Extracellular Vesicle-Packaged ACSL4 Induces Hepatocyte Senescence to Promote Hepatocellular Carcinoma Progression.

Extracellular vesicles (EVs) derived from cancer cells are crucial mediators of intercellular communication during tumor progression. The cargo in tumor-derived EVs that facilitates the establishment of a tumor-supportive microenvironment could serve as a therapeutic target to improve cancer treatment. Here, we demonstrated that hepatocellular carcinoma (HCC) cells secreted the acyl-CoA synthetase ACSL4 in large extracellular vesicles (lEVs) to modulate tumor-microenvironment interactions that promote HCC progression. HCC-derived lEV ACSL4 increased the intracellular abundance of polyunsaturated fatty acid-containing lipids and remodeled the lipid profile to potentiate lipid peroxidation in peritumoral hepatocytes, resulting in hepatocyte senescence accompanied by the senescence-associated secretory phenotype (SASP). Depletion of senescent hepatocytes by senolytic treatment suppressed tumor progression. In HCC cells, SREBP2-mediated transcriptional activation upregulated ACSL4 expression, and Akt-mediated phosphorylation of ACSL4 induced its packaging into lEVs by augmenting its interaction with Annexin A2. This study identified the critical regulatory function of ACSL4 secreted from HCC cells in inducing lipid remodeling and senescence in hepatocytes to support HCC progression, suggesting that targeting lEV ACSL4 is a potential therapeutic strategy for HCC.

Label-Free Fiber-Optic Raman Spectroscopy for Intravascular Coronary Atherosclerosis and Plaque Detection.

The rupture of atherosclerotic plaques remains one of the leading causes of morbidity and mortality worldwide. The plaques have certain pathological characteristics including a fibrous cap, inflammation, and extensive lipid deposition in a lipid core. Various invasive and noninvasive imaging techniques can interrogate structural aspects of atheroma; however, the composition of the lipid core in coronary atherosclerosis and plaques cannot be accurately detected. Fiber-optic Raman spectroscopy has the capability of in vivo rapid and accurate biomarker detection as an emerging omics technology. Previous studies demonstrated that an intravascular Raman spectroscopic technique may assess and manage the therapeutic and medication strategies intraoperatively. The Raman spectral information identified plaque depositions consisting of lipids, triglycerides, and cholesterol esters as the major components by comparing normal region and early plaque formation region with histology. By focusing on the composition of plaques, we could identify the subgroups of plaques accurately and rapidly by Raman spectroscopy. Collectively, this fiber-optic Raman spectroscopy opens up new opportunities for coronary atherosclerosis and plaque detection, which would assist optimal surgical strategy and instant postoperative decision-making. In this paper, we will review the advancement of label-free fiber-optic Raman probe spectroscopy and its applications of coronary atherosclerosis and atherosclerotic plaque detection.

Nickel Foam Coated by Ni Nanoparticle-Decorated 3D Nanocarbons as a Freestanding Host for High-Performance Lithium-Sulfur Batteries.

Nanocarbons (NCs) consisting of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) were coated on the surface of nickel foam (NF) via a chemical vapor deposition method. The CNFs formed conductive networks on NF, while the CNTs grew perpendicular to the surface of the CNFs, accompanied with the formation of Ni nanoparticles (Ni NPs) at the end of CNTs. The unique Ni-NCs-coated NF with a porous structure was applied as the three-dimensional (3D) current collector of lithium-sulfur (Li-S) batteries, which provided enough space to accommodate the electrode materials inside itself. Therefore, the 3D interconnected conductive framework of the coated NF collector merged in the electrode materials shortened the path of electron transport, and the generated Ni NPs could adsorb lithium polysulfides (LiPSs) and effectively accelerated the conversion kinetics of LiPSs as well, thereby suppressing the "shuttle effect". Moreover, the rigid framework of NF would also constrain the movement of the electrode compositions, which benefited the stability of the Li-S batteries. As a matter of fact, the Li-S battery based on the Ni-NCs-coated NF collector delivered an initial discharge capacity as high as 1472 mAh g-1 at 0.1C and outstanding high rate capability at 3C (802 mAh g-1). Additionally, low decay rates of 0.067 and 0.08% at 0.2C (300 cycles) and 0.5C (500 cycles) have been obtained, respectively. Overall, our prepared Ni-NCs-coated NF collector is promising for the application in high-performance Li-S batteries.

HK1 from hepatic stellate cell-derived extracellular vesicles promotes progression of hepatocellular carcinoma.

Extracellular vesicles play crucial roles in intercellular communication in the tumor microenvironment. Here we demonstrate that in hepatic fibrosis, TGF-ß stimulates the palmitoylation of hexokinase 1 (HK1) in hepatic stellate cells (HSCs), which facilitates the secretion of HK1 via large extracellular vesicles in a TSG101-dependent manner. The large extracellular vesicle HK1 is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, the nuclear receptor Nur77 transcriptionally activates the expression of depalmitoylase ABHD17B to inhibit HK1 palmitoylation, consequently attenuating HK1 release. However, TGF-ß-activated Akt functionally represses Nur77 by inducing Nur77 phosphorylation and degradation. We identify the small molecule PDNPA that binds Nur77 to generate steric hindrance to block Akt targeting, thereby disrupting Akt-mediated Nur77 degradation and preserving Nur77 inhibition of HK1 release. Together, this study demonstrates an overlooked function of HK1 in HCC upon its release from HSCs and highlights PDNPA as a candidate compound for inhibiting HCC progression.

Multi-dimensional and large-sized optical phased array for space laser communication.

In this study, we propose a novel multi-dimensional and large-sized optical phased array theory for space laser communication that addresses the theoretical limitations of the conventional optical phased array. We theoretically analyzed the principle of this phased array technology. The results of simulation and laboratory experiment clearly showed it can realize the large scanning angle and high optical gain required for communication. The novel optical phased array theory is of great significance to the revolution of miniaturization and networking in the field of space laser communication.

Cs3CuAs4Q8 (Q = S, Se): unique two-dimensional layered inorganic thioarsenates with the lowest Cu-to-As ratio and remarkable photocurrent responses.

Inorganic chalcogenides containing cations with lone-pair electrons have attracted considerable attention because of their potential applications in photocatalysis. In this research, two new copper thioarsenates with the lowest Cu-to-As ratio in the quaternary X/Cu/As/Q (X = inorganic cations; Q = chalcogen) system, namely Cs3CuAs4Q8 (Q = S, Se), were obtained by a simple surfactant-thermal method at a low temperature. These two isostructural compounds belong to the monoclinic space group C2/c (no. 15) and are composed charge-balanced Cs+ cations and two-dimensional anionic [CuAs4Q8]3- layers. Notably, photo-electrochemical measurements indicate that Cs3CuAs4Q8 possesses a remarkable photocurrent response under simulated solar-light illumination. Further theoretical studies were performed to gain insights into the relationships between electronic structure and optical properties.

Extracellular vesicles in the tumor immune microenvironment.

Extracellular vesicles (EVs) have gained significant attention in recent decades as major mediators of intercellular communication that are involved in various essential physiological and pathological processes. They are secreted by almost all cell types and carry bioactive materials, such as proteins, lipids and nucleic acids, that can be transmitted from host cells to recipient cells, thereby eliciting phenotypic and functional alterations in the recipient cells. Recent evidence shows that EVs play essential roles in remodeling the tumor immune microenvironment (TIME). EVs derived from tumor cells and immune cells mediate mutual communication at proximal and distal sites, which determines tumor fate and antitumor therapeutic effectiveness. In this review, the current understanding of EVs and their roles in remodeling the TIME and modulating tumor-specific immunity are summarized. We mainly discuss the mutual regulation between tumor cells and tumor-infiltrating immune cells through the delivery of EVs in the TIME. We also describe the limitations of current studies and discuss directions for further research.

Revascularization of Coronary Artery Chronic Total Occlusion by Active Antegrade Reverse Wire Technique.

OBJECTIVES: To assess the effectiveness and safety of ARW for vascular recanalization in CTO patients. BACKGROUND: Chronic total occlusion (CTO) of coronary artery accompanied with large branch distal to the occluded segment (<2 mm) is one of the challenges physicians are facing during the coronary intervention. In cases where the antegrade wire passed the occluded segment reaching the branch vessel, but could not access the main vessel through various adjustments, application of active antegrade reverse wire technique (ARW) could be considered. Patients and Methods. A total of 301 consecutive CTO patients who received the antegrade percutaneous coronary intervention (PCI) between December 2015 and December 2019 at our institution were included, of whom 11 were treated with ARW (10 successfully) for vascular recanalization. The applicability and safety of ARW were assessed. RESULTS: Among the 301 CTO patients who received antegrade vascular recanalization, 11 were treated with ARW. ARW was successful in 10 patients as follows: from the diagonal branch (D) to anterior descending branch (LAD) in 4 patients; from the septal branch (S) to LAD in 1 patient; from D to S and LAD in 1 patient; from the circumflex branch (LCX) to obtuse marginal branch (OM) in 1 patient; from OM to LCX in 1 patient; from a posterior descending artery (PDA) to the posterior lateral vein (PLV) in 2 patients. Yet, ARW in patient with RCAm CTO failed, while the consequent retrograde PCI succeeded. The mean J-CTO score of the 11 patients was 2.7 ± 0.65, among whom eight were accompanied with calcifications. Sion Black and Fielder XTR reverse wires were used in 9 and 2 patients, respectively. No loss of side branches or severe procedure-related complications occurred in 11 patients. CONCLUSION: Therefore, ARW can improve procedural efficiency and should be popularized for further application.

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

Large field of view beaconless laser nutation tracking sensor based on a micro-electro-mechanical system mirror.

We propose a laser nutation tracking sensor for beaconless laser communication, which uses a micro-electro-mechanical system (MEMS) mirror to achieve high-efficiency and large-amplitude nutation at its resonant frequency. We derive a new formula for the case of incompletely detectable optical power in the nutation cycle. In the experiment, we measure the performance of the sensor in calculating boresight error under three different nutation radii. Combining with the proposed algorithm for the new scene, we complete the accurate boresight calculation in the range of ±200µrad, at the nutation radius of 4.9 µm. We trust that the receiving field of view (FOV) of this tracking sensor can be further expanded by increasing the nutation radius. The sensor, as proposed in this paper, will be of constructive help to simplify tracking systems in the future.

Two new members in the quaternary Cs-Ag-As-S family with different arrangements of Ag-S and As-S asymmetric building units: syntheses, structures, and theoretical studies.

New functional materials of As-based multinary chalcogenidometalates have received special attention due to their different oxidation states and flexible building blocks. In this work, two new quaternary thioarsenates(iii), namely Cs2Ag2As2S5 (I) and Cs3AgAs4S8 (II), have been obtained by a simple surfactant-thermal technique. Their structures were determined on the basis of single-crystal X-ray diffraction; compound I belongs to the triclinic space group P1[combining macron] (no. 2) [a = 7.49(2) Å, b = 9.30(2) Å, c = 9.94(2) Å, α = 63.28(3)°, ß = 82.11(3)°, γ = 87.78(3)°, V = 612.4(2) Å3 and Z = 2], whereas compound II crystallizes in the monoclinic space group C2/c (no. 12) [a = 27.76(6) Å, b = 6.98(2) Å, c = 19.68(4) Å, ß = 109.85(3)°, V = 3586.7(2) Å3 and Z = 8]. Both structures are shown to feature two-dimensional (2D) layers with different arrangements of Ag-S and As-S asymmetric building units (ABUs). In compound I, the layer is constructed from vertex-sharing dimeric [As2S5] units linked by tetrameric [Ag4S8] moieties. The layered structure in compound II is formed by 21 helical chains based on [As4S9] groups which are further interconnected by tetrahedral [AgS4] chains. The analysis of the quaternary X-Ag-As-S (X = cations) system shows that various combination ways of Ag-S and As-S ABUs in these sulfides can be attributed to the cation-cation repulsion and stereochemically active lone-pair effect. The UV-vis/NIR absorption spectrum indicates that the optical band energy (Eg) of compounds I and II is 2.48 eV and 2.24 eV, respectively. Moreover, theoretical calculations indicate that the As-S and Ag-S bonding states determine the optical properties of the title compounds. This work not only enriches the structural chemistry of thioarsenates, but also opens up a new avenue for exploring novel multinary chalcogenidometalates.

Ectosomal PKM2 Promotes HCC by Inducing Macrophage Differentiation and Remodeling the Tumor Microenvironment.

Tumor-derived extracellular vesicles are important mediators of cell-to-cell communication during tumorigenesis. Here, we demonstrated that hepatocellular carcinoma (HCC)-derived ectosomes remodel the tumor microenvironment to facilitate HCC progression in an ectosomal PKM2-dependent manner. HCC-derived ectosomal PKM2 induced not only metabolic reprogramming in monocytes but also STAT3 phosphorylation in the nucleus to upregulate differentiation-associated transcription factors, leading to monocyte-to-macrophage differentiation and tumor microenvironment remodeling. In HCC cells, sumoylation of PKM2 induced its plasma membrane targeting and subsequent ectosomal excretion via interactions with ARRDC1. The PKM2-ARRDC1 association in HCC was reinforced by macrophage-secreted cytokines/chemokines in a CCL1-CCR8 axis-dependent manner, further facilitating PKM2 excretion from HCC cells to form a feedforward regulatory loop for tumorigenesis. In the clinic, ectosomal PKM2 was clearly detected in the plasma of HCC patients. This study highlights a mechanism by which ectosomal PKM2 remodels the tumor microenvironment and reveals ectosomal PKM2 as a potential diagnostic marker for HCC.

Flightless-I Blocks p62-Mediated Recognition of LC3 to Impede Selective Autophagy and Promote Breast Cancer Progression.

p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, the regulatory mechanism(s) behind this process and its association with breast cancer remain to be elucidated. Here, we report that Flightless-I (FliI), a novel p62-interacting protein, promotes breast cancer progression by impeding selective autophagy. FliI was highly expressed in clinical breast cancer samples, and heterozygous deletion of FliI retarded the development of mammary tumors in PyVT mice. FliI induced p62-recruited cargoes into Triton X-100 insoluble fractions (TI) to form aggregates, thereby blocking p62 recognition of LC3 and hindering p62-dependent selective autophagy. This function of Flil was reinforced by Akt-mediated phosphorylation at Ser436 and inhibited by phosphorylation of Ulk1 at Ser64. Obstruction of autophagic clearance of p62-recruited cargoes by FliI was associated with the accumulation of oxidative damage on proteins and DNA, which could contribute to the development of cancer. Heterozygous knockout of FliI facilitated selectively autophagic clearance of aggregates, abatement of ROS levels, and protein oxidative damage, ultimately retarding mammary cancer progression. In clinical breast cancer samples, Akt-mediated phosphorylation of FliI at Ser436 negatively correlated with long-term prognosis, while Ulk1-induced FliI phosphorylation at Ser64 positively correlated with clinical outcome. Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer.Significance: Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer.Cancer Res; 78(17); 4853-64. ©2018 AACR.

Optical phase conjugation of diffused light with infinite gain by using gated two-color photorefractive crystal LiNbO3:Cu:Ce.

Light focusing in multiple scattering circumstances is important in biomedical imaging, manipulation, and therapy. Until now, many traditional photorefractive crystals have been used to generate an optical phase conjugated wavefront in an analogue time-reversed optical focusing technology. However, owing to erasure of a volume hologram during a reading procedure, the optical energy gain can never reach unity, limiting its application in delivering more energy into a target area. In this work, we investigated a gated two-color photorefractive crystal LiNbO3:Cu:Ce to generate optical phase conjugation of diffused light with infinite gain.

Retaining of PTCA guide wire in the left ventricular lead and subsequent application of epicardial electrode when CRT-D implantation in a patient with severe heart failure and persistent left superior vena cava: a case report.

OBJECTIVE: One patient with severe heart failure (LV 92 mm, EF 28%) was treated by cardiac resynchronization therapy (CRT). METHOD: During the operation, it was found that double superior vena cava coexisted, and selective coronary venography cannot clearly show every branch. It was difficult to push ventriculus sinister electrode to sideward vein, so the electrode was released to far end of frontal septal branch along great cardiac vein. RESULT: However, because of insufficient braced force of ventriculus sinister electrode, 0.014 PTCA guide wire was detained in the electrode. 2 years later, two spots of PTCA guide wire retained in ventriculus sinister electrode broke in atrium dextrum, so the implantation of epicardial electrode was conducted. CONCLUSION: After the operation, heart failure was relieved. After 43 months, the battery of pacemaker depleted, so the pacemaker was changed. The effect since follow-up visit was good, LV decreased to 86 mm, EF increased to 32%, and SPWMD time limit shortened from 147 ms to 45 ms. The therapeutic experience of this patient indicated that the effect of detaining PTCA guide wire to enhance braced force in implantation of ventriculus sinister is unreliable and inappropriate to be advocated.

Preparation of Porous Three-Dimensional Quaternary Thioantimonates(III) ACuSb2 S4 (A = Rb, Cs) through a Surfactant-Thermal Method.

Two novel porous three-dimensional (3D) quaternary thioantimonates(III) ACuSb2S4 (A = Rb, Cs) were successfully synthesized by employing the neutral surfactant PEG-400 (PEG = polyethyleneglycol) as reaction media, these are significantly different from the known quaternary A-Cu-Sb-S thioantimonates(III) with two-dimensional (2D) crystal structures. This is the first time that crystalline quaternary chalcogenides have been prepared in surfactant media. Both experimental and theoretical studies confirm they are semiconductors with narrow band gaps. Our results demonstrated that the surfactant-thermal strategy could offer a new opportunity to explore novel chalcogenides with diverse crystal structures and interesting physicochemical properties.

Hydrazine-hydrothermal synthesis and characterization of the two new quaternary thioantimonates(III) BaAgSbS3 and BaAgSbS3·H2O.

The two new quaternary thioantimonates(III) BaAgSbS3 (1) and BaAgSbS3·H2O (2) have been synthesized through a hydrazine-hydrothermal method at low temperature. Compound 1 possesses a two-dimensional (2D) layer structure, while compound 2 features a three-dimensional (3D) channel framework. The optical band gaps of 1 and 2 are approximately 2.2 and 2.4 eV, respectively. Our results clearly indicated that the hydrazine-hydrothermal method could offer exciting opportunities for exploring novel multinary chalcogenides with diverse crystal structures and interesting physical properties.

Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.

Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death.

Lensless optical image processing based on two-dimensional Fresnel diffraction for synthetic-aperture imaging ladar.

A principle scheme of a lensless optical processor for synthetic-aperture imaging ladar (SAIL) is proposed. The collected data from SAIL is initially digitally added with a quadratic phase in the range direction. These data are then uploaded on a liquid crystal spatial light modulator to modulate the incident light. The target image is obtained through two-dimensional (2D) free-space Fresnel diffraction. The imaging process is mathematically analyzed using a 2D data-collection equation of strip-mode side-looking SAIL. The design equation, imaging resolutions, and target-image compression ratios are presented. Based on this principle scheme, we construct an experimental optical SAIL processor and present the imaging result of data obtained from one SAIL demonstrator. The optical processor is found to exhibit the flexible property of digital processing, as well as the fast processing capability of optical means, because this optical processor is a lensless system.

Continuous angle steering of an optically- controlled phased array antenna based on differential true time delay constituted by micro-optical components.

We propose an optically controlled phased array antenna (PAA) based on differential true time delay constructed optical beamforming network (OBFN). Differential true time delay is realized by stack integrated micro-optical components. Optically-controlled angle steering of radio frequency (RF) beams are realized and demonstrated by this configuration. Experimental results demonstrate that OBFN based PAA can accomplish RF-independent broadband beam steering without beam squint effect and can achieve continuous angle steering. In addition, multi-beams for different steering angles are acquired synchronously.