Tuning the Chirality Evolution in Achiral Subnanometer Systems by Judicious Control of Molecule Interactions.

Chirality evolution from molecule levels to the nanoscale in an achiral system is a fundamental issue that remains undiscovered. Here, we report the assembly of polyoxometalate (POM) clusters into chiral subnanostructures in achiral systems by programmable single-molecule interactions. Driven by the competing binding of Ca2+ and surface ligands, POM assemblies would twist into helical nanobelts, nanorings, and nanotubes with tunable helicity. Chiral molecules can be used to differentiate the formation energies of chiral isomers and immobilize the homochiral isomer, where strong circular dichroism (CD) signals are obtained in both solutions and films. Chiral helical nanobelts can be used as circularly polarized light (CPL) photodetectors due to their distinct chiroptic responsivity for right and left CPL. By the fine-tuning of interactions at single-molecule levels, the morphology and CD spectra of helical assemblies can be precisely controlled, providing an atomic precision model for investigation of the structure-chirality relationship and chirality manipulation at the nanoscale.

[Exploration of Application of Reliability Standard YY/T 1837-2022 in Development of Active Implantable Medical Devices].

In the field of medical devices, there has been a long-term lack of a general technical requirements framework for reliability that can be applied in the development of high-risk active implantable medical devices. This study combines the requirements of YY/T 1837-2022 to comprehensively explain and explore the requirements for reliability work that can be performed at each stage of development of active implantable medical device products, and provides a reference for product reliability work in the industry.

Prognostic outcome prediction by semi-supervised least squares classification.

Although great progress has been made in prognostic outcome prediction, small sample size remains a challenge in obtaining accurate and robust classifiers. We proposed the Rescaled linear square Regression based Least Squares Learning (RRLSL), a jointly developed semi-supervised feature selection and classifier, for predicting prognostic outcome of cancer patients. RRLSL used the least square regression to identify the scale factors and then rank the features in available multiple types of molecular data. We applied the unlabeled multiple molecular data in conjunction with the labeled data to develop a similarity graph. RRLSL produced the constraint with kernel functions to bridge the gap between label information and geometry information from messenger RNA and microRNA expression profiling. Importantly, this semi-supervised model proposed the least squares learning with L2 regularization to develop a semi-supervised classifier. RRLSL suggested the performance improvement in the prognostic outcome prediction and successfully discriminated between the recurrent patients and non-recurrent ones. We also demonstrated that RRLSL improved the accuracy and Area Under the Precision Recall Curve (AUPRC) as compared to the baseline semi-supervised methods. RRLSL is available for a stand-alone software package (https://github.com/ShiMGLab/RRLSL). A short abstract We proposed the Rescaled linear square Regression based Least Squares Learning (RRLSL), a jointly developed semi-supervised feature selection and classifier, for predicting prognostic outcome of cancer patients. RRLSL used the least square regression to identify the scale factors to rank the features in available multiple types of molecular data. RRLSL produced the constraint with kernel functions to bridge the gap between label information and geometry information from messenger RNA and microRNA expression profiling. Importantly, this semi-supervised model proposed the least squares learning with L2 regularization to develop the semi-supervised classifier. RRLSL suggested the performance improvement in the prognostic outcome prediction and successfully discriminated between the recurrent patients and non-recurrent ones.

Adriamycin induces cardiac fibrosis in mice via PRMT5-mediated cardiac fibroblast activation.

Long-term treatment with adriamycin (ADR) is associated with higher incidences of cumulative cardiotoxicity manifest as heart failure. ADR-induced cardiomyopathy is characterized by extensive fibrosis that is caused by cardiac fibroblast activation. To date, however, no specific treatment is available to alleviate ADR-induced cardiotoxicity. Protein arginine methyltransferase 5 (PRMT5), a major enzyme responsible for methylation of arginine, regulates numerous cellular processes such as cell differentiation. In the present study we investigated the role of PRMT5 in cardiac fibrosis. Mice were administered ADR (3 mg/kg, i.p., every 2 days) for 2 weeks. We showed that aberrant PRMT5 expression was largely co-localized with α-SMA-positive activated cardiac fibroblasts in ADR-injected mice and in ADR-treated cardiac fibroblasts in vitro. PRMT5-overexpression exacerbated, whereas PRMT5 knockdown alleviated ADR-induced cardiac fibrosis in vivo and TGF-ß1-induced cardiac fibroblast activation in vitro. We demonstrated that PRMT5-overexpression enhanced methylated-Smad3 levels in vivo and in vitro. Pretreatment with a specific PRMT5 inhibitor EPZ015666 (5 nM) or overexpression of a catalytically inactive mutant of PRMT5, PRMT5(E444Q), reduced PRMT5-induced methylation of Smad3, thus suppressing PRMT5-mediated cardiac fibroblast activation in vitro. Furthermore, ADR activated cardiac fibroblasts was depending on autocrine TGF-ß1. Taken together, our results demonstrate that PRMT5 promotes ADR-induced cardiac fibrosis via activating cardiac fibroblasts, suggesting that it may be a potential therapeutic target of ADR-caused cardiotoxicity.

Mutational landscape of DNA damage response deficiency-related genes and its association with immune biomarkers in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) has limited effective treatment strategies. DNA damage response (DDR) genes are of therapeutic interest in multiple cancer types. This study aimed to depict the landscape of DDR mutations in ESCC and evaluate the association between DDR mutations and known immunotherapy biomarkers. We recruited 250 Chinese patients with ESCC and performed next-generation sequencing. A total of 107 patients underwent a PD-L1 examination. Among the 250 patients, 73 (29.2%) harbored at least one DDR gene mutation and were defined as DDR-mut. Among the six functional DDR pathways, homologous recombination (HR) accounted for 12.4% (31/250). DDR-mut patients were significantly associated with higher tumor mutational burden than those in the DDR-wt group (p=7.4e-07). Patients with PDL1-H accounted for 21.2% (36/107) of the patients. PDL1-H was more prevalent in DDR-mut than DDR-wt, although the p-value did not reach a significant level (40.5% vs. 30%, p=0.29). Further analysis revealed that BRCA1, one of the most frequently mutated genes in the HR pathway, was significantly associated with PDL1-H (p=0.01). Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.

Biofertilizers with beneficial rhizobacteria improved plant growth and yield in chili (Capsicum annuum L.).

Chemical fertilizers can supply essential nutrients to crops increasing their yield, however, they can also cause serious environmental problems. Biofertilizer has received more and more attention because of its environmentally friendly and pollution-free characteristics. Haloxylon ammodendron, a desert succulent shrub, has become an important plant species for vegetation restoration in several deserts in China because of its strong drought tolerance. Its extensive root systems and unique rhizosphere bacterial community aid H. ammodendron adapt to this extreme environment. In this study, Bacillus sp. WM13-24 and Pseudomonas sp. M30-35 isolated from the rhizosphere of H. ammodendron in our previous study and Bacillus amyloliquefaciens GB03 and Sinorhizobium meliloti ACCC17578 as well-studied beneficial strains were used to prepare two types of biofertilizer, WM13-24 biofertilizer containing Bacillus sp. WM13-24 and integrated biofertilizer containing all the four strains. Results presented here showed that WM13-24 biofertilizer and the integrated biofertilizer improved chili plant growth, fruit yield and quality and the rhizosphere soil nitrogen content, enzyme activities, and the quantity and biodiversity of viable bacteria. Compared to the control, WM13-24 biofertilizer and a commercial biofertilizer, the integrated biofertilizer performed best in significantly increasing plant height, stem diameter, leaf length and width, chlorophyll content, fruit yield, soluble sugar content, ascorbic acid content, organic acid content, soil urease activity, catalase activity and the quantity and biodiversity of viable bacteria. This study provided a theoretical and practical basis for large scale development of integrated biofertilizers using beneficial rhizobacterial strains from the desert plant rhizosphere.

Induced Salt Tolerance of Perennial Ryegrass by a Novel Bacterium Strain from the Rhizosphere of a Desert Shrub Haloxylon ammodendron.

Drought and soil salinity reduce agricultural output worldwide. Plant-growth-promoting rhizobacteria (PGPR) can enhance plant growth and augment plant tolerance to biotic and abiotic stresses. Haloxylon ammodendron, a C4 perennial succulent xerohalophyte shrub with excellent drought and salt tolerance, is naturally distributed in the desert area of northwest China. In our previous work, a bacterium strain numbered as M30-35 was isolated from the rhizosphere of H. ammodendron in Tengger desert, Gansu province, northwest China. In current work, the effects of M30-35 inoculation on salt tolerance of perennial ryegrass were evaluated and its genome was sequenced to identify genes associated with plant growth promotion. Results showed that M30-35 significantly enhanced growth and salt tolerance of perennial ryegrass by increasing shoot fresh and dry weights, chlorophyll content, root volume, root activity, leaf catalase activity, soluble sugar and proline contents that contributed to reduced osmotic potential, tissue K⁺ content and K⁺/Na⁺ ratio, while decreasing malondialdehyde (MDA) content and relative electric conductivity (REC), especially under higher salinity. The genome of M30-35 contains 4421 protein encoding genes, 12 rRNA, 63 tRNA-encoding genes and four rRNA operons. M30-35 was initially classified as a new species in Pseudomonas and named as Pseudomonas sp. M30-35. Thirty-four genes showing homology to genes associated with PGPR traits and abiotic stress tolerance were identified in Pseudomonas sp. M30-35 genome, including 12 related to insoluble phosphorus solubilization, four to auxin biosynthesis, four to other process of growth promotion, seven to oxidative stress alleviation, four to salt and drought tolerance and three to cold and heat tolerance. Further study is needed to clarify the correlation between these genes from M30-35 and the salt stress alleviation of inoculated plants under salt stress. Overall, our research indicated that desert shrubs appear rich in PGPRs that can help important crops tolerate abiotic stress.

Innovative magnetic rings for circumferential mucosectomy: preliminary research.

PURPOSE: To improve the procedures used to treat prolapse and hemorrhoids, novel magnetic rings were invented to use in circumferential mucosectomies to avoid the disadvantages of stapling techniques. METHODS: Thirty adult pigs were randomly divided into three groups: Group A (n = 10), which underwent circumferential mucosectomy with novel magnetic rings; Group B (n = 10), which underwent circumferential mucosectomy with conventional magnetic rings and Group C (n = 10), which underwent circumferential mucosectomy with a stapling technique. RESULTS: All pigs underwent the operation successfully, and the mean length of the procedure was similar among the three groups (p > 0.05). There was no bleeding in Group A or Group B, while there was a mean blood loss of 78.32 ± 26.03 ml in Group C (p < 0.01). Three cases of anastomotic stenosis were found in Group C (3/10); two cases were found in Group B (2/10) and no anastomotic stenosis was found in Group A (0/10). The difference between groups A and C was statistically significant (p < 0.05). The cost for the magnetic rings in groups A and B was noticeably lower than that of the stapling techniques in Group C (20.12 ± 3.35 vs. 15.76 ± 2.92 vs. 550.16 ± 29.71 US dollars, p < 0.001). The magnetic rings in groups A and B were spontaneously discharged from the body with the necrotic tissues within 1-2 weeks (8.20 ± 2.73 vs. 9.31 ± 3.62 days, p > 0.05), avoiding the permanent implantation of staples in Group C. The anastomosis site in Group A showed a smoother and more rapid healing process than that in Group B or C. CONCLUSIONS: The innovative magnetic rings we developed for circumferential mucosectomies provide a simple and novel surgical procedure for prolapse and hemorrhoids.

Increased CCL19 and CCL21 levels promote fibroblast ossification in ankylosing spondylitis hip ligament tissue.

BACKGROUND: It is well-documented that both chemokine (C-C motif) ligand 19 (CCL19) and 21 (CCL21) mediate cell migration and angiogenesis in many diseases. However, these ligands' precise pathological role in ankylosing spondylitis (AS) has not been elucidated. The objective of this study was to examine the expression of CCL19 and CCL21 (CCL19/CCL21) in AS hip ligament tissue (LT) and determine their pathological functions. METHODS: The expression levels of CCL19, CCL21 and their receptor CCR7 in AS (n = 31) and osteoarthritis (OA, n = 21) LT were analyzed via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). The expression of CCL19, CCL21 and CCR7 in AS ligament fibroblasts was also detected. The proliferation of ligament fibroblasts was measured via a cell counting kit-8 (CCK8) assay after exogenous CCL19/CCL21 treatment. Additionally, the role of CCL19/CCL21 in osteogenesis was evaluated via RT-PCR and enzyme-linked immunosorbent assay (ELISA) in individual AS fibroblast cultures. Furthermore, the expression of the bone markers alkaline phosphatase (ALP), osteocalcin (OCN), collagenase I (COL1), integrin-binding sialoprotein (IBSP) and the key regulators runt-related transcription factor-2 (Runx-2) and osterix were investigated. Moreover, the CCL19/CCL21 levels in serum and LT were measured via ELISA. RESULTS: The mRNA levels of CCL19/CCL21 in AS hip LT were significantly higher than that in OA LT, and IHC analysis revealed a similar result. Exogenous CCL19/CCL21 treatment did not affect the proliferation of ligament fibroblasts but significantly up-regulated the expression of bone markers, including ALP and OCN, and the key regulators Runx-2 and osterix. In addition, the serum levels of CCL19/CCL21 were apparently elevated in AS patients compared to healthy controls (HC), and the expression of the two chemokines correlated significantly in AS patients. CONCLUSIONS: CCL19 and CCL21, two chemokines displaying significantly associated expression in serum, indicating a synergistic effect on AS pathogenesis, may function as promoters of ligament ossification in AS patients.

A high figure of merit of phonon-polariton waveguide modes with hbn/SiO2/graphene /hBN ribs waveguide in mid-infrared range.

Natural hyperbolic materials can confine electromagnetic waves at the nanoscale. In this study, we propose a waveguide design that combines a high quality factor (FOM) with low loss, utilizing hexagonal boron nitride and graphene and gold substrate. The waveguide consists of a dielectric rib with a graphene layer sandwiched between two hBN ribs. Numerical simulations demonstrate the existence of two guided modes in the proposed waveguide within the second reststrahlen band (1360.0 cm-1<ω < 1609.8 cm-1) of hBN. These modes are formed by coupling the hyperbolic phonon polariton (HPhP) of two hBN rib in the middle dielectric rib and are subsequently modulated by a graphene layer. Interestingly, we observe variations in four transmission parameters, namely effective length, figure of merit, device length, and propagation loss of the guided modes, with respect to the operation frequency and gate voltage. By optimizing the waveguide's geometry parameters and dielectric permittivity, the modal properties were analyzed. Simulation results indicate that optimizing the waveguide size parameters enables us to achieve a high FOM of 4.0 × 107. The proposed waveguide design offers a promising approach for designing tunable mid infrared range waveguides on photonic chips, and this concept can be extended to other 2D materials and hyperbolic materials.

Calmodulin activation of polo-like kinase 1 is required during mitotic entry.

Polo-like kinase 1 (Plk1) is a conserved key regulator of the G2/M transition, but its upstream spatiotemporal regulators remain unknown. With the help of immunofluorescence, co-immunoprecipitation, and glutathione S-transferase (GST) pull-down assay, we found that calmodulin (CaM) is one such regulatory molecule that associates with Plk1 from G2 to metaphase. More importantly, this interaction results in considerable stimulation of Plk1 kinase activity leading to hyperphosphorylation of Cdc25C. Our results provide new insight into the role of CaM as an upstream regulator of Plk1 activation during mitotic entry.

Pilot validation of the Boston Bowel Preparation Scale in China.

BACKGROUND AND AIM: The Boston Bowel Preparation Scale (BBPS) is a novel bowel cleanliness rating scale that has undergone validation at Boston University Medical Center, Boston, MA, USA. Thus far, there is no standard recognized bowel preparation scale in China. The aim of the present study was to analyze the reliability and validity of the BBPS for the assessment of bowel preparation quality (BPQ) in China. METHODS: A group of 49 participants from several hospitals in Guangdong province viewed a video demonstration of BBPS provided by Boston Medical Center and participated in a continuing education seminar. Inter-observer reliability was assessed for three testing colonoscopies in the video. Three months later, 13 of the participants repeated the test, and intra-observer reliability was assessed. The BBPS was then applied prospectively in 1012 screening colonoscopies and BBPS scores were compared with polyp-detection rate. Intraclass correlation coefficients (ICC) and weighted Kappa values assessed inter- and intra-rater reliability, respectively. The association of BBPS scores with polyp-detection rates was calculated by χ(2) tests. RESULTS: The inter-observer ICC of BBPS scores was 0.987 (95% CI, 0.949-1.0). The weighted Kappa for BBPS scores was 0.671 (95%CI, 0.507-0.841). For 1012 screening colonoscopies, the mean BBPS score was 6.9 ± 1.8. BBPS scores ≥ 5 were associated with a higher polyp-detection rate (35%) than scores < 5 (18%) (P < 0.05). CONCLUSION: The BBPS is a valid and reliable measure of BPQ, and this validity and reliability was maintained for Chinese physicians taught via video.

Safety and environmental impact control of cross passage construction in soft soil strata using tunnel boring machine method.

The construction of cross passages using the tunnel boring machine (TBM) method represents an emerging construction technique with numerous advantages. However, owing to the scarcity of application instances, the safety control methodologies and the regulatory patterns concerning environmental impacts remain inconclusive. In this study, a cross passage excavated using the TBM method-the first of its kind in the Tianjin area-was investigated. We identified the key risk control measures for the construction and analysed the TBM operating parameters, monitored ground and building settlements, and monitored mainline tunnel deformations and mechanical responses, revealing the ground and tunnel structure deformation patterns. The following conclusions are drawn. (1) The ground surrounding the cross-passage break-out opening was stabilised by performing secondary grouting and small-range freezing, and the break-in opening was excavated using a completely enclosed steel sleeve. These measures prevented water and sand inflows during the excavation of the break-out and break-in openings in the silt and silty sand strata. (2) The torsional moment of the cutter disc was large during the break-out phase. Break-out mainline tunnel displacement monitoring data indicated that the thrust had a significant effect on the mainline tunnel during the break-out phase. (3) The TBM tunnelling caused ground loss. The ground settlement exhibited a U-shaped distribution along the cross-passage axis, with the maximum settlement being 10 mm. (4) During the break-out phase, the deformation of the break-out mainline tunnel exhibited a duck-egg-shaped distribution. The clearance convergence of the break-out mainline tunnel was within ± 4, and the clearance convergence of the break-in mainline tunnel was controlled within ± 1 mm.

Systems biology strategy and experimental validation to uncover the pharmacological mechanism of Xihuang Pill in treating non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for almost 85% of lung cancer-related deaths worldwide. Xihuang Pill (XHP) is a representative anticancer Chinese patented medicine used to treat NSCLC in China. However, to date, a systematic analysis of XHP's antitumour effects and its impact on the immune microenvironment has not been performed. PURPOSE: Based on the systems biology strategy and experimental validation, the present study aimed to investigate the pharmacological mechanisms involved in treating NSCLC with XHP. METHODS: A subcutaneous tumour model was established to evaluate XHP's tumour-inhibitory effect in BALB/c nude mice. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to XHP treatment. Network analysis based on network pharmacology and protein-to-protein networks was applied to identify the compounds and genes targeted by XHP. External data from the TCGA-NSCLC cohort were used to verify the clinical significance of XHP-targeted genes in NSCLC. The expression of survival-related candidate genes after XHP treatment was verified via qPCR. The protein expression of calcium voltage-gated channel subunit alpha 1C (CACNA1C) in different NSCLC cell lines was analysed in the Human Protein Atlas database (HPA) and DepMap Portal. Using the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm and the single-sample gene set enrichment analysis (ssGSEA) algorithm uncovered the role of CACNA1C in the NSCLC tumour microenvironment (TME). RESULTS: XHP (2 g/kg/d) significantly inhibited the growth of transplanted A549 tumours. RNA-seq identified a total of 529 DEGs (189 upregulated and 340 downregulated). In addition, 542 GO terms, 41 significant KEGG pathways, 9 upregulated hallmarks pathways, and 18 downregulated hallmark pathways were enriched. These GO terms and signalling pathways were closely related to cell proliferation, immunity, energy metabolism, and the inflammatory response of NSCLC. In addition, XHP's network pharmacology analysis identified 301 compounds and 1,432 target genes. A comprehensive strategic analysis identified CACNA1C as a promising gene by which XHP targets and regulates the TME of NSCLC, benefiting patient survival. CACNA1C expression was positively correlated with both the immune score and stromal score but negatively correlated with the tumour purity score. Additionally, CACNA1C expression was significantly correlated with the infiltration levels of 15 types of immune cells and the expression levels of 6 well-known checkpoint genes. CONCLUSIONS: Our results show that by regulating the pathways associated with cell proliferation and immunity, XHP can suppress cancer cell growth in NSCLC. Additionally, XHP may increase the expression of CACNA1C to suppress immune cell infiltration and regulate the expression of checkpoint-related genes, thereby improving the overall survival of NSCLC patients.

Anti-neuroinflammatory sesquiterpenoids from Chloranthus henryi.

Hupelactones A (1) and B (2), two new eudesmanolide-type enantiomers of the corresponding compounds, along with four mono- (3-6) and nine dimeric- (7-15) known sesquiterpenoids were isolated from the whole plant of Chloranthus henryi var. hupehensis (syn. C. henryi). The new structures including the absolute configurations were determined by comparison with previously reported enantiomers, extensive spectroscopic methods in combination with electronic circular dichroism (ECD) calculations. All the isolates were evaluated for their inhibitory activities against the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine BV-2 microglial cells. Among them, the dimeric lindenane sesquiterpenoids shizukaols F (8) and G (11) exhibited the most potent activities, with IC50 values of 2.65 and 4.60 µM, respectively.

[TG-FTIR and XRD spectroscopic analysis for the preparation of nitrogen-doped carbon supported cobalt electrocatalysts].

Nitrogen-doped carbon supported cobalt electrocatalysts for the reduction of oxygen were prepared from the high nitrogen content prepolymer of melamine formaldehyde resin and cobalt acetate. The preparation and structure of the electrocatalysts were investigated by TG-FTIR and XRD spectroscopic analysis methods. The electrochemical reduction of oxygen was studied at the nitrogen-doped carbon supported cobalt by using the rotating disk electrode method. The results indicated that the catalyst structure changed with the carbonization temperature under the protection of the inert gases. Some organic groups were decomposed into CO, CO2, HCHO, NH3 and NO2, which were taken away by the protecting gas. The electrocatalysts exhibited face-centered cubic structure. The RDE results showed that good electrocatalytic activity for oxygen reduction at these electrocatalysts was found under the experimental condition. The onset potential for oxygen reduction (E(onset)) was 0.5 V (vs. SCE). The catalyst prepared under 700 C was found to have the highest activity.

Further terpenoids from the Chloranthaceae plant Chloranthus multistachys and their anti-neuroinflammatory activities.

Three labdane-type [multisins A-C (1-3)], two guaiane-type [multisins D (4) and E (5)], and one eudesmane-type [multisin F (6)] previously undescribed terpenoids, together with 14 mono- (7-20) and seven dimeric- (21-27) known terpenoids, were isolated from the 90% MeOH extract of the whole plant of Chloranthus multistachys. Their structures and absolute configurations were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 are rare trinor-sesquiterpenes with a de-isopropyl guaiane skeleton, whereas compound 6 is a rearranged dinor-eudesmene featuring an uncommon octahydro-1H-indene ring system. Among the isolates, the dimeric lindenane sesquiterpenoid shizukaol C (25) exhibited the most potent (IC50 = 8.04 µM) anti-neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells.

Prognostic Signatures of Metabolic Genes and Metabolism-Related Long Non-coding RNAs Accurately Predict Overall Survival for Osteosarcoma Patients.

In this study, we identified eight survival-related metabolic genes in differentially expressed metabolic genes by univariate Cox regression analysis based on the therapeutically applicable research to generate effective treatments (n = 84) data set and genotype tissue expression data set (n = 396). We also constructed a six metabolic gene signature to predict the overall survival of osteosarcoma (OS) patients using least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Our results show that the six metabolic gene signature showed good performance in predicting survival of OS patients and was also an independent prognostic factor. Stratified correlation analysis showed that the metabolic gene signature accurately predicted survival outcomes in high-risk and low-risk OS patients. The six metabolic gene signature was also verified to perform well in predicting survival of OS patients in an independent cohort (GSE21257). Then, using univariate Cox regression and Lasso Cox regression analyses, we identified an eight metabolism-related long noncoding RNA (lncRNA) signature that accurately predicts overall survival of OS patients. Gene set variation analysis showed that the apical surface and bile acid metabolism, epithelial mesenchymal transition, and P53 pathway were activated in the high-risk group based on the eight metabolism-related lncRNA signature. Furthermore, we constructed a competing endogenous RNA (ceRNA) network and conducted immunization score analysis based on the eight metabolism-related lncRNA signature. These results showed that the six metabolic gene signature and eight metabolism-related lncRNA signature have good performance in predicting the survival outcomes of OS patients.

Beta-catenin signaling involves HGF-enhanced HepG2 scattering through activating MMP-7 transcription.

It is well accepted that cell scattering (dispersion of clustered cells into single cells) is the initial step of tumor metastasis, and the downregulation of E-cadherin is associated with metastatic potential of tumor cells; however, the molecular mechanisms underlying loss of E-cadherin during tumor development are still poorly understood. Here, we report that hepatocyte growth factor (HGF) induced E-cadherin downregulation and cell scattering are attributed to the activation of Wnt/beta-catenin signaling and transcriptional activation of matrix metalloproteinase MMP-7. Furthermore, the increased MMP-7 is secreted into the medium and cleaves the ectodomain of E-cadherin. Inhibition of HGF signal by siRNA of c-Met, blocking the beta-catenin transcriptional activity through a dominant negative form of TCF4, MMP-7 knockdown by siRNA or suppression of MMP-7 enzymatic activity with a neutralization antibody allowed inhibition of HGF-induced loss of E-cadherin and HepG2 scattering. Our data presented here revealed the intrinsic mechanism of HGF activated Wnt/beta-catenin signaling regulation of HepG2 cell scattering through MMP-7 transcription activation and E-cadherin degradation. The results suggest that the blocking of HGF/c-Met/beta-catenin/MMP-7/E-cadherin signaling pathway might present a practical therapeutic target for interference with hepatocellular carcinoma metastasis.