used as the mixed Si source, and cetyltrimethylammonium bromide (CTAB) was used as the structure directing agent. The DES formed by choline chloride (ChCl), urea (U), and ethylene glycol (EG) was used as a green solvent. The water needed for the hydrolysis of DHAQ-Si and TEOS was provided from free water in the sodium hydroxide solution. As characterized by small-angle X-ray scattering, nitrogen adsorption/desorption isotherms, and high-resolution transmission electron microscopy, the obtained mesoporous materials exhibit a two-dimensional hexagonal ( P 6 mm ) structure. DHAQ possesses double fluorescence emission peaks at ca. 520 and 580 nm due to the effect of the excited-state intramolecular proton transfer (ESIPT). For DHAQ-PMOs, the silica framework can provide a rigid environment that makes the fluorescence properties more stable and the fluorescence emission peak appears to red-shift obviously. The DHAQ-PMOs have high selectivity and sensitivity in a wide pH range that can be used to detect Cu 2+ , and the limit of detection (LOD) is as low as 2.39 × 10 -9 M. Fluorescence polarization experiments, high-resolution mass spectrometry, and Fourier transform infrared spectroscopy were used to study the coordination interaction between DHAQ and Cu 2+ . The density functional theory (DFT) was used to further prove the coordination ability and interaction between DHAQ and Cu 2+ . XPS spectra were also done to prove the coordination of DHAQ and DHAQ-PMO-10 with Cu 2+ . In addition, confocal fluorescence microscope images exhibit that DHAQ-PMOs can detect Cu 2+ in living cells. The results show that DHAQ-PMOs have great application potential as a sensor for the detection of Cu 2+ ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans' Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery., Clinical Trial Registration Number: ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370., Competing Interests: Authors XY and JZ are employees of Zhuhai Sanmed Biotech Ltd. RK is a consultant of Sanmed Biotech Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Tong, Zheng, Wang, Zhou, Zhu, Zhou, Zhao, Wang, Wang, Bai, Cai, Kong, Wang, Li, Feng, Ye, Yang, Liu, Zhang, Wang, Han, Sun, Zhao, Yu, Zhang, Zhang, Katz, Sun and Bai.)

Interactions between metals and oxide supports are crucial in determining catalytic activity, selectivity, and stability. For reducible oxide supported noble metals, a strong metal-support interaction (SMSI) has been widely recognized. Herein we report the intermediate selectivity and stability over an irreducible SiO 2 supported Pt catalyst in the hydrogenation of anthracene that are significantly boosted due to the SMSI-induced formation of intermetallic Pt silicide and Pt-SiO 2 interface. The limitation in the strong interaction between Pt nanoparticles and irreducible SiO 2 has been breached by combining the strong electrostatic adsorption method and following the high temperature reduction strategy. Due to the isolated Pt active sites by Si atoms, the activated H species produced over the Pt 2 Si/SiO 2 catalyst with an initial catalytic activity of 2.49 μmol/(m 2 /g)/h as well as TOF of 0.95 s -1 preferentially transfer to the outer ring of anthracene to 87% yield of symmetric octahydroanthracene ( sym -OHA) by subsequent hydrogenation. In addition, the Pt 2 Si/SiO 2 catalyst presents an excellent stability after five cycles, which can be attributed to the fact that intermetallic Pt 2 Si nanoparticles are anchored firmly onto the surface of the SiO 2 support. The discovery contributes to broaden the horizons on the SMSI effect in the irreducible oxide supported metal particle catalysts and provides guidance to design the metal-SiO 2 interface and tune the surface chemical properties in diverse application conditions.

Cancer drug resistance is a formidable obstacle that enhances cancer stem-like cell properties, tumour metastasis and relapse. Luteolin (Lut) is a natural flavonoid with strong antitumor effects. However, the underlying mechanism(s) by which Lut protects against paclitaxel-resistant (PTX-resistant) cancer cell remains unknown. Herein, we found that Lut significantly attenuated the stem-like properties of PTX-resistant cancer cells by downregulating the expression of SOX2 protein. Additionally, further study showed that Lut could inhibit the PI3K/AKT pathway to decrease the phosphorylation level of AKT(S473) and UBR5 expression, which is an ubiquitin E3 ligase that promotes SOX2 degradation. In addition, Lut also inhibited PTX-resistant cancer cell migration and invasion by blocking epithelial-mesenchymal transition (EMT). Importantly, Lut inhibited the tumorigenic ability of oesophageal PTX-resistant cancer cells and showed no obvious toxicity in vivo. Thus, Lut has potential as a promising agent for drug-resistant oesophageal cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway., (© 2021 John Wiley & Sons, Ltd.)

Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases., (© 2021 John Wiley & Sons Ltd.)

Background: Bispecific T cell engaging antibodies (TEAs) with one arm targeting a cancer antigen and another arm binding to CD3 have demonstrated impressive efficacy in multiple clinical studies. However, establishing a safety/efficacy balance remains challenging. For instance, some TEAs have severe safety issues. Additionally, not all patients or all cancer cells of one patient respond equally to TEAs., Methods: Here, we developed a next-generation bispecific TEA with better safety/efficacy balance and expanded mechanisms of action. Using the computer-aided antibody design strategy, we replaced heavy chain complementarity-determining regions (HCDRs) in one Rituximab arm with HCDRs from a CD3 antibody and generated a novel CD20/CD3 bispecific antibody., Results: After series of computer-aided sequence optimization, the lead molecule, GB261, showed great safety/efficacy balance both in vitro and in animal studies. GB261 exhibited high affinity to CD20 and ultra-low affinity to CD3. It showed comparable T cell activation and reduced cytokine secretion compared with a benchmark antibody (BM). ADCC and CDC caused by GB261 only killed CD20+ cells but not CD3+ cells. It exhibited better RRCL cell killing than the BM in a PBMC-engrafted, therapeutic treatment mouse model and good safety in cynomolgus monkeys., Conclusions: Thus, GB261 is a promising novel TEA against CD20+ cancers., (© The Author(s) 2021. Published by Oxford University Press on behalf of Antibody Therapeutics.)

The improvement of a plant's tolerance to drought is a major endeavor in agriculture. Polyploid plants often exhibit enhanced stress tolerance relative to their diploid progenitor, but the matching stress tolerance is still little understood. Own-rooted stem cuttings of mulberry (Morus alba L.) cultivar Shinichinose (2n = 2x = 28) and Shaansang-305 (2n = 3x = 42) were used in this study, of which the latter (triploid) has more production and application purposes. The responses of triploid Shaansang-305 and diploid progenitor ShinIchinose under drought stress were compared through an investigation of their physiological traits, RNA-seq, and secondary metabolome analysis. The results showed that the triploid exhibited an augmented abscisic acid (ABA) content and a better stress tolerance phenotype under severe drought stress. Further, in the triploid plant some genes ( TSPO, NCED3 , and LOC21398866 ) and ATG gene related to ABA signaling showed significantly upregulated expression. Interestingly, the triploid accumulated higher levels of RWC and SOD activity, as well as more wax on the leaf surface, but with less reductive flavonoid than in diploid . Our results suggest triploid plants may better adapt to with drought events. Furthermore, the flavonoid metabolism involved in drought resistance identified here may be of great value to medicinal usage of mulberry. The findings presented here could have substantial implications for future studies of crop breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Sun, Bao, Han, Hui, Zhang, Zhang, Su, Qian and Jiao.)

Hypoxia-inducible factor-1α (HIF-1α) has been implicated in the regulation of many genes responsible for aerobic glycolysis; however, the role of HIF-1α in B-cell metabolism has not been well defined. Here, we analyzed patterns of gene expression and oxygen consumption rates in B-cell subpopulations from humans and mice and described a model of HIF-1α-mediated B-cell metabolic reprogramming during the germinal center (GC) reaction. Importantly, we found that HIF-1α was highly expressed in GC B-cells, and HIF-1α deficiency in B-cells impaired a functional GC reaction, resulting in defective class-switch recombination and generation of high-affinity plasma cells. These results identified an important role of HIF-1α in regulating humoral immunity through metabolic reprogramming during the GC response. This newly discovered metabolic character of GC B-cells will advance our understanding of GC biology and B-cell lymphomagenesis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC)., Methods: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127)., Results: Between December 15 th , 2017, and May 15 th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25 th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15 th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups., Conclusions: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Although the phenomenon that omega-3 polyunsaturated fatty acids (n-3 PUFAs) shows to have a beneficial effect in patients suffering from multiple sclerosis (MS) and other autoimmune diseases has been empirically well-documented, the molecular mechanisms that underline the anti-inflammatory effects of n-3 PUFAs are yet to be understood. In experimental autoimmune encephalomyelitis (EAE), a model for MS, we show that one of the underlying mechanisms by which dietary docosahexaenoic acid (DHA) exerts its anti-inflammatory effect is regulating the functional activities of dendritic cells (DCs). In DHA-treated EAE mice, DCs acquire a regulatory phenotype characterized by low expression of co-stimulatory molecules, decreased production of pro-inflammatory cytokines, and enhanced capability of regulatory T-cell induction. The effect of DHA on DCs is mediated by the lipid-sensing receptor, G protein-coupled receptor 120 (GPR120). A GPR120-specific small-molecule agonist could ameliorate the autoimmune inflammation by regulating DCs, while silencing GPR120 in DCs strongly increased the immunogenicity of DCs. Stimulation of GPR120 induces suppressor of cytokine signaling 3 (SOCS3) expression and down-regulates signal transducer and activator of transcription 3 (STAT3) phosphorylation, explaining the molecular mechanism for regulatory DC induction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo . Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, He, Li, Wang, Han, Zhao, Dong, Ahmad, Li, Zhang, Huo, Liu, Pan and Wang.)

Macrophage polarization is a dynamic and integral process in tissue inflammation and remodeling. In this study, we describe that lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) plays an important role in controlling inflammatory macrophage (M1) polarization in rodent experimental autoimmune encephalomyelitis (EAE) and in monocytes from multiple sclerosis (MS) patients. Specific inhibition of Lp-PLA 2 led to an ameliorated EAE via markedly decreased inflammatory and demyelinating property of M1. The effects of Lp-PLA 2 on M1 function were mediated by lysophosphatidylcholine, a bioactive product of oxidized lipids hydrolyzed by Lp-PLA 2 through JAK2-independent activation of STAT5 and upregulation of IRF5. This process was directed by the G2A receptor, which was only found in differentiated M1 or monocytes from MS patients. M1 polarization could be inhibited by a G2A neutralizing Ab, which led to an inhibited disease in rat EAE. In addition, G2A-deficient rats showed an ameliorated EAE and an inhibited autoimmune response. This study has revealed a mechanism by which lipid metabolites control macrophage activation and function, modification of which could lead to a new therapeutic approach for MS and other inflammatory disorders., (Copyright © 2021 by The American Association of Immunologists, Inc.)

A new organosiloxane precursor ((E)-3-hydroxy-4-((2-(2-hydroxy-4-(3-(3-(triethoxysilyl)propyl)ureido)benzoyl)hydrazono)methyl)phenyl(3-(triethoxysilyl)propyl)carbamate, hereinafter referred to as AHBH-Si) and tetraethylorthosilicate (TEOS) were mixed as the mixed Si source, and bridged periodic mesoporous organic silica (AHBH-PMOs) nanoparticles were obtained through the co-condensation reaction. AHBH-PMO nanoparticles possess mechanisms of "Aggregation Induced Emission" (AIE) and "Intramolecular Charge Transfer" (ICT), which originate from the molecular structure of AHBH having "C[double bond, length as m-dash]N" bond, ortho hydroxyl groups, etc.. Therefore, the optical properties of AHBH are excellent with respect to the solvent effect and enhanced fluorescence. For hybrid materials, the silica framework provides a rigid environment that restricts the rotation of AHBH, thereby turning on the fluorescence of AHBH due to the regulation by the AIE effect. In particular, AHBH-PMOs are no longer restricted by organic solvents and could really achieve the response to Cu2+ with high sensitivity and selectivity in aqueous solutions of a wide pH range. In addition, the detection limit is as low as 3.26 × 10-9 M. Methods such as Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry have shown the coordination interaction between AHBH and Cu2+. The Gaussian 09 software of density functional theory to calculate the reducing changes of energy gaps among AHBH and AHBH-Si before and after the addition of Cu2+ showed that coordination interaction exists in the system. These results indicate that AHBH-PMO hybrid materials have potential applications in the field of environmental monitoring.

Background: Lung cancer is a leading cause of cancer-related mortality worldwide. The purpose of our meta-analysis was to assess the risk factors for brain metastases (BM) in patients with non-small cell lung cancer (NSCLC)., Methods: Multiple databases, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang, were systematically searched to recruit relevant studies investigating the risk factors for BM in NSCLC patients. The Newcastle-Ottawa Scale was used to evaluate literature quality, and the meta-analysis was performed using the Review Manager 5.3. Evidence quality evaluation was carried out according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) standard. The estimated odds ratio (OR) and 95% confidence intervals (CIs) were set as effect measures. Funnel plots and sensitivity analyses were used to assess publication bias and the robustness and reliability of the combined results, respectively., Results: A total of 43 studies with 11,415 participants were included in this meta-analysis. The results indicated that the following factors were significantly associated with an increased risk of BM in NSCLC patients (P<0.05): (I) gender (female) (OR =1.32, 95% CI: 1.17-1.49, P<0.00001); (II) adenocarcinoma (OR =2.34, 95% CI: 1.76-3.11, P<0.00001) or non-squamous cell carcinoma (OR =0.63, 95% CI: 0.42-0.94, P=0.02); (III) advanced tumor stage (OR =1.48, 95% CI: 1.01-2.17, P=0.04); (IV) node stage (OR =2.19, 95% CI: 1.39-3.45, P=0.0007); (V) lymphatic metastasis (OR =2.43, 95% CI: 1.76-3.36, P<0.00001); (VI) epidermal growth factor receptor (EGFR) gene mutation (OR =1.88, 95% CI: 1.26-2.80, P=0.002); (VII) kirsten rat sarcoma viral oncogene (KRAS) gene mutation (OR =2.99, 95% CI: 1.82-4.91, P<0.00001); (VIII) higher levels of carcinoembryonic antigen (P<0.00001), carbohydrate antigen 199 (P<0.0001), cytokeratin-19 fragment (P=0.04), neuron-specific enolase (P<0.00001), and carbohydrate antigen 125 (P=0.0005)., Conclusions: This meta-analysis demonstrated that NSCLC patients with BM have more aggressive clinical features.

Introduction: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC)., Materials and Methods: First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI., Results: In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest., Discussion: Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Sha et al.)

Mulberry (Morus spp.) is the sole plant consumed by the domesticated silkworm. However, the genome of domesticated mulberry has not yet been sequenced, and the ploidy level of this species remains unclear. Here, we report a high-quality, chromosome-level domesticated mulberry (Morus alba) genome. Analysis of genomic data and karyotype analyses confirmed that M. alba is a diploid with 28 chromosomes (2n = 2x = 28). Population genomic analysis based on resequencing of 134 mulberry accessions classified domesticated mulberry into three geographical groups, namely, Taihu Basin of southeastern China (Hu mulberry), northern and southwestern China, and Japan. Hu mulberry had the lowest nucleotide diversity among these accessions and demonstrated obvious signatures of selection associated with environmental adaptation. Further phylogenetic analysis supports a previous proposal that multiple domesticated mulberry accessions previously classified as different species actually belong to one species. This study expands our understanding of genome evolution of the genus Morus and population structure of domesticated mulberry, which would facilitate mulberry breeding and improvement., (Copyright © 2020 The Author. Published by Elsevier Inc. All rights reserved.)

Objective: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation-iron quantification (IDEAL-IQ) is a noninvasive and objective method used to quantitatively measure fat content. Although this technique has been used in the entire abdomen, IDEAL-IQ findings in the sacroiliac joint (SIJ) have rarely been reported. This preclinical study was performed to quantify the amount of fat in the SIJ in healthy volunteers by IDEAL-IQ., Methods: From April to November 2017, 60 healthy volunteers with low back pain were included in this retrospective study. The participants were allocated into groups by age (15-30, 31-50, and ≥51 years), sex (male and female), and body mass index (BMI) (<18.5, 18.5-23.9, and ≥24.0 kg/m 2 ). The iliac-side (Fi) and sacral-side (Fs) fat fractions were obtained in all groups. Two- and three-factor multivariate analyses were performed to analyze the effects of sex, age, and BMI on the Fi and Fs., Results: The interaction among sex, age, and BMI had no statistically significant effect on the dependent variable. Both Fi and Fs were significantly influenced by age. Fs was significantly influenced by sex., Conclusion: The IDEAL-IQ sequence can be used to quantitatively assess the SIJ fat content in healthy volunteers.

Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Although much research has focused on its regulation and function of GC B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that EAE is exacerbated in LysM Cre +/ - Bcl6 fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4 + Th17 cell response. In addition, LPS-induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the interleukin-6 (Il-6) promoter in macrophages, leading to a suppressed transcription of Il-6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il-6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The identification and lead optimization of a series of pyrazolo[3,4- d ]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8 . Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model., Competing Interests: The authors declare no competing financial interest.

The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer., Competing Interests: The authors declare no conflicts of interest in this work., (© 2019 Cao et al.)

Background: Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients., Methods: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg's test, Egger's test, and the funnel plot were applied to assess the significance of publication bias., Results: In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5-37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41-1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all)., Conclusions: These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer patients.

Chemotherapy is an effective method to treat patients with advanced malignant tumors. However, tumor cells can develop resistance to multiple drugs during the therapy process, leading to treatment failure. Circular RNAs (circRNAs) are a new class of regulatory RNAs that can regulate endogenous gene expression. Previous studies revealed the diagnostic and prognostic value of circRNAs in malignant cancer and other diseases, but few reports have examined their association with clinical drug resistance. In this review, we summarize the up-to-date information regarding the role of circRNAs in the resistance of tumors to chemotherapy and discuss specific regulatory mechanisms. This analysis is expected to provide direction for the prevention and management of drug resistance in tumors., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Delta-like protein 3 (DLL3) has been reported as a biomarker in various human tumors. However, the biological function and mechanism of it in advanced small cell lung cancer (SCLC) is rarely reported. This study was devised innovatively to explore the role of DLL3 in the progression of SCLC. Immunohistochemistry (IHC) analysis was used to examine DLL3 expression in paraffin-embedded SCLC tumor samples. Upregulation of DLL3 reduced chemotherapy sensitivity. Kaplan-Meier analysis was used to analyze the progression-free survival or overall survival of SCLC patients with high or low level of DLL3. The negative association between DLL3 expression and the PFS or OS rate of SCLC patients was identified. Relative high level of DLL3 was determined in SCLC cell lines by using qRT-PCR analysis. Loss-of function assays were performed to detect the biological functions of the silencing of DLL3 in SCLC. As a result, silencing of DLL3 led to the proliferative and migratory inhibition of SCLC cells and reversed EMT process. Mechanistically, DLL3 mRNA was stabilized by the RNA-binding protein lin-28 homolog B (LIN28B). Further mechanism investigation revealed that LIN28B and DLL3 are two downstream targets of miR-518d-5p. Finally, rescue assays demonstrated that LIN28B and miR-518d-5p could regulate DLL3-mediated cell proliferation and migration. Collectively, our present study revealed a novel molecular pathway in SCLC, which providing a new insight in exploring the therapeutic strategy for SCLC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A novel bis-benzimidazole organic siloxane precursor (BBM-Si) was prepared, and was combined with tetraethylorthosilicate (TEOS) as a mixed Si source. Then, bridged periodic mesoporous organosilica (BBM-PMO) spherical nanoparticles were synthesized by co-condensation using cetyltrimethylammonium bromide (CTAB) as structure directing agent. The optical properties showed that BBM qualifies as an "aggregation induced emission enhanced" (AIEE) molecule, exhibiting characteristics of excited-state intramolecular proton transfer (ESIPT), such as a large Stokes shift and dual fluorescence emission. For the BBM-PMO materials, the silica skeleton provides a rigid environment that limits molecular rotation, resulting in improved fluorescence emission. In particular, the BBM-PMOs exhibited dual emission of the enol and keto forms, achieving a ratiometric response to Cu 2+ with high sensitivity and selectivity in a broad pH range. Additionally, the limit of detection was as low as 7.15 × 10 -9 M in aqueous solution. The X-ray absorption near-edge spectroscopy (XANES) showed the coordination structure through the interaction between copper ions and N atoms of benzimidazole in the BBM-PMO coordinated to Cu 2+ . These results demonstrate that BBM-PMO hybrid materials have potential applications in the fields of bio-imaging and environmental monitoring., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Circular RNA (circRNA), as a covalently closed circular RNA molecule, is widely present, which is recognized as a competing endogenous RNA. A large number of differentially expressed circRNAs have been identified and are recognized as potential biomarkers for the diagnosis of tumors., Main Body: CircRNAs play an important role in the regulation of cell signaling pathways. The main biological functions of circRNAs include acting as miRNA sponges, regulating the transcription of the parental genes, and acting as adapters to regulate the interactions between proteins and encoding proteins. Compared with normal tissues, there are differentially expressed circRNAs in lung cancer tissue, and the expression levels of circRNAs are correlated with clinicopathological features of lung cancer. Their roles in pathway regulation are described, and the diagnostic and prognostic values are further evaluated., Conclusion: In lung cancer, circRNAs participate in the proliferation, migration, and invasion, acting as a competitive endogenous RNA. Differentially expressed circRNAs may serve as non-invasive diagnostic markers for lung cancers. Further investigation of the roles of circRNAs in the pathogenesis and regulatory pathways is conducive to the development of novel approaches for the diagnosis and accurate treatment of lung cancers.

Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibody-nanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) (trastuzumab/nab‑paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab‑paclitaxel by a 'one-step' synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI‑N87 cells and compared with paclitaxel (Taxol®), nab‑paclitaxel and trastuzumab/nab‑paclitaxel. In addition, GC xenograft models were established to evaluate antitumor efficacy in vivo. These results demonstrated that trastuzumab/nab‑paclitaxel was spherical with a suitable size (139.18±32.06 nm). The half-maximal inhibitory concentration (IC50) for NCI‑N87 cells was 0.24±0.08, 0.13±0.03 and 0.048±0.01 µg/ml of paclitaxel, nab‑paclitaxel and trastuzumab/nab‑paclitaxel, respectively. Compared with paclitaxel and nab‑paclitaxel, trastuzumab/nab‑paclitaxel could induce a higher rate of apoptosis and significant G2/M arrest. At 4 weeks after treatment, tumor-bearing mice had a mean tumor volume of 233±24 mm3 treated by trastuzumab/nab‑paclitaxel, 559±97 mm3 by nab‑paclitaxel, 871±94 mm3 by paclitaxel and 1,576±190 mm3 by PBS as control, respectively, which showed that trastuzumab/nab‑paclitaxel could surpass nab‑paclitaxel and paclitaxel in antitumor effect. Furthermore, the NIR imaging indicated that trastuzumab/nab‑paclitaxel labeled by NIR-797 could more precisely focus on tumor regions. In conclusion, trastuzumab/nab‑paclitaxel could mediate targeted therapy and enhance antitumor efficacy, which could represent a novel therapeutic agent for HER2‑positive GC.

Recent reports have indicated that circular RNA (circRNA) may regulate Lung adenocarcinoma (LAC) development. Our previous studies showed that hsa&#95;circ&#95;0012673 was up-regulated in a circRNA microarray. However, its expression level in LAC has not been verified, and the underlying molecular mechanisms in LAC are unknown. In this study, we found that the expression of hsa&#95;circ&#95;0012673 was up-regulated in LAC tissues compared to pair-matched adjacent non-tumor tissues (P = 0.0079), and that the expression level was associated with tumour size (P = 0.015). Furthermore, hsa&#95;circ&#95;0012673 was primarily localized in the cytoplasm and promoted cell proliferation of LAC cells by sponging miR-22, which targeted erb-b2 receptor tyrosine kinase 3 (ErbB3) in LAC. Hsa&#95;circ&#95;0012673 promotes LAC proliferation by suppressing miR-22, which targets ErbB3., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND The aim of this study was to evaluate the therapeutic effects of tiotropium bromide on asthma. MATERIAL AND METHODS A total of 160 patients with moderate persistent asthma were randomly divided into 4 groups (n=40): the 3 control groups were given fluticasone propionate aerosol (group A), salmeterol-fluticasone propionate inhalant (group B), and tiotropium bromide inhalation powder combined with salmeterol-fluticasone propionate inhalant (group C), respectively, and the experimental group received tiotropium bromide inhalation powder combined with fluticasone propionate aerosol (group D) and salbutamol was used to relieve symptoms when necessary. RESULTS After 8 weeks of treatment, the pulmonary function of group D, which was significantly better than those of group A (P<0.05), was similar to those of groups B and C (P>0.05). Group D had significantly better asthma control test scores and nighttime symptom scores than in group A (P<0.05), without significant differences from those of group B or group C (P>0.05). The number of times salbutamol was used to alleviate symptoms was significantly different (P<0.05) between group D and group A (P<0.05), as well as between group C and group D (P<0.05). Groups D and B had similar results (P>0.05). IL-13 levels in induced sputum had significant differences (P<0.05). The levels in group D, which were higher than those of groups A and B (P<0.05), were similar to those of group C (P>0.05). CONCLUSIONS Tiotropium bromide combined with fluticasone propionate improved the respiratory function and quality of life, and is a new therapy for moderate, persistent asthma.

A novel chemosensor TrisRh based on tris(2-aminoethyl)amine and rhodamine 6G is designed and synthesized as a fluorescence turn-on probe for Co 2+ ions that is paramagnetic with a property of quenching fluorescence. Rhodamine spirolactam forms are nonfluorescent, whereas, ring-opening of corresponding spirocyclic induced by Co 2+ results in strong fluorescence emission. Upon the addition of Co 2+ ions, TrisRh can display significant enhancements in absorbance and fluorescence intensity as well as evident colorific transformation, which can be perceived by the naked eye. The association stoichiometry of TrisRh to Co 2+ ions was inferred to be 1:1 through Job's plot and electrospray ionization mass spectrometry analysis. The binding model was speculated from Fourier transform infrared spectra and 1 H-nuclear magnetic resonance technologies. Significantly, the limit of detection was determined to be as low as 1.22 nmol. Furthermore, TrisRh can exhibit robust anti-jamming ability against other interference metal ions., (Copyright © 2017 John Wiley & Sons, Ltd.)

Circular RNAs (circRNAs) are associated with cancer progression and metastasis, although little is known about their role in lung adenocarcinoma (LAC). In the present study, microarrays were first used to screen for tumour-specific circRNA candidates in LAC tissue. Thirty-nine circRNAs were found to be up-regulated and 20 were down-regulated (fold change > 2.0). Among them, hsa&#95;circ&#95;0013958 was further confirmed to be up-regulated in all of the LAC tissues, cells and plasma. In addition, hsa&#95;circ&#95;0013958 levels were associated with TNM stage (P = 0.009) and lymphatic metastasis (P = 0.006). The area under the receiver operating characteristic curve was 0.815 (95% confidence interval = 0.727-0.903; P < 0.001). In addition, to further illustrate the bioactivities of hsa&#95;circ&#95;0013958 in LAC, siRNA-mediated inhibition of hsa&#95;circ&#95;0013958 was performed in vitro. The results showed that hsa&#95;circ&#95;0013958 promoted cell proliferation and invasion and inhibited cell apoptosis in LAC. Moreover, hsa&#95;circ&#95;0013958 was identified as a sponge of miR-134, and thus it up-regulated oncogenic cyclin D1, which plays a pivotal role in the development of non-small cell lung cancer. In conclusion, our results suggested that hsa&#95;circ&#95;0013958 could be used as a potential non-invasive biomarker for the early detection and screening of LAC., (© 2017 Federation of European Biochemical Societies.)

Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI 131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI 131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI 131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI 131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI 131 and GA intervention. NaI 131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI 131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

Diacetylene-bridged periodic mesoporous organosilicas (DAPMOs) with aggregates were synthesized and characterized. The DAPMO-based donor-acceptor charge-transfer (CT) system was prepared under ambient conditions, in which the diacetylenic groups in the pore walls were the electron donors and the decylviologen molecules acted as electron acceptors in the pore channels. The UV/Vis diffuse reflectance spectra and soft X-ray absorption near-edge structure (XANES) spectroscopy showed the formation of the CT complex. Importantly, energy transfer from the diacetylene aggregates to the CT complex occurred upon excitation at 330 nm, which was demonstrated by the fluorescence spectra of the CT systems. This design of hybrid organic-inorganic materials based on PMOs is promising to construct effective electron and energy transfer systems to fabricate optoelectronic materials., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cisplatin (DDP) has been one of the most widely used chemotherapy drugs for advanced non-small cell lung cancer. However, the increase in the number of DDP-resistant cancer cells has become a major impediment in the clinical management of cancer. In the present study, for the first time, the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay was used to demonstrate that nedaplatin (NDP) could have a stronger inhibitory effect than DDP alone in DDP-resistant A549 (A549DDP) cells and that it could attenuate the resistance of these cells. Additionally, flow cytometry analysis showed that the apoptosis rate of these resistant cells when exposed to NDP was markedly increased and the number of cells in the G2 stage of the cell cycle was significantly increased. Furthermore, western blot analysis indicated that NDP decreased the protein expression of P-glycoprotein, tumor protein p53 and B-cell lymphoma 2, and increased the expression of Bcl-2-associated X protein, all of which could possibly improve the NDP intracellular drug concentration and promote cell apoptosis. These observations suggested that NDP could have higher efficacy in DDP-resistant lung cancer cells, and further studies applying more detailed analyses are warranted to elucidate the mechanism(s) behind this effect.

We report the synthesis of high quality trimetallic Au/Ag/Pt nanorings (TAAPNs) by using Au/Ag alloy decahedra (AAAD) as templates. The alloying effect and AgCl-directing growth have been investigated in detail during the formation of TAAPN. It was found that the doping of Ag in AAAD changes the surrounding environment of Au atoms and decreases the oxidization reduction potential (ORP) of [AuCl(2)](-)/Au because of the alloying effect, resulting in the dissolved O(2) molecules that serve as an effective etchant for oxidizing Au to Au(I). Ascorbic acid (AA) and chloroplatinic acid (H(2)PtCl(6)) are weak acids which can accelerate the etching by increasing the concentration of H(+). The AgCl selectively absorbs on {100} of the decahedra and induces the preferential deposition of H(2)PtCl(6) here via their complexing interaction. AA reduces Pt(IV) and Ag(I) to atoms which grow on {100} facets. The formed Pt/Ag layer changes the etching direction from along [100] to [111] and generates the TAAPN. Besides, it has been noted that the TAAPNs exhibit good Surface Enhanced Raman Scattering (SERS) performance.

Lung cancer is one of the most common and highest mortality rates malignant tumors, further, 75%-80% is non-small cell lung cancer (NSCLC). For the majority of patients, lost the chance of radical operation or radiotherapy, chemotherapy is the main treatment. However, because of the diversities of tumor behavior and drug-resistant, the chemotherapy of advanced NSCLC is not optimistic. In recent years, with the application of molecular markers for individual chemotherapy, these patients have achieved prolong life and improved life quality. Individualized chemotherapy based on molecular markers to select the appropriate drug is the problem that needs to be solved. The paper gives a brief review on the role of ribonucleotide reductase subunit 1 (RRM1) in the treatment and prognosis of advanced NSCLC. Individualized chemotherapy by RRM1 can't become commonplace for advanced NSCLC and needs further research.

By using pentyl-linked bis(rhodamine)-derived tetra-siloxane (PRh-Si4 ) as the organosilica precursor, highly ordered PRh-bridged periodic mesoporous organosilicas (PRhPMOs) were prepared. When excited at λ=500 nm, the PRhPMO suspension that contained metal ions showed two separate emission peaks at λ=550 and 623 nm. The first peak, located at λ=550 nm, was due to ring-opening of the spiro structure in the rhodamine moiety and the second, located at λ=623 nm, originated from fluorescent aggregates of the PRh units embedded in the silica framework of the PRhPMO. By using the different intensity ratios of the two fluorescence signals (FI550/623), PRhPMOs could be used as turn-ON type fluorescent ratiometric chemosensors for Cu(2+). Furthermore, based on the single-exciton theory, it was deduced that the fluorescent aggregates formed were of the J-type and had a coplanar configuration. Consequently, PRhPMOs display a longer fluorescence lifetime and greater fluorescent quantum yield than the respective monomers dissolved in solution, which is consistent with the experimental results., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Nearly 85 % of lung-cancer-specific epidermal growth factor receptor (EGFR) sensitive mutations comprise a substitution at position 858 (21L858R) and deletion mutants in exon 19 (19del). The aim of this study was to assess the role of EGFR mutation subtypes in predicting the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) and the prognosis of patients with advanced non-small cell lung cancer (NSCLC)., Method: We systematically searched for eligible articles investigating the association between EGFR mutation subtypes and the efficacy of EGFR TKIs and the prognosis of patients with NSCLC. The summary risk ratio (RR) and mean difference (MD) were calculated using meta-analysis. In addition, we used variance analysis for the progression-free survival data (PFS) and used the rank sum test for the overall survival data., Results: We identified 22 eligible trials involving 1,082 patients. The objective response rate of the 19del mutation group was significantly higher than the 21L858R mutation group (RR 1.23; 95 % CI 1.12-1.36; P < 0.0001). The PFS (MD 3.55; 95 % CI 0.90-6.20; P = 0.009; MD 2.57; 95 % CI 0.51-4.62; P = 0.01) and overall survival (OS) (MD 10.52; 95 % CI 5.10-15.93; P = 0.0001) of the 19del mutation group were significantly longer than the 21L858R mutation group; the same results were observed in the variance analysis and rank sum test., Conclusion: The 19del mutation may be a more efficient clinical marker for predicting the response of patients with NSCLC to EGFR TKIs. Furthermore, patients with the 19del mutation have both a longer PFS and OS. The 19del mutation is also the prognostic factor for patients with NSCLC.