Rapid Preparation Triggered by Visible Light for Tough Hydrogel Sensors with Low Hysteresis and High Elasticity: Mechanism, Use and Recycle-by-Design.

Hydrogels have emerged as promising candidates for flexible devices and water resource management. However, further applications of conventional hydrogels are restricted due to their limited performance and lack of a recycling strategy. Herein, a tough, flexible, and recyclable hydrogel sensor via a visible-light-triggered polymerization is rapidly created. The Zn2+ crosslinked terpolymer is in situ polymerized using g-C3N4 as the sole initiator to form in situ chain entanglements, endowing the hydrogels with low hysteresis and high elasticity. In the use phase, the hydrogel sensor exhibited high ion conductivity, excellent mechanical properties, fast responsiveness, high sensitivity, and remarkable anti-fatigue ability, making it exceptionally effective in accurately monitoring complex human movements. At the end-of-life (EOL), leveraging the synergy between the photodegradation capacity of g-C3N4 and the adsorption function of the hydrogel matrix, the post-consumer hydrogel is converted into water remediation materials, which not only promoted the rapid degradation of organic pollutants, but also facilitated collection and reuse. This innovative strategy combined in situ entangling reinforcement and tailored recycle-by-design that employed g-C3N4 as key blocks in the hydrogel to achieve high performance in the use phase and close the loop through the reutilization at EOL, highlighting the cost-effective synthesis, specialized structure, and life cycle management.

Astaxanthin attenuates cigarette smoke-induced small airway remodeling via the AKT1 signaling pathway.

BACKGROUND: Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms. METHODS: First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments. RESULTS: AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1. CONCLUSIONS: The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.

Percutaneous Ultrasound-Guided Medication Injection, a Potential Technique for Subglottic Stenosis.

INTRODUCTION: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and antiinflammatory properties. Submucosal injection of glucocorticoids or mitomycin, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks. CASE PRESENTATION: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost. CONCLUSION: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis.

The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. METHODS: A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. RESULTS: A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. CONCLUSION: Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. TRAIL REGISTRATION: Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Effects of background music on numerical and spatial location working memory: differences between extraverts and introverts.

This experimental research explored background music's influence on the performance of numerical and spatial location working memory of extraverts and introverts. Sixty participants (30 extraverts and 30 introverts) were asked to complete numerical and spatial location working memory tests, under the conditions of background music and silence. Results showed a main negative effect of background music on the participants' performance of spatial location working memory. A significant interaction effect between music and personality (extroversion and introversion) on this performance was also observed. It revealed that a more negative effect of music in introverts as compared with extroverts. In contrast, no main or interaction effect was observed for the performance of numerical working memory. According to the influence of music on working memory, introversion-extraversion personality factors of workers such as cashiers or drivers require consideration.

This experimental study explored the influence of background music on the performance of numerical and spatial location working memory of extraverts and introverts. Results showed that the interaction effect between music and personality (extroversion and introversion) on spatial location working memory performance was significant. In contrast, no main or interaction effect was observed for the performance of numerical working memory.

Development and validation of a practical prognostic nomogram for evaluating inpatient mortality of cirrhotic patients with acute variceal hemorrhage.

INTRODUCTION AND OBJECTIVES: Cirrhotic patients with acute variceal hemorrhage (AVH) have high short-term mortality. Established prognostic scores are seldom applicable clinically, partially because they need external validation or contain subjective variables. We aimed to develop and validate a practical prognostic nomogram based on objective predictors to predict prognosis for cirrhotic patients with AVH. PATIENTS AND METHODS: We enrolled 308 AVH patients with cirrhosis from our center as the derivation cohort to develop a new nomogram using logistic regression and validated it in cohorts of patients from Medical Information Mart for Intensive Care (MIMIC) III (n = 247) and IV (n = 302). RESULTS: International normalized ratio (INR), albumin (ALB) and estimated glomerular filtration rate (eGFR) were identified as predictors for inpatient mortality and a nomogram was constructed based on them. The nomogram discriminated well in both derivation and MIMIC-III/-IV validation cohorts with the area under the receiver operating characteristic curves (AUROCs) of 0.846 and 0.859/0.833, respectively and showed a better agreement between expected and observed outcomes (Hosmer-Lemeshow tests, all comparisons, P > 0.05) than other scores in all cohorts. Our nomogram had the lowest Brier scores (0.082/0.114/0.119 in training/MIMIC-III/MIMIC-IV) and highest R2 (0.367/0.393/0.346 in training/MIMIC-III/MIMIC-IV) compared to the recalibrated model for end-stage liver disease (MELD), MELD-hepatic encephalopathy (MELD-HE) and cirrhosis acute gastrointestinal bleeding (CAGIB) scores in all cohorts. CONCLUSIONS: We developed a practical prognostic nomogram using easily verified indicators available in initial patient evaluation, which may serve as a reliable tool to accurately predict inpatient mortality for cirrhotic patients with AVH.

Efficacy of high-flow nasal cannula in patients with acute heart failure: a systematic review and meta-analysis.

BACKGROUND: Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF. METHODS: We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status. RESULTS: From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14-0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 - -0.47, P < 0.00001) and HR (SMD: -0.88, 95% CI: -1.07 - -0.69, P < 0.00001), and hospital stay (SMD: -0.94, 95% CI: -1.76 - -0.12, P = 0.03), and increase arterial oxygen partial pressure (PaO2), (SMD: 0.88, 95% CI: 0.70-1.06, P < 0.00001) and oxygen saturation (SpO2 [%], SMD: 0.70, 95% CI: 0.34-1.06, P = 0.0001). CONCLUSIONS: There were no significant differences in intubation rate, RR, HR, arterial blood gas parameters, and dyspnea scores between the HFNC and NIV groups. Compared with COT, HFNC effectively reduced the intubation rate and provided greater clinical benefits to patients with AHF. However, there was no significant difference in the clinical prognosis of patients with AHF between the HFNC and NIV groups. TRIAL REGISTRATION: PROSPERO (identifier: CRD42022365611).

Clinical impacts of sarcopenic obesity on chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. METHODS: In this cross-sectional study, the pulmonary function, St. George's Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. RESULTS: In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799-0.940). BMI (OR: 1.474, 95% CI: 1.124-1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. CONCLUSION: The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.

Single-cell sequencing analysis and transcriptome analysis constructed the macrophage related gene-related signature in lung adenocarcinoma and verified by an independent cohort.

BACKGROUND: Recent studies have emphasized the close relationship between macrophages and tumor immunity, and the prognosis of lung adenocarcinoma (LUAD) patients is intimately linked to this. Nonetheless, the prognostic signature and classification of different immune patterns in LUAD patients based on the macrophages is largely unexplored. METHODS: Two sc-RNAseq datasets of LUAD patients were collected and reprocessed. The differentially expressed genes (DEGs) related to macrophages between LUAD tissues and normal lung tissues were then identified. Based upon the above genes, three distinct immune patterns in the TCGA-LUAD cohort were identified. The ssGSEA and CIBERSORT were applied for immune profiling and characterization of different subtypes. A four-gene prognostic signature for LUAD patients was established based on the DEGs between the subtypes using stepwise multi-Cox regression. TCGA-LUAD cohort was used as training set. Five GEO-LUAD datasets and an independent cohort containing 112 LUAD samples were used for validation. TIDE (tumor immune dysfunction and exclusion) and drug sensitivity analyses were also performed. RESULTS: Macrophage-related differentially expressed genes were found out using the publicly available scRNA-seq data of LUAD. Three different immune patterns which were proved to have distinct immune infiltration characteristics in the TCGA-LUAD cohort were recognized based on the above macrophage-related genes. Thereafter, 174 DEGs among the above three different immune patterns were figured out; on the basis of this, a four-gene prognostic signature was constructed. This signature distinguished the prognosis of LUAD patients well in various GSE datasets as well as our independent cohort. Further analyses revealed that patients which had a higher risk score also accompanied with a lower immune infiltration level and a worse response to several immunotherapy biomarkers. CONCLUSION: This study highlighted that macrophage were significantly associated with TME diversity and complexity. The four-gene prognostic signature could be used for predicting outcomes and immune landscapes for patients with LUAD.

Mesoporous Carbon-Based Materials for Enhancing the Performance of Lithium-Sulfur Batteries.

The most promising energy storage devices are lithium-sulfur batteries (LSBs), which offer a high theoretical energy density that is five times greater than that of lithium-ion batteries. However, there are still significant barriers to the commercialization of LSBs, and mesoporous carbon-based materials (MCBMs) have attracted much attention in solving LSBs' problems, due to their large specific surface area (SSA), high electrical conductivity, and other unique advantages. The synthesis of MCBMs and their applications in the anodes, cathodes, separators, and "two-in-one" hosts of LSBs are reviewed in this study. Most interestingly, we establish a systematic correlation between the structural characteristics of MCBMs and their electrochemical properties, offering recommendations for improving performance by altering the characteristics. Finally, the challenges and opportunities of LSBs under current policies are also clarified. This review provides ideas for the design of cathodes, anodes, and separators for LSBs, which could have a positive impact on the performance enhancement and commercialization of LSBs. The commercialization of high energy density secondary batteries is of great importance for the achievement of carbon neutrality and to meet the world's expanding energy demand.

Sanguinarine inhibits melanoma invasion and migration by targeting the FAK/PI3K/AKT/mTOR signalling pathway.

CONTEXT: Sanguinarine (SAG) is the most abundant constituent of Macleaya cordata (Willd.) R. Br. (Popaceae). SAG has shown antimammary and colorectal metastatic effects in mice in vivo, suggesting its potential for cancer chemotherapy. OBJECTIVE: To determine the antimetastatic effect and underlying molecular mechanisms of SAG on melanoma. MATERIALS AND METHODS: CCK8 assay was used to determine the inhibition of SAG on the proliferation of A375 and A2058 cells. Network pharmacology analysis was applied to construct a compound-target network and select potential therapeutic targets of SAG against melanoma. Molecular docking simulation was conducted for further analysis of the selected targets. In vitro migration/invasion/western blot assay with 1, 1.5, 2 µM SAG and in vivo effect of 2, 4, 8 mg/kg SAG in xenotransplantation model in nude mice. RESULTS: The key targets of SAG treatment for melanoma were mainly enriched in PI3K-AKT pathway, and the binding energy of SAG to PI3K, AKT, and mTOR were -6.33, -6.31, and -6.07 kcal/mol, respectively. SAG treatment inhibited the proliferation, migration, and invasion ability of A375 and A2058 cells (p < 0.05) with IC50 values of 2.378 µM and 2.719 µM, respectively. It also decreased the phosphorylation levels of FAK, PI3K, AKT, mTOR and protein expression levels of MMP2 and ICAM-2. In the nude mouse xenograft model, 2, 4, 8 mg/kg SAG was shown to be effective in inhibiting tumour growth. CONCLUSIONS: Our research offered a theoretical foundation for the clinical antitumor properties of SAG, further suggesting its potential application in the clinic.

Bufalin inhibits peritoneal dissemination of gastric cancer through endothelial nitric oxide synthase-mitogen-activated protein kinases signaling pathway.

Peritoneal dissemination threatens the survival of patients with gastric cancer (GC). Bufalin is an extract of traditional Chinese medicine, which has been proved to have anticancer effect. The target of bufalin in suppressing gastric cancer peritoneal dissemination (GCPD) and the underlying mechanism are still unclear. In this research, GC cell line MGC-803 and high-potential peritoneal dissemination cell line MKN-45P were treated with bufalin or L-NAME. Malignant biological behavior and protein level of GC cell lines were detected with MTT, wound healing, transwell, adhesion, and western blotting. Bioinformatics analysis and patient tissues were used to verify the role of endothelial nitric oxide synthase (NOS3) in GC. Mice model was used to assess the effect of bufalin and role of NOS3 in vivo. We found that bufalin inhibited the proliferation, invasion, and migration in GC cell lines. NOS3, which was an independent prognostic factor of GC patients, was predicted to be a potential target of bufalin. Further experiments proved that bufalin reduced the phosphorylation of NOS3, thereby inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, and ultimately suppressed GCPD by inhibiting EMT process. In conclusion, NOS3 was a potential therapeutic target and prognostic biomarker of GC. Bufalin could suppress GCPD through NOS3-MAPK signaling pathway, which provided more evidence support for intraperitoneal perfusion of bufalin to treat GCPD.

Bufalin inhibits human diffuse large B-cell lymphoma tumorigenesis by inducing cell death through the Ca2+/NFATC1/cMYC pathway.

The 5-year survival rate of diffuse large B-cell lymphoma (DLBCL) can reach 60%. However, nearly half of patients undergo relapse/refractory issues with a survival period of less than 2 years. New therapeutic approaches are therefore needed to improve chemotherapy efficacy and patient survival. Bufalin (BF), isolated from the traditional Chinese medicine Chansu, has been reported to play an anticancer role in multiple cancer cell types. However, there are few reports of the effects of BF on the growth of DLBCL. In the present study, we demonstrated that BF exerts antitumor activity in DLBCL cells, both in vitro and in vivo. Treatment of DLBCL cells with BF resulted in increased proliferation and apoptosis in a dose- and time-dependent manner. Daily intraperitoneal injection of 1.5 mg/kg BF significantly delayed DLBCL xenograft growth in NOD/SCID mice without affecting body weight. Bioinformatics analysis showed that BF may regulate NFATC1 protein and affect expression of its downstream gene, cMYC. Our results suggest that BF can attenuate NFATC1 translocation by reducing the intracellular calcium concentration; BF may also have a low synergistic effect with cyclosporin A. In conclusion, we demonstrated that BF exerts antitumor activity that is mediated at least in part by the Ca2+/NFATC1/cMYC pathway. Our findings suggest that BF can be effectively applied as a novel potential therapeutic agent for DLBCL.

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma.

BACKGROUND: Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. METHODS: The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan-Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. RESULTS: In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. CONCLUSIONS: In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.

Ultrasound assessment of the rectus femoris in patients with chronic obstructive pulmonary disease predicts poor exercise tolerance: an exploratory study.

BACKGROUND: Reduced exercise tolerance is an important clinical feature of chronic obstructive pulmonary disease (COPD) and is associated with poor prognosis. The 6-min walk test (6MWT) is widely used to assess exercise capacity; however, it is not commonly administered in primary medical institutions because it requires a suitable site and professional training. Ultrasound has great potential for evaluating skeletal muscle dimensions in COPD. However, whether skeletal muscle ultrasound can predict impaired exercise tolerance is unclear. METHODS: The study included 154 stable patients with COPD, who were randomly divided into a development set and a validation set. The thickness (RFthick) and cross-sectional area (RFcsa) of the rectus femoris were measured using ultrasound. Standardized RFthick (STD- RFthick) and Standardized RFcsa (STD-RFcsa) were obtained via standardization of RFthick and RFcsa by patients' height. RESULTS: Strong correlations were observed between the 6MWD and RFthick (r = 0.84, p < 0.001) and between the 6MWD and RFcsa (r = 0.81, p < 0.001). In the development set, the optimal cut-off values for men and women for predicting poor exercise tolerance were < 3.098 cm/m and < 3.319 cm/m for STD-RFthick and < 4.052 cm2/m and < 4.366 cm2/m for STD-RFcsa, respectively. In the validation set, the area under the curve (AUC) values for the prediction of a 6MWD < 350 by STD-RFthick and STD-RFcsa were 0.881 and 0.903, respectively. Finally, the predictive efficacy of STD-RFthick (AUC: 0.922), STD-RFcsa (AUC: 0.904), and the derived nomogram model (AUC: 0.98) for exercise tolerance was superior to that of the sit-to-stand test and traditional clinical features. CONCLUSIONS: Rectus femoris ultrasound has potential clinical application to predict impaired exercise tolerance in patients with COPD.

Circular RNA circ_0046264 Suppresses Osteosarcoma Progression via microRNA-940/Secreted Frizzled Related Protein 1 Axis.

Circular RNAs (circRNAs) feature prominently in regulating tumor progression. The study aims to investigate the role and mechanism of circ_0046264 in osteosarcoma. In this study, dysregulated circRNAs in osteosarcoma tissues and adjacent tissues were screened out by analyzing circRNA microarray (GSE140256). The expressions of circ_0046264 in 58 osteosarcoma tissues and 4 osteosarcoma cell lines were detected by quantitative real-time polymerase chain reaction. Subsequently, the relationship of circ_0046264 expression level and clinical features were analyzed. Ethyldeoxyuridine assay and Transwell assay were employed to detect cell viability, migration and invasion. Dual-luciferase reporter assay was adopted to confirm the targeting relationships between circ_0046264 and microRNA-940 (miR-940), as well as miR-940 and secreted frizzled related protein 1 (SFRP1). SFRP1 expression was determined by western blot. Here, we demonstrated that circ_0046264 was greatly down-regulated in osteosarcoma and was inversely related to tumor size and Ki67 expression. Functional assays validated that circ_0046264 could restrain the proliferation, migration and invasion. Mechanistically, circ_0046264 could adsorb miR-940 and indirectly modulate SFRP1 expression. Furthermore, the transfection of miR-940 mimics or SFRP1 small interfering RNA could reverse the impact of circ_0046264 overexpression on the growth, migration and invasion of osteosarcoma cells. Taken together, circ_0046264 is a tumor suppressor to inhibit the osteosarcoma progression via modulating the miR-940 / SFRP1 axis.

Knockdown of G-protein-signaling modulator 2 promotes metastasis of non-small-cell lung cancer by inducing the expression of Snail.

Non-small-cell lung cancer (NSCLC) is the leading global cause of cancer-related death. Due to the lack of reliable diagnostic or prognostic biomarkers, the prognosis of NSCLC remains poor. Consequently, there is an urgent need to explore the mechanisms underlying this condition in order to identify effective biomarkers. G-protein-signaling modulator 2 (GPSM2) is widely recognized as a determinant of mitotic spindle orientation. However, its role in cancer, especially NSCLC, remains uncertain. In this study, we found that GPSM2 was downregulated in NSCLC tissues and was correlated with a poor prognosis. Furthermore, the knockdown of GPSM2 promoted NSCLC cell metastasis in vitro and in vivo and accelerated the process of epithelial-mesenchymal transition (EMT). Mechanistically, we showed that silencing GPSM2 induced cell metastasis and EMT through the ERK/glycogen synthase kinase-3ß/Snail pathway. These results confirm that GPSM2 plays an important role in NSCLC. Moreover, GPSM2, as an independent prognostic factor, could be a potential prognostic biomarker and drug target for NSCLC.

Lymecycline reverses acquired EGFR-TKI resistance in non-small-cell lung cancer by targeting GRB2.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were first-line treatments for NSCLC patients with EGFR-mutations. However, about 30 % of responders relapsed within six months because of acquired resistance. In this study, we used Connectivity Map (CMap) to discover a drug capable of reversing acquired EGFR-TKIs resistance. To investigate Lymecycline's ability to reverse acquired EGFR-TKIs resistance, two Icotinib resistant cell lines were constructed. Lymecycline's ability to suppress the proliferation of Icotinib resistant cells in vitro and in vivo was then evaluated. Molecular targets were predicted using network pharmacology and used to identify the molecular mechanism. Growth factor receptor-bound protein 2 (GRB2) is an EGFR-binding adaptor protein essential for EGFR phosphorylation and regulation of AKT/ERK/STAT3 signaling pathways. Lymecycline targeted GRB2 and inhibited the resistance of the cell cycle to EGFR-TKI, arresting disease progression and inducing apoptosis in cancer cells. Combined Lymecycline and Icotinib treatment produced a synergistic effect and induced apoptosis in HCC827R5 and PC9R10 cells. Cell proliferation in resistant cancer cells was significantly inhibited by the combined Lymecycline and Icotinib treatment in mouse models. Lymecycline inhibited the resistance of the cell cycle to EGFR-TKI and induced apoptosis in NSCLC by inhibiting EGFR phosphorylation and GRB2-mediated AKT/ERK/STAT3 signaling pathways. This provided strong support that Lymecycline when combined with EGFR targeting drugs, enhanced the efficacy of treatments for drug-resistant NSCLC.

A Water-Soluble Fluorescent Probe for the Selective Sensing of Ag+ and its Application in Imaging of Living Cells and Nematodes.

In this study, an imidazole-coumarin based fluorescent probe was developed for the selective and sensitive detection of Ag+ in aqueous solution. Using a combination of Job plot, NMR titrations, and DFT calculations, the binding properties between Ag+ and the probe were deeply investigated, and the results revealed a 1:1 binding stoichiometry between the probe and Ag+ with a binding constant of 1.02 × 106 M-1. The detection limit was found to be 150 nM, which satisfies the requirement for the quantitative detection of Ag+ in real water samples. Moreover, the new probe, Ic, was successfully applied to sense Ag+ in HeLa and HepG2 cells as well as in C. elegans, indicating that it could be a useful tool for the environmental monitoring of Ag+ pollution. These results demonstrated that Ic could serve as a high-efficiency and low-cost fluorescent probe for tracking Ag+ in an aquatic environment and biological organisms.