Inspired by their potential biosynthesis, we have developed divergent total syntheses of seven monoterpene indole alkaloids including mersicarpine, leuconodines B and D, leuconoxine, melodinine E, ...leuconolam, and rhazinilam, and one unnatural analogue with an unprecedented structural skeleton. The key steps involve a Witkop–Winterfeldt oxidative indole cleavage followed by transannular cyclization. The transannular cyclization product was then converted to the corresponding structural skeletons by pairing its functional groups into different reaction modes.
Due to the double-salient structure of the switched reluctance motor (SRM) and highly magnetic saturation, its rotor position shows highly nonlinear function with phase current and flux linkage. ...Therefore, the establishment of accurate and small-scale SRM rotor position model is crucial to realize SRM position sensorless control. This paper is based on SRM flux characteristics collected by actual measurement, then adopts back-propagation neural network (BPNN) with improved algorithm and radial basis function neural network (RBFNN), respectively, to build SRM rotor position model. It is concluded that the model built by BPNN based on the Levenberg-Marquardt algorithm has smaller network structure and higher accuracy than RBFNN. In order to optimize BPNN model further, two kinds of pretreatment methods are used to study SRM rotor position model, respectively, and the modeling results of these two methods are compared. Adopting pretreatment method could reduce scale and improve accuracy to achieve the model optimization. After initial rotor position was estimated accurately without rotor position sensor, experiments are performed based on a three-phase 12/8 SRM. The experimental results verify that the BPNN model of rotor position for SRM based on a pretreatment method could be applied to SRM position sensorless control.
Cadmium (Cd) is a toxic pollutant in industrial production that induces organ damage and apoptosis, While, selenium (Se) has the biological function of antagonizing Cd toxicity. Hence, to gain ...further insight into the protective mechanisms of selenium against Cd-induced damage in Ctenopharyngodon idella liver (L8824) cells, L8824 were exposed to 5 μM, 15 μM, 25 μM cadmium chloride for 24 h after pre-incubation with 25 μM sodium selenite for 9 h. Cell proliferation and morphological changes, the levels of reactive oxygen species (ROS) and antioxidant enzyme activity, mitochondrial membrane potential (MMP), endoplasmic reticulum stress (ERS)-related pathway genes expression, intracellular calcium levels and apoptosis were assessed to explore the protective effect of selenium in Cd-induced L8824 cell damage. The results showed that Cd caused decreased cell viability, ROS accumulation, reduced activity of antioxidant enzymes (SOD, CAT GPx and T-AOC) and apoptosis in L8824 cells. The incubation of Se prominently ameliorated cell proliferation, activated the Keap1-Nrf2 pathway, and restored antioxidant enzyme activity. Furthermore, the expression of grp78, perk, eif-2α, atf4, chop bax, jnk, caspase-3 and caspase-9 was significantly upregulated after Cd exposure, while the expression of bcl-2 was significantly downregulated. Se supplementation alleviated Cd-induced ERS and apoptosis. Moreover, Cd-induced elevation of intracellular Ca2+ levels were alleviated by dantrolene and 2-APB, suggesting that intracellular calcium disorders were caused by Ca2+ released by RyR and IP3R-mediated ER. The results of this study suggested that Cd could induce oxidative stress, ERS, mitochondrial damage and evoke apoptosis, whereas Se had protective effects in preventing Cd induced damage by inhibiting ERS, maintaining intracellular calcium homeostasis, enhancing the antioxidant capacity of L8824 cells and downregulating the Keap1/Nrf2 pathway.
•Selenium alleviates endoplasmic reticulum stress and intracellular calcium disorders caused by cadmium exposure.•Selenium reduces oxidative damage caused by cadmium exposure by activating the NRF2-Keap1 signaling pathway.•Selenium reduces L8824 cell proliferation inhibition and apoptosis caused by cadmium exposure.
Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that ...directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in
. The engineered
showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines
and
. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered
altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered
attenuated DSS-induced colitis in mice
suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.
Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue ...architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.
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Airborne electromagnetics is an effective and efficient exploration tool in shallow mineral exploration for its high efficiency and low cost. In 2016, airborne electromagnetic and airborne magnetic ...surveys have been carried out at the border of Xinjiang Uygur Autonomous Region and Gansu Province, the Northwest China. With an integrated system, the airborne electromagnetics and airborne magnetic data were collected simultaneously by AreoTEM-IV system from Aeroquest International Limited in Vancouver, BC, Canada, and the CS3 Cesium Vapor magnetometer from Scintrex in Concord, ON, Canada. About 3149 line-km of both data with 250 m line space were acquired. After data processing, the comprehensive analysis and interpretation of resistivity and magnetic anomalies has been carried out to infer lithological structure and outline the potential ore deposits. Verified by the ground surveys, seven outlined anomalies are consistent with the known ore sites, and one new gold deposit and several mineralization clues were found. The prospective reserves of gold are expected to exceed 10 tons. Besides, some prospecting target areas were outlined as the possible locations of copper–nickel deposits. The successful case shows the airborne magnetic data accords with geological structures, and the airborne electromagnetic method is effective in finding metal mineral resources, which can help to quickly identify potential ore targets with no surface outcrop.
Using the NCEP/NCAR reanalysis and station observations in China during 1979–2018, features of propagation of baroclinic wave packets in the upper troposphere and their relationships with ...precipitation over the middle and lower reaches of the Yangtze River (MLRYR) in daily climatology are investigated after having components with periods longer than 9 days filtered out. It is demonstrated that in the filtered daily climatology, the baroclinic wave packets still exist. The wave packet migrates eastward on the northern sides of the westerly jet stream axis whereas it does not move explicitly in the southern side of the axis in the upper troposphere. The filtered daily precipitation over MLRYR is mainly affected by the wave packets in the region south of the westerly jet axis. These results are very meaningful for better understanding behaviors of Rossby waves in daily climatology and the causes of daily precipitation variations in MLRYR.
One‐point time‐lag regressions (greenish shaded contours) as obtained by regressing wave envelope , which is derived from filtered time‐series of 40‐year mean summer in the study domain, onto at base point (30°N, 117.5°E) (black thick dot). Big red dots are for the center of wave packet in the region west of 60°E. Arrows in blue are for the wave activity fluxes, which are derived from the geostrophic stream function by employing the regression analysis considering the time‐lags. The time lags are set to be ‐3d‐0d.
A new solution to the high-quality 3D reverse modeling problem of complex surfaces for fine workpieces is presented using a laser line-scanning sensor. Due to registration errors, measurement errors, ...deformations, etc., a fast and accurate method is important in machine vision measurement. This paper builds a convenient and economic multi-view stereo (MVS) measurement system based on a linear stage and a rotary stage to reconstruct the measured object surface completely and accurately. In the proposed technique, the linear stage is used to generate the trigger signal and synchronize the laser sensor scanning; the rotary stage is used to rotate the object and obtain multi-view point cloud data, and then the multi-view point cloud data are registered and integrated into a 3D model. The measurement results show a measurement accuracy of 0.075 mm for a 360° reconstruction in 34 s, and some evaluation experiments were carried out to demonstrate the validity and practicability of the proposed technique.
The considerable heat treatment induced runout value in the end face of the automobile main reducer gear is always dimensionally out of tolerance. It directly affects the dimensional accuracy, the ...grade of carburized and hardened gears, and the post-quenching manufacturing costs. In this study, three dimensional numerical models were developed to simulate the carburizing-quenching process of gear based on the multi-field coupling theory using DEFORM software. The results indicated that the ununiform cooling rate of the gear caused by the asymmetry of the web structure would result in the ununiform distribution of martensite, leading to the large runout value at the end face of the gear. Therefore, a novel method was proposed to minimize the heat treatment induced runout value. It was found that the heat treatment induced runout value could be effectively controlled by the addition of a compensation ring and the support of a rod structure. Further experiments showed that the average runout value of the gear end face before and after the proposed heat treatment method were about 0.023 mm and 0.059 mm respectively, which was in good agreement with the simulated results. The novel approach proposed in this study led to a reduction of the gear runout value by 70.0%‒76.9% compared to that of the original heat treatment process, which may serve as a practical and economical way to predict and minimize the heat treatment induced distortion in drive gear.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that affects premenopausal women. The etiology of PCOS is multifaceted, involving various genetic and epigenetic ...factors, hypothalamic-pituitary-ovarian dysfunction, androgen excess, insulin resistance, and adipose-related mechanisms. High-fat diets (HFDs) has been linked to the development of metabolic disorders and weight gain, exacerbating obesity and impairing the function of the hypothalamic-pituitary-ovarian axis. This results in increased insulin resistance, hyperinsulinemia, and the release of inflammatory adipokines, leading to heightened fat synthesis and reduced fat breakdown, thereby worsening the metabolic and reproductive consequences of PCOS. Effective management of PCOS requires lifestyle interventions such as dietary modifications, weight loss, physical activity, and psychological well-being, as well as medical or surgical interventions in some cases. This article systematically examines the pathological basis of PCOS and the influence of HFDs on its development, with the aim of raising awareness of the connection between diet and reproductive health, providing a robust approach to lifestyle interventions, and serving as a reference for the development of targeted drug treatments.