TCM-HIN2Vec:A strategy for uncovering biological basis of heart qi deficiency pattern based on network embedding and transcriptomic experiment

Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.

Flotillin1 promotes EMT of human small cell lung cancer via TGF-β signaling pathway

Objective:Small cell lung carcinoma(SCLC)is considered one of the most aggressive types of lung cancer due to its rapid growth and early metastasis.No tumor markers or therapeutic targets have been demonstrated to be specific or effective in SCLC to date.This study aims to evaluate the potential of Flotillin1(Flot1)as a target of SCLC treatment.Methods:Flot1 expression level in the tissue of SCLC and other tissue of lung disease was detected using immunohistochemical staining.Transwell and Matrigel assays were employed to examine migration and invasion of cancer cells.Flow cytometry and xCELLigence system were used to evaluate cell apoptosis and cell viability,respectively.Expression levels of Flot1,epithelialmesenchymal transition(EMT)marker E-cadherin,vimentin,cyclinD1,TGF-β-Smad2/3,and p-AKT were examined using Western blot.Furthermore,xenograft tumor in nude mice was used to evaluate the growth and metastasis of NCI-H446 cells in vivo.Results:Our results demonstrated that Flot1 is highly expressed in SCLC samples and that its expression correlates strongly with clinical stage,distant metastasis,and poor survival.The knockdown of Flot1 decreased the growth,migration,and invasiveness of SCLC cells and reversed EMT phenotype in vitro and in vivo,while enhanced Flot1 expression exhibited the opposite behavior.Gene expression profile analysis demonstrated that Flot1-regulated genes frequently mapped to the AKT and TGF-β-Smad2/3pathways.Our results further revealed that Flot1 affected the progression of SCLC via regulation of EMT progression.Conclusions:These findings indicated an oncogenic role of Flot1 via promoting EMT in SCLC and suggested its potential as a tumor marker and prognostic indicator.

Boosting bulk charge transport of CuWO_(4) photoanodes via Cs doping for solar water oxidation

Copper tungstate(CuWO_(4))is a promising photoanode for photoelectrochemical(PEC)water splitting due to its appropriate energy band position and broad light absorption range.However,the inherent unfilled 3d atomic orbital of Cu acts as a natural electron-hole recombination site,significantly constraining the PEC performance of CuWO_(4).Herein,Cs atoms with complete atomic orbitals are doped into CuWO_(4)in order to obtain better bulk charge separation capability.As a result,the photocurrent of Cs@CuWO_(4)increases from 0.57 to 0.99 mA cm^(-2)compared to CuWO_(4)at 1.23 V vs.reversible hydrogen electrode(RHE)under AM 1.5G illumination,as well as the bulk charge transfer efficiencies rising from 13.5%to 19.3%.In addition,density of states(DOS)calculations further prove that the introduction of Cs atoms effectively suppresses the contribution of Cu 3d orbitals at the Fermi level.This work offers a valuable reference for the advancement of CuWO_(4)as the next-generation PEC photoanode material.

Enhanced Expression of miR-425 Promotes Esophageal Squamous Cell Carcinoma Tumorigenesis by Targeting SMAD2

Esophageal squamous cell carcinoma （ESCC） is one of the most common and deadly cancers in the world, Currently, clinical therapy of ESCC remains limited and the five-year survival rate is poor. The function of miR-425 has been reported in multiple human cancers. However. the tumorigenic role and clinical significance of miR-425 in ESCC remains unclear. We found that enhanced expression of miR- 425 in ESCC cell lines not only promoted cell proliferation and colony formation, but also increased cellular metastasis. Furthermore, we revealed the mechanism that miR-425 inhibited the expression of SMAD2 by targeting the second binding site in the 3＇-untranslated region （3＇-UTR） in ESCC. This mode of action influenced not only SMAD2 rnRNA expression but also protein expression. In addition, we detected the expression of miR-425 in ESCC tissues and plasma. Moreover, we analyzed the relationship between miR-425 expression and SMAD2 mRNA expression. We found that miR-425 was overexpressed in ESCC tissues and the plasma relative to adjacent normal tissues and plasma of healthy individuals. Furthermore, there was a negative correlation between miR-425 expression and SMAD2, Taken together, our results show that miR-425 functions as an oncogene by targeting the 3＇-UTR of SMAD2 and indicate the potential utility of plasma miR-425 as a novel biomarker for ESCC diagnosis.

miR-503-3p promotes epithelialemesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin

Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of mi R-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined.Here, we found that mi R-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified mi R-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of mi R-503-3p in breast cancer cells inhibited expression of epithelialemesenchymal transition（EMT）-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their m RNA30 untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for mi R-503-3p in induction of breast cancer EMT and suggest that plasma mi R-503-3p may be a useful diagnostic biomarker for breast cancer.

Defect passivation and electrical conductivity enhancement in perovskite solar cells using functionalized graphene quantum dots

Organic–inorganic halide perovskites have been intensively investigated as potential photovoltaic materials due to their exceptional optoelectronic properties and their successful applications in perovskite solar cells(PSCs).However,a large number of defect states still exist in the PSCs so far and are detrimental to their power conversion efficiencies(PCEs)and stability.Here,an effective strategy of incorporating single-crystalline graphene quantum dots(GQDs)into the perovskite films is proposed to passivate the defect states.Intriguingly,the GQD-modified perovskite films exhibit purer phase structure,higher quality of morphology,and higher electrical conductivity when compared with the control perovskite films.All of the advantages caused by the incorporation of the GQDs lead to fast carrier separation and transport,long carrier lifetime,and low nonradiative recombination in the PSCs based on the GQD-modified perovskite films.As a result,this kind of PSC displays an increase in all photovoltaic parameters,and its PCE shows an enhancement of more than 20%when compared with the control PSC.Moreover,this novel PSC is demonstrated to have long-term stability and resistibility against heat and moisture.Our findings provide an insight into how to passivate the defect states and enhance the electrical conductivities in the perovskites and pave the way for their further exploration to achieve higher photovoltaic performances.