Compound four-cavity single-longitudinal mode fiber laser.

A compound resonant cavity-type single longitudinal mode erbium-doped fiber laser is proposed and verified in this paper. We use a compound four-cavity to expand the longitudinal mode spacing of the laser and a homemade grating F-P filter and a saturable absorber to narrow the gain spectral bandwidth, enabling the laser to operate in a single-frequency state. Through theoretical analysis and experimental verification of the important roles of the main constructed fiber laser parts, the center wavelength of the laser output of 1550.06 nm is obtained, and the optical signal-to-noise ratio is 65 dB. In a 50 minute period, the wavelength fluctuation is exhibited along with the maximum power fluctuation of 0.28 dB. The value of the laser output linewidth is ∼250 Hz, measured by using the delayed self-heterodyne method.

A perovskite-based electrochemiluminescence aptasensor for tetracycline screening.

Tetracyclines are currently the most commonly used class of antibiotics, and their residue issue significantly impacts public health safety. In this study, a surface modification of perovskite with cetyltrimethylammonium bromide led to the generation of stable electrochemiluminescence (ECL) emitters in aqueous systems and improved the biocompatibility of perovskite. A perovskite quantum dot-based ECL sensing strategy was developed. Utilizing the corresponding aptamer of the antibiotics, strain displacement reactions were triggered, disrupting the ECL quenching system composed of perovskite and Ag nanoclusters (Ag NCs) on the electrode surface, generating a signal to achieve quantitative detection of several common tetracycline antibiotics. The perovskite quantum dot provided a strong and stable initial signal, while the efficient catalytic activity of the silver cluster enhanced the recognition sensitivity. Tetracycline, chlortetracycline, and oxytetracycline were used as examples to demonstrate the differentiation and quantitative detection through this method. In addition, the aptasensor exhibited analytical performance with the linear range (0.1-10 µM OTC) and good recovery rates of 94.7% to 101.6% in real samples. This approach has the potential to become a sensitive and practical approach for assessing antibiotic residues.

Nano-Micro Core-Shell Fibers for Efficient Pest Trapping.

Insect sex pheromones as an alternative to chemical pesticides hold promising prospects in pest control. However, their burst release and duration need to be optimized. Herein, pheromone-loaded core-shell fibers composed of degradable polycaprolactone and polyhydroxybutyrate were prepared by coaxial electrospinning. The results showed that this core-shell fiber had good hydrophobic performance and thermal stability, and the light transmittance in the ultraviolet band was only below 40%, which provided protection to pheromones. The core-shell structure alleviated the burst release of pheromone in the fiber and extended the release time to about 133 days. In the field, the pheromone-loaded core-shell fibers showed the same continuous and efficient trapping of Spodoptera litura as the commercial carriers. More importantly, the electrospun fibers combined with biomaterials had a degradability unmatched by commercial carriers. The structure design strategy provides ideas for the innovative design of pheromone carriers and is a potential tool for the management of agricultural pests.

Biphasic alcoholysis coupled with high-speed countercurrent chromatography for high performance on separating phorbol from Croton tiglium Linn extracts.

Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high-speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2 SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.

Identification of a novel adjuvant loperamide that enhances the antibacterial activity of colistin against MCR-1-positive pathogens in vitro/vivo.

Severe infection with multidrug-resistant Enterobacterales caused by the plasmid-induced colistin resistance gene MCR-1 is a serious public health challenge. In this case, it is necessary and pressing to find a treatment to overcome antibiotic resistance. Here, we investigated the synergistic effect and mechanism of loperamide combined with colistin against MCR-1-positive pathogens. We evaluated the combined effect of loperamide and colistin using the checkerboard method and the time-kill experiment. The results showed that loperamide could enhance the bactericidal ability of colistin, and this combination regimen could completely kill the tested bacteria within 4 h. Subsequently, spectrofluorimetric methods were used to explore the mechanism of loperamide combined with colistin. The results indicated that the mode of action of loperamide combined with colistin was found to involve mechanical disruption of the membrane. Furthermore, molecular simulation and microscale thermophoresis results revealed that loperamide reduced the impact of MCR-1 protein by directly binding to its active site. In addition, the combined regimen of loperamide and colistin effectively reduced the bacterial load in the thighs of mice while increasing the protection rate by 70%. In short, as a potential lead compound, loperamide can enhance the killing effect of colistin on pathogenic Enterobacterales carrying MCR-1 by causing membrane damage and inhibiting MCR-1 protein activity.

Epinodosin suppresses the proliferation, invasion, and migration of esophageal squamous cell carcinoma by mediating miRNA-143-3p/Bcl-2 axis.

Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.

IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells.

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.

Paeonol inhibits human lung cancer cell viability and metastasis in vitro via miR-126-5p/ZEB2 axis.

Paeonol exerted an effect in lung cancer, but the underlying mechanism remained vague. In this research, we assessed the effects of Paeonol and microRNA (miR)-126-5p on the viability, migration, invasion, and epithelial-mesenchymal transition (EMT) of lung cancer cells. Lung cancer cells and BEAS-2B cells were treated with Paeonol, and viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay. The migration and invasion of lung cancer cells after treatment with Paeonol at 40 µg/mL or 80 µg/mL were detected by wound healing assay and Transwell assay, respectively. The effects of Paeonol on transforming growth factor-ß1 (TGF-ß1)-induced EMT and relative expressions of EMT-related proteins were determined using Western blot. The target gene of miR-126-5p and the binding sites between them were predicted by TargetScan, and confirmed using dual-luciferase reporter assay. Relative expressions of miR-126-5p, its target gene and EMT-related proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Rescue assay was performed to analyze the relation between Paeonol and miR-126-5p. Paeonol down-regulated cell viability and inhibited migration, invasion and TGF-ß1-induced EMT while up-regulating miR-126-5p expression in lung cancer cells as the dose increased. However, miR-126-5p inhibitor could reverse the effect of Paeonol. ZEB2 was the target gene of miR-126-5p, and silencing ZEB2 expression reversed the effects of miR-126-5p downregulation. Paeonol also regulated the expression of ZEB2 in lung cancer cells, and this regulation depends on the regulation of miR-126-5p. Paeonol inhibits human lung cancer cell viability and metastasis via the miR-126-5p/ZEB2 axis, and could be adopted as a potential agent for lung cancer treatment.

Preparation and Characterization of Protein Molecularly Imprinted Poly (Ionic Liquid)/Calcium Alginate Composite Cryogel Membrane with High Mechanical Strength for the Separation of Bovine Serum Albumin.

In order to improve the mechanical strength and imprinting efficiency, a novel bovine serum albumin (BSA) molecularly imprinted poly(ionic liquid)/calcium alginate composite cryogel membrane (MICM) was prepared. The results of the tensile test indicated that the MICM had excellent mechanical strength which could reach up to 90.00 KPa, 30.30 times higher than the poly (ionic liquid) membrane without calcium alginate; the elongation of it could reach up to 93.70%, 8.28 times higher than the poly (ionic liquid) membrane without calcium alginate. The MICM had a very high welling ratio of 1026.56% and macropore porosity of 62.29%, which can provide effective mass transport of proteins. More remarkably, it had a very high adsorption capacity of 485.87 mg g-1 at 20 °C and 0.66 mg mL-1 of the initial concentration of BSA. Moreover, MICM also had good selective and competitive recognition toward BSA, exhibiting potential utility in protein separation. This work can provide a potential method to prepare the protein-imprinted cryogel membrane with both high mechanical strength and imprinting efficiency.

Macrophage-derived exosomes mediate silica-induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress-dependent manner.

Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage-derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage-derived exosomes promote or inhibit lung fibrosis, in vitro, silica-exposed macrophage-derived exosomes (SiO2 -Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α-SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P-eIF2α were assessed after treatment with or without the ER stress inhibitor 4-PBA. In vivo, mice were pre-treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF-α, IL-1ß and IL-6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α-SMA was up-regulated after treatment with SiO2 -Exos, accompanied by increased expression of BIP, XBP1s and P-eIF2α. Pre-treatment with 4-PBA reversed this effect. More importantly, an in vivo study demonstrated that pre-treatment with GW4869 decreased lung fibrosis and the expression of TNF-α, IL-1ß and IL-6 in BALF. These results suggested that SiO2 -Exos are profibrogenic and that the facilitating effect is dependent on ER stress.

Design, synthesis and anticancer evaluation of new 4-anilinoquinoline-3-carbonitrile derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers.

Dual targeting of EGFR/HER2 receptor is an attractive strategy for cancer therapy. Four series of 4-anilinoquinoline-3-carbonitrile derivatives were designed and prepared by introducing various functional groups, including a polar hydrophilic group (carboxylic acid), a heterocyclic substituent possessing polarity to some extent, and an unpolar hydrophobic phenyl portion, at the C-6 position of the quinoline skeleton. All of the prepared derivatives were screened for their inhibitory activities against EGFR /HER2 receptors and their antiproliferative activities against the SK-BR-3 and A431 cell lines. Compounds 6a, 6 g and 6d exhibited significant activities against the target cell lines. In particular, the antiproliferative activity of 6d (IC50 = 1.930 µM) against SK-BR-3 was over 2-fold higher than that of neratinib (IC50 = 3.966 µM), and comparable to that of Lapatinib (IC50 = 2.737 µM). On the other hand, 6d (IC50 = 1.893 µM) was more active than the reference drug Neratinib (IC50 = 2.151 µM), and showed comparable potency to Lapatinib (IC50 = 1.285 µM) against A431. Cell cycle analysis and apoptosis assays indicated that 6d arrests the cell cycle in the S phase, and it is a potent apoptotic inducer. Moreover, molecular docking exhibited the binding modes of compound 6d in EGFR and HER2 binding sites, respectively. Compound 6d can be considered as a candidate for further investigation as a more potent anticancer agent.

Interaction between endogenous H2O2 and OsVPE3 in the GA-induced PCD of rice aleurone layers.

KEY MESSAGE: Endogenous hydrogen peroxide (H2O2) is involved in regulating the gibberellic acid-induced programmed cell death (PCD) of the aleurone layers by cooperating with OsVPE3 during rice seed germination. Preliminary experiments revealed that H2O2 produced by the NOX pathway is the key factor affecting rice germination. Histochemical analysis indicated that H2O2 is located in the aleurone layer. Both the H2O2 scavenger DMTU and the NOX inhibitor DPI decreased H2O2 content and significantly slowed down vacuolation in a dose-dependent manner. Interestingly, DMTU down-regulated the OsNOX8 transcript or DMTU and DPI decreased the intracellular H2O2 level, resulting in a delay of PCD. In contrast, GA and H2O2 up-regulated the OsNOX8 transcript and intracellular H2O2 level, leading to premature PCD, and the effects of GA and H2O2 were reversed by DMTU and DPI, respectively. These results showed that the imbalance of intracellular H2O2 levels leads to the delayed or premature PCD. Further experiments indicated that GA up-regulated the OsVPE3 transcript and VPE activity, and the effect was reversed by DPI. Furthermore, Ac-YVAD-CMK significantly blocked H2O2 accumulation, and DPI + Ac-YVAD-CMK had a more significant inhibitory effect compared with DPI alone, resulting in the delayed PCD, suggesting that OsVPE3 regulates PCD by promoting H2O2 generation. Meanwhile, DPI significantly inhibited the OsVPE3 transcript and VPE activity, and in turn delayed PCD occurrence, suggesting that the H2O2 produced by the NOX pathway may regulate PCD by up-regulating the OsVPE3 transcript. Thus, the endogenous H2O2 produced by the NOX pathway mediates the GA-induced PCD of rice aleurone layers by interacting with OsVPE3.

Online violent video games and online aggressive behavior among Chinese college students: The role of anger rumination and self-control.

Online aggressive behavior (OAB) has received increasing attention in recent years, and that playing online violent video games (OVVG) is an important predictor of OAB. However, little is known of the mediating and moderating mechanisms underlying this relationship. This study aims to investigate (a) the mediating role of anger rumination in the association between OVVG and OAB and (b) the moderating role of self-control in the relationship between anger rumination and OAB. A total of 595 Chinese college students (M age = 19.59 years, SD age = 1.40) completed measurements regarding OVVG, anger rumination, self-control, and OAB. The correlation analyses showed that OVVG was significantly positively associated with anger rumination and OAB. Mediation analyses revealed anger rumination partially mediated the link between OVVG and OAB. Moderated mediation further indicated that anger rumination was not associated with OAB for individuals with high levels of self-control. However, for those with low levels of self-control, anger rumination was significantly associated with OAB. These findings suggest that the improvement of self-control and the decline of anger rumination could be a practicable way to address the issue of OAB effectively.

Enhanced Fungicidal Efficacy by Co-Delivery of Azoxystrobin and Diniconazole with Cauliflower-Like Metal-Organic Frameworks NH2-Al-MIL-101.

Long-term use of a single fungicide increases the resistance risk and causes adverse effects on natural ecosystems. Controlled release formulations of dual fungicides with different modes of action can afford a new dimension for addressing the current issues. Based on adjustable aperture and superhigh surface area, metal-organic frameworks (MOFs) are ideal candidates as pesticide release carriers. This study used Al3+ as the metal node and 2-aminoterephthalic acid as the organic chain to prepare aluminum-based metal-organic framework material (NH2-Al-MIL-101) with "cauliflower-like" structure and high surface area of 2359.0 m2/g. Fungicides of azoxystrobin (AZOX) and diniconazole (Dini) were simultaneously encapsulated into NH2-Al-MIL-101 with the loading content of 6.71% and 29.72%, respectively. Dual fungicide delivery system of AZOX@Dini@NH2-Al-MIL-101 demonstrated sustained and pH responsive release profiles. When the maximum cumulative release rate of AZOX and Dini both reached about 90%, the release time was 46 and 136 h, respectively. Furthermore, EC50 values as well as the percentage of inhibition revealed that AZOX@Dini@NH2-Al-MIL-101 had enhanced germicidal efficacy against rice sheath blight (Rhizoctonia solani), evidenced by the synergistic ratio of 1.83. The present study demonstrates a potential application prospect in sustainable plant protection through co-delivery fungicides with MOFs as a platform.

[Difference of silicon dioxide-stimulated macrophage-derived exosomal miRNA expression profile].

OBJECTIVE: To analyze the differential expression of RAW264.7 macrophage-derived exosomes miRNA stimulated by free silicon dioxide (SiO2).
 Methods: RAW264.7 was stimulated with SiO2 (200 mg/L) for 48 h (exo_48 h group), and the supernatant was collected. The exosomes in the supernatant were extracted by ultracentrifugation. Transmission microscopy, nanoparticle tracking analysis (NTA) and Western blotting were used to identify exosomes. High-throughput sequencing was performed to compare the differential expression of exosome miRNAs between the exo_control group (RAW264.7 cultured for 48 h without SiO2) and the exo_48 h group; miRanda, TargetScan and starBase were used to predict target genes of differential miRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on target genes to further analyze the biological functions of genes.
 Results: The transmission microscopy showed that the exosomes were lipid membrane coated vesicles, which were heterogeneously distributed, with a diameter ranging from 30 to 100 nm, and the shape was round or elliptical. The volume kurtosis was concentrated between 40 and 100 nm and the exosome marker protein TSG101 was positive. High-throughput sequencing screened 148 differentially expressed exosomal miRNAs. MiR-219c-3p, let-7d-3p, let-7a-1-3p, miR-328-3p, miR-365-3p, and miR-7219-3p were significantly up-regulated, and miR-378d and miR-5106 were significantly down-regulated compared with the control group. Target genes were mainly enriched in mTOR signaling pathway, Wnt signaling pathway, TGF-ß signaling pathway, and so on.
 Conclusion: The exosomes secreted by SiO2-induced macrophages contain abundant miRNAs, and their expressions are significantly different. These differential miRNAs may be involved in the activation of lung fibroblasts and epithelial-mesenchymal transition.

Identification of AUXIN RESPONSE FACTOR gene family from Prunus sibirica and its expression analysis during mesocarp and kernel development.

BACKGROUND: Auxin response factors (ARFs) in auxin signaling pathway are an important component that can regulate the transcription of auxin-responsive genes involved in almost all aspects of plant growth and development. To our knowledge, the comprehensive and systematic characterization of ARF genes has never been reported in Prunus sibirica, a novel woody biodiesel feedstock in China. RESULTS: In this study, we identified 14 PsARF genes with a perfect open reading frame (ORF) in P. sibirica by using its previous transcriptomic data. Conserved motif analysis showed that all identified PsARF proteins had typical DNA-binding and ARF domain, but 5 members (PsARF3, 8 10, 16 and 17) lacked the dimerization domain. Phylogenetic analysis of the ARF proteins generated from various plant species indicated that ARFs could be categorized into 4 major groups (Class I, II, III and IV), in which all identified ARFs from P. sibirica showed a closest relationship with those from P. mume. Comparison of the expression profiles of 14 PsARF genes in different developmental stages of Siberian apricot mesocarp (SAM) and kernel (SAK) reflected distinct temporal or spatial expression patterns for PsARF genes. Additionally, based on the expressed data from fruit and seed development of multiple plant species, we identified 1514 ARF-correlated genes using weighted gene co-expression network analysis (WGCNA). And the major portion of ARF-correlated gene was characterized to be involved in protein, nucleic acid and carbohydrate metabolic, transport and regulatory processes. CONCLUSIONS: In summary, we systematically and comprehensively analyzed the structure, expression pattern and co-expression network of ARF gene family in P. sibirica. All our findings provide theoretical foundation for the PsARF gene family and will pave the way for elucidating the precise role of PsARF genes in SAM and SAK development.

MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2.

OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. CONCLUSION: MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.

Study on the Polar Extracts of Dendrobium nobile, D. officinale, D. loddigesii, and Flickingeria fimbriata: Metabolite Identification, Content Evaluation, and Bioactivity Assay.

The polar extract of the Dendrobium species or F. fimbriata (a substitute of Dendrobium), between the fat-soluble extract and polysaccharide has barely been researched. This report worked on the qualitative and quantitative studies of polar extracts from D. nobile, D. officinale, D. loddigesii, and F. fimbriata. Eight water-soluble metabolites containing a new diglucoside, flifimdioside A (1), and a rare imidazolium-type alkaloid, anosmine (4), were identified using chromatography as well as spectroscopic techniques. Their contents in the four herbs were high, approximately 0.9⁻3.7 mg/g based on the analysis of quantitative nuclear magnetic resonance (qNMR) spectroscopy. Biological activity evaluation showed that the polar extract of F. fimbriata or its pure component had good antioxidant and neuroprotective activity; compounds 1‒4 and shihunine (8) showed weak α-glucosidase inhibitory activity; 4 and 8 had weak anti-inflammatory activity. Under trial conditions, all samples had no cytotoxic activity.

Effects of Rich-Polyphenols Extract of Dendrobium loddigesii on Anti-Diabetic, Anti-Inflammatory, Anti-Oxidant, and Gut Microbiota Modulation in db/db Mice.

Dendrobium is a traditional Chinese herb with anti-diabetic effects and has diverse bibenzyls as well as phenanthrenes. Little is known about Dendrobium polyphenols anti-diabetic activities, so, a rich-polyphenols extract of D. loddigesii (DJP) was used for treatment of diabetic db/db mice; the serum biochemical index and tissue appearance were evaluated. In order to gain an insight into the anti-diabetic mechanism, the oxidative stress index, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and gut microbiota modulation were determined by ELISA, immunohistochemistry or high throughput sequencing 16S rRNA gene. The results revealed that DJP had the effects to decrease the blood glucose, body weight, low density lipoprotein cholesterol (LDL-C) levels and increase insulin (INS) level in the mice. DJP improved the mice fatty liver and diabetic nephropathy. DJP showed the anti-oxidative abilities to reduce the malondialdehyde (MDA) level and increase the contents of superoxide dismutase (SOD), catalase (CAT) as well as glutathione (GSH). DJP exerted the anti-inflammatory effects of decreasing expression of IL-6 and TNF-α. After treatment of DJP, the intestinal flora balance of the mice was ameliorated, increasing Bacteroidetes to Firmicutes ratios as well as the relative abundance of Prevotella/Akkermansia and reducing the relative abundance of S24-7/Rikenella/Escherichia coli. The function's prediction of gut microbiota indicated that the microbial compositions involved carbohydrate metabolism or lipid metabolism were changed. This study revealed for the first time that DJP improves the mice symptoms of diabetes and complications, which might be due to the effects that DJP induced the decrease of inflammation as well as oxidative stress and improvement of intestinal flora balance.

Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have demonstrated clinical benefits in the treatment of several tumour types. However, the emergence of TKI resistance restricts the therapeutic effect. This study uses non-small cell lung cancer (NSCLC) to explore the mechanisms contributing to TKI resistance in tumours. METHODS: Biological phenotypes and RNA microarray expression data were analysed in NSCLC cells with and without TKI pretreatment. Specific inhibitors and siRNAs were used to validate the direct involvement of an AKT/FOXM1/STMN1 pathway in TKI resistance. Patients' tissues were analysed to explore the clinical importance of FOXM1 and STMN1. RESULTS: In vitro and in vivo studies showed that TKIs induced the enrichment of cancer stem cells (CSC), promoted epithelial to mesenchymal transition (EMT), and conferred multidrug resistance on NSCLC cells in a cell type- and TKI class-dependent manner. Mechanistically, TKIs activated an AKT/FOXM1/STMN1 pathway. The crucial role of this pathway in TKI-induced enrichment of CSC and drug resistance was verified by silencing FOXM1 and STMN1 or blocking the AKT pathway. Additionally, overexpression of STMN1 was associated with upregulation of FOXM1 in advanced NSCLC patients, and STMN1/FOXM1 upregulation predicted a poor outcome. CONCLUSIONS: Our findings elucidate an additional common mechanism for TKI resistance and provide a promising therapeutic target for reversing TKI resistance in NSCLC.