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Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J − L (5–7), linderaguaianols A and B (8 and 9), together with six known ones 10–15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1–4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 μM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.

Objectives To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. Methods We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan–Meier curves, log–rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. Results Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P =

TiBw/TC4 composite was brazed to Ti60 alloy successfully using TiZrNiCu amorphous filler alloy, and the interfacial microstructures and mechanical properties were characterized by SEM, EDX, XRD and universal tensile testing machine. The typical interfacial microstructure was TiBw/TC4 composite/β-Ti + TiB whiskers/(Ti, Zr)2(Ni, Cu) intermetallic layer/β-Ti/Ti60 alloy when being brazed at 940 °C for 10 min. The interfacial microstructure evolution was influenced strongly by the diffusion and reaction between molten fillers and the substrates. Increasing brazing temperature decreased the thickness of brittle (Ti, Zr)2(Ni, Cu) intermetallic layer, which disappeared finally when the brazing temperature exceeded 1020 °C. Fracture analyses indicated that cracks were initialized in the brittle intermetallic layer when (Ti, Zr)2(Ni, Cu) phase existed in the brazing seam. The maximum average shear strength of joints reached 368.6 MPa when brazing was conducted at 1020 °C. Further increasing brazing temperature to 1060 °C, the shear strength was decreased due to the formation of coarse lamellar (α+β)-Ti structure.

Background Antidepressant agents have been shown to be an effective and safe treatment method for patients with globus. However, there are few clinical trials dedicated to studying the effects of antidepressant agents on the natural history and upper oesophageal sphincter (UES) pressure of treated globus patients. Aims To evaluate the effect of paroxetine and amitriptyline to prevent relapses in patients with globus, the simultaneous relationship between changes in UES pressure and improvement of globus symptoms were measured. Methods Globus patients were randomised into amitriptyline, paroxetine and lansoprazole groups for a 6-week treatment period, and follow-up was extended to 12 additional months. Efficacy was evaluated in terms of the Glasgow-Edinburgh Throat Scale (GETS), and UES pressure was measured by standard oesophageal manometry. Results Paroxetine therapy resulted in a higher withdrawal rate due to symptom relapse (15.9% vs 44.1%, P = 0.01; 15.9% vs 64.7, P = 0.001) than amitriptyline and lansoprazole. Furthermore, globus symptoms were alleviated with the decrease of UES pressure after paroxetine and amitriptyline treatment (r = 0.620, P = 0.02; r = 0.575, P = 0.03) Conclusions This follow-up study indicates that paroxetine may alter the natural history of globus and can effectively be used for the long-term management of patients with the disease. Apart from the clinical benefits, paroxetine and amitriptyline can potentially decrease UES pressure.

With 2-(trimethylsilyl)aryl triflates as aryne precursors, an unprecedented three-component carboarylation reaction of unactivated imines with arynes and carbon nucleophiles has been developed to access a variety of functionalized tertiary amines under transition metal-free conditions. Suitable carbon nucleophiles include chloroform, acetonitrile, and methyl propiolate.

An unprecedented use of trifluoromethanesulfonyl hydrazides as effective SCF3 sources has been established in the sulfenylation of indoles. A range of substituted indoles participated in CuCl-catalyzed oxidative sulfenylation reaction with TfNHNHBoc in the presence of dimethyl sulfoxide to furnish structurally diverse 3-indolyl trifluoromethyl thioethers in moderate to good yields with very high regioselectivity.

Ethnopharmacological relevance Diabetic nephropathy (DN) is a major complication of diabetes. The kidney disease develops in nearly 20%–40% of type 2 diabetes (T2D) patients. Ginseng is the root of Panax ginseng C. A. Meyer and has been used in prevention and treatment of diseases for more than 2000 years as a traditional oriental medicine. The 20(R)-ginsenoside Rg3, an active saponin isolated from ginseng, can prevent and treat many diseases. The object of this research was to explore the alleviative effects of 20(R)-Rg3 on DN in mice. Materials and methods The T2D animal model was induced by continuous access to a high fat diet (HFD) combined with a single injection of 100 mg/kg streptozotocin (STZ) in C57BL/6 mice. The mice were treated by oral gavage of the 20(R)-Rg3 (10, 20 mg/kg) for 8 weeks. Functional and histopathological analyses of the kidneys were then performed. Protein expression levels of MAPKs and NF-κB signal pathways in the kidney were evaluated by western blotting. The expressions of HO-1 and NF-κB in the kidney were measured by fluorescent labeling staining. Other assessments including fasting blood glucose (FBG) levels, blood lipids, oxidative indicators, and inflammatory factors were all performed. Results Abnormally elevated FBG levels were observed in HFD/STZ mice, contributing significantly to the occurrence of DN. Simultaneously, HFD/STZ mice showed the rise of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the decrease in high density lipoprotein cholesterol (HDL-C). DN was evidenced by the overproduction of malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, high levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Simultaneously, the results of the immunofluorescence assay showed an increased expression level in NF-κB p65 while a decrease in antioxidant enzyme HO-1 was observed. Herein, 20(R)-Rg3 treatment for 8 weeks not only attenuated FBG levels and advanced glycation end products (AGEs) levels but also improved insulin (INS) level, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF-κB signal pathways in DN mice. Conclusion Taken together, the findings from the present study explicitly confirmed that 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation.

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R 2 = 0.318, P

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P0.01, n = 8) and blood vessel wall thickness in SHR (P0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.

Recently, car-parts suppliers all over the world are facing their margins under growing pressure due to intensified competition and the cost of innovation. In order to address these issues, most companies engage in redesigning production operations. This paper proposes an innovative approach consist of TRIZ and simulation technology, through which the unbalanced issues occurring in production lines could be found out, and suggestions for improvement can be put forward. The first step of this methodology framework is to define the technical problems using the FAA model. Secondly, a contradiction matrix is used for selecting tools resolving the problem potentially. Thirdly, the inventive principle are applied to generate the solutions against actual conditions. Fourthly, during the evaluation phase, the simulation software Witness and it’s optimization module are used to get an accurate flexible production schedule. In this study, an car-part supplier named HT company was taken as a case study; the comparative data showed that the company’s direct economic benefits is increased, the customer satisfaction and the workshop management level are improved.

Objectives: Based on previous reports that ginsenosides have been shown to exert better preventive effects on cisplatin‐induced kidney injury, the present work aims to evaluate the protective effects of ginsenoside Rb3 (G‐Rb3) on cisplatin‐induced renal damage and underlying mechanisms in vivo and in vitro. Materials and methods: The protective effect of G‐Rb3 on cisplatin‐induced acute renal failure in ICR mouse model and HEK293 cell model was investigated, and the underlying possible mechanisms were also explored. For animal experiment, renal function, kidney histology, inflammation, oxidative stress, relative protein molecules involved in apoptosis and autophagy signalling pathways were assessed. In addition, rapamycin (a specific inhibitor of mTOR), compound C (a specific inhibitor of AMPK) and acetylcysteine (NAC, a specific ROS scavenger) were employed to testify the effects of AMPK/mTOR signal pathway on the protective effects of G‐Rb3 in HEK293 cells. Results: Pre‐treatment with G‐Rb3 at doses of 10 and 20 mg/kg for ten days significantly reversed the increases in serum creatinine (CRE), blood urea nitrogen (BUN) and malondialdehyde (MDA), and decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Histopathological examination further revealed that G‐Rb3 inhibited cisplatin‐induced nephrotoxicity. G‐Rb3 diminished cisplatin‐induced increase in protein expression levels of p62, Atg3, Atg5 and Atg7, and decrease in protein expression level of p‐mTOR and the ratio of LC3‐I/LC3‐II, indicating that G‐Rb3 suppressed cisplatin‐induced activation of autophagy. Inhibition of autophagy induced inactivation of apoptosis, which suggested that autophagy played an adverse effect on cisplatin‐evoked renal damage. Further, we found that G‐Rb3 might potentially modulate the expressions of AMPK‐related signal pathways. Conclusions: These findings clearly suggested that G‐Rb3‐mediated alleviation of cisplatin‐induced nephrotoxicity was in part due to regulation of AMPK‐/mTOR‐mediated autophagy and inhibition of apoptosis in vitro and in vivo.

To ensure that vertical lifeline systems (VLLSs) are well designed, calculation methods are required to estimate the extension of a personal energy absorber (PEA) (xPEA) and the total fall distance...

Recently, although ginseng ( Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by β-adrenergic receptors (β-ARs). However, α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

Azobenzene is a switchable compound that exhibits reversible trans–cis photoisomerization. Photoresponsive polymers have been prepared by incorporating azobenzene groups into polymers. Most of the reported azobenzene-containing polymers (azopolymers) have only one azobenzene group in the repeat unit of the polymers (mono-azopolymers). To improve photoresponsiveness, multi-azobenzene groups have been covalently or non-covalently introduced into the repeat units of azopolymers (multi-azopolymers). In this Perspective, we introduce photoresponsive multi-azopolymers. We summarize the preparation of such polymers and highlight their potential applications in photoactuation, photo-patterning, and photoinduced birefringence. The innovative potential, open questions, and remaining challenges in this field are also discussed.

Recent timing observation provides an intriguing result for the braking index of the X-ray pulsar PSR J1640-4631, which has a measured braking index $n=3.15\pm0.03$. The decrease of the inclination angle between between the spin axis and the magnetic axis can be responsible for such a high braking index. However, the physical mechanisms causing the change of the magnetic inclination angle have not been fully understood. In this Letter, we apply a two-dipole model given by Hamil et al (2016) to explain the decrease of the magnetic inclination angle of PSR J1640-4631. The rotation effect of a charged sphere and the magnetization of ferromagnetically ordered material produce magnetic moments $M_{1}$ and $M_{2}$, respectively. There exist a minimum of the potential energy for the magnetic moment $M_{2}$ in the magnetic field of $M_{1}$, hence the $M_{2}$ will freely rotate around the minimum energy position (i. e equilibrium position), similar to a simple pendulum. Our calculation indicate the magnetic moment $M_{2}$ would evolve towards alignment with the spin axis for PSR J1640-4631, and cause the magnetic inclination angle to decrease. The single peak in the pulse profile favors a relatively low change rate of the magnetic inclination angle., Comment: 5 pages, 2 figures, PASJ in press

According to the recycling model, neutron stars in low-mass X-ray binaries were spun up to millisecond pulsars (MSPs), which indicates that all MSPs in the Galactic plane ought to be harbored in binaries. However, about $20\%$ Galactic field MSPs are found to be solitary. To interpret this problem, we assume that the accreting neutron star in binaries may collapse and become a strange star when it reaches some critical mass limit. Mass loss and a weak kick induced by asymmetric collapse during the phase transition (PT) from neutron star to strange star can result in isolated MSPs. In this work, we use a population-synthesis code to examine the PT model. The simulated results show that a kick velocity of $\sim60~{\rm km~s}^{-1}$ can produce $\sim6\times10^3$ isolated MSPs and birth rate of $\sim6.6\times10^{-7} {\rm ~yr}^{-1}$ in the Galaxy, which is approximately in agreement with predictions from observations. For the purpose of comparisons with future observation, we also give the mass distributions of radio and X-ray binary MSPs, along with the delay time distribution., Comment: 9 pages, 11 figures, accepted to publish on A&A

Colorectal cancer (CRC) is the third most common type of cancer. In recent decades, genomic analysis has played an increasingly important role in understanding the molecular mechanisms of CRC. However, its pathogenesis has not been fully uncovered. Identification of genes related to CRC as complete as possible is an important way to investigate its pathogenesis. Therefore, we proposed a new computational method for the identification of novel CRC-associated genes. The proposed method is based on existing proven CRC-associated genes, human protein-protein interaction networks, and random walk with restart algorithm. The utility of the method is indicated by comparing it to the methods based on Guilt-by-association or shortest path algorithm. Using the proposed method, we successfully identified 298 novel CRC-associated genes. Previous studies have validated the involvement of the majority of these 298 novel genes in CRC-associated biological processes, thus suggesting the efficacy and accuracy of our method.

In order to reduce SO2 emissions and achieve green utilization of sulfur resources, a desulfurization method of SO2 removal using hydrogen peroxide (H2O2) in rotating packed bed (RPB) is proposed. It can not only achieve the efficient removal of SO2, but also lead to the effective utilization of sulfur resources. A mathematic model was first developed to describe the reaction and mass transfer process between H2O2 and SO2 in RPB. The influences of different operating conditions including RPB rotating speed, H2O2 mass fraction, gas–liquid volumetric flow rate ratio, gas flux, and inlet SO2 concentration on desulfurization performance were studied. Under the optimized conditions, it turned out that the desulfurization efficiency was above 99% and the outlet SO2 concentration was ultra-low, below 35 mg/m3. The validity of the model was confirmed by the fact that most of the predicted desulfurization efficiency agreed well with the experimental result with a deviation within 5%. The height of mass transfer unit HTU for RPB is calculated to be 1.60–2.07 cm, which is one order of magnitude lower than that of conventional reactors, indicating the investment of the desulfurization reactor can be greatly reduced by using RPB.

Asgard is a newly proposed archaeal superphylum, which has been suggested to hold the key to decipher the origin of Eukaryotes. However, their ecology remains largely unknown. Here, we conducted a meta-analysis of publicly available Asgard-associated 16S rRNA gene fragments, and found that just three previously proposed clades (Lokiarchaeota, Thorarchaeota, and Asgard clade 4) are widely distributed, whereas the other seven clades (phylum or class level) are restricted to the sediment biosphere. Asgard archaea, especially Loki- and Thorarchaeota, seem to adapt to marine sediments, and water depth (the depth of the sediment below water surface) and salinity might be crucial factors for the proportion of these microorganisms as revealed by multivariate regression analyses. However, the abundance of Asgard archaea exhibited distinct environmental drivers at the clade-level; for instance, the proportion of Asgard clade 4 was higher in less saline environments (salinity6.35 psu), while higher for Heimdallarchaeota-AAG and Asgard clade 2 in more saline environment (salinity ≥35 psu). Furthermore, co-occurrence analysis allowed us to find a significant non-random association of different Asgard clades with other groups (e.g., Lokiarchaeota with Deltaproteobacteria and Anaerolineae; Odinarchaeota with Bathyarchaeota), suggesting different interaction potentials among these clades. Overall, these findings reveal Asgard archaea as a ubiquitous group worldwide and provide initial insights into their ecological features on a global scale.

In Huang and Teng (2020), the effects of the channel walls on the second-order hydrodynamic characteristics of three-dimensional bodies in monochromatic incident waves were investigated. To ensure the high accuracy and efficiency of the calculation, robust numerical algorithms have been developed to treat the troublesome integrals over the free surface, body surface and up- and down-wave vertical surfaces involved in the second-order analysis. In the present study, Huang and Teng (2020)'s work is extended to the cases of bichromatic incident waves, and some improvements in the numerical algorithms are made. The expressions of the locked potentials including both the propagating and evanescent modes are derived. Since the up- and down-wave vertical surfaces are allowed to be placed close to the body, the calculation of the free surface integral can be performed in a small region, and an analytical method is developed to directly evaluate the up- and down-wave vertical surface integrals. After solving the boundary integral equation, the sum- and difference-frequency radiation and diffraction potentials are obtained explicitly. Numerical results for the quadratic transfer functions of the second-order free surface elevation, pressure and force are given for a series of geometries in channels.

An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K+- and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction.