Study on the immune-enhancing and inhabiting transmissible gastroenteritis virus effects of polysaccharides from Cimicifuga rhizoma.

Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 µg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1ß content compared with control group. 250 µg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.

Real-Time Measurement and Uncertainty Evaluation of Optical Path Difference in Fiber Optic Interferometer Based on Auxiliary Interferometer.

Optical interferometers are the main elements of interferometric sensing and measurement systems. Measuring their optical path difference (OPD) in real time and evaluating the measurement uncertainty are key to optimizing system noise and ensuring system consistency. With the continuous sinusoidal wavelength modulation of the laser, real-time OPD measurement of the main interferometer is achieved through phase comparison of the main and auxiliary interferometers. The measurement uncertainty of the main interferometer OPD is evaluated. It is the first evaluation of the impact of different auxiliary interferometer calibration methods on OPD measurements. A homodyne quadrature laser interferometer (HQLI) is used as the main interferometer, and a 3 × 3 interferometer is used as the auxiliary interferometer. The calibration of the auxiliary interferometer using optical spectrum analyzer scanning and ruler measurement is compared. The evaluation shows that the auxiliary interferometer is the most significant source of uncertainty and causes the total uncertainty to increase linearly with increasing OPD. It is proven that a high-precision calibration and large-OPD auxiliary interferometer can improve the real-time accuracy of OPD measurements based on the auxiliary interferometer. The scheme can determine the minimum uncertainty to optimize the system noise and consistency for vibration, hydroacoustic, and magnetic field measurements with OPDs of the ~m level.

Zebrafish facilitate non-alcoholic fatty liver disease research: Tools, models and applications.

Non-alcoholic fatty liver disease (NAFLD) has become an increasingly epidemic metabolic disease worldwide. NAFLD can gradually deteriorate from simple liver steatosis, inflammation and fibrosis to liver cirrhosis and/or hepatocellular carcinoma. Zebrafish are vertebrate animal models that are genetically and metabolically conserved with mammals and have unique advantages such as high fecundity, rapid development ex utero and optical transparency. These features have rendered zebrafish an emerging model system for liver diseases and metabolic diseases favoured by many researchers in recent years. In the present review, we summarize a series of tools for zebrafish NAFLD research and the models established through different dietary feeding, hepatotoxic chemical treatments and genetic manipulations via transgenic or genome editing technologies. We also discuss how zebrafish models facilitate NAFLD studies by providing novel insights into NAFLD pathogenesis, toxicology research, and drug evaluation and discovery.

Fiber optic jerk sensor.

Jerk is directly related to a physical mutation process of structural damage and human comfort. A fiber optic jerk sensor (FOJS) based on a fiber optic differentiating Mach-Zehnder interferometer is proposed. It can directly measure jerk by demodulating the phase of interference light, which avoids the high-frequency noise interference caused by differentiating the acceleration. The sensing theory and sensor design are given in detail. The experimental and theoretical results agree, demonstrating that the FOJS has a high sensitivity, an ultralow phase noise floor, a wide measuring range, and good linearity. The impact test shows that the FOJS can directly measure jerk and has good consistency with a standard piezoelectric accelerometer. The FOJS has potential applications in earthquake engineering, comfort evaluations, and railway design. This is the first time that directly measuring jerk with an optical sensor is reported.

Computational Studies on the Materials Combining Graphene Quantum Dots and Pt Complexes with Adjustable Luminescence Characteristics.

Graphene materials with particular properties are proved to be beneficial to photoelectric devices, but there are rare reports on a positive effect by graphene on emissive layer materials of organic light-emitting diodes (OLEDs) previously. On the basis of the latest important experiments, an OLED device with the aid of graphene quantum dots shows the dawn of their application for luminescent materials. The luminescence performance has been improved, but the understanding of the internal excited-state radiation mechanism of the material needs further study. In this work, the Pt(II)-coordinated graphene quantum dot coplanar structures with different shapes are studied theoretically in detail, and the results present the improvement in phosphorescence under the promoted radiative decay and suppressed nonradiative decay. This composite combines the advantages of transition metal complexes and graphene quantum dots and also exhibits excellent properties in the light absorption region and carrier transportation for the OLED. This comprehensive theoretical calculation research can provide a comprehensive basis of the material design in the future.

Dynamics and asymptotic profiles of endemic equilibrium for SIS epidemic patch models.

In this paper, we perform qualitative analysis to two SIS epidemic models in a patchy environment, without and with linear recruitment. The model without linear recruitment was proposed and studied by Allen et al. (SIAM J Appl Math 67(5):1283-1309, 2007). This model possesses a conserved total population number, whereas the model with linear recruitment has a varying total population. However, both models have the same basic reproduction number. For both models, we establish the global stability of endemic equilibrium in a special case, which partially solves an open problem. Then we investigate the asymptotic behavior of endemic equilibrium as the mobility of infected and/or susceptible population tends to zero. Though the basic reproduction number is a well-known critical index, our theoretical results strongly suggest that other factors such as the variation of total population number and individual movement may also play vital roles in disease prediction and control. In particular, our results imply that the variation of total population number can cause infectious disease to become more threatening and difficult to control.

miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/ß-catenin signaling pathway.

BACKGROUND: miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-ß signaling in vivo. However, the detailed role of miR-214 in acute kidney injury (AKI) and its underlying mechanism are still largely unknown. METHODS: In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell model were used to study AKI. The concentrations of kidney injury markers serum creatinine, blood urea nitrogen, and kidney injury molecule-1 were measured. The expressions of miR-214, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, ß-catenin, c-myc, and cyclinD1 were determined by western blot. Cell apoptosis and caspase 3 activity were evaluated by flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-214 and Dkk3. RESULTS: miR-214 expression was induced in ischemia-reperfusion (I/R)-induced AKI rat and hypoxic incubation of NRK-52E cells. Overexpression of miR-214 alleviated hypoxia-induced NRK-52E cell apoptosis while inhibition of miR-214 expression exerted the opposite effect. Dkk3 was identified as a target of miR-214. Anti-miR-214 abolished the inhibitory effects of DKK3 knockdown on hypoxia-induced NRK-52E cell apoptosis by inactivation of Wnt/ß-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/ß-catenin pathway. CONCLUSION: miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/ß-catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI.

Pathogen distribution and drug resistance of nephrology patients with urinary tract infections.

OBJECTIVE: Pathogen distribution characteristics of nephrology patients with urinary tract infections are studied, and drug resistance of nephrology and urinary tract infection disease are analyzed, so as to provide sufficient evidence for treatment of patients. METHODS: Conduct randomized control study of 3500 cases of nephrology patients with urinary tract infections treated in different hospitals from December 2013 to December 2015, isolate pathogens in patients' urine samples, perform identification and drug sensitive test and then conduct detailed analysis of drug resistance of pathogens. RESULTS: Through isolation of pathogens, it can be found that all pathogens include Escherichia coli, Gram-positive cocci, gram-negative bacteria, fungi, Acinetobacter baumannii, Enterococcus faecalis, and urinary Enterococcus. Among them, proportion of E. coli is the largest. Patients have relatively high drug resistance to ceftriaxone, gentamicin, ciprofloxacin and cotrimoxazole. CONCLUSION: For nephrology patients with urinary tract infection, the main pathogen is E. coli, which has had some drug resistance. Drug resistance detection of pathogen should be strengthened in clinics, so as to provide strong guidance for clinical treatment and promote effective treatment of patients.

The wheat NHX antiporter gene TaNHX2 confers salt tolerance in transgenic alfalfa by increasing the retention capacity of intracellular potassium.

Previous studies have shown that TaNHX2 transgenic alfalfa (Medicago sativa L.) accumulated more K(+) and less Na(+) in leaves than did the wild-type plants. To investigate whether the increased K(+) accumulation in transgenic plants is attributed to TaNHX2 gene expression and whether the compartmentalization of Na(+) into vacuoles or the intracellular compartmentalization of potassium is the critical mechanism for TaNHX2-dependent salt tolerance in transgenic alfalfa, aerated hydroponic culture was performed under three different stress conditions: control condition (0.1 mM Na(+) and 6 mM K(+) inside culture solution), K(+)-sufficient salt stress (100 mM NaCl and 6 mM K(+)) and K(+)-insufficient salt stress (100 mM NaCl and 0.1 mM K(+)). The transgenic alfalfa plants had lower K(+) efflux through specific K(+) channels and higher K(+) absorption through high-affinity K(+) transporters than did the wild-type plants. Therefore, the transgenic plants had greater K(+) contents and [K(+)]/[Na(+)] ratios in leaf tissue and cell sap. The intracellular compartmentalization of potassium is critical for TaNHX2-induced salt tolerance in transgenic alfalfa.

Preparation, characteristic, biological activities, and application of polysaccharide from Lilii Bulbus: a review.

OBJECTIVES: This review highlights the current knowledge of polysaccharide from Lilii Bulbus, including the extraction, purification, structure, structure modification , biological activities and application, which will hopefully provide reference for further research and development of polysaccharide from Lilii Bulbus. MATERIALS AND METHODS: Literature searches were conducted on the following databases: Pubmed, ACS website, Elsevier, Google Scholar, Web of Science and CNKI database. Keywords such as "Lilii Bulbus", "polysaccharide", "preparation", "biological activities" and "application" were used to search relevant journals and contents, and some irrelevant contents were excluded. RESULTS: In general, the study of Lilium Bulbus polysaccharide extraction and purification, structure characterization and biological activity has made substantial progress, these findings highlight the lilium brownii polysaccharide enormous potential in biomedical applications, of lilium brownii polysaccharide laid a solid foundation for further research. DISCUSSION AND CONCLUSIONS: However, it should be noted that the relevant mechanism of the effective effect of lily bulb polysaccharide still needs to be worked on by researchers. These findings highlight the great potential of lily polysaccharides in biomedical applications, and lay a solid foundation for further research on lily polysaccharides.

Polygonum cillinerve polysaccharide inhibits transmissible gastroenteritis virus by regulating microRNA-181.

Transmissible gastroenteritis virus (TGEV) is an important pathogen capable of altering the expression profile of cellular miRNA. In this study, the potential of Polygonum cillinerve polysaccharide (PCP) to treat TGEV-infected piglets was evaluated through in vivo experiments. High-throughput sequencing technology was employed to identify 9 up-regulated and 17 down-regulated miRNAs during PCP-mediated inhibition of TGEV infection in PK15 cells. Additionally, miR-181 was found to be associated with target genes of key proteins in the apoptosis pathway. PK15 cells were treated with various concentrations of PCP following transfection with miR-181 mimic or inhibitor. Real-time PCR assessed the impact on TGEV replication, while electron microscopy (TEM) and Hoechst fluorescence staining evaluated cellular functionality. Western blot analysis was utilized to assess the expression of key signaling factors-cytochrome C (cyt C), caspase 9, and P53-in the apoptotic signaling pathway. The results showed that compared with the control group, 250 µg/mL PCP significantly inhibited TGEV gRNA replication and gene N expression (P < 0.01). Microscopic examination revealed uniform cell morphology and fewer floating cells in PCP-treated groups (250 and 125 µg/mL). TEM analysis showed no typical virus structure in the 250 µg/mL PCP group, and apoptosis staining indicated a significant reduction in apoptotic cells at this concentration. Furthermore, PCP may inhibit TGEV-induced apoptosis via the Caspase-dependent mitochondrial pathway following miR-181 transfection. These findings provide a theoretical basis for further exploration into the mechanism of PCP's anti-TGEV properties.

Nonmetallic Active Sites on Nickel Phosphide in Oxygen Evolution Reaction.

Efficient and durable catalysts are crucial for the oxygen evolution reaction (OER). The discovery of the high OER catalytic activity in Ni12P5 has attracted a great deal of attention recently. Herein, the microscopic mechanism of OER on the surface of Ni12P5 is studied using density functional theory calculations (DFT) and ab initio molecular dynamics simulation (AIMD). Our results demonstrate that the H2O molecule is preferentially adsorbed on the P atom instead of on the Ni atom, indicating that the nonmetallic P atom is the active site of the OER reaction. AIMD simulations show that the dissociation of H from the H2O molecule takes place in steps; the hydrogen bond changes from Oa-H⋯Ob to Oa⋯H-Ob, then the hydrogen bond breaks and an H+ is dissociated. In the OER reaction on nickel phosphides, the rate-determining step is the formation of the OOH group and the overpotential of Ni12P5 is the lowest, thus showing enhanced catalytic activity over other nickel phosphides. Moreover, we found that the charge of Ni and P sites has a linear relationship with the adsorption energy of OH and O, which can be utilized to optimize the OER catalyst.

The roles and activation of endocardial Notch signaling in heart regeneration.

As a highly conserved signaling pathway in metazoans, the Notch pathway plays important roles in embryonic development and tissue regeneration. Recently, cardiac injury and regeneration have become an increasingly popular topic for biomedical research, and Notch signaling has been shown to exert crucial functions during heart regeneration as well. In this review, we briefly summarize the molecular functions of the endocardial Notch pathway in several cardiac injury and stress models. Although there is an increase in appreciating the importance of endocardial Notch signaling in heart regeneration, the mechanism of its activation is not fully understood. This review highlights recent findings on the activation of the endocardial Notch pathway by hemodynamic blood flow change in larval zebrafish ventricle after partial ablation, a process involving primary cilia, mechanosensitive ion channel Trpv4 and mechanosensitive transcription factor Klf2.

How does the porphyrin-like vacancy affect the spectral properties of graphene quantum dots? A theoretical study.

By processing graphene quantum dot, an ideal semiconductor material with suitable band gap and higher electron mobility can be obtained. Thus, it has a broad prospect in the application of photoelectric response materials. Here, a graphene defect with porphyrin-like structure is selected to achieve the controlable light absorption. The double five-membered-ring parallel vacancy are based on self-healing properties of popular graphene defects. Aimed to separate exciton and hole more effectively and achieve higher photoelectric conversion efficiency, the occupied orbital and unoccupied orbital of the quantum dot with objected defect structure is taken as orderly dispersion to form an obvious charge separation state under the demonstration with first principles calculation. Most importantly, a real time real space charge separation is calculated by time-dependent ab-initio quantum dynamics based on numerical atomic basis sets. The result shows the specific graphene defects can form an efficient pure graphene photoelectric response medium like porphyrin skeleton, and the vacancy will induce to adjust and control the specific wavelength of the response light and charge separated state manipulably with odevity of number of peripheral carbon rings by the calculation of ultrafast process.

Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition.

Forkhead box O 6 (FOXO6), a FOX transcription factor, has been found to be involved in diabetes mellitus and related complications. However, the role of FOXO6 in diabetic nephropathy (DN) has not been fully understood. In the present study, we evaluated the functions of FOXO6 in high glucose (HG)-induced glomerular mesangial cells (MCs). The results showed that FOXO6 expression was significantly elevated in MCs after HG stimulation. Knockdown of FOXO6 by transfection with small interfering RNA (siRNA) targeting FOXO6 (siRNA-FOXO6) suppressed cell proliferation in MCs. The productions of extracellular matrix (ECM) components including collagen IV (Col IV) and fibronectin (FN) were markedly decreased after FOXO6 knockdown in MCs. Furthermore, knockdown of FOXO6 inhibited HG-induced activation of p38 MAPK signaling pathway in MCs. Collectively, these findings suggested that knockdown of FOXO6 inhibited cell proliferation and ECM accumulation in HG-induced MCs via inhibiting p38 MAPK signaling pathway. FOXO6 might be a beneficial therapeutic target for the prevention and treatment of DN.

Retracted Article: TMEM88 inhibits fibrosis in renal proximal tubular epithelial cells by suppressing the transforming growth factor-ß1/Smad signaling pathway.

Transmembrane protein 88 (TMEM88) belongs to a member of the TMEM family, and was reported to be involved in fibrogenesis. However, the biological role of TMEM88 in renal fibrosis has not been elucidated. Therefore, the objective of this study was to investigate the effect of TMEM88 on cell proliferation and extracellular matrix (ECM) accumulation in a TGF-ß1-induced human renal proximal tubular epithelial cell line (HK2). Our results showed that TMEM88 was downregulated in renal fibrotic tissues and TGF-ß1-treated HK2 cells. In addition, TMEM88 overexpression inhibited TGF-ß1-induced cell proliferation and migration in HK2 cells. Furthermore, TMEM88 overexpression reduced the production of α-SMA, collagen I, and collagen III in TGF-ß1-stimulated HK2 cells. Mechanistically, TMEM88 overexpression suppressed the phosphorylation status of Smad2 and Smad3 in TGF-ß1-stimulated HK2 cells. In conclusion, data from our experiments demonstrate that TMEM88 plays a pivotal role in the pathological process of renal fibrosis. TMEM88 inhibited fibrosis in renal proximal tubular epithelial cells by suppressing the TGF-ß1/Smad signaling pathway.

Liquiritigenin attenuates high glucose-induced mesangial matrix accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways.

Oxidative stress, inflammation, and hyperglycemia are considered to play crucial roles in the pathogenesis and progression of diabetic nephropathy (DN). Liquiritigenin, one of the flavonoid compounds, has been shown to possess anti-inflammatory, anti-hyperlipidemic, and anti-oxidative properties. Our study aimed to explore the effects of liquiritigenin on high glucose (HG)-induced extracellular matrix (ECM) accumulation, oxidative stress and inflammatory response and delineate the underlying mechanism. In our study, glomerular mesangial cells (HBZY-1) were co-treated with various doses of liquiritigenin and HG. We found that HG, but not normal glucose or mannitol, promoted the proliferation of HBZY-1 cells, which was suppressed by liquiritigenin. Liquiritigenin inhibited HG-induced ECM accumulation in HBZY-1 cells by reducing the expressions and production of collagen IV (Col IV) and fibronectin (FN). Moreover, liquiritigenin attenuated HG-induced oxidative stress, as evidenced by the decreased MDA content and NADPH oxidase 4 (NOX4) expression, and the increased SOD activity in HBZY-1 cells. Liquiritigenin suppressed HG-induced inflammatory response, as demonstrated by the reduced expressions and secretion of interleukin (IL)-6 and IL-1ß in HBZY-1 cells. Furthermore, we found that liquiritigenin inhibited HG-induced activation the nuclear factor-kappa B (NF-κB) and nod-like receptor protein 3 (NLRP3) inflammasome pathways. In conclusion, these results demonstrated that liquiritigenin attenuated HG-induced ECM accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways, suggesting that liquiritigenin might be a promising therapeutic agent for preventing the development of DN.

Silencing of PAQR3 suppresses extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via PI3K/AKT signaling pathway.

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism. Our results demonstrated that HG significantly up-regulated the expression of PAQR3 in human MCs. In addition, knockdown of PAQR3 efficiently suppressed MC proliferation and ECM production in HG-stimulated MCs. Furthermore, knockdown of PAQR3 markedly reversed HG-induced PI3K/AKT activation in MCs. In summary, our present study demonstrated that knockdown of PAQR3 suppressed HG-induced the proliferation and ECM accumulation in human MCs, via inhibiting the PI3K/AKT signaling pathway. Thus, PAQR3 may be a potential therapeutic target for the treatment of diabetic nephropathy.

miR-182 enhances acute kidney injury by promoting apoptosis involving the targeting and regulation of TCF7L2/Wnt/ß-catenins pathway.

Acute kidney injury (AKI) is a sudden decay in renal function leading to increasing morbidity and mortality. miR-182 has been reported to be actively involved in kidney diseases. However, the function and molecular mechanism of miR-182 in AKI still need to be elucidated. The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urine Kim-1 in I/R-induced rat AKI model were detected by a Beckman Autoanalyzer. miR-182 and transcription factor 7-like-2 (TCF7L2) mRNA expression were measured by qRT-PCR. Flow cytometry and caspase-3 colorimetry analysis were performed to determine NRK-52E cell apoptosis. Bioinformatics and dual-luciferase reporter were used to identify the interaction between miR-182 and TCF7L2. miR-182 expression was increased in both I/R-induced rat models and hypoxia-treated NRK-52E cells, and miR-182 overexpression stimulated the apoptosis of hypoxia-induced NRK-52E cells. Dual-luciferase analysis disclosed that TCF7L2 was a target of miR-182. TCF7L2 suppressed hypoxia-induced apoptosis in NRK-52E cells, and the inhibitory effect of TCF7L2 on cell apoptosis could be reversed with miR-182 restoration. Moreover, the activity of Wnt/ß-catenin signaling pathway was promoted following overexpression of TCF7L2 in NRK-52E cells with hypoxia treatment, and this effect was greatly attenuated by the increased miR-182 expression. Finally, in vivo experiment also validated the alleviation of miR-182 inhibitor on I/R-induced kidney injury and apoptosis via regulating TCF7L2/ Wnt/ß-catenin pathway. miR-182 exacerbated AKI involving the targeting and regulation of TCF7L2/Wnt/ß-catenin signaling, unveiling a novel regulatory pathway in ischemia-reperfusion injury and elucidating a potential biomarker for AKI treatment.