CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-ß1/Smad2/3 signaling in mouse viral myocarditis.

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

Dual-Mode Conversion of Photodetector and Neuromorphic Vision Sensor via Bias Voltage Regulation on a Single Device.

Simultaneous implementation of photodetector and neuromorphic vision sensor (NVS) on a single device faces a great challenge, due to the inherent speed discrepancy in their photoresponse characteristics. In this work, a trench-bridged GaN/Ga2 O3 /GaN back-to-back double heterojunction array device is fabricated to enable the advanced functionalities of both devices on a single device. Interestingly, the device shows fast photoresponse and persistent photoconductivity behavior at low and high voltages, respectively, through the modulation of oxygen vacancy ionization and de-ionization processes in Ga2 O3 . Consequently, the role of the optoelectronic device can be altered between the photodetector and NVS by simply adjusting the magnitude of bias voltage. As a photodetector, the device is able to realize fast optical imaging and optical communication functions. On the other hand, the device exhibits outstanding image sensing, image memory, and neuromorphic visual pre-processing as an NVS. The utilization of NVS for image pre-processing leads to a noticeable enhancement in both recognition accuracy and efficiency. The results presented in this work not only offer a new avenue to obtain complex functionality on a single optoelectronic device but also provide opportunities to implement advanced robotic vision systems and neuromorphic computing.

Intracellular TMEM16A is necessary for myogenesis of skeletal muscle.

Transmembrane protein 16A (TMEM16A) localizes at plasma membrane and controls chloride influx in various type of cells. We here showed an intracellular localization pattern of TMEM16A molecules. In myoblasts, TMEM16A was primarily localized to the cytosolic compartment and partially co-localized with intracellular organelles. The global deletion of TMEM16A led to severe skeletal muscle developmental defect. In vitro observation showed that the proliferation of Tmem16a-/- myoblasts was significantly promoted along with activated ERK1/2 and Cyclin D expression; the myogenic differentiation was impaired accompanied by the enhanced caspase 12/3 activation, implying enhanced endoplasmic reticulum (ER) stress. Interestingly, the bradykinin-induced Ca2+ release from ER calcium store was significantly enhanced after TMEM16A deletion. This suggested a suppressing role of intracellular TMEM16A in ER calcium release whereby regulating the flux of chloride ion across the ER membrane. Our findings reveal a unique location pattern of TMEM16A in undifferentiated myoblasts and its role in myogenesis.

Numerical Investigation of Safety Strategy for Gas Disaster Prevention in Successive Panels Using Upper Protective Layer Mining: A Case Study.

Mine gas disasters are a major safety concern in underground coal mining. Protective layer mining is widely used in gas disaster control, but there are limited theoretical and experimental results that can provide guidance for site-specific mining circumstances. Taking the Xinji No. 1 mine as an example, gas disaster treatments were conducted in a new panel with overlying goaf located 85 m above the coal mine and adjacent goaf located at 30 m intervals. This study involved a comprehensive investigation, which included four steps: the selection of the first mining face, gas control and prevention, tracking and investigation, and effect analysis and assessment. The safety strategy focused on gas control planning in new mining areas or panels. The distribution and evolution characteristics of the stress, the gas permeability coefficient and the deformation volume within the protected layer were determined by numerical simulation. The coal deformation, gas emission and extraction effect were analyzed by field observation. The deformation and gas permeability of the coal seam were consistent with the stress evolution, for which the maximum compressional and expansional deformation of 6-1 coal were 18‱ and 28‱, respectively. Gas disaster control and prevention treatment of the mining face produced a significant protective effect on the underlying No. 6-1 coal seam. This work is beneficial for the planning of gas control in successive panels.

Patterning of Wafer-Scale MXene Films for High-Performance Image Sensor Arrays.

As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high-performance MXene image sensor array fabricated by a wafer-scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin-coating, photolithography, and dry-etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large-area patterning methods reported previously. As a result, a high-density integrated array of 1024-pixel Ti3 C2 Tx /Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light-dark current ratio (Ilight /Idark ) of 6.22 × 106 , which is the ultrahigh value among all reported MXene-based photodetectors, is fabricated. This patterning technique paves a way for large-scale high-performance MXetronics compatible with mainstream semiconductor processes.

Understanding charge storage in Nb2CTx MXene as an anode material for lithium ion batteries.

MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.

Genomic and transcriptomic landscapes and evolutionary dynamics of molluscan glycoside hydrolase families with implications for algae-feeding biology.

The hydrolysis of sugar-containing compounds by glycoside hydrolases (GHs) plays essential roles in many major biological processes, but to date our systematic understanding of the functional diversity and evolution of GH families remains largely limited to a few well-studied terrestrial animals. Molluscs represent the largest marine phylum in the animal kingdom, and many of them are herbivorous that utilize algae as a main nutritional source, making them good subjects for studying the functional diversity and adaptive evolution of GH families. In the present study, we conducted genome-wide identification and functional and evolutionary analysis of all GH families across major molluscan lineages. We revealed that the remarkable expansion of the GH9, GH10, GH18 and GH20 families and the wide adoption of carbohydrate-binding modules in molluscan expanded GH families likely contributed to the efficient hydrolysis of marine algal polysaccharides and were involved in the consolidation of molluscan algae-feeding habits. Gene expression and network analysis revealed the hepatopancreas as the main organ for the prominent expression of approximately half of the GH families (well corresponding to the digestive roles of the hepatopancreas) and key or hub GHs in the coexpression gene network with potentially diverse functionalities. We also revealed the evolutionary signs of differential expansion and functional divergence of the GH family, which possibly contributed to lineage-specific adaptation. Systematic analysis of GH families at both genomic and transcriptomic levels provides important clues for understanding the functional divergence and evolution of GH gene families in molluscs in relation to their algae-feeding biology.

Interlayer engineering of Ti3C2Tx MXenes towards high capacitance supercapacitors.

Electrochemical pseudocapacitors store energy via intercalation or electrosorption and faradaic charge transfer with redox reactions. MXenes represent the promising intercalation pseudocapacitive electrode materials for supercapacitors due to their ultrahigh theoretical capacitances. Achieving a high capacitance will greatly advance the large-scale applications as in power grids. However, a rational design concept has not been exploited to achieve the theoretical limit. Here, we show how interlayer engineering helps to achieve the limit. Interlayer engineering in this manner simultaneously creates a broadened yet uniform interlayer spacing - providing a "highway" for fast ion diffusion, and incorporates heteroatoms with lower electronegativity - offering "trucks" (redox active sites) on such a "highway" for speeding charge transfer, enabling high capacitance. Following the concept, through annealing the as-prepared Ti3C2Tx MXene under an ammonia atmosphere, the engineered MXene delivers much improved capacitance with excellent rate performance and cyclability. The overall performance of the engineered MXene outperforms that of all other pseudocapacitive electrode materials.

Inhibition of LOX-1 alleviates the proinflammatory effects of high-mobility group box 1 in Aspergillus fumigatus keratitis.

AIM: To investigate the inflammatory amplification effect of high-mobility group box 1 (HMGB1) in Aspergillus fumigatus (A. fumigatus) keratitis and the relationship between lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) and HMGB1 in keratitis immune responses. METHODS: Phosphate buffer saline (PBS), and Boxb were injected into BALB/c mice subconjunctivally before the corneas were infected with A. fumigatus. RAW264.7 macrophages and neutrophils were pretreated with PBS and Boxb to determine the HMGB1 inflammatory amplification effects. Abdominal cavity extracted macrophages were pretreated with Boxb and Poly (I) (a LOX-1 inhibitor) before A. fumigatus hyphae stimulation to prove the the relationship between the two molecules. LOX-1, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and IL-10 were assessed by polymerase chain reaction and Western blot. RESULTS: Pretreatment with Boxb exacerbated corneal inflammation. In macrophages and neutrophils, A. fumigatus induced LOX-1, IL-1ß, TNF-α and MIP-2 expression in Boxb group was higher than those in PBS group. Poly (I) treatments before infection alleviated the proinflammatory effects of Boxb in abdominal cavity extracted macrophages. Pretreatment with Boxb did not influence Dectin-1 mRNA levels in macrophages and neutrophils. CONCLUSION: In fungal keratitis, HMGB1 is a proinflammatory factor in the first line of immune response. HMGB1 mainly stimulates neutrophils and macrophages to produce inflammatory cytokines and chemokines during the immune response. LOX-1 participates in HMGB1 induced inflammatory exacerbation in A. fumigatus keratitis.

High-Energy-Density Hydrogen-Ion-Rocking-Chair Hybrid Supercapacitors Based on Ti3C2 T x MXene and Carbon Nanotubes Mediated by Redox Active Molecule.

MXenes have emerged as promising high-volumetric-capacitance supercapacitor electrode materials, whereas their voltage windows are not wide. This disadvantage prevents MXenes from being made into aqueous symmetric supercapacitors with high energy density. To attain high energy density, constructing asymmetric supercapacitors is a reliable design choice. Here, we propose a strategy to achieve high energy density of hydrogen ion aqueous-based hybrid supercapacitors by integrating a negative electrode of Ti3C2 T x MXene and a positive electrode of redox-active hydroquinone (HQ)/carbon nanotubes. The two electrodes are separated by a Nafion film that is proton permeable in H2SO4 electrolyte. Upon charging/discharging, hydrogen ions shuttle back and forth between the cathode and anode for charge compensation. The proton-induced high capacitance of MXene and HQ, along with complementary working voltage windows, simultaneously enhance the electrochemical performance of the device. Specifically, the hybrid supercapacitors operate in a 1.6 V voltage window and deliver a high energy density of 62 Wh kg-1, which substantially exceeds those of the state-of-the-art aqueous asymmetric supercapacitors reported so far. Additionally, the device exhibits excellent cycling stability and the all-solid-state planar hybrid supercapacitor displays exceptional flexibility and integration for bipolar cells to boost the capacitance and voltage output. These encouraging results provide the possibility of designing high-energy-density noble-metal-free asymmetric supercapacitors for practical applications.

Nanosecond Laser Fabrication of Hydrophobic Stainless Steel Surfaces: The Impact on Microstructure and Corrosion Resistance.

Creation of hydrophobic and superhydrophobic surfaces has attracted broad attention as a promising solution for protection of metal surfaces from corrosive environments. This work investigates the capability of nanosecond fiber laser surface texturing followed by a low energy coating in the fabrication of hydrophobic 17-4 PH stainless steel surfaces as an alternative to the ultrashort lasers previously utilized for hydrophobic surfaces production. Laser texturing of the surface followed by applying the hydrophobic coating resulted in steady-state contact angles of up to 145°, while the non-textured coated base metal exhibited the contact angle of 121°. The microstructure and compositional analysis results confirmed that the laser texturing process neither affects the microstructure of the base metal nor causes elemental loss from the melted regions during the ultrafast melting process. However, the electrochemical measurements demonstrated that the water-repelling property of the surface did not contribute to the anticorrosion capability of the substrate. The resultant higher corrosion current density, lower corrosion potential, and higher corrosion rate of the laser textured surfaces were ascribed to the size of fabricated surface micro-grooves, which cannot retain the entrapped air inside the hierarchical structure when fully immersed in a corrosive medium, thus degrading the material's corrosion performance.

High-capacitance Ti3C2Tx MXene obtained by etching submicron Ti3AlC2 grains grown in molten salt.

Submicron Ti3AlC2 grains are grown in molten salt. Etching the grains gives rise to small-sized Ti3C2Tx MXene particulates with capacitance more than twice that of the large ones derived from conventional high-temperature synthesis. Detailed electrochemical, structural, and spectroscopic studies demonstrate that increased capacitance predominantly originates from a decrease in the lateral size of the small Ti3C2Tx MXene particulates.

Surface Functional Groups and Interlayer Water Determine the Electrochemical Capacitance of Ti3C2 T x MXene.

MXenes, an emerging class of conductive two-dimensional materials, have been regarded as promising candidates in the field of electrochemical energy storage. The electrochemical performance of their representative Ti3C2 T x, where T represents the surface termination group of F, O, or OH, strongly relies on termination-mediated surface functionalization, but an in-depth understanding of the relationship between them remains unresolved. Here, we studied comprehensively the structural feature and electrochemical performance of two kinds of Ti3C2 T x MXenes obtained by etching the Ti3AlC2 precursor in aqueous HF solution at low concentration (6 mol/L) and high concentration of (15 mol/L). A significantly higher capacitance was recognized in a low-concentration HF-etched MXene (Ti3C2 T x-6M) electrode. In situ Raman spectroscopy and X-ray photoelectron spectroscopy demonstrate that Ti3C2 T x-6M has more components of the -O functional group. In combination with X-ray diffraction analysis, low-field 1H nuclear magnetic resonance spectroscopy in terms of relaxation time unambiguously underlines that Ti3C2 T x-6M is capable of accommodating more high-mobility H2O molecules between the Ti3C2 T x interlayers, enabling more hydrogen ions to be more readily accessible to the active sites of Ti3C2 T x-6M. The two main key factors ( i.e., high content of -O functional groups that are involved bonding/debonding-induced pseudocapacitance and more high-mobility water intercalated between the MXene interlayers) simultaneously account for the superior capacitance of the Ti3C2 T x-6M electrode. This study provides a guideline for the rational design and construction of high-capacitance MXene and MXene-based hybrid electrodes in aqueous electrolytes.

DNA in serum extracellular vesicles is stable under different storage conditions.

BACKGROUND: Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, can be secreted by most cell types and released in perhaps all biological fluids. EVs contain multiple proteins, specific lipids and several kinds of nucleic acids such as RNAs and DNAs. Studies have found that EVs contain double-stranded DNA and that genetic information has a certain degree of consistency with tumor DNA. Therefore, if genes that exist in exosomes are stable, we may be able to use EVs genetic testing as a new means to monitor gene mutation. METHODS: In this study, EVs were extracted from serum under various storage conditions (4 °C, room temperature and repeated freeze-thaw). We used western blotting to examine the stability of serum EVs. Then, we extracted DNA from EVs and tested the concentration changing under different conditions. We further assessed the stability of EVs DNA s using polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: EVs is stable under the conditions of 4 °C (for 24 h, 72 h, 168 h), room temperature (for 6 h, 12 h, 24 h, 48 h) and repeated freeze-thaw (after one time, three times, five times). Also, serum DNA is mainly present in EVs, especially in exosomes, and that the content and function of DNA in EVs is stable whether in a changing environment or not. We showed that EVs DNA stayed stable for 1 week at 4 °C, 1 day at room temperature and after repeated freeze-thaw cycles (less than three times). However, DNA from serum EVs after 2 days at room temperature or after five repeated freeze-thaw cycles could be used for PCR and sequencing. CONCLUSIONS: Serum EVs and EVs DNA can remain stable under different environments, which is the premise that EVs could serve as a novel means for genetic tumor detection and potential biomarkers for cancer diagnostics and prognostics.