Intra-Articular Injection of Fructus Ligustri Lucidi Extract Attenuates Pain Behavior and Cartilage Degeneration in Mono-Iodoacetate Induced Osteoarthritic Rats

Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study established a rat OA model by intra-articular (IA) injection of mono-iodoacetate (1.5 mg) and weekly treated by IA administration of FLL at 100 μg/mL for 4 weeks. Thermal withdrawal latency, mechanical withdrawal threshold, and spontaneous activity were tested for evaluation of pain behavior, and histopathological (HE, SO, and ABH staining) and immunohistochemical (Col2, Col10, and MMP13) analyses were conducted for observation of cartilage degradation. In vitro effect of FLL on chondrocytes was evaluated by MTT assay and qPCR analysis. Moreover, HPLC analysis was performed to determine its chemoprofile. The pain behavioral data showed that FLL attenuated joint pain hypersensitivity by increasing thresholds of mechanical allodynia and thermal hyperalgesia as well as spontaneous activity. The histopathological result showed that FLL reversed OA cartilage degradation by protecting chondrocytes and extracellular matrix in cartilage, and the immunohistochemical analysis revealed its molecular actions on protein expressions of MMP13, Col2, and Col10 in cartilage. The MTT assay showed its proliferative effects on chondrocytes, and qPCR assay clarified its mechanism associated with gene expressions of Mmp13, Col2, Col10, Adamts5, Aggrecan, and Runx2 in TNF-α treated chondrocytes. Our results revealed an anti-OA effect of FLL on pain behavior and cartilage degradation in OA rats and clarified a molecular mechanism in association with the suppression of chondrocyte hypertrophy and catabolism. IA FLL can be regarded as novel and promising option for OA therapy

Cyclophilin E Functions as a Negative Regulator to Influenza Virus Replication by Impairing the Formation of the Viral Ribonucleoprotein Complex

The nucleoprotein (NP) of influenza A virus is a multifunctional protein that plays a critical role in the replication and transcription of the viral genome. Therefore, examining host factors that interact with NP may shed light on the mechanism of host restriction barriers and the tissue tropism of influenza A virus. Here, Cyclophilin E (CypE), a member of the peptidyl-propyl cis-trans isomerase (PPIase) family, was found to bind to NP and inhibit viral replication and transcription.In the present study, CypE was found to interact with NP but not with the other components of the viral ribonucleoprotein complex (vRNP): PB1, PB2, and PA. Mutagenesis data revealed that the CypE domain comprised of residues 137–186 is responsible for its binding to NP. Functional analysis results indicated that CypE is a negative regulator in the influenza virus life cycle. Furthermore, knock-down of CypE resulted in increased levels of three types of viral RNA, suggesting that CypE negatively affects viral replication and transcription. Moreover, up-regulation of CypE inhibited the activity of influenza viral polymerase. We determined that the molecular mechanism by which CypE negatively regulates influenza virus replication and transcription is by interfering with NP self-association and the NP-PB1 and NP-PB2 interactions.CypE is a host restriction factor that inhibits the functions of NP, as well as viral replication and transcription, by impairing the formation of the vRNP. The data presented here will help us to better understand the molecular mechanisms of host restriction barriers, host adaptation, and tissue tropism of influenza A virus

Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis

Asymmetrical growth of the vertebrae has been implicated as one possible etiologic factor in the pathogenesis of adolescent idiopathic scoliosis. The longitudinal vertebral growth derives from the endochondral ossification of the vertebral growth plate. In the present study, the growth plates from the convex and concave side of the vertebrae were characterized by the method of histology and immunohistochemistry to evaluate the growth activity, cell proliferation, and apoptosis. Normal zoned architectures were observed in the convex side of the growth plate and disorganized architectures in the concave side. The histological grades were significantly different between the convex and the concave side of the growth plate in the apex vertebrae (P < 0.05). The histological difference was also found significant statistically between end vertebrae and apex vertebrae in the concave side of vertebral growth plates (P < 0.05). The proliferative potential indexes and apoptosis indexes of chondrocytes in the proliferative and hypertrophic zone in the convex side were significantly higher than that in the concave side in the apex vertebral growth plate (P < 0.05). There was a significant difference of the proliferative potential index (proliferating cell nuclear antigen, PCNA index) between convex side and concave side at the upper end vertebra (P < 0.05). The difference of the proliferative potential index and apoptosis index were found significant statistically in the concave side of the vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). The same result was also found for the apoptosis index (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling assay, TUNEL index) in the convex side of vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). Some correlation were found between radiographic measurements and proliferation and apoptosis indexes. The difference in histological grades and cellular activity between the convex and concave side indicated that the bilateral growth plate of the vertebrae in AIS patients have different growth kinetics which may affect the curve progression

Supplemental Enzyme and Probiotics on the Growth Performance and Nutrient Digestibility of Broilers Fed with a Newly Harvested Corn Diet

A new grain phenomenon happens in newly harvested corn because of its high content of anti-nutritional factors (ANFs), which can cause low nutrient digestibility and diarrhea in animals. Enzymes and probiotics have been shown to relieve the negative effect of ANFs for animals. The purpose of this study was to investigate the effect of enzymes and probiotics on the performance and nutrient digestibility of broilers, fed with newly harvested corn diets. A total of 624 Arbor Acres Plus male broiler chickens were randomly divided into eight treatment groups (A: normal corn diet, CT: newly harvested corn diet, DE: newly harvested corn diet + glucoamylase, PT: newly harvested corn diet + protease, XL: newly harvested corn diet + xylanase, BCC: newly harvested corn diet + Pediococcus acidilactici BCC-1, DE + PT: newly harvested corn diet + glucoamylase + protease, XL + BCC: newly harvested corn diet + xylanase + Pediococcus acidilactici BCC-1). Each group was divided into six replicates, with 13 birds each. On day 21, growth performance, nutrient digestibility, and digestive enzyme activity were measured. Compared with the normal corn diet (PC), the newly harvested corn diet (NC) produced shorter digesta emptying time (p = 0.015) and increased visual fecal water content (p = 0.002) of broilers, however, there was no effect on performance. Compared to the newly harvested corn diet (NC), supplemental enzyme of DE increased the activity of chymotrypsin (p = 0.016), however, no differences in the digestibility of three kinds of organic matter, digesta emptying time, visual fecal water content, or performance were found. Supplemental protease (PT) significantly increased digesta emptying time (p = 0.004) and decreased the activity of maltase (p = 0.007). However, it had no effect on the digestibility of three kinds of organic matter or the performance of broilers. Supplemental xylanase (XL) decreased the activity of amylase (p = 0.006) and maltase (p &lt; 0.001); however, it had no effect on digesta emptying time, visual fecal water content, the digestibility of three kinds of organic matter, or performance of broilers. Supplemental DE, combined with PT (DE + PT), increased the digesta emptying time (p = 0.016) while decreasing the visual fecal water content (p = 0.011), and the activity of amylase (p = 0.011), lipase (p = 0.021), and maltase (p &lt; 0.001), however, there was no effect on performance. Supplemental BCC individually decreased the activity of amylase (p = 0.024) and maltase (p &lt; 0.001), however, it increased the activity of trypsin (p &lt; 0.001) and tended to improve feed conversion ratio (FCR) (p = 0.081). Supplemental BCC-1, combined with XL (XL + BCC), increased the activity of trypsin (p = 0.001) but decreased the activity of amylase (p = 0.013), lipase (p = 0.019), and maltase (p &lt; 0.001). Pediococcus acidilactici BCC-1 (109 cfu/kg), protease (800,000 U/g) individually, or protease (800,000 U/g) in combination with glucoamylase (800,000 U/g) were supplemented in newly harvested corn diets for growing broilers. Hence, this study mainly explores the alleviation effect of enzyme and probiotics on the negative phenomenon caused by the utilization of newly harvested corn in broilers and provides a better solution for the utilization of newly harvested corn in production practice

Brillouin zone folding driven bound states in the continuum

Non-radiative bound states in the continuum (BICs) allow construction of resonant cavities with confined electromagnetic energy and high-quality (Q) factors. However, the sharp decay of the Q factor in the momentum space limits their usefulness for device applications. Here we demonstrate an approach to achieve sustainable ultrahigh Q factors by engineering Brillouin zone folding-induced BICs (BZF-BICs). All the guided modes are folded into the light cone through periodic perturbation that leads to the emergence of BZF-BICs possessing ultrahigh Q factors throughout the large, tunable momentum space. Unlike conventional BICs, BZF-BICs show perturbation-dependent dramatic enhancement of the Q factor in the entire momentum space and are robust against structural disorders. Our work provides a unique design path for BZF-BIC-based silicon metasurface cavities with extreme robustness against disorder while sustaining ultrahigh Q factors, offering potential applications in terahertz devices, nonlinear optics, quantum computing, and photonic integrated circuits.National Research Foundation (NRF)Published versionW.W. and Z.W. acknowledge the support from the National Key Research and Development Program of China (No. 2019YFB2203400) and the “111 Project” (Grant No. B20030). W.W., Y.K.S., T.C.W.T. and R.S. acknowledge funding support from Singapore NRF-CRP23-2019-0005 (TERACOMM). W.W. acknowledges the China Scholarship Council for financial support (202006070143)

Daidzein alleviates high glucose-induced pyroptosis of renal tubular epithelial cells

Objective To investigate the impact of daidzein (DAI) on the pyroptosis of renal tubular epithelial cells induced by high glucose by regulating NOD-like receptor protein 3 (NLRP3)/caspase-1 signal pathway. Methods HK-2 cells were divided into control group (NC group) (5.5 mmol/L D-glucose), HG group(30 mmol/L D-glucose), DAI-L, DAI-M, DAI-H groups (HK-2 cells were incubated with 30 mmol/L D-glucose and 25, 50, 100 μmol/L DAI,respectively), and DAI-H+LPS group (HK-2 cells were incubated with 30 mmol/L D-glucose, 100 μmol/L DAI and 1 μg/mL LPS). MTT assay was applied to detect the cytotoxicity and proliferation of HK-2 cells; the apoptosis of HK-2 cells was detected by flow cytometry. The level of interleukin-1β (IL-1β) and inter-leukin-18 (IL-18) in HK-2 cells was detected by ELISA. The morphology of pyroptosis cells was observed by scanning electron microscope. Immunofluorescence staining was applied to detect pyroptosis related proteins. The expression of NLRP3, cleaved casase-1 and GSDMD-N was detected by Western blot. Results In NC group, the cells were spherical with regular boundaries, while in HG group, the cells swelled and became larger with irregular boundaries; the OD value (490 nm) of HK-2 cells in HG group was obviously lower than that in NC group(P＜0.05), the apoptosis rate, IL-1β, IL-18 contents, NLRP3, cleaved casase-1, GSDMD-N protein level of HK-2 cells were obviously higher (P＜0.05); After DAI treatment, the swelling of cells was alleviated, the A value (490 nm) of HK-2 cells increased significantly (P＜0.05), the apoptosis rate of HK-2 cells, IL-1 β, IL-18 content, NLRP3, cleaved-caspase-1 and GSDMD-N protein levels were significantly decreased(P＜0.05) and the therapeutic effect of DAI was dose-dependent; LPS eliminated the beneficial effect of DAI-H on high glucose induced apoptosis of renal tubular epithelial cells. Conclusions DAI may alleviate pyroptosis of renal tubular epithelial cells induced by high glucose through inhibition of NLRP3/caspase-1 signaling pathway

MIE-NSCT: Adaptive MRI Enhancement Based on Nonsubsampled Contourlet Transform

Image enhancement technology is often used to improve the quality of medical images and helps doctors or expert systems identify and diagnose diseases. This paper aimed at the characteristics of magnetic resonance imaging (MRI) with complex and difficult-to-enhance details and to propose a nonsubsampled contourlet transform- (NSCT-) based enhancement algorithm called MIE-NSCT. NSCT was used for MRI sub-band decomposition. For high-pass sub-bands, four fuzzy rules were proposed to enhance multiscale and multidirectional edge contour details from adjacent eight directions, whilst for low-pass sub-bands, a new adaptive histogram enhancement algorithm was proposed. The problem of noise amplification and loss of details during the enhancement process was solved. The algorithm was verified on the public dataset BraTS2017 and compared with other advanced methods. Experimental results showed that MIE-NSCT had obvious advantages in improving the quality of medical images, and high-quality medical images showed enhanced performance in grading tumour. MIE-NSCT is suitable for integration into an interactive expert system to provide support for the visualization of disease diagnosis

Interface Optimization of Metal Quantum Dots/Polymer Nanocomposites and their Properties: Studies of Multi-Functional Organic/Inorganic Hybrid

Nanomaterials filled polymers system is a simple method to produce organic/inorganic hybrid with synergistic or complementary effects. The properties of nanocomposites strongly depend on the dispersion effects of nanomaterials in the polymer and their interfaces. The optimized interface of nanocomposites would decrease the barrier height between filler and polymer for charge transfer. To avoid aggregation of metal nanoparticles and improve interfacial charge transfer, Pt nanodots filled in the non-conjugated polymer was synthesized with an in situ method. The results exhibited that the absorbance of nanocomposite covered from the visible light region to NIR (near infrared). The photo-current responses to typical visible light and 808 nm NIR were studied based on Au gap electrodes on a flexible substrate. The results showed that the size of Pt nanoparticles was about 1–2 nm and had uniformly dispersed in the polymer matrix. The resulting nanocomposite exhibited photo-current switching behavior to weak visible light and NIR. Simultaneously, the nanocomposite also showed electrical switching responses to strain applied to a certain extent. Well-dispersion of Pt nanodots in the polymer is attributable to the in situ synthesis of metal nanodots, and photo-current switching behavior is due to interface optimization to decrease barrier height between metal filler and polymer. It provided a simple way to obtain organic/inorganic hybrid with external stimuli responses and multi-functionalities

Engineering of edge nitrogen dopant in carbon nanosheet framework for fast and stable potassium-ion storage

Abstract Amorphous carbons are promising candidates as the anode materials for potassium-ion hybrid capacitors (PIHCs). The insufficient storage sites and inferior diffusion kinetics limit their potassium-ion storage capability. Edge nitrogen and morphology engineering are effective pathways to construct accessible active sites and enhanced diffusion kinetics. However, the organic integration of both pathways in amorphous carbon is still challenging. Herein, a “twice-cooking” strategy, including two-step carbonization processes at 700 °C, is designed to synthesize edge-nitrogen-rich lignin-derived carbon nanosheet framework (EN-LCNF). In the first-step carbonization process, the staged gas releases of CO and CO2 from CaC2O4 decomposition exfoliate the carbon matrix into a carbon nanosheet framework. In the second-step carbonization process, the generated CaO reacts with the cyanamide units of graphitic carbon nitride (g-C3N4) to form an edge-nitrogen-rich framework, which is then integrated into the meso-/macropores of carbon nanosheet framework through sp3-hybridized C–N bonds. EN-LCNF with a high edge-nitrogen level of 7.0 at.% delivers an excellent capacity of 310.3 mAh g−1 at 50 mA g−1, a robust rate capability of 126.4 mAh g−1 at 5000 mA g−1, and long cycle life. The as-assembled PIHCs based on EN-LCNF anode and commercial activated carbon cathode show a high energy density of 110.8 Wh kg−1 at a power density of 100 W kg−1 and excellent capacitance retention of 98.7% after 6000 cycles. This work provides a general strategy for the synthesis of edge-nitrogen-rich lignin-derived carbon materials for advanced potassium-ion storage. Graphical Abstrac