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The goal of this contribution is to construct the inter-satellite links (ISLs) between Global Navigation Satellite System (GNSS) and Low Earth Orbit (LEO) satellite to recover the Earth's gravity field based on the concept of Geodesy and Time Reference in Space (GETRIS). Taking the constellation of the Beidou Navigation Satellite System (BDS) as an example, several types of high-low satellite-to-satellite tracking (H-L SST) modes combining BDS and GETRIS are used to research the tracking mode of high orbit satellites and the distribution of LEO satellite constellations to explore the optimal mode for gravity field recovery. The effects of multiple H-L SST modes on the accuracy of gravity field recovery are studied. In addition, the contribution of each error source is also analyzed. Finally, this study varies LEO satellite constellations to show reduced errors in the temporal gravity field solutions for the improved ISLs. The results showed that the Inclined GeoSynchronous Orbit (IGSO) satellite greatly improved the Geosynchronous orbit (GEO) satellite tracking LEO satellite mode in the high latitude regions. Compared with the Medium Earth Orbit (MEO) satellite tracking LEO satellite, the error of gravity field recovered by combining with GEO, IGSO and MEO can be reduced by 16 %. The largest error is the non-tidal signal, followed by the ocean tidal model difference, and the smallest is the instrument error. For a single LEO satellite, the combination model is more sensitive to the satellite orbital altitude, the cumulative error was decreased from 5.08 mm (550 km) to 0.33 mm (250 km). For LEO constellations, adding inclined orbit satellites can improve the accuracy of the solution to some extent. But the optimal solution can be obtained by the constellation composed of polar orbit satellites with different Right Ascension of Ascending Node (RAAN), the cumulative errors are 0.27 mm (two satellites), 0.19 mm (three satellites), and 0.19 mm (four satellites). [ABSTRACT FROM AUTHOR]

Groundwater potential maps are crucial tools for effectively managing water resources, particularly in agriculturally focused countries such as Vietnam. However, creating these maps is a challenging task that requires reliable data and methods. In this study, we integrated the Split‐Point Sampling and Node Attribute Subsampling Classifier (SPAARC) with the Bagging (B), MultiBoostAB (MBAB), and Random Subspace (RSS) ensemble learning techniques and developed three ensemble models: B‐SPAARC, MBAB‐SPAARC, and RSS‐SPAARC. We selected 13 geoenvironmental factors based on their availability, relevance, and association with groundwater potential in the Sesan River basin of Vietnam. We assessed the models' performance using various metrics such as area under the curve (AUC), accuracy, sensitivity, specificity, and RMSE. The findings indicated that the ensemble models performed better than the single SPAARC model in mapping groundwater potential. The MBAB‐SPAARC model demonstrated the highest accuracy with an AUC value of 0.891, followed by B‐SPAARC (AUC = 0.844), RSS‐SPAARC (AUC = 0.871), and the single SPAARC (AUC = 0.853) models. The results also highlighted that elevation, rainfall, land use/cover, and altitude were the most significant factors for mapping groundwater potential in the Sesan River basin. The innovative ensemble models and reliable potential maps developed in this study assist water resource managers in planning water usage based on the benefits and costs for various users and in devising sustainable strategies for using, protecting, and managing groundwater. Key Points: Groundwater potential mapping was carried out at the Central Highlands of VietnamHybrid Machine learning Models based on Naïve Bayes Tree were developed and usedResults showed that the proposal models are potential and accurate tools [ABSTRACT FROM AUTHOR]

The sequential approximate optimization (SAO) method is widely adopted in aircraft optimization design, whose further improvement in efficacy and efficiency has encountered bottlenecks. In this paper, a collaboratively iterative sequential approximate optimization (CISAO) method with field metamodel (FM) accelerating computational fluid dynamics (CFD) is proposed for aerodynamic optimization problems to enhance the coupling between metamodels and CFD high-fidelity models (HFMs). In this method, the field metamodel is used to predict the flow field distributions with respect to the design variables to accelerate the numerical solution of CFD HFMs. Two benchmark aerodynamic optimization cases are performed to validate the proposed method. The time costs for single CFD HFMs in the two test cases are shortened by 37.76% and 12.11%, respectively, and the total time costs of the two test cases are shrunk by 64.11% and 44.47% compared with the conventional SAO method. The optimization results indicate that the proposed method significantly reduces the time costs and improves the optimization efficiency. The proposed method shows a promising prospect in aircraft optimization design. [ABSTRACT FROM AUTHOR]

Weighted average temperature (Tm) plays a crucial role in global navigation satellite system (GNSS) precipitable water vapor (PWV) retrieval. Aiming at the poor applicability of the existing Tm models in Europe, in the article, we used observations from 48 radiosonde stations over Europe from 2014 to 2020 to establish a weighted average temperature model in Europe (ETm) by the nonlinear least squares estimation method. The ETm model takes into account factors such as ground temperature, water vapor pressure, latitude, and their annual variation, semiannual variation and diurnal variation. Taking the Tm obtained from the radiosonde data by the integration method in 2021 as the reference value, the accuracy of the ETm model was evaluated and compared with the commonly used Bevis model, ETmPoly model, and GPT2w model. The results of the 48 modeled stations showed that the mean bias and root mean square (RMS) values of the ETm model were 0.06 and 2.85 K, respectively, which were 21.7%, 11.5%, and 31.8% higher than the Bevis, ETmPoly, and GPT2w-1 (1° × 1° resolution) models, respectively. In addition, the radiosonde data of 12 non-modeling stations over Europe in 2021 were selected to participate in the model accuracy validation. The mean bias and RMS values of the ETm model were –0.07 and 2.87 K, respectively. Compared with the Bevis, ETmPoly, and GPT2w-1 models, the accuracy (in terms of RMS values) increased by 20.5%, 10.6%, and 35.2%, respectively. Finally, to further verify the superiority of the ETm model, the ETm model, and other Tm models were applied to the GNSS PWV calculation. The ETm model had mean RMSPWV and RMSPWV/PWV values of 0.17 mm and 1.03%, respectively, which were less than other Tm models. Therefore, the ETm model has essential applications in GNSS PWV over Europe. [ABSTRACT FROM AUTHOR]

Geodetic networks are important for most engineering projects. Generally, a geodetic network is designed according to precision, reliability, and cost criteria. This paper provides a new criterion considering the distances between the Net Points (NPs) and the Project Border (PB) in terms of Neighboring (N). Optimization based on the N criterion seeks to relocate the NPs as close as possible to PB, which leads to creating shorter distances between NPs or those distances linking NPs with Target Points (TPs) to be measured inside PB. These short distances can improve the precision of NPs and increase the accuracy of observations and transportation costs between NPs themselves or between NPs and TPs (in real applications). Three normalized N objective functions based on L1, L2, and L∞‒norms were formulated to build the corresponding N optimization models, NL1; NL2; and NL∞ and to determine the best solution. Each model is subjected to safety, precision, reliability, and cost constraints. The feasibility of the N criterion is demonstrated by a simulated example. The results showed the ability of NL∞ to determine the safest positions for the NPs near PB. These new positions led to improving the precision of the network and preserving the initial reliability and observations cost, due to contradiction problems. Also, N results created by all N models demonstrate their theoretical feasibility in improving the accuracy of the observations and transportation cost between points. It is recommended to use multi-objective optimization models to overcome the contradiction problem and consider the real application to generalize the benefits of N models in designing the networks. [ABSTRACT FROM AUTHOR]

• Novel STLF method considering DR deviation correction. • Two-stage approach based on LSTM. • Hankel matrix adopted during Dynamic Mode Decomposition. • Four different time dimensions analyzed in case study. With the increasing deployment of demand response (DR), accurate short-term load forecasting (STLF) is playing an essential role in smart grid operation. This paper addressed the task of improving the accuracy of STLF using a two-stage approach, which adopts the results of traditional algorithms as baselines. The target DR deviation sequence is constructed by the mode decomposition and reorganization of the initial prediction deviation. In the above process, the deviation sequences caused by DR are obtained using dynamic mode decomposition (DMD), where the Hankel matrix is constructed to simplify the process. The final forecast accuracy is improved by superposing the results from traditional algorithms and the obtained deviation sequence. Multiple case studies on the data from DR pilot areas and comparison with existing models show that demand response deviation correction based on existing algorithms effectively improves power load forecasting accuracy and has good generalization. [ABSTRACT FROM AUTHOR]

Background: The renin–angiotensin system produces a series of biologically active angiotensin (Ang) peptides. These Ang peptides are the major regulators of blood pressure and Na homeostasis, and play a critical role in maintaining cardiovascular and fluid homeostasis. The concentration of Ang peptides in the body is at trace levels, making their detection and quantification a challenge. In this study, a rapid and sensitive analytical method using mass spectrometry coupled with ultrahigh‐performance liquid chromatography (UHPLC/MS) was developed to simultaneously quantify 14 Ang peptides. Methods: UHPLC/MS was employed to quantify 14 Ang peptides in mouse and human plasma. An HSS T3 column (2.1 × 100 mm, 1.8 μm) with an HSS T3 precolumn and triple‐quadrupole mass spectrometer combined with an electrospray ionization source were utilized. Sample pretreatment involved a one‐step protein precipitation using methanol. The total analysis time was within 7.5 min and the target peptides were detected in positive ion mode and quantified by selected reaction monitoring mode. Results: The method was validated for linearity, detection and quantification limits, precision, stability, recovery and matrix effect. The limits of detection of Ang II, Ang III, Ang‐(1–7), Ang‐(2–7), Ang‐(3–7), Ang‐(1–9), bradykinin, Asn1 and Val5‐Ang II are all less than 1 pg mL−1, indicating high sensitivity. The intra‐day and inter‐day precision was within 15%, and the accuracy was between 85% and 115%. Meanwhile, the sample and reference solution were stable within 48 h, and the recovery and matrix effect met the quantitative requirements. Conclusions: The method is currently reported to allow the largest number of Ang peptide species to be detected at one time. In addition, the proposed method offers a fast and reliable approach for comprehensive analysis of Ang metabolism in biological samples, facilitating research on the physiological and pathological states of cardiovascular, kidney and respiratory diseases. [ABSTRACT FROM AUTHOR]

The Qinghai–Tibet Plateau region has significant altitude fluctuations and complex climate changes. However, the current global weighted average temperature (Tm) model does not fully consider the impact of meteorological and elevation factors on it, resulting in existing models being unable to accurately predict the Tm in the region. Therefore, this study constructed a weighted average temperature refinement model (XTm) related to surface temperature, water vapor pressure, geopotential height, annual variation, and semi-annual variation based on measured data from 13 radiosonde stations in the Qinghai–Tibet Plateau region from 2008 to 2017. Using the Tm calculated via the numerical integration method of radiosonde observations in the Qinghai–Tibet Plateau region from 2018 to 2019 as a reference value, the quality of the XTm model was tested and compared with the Bevis model and GPT2w (global pressure and temperature 2 wet) model. The results show that for 13 modeling stations, the bias and root-mean-square (RMS) values of the XTm model were −0.02 K and 2.83 K, respectively; compared with the Bevis, GPT2-1, and GPT2w-5 models, the quality of XTm was increased by 47%, 38%, and 47%, respectively. For the four non-modeling stations, the average bias and RMS values of the XTm model were 0.58 K and 2.78 K, respectively; compared with the other three Tm models, the RMS values and the mean bias were both minimal. In addition, the XTm model was also used to calculate the global navigation satellite system (GNSS) precipitable water vapor (PWV), and its average values for the theoretical RMSPWV and RMSPWV/PWV generated by water vapor calculation were 0.11 mm and 1.03%, respectively. Therefore, in the Qinghai–Tibet Plateau region, the XTm model could predict more accurate Tm values, which, in turn, is important for water vapor monitoring. [ABSTRACT FROM AUTHOR]

• A data-mechanism-driven method for assessing the peak shaving potential of VPP users. • The multidimensional uncertainty of the peak shaving capacity is considered using LSTM and MDN. • Risk preference of decision-makers is considered using chance constraint theory and relevant chance constraint theory. There is a consensus regarding the need to realize the transformation of renewable energy by enhancing demand-side regulating ability. This paper proposes a peak shaving potential assessment model based on the price elasticity mechanism and consumer psychology, focusing on the adjustable user load in virtual power plants. The values of deterministic parameters and the distribution of the uncertain parameter of the model are obtained through the long short-term memory network (LSTM) and mixture density network (MDN). Then, the refined distribution of peak shaving potential considering external conditions, incentive inputs, and spatial and temporal scales is obtained. Based on the evaluation results, a peak shaving decision-making model for virtual power plants is constructed using a scenario scheme. Differentiated schemes for traditional, risk-averse, and risk-seeking virtual power plant decision-makers are considered. Case studies using the data of a virtual power plant pilot area show that the proposed model can better characterize the features of virtual power plant users, and a refined control strategy with better economic benefits can be obtained. [ABSTRACT FROM AUTHOR]

Using total electron content (TEC) data over one and a half solar cycles (1999–2015) provided by the Center for Orbit Determination in Europe (CODE), this paper proposes a new empirical TEC model for northeast China (40–50N, 120–130E). The model, called TECM-NEC, involves the multiplication of four separable components, including diurnal variation, seasonal variation, geomagnetic field dependency, and solar dependency. Diurnal variation is composed of three parts: the typical daily variation of TEC; corrections of Mid-latitude Summer Nighttime Anomaly (MSNA) that depend on geographic location, season, and local time; and corrections of day-to-night ratio under different seasons and solar activities. Four sub-harmonics of the year with annual, semiannual, four-, and three-month periods are used to describe seasonal variations. For geomagnetic variation, geomagnetic latitude is based on the latest International Geomagnetic Reference Field (IGRF12) model. Compared with similar empirical models, the solar proxy index F10.7P = (F10.7 + F10.7A)/2, where F10.7A is the 81-day running mean of daily F10.7, is chosen as having linear relationship with TEC for the model. This model has 43 coefficients, which are determined by nonlinear least squares fitting (NLSF) technique. The TECM-NEC model fits with the TEC/CODE input data with a bias of 0.03TECU and a RMS deviation of 2.76TECU. The proposed TECM-NEC model can reproduce the MSNA and nighttime TEC enhancements phenomenon over northeast China. [ABSTRACT FROM AUTHOR]

A quantitative approach for hydrological drought characterization, based on non-seasonal water storage deficit data from NASA's Gravity Recovery and Climate Experiment (GRACE) satellite mission, is assessed. Non-seasonal storage deficit is the negative terrestrial water storage after deducting trend, acceleration and seasonal signals, and it is designated as a drought event when it persists for three or more continuous months. The non-seasonal water storage deficit is used for measuring the hydrological drought in southwestern China. It is found that this storage-deficit method clearly identifies hydrological drought onset, end and duration, and quantifies instantaneous severity, peak drought magnitude, and time to recovery. Moreover, it is found that severe droughts have frequently struck southwestern China in the past several decades, among which, the drought of 2011-2012 was the most severe; the duration was 10 months, the severity was −208.92 km/month, and the time to recovery was 17 months. These results compare well with the National Climate Center of China drought databases, which signifies that the GRACE-based non-seasonal water storage deficit has a quantitative effect on hydrological drought characterization and provides an effective tool for researching droughts. [ABSTRACT FROM AUTHOR]

An automated on-line solid-phase extraction (SPE) high-performance liquid chromatography (HPLC) method was developed for the determination of six protoberberine alkaloids in compound Chinese medicines containing Coptidis Rhizoma and Phellodendri Cortex. The sample solution extracted by acidic-methanol was loaded into the constructed system directly to perform enrichment and the purification of the analytes was performed automatically. A cation-exchanged sorbent based on turbulent chromatography was employed for on-line SPE to remove macro and neutral matrix interferences from samples. The target alkaloids were retained on the SPE column and eluted onto the trapping C18 column by a mobile phase of methanol/500 mM ammonium acetate (85:15) at a flow rate of 0.3 mL/min. Ion pair reverse phase high-performance liquid chromatography was employed to complete the determination of six analytes. The results showed the linear correlation coefficients for all analytes were above 0.999. The peak area of relative standard deviation in reproducibility measurements were from 0.55% to 2.39%. Recovery measurements spiked at two levels were from 92.71% to 104.28%. The reported method was suitable for the determination of six active alkaloids in multicomponent Chinese medicines containing Coptidis rhizoma and Phellodendri cortex. [ABSTRACT FROM AUTHOR]

The height of the peak electron density (hmF2) and the critical frequency of the F2 layer (foF2) are very important in the research of ionospheric electrodynamics and high frequency (HF) wireless communication. In the article, we validated the hmF2/foF2 model values of the latest version of the International Reference Ionosphere (IRI-2016) with observations from three ionosonde stations which belong to low, middle, and high latitudes (i.e., Sanya, Beijing and Mohe) over China during a high solar activity year (2014, F10.7 = 145.9 sfu) and a low solar activity year (2016, F10.7 = 88.7 sfu). Among them, foF2 model values can be obtained through the International Radio Consulting Committee (CCIR) model or the International Union of Radio Science (URSI) model, both of which have the "F-peak storm model" on or 'off' options; hmF2 model values can be obtained through Bilitza-Sheikh-Eyfrig (BSE-1979), Altadill-Magdaleno-Torta-Blanch (AMTB-2013), or SHUbin (SHU-2015) model. The IRI-2016 hmF2/foF2 model values were evaluated by root mean square (RMS) values and mean absolute relative error (MARE). The results show that for the foF2 parameter, the performance of IRI-2016 can be improved by choosing "F-peak storm model" on option in geomagnetic-disturbed days. Whether in high or low solar activity years, for foF2, the IRI-2016 options of CCIR have better prediction ability than IRI-2016 options of URSI in low and high latitudes over China, and the IRI-2016 options of URSI have better prediction ability than IRI-2016 options of URSI in middle latitudes. For hmF2, the IRI-2016 option of SHU-2015 has better prediction ability than the IRI-2016 options of AMTB-2013 and BSE-1949 in high latitudes over China, the IRI-2016 options of SHU-2015 and BSE-1979 have better prediction ability than IRI-2016 options of AMTB-2013 in mid and low latitudes over China. [ABSTRACT FROM AUTHOR]

Viral DNA and RNA polymerases are two kinds of very important enzymes that synthesize the genetic materials of the virus itself, and they have become extremely favorable targets for the development of antiviral drugs because of their relatively conserved characteristics. There are many similarities in the structure and function of different viral polymerases, so inhibitors designed for a certain viral polymerase have acted as effective universal inhibitors on other types of viruses. The present review describes the development of classical antiviral drugs targeting polymerases, summarizes a variety of viral polymerase inhibitors from the perspective of chemically synthesized drugs and natural product drugs, describes novel approaches, and proposes promising development strategies for antiviral drugs. [ABSTRACT FROM AUTHOR]

Stromal cell-derived factor (SDF-1) is a CXC chemokine that selectively activates the CXCR4 chemokine receptor. Fibronectin is an intracellular matrix component that binds integrin and mediates cell-matrix adhesion. Activation of the integrin receptor can occur in two ways: by ligand binding (outside-in signaling), and in response to intracellular events (inside-out signaling). In the current study we showed that SDF-1α inhibited adhesion of T lymphocyte Jurkat cells resulting from binding high concentrations of fibronectin as well as that of THP-1 monocytes. The effect of SDF-1α on fibronectin-mediated adhesion was partly reversed by the CXCR4 receptor antagonist T140. Our results suggest that an SDF-1/ CXCR4 signal pathway modulates fibronectin-mediated lymphocytes adhesion. [ABSTRACT FROM AUTHOR]

Abstract: A new method of analysis of 11 phenols, including five bibenzyls, three phenanthrenes, and three fluorenones, using high-performance liquid chromatography (HPLC)–diode array detection (DAD) was described. The separation of 11 phenols was effected by RP-HPLC (Beckman Coulter™ ODS column, 5μm, 250mm×4.6mm) using linear gradient elution systems of acetonitrile–1‰ trifluoroacetic acid (TFA). Satisfactory separation of these compounds was obtained in less than 45min. The method was validated for linearity, repeatability, limits of detection (LOD) and limits of quantification (LOQ). Good results were obtained with respect to repeatability (relative standard deviation (RSD)<3.5%) and recovery (85.77–104.92%). The developed method was applied to the simultaneous determination of 11 phenols from totally 31 Dendrobium species (mainly of medicinal plants) as well as other four samples from the similar genera as Pholidota, Flickingeria and Bulbophyllum. The range of the total amounts of bibenzyl, phenanthrene and fluorenone were found to from trace: 4.00, not detected (nd): 0.42 and nd: 0.24μgmg−1, respectively. [Copyright &y& Elsevier]

The Gravity Recovery and Climate Experiment (GRACE) satellite provides time-varying gravity field models that can detect total water storage change (TWSC) from April 2002 to June 2017, and its second-generation satellite, GRACE Follow-On (GRACE-FO), provides models from June 2018, so there is a one year gap. Swarm satellites are equipped with Global Positioning System (GPS) receivers, which can be used to recover the Earth's time-varying gravitational field. Swarm's time-varying gravitational field models (from December 2013 to June 2018) were solved by the International Combination Service for Time-variable Gravity Field Solutions (COST-G) and the Astronomical Institute of the Czech Academy of Sciences (ASI). On a timely scale, Swarm has the potential to fill the gap between the two generations of GRACE satellites. In this paper, using 26 global watersheds as the study area, first, we explored the optimal data processing strategy for Swarm and then obtained the Swarm-TWSC of each watershed based on the optimal results. Second, we evaluated Swarm's accuracy in detecting regional water storage variations, analyzed the reasons for its superior and inferior performance in different regions, and systematically explored its potential in detecting terrestrial water storage changes in land areas. Finally, we constructed the time series of terrestrial water storage changes from 2002 to 2019 by combining GRACE, Swarm, and GRACE-FO for the Amazon, Volga, and Zambezi Basins. The results show that the optimal data processing strategy of Swarm is different from that of GRACE. The optimal results of Swarm-TWSC were explored in 26 watersheds worldwide; its accuracy is related to the area size, runoff volume, total annual mass change, and instantaneous mass change of the watershed itself, among which the latter is the main factor affecting Swarm-TWSC. Knowledge of the Swarm-TWSC of 26 basins constructed in this paper is important to study long-term water storage changes in basins. [ABSTRACT FROM AUTHOR]

The Gravity Recovery and Climate Experiment (GRACE) mission has measured total water storage change (TWSC) and interpreted drought patterns in an unparalleled way since 2002. Nevertheless, there are few sources that can be used to understand drought patterns prior to the GRACE era. In this study, we extended the gridded GRACE TWSC to 1993 by combining principal component analysis (PCA), least square (LS) fitting, and multiple linear regression (MLR) methods using climate variables as input drivers. We used the extended (climate-driven) TWSC to interpret drought patterns (1993–2019) over the Amazon basin. Results showed that, in the Amazon area with the resolution of 0.5°, GRACE, GRACE follow on, and Swarm had correlation coefficients of 0.95, 0.92, and 0.77 compared with climate-driven TWSCS, respectively. The drought patterns assessed by the climate-driven TWSC were consistent with those interpreted by the Palmer Drought Severity Index and GRACE TWSC. We also found that the 1998 and 2016 drought events in the Amazon, both induced by strong El Niño events, showed similar drought patterns. This study provides a new perspective for interpreting long-term drought patterns prior to the GRACE period. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), which is characterized by disruption of lipid homeostasis, has been the leading cause of chronic liver disease worldwide. However, currently there is no effective therapy for NAFLD. Consequently, it is extremely urgent to explore the specific and effective target functioned as lipids regulator during the pathological process of NAFLD for the drug development. Transcription factor EB (TFEB) plays a crucial role in the regulation of lipid homeostasis through linking autophagy to energy metabolism at the transcriptional level. In this review, we summarize the currently available information regarding the mediation of TFEB in lipid metabolism during the pathological process of NAFLD, and the specific regulatory mechanism of TFEB activity. We further recapitulate TFEB as a promising therapeutic target for NAFLD, primarily through the regulation of lipid homeostasis, energy metabolism as well as immune defense. A better understanding of these key issues will be helpful to promote the development of therapeutic agents which specifically target TFEB to halt or reverse the pathological progression of NAFLD. Unlabelled Image [ABSTRACT FROM AUTHOR]

Agarwood holds significant importance as a valuable resource for aromatic purposes, however, key components responsible for aroma and the differences between regions and grades remain to be deeply elucidated. Thus, the odors of agarwood sourced from typical zones, as well as the renowned Kynam agarwood, were analyzed by HS-SPME Arrow GC-MS in SCAN and MRM modes. The integrated strategy proposed herein exploits the respective advantages of non-targeted and targeted analysis. In addition to a total of 55 volatile components identified from the NIST database, 114 odor components were matched according to the Smart Aroma Database, and a series of differential compounds was also unearthed and quantified. [ABSTRACT FROM AUTHOR]

Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase PlGH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli. Sequence analysis revealed that PlGH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of PlGH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p-nitrophenyl-β-d-glucopyranoside as a substrate, respectively. The Km and kcat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s−1, respectively. PlGH3 exhibits a highly specific activity on hydrolyzing the 28-O-β-d-glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus. This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. Key points: • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis. [ABSTRACT FROM AUTHOR]

Wearable heaters are essential for people living in cold regions, but creating heaters that are low-cost, lightweight, and high air permeability poses challenges. In this study, we developed a wearable heater using carbon nanotube/water polyurethane (CNT/WPU) nanocomposite fibers that achieve high extension rate and conductivity. We produced low-cost and mass-produced fibers using the wet spinning. With heat treatment, we increased the elongation rate of the fibers to 1893.8% and decreased the resistivity to 0.07 Ω*m. then wove the fibers into a heating fabric using warp knitting, that resistance is 493 Ω. Achieved a uniform temperature of 58 °C at voltage of 36 V, with a thermal stability fluctuation of −5.0 °C to +6.3 °C when bent from 0° to 360°. Our results show that wearable heaters have excellent flexibility and stretchability, due to nanocomposite fibers and special braided structure, which offer a novel idea for wearable heaters. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents have received increasing attention over the past decade, and the green and versatile nature makes them important media for developing environmentally friendly and sustainable technologies. In addition to act as green alternatives to traditional organic solvents, deep eutectic solvents offer tremendous opportunities to produce different kinds of emerging functional materials. The present review highlights the recent development and applications of deep functional materials based on deep eutectic solvents as novel adsorbents for diverse analytes in complex matrices. The type, preparation, and unique properties of deep eutectic solvents, the synthesis of deep eutectic solvent derived materials, as well as their applications in chromatographic separation are described. We aim to demonstrate that deep eutectic solvents not only allow the design of eco‐friendly extraction processes but also open straightforward access to advanced materials in sample preparation. [ABSTRACT FROM AUTHOR]

Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase PlGH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli. Sequence analysis revealed that PlGH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of PlGH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p-nitrophenyl-β-d-glucopyranoside as a substrate, respectively. The Km and kcat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s−1, respectively. PlGH3 exhibits a highly specific activity on hydrolyzing the 28-O-β-d-glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus. This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. Key points: • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis. [ABSTRACT FROM AUTHOR]

Groundwater depletion is adversely affecting Beijing's ecology and environment. However, the effective execution of the South-to-North Water Diversion Project's middle route (SNDWP-MR) is anticipated to mitigate Beijing's groundwater depletion. Here, we propose a robust hybrid statistical downscaling method aimed at enhancing the capability of the Gravity Recovery and Climate Experiment (GRACE) to detect the small-scale groundwater storage anomaly (GWSA) in Beijing. We used three deep learning (DL) methods to reconstruct the 0.5° × 0.5° terrestrial water storage anomaly (TWSA) between 2004 and 2021. Moreover, multiple processing strategies were used to downscale the GWSA to 0.25° from 2004 to 2021 by integrating wells and GRACE/GRACE follow-on data from the optimal DL model. Additionally, we analyzed the spatiotemporal evolution trends of GW in Beijing before and after the implementation of the SNDWP-MR. The results show that the long short-term memory model delivers optimal performance in the TWSA reconstruction of Beijing, with the correlation coefficient (CC), Nash–Sutcliffe coefficient (NSE), and root mean square error (RMSE) being 0.98, 0.96, and 10.19 mm, respectively. The GWSA before and after downscaling is basically consistent with wells data, but the CC and RMSE of downscaling the GWSA from 2004 to 2021 are improving by 34% and 31%, respectively. Before the SNDWP-MR (2004–2014), the trend of GWSA in Beijing was − 17.68 ± 4.46 mm/y, with a human contribution of 69.30%. After SNDWP-MR (2015–2021), GWSA gradually increased by 10.00 mm per year, with the SNDWP-MR accounting for 18.30%. This study delivers a technical innovation reference for dynamically monitoring a small-scale GWSA from GRACE/GRACE-FO data. [ABSTRACT FROM AUTHOR]

• Modular co-culture engineering for the production of natural products. • Advantages of modular co-culture engineering in the field of biosynthesis. • Designs and strategies for engineering microbial co-cultures. • Novel approaches are helping to improve properties of modular co-culture system. The microbial production of natural products has been traditionally accomplished in a single organism engineered to accommodate target biosynthetic pathways. Often times, such approaches result in large metabolic burdens as key cofactors, precursor metabolites and energy are channeled to pathways of structurally complex chemicals. Recently, modular co-culture engineering has emerged as a new approach to efficiently conduct heterologous biosynthesis and greatly enhance the production of natural products. This review highlights recent advances that leverage Escherichia coli -based modular co-culture engineering for making natural products. Potential future perspectives for studies in this promising field are addressed as well. [ABSTRACT FROM AUTHOR]

Safety issues caused by pharmaceuticals have frequently occurred worldwide, posing a tremendous threat to human health. As an essential part of drug development, the toxicological analysis and safety evaluation is of great significance. In addition, the risk of pharmaceuticals accumulation in the environment and the monitoring of the toxicity from natural medicines have also received ongoing concerns. Due to a lack of spatial distribution information provided by common analytical methods, analyses that provide spatial dimensions could serve as complementary safety evaluation methods for better prediction and evaluation of drug toxicity. With advances in technical solutions and software algorithms, mass spectrometry imaging (MSI) has received increasing attention as a popular analytical tool that enables the simultaneous implementation of qualitative, quantitative, and localization without complex sample pretreatment and labeling steps. In recent years, MSI has become more attractive, powerful, and sensitive and has been applied in several scientific fields that can meet the safety assessment requirements. This review aims to cover a detailed summary of the various MSI technologies utilized in the biomedical and pharmaceutical area, including technical principles, advantages, current status, and future trends. Representative applications and developments in the safety‐related issues of different pharmaceuticals and natural medicines are also described to provide a reference for pharmaceutical research, improve rational clinical medicine use, and ensure public safety. [ABSTRACT FROM AUTHOR]

Abstract: Quantitative estimates of the groundwater depletion and droughts in the Tigris‐Euphrates Basin (TEB) can be useful for sustainably managing its water resources. Here, data from the Gravity Recovery and Climate Experiment (GRACE) satellite mission are used to infer the monthly changes in the total water storage of the TEB from January 2003 to December 2015. Additionally, the data of altimetry and output from land surface models are used to remove the contributions from lake water changes and other hydrological factors to obtain the total groundwater depletion (TGWD), human‐driven groundwater depletion (HGWD), and climate‐driven groundwater depletion. We conclude that an alarming rate of decrease in the total water storage and the loss of TGWD have an “accelerating” trend, as the trend during 2007 to 2015 was 3.6 times that during 2003 to 2006. Moreover, the HGWD is 116.09 Gt, which accounts for 98% of the TGWD. Finally, the total storage deficit index (TSDI) is derived from the GRACE data to characterize the drought of the TEB. The results show that TSDI agrees well with the actual drought rather than the Palmer drought severity index (PDSI) and that the TEB has been undergoing a severe drought since September 2007 according to both the TSDI and PDSI. The research in this study provides an effective and unique method for understanding the hydrological processes and sustainable use of water resources in regions or countries with little data, which is essential for more efficient, sustainable, and cross‐boundary cooperative water resource management. [ABSTRACT FROM AUTHOR]

Global empirical total electron content (TEC) models based on TEC maps effectively describe the average behavior of the ionosphere. However, the accuracy of these global models for a certain region may not be ideal. Due to the number and distribution of the International GNSS Service (IGS) stations, the accuracy of TEC maps is geographically different. The modeling database derived from the global TEC maps with different accuracy is likely one of the main reasons that limits the accuracy of the new models. Moreover, many anomalies in the ionosphere are geographic or geomagnetic dependent, and as such the accuracy of global models can deteriorate if these anomalies are not fully incorporated into the modeling approach. For regional models built in small areas, these influences on modeling are immensely weakened. Thus, the regional TEC models may better reflect the temporal and spatial variations of TEC. In our previous work (Feng et al., 2016), a regional TEC model TECM-NEC is proposed for northeast China. However, this model is only directed against the typical region of Mid-latitude Summer Nighttime Anomaly (MSNA) occurrence, which is meaningless in other regions without MSNA. Following the technique of TECM-NEC model, this study proposes another regional empirical TEC model for other regions in mid-latitudes. Taking a small area Bei J ing–Tian J in– T angshan (JJT) region (37.5°–42.5° N, 115°–120° E) in China as an example, a regional empirical TEC model (TECM–JJT) is proposed using the TEC grid data from January 1, 1999 to June 30, 2015 provided by the Center for Orbit Determination in Europe (CODE) under quiet geomagnetic conditions. The TECM–JJT model fits the input CODE TEC data with a bias of 0.11TECU and a root mean square error of 3.26TECU. Result shows that the regional model TECM–JJT is consistent with CODE TEC data and GPS–TEC data. [ABSTRACT FROM AUTHOR]

Septic shock is defined as a subset of sepsis, which is associated with a considerably high mortality risk. The caspase-11 non-canonical inflammasome is sensed and activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis, it plays a critical role in septic shock. However, there are few known drugs that can control caspase-11 non-canonical inflammasome activation. We report here that goitrin, an alkaloid from Radix Isatidis, shows protective effects in LPS-induced septic shock and significant inhibitory effect in caspase-11 non-canonical inflammasome pathway. Male C57BL/6J were injected intraperitoneally with LPS (20 mg/kg) to induce experimental septic shock. The results demonstrated that the survival rates of mice pretreated with goitrin or Toll-like receptor 4 (TLR4) inhibitor TKA-242 increased, and LPS-induced hypothermia and lung damage improved by inhibiting inflammatory response. Elucidating the detailed mechanism, we surprisingly found goitrin is really different from TAK-242, it independent of the TLR4 signal activation, but significantly inhibited the activation of caspase-11 non-canonical inflammasome, including cleaved caspase-11 and N-terminal fragment of gasdermin D (GSDMD-NT). Furthermore, with a nonlethal dose of the TLR3 agonist poly(I:C)-primed and subsequently challenged with LPS to induce caspase-11-mediated lethal septic shock, the efficacy of goitrin had been verified. Those results revealed the effect of goitrin in protective against LPS-induced septic shock via inhibiting caspase-11 non-canonical inflammasome, which provided a new therapeutic strategy for clinical treatment of septic shock. [ABSTRACT FROM AUTHOR]

Organohalogens play an important role in the drug discovery and functional materials. However, the convenient preparation of organohalogens still remains a challenging task. Herein, we report a metal‐free cascade dihalogenation‐cyclization of cyclohexadienone‐containing 1,6‐enynes in a biodegradable solvent to generate the dibrominated cis‐tetrahydrobenzofuran‐5(4H)‐ones and cis‐dihydrobenzopyran‐6(5H)‐ones respectively bearing 1,4‐dibromobut‐1‐enyl subunit in trans‐trans and trans‐cis form. A subgram‐scale experiment and several downstream transformations are presented for elaborating the synthetic utility. Moreover, the potent anticancer activity is observed against MDA‐MB‐468 cells for the corresponding products. [ABSTRACT FROM AUTHOR]

Gentiana crassicaulis and G. straminea are alpine plants of Gentiana with important medicinal value and complex genetic backgrounds. In this study, the mitochondrial genomes (mtDNAs) of these two species were sequenced. The mtDNAs of G. crassicaulis and G. straminea are 368,808 and 410,086 bp long, respectively, 52 and 49 unique genes are annotated in the two species, and the gene arrangement varies widely. Compared to G. crassicaulis, G. straminea loses three effective genes, namely atp6, trnG-GCC and trnV-GAC. As a pseudogene, the atp6 gene of G. straminea is incomplete, which is rare in higher plants. We detected 1696 and 1858 pairs of long repeats and 213 SSRs and 250 SSs in the mtDNAs of G. crassicaulis and G. straminea, respectively. There are 392 SNPs and 18 InDels between the two genomes, and syntenic sequence and structural variation analysis show low collinearity between the two genomes. Chloroplast DNA transferring to mtDNA is observed in both species, and 46,511 and 55,043 bp transferred segments containing three tRNA genes are identified, respectively. Comparative analysis of mtDNAs of G. crassicaulis, G. straminea and four species of Gentianales determined 18 core genes, and there is no specific gene in G. crassicaulis and G. straminea. The phylogenetic tree based on mtDNAs places Gentianaceae in a branch of Gentianales. This study is the first to analyze the mtDNAs of Gentianaceae, which could provide information for analysis of the structure of mtDNAs of higher plants and phylogenetic research of Gentianaceae and Gentianales. [ABSTRACT FROM AUTHOR]

Owing to increasing demand for Panax notoginseng‐based medicines and health products, establishing a fast, simple, and reliable assay to analyze the chemical differences between its root and rhizome is important. Although previous studies showed that the chemical and biological differences between the root and rhizome of P. notoginseng seem to be small, efforts should be taken to investigate such differences to ensure the safety and efficacy of the products. This work describes a holistic approach that combines characteristic fingerprinting using ultra‐high performance liquid chromatography‐tandem mass spectrometry parent ion scanning with charged aerosol detection and targeted separation by online heart‐cutting two‐dimensional liquid chromatography, to identify and evaluate characteristic markers allowing differentiation of the root and rhizome. A total of five potential markers chikusetsusaponin L5, ginsenoside Rb2, stipuleanoside R2, malonyl‐ginsenoside Rb1, and malonyl‐ginsenoside Rd, were identified and confirmed by comparing chromatographic retention time, the accurate mass of molecular weight, and the fragments of secondary MS with the available reference materials. The results showed that all five markers were 2.8–7 times higher in content in the rhizome than in the root. [ABSTRACT FROM AUTHOR]

Highly efficient, economic and environment-friendly extraction of target bioactive components from the complex matrices of food supplements or natural medicines has always been a challenge, whether it is for the purposes of bioactivity assay, batch preparation, and more constantly the quality assessment of natural products. Mechanochemical assisted extraction (MCAE), as a green technology, shows distinctive superiority in application of high energy mechanical force acting on the raw materials to dissociate the target components from nature products in aqueous media under normal temperature and without the use of any harmful, dangerous and costly organic solvents. Furthermore, the one pot reaction of MCAE provides a quick process, good reproducibility and a direct transfer of the solution into the instruments like a reverse-phase HPLC system for the subsequent analysis. This review represents the recent advances in MCAE dealing with the mechanisms, types of equipment, impact parameters, advantages/disadvantages comparing with the other extraction technologies and the application in extraction of food, nutrition and health products derived from natural sources, focusing on samples preparation for the purposes of quality control and physiological & biological activity assay. Different types of equipment that meet the needs of experiment research and industrial production, and the conditions and impact parameters depending on the diversity of the target compounds to be extracted from the natural raw materials. In one word, MCAE can play a very important role in the sustainable green industrial production of food, nutraceutical and health products. • An extraction method for natural products that reduces use of organic solvents. • Solid auxiliaries are beneficial to the storage and transport during production. • Different equipment can meet the different needs of industrial production. • One pot reaction provides a quick process and good reproducibility. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in various types of cancer. Current developments in transcriptome analyses unveiled the existence of lncRNAs; however, their functional characterization remains a challenge. Methods: A bioinformatics screen was performed by integration of multiple omics data in hepatocellular carcinoma (HCC) prioritizing a novel oncogenic lncRNA, LINC01132. Expression of LINC01132 in HCC and control tissues was validated by qRT-PCR. Cell viability and migration activity was examined by MTT and transwell assays. Finally, our results were confirmed in vivo mouse model and ex vivo patient derived tumor xenograft experiments to determine the mechanism of action and explore LINC01132-targeted immunotherapy. Results: Systematic investigation of lncRNAs genome-wide expression patterns revealed LINC01132 as an oncogene in HCC. LINC01132 is significantly overexpressed in tumor and associated with poor overall survival of HCC patients, which is mainly driven by copy number amplification. Functionally, LINC01132 overexpression promoted cell growth, proliferation, invasion and metastasis in vitro and in vivo. Mechanistically, LINC01132 acts as an oncogenic driver by physically interacting with NRF and enhancing the expression of DPP4. Notably, LINC01132 silencing triggers CD8+ T cells infiltration, and LINC01132 knockdown combined with anti-PDL1 treatment improves antitumor immunity, which may prove a new combination therapy in HCC. Conclusions: LINC01132 functions as an oncogenic driver that induces HCC development via the NRF1/DPP4 axis. Silencing LINC01132 may enhance the efficacy of anti-PDL1 immunotherapy in HCC patients. [ABSTRACT FROM AUTHOR]

Rationale: Bear bile powder (BBP) is a widely used traditional Chinese medicine (TCM), and bile acids (BAs) are the main active components in BBP. Due to the scarcity of BBP resources, adulterations often occur in the market. Conventional methods to distinguish them are usually complicated and time‐consuming. To enhance effectiveness and accuracy, a rapid and rough analytical method is desperately needed. Methods: In this study, a rapid strategy using chip‐based nano‐electrospray ionization tandem mass spectrometry (nano‐ESI‐MS/MS) was established to distinguish BBP from other sources of bile powder (BP). In addition, the results were further verified by ultra‐high‐performance liquid chromatography combined with high‐resolution mass spectrometry (UPLC/MS). Results: The precision of the chip‐based nano‐ESI‐MS/MS method was validated to be acceptable with relative standard deviation (RSD) <15%. The distinction between BBP and other sources of BP, including common adulterants of pig bile powder (PBP), cattle bile powder (CBP), sheep bile powder (SBP), and chicken bile powder (CkBP), can be observed in the spectra. By using orthogonal partial least‐squares discriminant analysis (OPLS‐DA), more potential m/z markers were investigated. A BAs‐related m/z marker of 498.3 was discovered as a typical differential molecular ion peak and was identified as tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) in BBP. Conclusions: The proposed strategy has simple sample pretreatment steps and significantly shortened analysis time. As an emerging technology, chip‐based nano‐ESI‐MS not only provides a reference for the rapid distinction of adulterated Chinese medicines, but also provides some insights into the identification of other chemicals and foods. [ABSTRACT FROM AUTHOR]

Panax ginseng C.A. Meyer., a famous and valuable traditional Chinese medicine with thousand years of history for its healthcare and therapeutic effects. It is necessary and meaningful to study the pharmacokinetic behavior of ginsenosides in vivo as they are the most active components. Dried blood spots (DBS) are a mature and advanced blood collection method with meet the needs for the measurement of numerous analytes. This study aimed to explore the feasibility on DBS in the metabolic profile analysis of complex herbal products. An ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ginsenosides. The preparation of DBS samples was conducted by spiking the whole blood with analytes to obtain 20 μL of blood spots on Whatman 903 collection card. A punched dish of 10 mm in diameter was extracted with 70 % methanol aqueous solution, digoxin was used as an internal standard. Target compounds were separated on a Waters T3 column (2.1 × 100 mm, 1.8 μm) with acetonitrile and water (0.1 % formic acid) at a flow rate of 0.4 mL/min. The various ginsenosides showed good linearity in the range of 1–2000 ng/mL. The extraction recoveries and matrix effects of the target analytes were above 82.2%. The intra- and inter-batch accuracy and precision were within the limits of ≤15% for all tested concentrations. Moreover, the collected dried blood spot samples could be stably stored at room temperature for 14 days and 4 °C for 1 month without being affected. And it is delightful that the DBS-based analysis is compatible or even superior to the conventional protein precipitation in terms of sensitivity, linearity, and stability. In particular, the target analytes are stable in the DBS sampling under normal storing condition and the sensitivity for some trace metabolites of ginsenosides, such as 20(S)-Rg3, 20(R)-Rg3, F1, Rk1, Rg5, etc. increases 3–4 folds as evaluated by LLOQ. The established method was successfully applied to pharmacokinetic studies of ginseng extract in mice, this suggests a more feasible strategy for pharmacokinetic study of traditional and natural medicines both in animal tests and clinical trials. [Display omitted] • A new strategy using DBS with 20 μL of blood for pharmacokinetics of ginseng extract. • Ginsenosides were quantified with comprehensive advantages by DBS treatment. • Four pairs of epimeric rare ginsenosides metabolites were monitored at the same time. [ABSTRACT FROM AUTHOR]

Ten diterpenoids including six unreported abietane-type diterpenoids Glecholmenes A-F (1–6) and an undescribed labdane-type diterpenoid Glecholmene G (9), together with three known diterpenoids (7 , 8 , 10), were firstly isolated from the aerial part of G. longituba. Their structures were established mainly by nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) methods. Electronic circular dichroism (ECD) calculations and X-ray crystallographic analyses were used for the determination of their absolute configurations. The anti-inflammatory activity of all compounds was evaluated using the classical LPS-induced NO release model in RAW264.7 cells. Compound 2 displayed significant anti-inflammatory activities with IC 50 values of 29.08 ± 1.40 μM (Aminoguanidine hydrochloride as the positive control, IC 50 = 21.84 ± 0.48 μM). [Display omitted] • Seven previously undescribed diterpenoids were discovered from G. longituba. • All the compounds were isolated from this plant for the first time. • Labdane-type diterpenoids were found in G. longituba for the first time. • The absolute configurations were determined by X-ray single crystal diffraction and ECD calculations. • Compound 2 exhibited significant anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cutting-edge mass spectrometry as the cornerstone for pyrrolizidine alkaloid analysis in complex samples. • Innovative analytical strategies reshaping PAs analysis are presented. • Different applications of PAs containing related samples has been summarized. Pyrrolizidine alkaloids (PAs) in food and natural preparations have received widespread attention due to their hepatotoxicity, genotoxicity, and embryotoxicity. Mass spectrometry (MS), as a high resolution, high sensitive, and high throughput detection tool, has been the most commonly used technique for the determination of PAs. The continuous advancement of new technologies, methods, and strategies in the field of MS has contributed to the improvement of the analytical efficiency and methodological enhancement of PAs. This paper provides an overview of the structure, toxicity properties and commonly employed analytical methods, focusing on the concepts, advances, and novel techniques and applications of MS-based methods for the analysis of PAs. Additionally, the remaining challenges, future perspectives, and trends for PA detection are discussed. This review provides a reference for toxicological studies of PAs, content monitoring, and the establishment of quality control and safety standards for herbal and food products. [ABSTRACT FROM AUTHOR]

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908–0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics. [ABSTRACT FROM AUTHOR]

The extraction of active constituents from natural sources in a green and efficient manner is considered an important field in the pharmaceutical industry. In recent years, deep eutectic solvents (DESs), a new type of green solvent, have attracted increasing attention. Therefore, we aimed to establish a green and high-efficiency extraction method for ginsenosides based on DESs. This study takes Panax ginseng as a model sample. Eighteen different DESs were produced to extract polar ginsenosides. Ultrasound-assisted extraction (UAE) was applied for simplicity and efficiency. A binary DES synthesized using choline chloride and urea at a proportion of 1:2 prepared by a heating stirring method is proven to be more effective than other solvents, such as the widely used 70% ethanol for the extraction of ginsenosides. Three variables that might affect the extraction, including the DES content in the extraction solvent, liquid/solid ratio, and ultrasound extraction time, were evaluated for optimization. The optimum extraction conditions for ginsenosides were determined as follows: DES water content of 20 wt%, liquid/solid ratio of 15 mL g−1, and an ultrasonic extraction time of 15 min. The extraction yield for the optimized method is found to be 31% higher than that for 70% ethanol, which achieves efficient extraction. This study shows that DESs are available to extract ginsenosides for use in traditional Chinese medicine. The discovery also contributes to further research into the green extraction of ginsenosides. [ABSTRACT FROM AUTHOR]

Poria cocos, with medicinal and edible properties, contains multiple chemical components that pose difficulties in its quality control. Herein, we established a simple thin-layer chromatography spray ionization-mass spectrometry (TLCSI-MS) device that allows the simultaneous separation and identification of bioactive compounds. The triterpene acids in different medicinal parts of Poria cocos were characterized, and the markers of differences were revealed. The quantitative analysis of its pharmaceutical preparation has also been performed to verify the feasibility. The study provides a new analytical perspective for the screening and identification of multiple compounds and a good option for the quality evaluation of herbal medicines and foods. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction disease (HSOS) is a rare but life-threatening vascular liver disease. However, its underlying mechanism and molecular changes in HSOS are largely unknown, thus greatly hindering the development of its effective treatment. Hepatic sinusoidal endothelial cells (HSECs) are the primary and essential target for HSOS. A tandem mass tag-based shotgun proteomics study was performed using primary cultured HSECs from mice with HSOS induced by senecionine, a representative toxic pyrrolizidine alkaloid (PA). Dynamic changes in proteome were found at the initial period of damage and the essential role of thrombospondin 1 (TSP1) was highlighted in PA-induced HSOS. TSP1 over-expression was further confirmed in human HSECs and liver samples from patients with PA-induced HSOS. LSKL peptide, a known TSP1 inhibitor, protected mice from senecionine-induced HSOS. In addition, TSP1 was found to be covalently modified by dehydropyrrolizidine alkaloids in human HSECs and mouse livers upon senecionine treatment, thus to form the pyrrole-protein adduct. These findings provide useful information on early changes in HSECs upon PA treatment and uncover TSP1 overexpression as a contributor in PA-induced HSOS. [ABSTRACT FROM AUTHOR]

The efficient preparation of the stilbenoid lusianthridin is described. This synthesis relies on a Suzuki–Miyaura coupling and an intramolecular nucleophilic substitution as key reactions to construct the 9,10-dihydrophenanthrene core. The synthesis is completed in seven steps with a 13.2% overall yield, and each step can be conducted on a >20 gram scale. The route has provided 20 grams of lusianthridin for further biological activity studies. [ABSTRACT FROM AUTHOR]

Red ginseng and white ginseng, with different chemical constituents, exhibit different antioxidative, anticancer, antiasthmatic and immunomodulatory properties. The aim of this study was to determine the amount of ginsenoside contents (Rg1, Re, Rb1, Rb2, Rc, Rd and Ro) in red and white ginseng. A rapid and comprehensive method was developed using the quality-by-design (QbD) and heart-cutting two-dimensional liquid chromatography (2D-LC) techniques. The temperature (25°C), mobile phase constituent (0.1%H3PO4), flow rate (0.35 mL/min) and concentrations of the final (45%) and initial (19.5%) organic solvents were optimized to efficient chromatography-based isolation method. The gradient program was optimized by QbD Fusion AE system. A selective column (Thermo Acclaim RSLC Polar Advantage II 2.2 μm, 100 × 2.1 mm) was used for the studies. The ginsenoside Rb1, Rc and Ro exhibiting poor separation resolution were separated using the heart-cutting 2D-LC technique. The average Rb1, Rb2 and Rc contents in red ginseng were significantly higher than the average Rb1, Rb2 and Rc contents in white ginseng. Ginsenoside Ro can be potentially used as a marker to evaluate the qualities of white and red ginseng. This comprehensive and rapid method can be potentially used to screen the quality of the markers in the future. [ABSTRACT FROM AUTHOR]

Three new alkaloids, seneciobipyrrolidine ( 1), seneciopiperidine ( 2), and 4- pyrrolidinophenyl acetate ethyl ester ( 3) were isolated from Senecio scandens. Their structures were elucidated on the basis of spectroscopic data. [ABSTRACT FROM AUTHOR]

Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng , shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d -borneol (DB), l -borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO. [Display omitted] • Borneol (BO) promoted the oral absorption of Panax notoginseng saponins (PNS) in rat. • Dl -borneol (synthetic) increased PNS exposure in rats more than d - or l -borneol. • Compatibility ratio of BO and PNS at 1:1 can better promote the absorption of PNS. [ABSTRACT FROM AUTHOR]