MiR-431 promotes cardiomyocyte proliferation by targeting FBXO32 expression.

BACKGROUND: The induction of cardiomyocyte (CM) proliferation is a promising approach for cardiac regeneration following myocardial injury. MicroRNAs (miRNAs) have been reported to regulate CM proliferation. In particular, miR-431 expression decreases during cardiac development, according to Gene Expression Omnibus (GEO) microarray data. However, whether miR-431 regulates CM proliferation has not been thoroughly investigated. METHODS: We used integrated bioinformatics analysis of GEO datasets to identify the most significantly differentially expressed miRNAs. Real-time quantitative PCR and fluorescence in situ hybridization were performed to determine the miRNA expression patterns in hearts. Gain- and loss-of-function assays were conducted to detect the role of miRNA in CM proliferation. Additionally, we detected whether miR-431 affected CM proliferation in a myocardial infarction model. The TargetScan, miRDB and miRWalk online databases were used to predict the potential target genes of miRNAs. Luciferase reporter assays were used to study miRNA interactions with the targeting mRNA. RESULTS: First, we found a significant reduction in miR-431 levels during cardiac development. Then, by overexpression and inhibition of miR-431, we demonstrated that miR-431 promotes CM proliferation in vitro and in vivo, as determined by immunofluorescence assays of 5-ethynyl-2'-deoxyuridine (EdU), pH3, Aurora B and CM count, whereas miR-431 inhibition suppresses CM proliferation. Then, we found that miR-431 improved cardiac function post-myocardial infarction. In addition, we identified FBXO32 as a direct target gene of miR-431, with FBXO32 mRNA and protein expression being suppressed by miR-431. FBXO32 inhibited CM proliferation. Overexpression of FBXO32 blocks the enhanced effect of miR-431 on CM proliferation, suggesting that FBXO32 is a functional target of miR-431 during CM proliferation. CONCLUSION: In summary, miR-431 promotes CM proliferation by targeting FBXO32, providing a potential molecular target for preventing myocardial injury.

Design and synthesis of 3,3'-triazolyl biisoquinoline N,N'-dioxides via Hiyama cross-coupling of 4-trimethylsilyl-1,2,3-triazoles.

A new strategy to effectively lock the conformation of substituents at the 3,3'-positions of axial-chiral biisoquinoline N,N'-dioxides was developed based on the strong dipole-dipole interaction between 1,2,3-triazole and pyridine N-oxide rings. The crystal structure and the DFT calculations of 3,3'-bis(1-benzyl-1H-1,2,3-triazole-4-yl)-1,1'-biisoquinoline N,N'-dioxide (3a) provided strong support for this strategy. Furthermore, we successfully demonstrated that readily available 4-trimethylsilyl-1,2,3-triazoles are viable nucleophiles for Hiyama cross-coupling.

An improved performance frequency estimation algorithm for passive wireless SAW resonant sensors.

Passive wireless surface acoustic wave (SAW) resonant sensors are suitable for applications in harsh environments. The traditional SAW resonant sensor system requires, however, Fourier transformation (FT) which has a resolution restriction and decreases the accuracy. In order to improve the accuracy and resolution of the measurement, the singular value decomposition (SVD)-based frequency estimation algorithm is applied for wireless SAW resonant sensor responses, which is a combination of a single tone undamped and damped sinusoid signal with the same frequency. Compared with the FT algorithm, the accuracy and the resolution of the method used in the self-developed wireless SAW resonant sensor system are validated.

Advances in Functional Hydrogel Wound Dressings: A Review.

One of the most advanced, promising, and commercially viable research issues in the world of hydrogel dressing is gaining functionality to achieve improved therapeutic impact or even intelligent wound repair. In addition to the merits of ordinary hydrogel dressings, functional hydrogel dressings can adjust their chemical/physical properties to satisfy different wound types, carry out the corresponding reactions to actively create a healing environment conducive to wound repair, and can also control drug release to provide a long-lasting benefit. Although a lot of in-depth research has been conducted over the last few decades, very few studies have been properly summarized. In order to give researchers a basic blueprint for designing functional hydrogel dressings and to motivate them to develop ever-more intelligent wound dressings, we summarized the development of functional hydrogel dressings in recent years, as well as the current situation and future trends, in light of their preparation mechanisms and functional effects.

Efficacy of a Novel Antibacterial Agent Exeporfinium Chloride, (XF-73), Against Antibiotic-Resistant Bacteria in Mouse Superficial Skin Infection Models.

Background: The number of incidences of antimicrobial resistance is rising continually, necessitating new and effective antibacterial drugs. The present study aimed to assess the in vitro and in vivo activity of XF-73 against antibiotic-resistant Staphylococcus aureus (S. aureus) isolates and to investigate the potential mechanism of action of XF-73. Methods: The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. Two different superficial Staphylococcal skin infection murine models were established to study the in vivo efficacy of XF-73 against antibiotic-resistant strains. The effect of XF-73 on the ultrastructure and cellular morphology of S. aureus was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results: The MICs (minimum inhibitory concentration) determined by the broth microdilution method for XF-73 demonstrated that the compound had a high potency against S. aureus isolates with varying susceptibility to the study drugs. Also, the antibacterial activity of XF-73 was superior or similar to most of the tested antibacterial drugs. We also found that the XF-73 dermal formulation significantly inhibited S. aureus survival in both the murine skin tape-stripping and suture superficial skin infection models, maintained a consistently high inhibitory capacity against the antibiotic-resistant strains tested and was significantly more effective than mupirocin ointment, a commonly used antibiotic for the treatment of skin infections. The morphological studies using TEM suggest that XF-73 had a rapid (2 minute) bacterial cell wall disruption activity, with longer incubation (10 minute) subsequently causing membrane damage. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis. Conclusion: Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting.

Physiological response mechanism of heavy metal-resistant endophytic fungi isolated from the roots of Polygonatum kingianum.

This study aims to evaluate the tolerance of endophytic fungi isolated from the fibrous roots of Polygonatum kingianum to arsenic (As) and cadmium (Cd) and their physiological response mechanisms. Five isolated strains were obtained with EC50 values for As(V) ranging from 421 to 1281 mg/L, while the other three strains tolerated Cd(II) with an EC50 range of 407-1112 mg/L. Morphological and molecular identification indicated that these eight strains were Cladosporium spp. belonging to dark septate endophytes (DSEs). The contents of metal ions in mycelium sharply increased, reaching 38.87 mg/kg for strain MZ-11 under As(V) stress and 0.33 mg/kg for fungus PR-2 under Cd(II). The physiological response revealed that the biomass decreased with increasing concentrations of As(V) or Cd(II), and the activity of superoxide dismutase significantly improved under the corresponding EC50 -concentration As/Cd of the strains, as well as the contents of antioxidant substances, including metallothionein, glutathione, malondialdehyde, melanin, and proline. Taken together, the filamentous fungi of Cladosporium spp. accounted for a high proportion of fungi isolated from the fibrous roots of P. kingianum and had a strong capacity to tolerate As(V) or Cd(II) stress by improving antioxidase activities and the content of antioxidant substances, and immobilization of metal ions in hyphae.

On the mechanical aspect of additive manufactured polyether-ether-ketone scaffold for repair of large bone defects.

Polyether-ether-ketone (PEEK) is widely used in producing prosthesis and have gained great attention for repair of large bone defect in recent years with the development of additive manufacturing. This is due to its excellent biocompatibility, good heat and chemical stability and similar mechanical properties which mimics natural bone. In this study, three replicates of rectilinear scaffolds were designed for compression, tension, three-point bending and torsion test with unit cell size of 0.8 mm, a pore size of 0.4 mm, strut thickness of 0.4 mm and nominal porosity of 50%. Stress-strain graphs were developed from experimental and finite element analysis models. Experimental Young's modulus and yield strength of the scaffolds were measured from the slop of the stress-strain graph to be 395 and 19.50 MPa respectively for compression, 427 and 6.96 MPa respectively for tension, 257 and 25.30 MPa respectively for three-point bending and 231 and 12.83 MPa respectively for torsion test. The finite element model was found to be in good agreement with the experimental results. Ductile fracture of the struct subjected to tensile strain was the main failure mode of the PEEK scaffold, which stems from the low crystallinity of additive manufacturing PEEK. The mechanical properties of porous PEEK are close to those of cancellous bone and thus are expected to be used in additive manufacturing PEEK bone implants in the future, but the lower yield strength poses a design challenge.

Analysis of Leakage Current of HfO2/TaOx-Based 3-D Vertical Resistive Random Access Memory Array.

Three-dimensional vertical resistive random access memory (VRRAM) is proposed as a promising candidate for increasing resistive memory storage density, but the performance evaluation mechanism of 3-D VRRAM arrays is still not mature enough. The previous approach to evaluating the performance of 3-D VRRAM was based on the write and read margin. However, the leakage current (LC) of the 3-D VRRAM array is a concern as well. Excess leakage currents not only reduce the read/write tolerance and liability of the memory cell but also increase the power consumption of the entire array. In this article, a 3-D circuit HSPICE simulation is used to analyze the impact of the array size and operation voltage on the leakage current in the 3-D VRRAM architecture. The simulation results show that rapidly increasing leakage currents significantly affect the size of 3-D layers. A high read voltage is profitable for enhancing the read margin. However, the leakage current also increases. Alleviating this conflict requires a trade-off when setting the input voltage. A method to improve the array read/write efficiency is proposed by analyzing the influence of the multi-bit operations on the overall leakage current. Finally, this paper explores different methods to reduce the leakage current in the 3-D VRRAM array. The leakage current model proposed in this paper provides an efficient performance prediction solution for the initial design of 3-D VRRAM arrays.

Modulation of MoS2 interlayer dynamics by in situ N-doped carbon intercalation for high-rate sodium-ion half/full batteries.

In comparison with lithium-ion batteries, sodium-ion batteries (SIBs) have been proposed as an alternative for large-scale energy storage. However, finding an anode material that can overcome the sluggish electrochemical reaction kinetics and fast capacity fading caused by large volume expansion during cycling is problematic. In this study, the intercalation technique for nitrogen-doped carbon layers is implemented for the molybdenum disulfide (MoS2/NC) structure to improve the rate and cycling stability of SIBs by increasing the diffusion rate of sodium ions and mitigating excessive volume structural expansion. The as-synthesized MoS2/NC anode has a high discharge specific capacity of 546 mA h g-1 at 1 A g-1 after 160 cycles, as well as a high rate and stable cycle performance of 406 mA h g-1 at 10 A g-1 after 1000 cycles. Upon coupling with a high-voltage Na3V2(PO4)2O2F cathode, the sodium-ion full battery displays high specific energies of 78.57 W h kg-1 and 49.70 W h kg-1 at specific powers of 193.76 W kg-1 and 3756.80 W kg-1, respectively, with commercialization potential demonstrated.

APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and has high morbidity and mortality. Elucidating the molecular mechanisms underlying HCC recurrence and metastasis is critical to identify new therapeutic targets. This study aimed to determine the roles of aminopeptidase N (APN, also known as CD13) in HCC proliferation and metastasis and its underlying mechanisms. We detected APN expression in clinical samples and HCC cell lines using immunohistochemistry, flow cytometry, real-time PCR, and enzyme activity assays. The effects of APN on HCC metastasis and proliferation were verified in both in vitro and in vivo models. RNA-seq, phosphoproteomic, western blot, point mutation, co-immunoprecipitation, and proximity ligation assays were performed to reveal the potential mechanisms. We found that APN was frequently upregulated in HCC tumor tissues and high-metastatic cell lines. Knockout of APN inhibited HCC cell metastasis and proliferation in vitro and in vivo. Functional studies suggested that a loss of APN impedes the ERK signaling pathway in HCC cells. Mechanistically, we found that APN might mediate the phosphorylation at serine 31 of BCKDK (BCKDKS31), promote BCKDK interacting with ERK1/2 and phosphorylating it, thereby activating the ERK signaling pathway in HCC cells. Collectively, our findings indicate that APN mediates the phosphorylation of BCKDKS31 and activates its downstream pathway to promote HCC proliferation and metastasis. Therefore, the APN/BCKDK/ERK axis may serve as a new therapeutic target for HCC therapy, and these findings may be helpful to identify new biomarkers in HCC progression.

Dual-Frequency Interrogation and Hierarchical Evaluation Scheme for SAW Reflective Delay-Line Sensors.

The resolution of phase difference ambiguity is critically important for simultaneously achieving wide range and high accuracy sensing with surface acoustic wave (SAW) reflective delay-line sensors. A novel scheme called dual-frequency interrogation and hierarchical evaluation (DFI-HE) is proposed to resolve integer ambiguity of phase difference and obtain precise time delay between reflectors. With DFI-HE, only two reflectors are needed as the sensing elements for SAW reflective delay-line sensors. Additionally, DFI-HE has the advantage of fast ambiguity resolution to enable both a wide range and high accuracy sensing. The basic principle of sensing with DFI-HE is elaborated, and simulations and temperature sensing experiments are carried out to verify the proposed scheme, based on a SAW reflective delay-line temperature sensor with two reflectors fabricated on 128° YX-LiNbO3 substrate. The experimental results demonstrate that the temperature measurement accuracy reaches ±2 °C in the range of 8 °C-300 °C.