Identification of Therapeutic Targets and Prognostic Biomarkers Among Chemokine (C-C Motif) Ligands in the Liver Hepatocellular Carcinoma Microenvironment.

Background: Liver hepatocellular carcinoma (LIHC) is the third leading cause of cancer-related death and the sixth most common solid tumor worldwide. In the tumor microenvironment, the cross-talk between cancer cells, immune cells, and stromal cells exerts significant effects on neoplasia and tumor development and is modulated in part by chemokines. Chemokine (C-C motif) ligands (CCL) can directly target tumor cells and stromal cells, and they have been shown to regulate tumor cell proliferation, cancer stem-like cell properties, cancer invasiveness and metastasis, which directly and indirectly affect tumor immunity and influence cancer progression, therapy and patient outcomes. However, the prognostic values of chemokines CCL in LIHC have not been clarified. Methods: In this study, we comprehensively analyzed the relationship between transcriptional chemokines CCL and disease progression of LIHC using the ONCOMINE dataset, GEPIA, UALCAN, STRING, WebGestalt, GeneMANIA, TRRUST, DAVID 6.8, LinkedOmics, TIMER, GSCALite, and Open Targets. We validated the protein levels of chemokines CCL through western blot and immunohistochemistry. Results: The transcriptional levels of CCL5/8/11/13/15/18/20/21/25/26/27/28 in LIHC tissues were significantly elevated while CCL2/3/4/14/23/24 were significantly reduced. A significant correlation was found between the expression of CCL14/25 and the pathological stage of LIHC patients. LIHC patients with low transcriptional levels of CCL14/21 were associated with a significantly poor prognosis. The functions of differentially expressed chemokines CCL were primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interactions, and TNF-α signaling pathway. Our data suggested that RELA/REL, NFKB1, STAT1/3/6, IRF3, SPI1, and JUN were key transcription factors for chemokines CCL. We found significant correlations among the expression of chemokines CCL and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) and immune checkpoints (PD-1. PD-L1, and CTLA-4). The western blot and immunohistochemistry results showed that protein expression levels of CCL5 and CCL20 were upregulated in LIHC. CCL5 and CCL20 were significantly correlated with the clinical outcome of patients with LIHC, and could be negatively regulated by some drugs or small molecules. Conclusions: Our results may provide novel insights for the potential suitable targets of immunological therapy and prognostic biomarkers for LIHC.

Correction: Ultra-fast synthesis of water soluble MoO3-x quantum dots with controlled oxygen vacancies and their near infrared fluorescence sensing to detect H2O2.

Correction for 'Ultra-fast synthesis of water soluble MoO3-x quantum dots with controlled oxygen vacancies and their near infrared fluorescence sensing to detect H2O2' by Shichuan Zhong et al., Nanoscale Horiz., 2020, 5, 1538-1543, DOI: 10.1039/D0NH00394H.

Downregulation of NAGLU in VEC Increases Abnormal Accumulation of Lysosomes and Represents a Predictive Biomarker in Early Atherosclerosis.

Cardiovascular diseases (CVDs), predominantly caused by atherosclerosis (AS), are the leading cause of mortality worldwide. Although a great number of previous studies have attempted to reveal the molecular mechanism of AS, the underlying mechanism has not been fully elucidated. The aberrant expression profiling of vascular endothelial cells (VECs) gene in early atherosclerosis (EAS) was analyzed according to the dataset (GSE132651) downloaded from the Gene Expression Omnibus (GEO) database. We primarily performed functional annotation analysis on the downregulated genes (DRGs). We further identified that α-N-acetylglucosaminidase (NAGLU), one of the DRGs, played a critical role in the progression of EAS. NAGLU is a key enzyme for the degradation of heparan sulfate (HS), and its deficiency could cause lysosomal accumulation and lead to dysfunctions of VECs. We found that siRNA knockdown of NAGLU in human umbilical vein endothelial cell (HUVEC) aggravated the abnormal accumulation of lysosomes and HS. In addition, the expression of NAGLU was reduced in the EAS model constructed by ApoE -/- mice. Furthermore, we also showed that heparin-binding EGF-like growth factor (HB-EGF) protein was upregulated while NAGLU knockdown in HUVEC could specifically bind to vascular endothelial growth factor receptor 2 (VEGFR2) and promote its phosphorylation, ultimately activating the phosphorylation levels of extracellular signal-regulated kinases (ERKs). However, the application of selective VEGFR2 and ERKs inhibitors, SU5614 and PD98059, respectively, could reverse the abnormal lysosomal storage caused by NAGLU knockdown. These results indicated that downregulation of NAGLU in HUVEC increases the abnormal accumulation of lysosomes and may be a potential biomarker for the diagnosis of EAS.

Ultra-fast synthesis of water soluble MoO3-x quantum dots with controlled oxygen vacancies and their near infrared fluorescence sensing to detect H2O2.

We report a facile method for the synthesis of water soluble MoO3-x quantum dots (QDs) at room temperature by injecting hydrochloric acid and mercaptosuccinic acid into ammonium molybdate solution within 5 seconds. The optical properties and oxygen vacancy concentration of the QDs could be well controlled by the competitive absorption of a carboxyl group and sulfhydryl group of the ligand with QDs by coordination interaction. The obtained QDs could be used as near infrared region (NIR) fluorescence probes to detect hydrogen peroxide with a low detection limit (3 nM).

Highly Selective and Sensitive Detection of Hydrogen Sulfide by the Diffraction Peak of Periodic Au Nanoparticle Array with Silver Coating.

The two-dimensional (2D) periodic Au nanosphere array with silver coating was prepared by using a colloidal monolayer template to obtain a Au nanosphere array and subsequently depositing silver thin coating on it, which could be used as an optical sensor to effectively detect H2S. Such periodic Au nanosphere array with silver coating displayed a surface plasmonic resonance (SPR) peak and an optical diffraction peak. Compared with the SPR peak, the diffraction peak, originated from the periodic arrangements of the obtained array, demonstrated a more sensitive optical change to detect H2S with a significant redshift as the H2S concentration increased. It was attributed to the increase of the refractive index of the environment around the Au nanosphere arrays with silver coating due to the partial formation of Ag2S after detecting H2S. Furthermore, the H2S sensor based on the change of the optical diffraction peak, showed an excellent selectivity and it was very sensitive to detect H2S from 2 to 30 µM. This method was investigated by the analysis in H2S-spiked blood samples, which indicates that the method has the potential to detect H2S in blood samples. The presented work provides a new strategy of utilizing the optical diffraction peak of the periodic array to develop promising sensors.

Dynamically Tunable Plasmonic Band for Reversible Colorimetric Sensors and Surface-Enhanced Raman Scattering Effect with Good Sensitivity and Stability.

A colorimetric sensor based on plasmonic nanoparticles (NPs) is a promising and convenient detection tool, but its reproducibility and adjustability remain a challenge because the NPs are mainly random and uncontrollable. Herein, a colorimetric sensor with good reversibility and reproducibility was prepared by embedding the two-dimensional (2D) Au NP arrays on the surface of the polyacrylamide hydrogel film to form 2D Au NP arrays attached a hydrogel composite. For this composite, with the change of the interspacing distance of Au NPs driven by the swelling-shrinking behavior of the hydrogel carrier, the diffraction peaks faded away and plasmonic coupling peaks appeared, accompanied by a series of obvious color changes (iridescence ↔ violet ↔ golden yellow ↔ red), which can be correlated to the applied water content. Importantly, the composite had good reproducibility as a result of a highly ordered array structure. Additionally, this colorimetric sensor with a dynamically tunable plasmonic band can be used as a high-quality surface-enhanced Raman scattering (SERS) substrate because the gap distance of the Au NPs can be uniformly controlled. We demonstrated that, as the active gap distance decreased, the SERS signals can be significantly intensified. When the water content reached 40%, this SERS substrate exhibited high sensitivity (10-10 M for 4-aminothiophenol and 10-9 M for thiram) and good reproducibility (relative standard deviation of <20%) using the excitation laser of 785 nm because of the small gap between two adjacent Au NPs and the highly ordered periodic structure. Such 2D Au NP arrays attached to a hydrogel composite could be a new strategy to obtain a high-quality colorimetric sensor and dynamic SERS substrate.

Cr-Dopant Induced Breaking of Scaling Relations in CoFe Layered Double Hydroxides for Improvement of Oxygen Evolution Reaction.

Monodentate adsorption of oxygen intermediates results in a theoretical overpotential limit of ≈0.35 V for oxygen evolution reaction (OER), which causes the sluggish kinetics of the OER process. In this work, nonprecious chromium dopant is introduced into the self-supported CoFe layered double hydroxides (LDHs) on nickel foam (Cr-CoFe LDHs/NF) via a facile one-step hydrothermal method, which exhibits a preeminent electrocatalytic activity toward the OER with an ultralow overpotential of 238 mV to obtain 10 mA cm-2 and a high stability after cyclic voltammetry for 5000 cycles in alkaline solution (1 m KOH). Density functional theory (DFT) calculations unveil that Cr dopants as new active sites could improve the electron-donation ability of the resultant Cr-CoFe LDHs due to the smaller electronegativity of Cr in comparison with Fe and Co. Therefore, the scaling relation of adsorption energy among four oxygen intermediates is broken and consequently the OER performance is further promoted. This work provides a strategy to develop efficient metal layered double hydroxide OER catalysts.

Flexible vanadium-doped Ni2P nanosheet arrays grown on carbon cloth for an efficient hydrogen evolution reaction.

Tuning the electronic structure, morphology, and structure of electrocatalysts is of great significance to achieve a highly active and stable hydrogen evolution reaction (HER). Herein, combining hydrothermal and low temperature phosphidation methods, V-doped Ni2P nanosheet arrays grown on carbon cloth (V-Ni2P NSAs/CC) were successfully prepared for the HER. It is found that the prepared V-Ni2P NSAs/CC exhibits preeminent performance for the HER. Specifically, it only requires an overpotential of 85 mV to achieve a current density of 10 mA cm-2 in 1.0 M KOH solution. Moreover, the V-Ni2P NSAs/CC shows superior electrochemical stability, maintaining its HER performance up to 3000 cyclic voltammetry cycles. This work affords a guiding strategy for the synthesis of a high-performance and stable electrocatalyst for the HER.