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Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive., Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach., Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro., Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro., Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy., 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. Production and hosting by Elsevier B.V.)

Objective: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia., Methods: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 β, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 β were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay., Results: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 β, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05)., Conclusions: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms., Methods: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo., Results: The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01)., Conclusion: Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: There is a large population of patients classified as complex higher-risk and indicated patients (CHIPs) in China with a poor prognosis. The treatment of these patients is complex and challenging, especially when acute cardiac events occur, such as acute coronary syndrome (ACS) or heart failure. Pharmacotherapy and some mechanical circulatory support (MCS) therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention (PCI). LDL-C is an important pathogenic factor in atherosclerosis, and the target of blood lipid control. Recent studies have revealed that lipoprotein(a) [Lp(a)], which is formed when a covalent bond between apolipoprotein(a) and apolipoprotein B-100 is made, produces an LDL-like particle. This particle is an independent risk factor for the development of atherosclerosis, and is closely correlated to stent thrombosis and restenosis. Furthermore, this requires active intervention. PCSK9 inhibitors have been used in lipid-lowering treatment, and preventing atherosclerosis. The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS, and the association between the change in Lp(a) and survival after 2 years of follow-up., Methods: The present real-world, prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020, and these patients were followed up for 2 years. These patients were divided into two groups: PCSK9 group (n=161) given the combined PCSK9 inhibitor (140 mg of evolocumab every 2 weeks) and statins-based therapy, and SOC group (n=160) treated with statin-based lipid-lowering therapy alone. Then, the change in lipid index was measured, and the cardiovascular (CV) event recurrence rate was evaluated after one month and 2 years. Afterwards, the contribution of serum lipid parameters, especially the Lp(a) alteration, in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed., Results: The LDL-C level was significantly reduced in both groups: 52.3% in the PCSK9 group and 32.3% (P<0.001) in the SOC group. It is noteworthy that the Lp(a) level decreased by 13.2% in the PCSK9 group, but increased by 30.3% in the SOC group (P<0.001). Furthermore, the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period. In the PCSK9 group, the Lp(a) reduction was associated with the baseline Lp(a) levels of the patients (r 2 =-0.315, P<0.001). Moreover, the decrease in Lp(a) contributed to the decline in CV events in patients who received ACS CHIPs-PCI, and the decrease in Lp(a) level was independent of the LDL-C level reduction., Conclusion: The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a) levels in ACS CHIPs-PCI. However, further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs., (© 2023. Huazhong University of Science and Technology.)

Background: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet., Purpose: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored., Methods: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS., Results: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads., Conclusion: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV., 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 © 2023 Elsevier GmbH. All rights reserved.)

The lumen-occlusion type of tracheobronchial tuberculosis is the most severe type of tracheobronchial stenosis of tuberculosis, often leading to atelectasis or even lung damage in patients. Some patients require surgical resection of the diseased airways and lungs, which can seriously affect their quality of life and even be life-threatening. In order to improve the treatment ability of bronchoscopy physicians for lumen occlusion type of tracheobronchial tuberculosis, this article retrospectively analyzed 30 cases of tracheobronchial tuberculosis with lumen occlusion in Hunan Chest Hospital, and summarized the experience of achieving better results by high-frequency electrotome combined with balloon dilatation and cryotherapy.

Background: Although hundreds of studies have been conducted, our understanding of the pathogenesis, indications for surgical intervention, and disease markers of Takayasu arteritis (TAK) are still limited. Collection of biological specimens, clinical data and imaging data will facilitate translational research and clinical studies. In this study, we aim to introduce the design and protocol for the Beijing Hospital Takayasu Arteritis (BeTA) Biobank., Methods: Based in the Department of Vascular Surgery of Beijing Hospital and Beijing Hospital Clinical Biological Sample Management Center, the BeTA Biobank is composed of clinical data and sample data from patients with TAK requiring surgical treatment. All clinical data of participants are collected, including demographic characteristics, laboratory tests, imaging results, operation information, perioperative complications, follow-up data, etc. Both blood samples including plasma, serum and cells, and vascular tissues or perivascular adipose tissue are collected and stored. These samples will promote the establishment of a multiomic database for TAK and help to identify disease markers and to explore potential targets for specific future drugs for TAK.

Background: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n -butanol extract from Glycyrrhizae Radix et Rhizome (GRE)., Methods: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo., Results: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice., Conclusions: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.

The decrease of seawater pH can affect the metabolism, acid-base balance, immune response and immunoprotease activity of aquatic animals, leading to aquatic animal stress, impairing the immune system of aquatic animals and weakening disease resistance, etc. In this study, we performed high-throughput sequencing analysis of the hepatopancreas transcriptome library of low pH stress penaeus monodon, and after sequencing quality control, a total of 43488612-56271828 Clean Reads were obtained, and GO annotation and KEGG pathway enrichment analysis were performed on the obtained Clean Reads, and a total of 395 DEGs were identified. we mined 10 differentially expressed and found that they were significantly enriched in the Metabolic pathways (ko01100), Biosynthesis of secondary metabolites (ko01110), Nitrogen metabolism (ko00910) pathways, such as PIGA, DGAT1, DGAT2, UBE2E on Metabolic pathways; UGT, GLT1, TIM genes on Biosynthesis of secondary metabolites; CA, CA2, CA4 genes on Nitrogen metabolism, are involved in lipid metabolism, induction of oxidative stress and inflammation in the muscular body of spot prawns. These genes play an important role in lipid metabolism, induction of oxidative stress and inflammatory response in the muscle of the shrimp. In summary, these genes provide valuable reference information for future breeding of low pH-tolerant shrimp., (Copyright © 2022. Published by Elsevier Ltd.)

Epidermal growth factor receptor (EGFR) is a therapeutic target in nasopharyngeal carcinoma (NPC). The optimal combined modality of optimal combined modality of anti--EGFR monoclonal antibodies, induction chemotherapy (ICT), concurrent chemotherapy and radiotherapy for NPC remains poorly defined. None of previous studies have developed subsequent treatment strategies on the basis of stratification according to the efficacy following ICT plus anti-EGFR mAbs. This study aims to increase treatment intensity for patients with poor efficacy of ICT and reduce treatment toxicity for patients with favourable efficacy of ICT by assessing whether the efficacy of this treatment regimen is non-inferior to ICT plus concurrent chemoradiotherapy (historic controls)., Introduction: METHODS AND ANALYSIS: Pathology-confirmed WHO type II/III NPC patients at clinical stage III-IVA (eighth American Joint Committee on Cancer/Union for International Cancer Control staging system) will be included in the study. They will receive ICT plus nimotuzumab (NTZ), followed by radiotherapy plus NTZ or concurrent chemoradiotherapy plus NTZ (stratified based on the efficacy of ICT plus NTZ). The primary endpoint is 3-year failure-free survival rate; while the secondary endpoints are 3-year overall survival rate, distant metastasis-free survival rate and locoregional recurrence-free survival rate, and short-term remission rate of tumour and treatment toxicity., Ethics and Dissemination: The study protocol has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Our findings will be disseminated in a peer-reviewed journal. Implementation strategies are in place to ensure privacy and confidentiality of participants., Trial Registration Number: ChiCTR2000041139., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Circular RNAs (circRNAs),a group of highly conserved small RNAs,are characterized by a closed circular structure from precursor linear RNA through reverse splicing.They are powerful regulators of the physiological and pathological processes in organisms at different development stages.Zebrafish can be used for the high-throughput drug screening with low cost.Thus,the circRNAs associated with development and inflammation can be mined from zebrafish.Recently,a variety of circRNAs in zebrafish have been identified and characterized.Studies have proved that circRNAs play a vital role in the development and inflammation of zebrafish.The paper summarizes the classification,characteristics,and biological functions of circRNAs,and reviews the research progress in zebrafish's circRNAs.

Background and Purpose: This study sought to improve methods to identify biomarkers in the neuroendocrine system related to stroke progression to improve the accuracy of traditional tools for evaluating stroke prognosis., Methods: Seventy-four stroke patients and 237 healthy controls were prospectively included. We measured urinary epinephrine (E), noradrenaline (NE), dopamine (DA) and cortisol (F) on days 1, 3, and 5 after stroke onset and plasma F, adrenocorticotropic hormone (ACTH), thyrotropin (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH). The correlation between these hormone levels and 90-day prognosis was analyzed, their value in assessing prognosis was compared with lesion volume and National Institutes of Health Stroke Scale (NIHSS) scores using receiver operating characteristic (ROC) curves, and their correlation with conventional clinical variables was assessed., Results: Levels of F, 24-h urinary free cortisol(UFC), E, NE, DA, and GH on days 1, 3, and 5 were significantly higher in stroke patients than in controls ( P < 0.01), while ACTH and TSH decreased, gradually approaching normal within 5 days of onset. Levels of E, NE, F, and 24-h UFC were proportional to severity, and all gradually decreased within 5 days of onset in patients with a good prognosis and gradually increased or remained high in those with a poor prognosis. After adjustment for age, sex, NIHSS, or Glasgow Coma Scale (GCS) score, F > 13.6 μg/dL, ACTH > 22.02 pg/mL and NE > 123.5 μg/ 24 h were identified as risk factors for a poor prognosis 90 days after stroke ( P < 0.05). The combination of F, ACTH, NE, white blood cell count (WBC), glucose (Glu), and hemoglobin (Hb) was significantly more accurate than lesion volume (AUC: 0.931 vs. 0.694 P = 0.019) and NIHSS score (AUC: 0.931 vs. 0.746 P = 0.034) in predicting poor prognosis of stroke 1 day after onset. Hormones and traditional clinical variables were correlated to varying degrees, with NE correlating most strongly with 24-h UFC ( r = 0.54) and moderately positively with lesion volume ( r = 0.40) and NIHSS score ( r = 0.45)., Conclusions: Stroke causes significant time-phased dynamic changes in the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, and plasma F, ACTH, and urinary NE levels can be used to assess stroke severity and prognosis., Chinese Clinical Trial Registry: Registration Number: ChiCTR1900024992. Registration Date: 2019/8/6., 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 © 2022 Chen, Shi, Hu, Chen, Sun, Zhou, Lu, Wang, Wang, Yu, Zhao, Lu and Ye.)

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage-specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage-specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron-like state. These neuron-like cells can be further converted into mature neurons, while single-cell RNA-seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Acute lung injury (ALI) is a serious inflammatory disease with clinical manifestations of hypoxemia and respiratory failure. Presently, there is no effective treatment of ALI. Although emodin from Rheum palmatum L. exerts anti-ALI properties, the underlying mechanisms have not been fully explored. Purpose: This study aimed to investigate the therapeutic effect and mechanism of emodin on LPS-induced ALI in mice. Methods: RAW264.7 cells and zebrafish larvae were stimulated by LPS to establish inflammatory models. The anti-inflammatory effect of emodin was assessed by ELISA, flow cytometric analysis, and survival analysis. In vitro mechanisms were explored by using Western blotting, luciferase assay, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) approach. The acute lung injury model in mice was established by the intratracheal administration of LPS, and the underlying mechanisms were assessed by detecting changes in histopathological and inflammatory markers and Western blotting in lung tissues. Results: Emodin inhibited the inflammatory factor production and oxidative stress in RAW264.7 cells, and prolonged the survival of zebrafish larvae after LPS stimulation. Emodin suppressed the expression levels of phosphorylated JNK at Thr183/tyr182 and phosphorylated Nur77 at Ser351 and c-Jun, and increased the expression level of Nur77 in LPS-stimulated RAW264.7 cells, while these regulatory effects of emodin on Nur77/c-Jun were counteracted by JNK activators. The overexpression of JNK dampened the emodin-mediated increase in Nur77 luciferase activity and Nur77 expression. Moreover, the inhibitory effect of emodin on c-Jun can be attenuated by Nur77 siRNA. Furthermore, emodin alleviated LPS-induced ALI in mice through the regulation of the JNK/Nur77/c-Jun pathway. Conclusions: Emodin protects against LPS-induced ALI through regulation on JNK/Nur77/c-Jun signaling. Our results indicate the potential of emodin in the treatment of ALI., 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 © 2022 Xie, Yan, Zhou, Cao, Zheng, Lu, Yang, Ma, Chen, Huo, Tian, Liu and Yu.)

Fibrosis can occur in almost all tissues and organs and affects normal physiological function, which may have serious consequences, such as organ failure. However, there are currently no effective, broad-spectrum drugs suitable for clinical application. Revealing the process of fibrosis is an important prerequisite for the development of new therapeutic targets and drugs. Studies have shown that the limiting of myofibroblast activation or the promoting of their elimination can ameliorate fibrosis. However, it has not been reported whether a direct decrease in cell contraction can inhibit fibrosis in vivo . Here, we have shown that (-)-blebbistatin (Ble), a non-muscle myosin Ⅱ inhibitor, displayed significant inhibition of liver fibrosis in different chronic injury mouse models in vivo . We found that Ble reduced the stiffness of fibrotic tissues from the early stage, which reduced the extent of myofibroblast activation induced by a stiffer extracellular matrix (ECM). Moreover, Ble also reduced the activation of myofibroblasts induced by TGF-β1, which is the most potent pro-fibrotic cytokine. Mechanistically, Ble reduced mechanical contraction, which inhibited the assembly of stress fibers, decreased the F/G-actin ratio, and led to the exnucleation of YAP1 and MRTF-A . Finally, we verified its broad-spectrum antifibrotic effect in multiple models of organ fibrosis. Our results highlighted the important role of mechanical contraction in myofibroblast activation and maintenance, rather than just a characteristic of activation, suggesting that it may be a potential target to explore broad-spectrum drugs for the treatment of fibrotic diseases., Competing Interests: 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., (© 2021 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Objective: To investigate the effects of lncRNA SDHAP1 on the multiplication, migration and invasiveness of NSCLC cells., Methods: From The Cancer Genome Atlas (TCGA) database, the clinical data of NSCLC patients were retrieved to analyze the expression of lncRNA SDHAP1 in LC. In this study, lncRNA SDHAP1 in NSCLC cell lines was regulated, and its expression profiling in non- and cis-platinum (CDDP) resistant NSCLC cell lines was identified by qPCR. The levels of multidrug resistance-related protein 1 (MRP1), p-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) were measured by Western blotting (WB), the migration and invasion of LC cells were detected by Transwell assay, and the cell multiplication and activity were determined by MTT assays., Results: TCGA database identified upregulated lncRNA SDHAP1 expression in LC. qPCR results revealed that lncRNA SDHAP1 was highly expressed in NSCLC. LncRNA SDHAP1 showed higher expression in patients with stage IV than in those with stage I, II or III, as well as in people aged 21-40 years old. Compared with normal lung epithelial cells, lncRNA SDHAP1 was upregulated in NSCLC cell lines, especially in those resistant to CDDP. LncRNA SDHAP1 downregulation led to a decrease in multiplication, migration and invasiveness of NSCLC cells, and a reduction in activity, migration and invasiveness of CDDP-resistant NSCLC cell lines. In addition, lncRNA SDHAP1 knockdown down-regulated the expression levels of Multidrug resistance-associated proteins MRP1, P-gp and GST-π., Conclusions: LncRNA SDHAP1 is upregulated in NSCLC and is associated with LC staging and age of patients. Silencing lncRNA SDHAP1 can suppress the multiplication, migration, invasiveness and CDDP resistance of cancer cells. Therefore, lncRNA SDHAP1 may serve as a prognostic biomarker and treatment target for NSCLC., Competing Interests: None., (AJTR Copyright © 2021.)

Background: Blue laser imaging (BLI) can provide useful information on colorectal laterally spreading tumors (LSTs) by visualizing the surface and vessel patterns in detail. The present research aimed to evaluate the diagnostic performance of BLI-combined JNET (Japan NBI Expert Team) classification for identifying LSTs., Methods: This retrospective, multicenter study included 172 LSTs consisted of 6 hyperplastic polyps/sessile serrated polyps, 94 low-grade dysplasias (LGD), 60 high-grade dysplasias (HGD), 6 superficial submucosal invasive (m-SMs) carcinomas, and 4 deep submucosal invasive carcinomas. The relationship between the JNET classification and the histologic findings of these lesions were then analyzed., Results: For all LSTs, non-experts and experts had a 79.7% and 90.7% accuracy for Type 2A (P = 0.004), a sensitivity of 94.7% and 96.8% (P = 0.718), and a specificity of 61.5% and 83.3% (P = 0.002) for prediction of LGD, respectively. The results also demonstrated 80.8% and 91.3% accuracy for Type 2B (P = 0.005), a sensitivity of 65.2% and 83.3% (P = 0.017), and a specificity of 90.6% and 96.2% (P = 0.097) for predicting HGD or m-SMs. For LST-granular (LST-G) lesions, Type 2A in experts had higher specificity (65.6% vs. 83.6%, P = 0.022) and accuracy (81.8% vs. 91.2%, P = 0.022). Type 2B in experts only had higher accuracy (82.5% vs. 92.0%, P = 0.019). However, no significant differences were noted for any comparisons between non-experts and experts for LST-non-granular (LST-NG) lesions., Conclusions: BLI combined with JNET classification was an effective method for the precise prediction of pathological diagnosis in patients with LSTs. Diagnostic performance of JNET classification by experts was better than that by non-experts for all examined LST or LST-G lesions when delineating between Type 2A and 2B, but there was no difference for the identification of LST-NG lesions by these two groups., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

As an important trace element, iron plays an essential role in many biology processes like cell proliferation, metabolism, and mitochondrial function. However, the disruption of iron homeostasis tends to cells death and human diseases due to it servers as mediator to promote the production of reactive oxygen species (ROS). In this review, first we introduced the mechanism of complex iron-mediated ROS involved in apoptosis, necroptosis, ferroptosis and pyroptosis. Next, we discussed the controversial role of excess iron and iron deficiency in tumor. Finally, we discussed the anti-cancer effects of iron on both sides, and novel iron-related strategies. This review outlined the mechanisms and regulation of iron homeostasis and iron-mediated ROS in tumors, and discussed the iron-related treatments., Competing Interests: None., (AJCR Copyright © 2021.)

Objective: To investigate the efficacy of balloon dilatation performed for patients who suffered from actively caseating endobronchial tuberculosis (EBTB) and central airway stenosis in clinical improving period who's bronchus has not formed mature scar tissue. Methods: A total of 152 tuberculous unilateral main bronchus stenosis patients (23 male and 129 female) who received treatment in Hunan Chest Hospital from January 1 st 2014 to December 31 st 2018 were included in this retrospective analysis. The age was 15-66 (33.3±11.9) years old. All patients received routine anti-tuberculosis chemotherapy. Sixty-four of them who suffered from actively caseating EBTB and unilateral main bronchus stenosis received cryotherapy and endobronchial isoniazid (INH) administration till the caseating necrosis in stenotic bronchus was disappeared and ulcers were recovered, and then received balloon dilatation combined with cryotherapy, were test group. Eighty-eight of them who suffered from fibrostenotic EBTB received balloon dilatation combined with cryotherapy were control group. We analyzed the efficacy and complications after treatments. Results: The lung re-expansion rate after treatment in test group was higher than the control group, and the differences were statistically significant [74.0%(37/50) vs. 37.9%(22/58), χ²= 14.094, P <0.001]. The 6-month re-stenosis rate in test group was lower than control group, and the differences were statistically significant [10.9%(7/64) vs . 30.7% (27/88), χ²= 8.318, P =0.004]. The differences of diameter and diameter variation after balloon dilatation, immediate effective rates, average times of balloon dilatation and procedure-related bleeding (<10 ml) rates, chest pain rates had no statistical signification in two groups. Severe complications including fatal bleeding (>100 ml) and mediastinal emphysema did not occur during our procedures. Conclusions: Performing balloon dilatation for patients who suffered from actively caseating EBTB and central airway stenosis in the clinical improvement period, when caseous necrosis tissue disappeared and ulcers were recovered, not only helps to perform interventional procedures on distal bronchus in time, increase the rate of lung re-expansion, can also reduce the rate of re-stenosis after 6 months, so it is effective and safe.

Cancer is a complex process in which protein-coding and non-coding genes play essential roles. Long noncoding RNAs (lncRNAs), as a subclass of noncoding genes, are implicated in various cancer processes including growth, proliferation, metastasis, and angiogenesis. Due to presence in body fluids such as blood and urine, lncRNAs have become novel biomarkers in cancer detection, diagnosis, progression, and therapy response. Remarkably, increasing evidence has verified that lncRNAs play essential roles in chemoresistance by targeting different signalling pathways. Autophagy, a highly conserved process in response to environmental stresses such as starvation and hypoxia, plays a paradoxical role in inducing resistance or sensitivity to chemotherapy agents. In this regard, we reviewed chemoresistance, the role of lncRNAs in cancer, and the role of lncRNAs in chemoresistance by modulating autophagy.

Objective: This study aimed to explore the significance of renal Doppler ultrasound in evaluating systemic and renal perfusion in sepsis patients before and after fluid resuscitation., Patients and Methods: Forty sepsis patients admitted to the Department of Intensive Medicine and intensive care unit (ICU) of the Fourth Hospital of Hebei Medical University from June 2014 to December 2014 were enrolled in this study, and 35 patients were included in the final analysis. These patients were divided into positive and negative fluid responsiveness groups. They were also divided into an acute kidney injury (AKI) group and a non-AKI group according to changes in creatinine and urine volume. The correlations of the changes in hemodynamics before and after fluid resuscitation in each group with the changes in renal resistance index (RRI) and renal blood flow (RBF) grades were evaluated., Results: Before and after fluid resuscitation, the heart rate (HR), blood creatinine (Cre), and lactate (Lac) levels of all patients, including the patients in the positive fluid responsiveness group decreased, and the stroke volume (SV) and central venous pressure (CVP) increased. Only HR decreased in the negative fluid responsiveness group. In the AKI group, HR, Cre, and Lac decreased, while in the non-AKI group, HR decreased, but CVP and SV increased. There were differences between HR, Lac, and change rate of Lac (Lac%) after fluid resuscitation for the positive and negative fluid responsiveness groups. There was no statistical difference between the RRI values of each group before and after fluid resuscitation. The RRI values of the AKI group were higher than those of the non-AKI group, while the AKI group's RBF grades were lower than those of the non-AKI group. The change rate of RRI (RRI%) was higher in the AKI group than in the non-AKI group. Except for the negative fluid responsiveness group, the RBF grade of each group increased., Conclusions: The approach of RBF classification based on Doppler ultrasound can be used to evaluate the systemic and renal perfusion of patients with severe sepsis before and after fluid resuscitation, while the RRI value cannot be used for evaluation. However, the RRI value can be used as a dynamic index for the evaluation of renal perfusion in patients with AKI.

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/β-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC., (© 2020 Wiley Periodicals, Inc.)

Lipopolysaccharide (LPS)-induced inflammation causes massive threatening diseases, such as sepsis, acute lung injury and multiple organ dysfunction syndrome. Efficient treatment to prevent inflammation is crucial in LPS-induced inflammatory diseases. Heat-clearing Chinese medicines (CMs) have been used to ameliorate LPS-induced inflammation in China for centuries. Heat-clearing CMs regulate inflammatory pathways, thereby inhibiting the release of inflammatory factors. This review aimed to introduce promising heat-clearing CMs countering LPS-induced inflammation in the last 5 years, exploring the underlying molecular mechanisms.

Background: Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. Circular RNAs (circRNAs) are recently identified as important gene regulators with critical roles in cancer biology. In this study, we focus on the effect of circ&#95;0000376 targeting miR-384 on malignant phenotypes of NSCLC cells., Methods: Circ&#95;0000376 and miR-384 expression in NSCLC tissue samples were measured using qRT-PCR. The association between pathological parameters and the circ&#95;0000376 expression was analyzed as well. Human NSCLC cell lines A549 and NCI-H460 were used as cell models. CCK-8 and BrdU assay were used to assess the effect of circ&#95;0000376 on NSCLC cell line proliferation and drug sensitivity. Transwell assay was conducted to detect the effect of circ&#95;0000376 on migration and invasion. Further, luciferase reporter assay was employed to validate the targeting of miR-384 by circ&#95;0000376., Results: Circ&#95;0000376 expression in NSCLC clinical samples was up-regulated and this was linked to unfavorable pathological parameters. Circ&#95;0000376 markedly accelerated the proliferation and metastasis, and enhanced chemoresistance of NSCLC cells. Mechanically, circ&#95;0000376 overexpression could bind with miR-384 and repress its expression., Conclusions: Circ&#95;0000376 is a newly discovered oncogenic circRNA in NSCLC, and can be potentially regarded as a diagnostic biomarker and therapy target.

Background: Hepatocellular carcinoma (HCC) ranks third among the most common causes of cancer-related deaths worldwide. The chemotherapy for HCC is still insufficient, so far. In searching for effective anti-HCC agents from traditional Chinese medicine, we discovered that aloperine (ALO), a quinolizidine alkaloid from Sophora alopecuroides L., exerts anti-HCC activities. However, the effects of ALO on HCC have been rarely studied, and its underlying mechanisms remain unknown., Purpose: This study aims to evaluate the anti-HCC activities of ALO and explore its underlying mechanisms., Methods: MTT assay and colony formation assay were used to investigate the anti-proliferative effects of ALO on human HCC Hep3B and Huh7 cells. Hoechst 33258 staining was used to observe the morphological changes of cells after ALO treatment. Flow cytometry was used to analyze apoptosis induction, the collapse of the mitochondrial membrane potential and cell cycle distribution. Western blotting was used to examine the expression levels of proteins associated with apoptosis and cell cycle arrest, and key proteins in the PI3K/Akt signaling pathway. Small interfering RNA (siRNA) transfection was used to investigate the role of Akt in ALO-induced apoptosis and cell cycle arrest. Zebrafish tumor model was used to evaluate the anti-HCC effects of ALO in vivo., Results: ALO inhibited the proliferation of Hep3B and Huh7 cells. ALO induced apoptosis in HCC cells, which was accompanied by the loss of mitochondrial potential, the release of cytochrome c into cytosol, as well as the increased cleavages of caspase-9, caspase-3 and PARP. Moreover, ALO induced G2/M cell cycle arrest by downregulating the expression levels of cdc25C, cdc2 and cyclin B1. In addition, ALO inhibited activation of the PI3K/Akt signaling pathway by decreasing the expression levels of p110α, p85, Akt and p-Akt (Ser473) . Further study showed that inhibition of Akt by siRNA augmented ALO-mediated apoptosis and G2/M cell cycle arrest in HCC cells. Critically, ALO inhibited the growth of Huh7 cells in vivo., Conclusion: We first demonstrated that ALO induced apoptosis and G2/M cell cycle arrest in HCC cells through inhibition of the PI3K/Akt signaling pathway. This study provides a rationale for ALO as a potential chemotherapeutic agent for HCC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: MicroRNAs play important roles in regulation of the cardiovascular system. The purpose of this study was to investigate microRNA-320 (miR-320) expression in myocardial ischemia-reperfusion (I/R) injury and the roles of miR-320 in cardiomyocyte apoptosis by targeting AKIP1 (A kinase interacting protein 1)., Methods: The level of miR-320 was detected using quantitative real-time polymerase chain reaction (qRT-PCR), and cardiomyocyte apoptosis was detected via terminal dUTP nick end-labeling assay. Cardiomyocyte apoptosis and the mitochondrial membrane potential were evaluated via flow cytometry. Bioinformatics tools were used to identify the target gene of miR-320. The expression levels of AKIP1 mRNA and protein were detected via qRT-PCR and Western blot, respectively., Results: Both the level of miR-320 and the rate of cardiomyocyte apoptosis were substantially higher in the I/R group and H9c2 cells subjected to H/R than in the corresponding controls. Overexpression of miR-320 significantly promoted cardiomyocyte apoptosis and increased the loss of the mitochondrial membrane potential, whereas downregulation of miR-320 had an opposite effect. Luciferase reporter assay showed that miR-320 directly targets AKIP1. Moreover, knock down and overexpression of AKIP1 had similar effects on the H9c2 cells subjected to H/R., Conclusions: miR-320 plays an important role in regulating cardiomyocyte apoptosis induced by I/R injury by targeting AKIP1 and inducing the mitochondrial apoptotic pathway., Competing Interests: The animal experiment was approved by the Laboratory Animal Ethics Committee of Wuhan University (Wuhan, People’s Republic of China [PRC]).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Surface sediment samples were collected from the Pacific sector of the Arctic Ocean during the 6 th Chinese National Arctic Research Expedition (CHINARE), 2014. Concentrations and extractabilities of six toxic metals (Cd, Cr, Cu, Ni, Pb, and Zn) were determined using a modified sequential extraction procedure as described by the European Community Bureau of Reference (BCR). A new analytical hierarchy approach to risk assessment, involving sediment quality guidelines and risk-assessment codes, is described for metals in marine sediments from the Arctic Ocean. Results indicate a mobility order of Pb > Cd > Cu > Zn > Ni > Cr with mean liable fraction (F1+F2+F3) being 83.0%, 81.6%, 62.0%, 47.1%, 42.1%, and 15.6%, respectively. Ni presents the most serious ecological risk in the study area, with most samples (93.9%) indicating medium risk, followed by Cu (54.5%) and Zn (27.3%). For Ni and Zn, there are also samples showing high ecological risk (Ni at site NB02, northern Bering Sea; Zn at R07, northern Chukchi Sea). The ecological risk for Cr indicates low ecological risk (93.9%) and some medium risk (6.1%). All Cd assessments indicate low ecological risk, while most Pb assessments indicate zero (33.3%) to low risk. The new ecological risk assessment method improves on assessments based on metal mobility or concentration alone.

Protoporphyrin IX (PpIX) is used as a photosensitizer in the photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of cancer and is synthesized intracellularly from 5-aminolevulinic acid (5-ALA) precursors. Thirteen novel 5-ALA derivatives were designed and synthesized appropriately with tailored hydrophilicity and lipophilicity. The generation of PpIX was detected and their antitumor activity in vitro and in vivo was also investigated. It was shown that compounds 9b-c, 11b-c and 13a displayed a characteristic long wavelength absorption peak at 593 nm after 5 h incubation in mice fibrosarcoma S180 cells. After being exposed to 600 nm laser light irradiation, these compounds can inhibit cell proliferation in S180 cells in vitro. The growth of S180 cell tumors in Kunming mice was significantly inhibited by these compounds in vivo. Among these compounds, 13a has low dark toxicity and high phototoxicity, which makes it an effective and promising prodrug for PDT.

Objective: To investigate the inhibitory effect of giganteaside D (GD) on hepatocellular carcinoma and its molecular mechanisms., Methods: The inhibitory effects of GD on Hep 3b cells were determined using MTT assay and colony formation assay. The morphological changes of Hep 3b cells after GD treatment were observed by electron microscopy, and the cell cycle changes was analyzed using flow cytometry. The cell apoptosis and mitochondrial potential collapse in the treated cells were tested with Hoechst staining assay and flow cytometry. The expression levels of Bcl-2, PARP and key proteins in MAPK pathway were detected using Western blotting., Results: GD showed a significant inhibitory effect on Hep 3b cells with an IC 50 value of 16.08 µmol/L at 72 h. Flow cytometric analysis demonstrated that the phases of cell cycle remained unchanged and a sub-G1 peak (from 3.3% to 33.6%) appeared as GD concentration increased. GD-induced apoptosis was further conformed by Hoechst staining assay, and flow cytometry showed increased mitochondrial potential collapse in the cells. Western blotting demonstrated the cleavage of PARP, decrease of Bcl-2 and p-Erk1/2 (Thr202/Tyr204), and activation of p-p38 (Thr180/Tyr182) and p-JNK (Thr183/Tyr185) in GD-treated cells., Conclusions: GD has significant inhibitory effect against hepatocellular carcinoma cells in vitro by inducing apoptosis possibly in association with the MAPK signaling pathway.

As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.

Neuroblastoma is the second most common extracranial malignant solid tumor that occurs in childhood, and metastasis is one of the major causes of death in neuroblastoma patients. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. Therefore, this study investigated the mechanism by which transforming growth factor (TGF)-β1 induces EMT in human neuroblastoma cells. Using quantitative RT-qPCR and western blot analyses, we found that the mRNA and protein expression levels of E-cadherin were significantly decreased, whereas that of α-SMA was significantly increased after neuroblastoma cells were treated with different concentrations of TGF-β1. A scratch test and Transwell migration assay revealed that cell migration significantly and directly correlated with the concentration of TGF-β1 indicating that TGF-β1 induced EMT in neuroblastoma cells and led to their migration. Inhibiting Smad2/3 expression did not affect the expression of the key molecules involved in EMT. Further investigation found that the expression of the glioblastoma transcription factor (Gli) significantly increased in TGF-β1-stimulated neuroblastoma cells undergoing EMT, accordingly, interfering with Gli1/2 expression inhibited TGF-β1-induced EMT in neuroblastoma cells. GANT61, which is a targeted inhibitor of Gli1 and Gli2, decreased cell viability and promoted cell apoptosis. Thus, TGF-β1 induced EMT in neuroblastoma cells to increase their migration. Specifically, EMT induced by TGF-β1 in neuroblastoma cells did not depend on the Smad signaling pathway, and the transcription factor Gli participated in TGF-β1-induced EMT independent of Smad signaling.

Athetis dissimilis (Hampson) has emerged as a serious pest on corn in recent years in China. Understanding the population response of A. dissimilis to temperature will be beneficial for adopting control strategies for this pest. The impact of five constant temperatures (17, 21, 25, 29, and 33 °C) on the life table of A. dissimilis was studied using age-stage, two-sex life table method in the laboratory. The results showed that the developmental time of egg, larva, pupa, and adult decreased when temperature increased from 17 °C to 33 °C. The TPOP (total preoviposition period) decreased with temperature increasing from 17 °C to 29 °C, while the longest APOP (adult preoviposition period) occurred at 21 °C (3.57 d) and the shortest at 33 °C (2.15 d). The fecundity increased from 407.52 to 763.94 eggs as temperatures were raised from 17 to 25 °C, but decreased at temperatures from 25 °C to 33 °C. The intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) increased as temperatures increased from 17 to 25 °C, then decreased when temperatures exceeded 25 °C. In contrast, the mean generation time (T) decreased as temperatures increased from 17 to 33 °C. Based on the estimated data, the highest female age-stage-specific fecundity (fx) and age-specific fecundity (mx) were 81.91 and 45.04 eggs, respectively, at 25 °C. The age-stage life expectancy (exj) of all stages decreased as the temperature increased. The reproductive value (vxj) increased gradually with age and stage. The developmental rates of A. dissimilis between 17 to 29 °C fit the linear equation y  = -0.01315 + 0.001303x, with a coefficient of determination (R2) of 0.9314. In conclusion, our finding clearly states that A. dissimilis has the greatest population increase at 25 °C, and this may help develop appropriate pest management strategies., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Panax ginseng C.A. Meyer is a valuable herb in China that has also gained popularity in the West because of its pharmacological properties. The constituents isolated and characterized in ginseng stems include ginsenosides, fatty acids, amino acids, volatile oils, and polysaccharides. In this study, the effects of fungicide azoxystrobin applied on antioxidant enzyme activity and ginsenosides content in ginseng stems was studied by using Panax ginseng C. A. Mey. cv. (the cultivar of Ermaya) under natural environmental conditions. The azoxystrobin formulation (25% SC) was sprayed three times on ginseng plants at different doses (150ga.i./ha and 225ga.i./ha), respectively. Two new fatty acids esters (ethyl linoleate and methyl linolenate) were firstly detected in ginseng stems by the application of azoxystrobin as foliar spray. The results indicated that activities of enzymatic antioxidants, the content of ginsenosides and two new fatty acids esters in ginseng stems in azoxystrobin-treated plants were increased. Azoxystrobin treatments to ginseng plants at all growth stages suggest that the azoxystrobin-induced delay of senescence is due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species (AOS). The activity of superoxide dismutase (SOD) in azoxystrobin-treated plants was about 1-3 times higher than that in untreated plants. And the effects was more significant (P=0.05) when azoxystrobin was applied at dose of 225ga.i./ha. This work suggests that azoxystrobin plays an important role in delaying of senescence by changing physiological and biochemical indicators and increasing ginsenosides content in ginseng stems., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation., Competing Interests: No potential conflicts of interest were identified by any of the authors.

Background: Transgenic rice producing the insecticidal protein from Bacillus thuringiensis Berliner (Bt) is protected from damage by lepidopteran insect pests. However, one of the main concerns about Bt rice is the potential impact on non-target herbivores. In the present study, the ecological impacts of two Bt rice lines, T1C-19 expressing Cry1C protein and T2A-1 expressing Cry2A protein, on the non-target herbivore brown planthopper (BPH), Nilaparvata lugens (Stål), were evaluated under laboratory and field conditions. The purpose was to verify whether these Bt rice lines could affect the performance of BPH at individual and population scales., Results: Laboratory results showed that most of the fitness parameters (development duration, survival rate, fecundity, fertility, amount of honeydew excreted) of BPH were not significantly affected by the two tested Bt rice lines, although the development duration of fourth-instar nymphs fed on T1C-19 was distinctly longer compared with that on T2A-1 and non-Bt rice plants. Five life-table parameters did not significantly differ among rice types. Two-year field trials also revealed no significant difference in population dynamics of BPH among rice types., Conclusion: It is inferred that the tested Bt rice lines are unlikely to affect the population growth of BPH., (© 2014 Society of Chemical Industry.)

Background: To report the preliminary experience of laparoscopic radical nephrectomy (LRN) in children with Wilms' tumor (WT) and renal cancer., Patients and Methods: From January 2010 to October 2013, the medical records of 7 cases of WT or renal cancer in children treated by LRN at two medical centers in China were reviewed., Results: All the patients were treated by LRN, and 3 of them underwent preoperative chemotherapy before surgery. The biggest tumor size was 10 cm without crossing the lateral edge of the vertebra at the time of operation. The median hospital stay was 8.5 days (range, 6-11 days). The pathologic investigation showed 5 cases of WT, 1 case of rhabdoid tumor, and 1 case of renal cell carcinoma. With a median follow-up of 1.9±1.5 years (range, 0.3-2.9 years), six children were in complete remission, and the remaining one was lost to follow-up. None of these patients presented evidence of oncological complications (tumoral recurrences, port-site implantation, or secondary lung metastases), and no small bowel obstruction occurred., Conclusions: LRN for WT and renal cancer may be considered as an option in selected children. Preoperative chemotherapy is to decrease tumor size and to facilitate the dissection, avoiding tumor rupture. For trained laparoscopic surgeons, the eventual indication of LRN is the tumor not crossing the midline. A long follow-up and more cases are necessary to evaluate the results of the laparoscopic approach.

Fluorinated amorphous carbon films exhibit superlow friction under vacuum, but are prone to catastrophic failure. Thus far, the intrinsic failure mechanism remains unclear. A prevailing view is that the failure of amorphous carbon film results from the plastic deformation of substrates or strong adhesion between two contacted surfaces. In this paper, using first-principles and molecular dynamics methodology, combining with compressive stress-strain relation, we firstly demonstrate that the plastic deformation induces graphitization resulting in strong adhesion between two contacted surfaces under vacuum, which directly corresponds to the cause of the failure of the films. In addition, sliding contact experiments are conducted to study tribological properties of iron and fluorinated amorphous carbon surfaces under vacuum. The results show that the failure of the film is directly attributed to strong adhesion resulting from high degree of graphitization of the film, which are consistent with the calculated results.

To evaluate risk via inhalation exposure of polybrominated diphenyl ethers (PBDEs) in office environment, thirty-six pairs air samples including PM2.5 (particles with aerodynamic diameter less than 2.5 μm), PM10 (particles with aerodynamic diameter less than 10 μm), total suspended particles (TSP) with matching gas phase were collected in office environment in Shanghai, China. The average concentrations of PM2.5, PM10 and TSP were 20.4, 27.2 and 50.3 μg/m3, respectively. Σ15PBDEs mean concentrations in PM2.5, PM10, TSP and gas phase were 51.8, 110.7, 148 and 59.6 pg/m3, respectively. Much more PBDEs distributed in fine fractions than coarse ones. PBDEs congener profiles found in PM2.5, PM10 and TSP (dominated by BDE-209) were different from that in gas phase (dominated by the tri- to penta-BDEs). Approximately 3.20 pg/kg/d PM2.5 bound PBDEs can be inhaled into the lung; 3.62 pg/kg/d PM10-PM2.5(particles with aerodynamic diameter of 2.5-10 μm) bound PBDEs tended to be deposited in the upper part of respiratory system, and the intake of PBDEs via gas-phase was 2.74 pg/kg/d. The exposure of PBDEs was far below the minimal risk levels (MRLs), indicating lower risk from PBDEs via inhalation in the studied office in Shanghai.

This study evaluated the levels and spatial distribution of PBDEs in 9 typical offices in Shanghai, China through the sample analysis of air and settled dust (floor dust, desktop dust and dust in computer case). PBDEs in air ranged from 93 to 322 pg/m(3), while the PBDEs levels in dust varied from 247 to 3.3 × 10(4) ng/g. Spatial variability of PBDEs in office dust was evident and likely influenced by air exchange and the use of electronic devices. A significant positive linear correlation was observed between the power usage rate and PBDE levels in both office air (R(2) = 0.81) and settled dust (R(2) = 0.94). The PBDEs exposure via inhalation and dust ingestion were both analyzed to estimate the life-time cancer risk, which is 1.34 × 10(-22) to 7.16 × 10(-22), significantly lower than the threshold level (10(-6)). Non-cancer risk indicated by the hazard index (<1) is also low in current exposure conditions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A 2-yr field trial was conducted to assess the impacts of two new transgenic Bt rice lines, T1C-19 expressing Cry1C protein and T2A-1 expressing Cry2A protein, on the arthropod community sampled via vacuum. All the arthropods were classified into five guilds, including herbivores, parasitoids, predators, detritivores, and others. The seasonal density and dominance distribution of each guild and community-level indices (species richness, Shannon-Wiener diversity index, Simpson diversity index, and evenness index) were compared among rice types. Principal response curves were used to investigate the differences of entire arthropod community of Bt rice plots relative to non-Bt rice plots. The results showed no significant difference was detected in the community-level indices and dominance distribution of guilds between Bt and non-Bt rice plots. The seasonal density of herbivores, detritivores, and others as well as density of the arthropod overall community were also not significantly affected by rice types in either year, although the density of predators and parasitoids in Bt rice plots was significantly lower than those in non-Bt rice plots. The lower abundances of Braconidae, Eulophidae, Cyrtorhinus lividipennis (Reuter) (Hemiptera: Miridae), and Theridiidae in Bt rice plots are likely attributed to the lower abundances of prey species or hosts. Principal response curves revealed that arthropod community in Bt was similar with that in non-Bt rice plots. In conclusion, our findings indicate that these two tested Bt rice lines had no marked negative effects on the arthropod community in the paddy fields.

Transgenic rice expressing Bacillus thuringiensis Berliner (Bt) protein can effectively control target insects including stem borers and leaf folders. However, the potential effects of Bt rice on nontarget organisms including nontarget herbivores have not been fully evaluated. In the current study, ecological fitness parameters of the nontarget herbivore, Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae), fed on T1C-19 (Cry1C) or T2A-1 (Cry2A) rice were compared with non-Bt rice (MH63) under laboratory conditions. A 2-yr field trial was also conducted to monitor the population dynamics of N. cincticeps in the Bt and control rice plots using the vacuum-suction machine and yellow sticky card traps. Laboratory results showed that there were no significant differences in some of biological parameters including egg developmental duration, adult fresh weight, adult longevity, and oviposition period when N. cincticeps fed on Bt or non-Bt rice was compared. However, the survival rate of N. cincticeps nymphs fed on T2A-1 Bt rice plants was significantly higher than that on the control. When N. cincticeps fed on T1C-19 Bt rice plants, its nymphal duration was significantly longer and fecundity significantly lower compared with those fed on both T2A-1 Bt and non-Bt rice plants; the preoviposition period of N. cincticeps fed on T1C-19 and T2A-1 Bt rice was also significantly shorter than those on non-Bt rice. Nonetheless, both seasonal density and population dynamics of N. cincticeps adults and nymphs were similar between Bt (T1C-19 and T2A-1) and non-Bt rice plots under field conditions. In conclusion, our results indicate that our two tested Bt rice lines would not lead to higher population of N. cincticeps. Long-term experiments to monitor the population dynamics of N. cincticeps at large scale need to be carried out to confirm the current results.

Taking stay-green sorghum (B35) and non-stay green sorghum (Sanchisan) as test materials, a pot experiment was conducted to study their leaf osmotic adjustment and chloroplast ultrastructure at flowering and filling stages under impacts of drought stress (45% -50% of maximum field capacity). For the two sorghum lines, drought stress caused the reduction of their leaf free water content and relative water content, and increased the leaf bound water content, water saturation deficit, and electrical conductivity, with the increment or dement being larger for Sanchisan than for B35. Drought stress increased the leaf soluble sugar content and proline content, with the increment of the soluble sugar content being larger for Sanchisan and the increment of the proline content being larger for B35, while decreased the leaf soluble protein content, with the decrement being larger for Sanchisan than for B35. The chloroplast ultrastructure of both B35 and Sanchisan under drought stress was damaged to some extent, but the damaged degree was obviously lower for B35 than for Sanchisan. The findings indicated that stay-green sorghum had a greater adaptation to drought stress through stronger osmotic adjustment.

A closed-loop-controlled surface perturbation technique was developed for controlling the flow-induced sound in a flow duct and acoustic resonance inside downstream cavities. The surface perturbation was created by piezo-ceramic THUNDER (THin layer composite UNimorph Driver and sEnsoR) actuators embedded underneath the surface of a test model with a semi-circular leading edge. A modified closed-loop control scheme based on the down-sampling theory was proposed and implemented due to the practical vibration characteristic limitation of THUNDER actuators. The optimally tuned control achieved a sound pressure reduction of 17.5 dB in the duct and 22.6 dB inside the cavity at the vortex shedding frequency, respectively. Changes brought up by the control in both flow and acoustic fields were analyzed in terms of the spectrum phase shift of the flow field over the upper surface of the test model, and a shift in the vortex shedding frequency. The physical mechanism behind the control was investigated in the view of developing an optimal control strategy.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma in HIV patients, which typically presents with lymphomatous effusions in the body cavities without forming mass lesions. PEL is associated with Kaposi sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus-8) with distinct clinical and pathologic features. Rare cases of KSHV-associated large B-cell lymphoma (KSHV-LBL) have been observed in the lymph nodes or extranodal sites without lymphomatous effusions during the course of disease. KSHV-LBL is generally similar to classic PEL on the basis of the clinical presentation (HIV(+) male), morphology (immunoblastic, plasmablastic, or anaplastic), immunophenotype (CD45(+), CD20(-), CD79a(-), CD30(+), CD138(+), and EMA(+)), presence of Epstein-Barr virus infection, and clonal immunoglobulin gene rearrangements. However, it is not clear whether KSHV-LBL is a distinct entity or represents part of the spectrum of classic PEL; in particular, there is no consensus diagnostic term for KSHV-LBL. In this study, we investigated the clinicopathologic features of 9 cases of KSHV-LBL from our files. An additional 43 such cases and 84 cases of classic PEL from the English literature were reviewed and compared with each other. In contrast to the classic PEL, KSHV-LBL had a very significant lower expression of CD45 (74% vs. 94%, P=0.004) but significant higher expression of CD20 (17% vs. 5%, P=0.04) and CD138 (70% vs. 38%, P=0.05). KSHV-LBL also had slightly higher positivity of CD79a (23% vs. 5%, P=0.13) and immunoglobulin light chain expression, although the difference was not statistically significant [κ chain (12% vs. 0%) and λ chain (31% vs. 21%)]. The expressions of EMA and CD30 were slightly lower in KSHV-LBL compared with those observed in PEL (57% vs. 75% and 63% vs. 76%, respectively). Interestingly, 29% (10/34) of cases of KSHV-LBL revealed aberrant CD3 expression, which may mislead to a diagnosis of T-cell lymphoma, particularly anaplastic large cell lymphoma in combination with the anaplastic morphology and expression of CD30 and EMA. Although KSHV-LBL shows different clinical presentations and some variations in immunophenotype from classic PEL, it is still uncertain, on the basis of our findings, whether it is justifiable to separate them as 2 distinct entities. Nevertheless, we feel it is necessary to have a consensus diagnostic term, and we recommend a tentative one as "KSHV-associated large B-cell lymphoma (KSHV-LBL)" to replace many different names previously used.

Members of group III histidine kinases from different filamentous fungi were previously shown to mediate osmoregulation and resistance to dicarboximide, phenylpyrrole and, aromatic hydrocarbon fungicides. In this study, we report the disruption of the gene encoding group III histidine kinase, AlHK1, in the economically important plant pathogen Alternaria longipes. The AlHK1 gene disruption had pleiotropic effects on this fungus. Besides the expected osmosensitivity and fungicides resistance, AlHK1 participated in the spore production process. In addition, the ΔAlHK1 strains had stronger aggressive ability to infect their host plant than that of their parental strain, the wild-type strain C-00, suggested that AlHK1 was involved in the pathogenicity of A. longipes and performed in this function by a negative manner. This is the first report to our knowledge.