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Development of nanomaterial-based electrochemiluminescence (ECL) emitters is highly desirable for the fabrication and wide applications of ECL sensors. Herein, nitrogen-doped graphene quantum dots (NGQDs) were easily synthesized as nanocarbon emitters with anodic ECL for sensitive ECL determination of catechol (CC). Facile synthesis of NGQDs was easily achieved using molecular fusion of a carbon precursor in a one-step hydrothermal process. The synthesis has advantages of simple and convenient operation and high yield. The as-prepared NGQDs have uniform size, good crystallinity, single-layered graphene structure, and excitation-independent fluorescence. In the presence of hydrogen peroxide (H

Purpose To establish a novel circRNA–miRNA–mRNA network associated with the poor prognosis of hepatocellular carcinoma (HCC). Materials and Methods Quantitative real-time PCR was used to verify the differentially expressed circRNA. Moreover, the competing endogenous RNA networks were established using bioinformatics methods. Meanwhile, the prognostic value and potential mechanism of ceRNA network in hepatocellular carcinoma (HCC) were analyzed. Results This work found that circ_0130911 was highly expressed in HCC tissues and early recurring HCC. Further, we effectively constructed a ceRNA network. The ceRNA network regulated by circ_0130911 might influence the prognosis of HCC by regulating cell cycle-related pathways. Conclusion The ceRNA network proposed here can be used as a novel biomarker for the prognosis of HCC, thereby providing new insights for the targeted therapy of HCC.

Cunqing Kong,1,* Banghao Xu,2,* Guanhua Qiu,1 Meng Wei,2 Mengqi Zhang,3 Shengxian Bao,1 Jiali Tang,1 Lequn Li,2 JunJie Liu1 1Department of Ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 3Department of Interventional Therapy Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: JunJie Liu, Department of ultrasound, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, People’s Republic of China, Email liujunjie@gxmu.edu.cn Lequn Li, Department of hepatobiliary surgery, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, People’s Republic of China, Email li_lequn@263.netIntroduction: Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues.Methods: In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional ICG@SANPs-cRGD nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer.Results: The experimental results show that ICG@SANPs-cRGD nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on ICG@SANPs-cRGD can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of ICG@SANPs-cRGD. PTT/PDT combined with Anti-PD-L1 immunotherapy based on ICG@SANPs-cRGD mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body’s immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor.Discussion: This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on ICG@SANPs-cRGD nanomaterials for breast cancer treatment and demonstrates the potential of ICG@SANPs-cRGD as a multifunctional therapeutic platform for future cancer therapy.Keywords: photodynamic therapy, photothermal therapy, immune checkpoint blocking, immune enhancement effect

In various reactive oxygen species (ROS)‐based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS‐based antitumor outcomes is not even explored yet. To address it, a photocleaved O2‐released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O2 release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5‐i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia‐induced resistance to ROS‐based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.

Genetically arming new chimeric antigen receptors (CARs) on T cells is a prevalent method to fulfill CAR-T immunotherapy. However, this approach fails to completely address the poor infiltration, complex immunosuppressive tumor microenvironment (ITM), and insufficient immune cells, which are recognized as the three dominant hurdles to discouraging the trafficking and persistence of CAR-T and immune checkpoint blockade (ICB) immunotherapies against solid tumors. To address the three hurdles, a sonoimmunity-engineered nanoplatform is designed in which a rattle-type-structured carrier enables intraparticle-double-scattering to generate massive reactive oxygen species (ROS) during the sonodynamic process. Abundant ROS accumulation can directly kill tumor cells, release antigens, and activate systematic immune responses for expanding effector T or CAR-T cells, while alleviating ITM via immunosuppressive macrophage polarization and reduction in pro-tumorigenic cytokine secretion. Furthermore, the co-loaded phosphodiesterase-5 inhibitors release nitric oxide (NO) to impel vascular normalization and open the infiltration barrier (IB) for allowing more T cells to enter into the tumor. Systematic experiments demonstrate the feasibility of such intraparticle-double-scattering-decoded sonogenetics in the sonoimmunity-engineered nanoplatforms for expanding effector T or CAR-T cells, thereby promoting their infiltration into tumors and alleviating ITM. These compelling actions lead to excellent CAR-T and ICB immunotherapies against solid tumors with repressed tumor metastasis.

BackgroundBlocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity.MethodsIR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy.ResultsIn vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects.ConclusionThe combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.

Background: Colorectal cancer (CRC) metastasis remains the major cause of the CRC mortality, while the underlying mechanisms remain to be fully understood. In this study we investigated the role of cancer exosomes in CRC lung metastasis in vivo and in vitro. Methods: Expressions of Integrinα6 and Integrin β4 were examined in CRC cells as well as released exosomes. Co-culture assay with vascular endothelial cells was also analyzed.Results: We found that Integrin α6 and Integrin β4 are overexpressed in highly tumorigenic and metastatic CRC cell lines HCT116 and SW620 and their secreted exosomes, compared to the low tumorigenic and non-metastatic CRC cell lines. Disruption of ITGA6 and ITGB4 expression in CRC decreased the proliferation and tubulogenic capacities of vascular endothelial cells significantly, while ectopic expression of ITGA6 and ITGB4 gave rise to opposite effects. Further more, we demonstrated that exosomal ITGA6 and ITGB4 promoted the lung metastasis of CRCs in vivo.Conclusions: Our study provides new insight into the molecular mechanism of CRC metastasis by which CRC-derived exosomal ITGA6 and ITGB4 induce organotropism to the lung, leading to increased tubulogenic capacity and metastasis. It also reveals a biomarker-based prediction for CRC metastasis and a novel potential therapeutic targets for CRC.

Background. A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods. The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results. QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001 ). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05 ), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05 ). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan–Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004 ) and overall survival (OS) times ( P = 0.010 ) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004 ) and OS times ( P = 0.014 ) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

Background. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer that has a high level of morbidity and mortality. Long noncoding RNA (lncRNA) is a novel regulatory factor of tumour proliferation, apoptosis, and metastasis. Our previous studies indicated that lncRNA FOXP4-AS1 is a functional oncogene in HCC; thus, this study is aimed at further evaluating the clinical and biological function of FOXP4-AS1 in HCC. Material and Methods. First, we detected the expression of FOXP4-AS1 in HCC tissues and paracarcinoma normal tissues by qRT-PCR. Second, the prognostic effects of FOXP4-AS1 in patients with HCC were analysed in a training group and a verification group. Subsequently, to investigate the biological effects of FOXP4-AS1 on HCC cells, downexpression tests were further conducted. Results. The expression of FOXP4-AS1 was higher in HCC tissues than adjacent nontumourous tissues, whereas the low expression of FOXP4-AS1 was correlated with optimistic treatment outcomes, which suggested that FOXP4-AS1 may be an independent prognostic biomarker for HCC. Moreover, the downregulation of FOXP4-AS1 significantly reduced the cell proliferation and clonal abilities and inhibited the invasion, migration, and angiogenesis of hepatoma cells ( P < 0.05 ). Conclusion. These results revealed the clinical significance and biological function of FOXP4-AS1 in HCC development, which may provide a new direction for finding therapeutic targets and potential prognostic biomarkers of HCC.

p-Chloronitrobenzene (p-CNB) is a persistent refractory and toxic pollutant with a concentration up to 200 mg/L in industrial wastewater. Here, a super-fast removal rate was found at 0.2–0.8 V of external voltage over a p-CNB concentration of 40–120 mg/L when a bioelectrochemical technology is used comparing to the natural biodegradation and electrochemical methods. The reduction kinetics (k) was fitted well according to pseudo-first order model with respect to the different initial concentration, indicating a 1.12-fold decrease from 1.80 to 0.85 h−1 within the experimental range. Meanwhile, the highest k was provided at 0.5 V with the characteristic of energy saving. It was revealed that the functional bacterial (Propionimicrobium, Desulfovibrio, Halanaerobium, Desulfobacterales) was selectively enriched under electro-stimulation, which possibly processed Cl-substituted nitro-aromatics reduction. The possible degradation pathway was also proposed. This work provides the beneficial choice on the rapid treatment of high-concentration p-CNB wastewater.