Exploring the association of POSTN+ cancer-associated fibroblasts with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) play a critical role in regulating TNBC tumor development. This study aimed to identify and characterize a specific subtype of CAFs associated with TNBC. Initially, using high-throughput bulk transcriptomic data in two cohorts, we identified three CAF-related subtypes (CS1, CS2, CS3) in TNBC samples. These three CAFs subtypes were closely linked to the tumor microenvironment. The CS1 subtype exhibited a relatively immune-rich microenvironment and a favourable prognosis, whereas the CS3 subtype displayed an immune-deprived tumor microenvironment and an unfavourable prognosis. Through WGCNA analysis, POSTN was identified as a key biomarker for CAFs associated with TNBC. Then, POSTN+CAFs was identified and characterized. Both POSTN and POSTN+CAFs showed significant positive correlations with stromal molecules HGF and MET at both the transcriptional and protein levels. Specifically co-localized with CAFs in the tumor stromal area, POSTN, produced by POSTN+CAFs, could modulate the HGF-MET axis, serving as a bypass activation pathway to regulate tumor cell proliferation in response to EGFR inhibitor and MET inhibitor. This study underscores the significance of POSTN and POSTN+CAFs as crucial targets for the diagnosis and treatment of TNBC.

HCC portal hypertension imaging score derived from CT predicts re-bleeding and mortality after acute variceal bleeding.

BACKGROUND/PURPOSE: Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. METHODS: This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. RESULTS: 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728-3.142, p < 0.001). The positive predictive value of HCCPHTIS cut off value > 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p < 0.001). 74(37.9%) death occurred within 6 weeks; HCCPHTIS > 4 was associated with increased risk of death within 6 weeks after AVB (p < 0.001). CONCLUSION: HCCPHTIS > 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.

ATP2C2 as a novel immune-related marker that defines the tumor microenvironment in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive cancer that affects about 13/100,000 women yearly. Patients with TNBC are often resistant to endocrine and molecular targeted therapy, making clinical treatment challenging. Researches indicate that tumor microenvironment (TME) is related to prognosis in many cancers. Therefore, we aim to identify TME immune-related biomarkers to enhance the prognosis and immunotherapy efficacy in patients with TNBC. Methods: The bulk mRNA transcriptome data and clinical information of the (GSE58812) and (GSE25055) datasets were downloaded from the Gene Expression Omnibus (GEO) database, and the ESTIMATE algorithm was used to calculate the ImmuneScore, StromalScore, and ESTIMATEScore. Patients were divided into low and high groups according to the quartiles of ImmuneScore, StromalScore, and the median of ESTIMATEScore to filter differential expression genes (DEGs), respectively. The DEGs were then evaluated using univariate and multivariate Cox regression to identify TME-related genes and its association with survival rate for the construction of a TMErisk model with three biomarkers. Then Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) data were used to compare the gene expression in cancer and normal tissues. xCell analysis calculated the proportion of tumor-infiltrating immune cells in low and high expression of ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2). In addition, samples from 20 TNBC patients admitted to our institution were used for immunohistochemical (IHC) examination. Results: Three immune-related DEGs were identified, including prolyl 3-hydroxylase 2 (P3H2), sodium voltage-gated channel beta subunit 3 (SCN3B), and ATP2C2 and a TMErisk model was constructed and validated. However, only ATP2C2 was selected for further analysis. ATP2C2 mRNA level of TNBC patients was higher than that of normal breast tissue. Survival analysis showed that patients with high expression of ATP2C2 had a bad prognosis. xCell analysis demonstrated that the expression of ATP2C2 was associated with 16 kinds of tumor-infiltrating immune cells. Protein expression of ATP2C2 in TNBC tissues was higher compared to paired normal tissues in IHC. Conclusions: This study constructed and validated a TMErisk model that can effectively predict 3- and 5-year survival rate for TNBC patients. TNBC patients with lower expression of ATP2C2 had a good prognosis.

Prediction of prognosis and immunotherapy response in lung adenocarcinoma based on CD79A, DKK1 and VEGFC.

Background: Tumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes. Methods: RNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools. Results: The risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P < 0.05). Low risk score was positively associated with plasma cells, memory B cells, CD8 T cells, regulatory T cells and γδT cells (P < 0.05). In low-risk group, programmed cell death 1 receptor (PD1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3) and indoleamine 2,3-dioxygenase (IDO) were more robustly expressed (P < 0.05). The treatment responses of immune checkpoint blockade (ICB) therapy and chemotherapy were likewise superior in low-risk group (P < 0.05). In immunohistochemical analysis, the tumor group had significantly higher levels of CD79A, DKK1, and VEGFC than the adjacent normal group (P < 0.01). Conclusions: CD79A, DKK1 and VEGFC are important differential genes related to LUAD, risk score could reliably predict prognosis, composition of TIME and immunotherapy responses in LUAD patients. The excellent performance of the risk model shows its strong and broad application potential.

A homogeneous hybridization magnetic biosensor based on electric field assistance for ultrafast nucleic acid detection.

Electrochemical biosensing is a sensitive strategy widely used in the field of nucleic acid detection. However, electrochemical biosensors generally involve time-consuming and labor-intensive probe immobilization processes. In this study, an electrochemical DNA biosensor based on homogeneous hybridization in solution was designed for nucleic acid detection without probe immobilization, which is different from most biosensors. The capture probe, detection probe, and target DNA were hybridized rapidly under an electric field to form a "sandwich" structure within 90 s, and the "sandwich" hybrid could be specifically coupled to streptavidin-modified magnetic beads within 5 min. Finally, the magnetic beads were enriched by using polypyrrole (PPy)/carbon nanotube (CNT)-modified magnetic electrodes and the signal was detected by differential pulse voltammetry (DPV). The magnetic biosensor constructed in this study could detect targets over a good linear dynamic range spanning 100 pM to 100 nM in 400 s, while those involving conventional hybridization methods always take 2 h or more. Because of the specific binding of streptavidin and biotin, this strategy showed high specificity. Taken together, the homogenous hybridization magnetic biosensor constructed with electric field assistance presents a potential diagnostic method for rapid DNA detection and provides a new idea for rapid nucleic acid detection in clinical practice.

Novel strategy of combined interstitial macrophage depletion with intravenous targeted therapy to ameliorate pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease with poor prognosis and high mortality rate. In the process of IPF, inflammatory dysregulation of macrophages and massive fibroblast aggregation and proliferation destroy alveoli, which cause pulmonary dysfunction, and ultimately lead to death due to respiratory failure. In the treatment of IPF, crossing biological barriers and delivering drugs to lung interstitium are the major challenges. In order to avoid the side effect of macrophages proliferation, we proposed, designed, and evaluated the strategy which combined macrophage depletion by intervaginal space injection and intravenous targeted therapy on bleomycin mouse model. We found that it inhibited pulmonary macrophages, reduced macrophage depletion in non-target organs, improved pulmonary drug targeting, impeded the progression of pulmonary fibrosis, and accelerated the recovery of pulmonary function. This combination therapeutic strategy shows good biosafety and efficacy, induces a targeted response, and is promising as a practical new clinical approach towards the treatment of pulmonary fibrosis.

Effect of concurrent training on physical performance and quality of life in children with malignancy: A systematic review and meta-analysis.

Objective: This study aims to evaluate the intervention effect of concurrent training on children with malignant tumors to provide evidence for prescribing exercise for children with malignant tumors. Methods: Twelve databases were searched from inception to October 15, 2022. Two researchers independently screened the literature, evaluated the quality, extracted the data, and performed the meta-analysis using R. Result: A total of nine randomized controlled trials involving 371 children were included in this study. The meta-analysis revealed that muscle strength was significantly greater in the exercise group compared to the usual care group [SMD = 0.26, 95% CI (0.04, 0.48), P = 0.023], with subgroup analysis showing no significant difference in upper limb [SMD = 0.13, 95% CI (-0.17, 0.43), P = 0.318] and a considerable difference in lower limb strength [SMD = 0.41, 95% CI (0.08, 0.74), P = 0.015]. Physical activity [SMD = 0.57, 95% CI (0.03, 1.1), P = 0.038], timed up and down stairs test [SMD = -1.22, 95% CI (-2.04, -0.4), P = 0.004], 6-min walking ability [SMD = 0.75, 95% CI (0.38, 1.11), P < 0.01], quality of life [SMD = 0.28, 95% CI (0.02, 0.53), P = 0.033], and cancer-related fatigue [SMD = -0.53, 95% CI (-0.86, -0.19), P = 0.002] were significantly better than the usual care group. There were no significant differences in peak oxygen uptake [SMD = 0.13, 95% CI (-0.18, 0.44), P = 0.397], depression [SMD = 0.06, 95% CI (-0.38, 0.5), P = 0.791], and withdrawal rates [RR = 0.59, 95% CI (0.21, 1.63), P = 0.308] between the two groups. Conclusion: Concurrent training could improve physical performance for children with malignancy but had no significant effect on mental health. Because the quality level of evidence is mostly very low, future high-quality randomized controlled trials are required to confirm these findings. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364140, identifier CRD42022308176.

The effect of audit team's emotional intelligence on reduced audit quality behavior in audit firms: Considering the mediating effect of team trust and the moderating effect of knowledge sharing.

Reduced audit quality behavior is widespread in the auditor's practice and is an important factor threatening audit quality. Some prior studies have investigated the relationship between auditors' psychological contract violation and reduced audit quality behavior. However, the research of relationship between emotional intelligence (EI) and auditors' behavior is still in its infancy despite the fact that the auditing profession would benefit greatly from improving audit team's EI. This study examines whether and why the audit team's EI restrains the audit quality reduction behavior in audit firms. In the study, our hypotheses are tested using a data set collected from 326 respondents in Chinese audit firms. The results are as follows: firstly, audit team's EI is directly negatively related to reduced audit quality behavior. Secondly, EI is indirectly related to reduced audit quality behavior, through team trust. The results of structural equation modeling (SEM) indicate a mediation model where team trust is negatively related to reduced audit quality behavior. Thirdly, knowledge sharing is a significant mechanism that moderates the effects of different types of EI on audit quality reduction behavior. In the audit team with high knowledge sharing, the audit team's EI can refrain the audit quality reduction behavior; In the audit team with low knowledge sharing, the audit team's EI has no significant effect on audit quality reduction behavior. This study expands the factors affecting audit quality to the psychological level of audit teams, enriches the literature on audit team's behavior characteristics, and provides direct evidence for the relationship between audit team's psychological characteristics and audit quality.

Peer effects of working capital management: Considering the moderating effect of knowledge flow.

An important form of human learning and cognition is imitation. In environments where uncertainty is more incremental, imitation of peers is a natural response to uncertainty. While there are substantial literature documenting peer effects in other settings, the study of peer effects in working capital management is novel; little research exists on peer effects in working capital management and their impact mechanism. Using data of China's listed firms from 2010 to 2021, we empirically demonstrate significant peer effects due to working capital management. Firstly, we find that the behavior of working capital management of firms in the same industry is positively related to a firm's working capital management. We used peer firms' target debt ratio as an instrumental variable to address potential endogeneity problem. Secondly, the moderating effects test shows that the positive relationship between the behavior of working capital management of firms in the same industry and a firm's working capital management behavior is moderated by knowledge flow. Meanwhile, the peer effects in the high group of knowledge flow are greater than that of in the low group of knowledge flow. The study is based on the Active Intermodal Matching theory of psychology. It enriches the research findings on the moderating effect of peer effects and has important implications for policymaking to stimulate the economy.

An engineered hydrogel with low-dose antitumor drugs enhances tumor immunotherapy through tumor interstitial wrap.

Stimulating immunogenic cell death (ICD) is the key to tumor immunotherapy. However, traditional chemoradiotherapy has limited effect on stimulating immunity and often requires repeated administration, which greatly reduces the tumor-killing effect. In this article, we created a sodium alginate hydrogel sustained-release system containing low-dose doxorubicin (Dox) and immune adjuvant R837, which were injected into the interstitial space to wrap around the tumor in situ, achieving a sustained release and long-lasting immune response. Cooperating with immune checkpoint blockade, Dox induced ICD, activated dendritic cells (DCs) and converted immunosuppressive M2-type tumor-associated macrophages (TAM) to tumor-killing M1-type TAMs. Simultaneously, it greatly promoted T cell proliferation and infiltration, and reduced tumor immunosuppressive factors, triggering a robust immune response to suppress tumors in vivo. In conclusion, this anti-tumor strategy based on interstitial injection can achieve continuous local immune stimulation by low-dose chemotherapy drugs, providing a potential approach for tumor immunotherapy.

High Energy Storage Performance in La-Doped AgNbO3 Ceramics via Tape Casting.

AgNbO3-based Pb-free antiferroelectric (AFE) ceramics have attracted increasing interest owing to their excellent potential in energy storage applications. Herein, a high recoverable energy storage density (Wrec) of 7.62 J/cm3 is realized in La-doped AgNbO3 ceramics prepared via tape casting. The high Wrec is attributed to high breakdown strength Eb of 380 kV/cm induced by dense microstructure as well as fine grain size and enhanced AFE stability stemming from M2 phase and reduced tolerance factor t. The high Wrec exceeding 6 J/cm3 was maintained in a wide temperature range of 20-150 °C and exhibited frequency stability with less than 8% variation in a range of 1-200 Hz. The discharge energy density Wd exhibited temperature stability at 30-110 °C with less than 9% variation. Our research provides a good method for producing AgNbO3-based ceramics having high energy storage performances.

Effect of caffeic acid esters on antioxidant activity and oxidative stability of sunflower oil: Molecular simulation and experiments.

Polyphenol, though used as antioxidants in food industry, suffers from poor solubility issues in vegetable oil. Usually, its solubility would be enhanced through esterification. This work investigated the antioxidant activity and oxidative stability of caffeic acid (CA) and its derivative modified esters by molecular simulation and experiments. Density functional theory (DFT) and molecular dynamic analysis revealed the antioxidant mechanism of CA esters attributing to the comprehensive effects. The lower hydrogen dissociation energy (ΔG) of CA esters with catechol moiety caused the transformation of antioxidant into quinone via the double hydrogen atom transfer reaction. Particularly, the second reduced hydrogen dissociation energy was the keypoint. The strong non-bond energy and hydrogen bond allowed CA esters and oil molecules to interact more efficiently. Hence, the ester moieties enhanced the antioxidant activity with 4.5-6.5 % ΔG reduction compared to CA. Rancimat and DSC assays validated the theoretical predictions. This result shows that the antioxidant activity of CA and its esters could be predicted by this molecular simulation way, which may aid in designing of new polyphenol antioxidant structure.

Low Temperature Aluminothermic Reduction of Natural Sepiolite to High-Performance Si Nanofibers for Li-Ion Batteries.

Nanostructure silicon is one of the most promising anode materials for the next-generation lithium-ion battery, but the complicated synthesis process and high cost limit its large-scale commercial application. Herein, a simple and low-cost method was proposed to prepare silicon nanofibers (SNF) using natural sepiolite as a template via a low-temperature aluminum reduction process. The low temperature of 260°C during the reduction process not only reduced the production cost but also avoided the destruction of the natural sepiolite structure caused by the high temperature above 600°C in the traditional magnesium thermal reduction process, leading to a more complete nanofiber structure in the final product. For the first time, the important role of Mg-O octahedral structure in the maintenance of nanofiber structure during the process of low-temperature aluminothermic reduction was verified by experiments. When used as an anode for lithium-ion batteries, SNF yield a high reversible capacity of 2005.4 mAh g-1 at 0.5 A g-1 after 50 cycles and 1017.6 mAh g-1 at 2 A g-1 after 200 cycles, remarkably outperforming commercial Si material. With a low-cost precursor and facile approach, this work provides a new strategy for the synthesis of a commercial high-capacity Si anode.

An ultrafast ratiometric electrochemical biosensor based on potential-assisted hybridization for nucleic acids detection.

The development of rapid nucleic acid detection methods, which are promising the diagnostic standard of the infectious disease, could expand more options for disease traceability and controllability. Nucleic acid hybridization-based biosensing techniques still encounter limitations in meeting the requirements for rapid detection. Therefore, we proposed a potential-assisted ratiometric electrochemical biosensor for rapid and accurate target DNA detection. This dual-signal analysis system actuated an enzyme-free detection process. The application of an external electric field accelerated molecular dynamics, resulting in highly efficient collision chances. This hybridization process was thus improved from hours to minutes compared with passive hybridization approach. The biosensor not only had a high sensitivity with the detection limit of 12 fM, but also features a robust capability in identifying single-base mismatch. Moreover, the biosensor realized sensitive detection of target DNA in complex biological environments. Overall, this sensing strategy exhibits a promising potential for application in point-of-care testing.

Evaluating PM2.5 -Related health costs in China-Evidence from 140 Chinese cities.

INTRODUCTION: In recent years, China's economy has grown rapidly, and the health condition of Chinese residents has significantly improved. However, this rapid economic and social development has also brought a series of environmental problems, such as serious haze pollution, of which the main contents are PM2.5 particles. The objective of this study is to quantitatively estimate the PM2.5 -related health costs in China. METHODS: Based on city-level data from 140 major Chinese cities as well as the Beijing-Tianjin-Hebei, Yangtze River Delta, and Pearl River Delta city clusters in 2010, the value of a statistical life method based on willingness to pay was employed. Moreover, global and local Moran's I values were calculated to examine the spatial distribution of the health cost of haze pollution in China. RESULTS: In areas with heavy haze pollution or a high level of economic development, residents' health costs will also be higher. In addition, there is a spatial aggregation phenomenon in the spatial distribution of health costs in China, which is mainly in the form of "high-high" aggregation, with high-value cities converging with other high-value cities. CONCLUSIONS: The health cost of haze pollution in China is very considerable, and there are regional differences.

Performance Analysis of Novel Nucleic Acid Detection Kit for Mycoplasma pneumoniae.

Respiratory tract infections caused by Mycoplasma pneumoniae is a serious risk for child health. It has been difficult to prevent and control for a variety of reasons; therefore, timely diagnosis is particularly important for treatment of patients. At present, the rapid M pneumoniae test kits based on nucleic acid amplification have been commercialized and used as primary diagnostic tools for M pneumoniae infection, but current kits are time-consuming, which is difficult to meet the requirement for accurate and rapid diagnosis of M pneumoniae during epidemics. Rapid and accurate test kits are urgently required to diagnose M pneumoniae infection. In this article, we evaluated the performance of a novel nucleic acid detection kit (A) for M pneumoniae from feasibility and sensitivity, and compared it with kit B. Results showed this kit has the advantage of being rapid, sensitive, and specific, which meets the demands for the diagnosis of M pneumoniae infection in clinical settings.

Over-Expression of Rose RrLAZY1 Negatively Regulates the Branch Angle of Transgenic Arabidopsis Inflorescence.

Branch angle is a key shoot architecture trait that strongly influences the ornamental and economic value of garden plants. However, the mechanism underlying the control of branch angle, an important aspect of tree architecture, is far from clear in roses. In the present study, we isolated the RrLAZY1 gene from the stems of Rosa rugosa 'Zilong wochi'. Sequence analysis showed that the encoded RrLAZY1 protein contained a conserved GΦL (A/T) IGT domain, which belongs to the IGT family. Quantitative real-time PCR (qRT-PCR) analyses revealed that RrLAZY1 was expressed in all tissues and that expression was highest in the stem. The RrLAZY1 protein was localized in the plasma membrane. Based on a yeast two-hybrid assay and bimolecular fluorescence complementation experiments, the RrLAZY1 protein was found to interact with auxin-related proteins RrIAA16. The over-expression of the RrLAZY1 gene displayed a smaller branch angle in transgenic Arabidopsis inflorescence and resulted in changes in the expression level of genes related to auxin polar transport and signal transduction pathways. This study represents the first systematic analysis of the LAZY1 gene family in R. rugosa. The results of this study will provide a theoretical basis for the improvement of rose plant types and molecular breeding and provide valuable information for studying the regulation mechanism of branch angle in other woody plants.

The lncRNA GATA3-AS1/miR-495-3p/CENPU axis predicts poor prognosis of breast cancer via the PLK1 signaling pathway.

The function of centromere protein U (CENPU) gene in breast cancer has not been well understood. Therefore, we explored the expression profiles of CENPU gene in breast carcinoma to better understand the functions of this gene, as well as the relationship between CENPU expression and the prognosis of breast carcinoma patients. Our results indicate that CENPU was expressed at significantly higher levels in cancerous tissues than in normal tissues. Furthermore, CENPU expression correlated significantly with many clinicopathological characteristics of breast cancer. In addition, we discovered that high levels of CENPU expression predicted poor prognosis in patients with breast cancer. Functional investigation revealed that 180 genes exhibited co-expression with CENPU. Functional annotation indicated that 17 of these genes were involved in the PLK1 signaling pathway, with most of them (16/17) being expressed at significantly higher levels in malignant tissues compared with normal controls and correlating with a poor prognosis. Subsequently, we found that four miRNAs, namely hsa-miR-543, hsa-miR-495-3p, hsa-miR-485-3p, and hsa-miR-337-3p, could be regarded as potential CENPU expression regulators. Then, five lncRNAs were predicted to potentially bind to the four miRNAs. Combination of the results from expression, survival, correlation analysis and functional experiments analysis demonstrated the link between lncRNA GATA3-AS1/miR-495-3p/CENPU axis and prognosis of breast cancer. In conclusion, CENPU could be involved in cell cycle progression through PLK1 signaling pathway.

Association between serum irisin concentrations and sarcopenia in patients with liver cirrhosis: a cross-sectional study.

Sarcopenia is an independent predictor of mortality in patients with liver cirrhosis. However, evidence has emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we investigated whether irisin was associated with sarcopenia in patients with liver cirrhosis. This was an observational cross-sectional study of data collected from 187 cirrhotic patients. Sarcopenia was defined by computed tomography (CT) scans using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning irisin levels were obtained in all patients. Of the 187 patients, sarcopenia was noted in 73 (39%). Irisin concentrations were lower in sarcopenic patients (32.40 pg/ml [interquartile range (IQR): 18.70, 121.26], p < 0.001) than in nonsarcopenic patients. There was a weak correlation between L3 SMI and irisin levels (r = 0.516, p < 0.001). Multivariable regression analysis including L3 SMI, body mass index (BMI), very-low-density lipoprotein (VLDL)-cholesterol, aspartate aminotransferase (AST), adiponectin, and irisin levels showed that L3 SMI (odds ratio [OR] = 0.915, p = 0.023), adiponectin levels (OR = 1.074, p = 0.014), irisin levels (OR = 0.993, p < 0.001) and BMI (OR = 0.456, p = 0.004) were independently associated with sarcopenia. Irisin levels are associated with sarcopenia in patients with liver cirrhosis. This paper addresses a gap in the literature and facilitates the future transition into clinical treatment.

C7 peptide inhibits hepatocellular carcinoma metastasis by targeting the HGF/c-Met signaling pathway.

Hepatocellular carcinoma (HCC), characterized by a high rate of metastasis and recurrence after surgery, is caused by malignant proliferation of hepatocytes with epigenetic and/or genetic mutations. In particular, abnormal activation of the hepatocyte growth factor (HGF)-/c-mesenchymal-epithelial transition receptor (c-Met) axis is closely associated with HCC metastasis. Unfortunately, effective treatments or drugs that target the HGF/c-Met signaling pathway are still in the research pipeline. Here, a c-Met inhibitor named the C7 peptide, which can inhibit both HGF and c-Met, can significantly inhibit HGF-induced (but not EGF-induced) cell migration and suppress the phosphorylation of c-Met, Akt and Erk1/2. Moreover, the C7 peptide can also significantly suppress tumor metastasis in nude mice and the phosphorylation of c-Met. Together, our current findings, demonstrated that the C7 peptide can inhibit HGF-induced cancer cell migration and invasion through the inhibition of Akt and Erk1/2. Identification of a peptide that can block HGF/c-Met signaling provides new insight into the mechanism of HCC and future clinical treatments.