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IntroductionThe increasing prevalence of recurrent spontaneous abortion (RSA) poses significant physical and psychological challenges for affected individuals. Quercetin, a natural plant flavonoid, shows promise in reducing miscarriage rates, yet its precise mechanism remains elusive. This study uses network pharmacology, molecular docking, and experimental validation to explore the molecular pathways through which quercetin mitigates RSA.MethodsQuercetin-related target genes were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and RSA target genes were retrieved from the Comparative Toxicogenomics Database (CTD), with overlapping targets identified using Venn diagrams. All genes were visualized using the STRING database, and core targets were selected with Cytoscape 3.7.3. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID and Reactome online resources. Subsequently, HTR-8/SVneo cells were stimulated with lipopolysaccharide (LPS) and treated with varying concentrations of quercetin (1, 5, and 10 μM), then subjected to CCK-8, wound healing, transwell, and annexin V-FITC/PI apoptosis assays. Reverse-transcription quantitative PCR was used to determine the mRNA expression levels of IL-1β, TNF-α, and IL-6 in LPS-induced cells post-quercetin intervention, and western blotting was used to measure AKT1, MMP9, and caspase-3 protein levels.ResultsA total of 139 quercetin-associated target genes were identified from the TCMSP database, and 98 disease-associated target genes were obtained from the CTD, resulting in 25 shared target genes. Gene ontology enrichment highlighted the involvement of these targets in positive regulation of apoptosis, response to hypoxia, and intrinsic apoptotic signaling pathway in response to DNA damage. KEGG pathway analysis indicated enrichment in pathways related to interleukin-4 and interleukin-13 signaling, cytokine signaling in the immune system, and apoptosis. Molecular docking studies revealed robust binding of quercetin with MMP9, AKT1, IL-1β, TNF, and caspase-3. In vitro experiments demonstrated that quercetin enhanced LPS-induced cell activity, fostering proliferation, migration, and invasion, and reducing apoptosis. Moreover, quercetin reduced IL-1β, TNF-α, and IL-6 mRNA expression, increased AKT1 and MMP9 protein levels, and reduced caspase-3 expression.ConclusionQuercetin could mitigate the incidence of RSA by modulating inflammatory responses and apoptotic processes, through upregulation of AKT1 and MMP9, and downregulation of caspase-3, IL-1β, TNF-α, and IL-6. Quercetin opens up a new way of thinking about treating RSA.

Abstract Background Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. Methods We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. Results In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. Conclusions Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Abstract Background Wilms’ tumour gene 1 (WT1) is clearly recognized as a tumour promoter in diversiform of human malignancies. Nevertheless, knowledge of its expression, functions and potential molecular mechanisms in non-small cell lung cancer (NSCLC) remains elusive. Methods Differential expression of WT1 mRNA and protein between NSCLC and normal tissues were assessed by analyzing RNA-seq data from Oncomine and protein data from Human Protein Atlas, respectively. Subsequently, prognosis significance and immune cell infiltration were analyzed by Kaplan-Meier plotter and CIBERSORT. 60 pairs of local NSCLC tissues were involved to validate WT1 expression by quantitative PCR (qPCR) and Western blot. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, transwell, dual luciferase reporter assays and in vivo xenograft tumour growth experiments were conducted to explore the function and mechanism of WT1 in NSCLC. Results Our solid data indicated that WT1 was increased in NSCLC tissues and cell lines in comparison with their matched controls. In particular, its upregulation correlated with worse prognosis and immune infiltration of the patients. Functional assays demonstrated that knockdown of WT1 inhibited NSCLC malignancy, including inhibiting cell proliferation, survival and invasion. Further exploration discovered that microRNA-498-5p (miR-498-5p) was the upstream suppressor of WT1 by directly targeting the 3’ untranslated region (UTR) of WT1 mRNA. Moreover, expression of miR-498-5p was notably decreased and inversely correlated with WT1 in NSCLC tissues. Finally, we proved that miR-498-5p was a potent tumour suppressor in NSCLC by suppressing cell proliferation, survival and invasion, while WT1 restoration could in turn disrupt this suppression both in vitro and in vivo. Conclusion The abnormal increase in WT1 contributes to the malignant properties of NSCLC cells, and miR-498-5p is a natural inhibitor of WT1. Our findings might facilitate the development of novel therapeutic strategies against NSCLC in the future.

Research Highlights: This study examined the emotional and cognitive health benefits of nature in comparison with working memory training. It considered the long-term effects, the application of mobile terminal technology, and routine-based approaches with the aim of integrating nature’s health benefits into people’s daily lives. Background and Objectives: Infectious diseases and aging may limit people’s activities indoors; the recovery effect of nature has been widely recognized, and terminal technology is developing rapidly. In this context, we want to explore the emotional and cognitive effects of viewing nature (VR) videos on mobile devices for a long time. Materials and Methods: The experiment employed a between-subjects design, with participants being randomly assigned to one of four groups: a forest VR video group, a water VR group, a working memory training group, and a control group. The participants watched the video three times a week for 20 min each for four weeks. The number of valid participants for compliance, preference, and willingness was 136, and the number of valid participants for the study of emotional and cognitive effects was 62. Brief Profile of Mood States (BPOMS) scales, running memory accuracy, shifting cost, etc., were used as indicators to reflect emotions and cognition. A repeated measures analysis of variance was performed on these indicators at four groups × two time points (pretest/post-test). Results: ① There were no significant differences in the participants’ adherence, preferences, and willingness to watch different natural videos and perform working memory training. ② Long-term home training (e.g., watching VR nature videos or working memory training) may have had a minimal effect on emotional responses to mobile terminals. However, home training may be more conducive to the stabilization of anger. ③ Watching forest VR videos had a positive effect on the updating function of the brain; watching water VR videos was beneficial for the shifting function and automatic processing speed; and working memory training had a positive effect on the updating and shifting functions. Conclusions: There were no significant differences in adherence, preference, willingness, and effects on emotion and cognition between long-term forest VR video viewing, water VR video viewing, and working memory training on mobile terminals. All three types of home training may be beneficial for the stabilization of emotion (especially anger), and all can have some positive effects on cognition.

Solid waste produced by the nonferrous smelting industry has a significant number of notable differences. The lack of recognition of solid waste characteristics is the main factor restricting its disposal and utilization. In this study, we analyzed the main production processes of the nonferrous smelting industry; identified the key production nodes of solid waste; and clarified the characteristics, including the physical, chemical, and pollution characteristics of solid wastes, through a large sample statistical analysis. We found similarities among solid wastes from a common generation source as well as notable differences among the different generation sources: slags and sludges from waste acid treatment and wastewater treatment units had a water content of 27.43–52.71% and 51.14–68.27%, respectively, which were significantly higher than those of other metallurgy and dust collection units; the pH of slags from an electrorefining unit was strongly alkaline; the mineral phase of sludges from wastewater treatment was only calcite; slags from a waste acid treatment unit were mainly in phase of gypsum, claudetite, and anglesite; the chemical composition of slags from pyrometallurgy and hydrometallurgy units was mainly SiO2 and Fe2O3. In this paper, we discuss a new classification method based on a common generation source for the first time. These results are beneficial to guide the disposal, utilization, and management of solid waste.

Optimize the ultrasonic extraction process of polysaccharides from Dendrobium denneanum by Response surface design (RSM). The main polysaccharide (DP40) from was separated by anion exchange chromatography, and its structure was modified by low-temperature plasma. The results showed that the polysaccharide extraction rate of ultrasonic was 22.98 ± 0.97%, which was significantly higher than water extraction method(P

Abstract Background Lung cancer screening may provide a “teachable moment” for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non‐smokers has not been reported. Methods A baseline smoking behavior survey was conducted in 2000 participants who were screened by low‐dose computed tomography (LDCT) from 2014 to 2018. All participants were re‐surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non‐smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression. Results From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non‐smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non‐smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27–6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08–0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes. Conclusions The overall decreased smoking prevalence indicated an overwhelming effect of “teachable moment” on “license to smoke.” A tailored smoking cessation strategy should be integrated into lung cancer screening.

Abstract Tracheal tumors are rare, accounting for 0.1% of all malignancies. Squamous cell carcinoma and adenoid cystic carcinoma are the two most prevalent tracheal cancers. Less than 20 cases of extramedullary plasmacytoma in the trachea and main bronchus have ever been documented in the literature, making it extremely uncommon. Although the origin of these lesions is unclear, viral pathogenesis and persistent inflammation are thought to be the main causes. Clinically, these individuals exhibit vague symptoms such as stridor, a persistent cough, dyspnea, or wheezing, making a correct diagnosis difficult.

Abstract Synergies of transcription factors, chromatin modifiers and their target genes are vital for cell fate determination in human cancer. Although the importance of numerous epigenetic machinery for regulating gliomagenesis has been previously recognized, how chromatin modifiers collaborate with specific transcription factors remains largely elusive. Herein we report that Pontin chromatin remodelling factor acts as a coactivator for LEF1 to activate TGFβ/SMAD signalling, thereby contributing to gliomagenesis. Pontin is highly expressed in gliomas, and its overexpression paralleled the grade elevation and poor prognosis of patients. Functional studies verified its oncogenic roles in GBM cells by facilitating cell proliferation, survival and invasion both in vitro and in vivo. RNA sequencing results revealed that Pontin regulated multiple target genes involved in TGFβ/SMAD signalling. Intriguingly, we found that Pontin amplified TGFβR2 gene transcription by recruiting LEF1, thereby activating TGFβ/SMAD signalling and facilitating gliomagenesis. Furthermore, higher TGFβR2 expression conferred worse patient outcomes in glioma. To conclude, our study revealed that the Pontin-LEF1 module plays a crucial role in driving TGFβR2 gene transcription, which could be exploited to target TGFβ/SMAD signalling for anti-glioma therapy.

Abstract Pulmonary mucoepidermoid carcinoma (PMEC) is uncommon. The purpose of this study was to evaluate the clinicopathological features, diagnostic criteria, treatment options, and prognostic factors relating to primary PMEC. Clinical data on 45 patients with primary PMEC were collected and analyzed retrospectively at Tianjin Medical University General Hospital and the First People’ Hospital of Longquanyi District Chengdu from January 2008 to December 2020. The 45 patients (25 males and 20 females) ranged in age from 22 to 72 years, with a median age of 49 and an average age of 47.7. All the patients underwent surgery, with 32 receiving only surgery and 13 receiving both surgery and postoperative chemotherapy. A total of 34 instances of low‐grade tumors and 11 cases of high‐grade tumors were discovered during postoperative pathological diagnosis. Forty‐five patients were followed for 13 to 78 months, and four died during this period. In all four instances, a lung infection unrelated to the tumor was determined to be the cause of death. The MAML2 gene translocation was detected in 40 of 45 patients, with 34 of them testing positive. Radical surgery with lymph node dissection is an efficient treatment for PMEC. The prognosis is poor for patients with advanced disease, a negative MAML2 gene translocation, lymph node metastases, and high‐grade tumors.

BackgroundUnderstanding the effects of demographic drivers on lung cancer mortality trends is critical for lung cancer control. We have examined the drivers of lung cancer mortality at the global, regional, and national levels.MethodsData on lung cancer death and mortality were extracted from the Global Burden of Disease (GBD) 2019. Estimated annual percentage change (EAPC) in the age-standardized mortality rate (ASMR) for lung cancer and all-cause mortality were calculated to measure temporal trends in lung cancer from 1990 to 2019. Decomposition analysis was used to analyze the contributions of epidemiological and demographic drivers to lung cancer mortality.ResultsDespite a non-significant decrease in ASMR [EAPC = −0.31, 95% confidence interval (CI): −1.1 to 0.49], the number of deaths from lung cancer increased by 91.8% [95% uncertainty interval (UI): 74.5–109.0%] between 1990 and 2019. This increase was due to the changes in the number of deaths attributable to population aging (59.6%), population growth (56.7%), and non-GBD risks (3.49%) compared with 1990 data. Conversely, the number of lung cancer deaths due to GBD risks decreased by 19.8%, mainly due to tobacco (−12.66%), occupational risks (−3.52%), and air pollution (−3.47%). More lung cancer deaths (1.83%) were observed in most regions, which were due to high fasting plasma glucose levels. The temporal trend of lung cancer ASMR and the patterns of demographic drivers varied by region and gender. Significant associations were observed between the contributions of population growth, GBD risks and non-GBD risks (negative), population aging (positive), and ASMR in 1990, the sociodemographic index (SDI), and the human development index (HDI) in 2019.ConclusionPopulation aging and population growth increased global lung cancer deaths from 1990 to 2019, despite a decrease in age-specific lung cancer death rates due to GBD risks in most regions. A tailored strategy is needed to reduce the increasing burden of lung cancer due to outpacing demographic drivers of epidemiological change globally and in most regions, taking into account region- or gender-specific risk patterns.

Abstract Background Lung cancer is a highly malignant tumor with a poor prognosis. The establishment of faithful ex vivo cell models is essential for investigating the metastatic mechanisms and developing new anticancer agents. In this study, we established and characterized a novel lung cancer cell line derived from metastatic lymph node tissue from a Chinese patient. Methods A primary culture of metastatic lymph node tissue from a patient with lung cancer was used to establish a cell line. The phenotypic characteristics of the cell line were characterized by colony‐formation, CCK8, and Transwell assays, and xenografting. The genetic characteristics were evaluated by chromosome analysis, short tandem repeat (STR) profiling, and quantitative real time‐polymerase chain reaction (qRT‐PCR). Results A novel lung cancer cell line, named ZX2021H, was successfully established from a metastatic lymph node lesion from a lung cancer patient. The cell line exhibited high capacities for proliferation and invasion, as validated by its phenotypic and genetic characteristics. This cell line had a unique STR profile and karyotype analysis revealed numerical and structural chromosome abnormalities. The growth rate of in vivo xenografted tumors established using ZX2021H cells was higher than that using H1299 cells. The cell stemness‐related gene SOX2 was overexpressed in ZX2021 compared with H1299 cells, as determined by qRT‐PCR. Conclusion We successfully established a novel, highly malignant lung cancer cell line, ZX2021H, derived from metastatic lymph node tissue from a Chinese lung cancer patient. This cell line may provide an ideal cell model for further studies of the molecular mechanisms underlying lung cancer metastasis and for the development of new anticancer agents.

(1) Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that threatens the population health of older adults. However, the mechanisms of the altered metabolism involved in AD pathology are poorly understood. The aim of the study was to identify the potential biomarkers of AD and discover the metabolomic changes produced during the progression of the disease. (2) Methods: Gas chromatography–mass spectrometry (GC–MS) was used to measure the concentrations of the serum metabolites in a cohort of subjects with AD (n = 88) and a cognitively normal control (CN) group (n = 85). The patients were classified as very mild (n = 25), mild (n = 27), moderate (n = 25), and severe (n = 11). The serum metabolic profiles were analyzed using multivariate and univariate approaches. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify the potential biomarkers of AD. Biofunctional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. (3) Results: Our results revealed considerable separation between the AD and CN groups. Six metabolites were identified as potential biomarkers of AD (AUC > 0.85), and the diagnostic model of three metabolites could predict the risk of AD with high accuracy (AUC = 0.984). The metabolic enrichment analysis revealed that carbohydrate metabolism deficiency and the disturbance of amino acid, fatty acid, and lipid metabolism were involved in AD progression. Especially, the pathway analysis highlighted that l−glutamate participated in four crucial nervous system pathways (including the GABAergic synapse, the glutamatergic synapse, retrograde endocannabinoid signaling, and the synaptic vesicle cycle). (4) Conclusions: Carbohydrate metabolism deficiency and amino acid dysregulation, fatty acid, and lipid metabolism disorders were pivotal events in AD progression. Our study may provide novel insights into the role of metabolic disorders in AD pathogenesis and identify new markers for AD diagnosis.

The growth of Dendrobium nobile is sensitive to heat stress. To find an effective method for enhancing heat tolerance, this study investigated the relieving effect of exogenous calcium at different concentrations (0 mmol/L, 5 mmol/L, 10 mmol/L, 15 mmol/L, 20 mmol/L CaCl2) on heat stress in D. nobile. Principal component analysis was used to screen the optimal exogenous calcium concentration, and transcriptome analysis was used to reveal its possible heat tolerance mechanism. The results showed that compared with the T0, a 10 mmol/L calcium treatment: increased the average leaf length, leaf width, plant height, and fresh matter accumulation of D. nobile by 76%, 103.39%, 12.97%, and 12.24%, respectively (p < 0.05); significantly increased chlorophyll a (Chla), chlorophyll b (Chlb), carotenoids(Car), ascorbic acid (ASA), glutathione (GSH), and flavonoids by 15.72%, 8.54%, 11.88%, 52.17%, 31.54%, and 36.12%, respectively; and effectively enhanced the enzyme activity of the antioxidant system, increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) by 1.38, 1.61, and 2.16 times, respectively (p < 0.05); At the same time, the treatment can effectively reduce the yellow leaf rate and defoliation rate of D. nobile under heat stress. The principal component analysis method and membership function were used to calculate the D value to rank the relief effects of each calcium treatment group, and the results also showed that 10 mmol/L CaCl2 had the best relief effect. Transcriptomics testing identified 7013 differentially expressed genes, of which 2719 were upregulated, and 294 were downregulated. Among them, genes such as HSPA1s, HSP90A, HSPBP1, ATG8, COMT, REF1, E1.11.1.7, along with transcription factors such as MYB, bHLH, WRKY, and NAC, formed the network of tolerance to heat stress in D. nobile. This study provides new insights for improving the cultivation techniques of D. nobile.

The shear process of small batch and multivariety copper strip processing enterprises are the bottleneck of production, which often faces the contradiction between working efficiency (less tool changing) and yield (reducing geometric waste). The high yield of copper strip embryo is the core index of high yield and high benefit for enterprise. Less tool changing is a key step for high efficiency and fast product delivery in shear station. In this paper, we took the cutting production of the production management system as a research example in Hubei Lean High Precision Copper Strip Company when the system is developing. We used the penalty function to deal with the length floating constraint. Then, we established a multiobjective optimization model with the roll weight and the number of tool changing as the weights, which were calculated by an integrated weighting method. Three algorithms, namely, adaptive particle swarm optimization, niche genetic algorithm based on crowding, and niche genetic algorithm based on seed retention (NGA), were used to solve the problem. Through production examples, it was concluded that the solution solved by NGA has the highest utilization rate of the coil when the number of tool changing was as little as possible. This paper provides a new solution combining the efficiency and benefit for shear process in finished product delivery of copper strip processing enterprises.

Objective To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). Methods By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. Results From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. Conclusions ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.

Abstract Background Chest radiograph (CXR) is still one of the most commonly used diagnostic tools for chest diseases. In this cohort study, we attempted to investigate the magnitude and temporal pattern of lung cancer risk following abnormal CXR findings. Methods We conducted an extended follow‐up of an occupational screening cohort in Yunnan, China. The associations between abnormal CXR results from baseline screening, the first four consecutive rounds of CXR screening, all previous rounds of screening and lung cancer risk were analyzed using time‐varying coefficient Cox regression model. The associations of lung cancer risk and previous CXR‐screening results according to histology were also considered. Sensitivity analyses were conducted to assess the robustness of the previous abnormal CXR findings on subsequent lung cancer risk. Results Abnormal CXR findings were associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared to negative screening results, the adjusted hazard ratios (HR) of baseline abnormal CXR results, and at least one abnormal result in the first four consecutive screening rounds during the first 5 years of follow‐up were 17.06 (95% CI: 11.74–24.79) and 13.77 (95%: 9.58–17.79), respectively. This significantly increased lung cancer risk continued over the next 5 years. These associations were stronger for persistent abnormal findings, and abnormal findings identified in recent screening rounds. Conclusions The increased risk was significant for both squamous cell carcinoma and adenocarcinoma. Although decreased over time, an increased lung cancer risk relative to abnormal CXR findings can continue for 10 years.

Abstract Background MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. Methods The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). Results miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3′untranslated region (3′UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What’s more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. Conclusions These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.

Cowpea (Vigna unguiculata) is one of the main edible legume vegetables in China, and it can improve spleen and stomach function. A polysaccharide component (VUP80-3) has been isolated from V. unguiculata in this study. The average molecular weight of VUP80-3 is 6.43 × 104 Da, and the main monosaccharide group is glucose. The mass ratio of monosaccharide groups in the polysaccharide was glucose:galactose:arabinose:rhamnose:xylose:mannose:fucose = 152.36:24.50:16.53:8.13:1.26:0.97:0.82. NMR analysis showed that VUP80-3 has →4)-α-D-Galp (1→ and →4)-α-D-Glcp(1→ main chain and →3,4)-β-D-Glcp(1→, →4,6)-α-D-Glcp(1→ branch chains, and the terminal sugar is α-D-Glcp(1→. Biological activity test results showed that VUP80-3 at 1000 μg·mL−1 significantly increased the activity of ethanol injured GES-1 cells (p < 0.01) and significantly reduced reactive oxygen species (ROS) in ethanol injured GES-1 cells and inflammatory factors (IL-8, IL-1β and TNF-α,) in GES-1 cells. This compound also reduced the apoptosis rate (p < 0.05), thereby significantly reducing the oxidative damage caused by ethanol in GES-1 cells. Therefore, VUP80-3 is a potential drug to protect the gastric mucosa from damage.

Cyclodextrins (CDs) are one of the most extensively studied cyclic-oligosaccharides due to their low toxicity, good biodegradability and biocompatibility, facile chemical modification, and unique inclusion capacity. However, problems such as poor pharmacokinetics, plasma membrane disruption, hemolytic effects and a lack of target specificity still exist for their applications as drug carriers. Recently, polymers have been introduced into CDs to combine the advantages of both biomaterials for the superior delivery of anticancer agents in cancer treatment. In this review, we summarize four types of CD-based polymeric carriers for the delivery of chemotherapeutics or gene agents for cancer therapy. These CD-based polymers were classified based on their structural properties. Most of the CD-based polymers were amphiphilic with the introduction of hydrophobic/hydrophilic segments and were able to form nanoassemblies. Anticancer drugs could be included in the cavity of CDs, encapsulated in the nanoparticles or conjugated on the CD-based polymers. In addition, the unique structures of CDs enable the functionalization of targeting agents and stimuli-responsive materials to realize the targeting and precise release of anticancer agents. In summary, CD-based polymers are attractive carriers for anticancer agents.

Abstract Pontin (RUVBL1) is a highly conserved ATPase of the AAA + (ATPases Associated with various cellular Activities) superfamily and is implicated in various biological processes crucial for oncogenesis. Its overexpression is observed in multiple human cancers, whereas the relevance of Pontin to gliomagenesis remains obscure. To gain insights into Pontin involvement in glioma, we performed bioinformatics analyses of Pontin co-expressed genes, Pontin-affected genes, and carried out experimental studies. The results verified that Pontin was upregulated in gliomas. Its higher levels might predict the worse prognosis of glioma patients. The Pontin co-expressed genes were functionally enriched in cell cycle progression and RNA processing. In the nucleus, Pontin promoted cell growth via facilitating cell cycle progression. Using RNA-seq, we found that Pontin knockdown resulted in altered expression of multiple genes, among which the E2F1 targets accounted for a large proportion. Mechanistic studies found that Pontin interacted with E2F1 and markedly amplified the E2F1 transcription response in an ATPase domain-dependent manner. By analyzing the RNA-seq data, we also found that Pontin could impact on the alternative splicing (AS). Both differential expressed genes and AS events affected by Pontin were associated with cell cycle regulation. Taken together, our findings provide novel insights of the importance of Pontin in gliomagenesis by regulating cell cycle and AS, and shed light on the possible application of Pontin as an antineoplastic target in glioma.

N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m6A RNA methylation is catalyzed by m6A writers, removed by m6A erasers and recognized by m6A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m6A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m6A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m6A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m6A’s function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy.

Coronavirus main protease is essential for viral polyprotein processing and maturation. Here Fu et al. report efficient inhibition of SARS-CoV-2 replication using two inhibitors - Boceprevir and GC376 - targeting the active site of the main viral protease.

Dendrobium denneanum is an important medicinal and ornamental plant. Its ornamental and medicinal values are affected by its vegetative growth conditions and chemical composition accumulation. This study adopted an orthogonal experimental design to treat D. denneanum with nine different levels of nitrogen (N), potassium (K), and phosphorus (P). The morphological indicators of the plant were positively correlated with the nitrogen concentration. The polysaccharide content was the highest at 1500 mg·L−1 nitrogen and 3000 mg·L−1 phosphorous and was 26.84% greater than the control. The flavonoid content increased by 36.2% at 500 mg·L−1 nitrogen, 2000 mg·L−1 phosphorous, and 300 mg·L−1 potassium. Principal component score analysis showed that nitrogen had the most significant impact on the various indicators of D. denneanum, followed by phosphorus and potassium. The comprehensive score showed that the T9 treatment (N: 1500 mg·L−1, P: 3000 mg·L−1, K: 500 mg·L−1) had the strongest effect on D. denneanum. Transcriptional analysis showed that compared with the control, the T9 treatment led to 2277 differentially expressed genes (1230 upregulated and 1047 downregulated). This includes fifteen genes enriched in the MAPK signaling pathway, five genes in phenylpropanoid biosynthesis, and two genes in flavonoid biosynthesis. These genes may be involved in regulating plant growth and the biosynthesis of polysaccharides and flavonoids. This study provides guidance for the optimal use of N, P, and K in the cultivation of D. denneanum.

A TCM formula has played an important role in the treatment of COVID-19 in China. However, the mechanism of TCM action is still unclear.

The golden tide, a large biomass bloom of the brown macroalgae Sargassum horneri, occurs yearly in the Yellow Sea, where it causes enormous economic and ecologic losses. To investigate the response of S. horneri to global warming and eutrophication, S. horneri was cultured under six conditions of varying temperature combinations (20 and 24 °C) and nitrogen levels (5, 30, and 300 μM). The growth, photosynthetic performance, pigment content, and contents of soluble protein were assessed. The growth of S. horneri followed an increasing trend with increasing N concentration at ambient temperature. Elevated temperatures had an inhibitory effect on growth and photosynthesis in S. horneri, which was further enhanced by eutrophication. This suggests that in the globally warming environment of the future, eutrophication may reduce the frequency and scale of gold tide outbreaks during the hot season.

This paper provides a comprehensive understanding of the amplitude- and frequency-dependent characteristics of rubber springs. The dynamic nonlinear inelasticity of rubber is a key academic problem for continuum mechanics and a bottleneck problem for the practical use of rubber structures. Despite intensive efforts witnessed in industrial applications, it still demands an unambiguous constitutive model for dynamic nonlinear inelasticity, which is known as the Payne effect. To this end, three types of rubber springs (shear-type (ST), compression-type (CT) and shear-compression-combination-type (SCCT)) were tested with amplitude and frequency sweeps in different conditions. We investigated and present changes in dynamic stiffness and loss factor with amplitude, frequency and the hysteresis loops of different rubber springs. We also propose a hypothesis and research strategy to study a constitutive model involving multiple factors of hyperelasticity, the Mullins effect, viscoelasticity and the Payne effect, which we hope will provide new ideas for the establishment of a constitutive equation.

The treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) has been proven to induce lasting tumor remission. Screening suitable populations for immunotherapy through predictive markers is an important approach to improving the clinical benefits of patients. Evidence has shown that there may be a close connection between NOTCH signaling and the tumor microenvironment (TME). Hence, we explored the impact of the mutation status of NOTCH signaling on the prognosis of NSCLC patients treated with immunotherapy with the aim to apply NSCLC immunotherapy to the greatest extent possible. We examined two clinical cohorts of NSCLC patients receiving ICIs (MSKCC and NG cohorts). The mutation and prognostic data of the ICI-treated cohort were used to evaluate the association between the mutation status of NOTCH signaling and prognosis following immunotherapy. The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to analyze the differences in the immune microenvironment under different NOTCH signaling mutation states. In the ICI-treated cohorts, the univariate and multivariate Cox regression analyses indicated that high-mutated NOTCH signaling could serve as an independent predictor of NSCLC patients receiving ICIs. Patients with high-mutated NOTCH signaling had significantly improved progression-free survival (PFS) (P = 0.03, HR = 0.69; MSKCC cohort) and prolonged overall survival (OS) (P = 0.004, HR = 0.34; NG cohort). Additionally, high-mutated NOTCH signaling was related to the inflammatory immune microenvironment, inflammatory expression profile, and enhanced immunogenicity. According to this study, high-mutated NOTCH signaling may serve as a biomarker for the prediction of the prognosis of NSCLC patients treated with ICIs. A series of prospective clinical studies and molecular mechanism explorations are still needed in the future.

According to the theory of reconsolidation, the contents of an original memory can be updated after reactivation with subsequent new learnings. However, there seems to be a lack of an appropriate behavioral paradigm to study the reconsolidation of explicit self-related memory, which is of great significance to further explore its cognitive neural mechanism in the future. In two separate experiments, we adapted a trial-by-trial interfering paradigm with a self-episodic simulation process and investigated (1) whether it is possible to reconsolidate negative memories under the new behavioral paradigm and (2) how the emotional valence of post-retrieval interference material affects the reconsolidation of negative memories. The results showed that the negative memories under trial-by-trial self-simulation can be degraded and updated via post-retrieval interference processes. Individuals whose original memories were reactivated by initial background cues and who were then presented with new interference situations were less able to recall original scenes and showed more memory intrusions on these scenes than those who had experienced new learning without reactivation or only reactivation without interference. Furthermore, the extent and manner of memory change/updating were greatly influenced by the characteristics of interference information. For memories with negative valences, new learning materials with the same valence produced superior interference effects in the form of lower correct recalls and more integrated false; whereas the neutral interference materials can cause more memory intrusion. Post-retrieval memory distortions of negative self-memory may underlie different functional mechanisms.

Abstract Background Hertwig’s epithelial root sheath (HERS) is important in guiding tooth root formation by differentiating into cementoblasts through epithelial–mesenchymal transition (EMT) and inducing odontoblastic differentiation of dental papilla through epithelial–mesenchymal interaction (EMI) during the tooth root development. Thus, HERS cells are critical for cementum and dentin formation and might be a potential cell source to achieve tooth root regeneration. However, limited availability and lifespan of primary HERS cells may represent an obstacle for biological investigation and therapeutic use of tooth tissue engineering. Therefore, we constructed, characterized, and tested the functionality of immortalized cell lines in order to produce a more readily available alternative to HERS cells. Methods Primary HERS cells were immortalized via infection with lentivirus vector containing the gene encoding simian virus 40 Large T Antigen (SV40LT). Immortalized HERS cell subclones were isolated using a limiting dilution method, and subclones named HERS-H1 and HERS-C2 cells were isolated. The characteristics of HERS-H1 and HERS-C2 cells, including cell proliferation, ability of epithelial–mesenchymal transformation and epithelial–mesenchymal interaction, were determined by CCK-8 assay, immunofluorescence staining, and real-time PCR. The cell differentiation into cementoblast-like cells or periodontal fibroblast-like cells was confirmed in vivo. And the inductive influence of the cell lines on dental papilla cells (DPCs) was also confirmed in vivo. Results HERS-H1 and HERS-C2 cells share some common features with primary HERS cells such as epithelial-like morphology, positive expression of CK14, E-Cadherin, and Vimentin, and undergoing EMT in response to TGF-beta. HERS-C2 cells showed the EMT characteristics and could differentiate into cementum-forming cells in vitro and generate cementum-like tissue in vivo. HERS-H1 could induce the differentiation of DPCs into odontoblasts in vitro and generation of dentin-like tissue in vivo. Conclusions We successfully isolated and characterized novel cell lines representing two key features of HERS cells during the tooth root development and which were useful substitutes for primary HERS cells, thereby providing a biologically relevant, unlimited cell source for studies on cell biology, developmental biology, and tooth root regeneration.

B lymphocyte-induced maturation protein-1 (Blimp1) is a key regulator that promotes the terminal differentiation of mature B lymphocytes into plasma cells, and is essential for the survival of Multiple myeloma (MM)cells. However, the expression of Blimp1 in MM and its effect on the signaling pathway remain unknown. Studies have found that during long-term endoplasmic reticulum (ER) stress, activated ATF4 may also stimulate the CCAAT-enhancer-binding protein homologous protein (CHOP) gene, triggering the unfolded protein response (UPR) terminal apoptotic pathway in plasma cells. Moreover Aspirin can induce MM cell apoptosis through mitochondria and death receptor pathway. Therefore, we aim to explore whether Aspirin could induce AFT4/CHOP apoptosis pathway in MM by inhibiting Blimp1 expression, thereby promoting MM cell apoptosis and exerting anti-tumor effects.

Rumination is an important etiological factor of anxiety pathology, with its mechanism related to the deficit of working memory. The current study examined whether working memory training (WM-T) and emotional working memory training (EWM-T) could reduce rumination in anxious individuals. The participants with high trait anxiety underwent 21 days of mobile applications-based WM-T (n = 34), EWM-T (n = 36) or placebo control (n = 36), with questionnaires, cognitive tasks, and resting electroencephalogram (EEG) as the pre-post-test indicators. The results revealed that two training groups obtained comparable operation span increases (WM-T: d = 0.53; EWM-T: d = 0.65), updating improvement (WM-T: d = 0.43; EWM-T: d = 0.60) and shifting improvement (WM-T: d = 0.49; EWM-T: d = 0.72). Furthermore, compared to the control group, the EWM-T showed significant self-reported rumination reduction (d = 0.69), increased inhibition ability (d = 0.72), as well as modification of resting EEG microstate C parameters (Duration C: d = 0.42, Coverage C: d = 0.39), which were closely related to rumination level (r ~ 0.4). The WM-T group also showed the potential to reduced self-reported rumination (d = 0.45), but with the absence of the observable inhibition improvement and resting EEG changes. The correlation analysis suggested that the emotional benefits of WM-T depending more on improved updating and shifting, and that of EWM-T depending more on improved inhibition ability. The advantage to add emotional distractions into general working memory training for targeting rumination related anxiety has been discussed.

Objectives: MET protein expression has been reported to be in relevance with the survival of NSCLC patients in various studies, yet the results were inconsistent. The purpose of our study set out to determine the prognostic role of both c-MET and p-MET expression among NSCLC that underwent surgical resection.Methods: Data were obtained from retrospective cohort studies by searching on PubMed, Cochrane Library, EMBASE and Web of Science, and a meta-analysis was performed to assess the prognostic role of MET expression among NSCLC.Results: Totally 18 literatures including 5,572 surgically resected NSCLC cases staged I-IV were included for data synthesis. The positive rate of c-MET and p-MET was 1,753/4,315 and 135/1,257. The pooled hazard ratios (HRs) regarding c-MET and p-MET expression for overall survival (OS) was 1.623 (95% CI: 1.176–2.240, p = 0.003) and 1.710 (95% CI: 0.823–3.533, p = 0.15), respectively. Subgroup analysis results on Asian (HR = 2.115, p < 0.001), adenocarcinoma (HR = 2.220, p < 0.001) and rabbit polyclonal antibodies (HR = 2.107, p < 0.001) etc. were also indicative.Conclusion: C-MET over-expression among NSCLC patients that underwent surgical resection is a prognostic factor that indicated adverse survival on OS. Whereas, p-met didn't appear to have an impact on the prognosis of NSCLC. The studies are need and the topic could be re-valued by then.

Uncertainty contributes to stress and anxiety-like behaviors by impairing the ability of participants to objectively estimate threat. Our study used the cue-picture paradigm in conjunction with the event-related potential (ERP) technique to explore the temporal dynamics of anticipation for and response to uncertain threat in healthy individuals. This task used two types of cue. While ‘certain’ cues precisely forecasted the valence of the subsequent pictures (negative or neutral), the valence of pictures following ‘uncertain’ cues was not predictable. ERP data showed that, during anticipation, uncertain cues elicited similar Stimulus-Preceding Negativity (SPN) to certain-negative cues, while both of them elicited larger SPN than certain-neutral cues. During affective processing, uncertainty enlarged the mean amplitude of late positive potential (LPP) for both negative and neutral pictures. Behavioral data showed that participants reported more negative mood ratings of uncertain-neutral pictures relative to certain-neutral pictures and overestimated the probability of negative pictures following uncertain cues. Importantly, the enlarged anticipatory activity evoked by uncertain cues relative to that evoked by certain-neutral cues positively modulated the more negative mood ratings of uncertain-neutral pictures relative to certain-neutral pictures. Further, this more negative mood ratings and the general arousal anticipation during anticipatory stage contributed to the covariation bias. These results can provide a novel insight into understanding the neural mechanism and pathological basis of anxiety.

Background and objective Our previous study found that nicotine could induce lung cancer cell epithelial-mesenchymal transition (EMT). The aim of this study is to explore the relationship between nicotine-induced EMT and lung cancer invasion and metastasis. Methods Real-time PCR and Western blot were used to detect the expression changes of EMT-related markers, E-cadherin and Vimentin, in A549 lung cancer cells treated with nicotine; The transposition of β-catenin protein expression was determined by immunofluorescence; Scratch test and Transwell invasion assay were used to detect the effects of nicotine on lung cancer cell migration and invasion. Results Nicotine can significantly down-regulate the expressional level of E-cadherin mRNA and protein of A549 cells in a manner of dose and time-dependent (P

The esterification of malic acid using traditional homogenous catalysts suffers from the difficulty in reuse of the catalyst and undesirable side reactions. In this work, Zr(SO4)2/SiO2 and Zr(SO4)2/activated carbon (AC) as solid acid catalysts were prepared for malic acid esterification with methanol. The conversion of malic acid over these two catalysts is comparable to that over H2SO4 and unsupported Zr(SO4)2∙4H2O catalysts; however; a 99% selectivity of dimethyl malate can be realized on these two supported catalysts, which is much higher than that of conventional H2SO4 (75%) and unsupported Zr(SO4)2∙4H2O (80%) catalysts, highlighting the critical role of AC and SiO2 supports in tuning the selectivity. We suggest that the surface hydroxyls of AC or lattice O2− ions from SiO2 donate electrons to Zr4+ in Zr(SO4)2/AC and Zr(SO4)2/SiO2 catalysts, which results in the increase in electron density on Zr4+. The enhanced electron density on Zr4+ reduces the degree of H delocalization from crystal water and then decreases the Brønsted acid strength. Consequently, the reduced Brønsted acid strength of Zr(SO4)2/AC and Zr(SO4)2/SiO2 catalysts suppresses the intermolecular dehydration side reaction. In addition, these two supported catalysts can be easily separated from the reaction system by simple filtration with almost no loss of activity.

The nickel (II) loading silica-alumina under various treatments in terms of aging temperature, Si/Al ratio and activation temperature were investigated by XRD, N2 adsorption-desorption, TEM, UV-Vis, NH3-TPD and XRF and then applied to catalyze the ethylene oligomerization. High aging temperature, low Si/Al ratio and high activation temperature were beneficial to high selectivity for C10+ products because of a reasonable match between Ni active sites and acid sites, high Ni loading content and less octahedral coordination Ni2+ species, respectively. Ni loading content was more important than the number of acid sites for high yield of C10+ products, and less octahedral coordination Ni2+ species favored less by-products produced at high reaction temperature. In addition, other experimental conditions, such as reaction temperature, weight hourly space velocity (WHSV) and nickel precursor were discussed in the paper.

According to the framework of emotion regulation (ER), both explicit and implicit forms are essential to our well-being. It is the interaction between these two processes that ensures adaptive emotional responses. Although many studies have focused on explicit ER deficits in anxiety, there is still a lack of awareness about the implicit form and its role in anxiety. To address this issue, we explored the time course of implicit ER processes in individuals with high and low trait anxiety (LTA). To do this, we employed the newly developed Priming-Identify (PI) paradigm, which includes a word-matching task (externally-generated implicit goals) and a facial expression identification task (emotion processing). We aimed to modulate the implicit ER goals of individuals through the application of different priming conditions (ER-related and -unrelated words). In addition to their behavioral effects, we recorded the influence of these priming conditions through event-related potentials (ERPs) during the facial expression identification task. Three ERP components were chosen as indexes of three stages of implicit ER processing: N170, early posterior negativity (EPN) and late positive potential (LPP). In individuals with LTA, the early N170 and the middle EPN were enlarged under the ER-related priming condition, while the LPP was not influenced. However, in individuals with high trait anxiety (HTA), we observed an absence of any significant differences between the ER-related and -unrelated priming conditions across all three ERP components. Furthermore, enlargements of N170 and EPN amplitudes were significantly correlated with a decrease in negative emotion experience scores. Our results suggest that HTA individuals experience implicit ER deficits during the early and middle stages of ER.

Background and objective Cisplatin-resistance in Lung cancer cells is widespread in the clinical treatment, seriously affecting the effects of the treatment of lung cancer. Therefore, the research of mechanisms of cisplain-resistance has significant meaning for developing new chemotherapeutic drug and solving the cisplain-resistance in clinic treatment. IKBKB is one of the most important catalytic subunits of IKK complexes. It plays an important regulatory role in activation of NF-κB. The aim of this study is to investigate the differential expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance induced by IKBKB gene. Methods MTT assay was employed to determine the sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB gene on A549 cell lines’ sensitivity to cisplatin. The mRNA level of IKBKB was determined by real-time PCR. Dual luciferase reporter gene experiment was employed to determine the activity of the NF-κB. Apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry. Results Apoptosis rate and IC50 were significantly different in A549 and A549/DDP cells, the expression of mRNA level of IKBKB gene in A549/DDP was significantly higher than that in A549. Compared with control group, IKBKB gene was able to reduce the cisplain sensitivity of A549 cells. After A549 was transfected with pcDNA3.1/IKBKB plasmid, mRNA level of IKBKB was significantly increased, the sensitivity of cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was decreased 59%, the activity of NF-κB has been greatly increased. Conclusion IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-κB pathway. It will be helpful in the development of new anticancer drug and solving the challenge of cisplatin-resistance.

Background and objective Cisplatin is the first-line drug for the chemotherapy of non-small cell lung cancer (NSCLC), but the acquired chemoresistance restricted the effect of its treatment. The aim of this study is to validate the miRNAs related to the Cisplatin resistance in lung cancer and elucidate the molecular mechanisms. Methods We performed miRNA microarray and RT-PCR to obtain the aberrant differential expressed miRNAs between A549 and its paired Cisplatin-resistant cell line A549/DDP cells, and then we investigated the biological functions of miR-192, which is the aberrant differential expressed miRNA. After transfection of the miR-192 into A549 cells, we measured the half inhibition concentration (IC50), cell apoptosis of the trasfectant cells, and then we used biological softwares and dual-luciferase report assay to explore the target gene of the miR-192, which was further validated by RT-PCR and Western blot. Result MiR-192 was highly over-expressed in A549/DDP cells , whose quantity was 37.59±0.35 fold higher than that in A549 cells. Overexpression of miR-192 in A549 cells significantly conferred resistance to Cisplatin and inhibited apoptosis. By contrast, down-expression of miR-192 in A549/DDP cells remarkably restrained the Cisplatin resistance and induced apoptosis. MiR-192 binded to Bim 3’-UTR and negatively regulated Bim expression at the post-transcriptional level in lung adenocarcinoma cells. Conclusion Our data suggested that miR-192 induced Cisplatin-resistance and inhibited cell apoptosis in lung cancer via negative targeting Bim expression.

The clinical application of HIV fusion inhibitor, enfuvirtide (T20), was limited mainly because of its short half-life. Here we designed and synthesized two PEGylated C34 peptides, PEG2kC34 and PEG5kC34, with the PEG chain length of 2 and 5 kDa, respectively, and evaluated their anti-HIV-1 activity and mechanisms of action. We found that these two PEGylated peptides could bind to the HIV-1 peptide N36 to form high affinity complexes with high α-helicity. The peptides PEG2kC34 and PEG5kC34 effectively inhibited HIV-1 Env-mediated cell−cell fusion with an effective concentration for 50% inhibition (EC50) of about 36 nM. They also inhibited infection of the laboratory-adapted HIV-1 strain NL4-3 with EC50 of about 4−5 nM, and against 47 HIV-1 clinical isolates circulating in China with mean EC50 of PEG2kC34 and PEG5kC34 of about 26 nM and 32 nM, respectively. The plasma half-life (t1/2) of PEG2kC34 and PEG5kC34 was 2.6 h and 5.1 h, respectively, and the t1/2 of PEGylated C34 was about 2.4-fold and 4.6-fold longer than C34 (~1.1 h), respectively. These findings suggest that PEGylated C34 with broad-spectrum anti-HIV-1 activity and prolonged half-life can be further developed as a peptide fusion inhibitor-based long-acting anti-HIV drug for clinical use to treat HIV-infected patients who have failed to respond to current anti-retrovirus drugs.

The CeO2 ordinary amorphous, nanopolyhedrons, nanorods, and nanocubes were prefabricated by the hydrothermal method, and employed as carriers of Fe/W–CeO2 catalysts to selectively catalyze the reduction of NO with ammonia. Characterization results indicated that the morphology of CeO2 support originated from selectively exposing different crystal surfaces, which has a significant effect on oxygen vacancies, acid sites and the dispersion of Fe2O3. The CeO2 nanopolyhedrons catalyst (Fe/W–CeO2–P) showed most oxygen vacancies, the largest the quantity of acid sites, the largest BET (Brunauer-Emmett-Teller) surface area and the best dispersion of Fe2O3, which was associated with predominately exposing CeO2 (111) planes. Consequently, the Fe/W–CeO2–P catalyst has the highest NO conversion rate in the temperature range of 100–325 °C among the ordinary amorphous, nanorods, and nanocubes Fe/W–CeO2 catalysts.

Lung cancer is one of the malignant tumors with fastest growing rates in incidence and mortality in our country, also with largest threat to human health and life. However, the exact mechanisms underlying lung cancer development remain unclear. The microenvironment of tumor hypoxia was discovered in 1955, but hypoxia in lung cancer tissues had not been successfully detected till 2006. Further studies show that hypoxia not only functions through the resistance to radiotherapy, but also regulates lung cancer development, invasion, metastasis, chemotherapy resistance and prognosis through an important oncogene HIF (hypoxia inducible factor), with its regulators PHD (prolyl hydroxylase domain) and pVHL (product of von Hippel-Lindau gene). Therefore, hypoxia, HIF, PHD and pVHL should be considered as potential therapeutic targets for lung cancer pathogenesis and progression.

Background and objective The aim of this study is to investigate difference of antiangiogenesis ablility and interaction about bevacizumab and endostatin in vivo in lung cancer animal model. Methods First, we construct a Balb/c mice model with A549 lung adenocarcinoma cell. Then, we divide the mice into four groups randomly. Every group has six mice. Control group: mice injected with normal saline every day aroud the tumor. Endostatin group: mice injected with endostatin (Recombinant endostatin) injection (3 mg/kg) every day Peritumoral. Bevacizumab group: mice injected with bevacizumab twice a week (biw/5 mg/kg) Peritumoral. Combing group: mice were injected with endostatin and bevacizumab (dose just like single drug group). After 16 days, we executed mice and got the tumor tissue for next analysis. Results Based on this experiment, we found bevacizumab and endostatin expressed the ability for inhibiting tumor growth in vivo. Bevacizumab was more powerful (52.36% vs 38.68%). Combining bevacizumab with endostatin could get better results (64.15%) than single drug did. Bevacizumab played the role by inhibiting VEGF-A expression (60.8%). Endostatin took effect by inhibiting VEGF-A/C (14.6%, 30.3%). Combining group present better antitumor efficacy than any single drug group did. (79.7%, 44.2%). Conclusion Both bevacizumab and endostatin present the antiangiogenesis ability in vivo of lung cancer animal model. In our test, bevacizumab show better ability in inhibiting tumor growth than endostatin does. Additional, combing bevacizumab with endostatin reveal better potential to inhibit tumor growth than single drug does.

Background and objectives It has been proven that epigermal growth factor receptor (EGFR) signal pathway plaied an important role in the oncogenesis and development of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR-TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC in this study. Methods The tissue samples of 59 advanced NSCLC patients (34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy) were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with X^2 test. Results EGFR gene mutations were identified in 22 of 59 samples (37.3%). EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others (50% vs 18.9%, P0.05). Conclusions EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.