Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Echinacoside from Cistanche tubulosa ameliorates alcohol-induced liver injury and oxidative stress by targeting Nrf2.

Cistanche tubulosa (Schrenk) Wight, named Guan hua Rou Cong-Rong in Chinese, is a traditional plant with liver, kidney, and intestine protective effects. Echinacoside (ECH) is its active constituent and has been found to have various biological effects, including antioxidative stress and anti-inflammatory effects. Liver injury caused by acetaminophen or CCL4 has been proven to benefit from ECH; however, the effects of ECH against alcoholic liver disease (ALD) remain unclear. This study was used to estimate the effect of echinacoside on nuclear factor erythroid 2-related factor 2 (Nrf2), which ameliorates ALD by inhibiting oxidative stress and cell apoptosis through affecting Nrf2.A mouse model of ALD was established with ethanol using hematoxylin and eosin (HE) staining, oiled staining, and biochemical indices. Alpha Mouse Liver 12 (AML-12) cells were induced with ethanol in vitro and analyzed using western blotting, flow cytometry, and biochemical assays. In the animal model of ALD, ECH dramatically reduced liver damage, as proven by the downregulation of aspartate aminotransferase (AST) and HE staining. In vitro, ECH distinctly reduced the damage caused by ethanol through the decreased expression of cleaved caspase-3 measured by western blotting. ECH significantly increased the activity of Nrf2 in vivo and in vitro. Nrf2 knockout may diminish the influence of ECH on ALD. Meanwhile, ECH also increased the expression of haem oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC), while it inhibited levels of oxidative stress and cell apoptosis. Our findings suggest that ECH protects against ethanol-induced liver injuries by alleviating oxidative stress and cell apoptosis by increasing the activity of Nrf2. Therefore, ECH is promising for the treatment of ALD.

Analysis of the 2p-manifold population distribution in a diode-pumped metastable Ar laser.

The complex excited energy levels in the diode-pumped metastable Ar laser may induce harmful effects in laser cycling. Significantly, the influence of the population distribution in 2p energy levels on the laser performance is unclear yet. In this work, the absolute populations in all the 2p states were measured online by the simultaneous applications of tunable diode laser absorption spectroscopy and optical emission spectroscopy. The results showed that most atoms were populated to the 2p8, 2p9, and 2p10 levels while lasing, and the majority of the 2p9 population was efficiently transferred to the 2p10 level with the aid of helium, which was beneficial for the laser performance.

Polarization insensitive efficient ultra-narrow diode laser strictly locked by a Faraday filter.

A Faraday anomalous dispersion optical filter (FADOF) could lock high-power diode lasers to atomic resonance lines with ultra-narrow bandwidth. However, the polarization sensitivity of the Faraday filter limits its applications since the standard diode module often employs polarization combination to increase pumping brightness. We proposed a polarization-insensitive mutual injection configuration to solve this problem and locked a standard polarization combined diode module to Rb D2-line. The laser bandwidth was narrowed from 4 nm to 0.005 nm (2.6 GHz, FWHM) with 38.3 W output and an external cavity efficiency of 80%. This FADOF-based polarization-insensitive external-cavity scheme would find many applications, such as high energy atomic gas laser pumping (alkali lasers, metastable rare gas lasers) and quantum optics, etc.

Fast on-line rubidium DPAL atomic concentration measurement by 420 nm probe laser: erratum.

We present an erratum to our recent work [Appl. Opt.60, 10862 (2021)APOPAI0003-693510.1364/AO.440435] that corrects errors in Fig. 4 and the body of the paper. The corrections do not affect the results and conclusions of the original paper.

18W ultra-narrow diode laser absolutely locked to the Rb D2 line.

We described a wavelength locked and spectral narrowed high-power diode laser with a Faraday anomalous dispersion optical filter (FADOF). By an external cavity with a 85Rb FADOF, the central wavelength of the diode laser was precisely locked to the Rb resonance D2 line. The bandwidth was narrowed from the free-running 4 nm to 0.002 nm (1.2 GHz, FWHM). At 4.9 A maximal driven current, the laser produced a continuous wave (CW) output of 18 W with an external cavity efficiency of 80%, either the current or the temperature had no impact on the central wavelength of the diode laser. The Rb cell works well without any damage under a long-time running. This ultra-stable and extreme-narrowed high power diode laser would find many applications in alkali lasers pumping, metastable rare gas laser pumping, spin-exchange optical pumping, and quantum optics.

Sennoside A prevents liver fibrosis by binding DNMT1 and suppressing DNMT1-mediated PTEN hypermethylation in HSC activation and proliferation.

Hepatic stellate cell (HSC) activation is an essential event during liver fibrogenesis. Phosphatase and tension homolog deleted on chromosome 10 (PTEN) is a negative regulator of this process. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of PTEN, is selectively induced in myofibroblasts from diseased livers. Sennoside A (SA), a major purgative constituent of senna and the Chinese herb rhubarb, is widely used in China and other Asian countries as an irritant laxative. SA is reported to improve hepatic steatosis. However, the effect and mechanism of SA on liver fibrosis remain largely unknown. We recently identified a novel strategy for protecting liver fibrosis via epigenetic modification by targeting DNMT1. A Surface Plasmon Resonance (SPR) assay first reported that SA could directly bind DNMT1 and inhibit its activity. Administration of SA significantly prevented liver fibrosis, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) protein levels in a CCl4 -induced mouse hepatic fibrosis model and in TGF-ß1-activated HSC-T6 cells, in vivo and in vitro. SA decreased the expression of Cyclin D1, CDK, and C-myc, indicating that SA may inhibit the activation and proliferation of TGF-ß1-induced HSC-T6. Moreover, SA significantly promoted the expression of PTEN and remarkably inhibited the expression of p-AKT and p-ERK in vitro. Blocking PTEN or overexpressing DNMT1 could reduce the effect of SA on liver fibrosis. These data suggest that SA directly binds and inhibits the activity and that attenuated DNMT1-mediated PTEN hypermethylation caused the loss of PTEN expression, followed by the inhibition of the AKT and ERK pathways and prevented the development of liver fibrosis. Hence, SA might be employed as a promising natural supplement for liver fibrosis drug therapy.

Sennoside A alleviates inflammatory responses by inhibiting the hypermethylation of SOCS1 in CCl4-induced liver fibrosis.

Liver fibrosis is the consequence of chronic liver injury and is a major challenge to global health. However, successful therapy for liver fibrosis is still lacking. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve hepatic disease, but the underlying mechanisms remain largely elusive. Here, we show for the first time that SA enhanced suppressor of cytokine signaling 1 (SOCS1) expression in a DNA methyltransferase 1 (DNMT1)-dependent manner and thereby attenuated liver fibrosis. Consistently, SA inhibited the expression of the liver fibrogenesis markers α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) and suppressed inflammatory responses in vivo and in vitro. Coculture experiments with macrophages/hepatic stellate cells (HSCs) revealed that SA suppressed HSC proliferation by downregulating proinflammatory cytokines in macrophages. Mechanically, SA promoted the aberrant expression of SOCS1 in liver fibrosis. However, blocking SOCS1 expression weakened the inhibitory effect of SA on HSC proliferation, indicating that SOCS1 may play an important role in mediating the antifibrotic effect of SA. Furthermore, SA inhibited DNMT1-mediated SOCS1 and reduced HSC proliferation by inhibiting inflammatory responses in carbon tetrachloride (CCl4) -induced liver fibrosis.

Fast online rubidium DPAL atomic concentration measurement by 420 nm probe laser.

The alkali atom concentration plays an important role in the performance of a diode pumped alkali vapor laser (DPAL). At the rubidium DPAL operational region, the alkali concentration is as high as 1013-1014cm-3, which is "optically thick," or opaque, for the 780 nm or 795 nm doublet D lines when the traditional scanning absorption spectrum method is used for concentration measurement. To solve this problem, we propose the use of a probe laser of 420 nm, which corresponds to the 52S1/2 to 62P3/2 transition and has a lower absorption cross section compared to the D-line doublet. Due to the moderate absorption strength at a fixed 420 nm probe wavelength, we realized fast, online measurement of the Rb concentration in a real-world DPAL. By combining it with the quasi-two-level model, we further provided the population distribution in the lower three energy levels. This fast, online diagnostic method could be well applied in DPAL concentration measurement, and could show the dynamics of a laser's performance.

Post-synthetic Covalent Organic Framework to Improve the Performance of Solid-State Li+ Electrolytes.

As a new class of crystalline materials, covalent organic frameworks (COFs) have long-range ordered channels and feasibility to functionalize. The well-arranged pores make it possible to contain and transport ions. Here, we designed a novel functionalized anionic COF-SS-Li by a post-synthetic method utilizing the Povarov reaction of BDTA-COF, anchoring -SO3- groups to the COF backbone and converting the imine linkage to a more stable quinoline unit. The grafted -SO3- groups and directional channels can promote the lithium-ion transport through a hopping mechanism. As a solid-state lithium-ion electrolyte, COF-SS-Li exhibits the conductivities of 9.63 × 10-5 S cm-1 at 20 °C and 1.28 × 10-4 S cm-1 at 40 °C and a wide electrochemical window of 4.85 V. The assembled Li|COF-SS-Li|Li symmetric cell can cycle stably for 600 h at 0.1 mA cm-2. Also, the Li|COF-SS-Li|LiFePO4 cell delivers an initial capacity of 117 mAh g-1 at 0.1 A g-1 and retains a capacity rate of 56.7% after 500 cycles. The research enriches the solid-state electrolytes for lithium-ion batteries.

Lymphocyte-Specific Protein Tyrosine Kinase Contributes to Spontaneous Regression of Liver Fibrosis may by Interacting with Suppressor of Cytokine Signaling 1.

Quiescent hepatic stellate cells (qHSCs), converted to myofibroblasts, produce fibrous scars, which is an essential event during liver fibrogenesis. Clinical and experimental fibrosis undergo remarkable regression when the underlying etiological agent is removed. Some myofibroblasts revert to an inactive phenotype (iHSCs) during the regression of fibrosis. However, the mechanisms underlying HSC activation and reversal remain unclear. The present study demonstrated that the expression of lymphocyte-specific protein tyrosine kinase (LCK) was increased in fibrotic livers but decreased after spontaneous recovery in vivo and in vitro, which was correlated with the expression of α-smooth muscle actin (α-SMA) and type I collagen (COL-1). Further investigation indicated that specific knockdown of LCK by a recombination adeno-associated virus 9 (rAAV9) in C57BL/6 mice ameliorated liver fibrosis. Co-incubation of TGF-ß1-induced HSC-T6 cells with LCK-siRNA inhibited cell proliferation and activation. Overexpression of LCK inhibited activated HSCs going to inactivated phenotype. Interestingly, we found that LCK may interact with suppressor of cytokine signaling 1 (SOCS1) and may influence the expression of p-JAK1 and p-STAT1/3. These data suggest that LCK may play a regulatory role in liver fibrosis by inhibiting SOCS1, indicating that LCK is a potential therapeutic target for liver fibrosis treatment.

Rational design of covalent organic frameworks with high capacity and stability as a lithium-ion battery cathode.

A two-dimensional covalent organic framework (NTCDI-COF) with rich redox active sites, high stability and crystallinity was designed and prepared. As a cathode material for lithium-ion batteries (LIBs), NTCDI-COF exhibits excellent electrochemical performance with an outstanding discharge capacity of 210 mA h g-1 at 0.1 A g-1 and high capacity retention of 125 mA h g-1 after 1500 cycles at 2 A g-1. A two-step Li+ insertion/extraction mechanism is proposed based on the ex situ characterization and density functional theory calculation. The constructed NTCDI-COF//graphite full cells can realize a good electrochemical performance.

Downregulating PDPK1 and taking phillyrin as PDPK1-targeting drug protect hepatocytes from alcoholic steatohepatitis by promoting autophagy.

The health risk stemming from drinking alcohol is serious, sometimes even life-threatening. Alcoholic steatohepatitis (ASH) is a critical stage leading to cirrhosis and end-stage liver disease. However, its pathogenesis is still far from clearly understood, and a treatment that is widely recognised as effective has not been discovered. Interestingly, PDPK1,3-phosphoinositide-dependent protein kinase 1, also known as PDK1, was observed to be obviously increased in the ASH model by our researchers. We also investigated the protective role of autophagy in ASH. Here, we studied the function of PDPK1 and found an efficient treatment to alleviate symptoms by targeting PDPK1 in ASH. In our study, PDPK1 affected hepatocyte self-healing by inhibiting autophagy. Both inhibiting PDPK1 and the phosphorylation of PDPK1 (ser241) could protect hepatocytes from suffering heavy alcoholic hepatitis.

Betulinic acid prevents liver fibrosis by binding Lck and suppressing Lck in HSC activation and proliferation.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum japonicum Thunb. ex Murray (Hypericaceae), named 'Tianjihuang' is a traditional Chinese medicine with hepatoprotective, antibacterial, and antitumour effects. Betulinic acid (BA) is its active constituent and has been found to have a number of biological effects, including antiviral, anti-inflammatory, and anti-malarial therapeutic properties. Non-alcoholic fatty liver disease and acute alcoholic liver injury have both been proven to benefit from BA. BA's effects and mechanism on liver fibrosis are still unknown. AIM OF THE STUDY: The purpose of this study was to explore the influence of BA on lymphocyte-specific protein tyrosine kinase (Lck), a non-receptor Src family kinase, that reduces liver fibrosis by inhibiting the phosphorylation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways through the interaction of Lck and SOCS1. MATERIALS AND METHODS: A liver fibrosis model was established in vivo with CCl4 using haematoxylin and eosin (HE) staining, Masson staining, immunohistochemical staining, and immunofluorescence staining. Hepatic stellate cells were induced with transforming growth factor (TGF)-ß1 in vitro, using Western blotting, immunofluorescence staining, and a cell scratch assay. RESULTS: In a CCl4-induced mouse hepatic fibrosis model and in TGF-ß1-activated HSC-T6 cells, BA markedly reduced fibrosis, as demonstrated by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) protein levels in vivo and in vitro. BA significantly suppressed the activity and expression of Lck in vitro. Overexpression of Lck may diminish the effect of BA on liver fibrosis. In vitro, BA also greatly increased the expression of suppressor of cytokine signalling 1 (SOCS1) while it considerably inhibited the expression of p-JAK and p-STAT1. CONCLUSIONS: These findings suggest that BA promotes the expression of SOCS1 by the inhibiting the interaction between Lck and SOCS1, followed by the inhibition of JAK/STAT phosphorylation to prevent the progression of liver fibrosis. Therefore, BA could be used as a promising natural supplement for the treatment of liver fibrosis.

Post-traumatic Growth Level and Its Influencing Factors Among Frontline Nurses During the COVID-19 Pandemic.

Objective: To assess post-traumatic growth (PTG) level and explore its influence factors among frontline nurses during the COVID-19 pandemic. Methods: From April 11th to 12th, 2020, a cross sectional study was conducted on 116 frontline nurses who had participated in fight against the COVID-19 in Wuhan city, China. General information and psychological discomfort were collected. Chinese version post-traumatic growth inventory with 20 items was applied to assess PTG level. Univariable analyses and multiple linear regression were performed to explore potential influencing factors of PTGI score. Results: The average score of PTGI in frontline nurses was 65.65 ± 11.50. In univariable analyses, gender, age, education level, marital status, living with parents, professional title, working years and professional psychological support was not statistically associated with the PTGI score. In both univariable and multivariable analyses, having support from family members and friends, being psychological comfort and having children and increased the PTGI score significantly. The three factors only explained 3.8% variance. Conclusion: Moderate PGT was observed in the frontline nurses who had battled against COVID-19. Social support and professional psychological intervention should be applied to further improve PTG level. Further studies with large sample size are required to explore more potential influencing factors.

PSTPIP2 inhibits cisplatin-induced acute kidney injury by suppressing apoptosis of renal tubular epithelial cells.

Cisplatin (CP) is an effective chemotherapeutic agent widely used in the treatment of various solid tumours. However, CP nephrotoxicity is an important limitation for CP use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Recently, we identified a specific role of proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) in cisplatin-induced AKI. PSTPIP2 was reported to play an important role in a variety of diseases. However, the functions of PSTPIP2 in experimental models of cisplatin-induced AKI have not been extensively studied. The present study demonstrated that cisplatin downregulated the expression of PSTPIP2 in the kidney tissue. Administration of AAV-PSTPIP2 or epithelial cell-specific overexpression of PSTPIP2 reduced cisplatin-induced kidney dysfunction and inhibited apoptosis of renal tubular epithelial cells. Small interfering RNA-based knockdown of PSTPIP2 expression abolished PSTPIP2 regulation of epithelial cell apoptosis in vitro. Histone acetylation may impact gene expression at the epigenetic level, and histone deacetylase (HDAC) inhibitors were reported to prevent cisplatin-induced nephrotoxicity. The UCSC database was used to predict that acetylation of histone H3 at lysine 27 (H3K27ac) induces binding to the PSTPIP2 promoter, and this prediction was validated by a ChIP assay. Interestingly, an HDAC-specific inhibitor (TSA) was sufficient to potently upregulate PSTPIP2 in epithelial cells. Histone acetylation-mediated silencing of PSTPIP2 may contribute to cisplatin nephrotoxicity. PSTPIP2 may serve as a potential therapeutic target in the prevention of cisplatin nephrotoxicity.

An objective estimation of the removability of three home reliners.

The purpose of this study was to investigate methods for evaluating objectively the removability of three commercially available home reliners (Cushion Correct, Tafugurippu Pink A and Liodent Pink). After immersing each of the reliners in distilled water at 37ºC for 24 h, we compared their removability using the peel test with a finger, which was evaluated based on a visual analogue scale and the percentage of the residual area. An experimental rake-up test was also undertaken to quantify removability, evaluated based on the total amount of work required to remove it. The Tafugurippu Pink A product was easier to remove with a finger than the other two home reliner products, and required the least total amount of work to be removed in the experimental rake-up test. Furthermore, the rake-up test performed could possibly be used for objective evaluation of the removability of home reliner.

Effects of temperature-responsive hydrogel on viscosity of denture adhesives.

The cream type of denture adhesives after use cannot be easily removed from oral mucosa and have the potential risk to change the oral flora. The effects of the temperature-responsive hydrogel Pluronic F-127 (PF) on the complex viscosity of denture adhesives were evaluated. Carboxy methylcellulose (CMC) mass fractions (1, 2, 3 and 4%) were added to 20 and 25% PF hydrogels. Complex viscosity was measured over a temperature cycle (40→10→40°C) and fixed temperature points (23 and 37°C). Adhesive strength tests were performed with 2 resin plates at 23 and 37°C. One commercial cream-type denture adhesive, New Poligrip® (NP), was evaluated as a control. Complex viscosity values for PF20% groups at 23°C were lower than those for NP at 37°C. Adhesive strength of PF20% with CMC2%, was higher at 23°C when compared to NP at 37°C, which suggests that PF20%CMC2% is an effective adhesive and is easily removed after mouth rinsing.