Denoising coherent Doppler lidar data based on a U-Net convolutional neural network.

The coherent Doppler wind lidar (CDWL) has long been thought to be the most suitable technique for wind remote sensing in the atmospheric boundary layer (ABL) due to its compact size, robust performance, and low-cost properties. However, as the coherent lidar exploits the Mie scattering from aerosol particles, the signal intensity received by the lidar is highly affected by the concentration of aerosols. Unlike air molecules, the concentration of aerosol varies greatly with time and weather, and decreases dramatically with altitude. As a result, the performance of the coherent lidar fluctuates greatly with time, and the detection range is mostly confined within the planetary boundary layer. The original data collected by the lidar are first transformed into a spectrogram and then processed into radial wind velocities utilizing algorithms such as a spectral centroid. When the signal-to-noise ratio (SNR) is low, these classic algorithms fail to retrieve the wind speed stably. In this work, a radial wind velocity retrieving algorithm based on a trained convolutional neural network (CNN) U-Net is proposed for denoising and an accurate estimate of the Doppler shift in a low-SNR regime. The advantage of the CNN is first discussed qualitatively and then proved by means of a numerical simulation. Simulated spectrum data are used for U-Net training and testing, which show that the U-Net is not only more accurate than the spectral centroid but also achieves a further detection range. Finally, joint observation data from the lidar and radiosonde show excellent agreement, demonstrating that the U-Net-based retrieving algorithm has superior performance over the traditional spectral centroid method both in accuracy and detection range.

Inhibition of NLRP1 inflammasome improves autophagy dysfunction and Aß disposition in APP/PS1 mice.

Increasing evidence has shown that the NOD-like receptor protein 1 (NLRP1) inflammasome is associated with Aß generation and deposition, which contributes to neuronal damage and neuronal-inflammation in Alzheimer's disease (AD). However, the specific mechanism of NLRP1 inflammasome in the pathogenesis of AD is still unclear. It has been reported that autophagy dysfunction can aggravate the pathological symptoms of AD and plays an important role in regulating Aß generation and clearance. We hypothesized that NLRP1 inflammasome activation may induce autophagy dysfunction contributing to the progression of AD. In the present study, we observed the relationship between Aß generation and NLRP1 inflammasome activation, as well as AMPK/mTOR mediated-autophagy dysfunction in WT 9-month-old (M) mice, APP/PS1 6 M and APP/PS1 9 M mice. Additionally, we further studied the effect of NLRP1 knockdown on cognitive function, Aß generation, neuroinflammation and AMPK/mTOR mediated autophagy in APP/PS1 9 M mice. Our results indicated that NLRP1 inflammasome activation and AMPK/mTOR mediated-autophagy dysfunction are closely implicated in Aß generation and deposition in APP/PS1 9 M mice, but not in APP/PS1 6 M mice. Meanwhile, we found that knockdown of NLRP1 significantly improved learning and memory impairments, decreased the expressions of NLRP1, ASC, caspase-1, p-NF-κB, IL-1ß, APP, CTF-ß, BACE1 and Aß1-42, and decreased the level of p-AMPK, Beclin 1 and LC3 II, and increased the level of p-mTOR and P62 in APP/PS1 9 M mice. Our study suggested that inhibition of NLRP1 inflammasome activation improves AMPK/mTOR mediated-autophagy dysfunction, resulting in the decrease of Aß generation, and NLRP1 and autophagy might be important targets to delay the progression of AD.

Metastable helium Faraday filter for helium lidar to measure the density of the thermosphere.

We demonstrate a metastable helium Faraday optical filter operating on the 23S1 - 23P1 and 23S1 - 23P2 transition at 1083 nm by using a 3 cm long helium cell. The influence of the magnetic field and gas pressure of the helium cell on the filter characteristics is experimental studied. When the magnetic field is 230 Gs and the gas pressure of helium cell is about 110 Pa, the peak transmission corresponding to the two energy level transitions is about 32% and 57%, respectively. The equivalent noise bandwidth (ENBW) under this working condition is about 1.9 GHz. The metastable helium Faraday filter can be used to improve the optical inefficiency of a helium resonance fluorescence lidar to achieve the metastable helium density detection at 200-1000 km thermosphere.

Fine gust front structure observed by coherent Doppler lidar at Lanzhou Airport (103°49$

Coherent Doppler lidar (CDL) has long been used to automatically identify gust front-induced wind shear signatures from the velocity data, but rare attention has been given to the fine structure of wind gust fronts. In this work, a compact and robust CDL with high efficiency and accuracy is equipped at Lanzhou Airport (103°49$^{\prime}$'E, 36°03$^{\prime}$'N) to conduct interpretation of wind gust front structures by using high-resolution CDL data. Outflows of gust fronts could be detected reliably from radial velocities, spectral widths, as well as radial shears. For the case study presented here, photographs of the velocity and spectrum width capacitates gust front characteristics such as height, advance speed, and radial shear, as well as vertical structure to be displayed in minute detail. Besides, the quasi-continuous vertical wind reveals the potential turbulent mixing and vertical transport process during the gust front event, which makes CDL a very attractive and essential technique for future development of gust front automatic detection systems.

Ultraviolet trifrequency Rayleigh DWL for stratosphere atmospheric wind measurements during the daytime based on an ultranarrow-bandwidth optical receiver.

An ultranarrow-bandwidth-optical-receiver-based ultraviolet trifrequency Rayleigh Doppler wind lidar (DWL) technology is proposed that is able to simultaneously detect stratospheric wind with high precision during the daytime. The lidar system is designed, and the principle of wind measurement is analyzed. An ultranarrow-bandwidth element used for suppressing strong background light is designed as an important part of the ultranarrow-bandwidth optical receiver. A three-channel Fabry-Perot interferometer (FPI) is capable of measuring wind speed. A non-polarized beam splitter cube optically contacted on the three-channel FPI can offer a stable splitting ratio. The parameters of the three-channel FPI are optimized. The structure and parameters of the ultranarrow-bandwidth element are designed, and the transmission curve is measured. The transmission curve and stability of the three-channel FPI are validated. The background photon number is collected with the ultranarrow-bandwidth element and with an interference filter (IF) alternately from 08:00 to 18:00. Based on the selected system parameters and measured background photon number, the detection performance of the proposed lidar is simulated. Simulation results show that with 200 m range resolution from 15 to 25 km, 500 m range resolution from 25 to 40 km, and 30 min total accumulation time for paired line-of-sight (LOS) measurement, within $\pm {100}\;{\rm m/s}$±100m/s LOS wind speed range, the daytime LOS wind speed error is below 4.77 m/s from 15 to 40 km altitude. Compared with the traditional IF-based dual-FPI Rayleigh Doppler lidar, the wind speed accuracies are improved by 1.29-16.29 times and the detection altitudes are improved from 23.55 to 40 km with the same wind-detecting precision.

Demonstration of daytime wind measurement by using mobile Rayleigh Doppler Lidar incorporating cascaded Fabry-Perot etalons.

A well-designed filter assembly is incorporated to an earlier mobile Rayleigh Doppler Lidar developed at University of Science and Technology of China (USTC) for wind measurement round the clock. The filter assembly consists of two cascaded Fabry-Perot Etalons (FPEs) and a narrow-band interference filter (IF), which are optimized to filter out strong solar background radiation during daytime. The high resolution FPE is mainly used to compress the whole bandwidth of the filter assembly, whereas the low resolution FPE with relatively large free spectral range (FSR) is primarily used to block the unwanted periodic transmission peaks of high resolution FPE arising within the narrow-band IF passband. Some test experiments are carried out and demonstrate that the filter assembly have an overall peak transmission of 33.32% with a bandwidth of 2.41 pm at 355 nm. When applying it to the USTC mobile Rayleigh Doppler Lidar, the daytime background is only 3% or less than before. Consequently, the detectable altitude during daytime increases to ∼51 km with wind velocity accuracy of ±7.6 m/s.

Novel Lidar algorithm for horizontal visibility measurement and sea fog monitoring.

Traditionally, Klett and Fernald inversion estimates an initial value using the slope method for horizontal visibility, which causes inversion uncertainty. We proposed an algorithm to retrieve the extinction coefficient and visibility distribution information from scanning Lidar to overcome instability due to initial atmospheric extinction coefficient choice and assuming the Lidar ratio. Numerical simulations showed that extinction coefficient maximum relative was much larger for inhomogeneous atmosphere using the Klett method, reaching 0.31. In contrast, it is only 0.049 using the proposed algorithm. Experimental showed that the proposed algorithm and scanning Lidar system provide very high stability and accuracy, can work in different weather conditions and monitor sea fog evolution over real time, and is suitable for various situations with different visibility.

Gravity waves observation of wind field in stratosphere based on a Rayleigh Doppler lidar.

Simultaneous wind and temperature measurements in stratosphere with high time-spatial resolution for gravity waves study are scarce. In this paper we perform wind field gravity waves cases in the stratosphere observed by a mobile Rayleigh Doppler lidar. This lidar system with both wind and temperature measurements were implemented for atmosphere gravity waves research in the altitude region 15-60 km. Observations were carried out for two periods of time: 3 months started from November 4, 2014 in Xinzhou, China (38.425°N,112.729°E) and 2 months started from October 7, 2015 in Jiuquan, China (39.741°N, 98.495°E) . The mesoscale fluctuations of the horizontal wind velocity and the two dimensional spectra analysis of these fluctuations show the presence of dominant oscillatory modes with wavelength of 4-14 km and period of around 10 hours in several cases. The simultaneous temperature observations make it possible to identify gravity wave cases from the relationships between different variables: temperature and horizontal wind. The observed cases demonstrate the Rayleigh Doppler Lidar's capacity to study gravity waves.

Mobile Rayleigh Doppler lidar for wind and temperature measurements in the stratosphere and lower mesosphere.

A mobile Rayleigh Doppler lidar based on the molecular double-edge technique is developed for measuring wind velocity in the middle atmosphere up to 60 km. The lidar uses three lasers with a mean power of 17.5 W at 355 nm each and three 1 m diameter telescopes to receive the backscattered echo: one points to zenith for vertical wind component and temperature measurement; the two others pointing toward east and north are titled at 30° from the zenith for zonal and meridional wind component, respectively. The Doppler shift of the backscattered echo is measured by inter-comparing the signal detected through each of the double-edge channels of a triple Fabry-Perot interferometer (FPI) tuned to either side of the emitted laser line. The third channel of FPI is used for frequency locking and a locking accuracy of 1.8 MHz RMS (root-mean-square) at 355 nm over 2 hours is realized, corresponding to a systematic error of 0.32 m/s. In this paper, we present detailed technical evolutions on system calibration. To validate the performance of the lidar, comparison experiments was carried out in December 2013, which showed good agreement with radiosondes but notable biases with ECMWF (European Centre for Medium range Weather Forecasts) in the height range of overlapping data. Wind observation over one month performed in Delhi (37.371° N, 97.374° E), northwest of China, demonstrated the stability and robustness of the system.

Stratospheric temperature measurement with scanning Fabry-Perot interferometer for wind retrieval from mobile Rayleigh Doppler lidar.

Temperature detection remains challenging in the low stratosphere, where the Rayleigh integration lidar is perturbed by aerosol contamination and ozone absorption while the rotational Raman lidar is suffered from its low scattering cross section. To correct the impacts of temperature on the Rayleigh Doppler lidar, a high spectral resolution lidar (HSRL) based on cavity scanning Fabry-Perot Interferometer (FPI) is developed. By considering the effect of the laser spectral width, Doppler broadening of the molecular backscatter, divergence of the light beam and mirror defects of the FPI, a well-behaved transmission function is proved to show the principle of HSRL in detail. Analysis of the statistical error of the HSRL is carried out in the data processing. A temperature lidar using both HSRL and Rayleigh integration techniques is incorporated into the Rayleigh Doppler wind lidar. Simultaneous wind and temperature detection is carried out based on the combined system at Delhi (37.371°N, 97.374°E; 2850 m above the sea level) in Qinghai province, China. Lower Stratosphere temperature has been measured using HSRL between 18 and 50 km with temporal resolution of 2000 seconds. The statistical error of the derived temperatures is between 0.2 and 9.2 K. The temperature profile retrieved from the HSRL and wind profile from the Rayleigh Doppler lidar show good agreement with the radiosonde data. Specifically, the max temperature deviation between the HSRL and radiosonde is 4.7 K from 18 km to 36 km, and it is 2.7 K between the HSRL and Rayleigh integration lidar from 27 km to 34 km.

Columbianadin ameliorates rheumatoid arthritis by attenuating synoviocyte hyperplasia through targeted vimentin to inhibit the VAV2/Rac-1 signaling pathway.

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease pathologically characterized by synovial inflammation. The abnormal activation of synoviocytes seems to accompany the progression of RA. The role and exact molecular mechanism in RA of columbianadin (CBN) which is a natural coumarin is still unclear. OBJECTIVES: The present research aimed to investigate the effect of vimentin on the abnormal growth characteristics of RA synoviocytes and the targeted regulatory role of CBN. METHODS: Cell migration and invasion were detected using the wound healing and transwell method. Mechanistically, the direct molecular targets of CBN were screened and identified by activity-based protein profiling. The expression of relevant proteins and mRNA in cells and mouse synovium was detected by western blotting and qRT-PCR. Changes in the degree of paw swelling and body weight of mice were recorded. H&E staining, toluidine blue staining, and micro-CT were used to visualize the degree of pathological damage in the ankle joints of mice. Small interfering RNA and plasmid overexpression of vimentin were used to observe their effects on MH7A cell proliferation, migration, apoptosis, and downstream molecular signaling. RESULTS: The TNF-α-induced proliferation and migration of MH7A cells could be significantly repressed by CBN (25,50 µM), and the expression of apoptosis and autophagy-associated proteins could be modulated. Furthermore, CBN could directly bind to vimentin and inhibit its expression and function in synoviocytes, thereby ameliorating foot and paw swelling and joint damage in CIA mice. Silencing and overexpression of vimentin might be involved in developing RA synovial hyperplasia and invasive cartilage by activating VAV2 phosphorylation-mediated expression of Rac-1, which affects abnormal growth characteristics, such as synoviocyte invasion and migration. CONCLUSION: CBN-targeted vimentin restrains the overactivation of RA synoviocytes thereby delaying the pathological process in CIA mice, which provides valuable targets and insights for understanding the pathological mechanisms of RA synovial hyperplasia.

The impact of climate change on the water quality of Baiyangdian Lake (China) in the past 30 years (1991-2020).

Climate change significantly influenced the water quality of lakes in recent decades. This study investigated the effects of climate change on the water quality of Baiyangdian Lake (China) in the past 30 years (1991-2020) using correlation analysis, regression analysis, and the generalized additive model (GAM). The results show that water quality grade, chemical oxygen demand (COD), total phosphorus (TP) concentrations, and annual average and minimum air temperatures of the lake showed significant differences (p < 0.05) in the one-way ANOVA during the studied period. The concentration of dissolved oxygen (DO) and TP, annual average and minimum air temperatures, and annual precipitation decreased, while the COD and total nitrogen (TN) concentration, annual maximum temperature, and monthly maximum precipitation increased. The annual average and minimum air temperature affected all water quality variables and explained 12.3 %-54.5 % of variation deviation in correlation and GAM analyses, indicating that the changes of air temperature influenced the water temperature, which then affected the biochemical reaction rates leading to changes in water quality. The precipitation factors explained 10.5 % (TN) to 54.8 % (TP) of variation deviation, implying that the increase in precipitation improved water quality by diluting the COD concentration. However, excessive precipitation also accelerated the endogenous release of phosphorus in sediments by increasing the TP concentration. Additionally, extreme climate factors correlated with some water quality variables and explained 57.7 %-95.9 % of the total variances in correlation and regression analyses, suggesting that the extreme temperatures changed the nitrogen and DO concentration to aggravate lake pollution. However, the extreme precipitation purified the water through dilution. This study will facilitate to understand the impacts of climate change on water quality and find appropriate adaptation measures for ecosystem management of shallow lakes.

Therapeutic effects of columbianadin from Angelicae Pubescentis radix on the progression of collagen-induced rheumatoid arthritis by regulating inflammation and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelicae pubescentis radix (APR) has a long history in the treatment of rheumatoid arthritis (RA) in China. It has the effects of dispelling wind to eliminate dampness, removing arthralgia and stopping pain in the Chinese Pharmacopeia, but its mechanisms was remained unclear. Columbianadin (CBN), one of the main bioactive compounds of APR, has many pharmacological effects including anti-inflammatory and immunosuppression. However, there are few reports on therapeutic effect of CBN on RA. AIM OF THE STUDY: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and multiple molecular biological methods was adopted to evaluate the therapeutic effects of CBN on collagen-induced arthritis (CIA) mice and explore the potential mechanisms. MATERIALS AND METHODS: A variety of pharmacodynamic methods were used to evaluate the therapeutic effect of CBN on CIA mice. The microbial and metabolic characteristics of CBN anti-RA were obtained by metabolomics and 16S rRNA sequencing technology. The potential mechanism of CBN anti-RA was predicted through bioinformatics network analysis, and verified by a variety of molecular biology methods. RESULTS: CBN can effectively improved symptoms of rheumatoid arthritis in CIA mice, including paw swelling and arthritic scores. The inflammatory and oxidative stress were effectively regulated by the treatment of CBN. The fecal microbial communities and serum and urine metabolic compositions were significantly altered in CIA mice, CBN can ameliorate the CIA-associated gut microbiota dysbiosis, and regulate the disturbance of serum and urine metabolome. The acute toxicity test showed that the LD50 of CBN was greater than 2000 mg kg-1. CONCLUSIONS: CBN exert anti-RA effects from four perspectives: inhibiting inflammatory response, regulating oxidative stress, and improving changes in gut microbiota and metabolites. The JAK1/STAT3, NF-κB and Keap1/Nrf2 pathway may be important mechanism for CBN's inflammatory response and oxidative stress activity. CBN could be considered as a potential anti-RA drug for further study.

Ginsenoside Rg1 attenuates glomerular fibrosis by inhibiting CD36/TRPC6/NFAT2 signaling in type 2 diabetes mellitus mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg1 (Rg1) is one of the main active components in Panax ginseng C. A. Meyer (ginseng), which has been widely used to delay senescence or improve health conditions for more than 2000 years. Increasing studies have revealed that Rg1 could regulate cell proliferation and differentiation, as well as anti-inflammatory and anti-apoptotic effects, and might have protective effects on many chronic kidney diseases. AIM OF THE STUDY: Diabetic nephropathy (DN) is one of the most dangerous microvascular complications of diabetes and is the leading cause of end-stage renal disease worldwide. However, the role and mechanism of Rg1 against high-glucose and high-fat-induced glomerular fibrosis in DN are not clear. This study aimed to investigate the protective effect of Rg1 on DN and its possible mechanism. MATERIALS AND METHODS: The type 2 diabetes mellitus (T2DM) mice models were established with a high-fat diet (HFD) combined with an intraperitoneal injection of streptozotocin (STZ). Urine protein and serum biochemical indexes were detected by corresponding kits. The kidney was stained with H&E, PAS, and Masson to observe the pathological morphology, glycogen deposition, and fibrosis. The expression of CD36 and p-PLC in the kidney cortex was detected by IHC. The expressions of FN and COL4 were detected by IF. Western blot and PCR were performed to examine protein and mRNA expressions of kidney fibrosis and TRPC6/NFAT2-related pathways in DN mice. Calcium imaging was used to examine the effect of Rg1 on [Ca2+]i in PA + HG-induced human mesangial cells (HMCs). Visualization of the interaction between Rg1 and CD36 was detected by molecular docking. RESULTS: Rg1 treatment for 8 weeks could prominently decrease urinary protein, serum creatinine, and urea nitrogen and downgrade blood lipid levels and renal lipid accumulation in T2DM mice. The pathological results indicated that Rg1 treatment attenuated renal pathological injury and glomerular fibrosis. The further results demonstrated that Rg1 treatment remarkably decreased the expressions of CD36, TRPC6, p-PLC, CN, NFAT2, TGF-ß, p-Smad2/3, COL4, and FN in renal tissues from T2DM mice. Calcium imaging results found that Rg1 downgraded the base levels of [Ca2+]i and ΔRatioF340/F380 after BAPTA and CaCl2 treatment. Molecular docking results showed that Rg1 could interact with CD36 with a good affinity. CONCLUSION: These results revealed that Rg1 could ameliorate renal lipid accumulation, pathological damage, and glomerular fibrosis in T2DM mice. The mechanism may be involved in reducing the overexpression of CD36 and inhibiting the TRPC6/NFAT2 signaling pathway in renal tissues of T2DM mice.

Mid-altitude wind measurements with mobile Rayleigh Doppler lidar incorporating system-level optical frequency control method.

A mobile Rayleigh Doppler lidar based on double-edge technique is developed for mid-altitude wind observation. To reduce the systematic error, a system-level optical frequency control method is proposed and demonstrated. The emission of the seed laser at 1064 nm is used to synchronize the FPI in the optical frequency domain. A servo loop stabilizing the frequency of the seed laser is formed by measuring the absolute frequency of the second harmonic against an iodine absorption line. And, the third harmonic is used for Rayleigh lidar detection. The frequency stability is 1.6 MHz at 1064 nm over 2 minutes. A locking accuracy of 0.3 MHz at 1064 nm is realized. In comparison experiments, wind profiles from the lidar, radiosonde and European Center for Medium range Weather Forecast (ECMWF) analysis show good agreement from 8 km to 25 km. Wind observation over two months is carried out in Urumqi (42.1°N, 87.1°E), northwest of China, demonstrating the stability and robustness of the system. For the first time, quasi-zero wind layer and dynamic evolution of high-altitude tropospheric jet are observed based on Rayleigh Doppler lidar in Asia.

SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in lipopolysaccharide-induced neuronal damage and Aß generation.

The level of lipopolysaccharide (LPS) is higher in the blood and brains of patients with Alzheimer's disease (AD), and this phenomenon is strongly linked to AD-related neuronal damage and ß-amyloid (Aß) generation. However, the mechanism by which LPS causes neuronal damage has still not been fully clarified. Oxidative stress, neuroinflammation, and Ca2+ overload are regarded as important factors influencing AD. NADPH oxidase 2 (NOX2) and the NOD-like receptor family protein 1 (NLRP1) inflammasome play important roles in promoting oxidative stress and inflammation in neurons. Ca2+ overload can activate calcineurin (CN), which further dephosphorylates nuclear factor of activated T cells (NFAT), leading to its translocation into the nucleus to regulate gene transcription. In the present study, LPS (250 µg/kg) exposure for 14 days was used to induce cognitive dysfunction in mice and LPS (20 µg/ml) exposure for 48 h was used to induce neuronal damage in HT22 cells. The results showed that LPS exposure activated phospholipase C (PLC), CN, and NFAT1; increased the expressions of NOX2- and NLRP1-related proteins; and promoted neuronal damage and Aß deposition in mice and HT22 cells. However, treatment with 2-APB (SOCE inhibitor), apocynin (NOX inhibitor), or tempol (reactive oxygen species scavenger) significantly reversed these LPS-induced changes, and improved neuronal damage and Aß deposition. Moreover, LPS exposure promoted PLC phosphorylation, increased the level of inositol-1,4,5-triphosphate, elevated the intracellular Ca2+ concentration ([Ca2+]i), and disrupted [Ca2+]i homeostasis in HT22 cells. These data indicated that the activation of SOCE-mediated NFAT1-NOX2-NLRP1 inflammasome involves in LPS-induced neuronal damage and Aß generation.

Chronic glucocorticoid exposure accelerates Aß generation and neurotoxicity by activating calcium-mediated CN-NFAT1 signaling in hippocampal neurons in APP/PS1 mice.

Glucocorticoid (GC) exposure can lead to deterioration of the structure and function of hippocampal neurons and is closely involved in Alzheimer's disease (AD). Amyloid-ß (Aß) overproduction is an important aspect of AD pathogenesis. Our study mainly investigated the mechanism of chronic GC exposure in accelerating Aß production in primary cultured hippocampal neurons from APP/PS1 mice. The results indicated that chronic dexamethasone (DEX, 1 µM) significantly accelerated neuronal damage and Aß accumulation in hippocampal neurons from APP/PS1 mice. Meanwhile, DEX exposure markedly upregulated APP, NCSTN, BACE1 and p-Tau/Tau expression in hippocampal neurons from APP/PS1 mice. Our study also indicated that chronic DEX exposure significantly increased intracellular Ca2+ ([Ca2+]i) levels and the expressions of p-PLC, CN and NFAT1 in hippocampal neurons from APP/PS1 mice. We further found that stabilizing intracellular calcium homeostasis with 2-APB (50 µM) and SKF-96365 (10 µM) significantly alleviated neuronal damage and Aß accumulation in chronic DEX-induced hippocampal neurons from APP/PS1 mice. Additionally, dual luciferase assays showed that NFAT1 upregulated NCSTN transactivation, which was further increased upon DEX treatment. This study suggests that chronic DEX exposure accelerates Aß accumulation by activating calcium-mediated CN-NFAT1 signaling in hippocampal neurons from APP/PS1 mice, which may be closely related to the acceleration of AD.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury due to inhibition of NOX2-mediated calcium homeostasis dysregulation in mice.

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and pole-climbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

Ginsenoside Rg1 ameliorates aging­induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice.

Aging is often accompanied by liver injury and fibrosis, eventually leading to the decline in liver function. However, the mechanism of aging­induced liver injury and fibrosis is still not fully understood, to the best of our knowledge, and there are currently no effective treatment options available for liver aging. Ginsenoside Rg1 (Rg1) has been reported to exert potent anti­aging effects due to its potential antioxidant and anti­inflammatory activity. The present study aimed to investigate the protective effect and underlying mechanism of action of Rg1 in aging­induced liver injury and fibrosis in senescence­accelerated mouse prone 8 (SAMP8) mice treated for 9 weeks. The histopathological results showed that the arrangement of hepatocytes was disordered, vacuole­like degeneration occurred in the majority of cells, and collagen IV and TGF­ß1 expression levels, that were detected via immunohistochemistry, were also significantly upregulated in the SAMP8 group. Rg1 treatment markedly improved aging­induced liver injury and fibrosis, and significantly downregulated the expression levels of collagen IV and TGF­ß1. In addition, the dihydroethylene staining and western blotting results showed that Rg1 treatment significantly reduced the levels of reactive oxygen species (ROS) and IL­1ß, and downregulated the expression levels of NADPH oxidase 4 (NOX4), p47phox, p22phox, phosphorylated­NF­κB, caspase­1, apoptosis­associated speck­like protein containing a C­terminal caspase recruitment domain and the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which were significantly upregulated in the liver tissues of elderly SAMP8 mice. In conclusion, the findings of the present study suggested that Rg1 may attenuate aging­induced liver injury and fibrosis by reducing NOX4­mediated ROS oxidative stress and inhibiting NLRP3 inflammasome activation.

Ginsenoside Rg1 alleviates Aß deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice.

BACKGROUND: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. METHODS: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aß) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. RESULTS: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aß generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. CONCLUSIONS: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aß deposition by inhibiting NOX2 activation in APP/PS1 mice.