Performance assessment of the effective core potentials under the fermionic neural network: First and second row elements.

The rapid development of deep learning techniques has driven the emergence of a neural network-based variational Monte Carlo (VMC) method (referred to as FermiNet), which has manifested high accuracy and strong predictive power in the electronic structure calculations of atoms, molecules, and some periodic systems. Recently, the implementation of the effective core potential (ECP) scheme has further facilitated more efficient calculations in practice. However, there is still a lack of comprehensive assessments of the ECP's performance under the FermiNet. In this work, we set sail to fill this gap by conducting extensive tests on the first two row elements regarding their atomic, spectral, and molecular properties. Our major finding is that, in general, the qualities of ECPs have been correctly reflected under FermiNet. Two recently built ECP tables, namely, correlation consistent ECP (ccECP) and energy consistent correlated electron pseudopotential (eCEPP), seem to prevail in terms of overall performance. In particular, ccECP performs slightly better on spectral precision and covers more elements, while eCEPP is more systematically built from both shape and energy consistency and better treats the core polarization. On the other hand, the high accuracy of the all-electron calculations is hindered by the absence of relativistic effects as well as the numerical instabilities in some heavier elements. Finally, with further in-depth discussions, we generate possible directions for developing and improving FermiNet in the near future.

Baicalein Attenuates Neuroinflammation in LPS-Treated BV-2 Cells by Inhibiting Glycolysis via STAT3/c-Myc Pathway.

More and more evidence shows that metabolic reprogramming is closely related to the occurrence of AD. The metabolic conversion of oxidative phosphorylation into glycolysis will aggravate microglia-mediated inflammation. It has been demonstrated that baicalein could inhibit neuroinflammation in LPS-treated BV-2 microglial cells, but whether the anti-neuroinflammatory mechanisms of baicalein were related to glycolysis is unclear. Our results depicted that baicalein significantly inhibited the levels of nitric oxide (NO), interleukin-6 (IL-6), prostaglandin 2 (PGE2) and tumor necrosis factor (TNF-α) in LPS-treated BV-2 cells. 1H-NMR metabolomics analysis showed that baicalein decreased the levels of lactic acid and pyruvate, and significantly regulated glycolytic pathway. Further study revealed that baicalein significantly inhibited the activities of glycolysis-related enzymes including hexokinase (HK), 6-phosphate kinase (6-PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and inhibited STAT3 phosphorylation and c-Myc expression. By using of STAT3 activator RO8191, we found that baicalein suppressed the increase of STAT3 phosphorylation and c-Myc expression triggered by RO8191, and inhibited the increased levels of 6-PFK, PK and LDH caused by RO8191. In conclusion, these results suggested that baicalein attenuated the neuroinflammation in LPS-treated BV-2 cells by inhibiting glycolysis through STAT3/c-Myc pathway.

Correction: Gong et al. Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix. Molecules 2016, 21, 549.

Error in Figure [...].

Prediction of the spatiotemporal evolution of vegetation cover in the Huainan mining area and quantitative analysis of driving factors.

The prediction of the spatiotemporal dynamic evolution of vegetation cover in the Huainan mining area and the quantitative evaluation of its driving factors are of great significance for protecting and restoring the environment in this area. This study uses the Landsat 5 TM and Landsat 8 OLI time-series data to estimate the vegetation cover and uses the transition matrix to analyze the spatiotemporal transfer of vegetation cover from 1989 to 2004, 2004 to 2021, and 2021 to 2030. In addition, a structural equation model (SEM) was established in this study to assess the driving factors of vegetation cover. The quantitative analysis and the cellular automata (CA)-Markov model were performed to predict the future vegetation cover in the Huainan mining area. The results are as follows: (1) In different periods, the vegetation cover types were mainly high cover types transferred to other vegetation cover types; (2) human activities are the key factors affecting the vegetation growth, while topographical factor is the most influential factor promoting the vegetation growth; (3) highly consistent CA-Markov and multi-criteria evaluation (MCE) predicted results of vegetation cover in 2030 compared to that in 2021. The proportion of bare soil and low cover types had increased significantly, mainly concentrated in the internal area of the mines. The prediction of the spatiotemporal evolution of vegetation cover in the Huainan mining area and the quantitative change in driving factors are of significant importance for the restoration of the environment in mining areas.

Synergistic neuroprotective effect of saikosaponin A and albiflorin on corticosterone-induced apoptosis in PC12 cells via regulation of metabolic disorders and neuroinflammation.

BACKGROUND: Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanisms are still unknown. METHODS AND RESULTS: The corticosterone-induced PC12 cells apoptosis model was employed to assess the neuroprotective effects of SSA and AF, and the synergistic effect was analyzed using three mathematical models. Meanwhile, cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites than a single agent and possessed a stronger adjustment effect on metabolites. The TCA cycle was regulated by SSA and AF via improving mitochondrial function. The purine metabolism was regulated by SSA via inhibition xanthine oxidase activity and the glutamate metabolism was regulated by AF via inhibition glutaminase activity. Moreover, the oxidative stress induced by the purine metabolism was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. CONCLUSIONS: This study for the first time demonstrated the synergistic neuroprotective effects of SSA and AF, and the synergistic mechanisms were involved in metabolic disorders regulation and neuroinflammation inhibition.

Reproductive-Stage Heat Stress in Cereals: Impact, Plant Responses and Strategies for Tolerance Improvement.

Reproductive-stage heat stress (RSHS) poses a major constraint to cereal crop production by damaging main plant reproductive structures and hampering reproductive processes, including pollen and stigma viability, pollination, fertilization, grain setting and grain filling. Despite this well-recognized fact, research on crop heat stress (HS) is relatively recent compared to other abiotic stresses, such as drought and salinity, and in particular, RSHS studies in cereals are considerably few in comparison with seedling-stage and vegetative-stage-centered studies. Meanwhile, climate change-exacerbated HS, independently or synergistically with drought, will have huge implications on crop performance and future global food security. Fortunately, due to their sedentary nature, crop plants have evolved complex and diverse transient and long-term mechanisms to perceive, transduce, respond and adapt to HS at the molecular, cell, physiological and whole plant levels. Therefore, uncovering the molecular and physiological mechanisms governing plant response and tolerance to RSHS facilitates the designing of effective strategies to improve HS tolerance in cereal crops. In this review, we update our understanding of several aspects of RSHS in cereals, particularly impacts on physiological processes and yield; HS signal perception and transduction; and transcriptional regulation by heat shock factors and heat stress-responsive genes. We also discuss the epigenetic, post-translational modification and HS memory mechanisms modulating plant HS tolerance. Moreover, we offer a critical set of strategies (encompassing genomics and plant breeding, transgenesis, omics and agronomy) that could accelerate the development of RSHS-resilient cereal crop cultivars. We underline that a judicious combination of all of these strategies offers the best foot forward in RSHS tolerance improvement in cereals. Further, we highlight critical shortcomings to RSHS tolerance investigations in cereals and propositions for their circumvention, as well as some knowledge gaps, which should guide future research priorities. Overall, our review furthers our understanding of HS tolerance in plants and supports the rational designing of RSHS-tolerant cereal crop cultivars for the warming climate.

Comprehensive Analysis Strategy of Nervous-Endocrine-Immune-Related Metabolites to Evaluate Arachidonic Acid as a Novel Diagnostic Biomarker in Depression.

Depression is one of the most complex multifactorial diseases affected by genetic and environmental factors. The molecular mechanism underlying depression remains largely unclear. To address this issue, a novel nervous-endocrine-immune (NEI) network module was used to find the metabolites and evaluate the diagnostic ability of patients with depression. During this process, metabolites were acquired from a professional depression metabolism database. Over-representation analysis was performed using IMPaLA. Then, the metabolite-metabolite interaction (MMI) network of the NEI system was used to select key metabolites. Finally, the receiver operating characteristic curve analysis was evaluated for the diagnostic ability of arachidonic acid. The results show that the numbers of the nervous system, endocrine system, and immune system pathways are 10, 19, and 12 and the numbers of metabolites are 38, 52, and 13, respectively. The selected shared metabolite-enriched pathways can be 97.56% of the NEI-related pathways. Arachidonic acid was extracted from the NEI system network by using an optimization formula and validated by in vivo experiments. It was indicated that the proposed model was good at screening arachidonic acid for the diagnosis of depression. This method provides reliable evidences and references for the diagnosis and mechanism research of other related diseases.

Efficient extraction of antimony(III) by titanate nanosheets: Study on adsorption behavior and mechanism.

Antimony has been listed as a critical pollutant in many countries because of its toxic effects on earth organisms. In this study, titanate nanosheets (TNS) were prepared with a high specific surface area by alkaline hydrothermal method. The adsorption mechanism and adsorption capacity of removing Sb(III) from aqueous solutions with TNS as an adsorbent were investigated for the first time. The FTIR and XPS analysis indicated that the interlayer sodium ions of TNS were responsible for Sb(III) adsorption. The batch experiments were conducted on solution pH, adsorbent dosage, initial concentration and reaction time. The results exhibited that when pH was 2, the removal rate was about 90% with the dosage of TNS was 0.1 g/L. The adsorption reaction was exceedingly rapid in the initial 5 min, and then the reaction was in equilibrium after about 30 min. The experimental data were better fitted with Langmuir isotherm model, and the maximum adsorption amount could attain 232.56 mg/g. The experiments showed that TNS had outstanding anti-interference performance to common cations. Therefore, TNS were considered to be an excellent material for removing Sb(III) from aqueous solutions.

Novel Anthraquinone Compounds Inhibit Colon Cancer Cell Proliferation via the Reactive Oxygen Species/JNK Pathway.

A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 µg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

Bioinformatic prediction of critical genes and pathways involved in longevity in Drosophila melanogaster.

The pursuit of longevity has been the goal of humanity since ancient times. Genetic alterations have been demonstrated to affect lifespan. As increasing numbers of pro-longevity genes and anti-longevity genes have been discovered in Drosophila, screening for functionally important genes among the large number of genes has become difficult. The aim of the present study was to explore critical genes and pathways affecting longevity in Drosophila melanogaster. In this study, 168 genes associated with longevity in D. melanogaster were collected from the Human Ageing Genomic Resources (HAGR) database. Network clustering analysis, network topological analysis, and pathway analysis were integrated to identify key genes and pathways. Quantitative real-time PCR (qRT-PCR) was applied to verify the expression of genes in representative pathways and of predicted genes derived from the gene-gene sub-network. Our results revealed that six key pathways might be associated with longevity, including the longevity-regulating pathway, the peroxisome pathway, the mTOR-signalling pathway, the FOXO-signalling pathway, the AGE-RAGE-signalling pathway in diabetic complications, and the TGF-beta-signalling pathway. Moreover, the results revealed that six key genes in representative pathways, including Cat, Ry, S6k, Sod, Tor, and Tsc1, and the predicted genes Jra, Kay, and Rheb exhibited significant expression changes in ageing D. melanogaster strain w1118 compared to young ones. Overall, our results revealed that six pathways and six key genes might play pivotal roles in regulating longevity, and three interacting genes might be implicated in longevity. The results will not only provide new insight into the mechanisms of longevity, but also provide novel ideas for network-based approaches for longevity-related research.

Protective effects of Scutellaria baicalensis Georgi extract on D-galactose induced aging rats.

Scutellaria baicalensis Georgi (SBG), a traditional Chinese herb, has attracted considerable attention for its wide range of pharmacological activities. This study aimed to investigate the intervention effects of SBG ethanol extract on aging rats induced by D-galactose (D-gal) and to explore potential mechanisms by serum and liver metabolic profiles. The aging rats were induced by the D-gal (100 mg/kg) for 10 weeks continuously with subcutaneous injection, while the control rats received physiological saline. Two other groups of rats were administered with 100 mg/kg/day and 200 mg/kg/day of SBG by oral route following D-gal injections. The abilities of spatial and learning memory were evaluated by open-field test and Morris water maze test. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature in hippocampal region was observed by Hematoxylin and eosin (HE) staining. The changes of metabolic profiles were evaluated using proton nuclear magnetic resonance (1H NMR) spectroscopy coupled with multivariate data analysis. Results showed that SBG could significantly improve the learning and memory functions, reducing oxidative damage and histological abnormalities of hippocampus neurons. In addition, significant differences in the metabolic profiles were observed both in serum and liver between the model group and the control group. After the treatment using SBG, the levels of these metabolites are significantly changed back to their similar levels in the control group. These metabolic changes are related to the disturbance in amino acid metabolism, glycometabolism and choline metabolism. Hence, SBG may have the potential to improve neurodegeneration and provide brain protection. Graphical abstract A 1H NMR-based metabonomic study was conducted to provide a global view of metabolites related to D-gal induced aging rats and assess the holistic efficacy of Scutellaria baicalensis Georgi.

[Advances in the study of the rat model of aging induced by D-galactose]

D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.

[Quantitative analysis of eight polyacetylenes derived from Bupleuri Radix by ultra-performance liquid chromatography coupled with photodiode array detector].

To establish quantitative methods for determination of polyacetylenes in Bupleuri Radix, an ultra-performance liquid chromatography method coupled with photodiode array detector (UPLC-PDA) was developed. The analysis was performed on a Waters BEH C18 column (2.1 mm×100 mm, 1.7 µm) using a gradient system of methanol and water. The flow rate was 0.3 mL•min⁻¹ and the detection wavelength was 315 nm. Eight polyacetylenes were prepared using traditional extraction and isolation method, of which compounds 7 and 8 were two new polyacetylenes. All calibration curves showed good linearity (r>0.999 0) within the concentration range. Both the intra- and inter-day precisions for eight analytes were less than 1.9%, respectively, with the mean recovery at the range of 93.21%-108.4%. Meanwhile, 17 bupleurum samples were examined with this process. The results showed a variety either the chemotaxonomic or content of polyacetylenes. The method indicated good linearity, limit of detection and quantification, precision, accuracy and recovery. The developed method allows quantitative assessment and quality control of polyacetylenes, and might be a good alternative according to detection levels in polyacetylenes from Bupleurum Radix.

Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix.

Seven phthalides, including a new dimeric one named tokinolide C (7), were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4) showed cytotoxicity against three cancer cell lines, with IC50 values of 13.82, 6.79, and 7.92 µM, respectively. Tokinolide A (6) and tokinolide C (6) exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4). We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1), Z-butylidenephthalide (3) and tokinolide A (6) exhibited significant neuroprotective effects.

[Baicalein prolongs the lifespan of Drosophila melanogaster through antioxidation activity].

In order to explore the anti-aging effect of baicalein, female Drosophila melanogaster as a model organism was used to study the effects of baicalein on natural aging model and aging models induced by hydrogen peroxide（H2O2） and paraquat. The bioinformatics approach was used to predict the possible target for the anti-aging activity of baicalein, and the target pathways were identified. The oxidative stress pathway was a focus in experiment. Baicalein at concentrations of 0.04 mg·m L-1 and 0.2 mg·m L-1 extended the mean and maximum lifespans in the natural aging model, and effectively reduced the damages of oxidative stress by H2O2 and paraquat. 31 senescence-related targets together with the oxidative stress pathway were modulated by baicalein. The experiments revealed that baicalein might delay aging process through attenuation of the oxidative stress response by decreasing the reactive oxygen species（ROS）, malondialdehyde（MDA） and oxidized glutathione（GSSG） in Drosophila melanogaster.

[Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats].

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, ß-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

[An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology].

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

[Anti-depressive mechanism of Fufang Chaigui prescription based on neuroendocrine hormone and metabolomic correlation analysis].

To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T3and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.

[Study on supercritical CO2 extraction of xiaoyaosan and its GC-MS fingerprint].

To determine the optimum conditions of supercritical CO2 extraction of Xiaoyaosan, and establish its fingerprint by gas chromatography-mass spectrometry (GC-MS), the yield of extract were investigated, an orthogonal test was used to quantify the effects of extraction temperature, pressure, CO2 flow rate and time, and fingerprint analysis of different batches of extracts were by GC-MS. The optimal extraction conditions were determined as follows: extraction pressure 20 MPa, extraction temperature 50 degrees C, CO2 flow rate 25 kg x h(-1), extraction time 3 h, and average yield 2.2%. The GC-MS fingerprint was established and 27 common peaks were found, whose contents add up to 81.89% of the total peak area. Among them, 21 compounds were identified, accounting for 53.20% of the total extract. The extraction process is reasonable and favorable for industrial production. The GC-MS method is accurate, reliable, reproducible, and can be used for quality control of supercritical CO2 extract from Xiaoyaosan.

[Anti-depressant effect and mechanism of supercritical CO2 extract from Compound Chaigui Fang].

The tail suspension test (TST), forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were used to evaluate the anti-depressant effect of supercritical CO2 extract from Compound Chaigui Fang (FFCGF). A nuclear magnetic resonance (NMR)-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight, sucrose preference, crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats' urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats' body weight, sucrose preference, crossings and rearings in CUMS, which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed, which were consistent with the results of behavioral tests. Decreased levels of acetic acid, succinic acid, 2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism, lipid metabolism and amino acid metabolism.