HOTTIP-dependent R-loop formation regulates CTCF boundary activity and TAD integrity in leukemia.

HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) driven by MLL rearrangements or NPM1 mutations to mediate HOXA topologically associated domain (TAD) formation and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CCCTC-binding factor (CTCF) chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly interacts with and regulates a fraction of CTCF-binding sites (CBSs) in the AML genome by recruiting CTCF/cohesin complex and R-loop-associated regulators to form R-loops. HOTTIP-mediated R-loops reinforce the CTCF boundary and facilitate formation of TADs to drive gene transcription. Either deleting CBS or targeting RNase H to eliminate R-loops in the boundary CBS of ß-catenin TAD impaired CTCF boundary activity, inhibited promoter/enhancer interactions, reduced ß-catenin target expression, and mitigated leukemogenesis in xenograft mouse models with aberrant HOTTIP expression. Thus, HOTTIP-mediated R-loop formation directly reinforces CTCF chromatin boundary activity and TAD integrity to drive oncogene transcription and leukemia development.

Targeting BET proteins inhibited the growth of non-small cell lung carcinoma through downregulation of Met expression.

Hepatocyte growth factor receptor (HGFR or Met) upregulation has been proven to play important roles in non-small cell lung carcinoma (NSCLC). Interestingly, chemoresistance against epidermal growth factor receptor (EGFR) inhibitors including erlotinib and gefitinib was also related to Met. Targeting bromodomain and extra terminal domain (BET) proteins, especially BRD4, has shown inhibitory effects on lung cancer, but the mechanism is unclear. Herein, we found that JQ1 (BET inhibitor) suppressed NSCLC cell growth, reduced the Met expression, and contributed to inactivation of PI3K/Akt and MAPK/ERK pathways. Moreover, another BET protein inhibitor I-BET151, or BRD4 depletion, also inhibited NSCLC cell growth and downregulated Met. JQ1 inhibited HGF-induced cell growth and Met/PI3K/Akt activation, also inhibited A549 tumor growth in xenograft mouse models, in parallel with Met downregulation. Moreover, JQ1 inhibited the growth of paired erlotinib-sensitive and resistant HCC827 cells in parallel with Met downregulation and PI3K/Akt signaling inactivation. JQ1 also exerted inhibitory influences on the growth of erlotinib-sensitive and resistant HCC827 tumors in xenograft mouse models. These results suggested that targeting BET proteins inhibited NSCLC via downregulating Met and inactivating PI3K/AKT pathway. Our findings reveal a novel mechanism of BET proteins implicated in NSCLC progression with Met taken into consideration.

The CSN5/HSF/SPI1/PU.1 Axis Regulates Cell Proliferation in Hypocellular Myelodysplastic Syndrome Patients.

OBJECTIVE: This study explored the relationship between the activation of the jak/stat3 signaling pathway and the CSN5 gene transcript and protein expression levels in the hematopoietic stem cells of patients with myelodysplastic syndromes (MDSs). This study also aimed to investigate the correlation between the expression level of CSN5 and the deubiquitination of HSF1, as well as the transcript level of the spi1/pu.1 genes to explore the pathogenesis of MDS. MATERIALS AND METHODS: We isolated cells from normal individuals and MDS patients, and the mRNA and protein expression levels of spi1/pu.1 in cd34+ cells (hematopoietic stem cells) were measured by PCR and western blotting, respectively. A ChIP assay was used to detect the binding of HSF1 to the spi1/pu.1 promoter in cd34+ cells. The ubiquitination of HSF1 in cd34+ cells was detected by CO-IP. The binding of HSF1 and Fbxw7α was detected in in cd34+ cells by CO-IP. The binding of HSF1 and CSN5 was evaluated. A luciferase reporter assay was used to detect the effect of STAT3 on CSN5 promoter activation in cd34+ cells. Western blotting was used to detect the phosphorylation of STAT3 in cd34+ cells of MDS patients. The binding of STAT3 and C/EBP beta in cd34+ cells was detected by CO-IP. RESULTS: Inhibition of SPI1/PU.1 expression was observed in MDS samples with low proliferation ability. Further experiments proved that phosphorylation of STAT3 affected CSN5 function and mediated the ubiquitination of HSF, the upstream regulator of SPI1/PU.1 transcription, which led to the inhibition of SPI1/PU.1 expression. Restoration of CSN5 rescued the inhibition of HSF1 ubiquitination, causing SPI1/PU.1 transcription to resume and increasing SPI1/PU.1 expression, promoting the recovery of cell proliferation in hypocellular MDS. CONCLUSIONS: Our research revealed the regulatory role of the CSN5/HSF/SPI1/PU.1 axis in hypocellular MDS, providing a probable target for clinical intervention.

Combination of TACE and Lenvatinib as a promising option for downstaging to surgery of initially unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Conversion therapy has been widely applied in various cancer types including intrahepatic cholangiocarcinoma (ICC). The aim of this retrospective study was to evaluate the efficacy and safety of transarterial chemoembolization combined with lenvatinib (TACE-L) as a novel conversion therapy in patients with initially unresectable ICC. METHODS: Enrolled in this retrospective study were patients with unresectable ICC who received TACE-L between January 2015 and May 2018. The patients were evaluated every 2 months for possible secondary resection. RESULTS: Of the 44 eligible patients, 28 (63.6%) were successfully downstaged to receive surgical resection and the other 16 patients were included into the unsuccessfully downstaged group. The overall adverse events during TACE-L were moderate, including 12 patients (27.3%) with Grade 3 or 4 toxicities. Of the 28 downregulated patients, 23 (82.1%) achieved an R0 resection, and 6 (21.4%) had Clavien-Dindo grade ≥ 3 complications, including one postoperative death. Kaplan-Meier curves showed that the successfully downstaged patients had better overall survival (OS) than the unsuccessfully downstaged patients (P = 0.006). Multivariable analysis identified successful TACE-L conversion therapy as a significantly favorable prognostic factor for OS. CONCLUSIONS: TACE-L proves to be a safe and efficacious conversion therapy modality that allows for secondary resectability in patients with initially unresectable ICC.

Exosome-transmitted circ_002136 promotes hepatocellular carcinoma progression by miR-19a-3p/RAB1A pathway.

BACKGROUND: Circular RNAs (circRNAs) are enriched in exosomes and are extremely stable. Exosome-mediated intercellular transfer of specific biologically active circRNA molecules can drive the transformation of the tumor microenvironment and accelerate or inhibit the local spread and multifocal growth of hepatocellular carcinoma (HCC). In this study, we explored in depth about the biological roles of HCC cell-derived exosomes and exosome-transported circRNAs on HCC in vivo and in vitro. METHODS: Exosomes extracted from HCC cells (Huh7 and HA22T) were characterized using transmission electron microscopy, nanoparticle size tracer analysis, and western blotting. Exosomes were observed for endocytosis using fluorescent labeling. The effects of HCC cell-derived exosomes and the circ_002136 they carried on cell growth, metastasis and apoptosis were determined by CCK-8 assay, transwell assay, flow cytometry analysis and TUNEL staining, respectively. The expressions of circ_002136, miR-19a-3p and RAB1A were detected by quantitative RT-PCR (qRT-PCR). Targeted binding between miR-19a-3p and circ_002136 or RAB1A was predicted and verified by bioinformatics analysis, dual-luciferase reporter and RNA pull-down experiments. The in vivo effect of circ_002136 was determined by constructing a xenograft tumor model. RESULTS: The findings revealed that Huh7 and HA22T exosomes conferred enhanced viability as well as invasive ability to recipient HCC cells. Circ_002136 was shown for the first time to be differentially upregulated in HCC tissues and cells and transferred by HCC cell-derived exosomes. More importantly, selective silencing of circ_002136 depleted the malignant biological behaviors of HCC exosome-activated Huh7 and HA22T cells. Depletion of circ_002136 in vivo effectively retarded the growth of HCC xenograft tumors. Furthermore, a well-established circ_002136 ceRNA regulatory network was constructed, namely circ_002136 blocked miR-19a-3p expression, elevated RAB1A expression activity and stimulated HCC development. Finally, high levels of circ_002136 or RAB1A, as well as low levels of miR-19a-3p, negatively affected HCC patient survival. CONCLUSION: The study on circ_002136 provides good data to support our insight into the mechanism of to-be-silenced circRNA as a therapeutic agent in the progression of HCC.

CCAT1/FABP5 promotes tumour progression through mediating fatty acid metabolism and stabilizing PI3K/AKT/mTOR signalling in lung adenocarcinoma.

Long non-coding RNA (lncRNA) colon cancer associated transcript 1 (CCAT1) has been identified as an oncogene in many cancers, but its role in lung adenocarcinoma (LUAD) remains to be further investigated. We identified the upregulation of CCAT1 in LUAD tissues and LUAD cells. Through RNA pull-down and mass spectrometry analysis, we obtained the interacting proteins with CCAT1 and discovered their functional relation with 'signal transduction', 'energy pathways' and 'metabolism' and revealed the potential of CCAT1 on fatty acid (FA) metabolism. For mechanism exploration, we uncovered the mediation of CCAT1 on the translocation of fatty acid binding protein 5 (FABP5) into nucleus by confirming their interaction and localization. Also, CCAT1 was discovered to promote the formation of the transcription complex by RXR and PPARγ so as to activate the transcription of CD36, PDK1 and VEGFA. Moreover, we found that CCAT1 regulated the activity of AKT by promoting the ubiquitination of FKBP51 through binding with USP49. Subsequently, cell function assays revealed the enhancement of CCAT1 on LUAD cell proliferation and angiogenesis in vitro and in vivo. Collectively, CCAT1 regulated cell proliferation and angiogenesis through regulating FA metabolism in LUAD, providing a novel target for LUAD treatment.

The clinical efficiency of TACE combined with simultaneous computed tomography-guided radiofrequency ablation for advanced hepatocellular carcinoma.

Background To investigate the clinical efficiency of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) for advanced hepatocellular carcinoma (HCC). Methods This retrospective study enrolled 177 HCC patients, and they were divided into TACE monotherapy group (n = 129) and TACE + RFA group (n = 48) between January 2015 and October 2017. The objective response rate (ORR), disease control rate (DCR), and the survival outcomes were compared between the TACE monotherapy and the treatment of TACE + RFA after propensity score matching (PSM). Results After PSM matching, the confounding factors had no significant differences between the 48 pairs of patients. The DCR was calculated as 33 (69 %) and 42 (88 %) for the TACE monotherapy group and TACE + RFA group, respectively (P < 0.05). And the ORR was calculated as 23 (48 %) and 35 (73 %), respectively (P < 0.05). Moreover, the PFS rate of the TACE + RFA group was significantly higher than the TACE alone group (P < 0.001). Conclusions The treatment of TACE combined with RFA has better tumor response rate and survival rate than the TACE monotherapy for patients with advanced HCC.

Trichostatin A downregulates bromodomain and extra-terminal proteins to suppress osimertinib resistant non-small cell lung carcinoma.

BACKGROUND: The third-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients with non-small cell lung carcinoma (NSCLC) who carry active EGFR mutations, as well as those who have developed acquired resistance to the first-generation of EGFR-TKIs due to the T790M mutation. However, most patients develop drug resistance after 8-10 months of treatment. Currently, the mechanism has not been well clarified, and new therapeutic strategies are urgently needed. METHODS: Osimertinib resistant cell lines were established by culturing sensitive cells in chronically increasing doses of osimertinib. The anticancer effect of reagents was examined both in vitro and in vivo using the sulforhodamine B assay and a xenograft mouse model. The molecular signals were detected by western blotting. The combination effect was analyzed using CompuSyn software. RESULTS: We found that bromodomain and extra-terminal proteins (BETs) were upregulated in osimertinib resistant (H1975-OR) cells compared with those in the paired parental cells (H1975-P), and that knockdown of BETs significantly inhibited the growth of H1975-OR cells. The BET inhibitor JQ1 also exhibited stronger growth-inhibitory effects on H1975-OR cells and a greater expression of BETs and the downstream effector c-Myc than were observed in H1975-P cells. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) showed stronger growth suppression in H1975-OR cells than in H1975-P cells, but vorinostat, another HDAC inhibitor, showed equal inhibitory efficacy in both cell types. Consistently, downregulation of BET and c-Myc expression was greater with TSA than with vorinostat. TSA restrained the growth of H1975-OR and H1975-P xenograft tumors. The combination of TSA and JQ1 showed synergistic growth-inhibitory effects in parallel with decreased BET and c-Myc expression in both H1975-OR and H1975-P cells and in xenograft nude mouse models. BETs were not upregulated in osimertinib resistant HCC827 cells compared with parental cells, while TSA and vorinostat exhibited equal inhibitory effects on both cell types. CONCLUSION: Upregulation of BETs contributed to the osimertinib resistance of H1975 cells. TSA downregulated BET expression and enhanced the growth inhibitory effect of JQ1 both in vitro and in vivo. Our findings provided new strategies for the treatment of osimertinib resistance.

Current applications of platelet gels in wound healing-A review.

Human platelets play important roles in several physiologic and pathologic processes. Platelet concentrates are activated with thrombin or calcium, resulting in a viscous coagulum (platelet gel [PG]), composed of 95% platelets at least. PG is increasingly used for the treatment of a variety of soft and hard tissue defects, most notably in the management of chronic non-healing wounds. During wound healing, platelets not only play a critical role in primary hemostasis and thrombosis, but also release growth factors and cytokines to promote tissue regeneration, enhance collagen synthesis, and trigger an immune response. This review addresses a variety of aspects relevant to the functions of well-known platelet growth factors, animal and clinical studies of PG in the last decade, and different sources of platelets for PG. PG is used for non-healing chronic wounds, such as oral ulcerations related to epidermolysis bullosa and chronic graft-versus-host disease, for those, the traditional treatment effect is poor. PG maybe provide a new therapeutic direction for these diseases. Nevertheless, some uncertainty is present, the number of clinical studies is not enough. Hence, randomized controlled trials are still required to study the potential of the use of PG in the near future.

Sudden coma at the onset of severe refractory thrombotic thrombocytopenic purpura with successful treatment.

Most patients develop coma several days after the onset of thrombotic thrombocytopenic purpura (TTP) caused by microvascular occlusion. However, aggravated coma as the first symptom of TTP has rarely been reported. Although plasma exchange (PEX) and steroids have reduced mortality, the prognosis of patients with TTP is still poor. We reported a patient with refractory TTP presenting with aggravated coma on admission. After days of successful PEX, rituximab, and glucocorticoid therapy for clinical remission, the patient regained consciousness and returned to his normal life with a good outcome. Our case highlights that TTP should be considered when coma occurs as the first symptom.

CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia.

HOX gene dysregulation is a common feature of acute myeloid leukemia (AML). The molecular mechanisms underlying aberrant HOX gene expression and associated AML pathogenesis remain unclear. The nuclear protein CCCTC-binding factor (CTCF), when bound to insulator sequences, constrains temporal HOX gene-expression patterns within confined chromatin domains for normal development. Here, we used targeted pooled CRISPR-Cas9-knockout library screening to interrogate the function of CTCF boundaries in the HOX gene loci. We discovered that the CTCF binding site located between HOXA7 and HOXA9 genes (CBS7/9) is critical for establishing and maintaining aberrant HOXA9-HOXA13 gene expression in AML. Disruption of the CBS7/9 boundary resulted in spreading of repressive H3K27me3 into the posterior active HOXA chromatin domain that subsequently impaired enhancer/promoter chromatin accessibility and disrupted ectopic long-range interactions among the posterior HOXA genes. Consistent with the role of the CBS7/9 boundary in HOXA locus chromatin organization, attenuation of the CBS7/9 boundary function reduced posterior HOXA gene expression and altered myeloid-specific transcriptome profiles important for pathogenesis of myeloid malignancies. Furthermore, heterozygous deletion of the CBS7/9 chromatin boundary in the HOXA locus reduced human leukemic blast burden and enhanced survival of transplanted AML cell xenograft and patient-derived xenograft mouse models. Thus, the CTCF boundary constrains the normal gene-expression program, as well as plays a role in maintaining the oncogenic transcription program for leukemic transformation. The CTCF boundaries may serve as novel therapeutic targets for the treatment of myeloid malignancies.

Prognostic nutritional index and the prognosis of diffuse large b-cell lymphoma: a meta-analysis.

BACKGROUND: Some studies have investigated the prognostic value exhibited by the Prognostic Nutritional Index (PNI) in patients suffering diffuse large B-cell lymphoma (DLBCL), but varying results were obtained. In order to determine the specific prognostic value more accurately, a meta-analysis was conducted in this study. METHODS: Literatures were searched from the China National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, the Cochrane Library, and Web of Science. Pooled hazard ratio (HR) and the 95% confidence interval (CI) were calculated to assess the association between PNI and the overall survival (OS) and the progression-free survival (PFS) of patients with DLBCL. RESULTS: Based on seven studies with a total number of 1311 patients, our meta-analysis revealed that low PNI may meant poor OS (HR = 2.14, 95% CI 1.66-2.75, p < 0.001) and poor PFS (HR = 1.75, 95% CI 1.36-2.25, p = 0.438). Subgroup analysis showed that, in Asians, low PNI was correlated to poor OS (pooled HR = 2.06 95% CI 1.59-2.66) and poor PFS (pooled HR = 1.66, 95% CI 1.28-2.15). Similar results were obtained from one European study, which is the only study performed outside of Asia from our literature search. CONCLUSION: For patients with DLBCL, low PNI may be interpreted as adverse prognosis. More data from European patients are required in this study to avoid analysis bias.

Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease.

It is well acknowledged that allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for numerous malignant blood diseases, which has also been applied to autoimmune diseases for more than a decade. Whereas graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a common serious complication, seriously affecting the efficacy of transplantation. Mesenchymal stem cells (MSCs) derived from a wealth of sources can easily isolate and expand with low immunogenicity. MSCs also have paracrine and immune regulatory functions, leading to a broad application prospect in treatment and tissue engineering. This review focuses on immunoregulatory function of MSCs, factors affecting mesenchymal stem cells to exert immunosuppressive effects, clinical application of MSCs in GVHD and researches on MSC-derived extracellular vesicles (EVs). The latest research progress on MSC in related fields is reviewed as well. The relevant literature from PubMed databases is reviewed in this article.

HLA-DPA1 gene is a potential predictor with prognostic values in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM. METHODS: Differentially expressed genes (DEGs) were filtrated with R package "limma". Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using "clusterProfiler" package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance. RESULTS: HLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017). CONCLUSION: We identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients' poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.

A SERS-colorimetric dual-mode aptasensor for the detection of cancer biomarker MUC1.

Human mucin-1 (MUC1) has attracted considerable attention owing to its overexpression in diverse malignancies. Here, for the rapid and efficient detection of MUC1, we present a SERS-colorimetric dual-mode aptasensor, by integrating SERS probes with magnetic separation, which has several distinctive advantages. Using such a dual-mode aptasensor, the colorimetric functionality is distinguishable by the naked eye, providing a fast and straightforward screening ability for the detection of MUC1. Moreover, SERS-based detection greatly improves the detection sensitivity, reaching a limit of detection of 0.1 U/mL. In addition, the combination of SERS and colorimetric method holds the advantages of these two techniques and thereby increases the reliability and efficiency of MUC1 detection. On the one hand, the magnetic nanobeads functionalized with MUC1-specific aptamer were utilized as an efficient capturing substrate for separating MUC1 from biological complex medium. On the other hand, the gold-silver core-shell nanoparticles modified with Raman reporters and the complementary sequences of MUC1 were used as the signal indicator, which could simultaneously report the SERS signal and colorimetric change. This strategy can achieve a good detection range and realize MUC1 analysis in real patients' samples. Thus, we anticipate that this kind of aptasensor would provide promising potential applications in the diagnosis and prognosis of cancers. Graphical abstract.

Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer.

BACKGROUND: 5-Fluorouracil (5-FU) has been commonly prescribed for patients with colorectal cancer (CRC), but resistance to 5-FU is one of the main reasons for failure in CRC. Recently, microRNAs (miRNAs) have been established as a means of reversing the dilemma by regulating signaling pathways involved in initiation and progression of CRC. However, how to safely and effectively deliver miRNA to target cells becomes a main challenge. RESULTS: In this study, Engineered exosomes were exploited to simultaneously deliver an anticancer drug 5-FU and miR-21 inhibitor oligonucleotide (miR-21i) to Her2 expressing cancer cells. Purified engineered exosomes from the donor cells loaded with 5-FU and miR-21i via electroporation to introduce into 5-FU-resistant colorectal cancer cell line HCT-1165FR. Furthermore, systematic administration of 5-FU and miR-21i loaded exosomes in tumor bearing mice indicated a significantly anti-tumor effect. The results showed that the engineered exosome-based 5-FU and miR-21i co-delivery system could efficiently facilitate cellular uptake and significantly down-regulate miR-21 expression in 5-FU resistant HCT-1165FR cell lines. Consequently, the down-regulation of miR-21 induced cell cycle arrest, reduced tumor proliferation, increased apoptosis and rescued PTEN and hMSH2 expressions, regulatory targets of miR-21. Of particular importance was the significant reduction in tumor growth in a mouse model of colon cancer with systematic administration of the targeting miR-21i. More excitedly, the combinational delivery of miR-21i and 5-FU with the engineered exosomes effectively reverse drug resistance and significantly enhanced the cytotoxicity in 5-FU-resistant colon cancer cells, compared with the single treatment with either miR-21i or 5-FU. CONCLUSION: The strategy for co-delivering the functional small RNA and anticancer drug by exosomes foreshadows a potential approach to reverse the drug resistance in CRC and thus to enhance the efficacy of the cancer treatment.

Profiling of Exosomal Biomarkers for Accurate Cancer Identification: Combining DNA-PAINT with Machine- Learning-Based Classification.

Exosomes are endosome-derived vesicles enriched in body fluids such as urine, blood, and saliva. So far, they have been recognized as potential biomarkers for cancer diagnostics. However, the present single-variate analysis of exosomes has greatly limited the accuracy and specificity of diagnoses. Besides, most diagnostic approaches focus on bulk analysis using lots of exosomes and tend to be less accurate because they are vulnerable to impure extraction and concentration differences of exosomes. To address these challenges, a quantitative analysis platform is developed to implement a sequential quantification analysis of multiple exosomal surface biomarkers at the single-exosome level, which utilizes DNA-PAINT and a machine learning algorithm to automatically analyze the results. As a proof of concept, the profiling of four exosomal surface biomarkers (HER2, GPC-1, EpCAM, EGFR) is developed to identify exosomes from cancer-derived blood samples. Then, this technique is further applied to detect pancreatic cancer and breast cancer from unknown samples with 100% accuracy.

Influence of diet and dietary nanoparticles on gut dysbiosis.

Human gut comprises of a huge mixture of microorganisms as they had co-existed for millions of years. The change in co-existence of microbial genera leads to dysbiosis, which creates several disorders in humans. Diet and diet associated agents can have a considerable influence on host health by regulating the gut microbiome, which can thereby maintain the homeostasis of the gut. Analysis of the gut microbiome and the agents that can have an influence on the gut need a profound understanding, which is the need of the hour. The current review therefore focuses on the influence of diet and dietary nanoparticles on the gut microbiota and their positive or adverse effect.

Effects of dopants on the adhesion and electronic structure of a SnO2/Cu interface: a first-principles study.

Doping has been adopted as a versatile approach for tuning the adhesion of metal oxide/metal interfaces. Understanding the mechanism of doping at the interface adhesion on the atomic and electronic scale is crucial for the rational design and optimization of metal oxide/metal composites. In this work, we have investigated the effects of dopants on the adhesion of SnO2/Cu interfaces through first-principles calculations. Firstly, O-terminated a SnO2(110)/Cu(111) interface (denoted as I) was considered and the work of separation values of the interfaces with various dopants (Mo, Sb, Ti, Zn and Cu) were calculated to evaluate the interface adhesion strength. It was demonstrated that low-valence dopants (Zn2+ and Cu2+) enhance the adhesion strength of interface I, while high-valence dopants (Mo6+ and Sb5+) play the opposite role. Secondly, the strengthening effects of low-valence dopants were further verified in four candidate interfacial models with different atomic structures (denoted as II-V). The work of separation values indicated that the adhesion of all of the interfaces involved could be enhanced by low-valence doping. The electronic structure of the interface was demonstrated through density of states, charge density and charge density difference analyses. The results revealed that upon low-valence doping, the holes facilitate charge transfer between Cu and SnO2, which generates strong covalent bonds across the interface and thus significantly enhances the interface adhesion. This work not only provides insight into rational doping to enhance the adhesion of SnO2/Cu composites but can also be expanded upon for the design of other metal oxide/metal composites with strong interface adhesion.