The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma.

BACKGROUND: Pyrimidine metabolism is critical for tumour progression. Uridine-cytidine kinase 2 (UCK2), a key regulator of pyrimidine metabolism, is elevated during hepatocellular carcinoma (HCC) development and exhibits carcinogenic effects. However, the key mechanism of UCK2 promoting HCC and the therapeutic value of UCK2 are still undefined. The aim of this study is to investigate the potential of UCK2 as a therapeutic target for HCC. METHODS: Gene expression matrices were obtained from public databases. RNA-seq, co-immunoprecipitation and RNA-binding protein immunoprecipitation were used to determine the mechanism of UCK2 promoting HCC. Immune cell infiltration level and immune-related functional scores were evaluated to assess the link between tumour microenvironment and UCK2. RESULTS: In HCC, the expression of UCK2 was upregulated in part by TGFß1 stimulation. UCK2 promoted cell cycle progression of HCC by preventing the degradation of mTOR protein and maintaining the stability of PDPK1 mRNA. We also identified UCK2 as a novel RNA-binding protein. Downregulation of UCK2 induced cell cycle arrest and activated the TNFα/NFκB signalling pathway-related senescence-associated secretory phenotype to modify the tumour microenvironment. Additionally, UCK2 was a biomarker of the immunosuppressive microenvironment. Downregulated UCK2 induced a secretory phenotype, which could improve the microenvironment, and decreased UCK2 remodelling metabolism could lower the resistance of tumour cells to T-cell-mediated killing. CONCLUSIONS: Targeting UCK2 inhibits HCC progression and could improve the response to immunotherapy in patients with HCC. Our study suggests that UCK2 could be an ideal target for HCC.

miR-124 Suppresses Pancreatic Ductal Adenocarcinoma Growth by Regulating Monocarboxylate Transporter 1-Mediated Cancer Lactate Metabolism.

BACKGROUND/AIMS: Increasing evidence shows that reprogramming of energy metabolism is a hallmark of cancer. Considering the emergence of microRNAs as crucial modulators of cancer, this study aimed to better understand the molecular mechanisms of miR-124 in regulating glycolysis in human pancreatic cancer. METHODS: RT-PCR was used to investigate the expression of monocarboxylate transporters (MCTs) in pancreatic ductal adenocarcinoma (PDAC) patient samples and the PANC-1 cell line. A public database and immunochemistry were used for comprehensive analysis of MCT1 expression. The targeting of MCT1 by miR-124 was predicted by software and validated for the MCT1 3'-UTR by dual-luciferase reporter analysis. Cell proliferation, apoptosis, migration, xenografting, and the intracellular pH and L-lactate levels were assessed. Hypoxia-inducible factor-α (HIF-1α) and lactate dehydrogenase A (LDH-A) expression levels were determined by RT-PCR and western blotting. RESULTS: MCT1 expression was higher in PDAC tissue than in normal tissue. Inhibition of MCT1 affected lactate metabolism, resulting in a higher intracellular pH and less proliferation of PANC-1 cells. MCT1 was the target gene of miR-124. In in vitro experiments, miR-124 inhibited the glycolytic activity of PANC-1 cells by targeting MCT1, further decreasing the tumor phenotype by increasing the intracellular pH through LDH-A and HIF-1α. In in vivo experiments, overexpression of miR-124 and silencing of MCT1 significantly inhibited tumor growth. CONCLUSION: miR-124 inhibits the progression of PANC-1 by targeting MCT1 in the lactate metabolic pathway. Our findings provide novel evidence for further functional studies of miR-124, which might be useful for future therapeutic approaches to PDAC.

Hierarchically designed three-dimensional macro/mesoporous carbon frameworks for advanced electrochemical capacitance storage.

Mesoporous carbon (m-C) has potential applications as porous electrodes for electrochemical energy storage, but its applications have been severely limited by the inherent fragility and low electrical conductivity. A rational strategy is presented to construct m-C into hierarchical porous structures with high flexibility by using a carbon nanotube (CNT) sponge as a three-dimensional template, and grafting Pt nanoparticles at the m-C surface. This method involves several controllable steps including solution deposition of a mesoporous silica (m-SiO2 ) layer onto CNTs, chemical vapor deposition of acetylene, and etching of m-SiO2 , resulting in a CNT@m-C core-shell or a CNT@m-C@Pt core-shell hybrid structure after Pt adsorption. The underlying CNT network provides a robust yet flexible support and a high electrical conductivity, whereas the m-C provides large surface area, and the Pt nanoparticles improves interfacial electron and ion diffusion. Consequently, specific capacitances of 203 and 311 F g(-1) have been achieved in these CNT@m-C and CNT@m-C@Pt sponges as supercapacitor electrodes, respectively, which can retain 96 % of original capacitance under large degree compression.

Fabrication and oil adsorption of carbon nanotube/polyvinylpyrrolidone surface composite.

It needs to assemble the industrial CNT powders into macroscopic porous surface composite to utilize the surface properties of CNTs, as well as to prevent them entering into environments. We demonstrate a method to fabricate the surface composites from CNTs and polyvinylpyrrolidone (PVP) by electrospinning, where CNTs distribute firmly and mainly on the surface PVP nanofibers. The CNTs/PVP surface composites have high pore volume of 10 cc/g and remarkable CNTs load of 98%. Thus the surface composites show high oil adsorption capacity of 0.9~1.1 g/cm3. It can absorb more oil than commercial sponges due to the surface composite swells after absorbing oil. It shows attractive potential application of the CNT/PVP surface composite in oil spill cleanup.

Colloidal antireflection coating improves graphene-silicon solar cells.

Carbon nanotube-Si and graphene-Si solar cells have attracted much interest recently owing to their potential in simplifying manufacturing process and lowering cost compared to Si cells. Until now, the power conversion efficiency of graphene-Si cells remains under 10% and well below that of the nanotube-Si counterpart. Here, we involved a colloidal antireflection coating onto a monolayer graphene-Si solar cell and enhanced the cell efficiency to 14.5% under standard illumination (air mass 1.5, 100 mW/cm(2)) with a stable antireflection effect over long time. The antireflection treatment was realized by a simple spin-coating process, which significantly increased the short-circuit current density and the incident photon-to-electron conversion efficiency to about 90% across the visible range. Our results demonstrate a great promise in developing high-efficiency graphene-Si solar cells in parallel to the more extensively studied carbon nanotube-Si structures.

Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2.

Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.

Controllable synthesis of spongy carbon nanotube blocks with tunable macro- and microstructures.

Macroscopic carbon nanotubes (CNTs) with uniform structures are in great demand for use in composites and environmental materials. Here we demonstrate the controlled synthesis of spongy CNT blocks with isotropic properties and flexible, freestanding structures. The formation mechanism of the isotropic CNT sponges is discussed, based on its open-ended structure and initial formation in the vapor phase. The microstructure of the CNT sponges can be tuned by changing the flow rate of the carrier gas, resulting in CNT sponges with diameters ranging from 30.2 to 47.8 nm and wall thicknesses from 7 to 16 nm. The bulk density (5-25 mg cm(-3)), mechanical strength of the CNT sponges, and filling rate of ferromagnetic catalyst in the CNT sponges can also be modulated by controlling the supply rate of the carbon source, suggesting potential applications in mechanical energy absorption and environmental materials.

Suppression of the coffee-ring effect by self-assembling graphene oxide and monolayer titania.

The in situ self-assembly of two types of typical two-dimensional (2D) nanomaterials (i.e., graphene oxide (GO) and monolayer titania (TO)) is realized using a simple drop-casting method. Within the as-prepared hybrid films, the GO and TO nanosheets arrange alternately into a lamellar structure. Notably, the hybridization of GO and TO suppresses the formation of coffee-rings when drop-cast, which is attributed to the strong interactions between the GO and TO nanosheets. Finally, the mechanism for the in situ hybridization of these two types of nanosheets into heterogeneous lamellar films and the suppression of the coffee-ring effect are discussed. These results demonstrate the potential applications of drop-cast hybrid films for high-quality membrane deposition from liquid phases.

Flexible all solid-state supercapacitors based on chemical vapor deposition derived graphene fibers.

Flexible all-solid-state supercapacitors based on graphene fibers are demonstrated in this study. Surface-deposited oxide nanoparticles are used as pseudo-capacitor electrodes to achieve high capacitance. This supercapacitor electrode has an areal capacitance of 42 mF cm(-2), which is comparable to the capacitance for fiber-based supercapacitors reported to date. During the bending and cycling of the fiber-based supercapacitor, the stability could be maintained without sacrificing the electrochemical performance, which provides a novel and simple way to develop flexible, lightweight and efficient graphene-based devices.

Boosting supercapacitor performance of carbon fibres using electrochemically reduced graphene oxide additives.

Modifying conventional materials with new recipes represents a straightforward yet efficient way to realize large-scale applications of new materials. Electrochemically reduced graphene oxide (ERGO) coated carbon fibres (CFs), prepared as fibre-like supercapacitor electrodes, exhibited excellent electrochemical energy storage performance. Upon addition of only a small amount (~1 wt%) of ERGO, the hybrid fibres showed superior electrochemical capacitances (nearly three orders of magnitude enhanced) compared to pure CFs in both aqueous and gel electrolytes. Meanwhile, the energy density did not decrease notably as the power density increased. The superior capacitive performance could be attributed to the synergistic effect between wrinkled and porous ERGO sheets and highly conductive CFs. This fibre electrode material also offered advantages such as easy operation, mass production capability, mechanical flexibility and robustness, and could have an impact on a wide variety of potential applications in energy and electronic fields.

Downregulated Acetyl-CoA Acyltransferase 2 Promoted the Progression of Hepatocellular Carcinoma and Participated in the Formation of Immunosuppressive Microenvironment.

Background: The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC). Methods: Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism. Results: We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4+TCF7+T, CD4+FOXP3+T, CD8+GZMK+T, and CD8+KLRD1+T cells was inversely correlated with the composition of CD8+PDCD1+T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks. Conclusion: In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.

Controllable growth of triangular hexagonal boron nitride domains on copper foils by an improved low-pressure chemical vapor deposition method.

We demonstrate an improved low-pressure chemical vapor deposition method to fabricate hexagonal boron nitride (h-BN) domains of a few layers (one-four layers) from ammonia borane by adding a small quartz tube to stabilize the gas flow over the copper substrate and reducing the growing rate of h-BN. The h-BN grows freely and spontaneously to form triangular domains on the Cu (100) plane. The triangular domains are prone to be parallel to each other on the copper substrate. The h-BN domains grow by extending in the normal direction of the triangle and form a large thin film by joining together. Both the size and coverage rate on Cu foils are well controlled by tuning the amount of ammonia borane.

Topology evolution of graphene in chemical vapor deposition, a combined theoretical/experimental approach toward shape control of graphene domains.

Morphology control of thin film relies on understanding multiple ongoing processes during deposition and growth. To reveal the shape evolution of graphene domains on copper surfaces in chemical vapor deposition (CVD), a combinative study is performed on the CVD growth of graphene on copper surfaces. To identify the factors that influence the adsorption and diffusion of carbon atoms and further determine the domain shape, simulations based on kinetic Monte Carlo techniques are carried out. The results reveal the dependence of the graphene domain shapes on the crystalline orientation of the underlying copper substrate surfaces.

Preparation of highly oxidized nitrogen-doped carbon nanotubes.

A method for the preparation of highly oxidized nitrogen-doped carbon nanotubes (N-CNTs) from KMnO(4) + H(2)SO(4) solution is described. The atomic ratio of C/O in oxidized N-CNTs is as low as 1.2. The x-ray photoelectron spectroscopy results show that about 75% of the carbon atoms are oxidized and bound to oxygen-containing functional groups. The oxidation reaction mainly occurs at the outer sidewalls, which destroys the graphene stack to an sp(3)-rich structure and helps to preserve the tubular structure of the inner N-CNTs. The oxidized N-CNTs show an energy gap of ~2.1 eV.

Wire-supported CdSe nanowire array photoelectrochemical solar cells.

Previous fiber-shaped solar cells are based on polymeric materials or dye-sensitized wide band-gap oxides. Here, we show that efficient fiber solar cells can be made from semiconducting nanostructures (e.g. CdSe) with smaller band-gap as the light absorption material. We directly grow a vertical array of CdSe nanowires uniformly around a core metal wire and make the device by covering the top of nanowires with a carbon nanotube (CNT) film as the porous transparent electrode. The CdSe-CNT fiber solar cells show power conversion efficiencies of 1-2% under AM 1.5 illumination after the nanowires are infiltrated with redox electrolyte. We do not use a secondary metal wire (e.g. Pt) as in conventional fiber-shaped devices, instead, the end part of the CNT film is condensed into a conductive yarn to serve as the secondary electrode. In addition, our CdSe nanowire-based photoelectrochemical fiber solar cells maintain good flexibility and stable performance upon rotation and bending to large angles.

Strong and reversible modulation of carbon nanotube-silicon heterojunction solar cells by an interfacial oxide layer.

Deposition of nanostructures such as carbon nanotubes on Si wafers to make heterojunction structures is a promising route toward high efficiency solar cells with reduced cost. Here, we show a significant enhancement in the cell characteristics and power conversion efficiency by growing a silicon oxide layer at the interface between the nanotube film and Si substrate. The cell efficiency increases steadily from 0.5% without interfacial oxide to 8.8% with an optimal oxide thickness of about 1 nm. This systematic study reveals that formation of an oxide layer switches charge transport from thermionic emission to a mixture of thermionic emission and tunneling and improves overall diode properties, which are critical factors for tailoring the cell behavior. By controlled formation and removal of interfacial oxide, we demonstrate oscillation of the cell parameters between two extreme states, where the cell efficiency can be reversibly altered by a factor of 500. Our results suggest that the oxide layer plays an important role in Si-based photovoltaics, and it might be utilized to tune the cell performance in various nanostructure-Si heterojunction structures.

Achieving high efficiency silicon-carbon nanotube heterojunction solar cells by acid doping.

Various approaches to improve the efficiency of solar cells have followed the integration of nanomaterials into Si-based photovoltaic devices. Here, we achieve 13.8% efficiency solar cells by combining carbon nanotubes and Si and doping with dilute HNO(3). Acid infiltration of nanotube networks significantly boost the cell efficiency by reducing the internal resistance that improves fill factor and by forming photoelectrochemical units that enhance charge separation and transport. Compared to conventional Si cells, the fabrication process is greatly simplified, simply involving the transfer of a porous semiconductor-rich nanotube film onto an n-type crystalline Si wafer followed by acid infiltration.

Exploring the role of mast cells in the progression of liver disease.

In addition to being associated with allergic diseases, parasites, bacteria, and venoms, a growing body of research indicates that mast cells and their mediators can regulate liver disease progression. When mast cells are activated, they degranulate and release many mediators, such as histamine, tryptase, chymase, transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α(TNF-α), interleukins cytokines, and other substances that mediate the progression of liver disease. This article reviews the role of mast cells and their secretory mediators in developing hepatitis, cirrhosis and hepatocellular carcinoma (HCC) and their essential role in immunotherapy. Targeting MC infiltration may be a novel therapeutic option for improving liver disease progression.

Cytochrome B5 type A alleviates HCC metastasis via regulating STOML2 related autophagy and promoting sensitivity to ruxolitinib.

The incidence of hepatocellular carcinoma (HCC) is increasing in the world. However, its role and underlying molecular mechanism in HCC progression remain unclear. We found that CYB5A plays a key role in HCC metastasis by inhibiting the JAK1/STAT3 pathway through binding to STOML2. CYB5A combined with STOML2 can predict the outcome of patients. To demonstrate the effect of CYB5A on JAK1 inhibitor function, we applied Ruxolitinib in metastatic tumors with high CYB5A expression and found that it slowed disease progression and prolonged survival in mice. To the best of our knowledge, this study is the first to report the Ruxolitinib effect on the metastatic ability of HCC cells in vivo and in vitro.