Tian Ma Research Articles

The Combination of Gastrodin and Gallic Acid Synergistically Attenuates AngII-Induced Apoptosis and Inflammation via Regulation of Sphingolipid Metabolism.

Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear. This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms. The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting. In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways. Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN.

Neuroprotective effects of Gastrodia elata Blume on promoting M2 microglial polarization by inhibiting JNK/TLR4/T3JAM/NF-κB signaling after transient ischemic stroke in rats.

Gastrodia elata Blume, also called Tian Ma (TM), has been used to treat stroke for centuries. However, its effects on inflammation in acute cerebral ischemic injury and underlying mechanisms involved in microglial polarization remain unknown. The present study explored the effects of the TM extract on the modulation of microglial M1/M2 polarization 2days after transient cerebral ischemia. Male Sprague Dawley rats were intracerebroventricularly administered with 1% dimethyl sulfoxide 25min before cerebral ischemia and subsequently intraperitoneally administered 0.25g/kg (DO + TM-0.25g), 0.5g/kg (DO + TM-0.5g), or 1g/kg (DO + TM-1g) of the TM extract after cerebral ischemia onset. DO + TM-0.5g and DO + TM-1 g treatments downregulated the following: phospho-c-Jun N-terminal kinase (p-JNK)/JNK, tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3), TRAF3-interacting JNK-activating modulator (T3JAM), p-nuclear factor-kappa B p65 (p-NF-κB p65)/NF-κB p65, ionized calcium-binding adapter molecule 1 (Iba1), CD86, TNF-α, interleukin (IL)-1β, and IL-6 expression and toll-like receptor 4 (TLR4)/Iba1, CD86/Iba1, and p-NF-κB p65/Iba1 coexpression. These treatments also upregulated IL-10, nerve growth factor, and vascular endothelial growth factor A expression and YM-1/2/Iba1 and IL-10/neuronal nuclei coexpression in the cortical ischemic rim. The JNK inhibitor SP600125 exerted similar treatment effects as the DO + TM-0.5g and DO + TM-1 g treatments. DO + TM-0.5g and DO + TM-1 g/kg treatments attenuate cerebral infarction by inhibiting JNK-mediated signaling. TM likely exerts the neuroprotective effects of promoting M1 to M2 microglial polarization by inhibiting JNK/TLR4/T3JAM/NF-κB-mediated signaling in the cortical ischemic rim 2days after transient cerebral ischemia.

Clonostachys rosea, a Pathogen of Brown Rot in Gastrodia elata in China.

Gastrodia elata, commonly known as Tian Ma, is a perennial mycoheterotrophic orchid. Qianyang Tian Ma (QTM), a geographical indication agricultural product from Hongjiang City, Hunan Province, China, is primarily characterized by the red variety, G. elata f. elata. A severe outbreak of tuber brown rot disease was documented in QTM during the harvesting season in Hunan. The fungal pathogen associated with the disease was isolated on potato saccharose agar (PSA) and identified through morphological and phylogenetic analyses. Pathogenicity tests were performed on healthy tubers of G. elata f. elata. The results showed that the representative isolate, named TMB, produced white hyphal colonies with a ring structure, broom-like phialides, partially curved ellipsoidal conidia, and orange-yellow spherical ascocarps on PSA. Phylogenetic analysis of the ITS, LSU, rpb2 and tub2 sequences using Bayesian and maximum-likelihood methods identified the isolate TMB as Clonostachys rosea, based on morphological and phylogenetic data. Pathogenicity tests revealed typical disease symptoms on healthy G. elata tubers 15 days post-inoculation with the isolate TMB. C. rosea is known to cause diseases in economically important crops, but there are no reports of its occurrence on G. elata f. elata in China. This study provides valuable insights into the occurrence, prevention, and control of brown rot disease in G. elata f. elata.

Study on the chemical composition of Gegen-Tianma decoction and its absorbed constituents in rat plasma, brain based on UPLC-Q-TOF-MS and DESI-MSI

In traditional Chinese medicinal practices, Gegen (GG) and Tianma (TM) are widely utilized for headache relief, but their material basis has not been comprehensively characterized. This research utilized ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) for precise determination of Gegen-Tianma's (GGTM) material composition, and employed desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to pinpoint the brain-absorbed components and various metabolites post oral administration to rats. A total of 80 chemical constituents were identified from GGTM, 11 prototypes and 18 metabolites were identified from plasma. The brain tissue was identified in total 4 prototypes and 5 metabolites, these constituents were basically located in the prefrontal cortex and thalamus. The absorption patterns of components in the rat brain aligned with the varied distribution of metabolites within the brain. This study provides a solid theoretical basis for in-depth exploration of potential drug targets and elucidation of the specific mechanism of action of GGTM in the treatment of migraine.

Abstract 3124: MRG006A, a novel glypican-3-targeting antibody-drug conjugate, demonstrated potent anti-tumor activity and good safety profile in preclinical studies

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most challenging cancers with high unmet medical need. Glypican-3 (GPC3) is an oncofetal glycoprotein anchored to the cell surface via GPI (glycosylphosphatidylinositol) and frequently over-expressed in HCC with limited expression in normal adult tissues, which makes it an appealing antibody-drug conjugate (ADC) target for HCC. MRG006A is a potentially first-in-class GPC3-targeting ADC composed of a novel humanized IgG1 antibody conjugated to a proprietary linker-payload platform utilizing a potent topoisomerase 1 inhibitor via a peptide-based cleavable linker. Materials and Methods: As a GPC3-targeting ADC intended for clinical therapy of GPC3-expressing cancers, the mechanism of action and therapeutic potential of MRG006A were investigated in a series of preclinical studies, including (1) MRG006A and its antibody moiety binding to human GPC3 expressed on cells assessed by flow cytometry; (2) binding affinity to human and cynomolgus monkey GPC3 measured by SPR (surface plasmon resonance); (3) internalization in Huh7 cells assessed by pHAb Reactive Dye and confocal microscopy; (4) in vitro cytotoxicity against a panel of HCC cell lines (Huh7, HepG2, Hep3B and GPC3-negative SK-HEP-1); (5) anti-tumor activity of MRG006A evaluated in Huh7 and HepG2 cell line-derived xenograft (CDX) as well as a panel of HCC patient-derived xenograft (PDX) mouse models with a different expression level of GPC3; (6) plasma stability of MRG006A evaluated in human, cynomolgus monkey, rat and mouse plasma; and (7) an exploratory pharmacokinetic (PK) and toxicology study of MRG006A in cynomolgus monkey. Results: The GPC3-targeting ADC, MRG006A, and its antibody moiety exhibited superior binding activity to GPC3-expressing cancer cell lines than a clinical antibody benchmark and similar nanomolar binding affinity to both human and cynomolgus monkey GPC3, which makes cynomolgus monkey suitable for toxicological studies. Rapid internalization of MRG006A antibody was observed in GPC3-expressing Huh7 cells, and MRG006A maintained comparable internalization capability to the naked antibody. More importantly, MRG006A exhibited potent GPC3-dependent cytotoxic activity in a panel of HCC cells expressing varying levels of GPC3. Administrations of MRG006A resulted in a robust and dose-dependent tumor growth inhibition of multiple CDX models and HCC PDX models. Remarkable stability of MRG006A was shown in the plasma of various species tested. MRG006A demonstrated a favorable PK and safety profile with good tolerability in the exploratory toxicology study. Conclusion: Overall, the preclinical study results suggest that MRG006A is a feasible ADC drug candidate for treating GPC3-expressing cancers in clinical studies. MRG006A was aimed to submit IND in China and the U.S in 2024. Citation Format: Yanchun Wang, Hongfeng Li, Hao Shen, Wenchao Liu, Shoujia Liu, Kequan Yin, Haili Xu, Xueyuan Cui, Wei Li, Wei Liu, Xiangyu Wu, Liu Yang, Tian Ma, Zhongrun Zhao, Jun Wang, Feifei Cui, Lei Fang, Minmin Qin, Chaohong Hu. MRG006A, a novel glypican-3-targeting antibody-drug conjugate, demonstrated potent anti-tumor activity and good safety profile in preclinical studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3124.

Observations of Nine Millisecond Pulsars at 8600 MHz Using the TMRT

We report detection results of nine millisecond pulsars (MSPs) at 8600 MHz using simultaneous 2250 and 8600 MHz observations conducted with the Shanghai Tian Ma Radio Telescope. Mainly benefiting from updated ephemerids with 2250 MHz observations, integrated profiles of all nine MSPs at 8600 MHz are successfully obtained by coherently adding multi-epoch (3–83 epochs) observation data spanning from 19–1210 days, which significantly increases the number of MSPs with published profiles (from 4 to 11) above 8000 MHz, as seven of our target MPSs had no related results previously. Combining our new flux density and pulse width measurements with previous low-frequency results, we study their integrated profile evolution and spectral behaviors in a wider frequency range. We find their component separations and pulse widths remain almost constant, which is consistent with previous findings. While dramatic evolution of integrated profiles exists at low frequencies, we observe a potential end of the related evolution around 5 GHz in eight MSPs. The spectra of four MSPs are found to deviate from a single power law, and we fit them with a broken power law. The change in the profile of PSR J1713+0747, which started around MJD 59320−59321, seems to be more prominent as the observation frequency increases. Compared with the effects of the interstellar medium, we prefer to explain this event as some changes in the magnetosphere. We also find its integrated profile possibly had not recovered to the pre-event state until MJD 59842–59857.

ANALYSIS OF TRADITIONAL CHINESE MEDICINE PRESCRIPTIONS FOR CEREBRAL STROKE-RELATED DISEASES

Cerebral stroke, a type of cerebrovascular disease, has become the second leading cause of death globally. It is closely related to many diseases, including hypertension, diabetes, senile dementia, and so forth. As traditional Chinese medicine formulas are increasingly used to treat stroke and its associated diseases, people have begun to use machine learning methods to analyze Chinese medicine prescriptions and summarize their laws. In this study, we collected the data from classic Chinese formulations. Using the Jaccard similarity coefficient method, we calculated the similarity between different prescriptions. We then employed average linkage clustering, categorizing medicine prescriptions for chronic diseases such as diabetes, hypertension, and coronary heart disease into 12 groups. Some of these included “Heart Failure and Warm Kidney Soup”, “Sinus Chamber Junction Syndrome, Quadruple One Depression, Yi Qi, Activating Blood and Feeding Heart Soup”, “Nerves One, Depression One, Tian Ma Hook and Vine Drink”, and “Bawei Antihypertensive Decoction, Anemia Decoction, Hypotension Decoction, Myocardial Live Drink”. We observed that similar prescriptions had more meaningful mutual references. Subsequently, a correlation algorithm was used to analyze the “indications” and “prescription composition”, revealing 11 effective correlation rules. Among these, palpitations were strongly correlated with Astragalus membranaceus, Angelica sinensis, and cassia twig; weakness with Salvia miltiorrhiza, A. membranaceus, and A. sinensis; headaches with Ligusticum wallichii; and vertigo with A. membranaceus. These findings provided a theoretical reference for using traditional Chinese medicine in treating cerebral stroke and associated illnesses.

Simultaneous 2.25/8.60 GHz Observations of the Magnetar XTE J1810-197

We did 194 epochs of simultaneous 2.25/8.60 GHz observations of XTE J1810−197 in 926 days shortly following its reactivation in 2018 with Shanghai Tian Ma Radio Telescope (TMRT). Although its integrated profiles changed with both time and frequency during this period, they could be classified into 12 types according to phase areas of active radiation components. After MJD 59015, XTE J1810−197 turned from the normal emission state into the spiky emission state that was manifesting as a series of bright narrow sub-pulse bursts at both 2.25 and 8.60 GHz. Due to its variable integrated profiles and unsteady rotations, we got the spin frequency ν and spin-frequency derivatives with the piecewise fitting method. In addition, its long-term declining trend of ν was also obtained as s−2 with the linear fitting method based on our observations spanning a comparatively longer period. We found its flux densities went through three stages: sharp decrease, stabilization, and day-to-day fluctuations in our dual-frequency observations. Although the flux density showed different stages, XTE J1810−197 showed a relatively flat spectrum (α > –1) in most observations. Assuming an ideal dipole magnetic field as some previous research works, we obtained the emission heights of XTE J1810−197 were about 7.5(9) × 104 km and 2.38(7) × 104 km at 2.25 and 8.60 GHz, respectively. We also found that its emission heights would decrease rapidly with the degree of magnetic field twisting.

HS-GC-IMS Analysis of Volatile Organic Compounds in Different Varieties and Harvesting Times of Rhizoma gastrodiae (Tian Ma) in Yunnan Province.

Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) coupled with principal component analysis (PCA) was used to investigate the differences in volatile organic compounds (VOCs) in four different varieties of Yunnan Huang Tian Ma (containing both winter and spring harvesting times), Yunnan Hong Tian Ma, Yunnan Wu Tian Ma, and Yunnan Lv Tian Ma. The results showed that the flavor substances of different varieties and different harvesting times of Rhizoma gastrodiae were mainly composed of aldehydes, alcohols, ketones, heterocycles, esters, acids, alkenes, hydrocarbons, amines, phenols, ethers, and nitrile. Among them, the contents of the aldehydes, alcohols, ketones, and heterocyclic compounds are significantly higher than those of other substances. The results of cluster analysis and fingerprint similarity analysis based on principal component analysis and Euclidean distance showed that there were some differences between different varieties of Yunnan Rhizoma gastrodiae and different harvesting times. Among them, Yunnan Lv Tian Ma and Wu Tian Ma contained the richest volatile components. Winter may be the best harvesting season for Tian Ma. At the same time, we speculate that the special odor contained in Tian Ma should be related to the aldehydes it is rich in, especially benzene acetaldehyde, Benzaldehyde, Heptanal, Hexanal, Pentanal, and butanal, which are aldehydes that contain a strong and special odor and are formed by the combination of these aldehydes.

Developmental neurotoxicity evaluation of three Chinese herbal medicines in zebrafish larvae by means of two behavioral assays: Touch-evoked response and light/dark transition

Chinese herbal medicine (CHM) is used among pregnant women. However, the question of its safety during pregnancy remains unclear. The use of these products relies on history of use data but there are specific toxicities like developmental neurotoxicity that are clearly understudied. Here we use the zebfrafish embryo developmental toxicity assay (ZEDTA) in combination with two behavioral assays: touch-evoked response and Light/Dark (L/D) transition assay to evaluate the neuro/developmental toxicity of three herbal products commonly used in CHM [Chinese name (abbreviation; part of the plant and Scientific name]: tian ma (TM; tuber form Gastrodia elata Blume), lei gong teng (LGT; root and rhizome of Tripterygium wilfordii Hook.f) and cha ye (green tea, leaves from Camellia sinensis (L.) Kuntze). In case significant alterations were detected, single components with potential exposure during pregnancy were identified in the literature and further tested. TM had no neurodevelopmental toxic potential in zebrafish embryos, while LGT and its main compounds triptolide and celastrol induced significant alterations in behavior. Developmental exposure to EGCG, the main catechin of green tea, also produced significant alterations in zebrafish embryos behavior after developmental exposure. A combination of ZEDTA with L/D Transition assay is proposed as a useful combination of alternative methods for DNT assessment of CHM products together with other New Approach Methodologies (NAMs).

Data mining analysis of professor Qiu Changlin's Chinese Medicinal therapy for Parkinson's disease

AbstractBackgroundParkinson's disease (PD) is a prevalent, progressive neurodegenerative disease that has been widely treated using dopamine replacement therapy. However, this therapy does not prevent the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Clinical experience has shown that Chinese medicines (CMs) can alleviate the side effects of Western medicines for PD and improve the quality of life of patients.ObjectiveThis paper describes the collection and analysis of Professor Qiu Changlin's decoctions for PD and proposes new ideas on the Law of CM Clinical Formula Administration and Syndrome Differentiation of PD.MethodsA database of Professor Qiu's prescriptions for PD patients of Zhejiang Provincial Hospital of Chinese Medicine over 5 years (January 2018 to May 2022) was established and analyzed using Microsoft Excel 2019 and SPSS Modeler 22.0.ResultsFrequency analysis of 1162 prescriptions comprising 232 CMs revealed 17 high‐frequency CMs, including Shu Di Huang (Rehmanniae Radix Praeparata) and Chao Bai Shao (Paeoniae Radix Alba), and correlations among the CMs. The property (nature) of these CMs is warm, and the flavors are mainly bitter, sweet, and sour. Most enter the liver meridian. Based on cluster analysis, we obtained a core effective prescription that mainly comprises Tian Ma, Gou Teng Yin and Zuo Gui Wan.ConclusionThe core effective prescription is expected to inspire new ideas for the administration of CM clinical formulas and syndrome differentiation in PD.

Differences in Volatile Organic Compounds in Rhizoma gastrodiae (Tian Ma) of Different Origins Determined by HS-GC-IMS

Headspace gas chromatography–ion mobility spectrometry (HS-GC-IMS) and principal component analysis (PCA) were used to compare the differences in volatile organic compounds (VOCs) of Rhizoma gastrodiae (Tian Ma) from six different origins in Yunnan, Sichuan, Shaanxi, Anhui, Hubei, and Guizhou. A total of 161 signal peaks were identified, and 84 compounds were characterized, including 23 aldehydes, 19 alcohols, 12 ketones, 8 heterocyclic compounds, 7 esters, 4 phenols, 4 acids, 4 ethers, 2 amines, and 1 alkane. The results of cluster analysis and fingerprint similarity analysis based on principal component analysis and Euclidean distance indicated that there were significant differences between the volatile components of Rhizoma gastrodiae from different origins. This study demonstrated that HS-GC-IMS is simple, rapid, accurate, and has a small sample size and can achieve rapid analysis of the differences in volatile compounds between samples of different origins of Rhizoma gastrodiae.

Assessment of the Effects of Structural Modification of Gastrodia elata Polysaccharide on Anti-Breast Cancer Activity Using Asymmetrical Flow Field-Flow Fractionation.

Gastrodia elata ("Tian Ma" in Chinese) is used as a food and medical ingredient in traditional Chinese medicine. In this study, to enhance the anti-breast cancer activity of Gastrodia elata polysaccharide (GEP), GEPs were modified via sulfidation (SGEP) and acetylation (AcGEP). The physicochemical properties (such as solubility and substitution degree) and structural information (such as molecular weight Mw and radius of gyration Rg) of GEP derivatives were determined by Fourier transformed infrared (FTIR) spectroscopy and asymmetrical flow field-flow fractionation (AF4) coupled online with multiangle light scattering (MALS) and differential refractive index (dRI) detectors (AF4-MALS-dRI). The effects of the structural modification of GEP on the proliferation, apoptosis, and cell cycle of MCF-7 cell were studied systematically. The ability of MCF-7 cell for the uptake of GEP was studied by laser scanning confocal microscopy (LSCM). The results suggested that the solubility and anti-breast cancer activity of GEP were enhanced and the average Rg and Mw of GEP decreased after chemical modification. The AF4-MALS-dRI results showed that the chemical modification process simultaneously caused the degradation and aggregation of GEPs. The LSCM results revealed that more SGEP can enter the MCF-7 cell interior compared with AcGEP. The results indicated that the structure of AcGEP could play a dominating role in antitumor activity. The data obtained in this work can be used as a starting point for investigating the structure-bioactivity of GEPs.

Review of Tian Ma, Contesting Crimmigration in Post-hukou China

Review of Tian Ma, Contesting Crimmigration in Post-hukou China

Natural products for migraine: Data-mining analyses of Chinese Medicine classical literature

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap. Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised. Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia. Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

The Tian Ma 65-m Telescope Automatic Early Warning System

The Tian Ma Radio Telescope (TMRT), which is mainly used for deep space exploration and radio astronomy observations, is the largest fully steerable radio telescope in Asia. For promoting the automation of the telescope, an automatic early warning system is designed and implemented. The system can conveniently aggregate heterogeneous sensor data, make use of established strategies to implement an alert system, and send real-time alarms through multiple channels, which is helpful to promote unmanned operation. In addition, we adopt DevOps (a compound of development (Dev) and operations (Ops) which means end-to-end automation in software development and delivery) to simplify the development, upgrading, and maintenance of the telescope automatic early warning system.

Cyanopolyyne line survey towards high-mass star-forming regions with TMRT

Context. Cyanopolyynes (HC2n+1 N, n = 1,2,3), which are the linear carbon chain molecules, are precursors for the prebiotic synthesis of simple amino acids. They are important for understanding prebiotic chemistry and may be good tracers of the star formation sequence. Aims. We aim to search for cyanopolyynes in high-mass star-forming regions (HMSFRs) at possibly different evolutionary stages, investigate the evolution of HC3N and its relation with shock tracers, and detect the existence of HC5N and HC7N in HMSFRs with a formed protostar. Methods. We carried out a cyanopolyyne line survey towards a large sample of HMSFRs using the Shanghai Tian Ma 65 m Radio Telescope (TMRT). Our sample consisted of 123 targets taken from the TMRT C band line survey. It included three kinds of sources, namely those with detection of the 6.7 GHz CH3OH maser alone, with detection of the radio recombination line (RRL) alone, and with detection of both (hereafter referred to as Maser-only, RRL-only, and Maser-RRL sources, respectively). For our sample with detection of cyanopolyynes, their column densities were derived using the rotational temperature measured from the NH3 lines. We constructed and fitted the far-infrared (FIR) spectral energy distributions (SED; obtained from the Herschel FIR data and the Atacama Pathfinder Experiment data at 870 µm) of our HC3N sources. Moreover, by analysing the relation between HC3N and other shock tracers, we also investigate whether HC3N is a good tracer of shocks. Results. We detected HC3N in 38 sources, HC5N in 11 sources, and HC7N in G24.790+0.084, with the highest detection rate being found for Maser-RRL sources and a very low detection rate found for RRL-only sources. The mean column density of HC3N was found to be (1.75 ± 0.42) × 1013, (2.84 ± 0.47) × 1013, and (0.82 ± 0.15) × 1013 cm−2 for Maser-only, Maser-RRL, and RRL-only sources, respectively. Based on a fit of the FIR SED, we derive their dust temperatures, H2 column densities, and abundances of cyanopolyynes relative to H2. The mean relative abundance of HC3N was found to be (1.22 ± 0.52) × 10−10 for Maser-only, (5.40 ± 1.45) × 10−10 for Maser-RRL, and (1.65 ± 1.50) × 10−10 for RRL-only sources, respectively. Conclusions. The detection rate, the column density, and the relative abundance of HC3N increase from Maser-only to Maser-RRL sources and decrease from Maser-RRL to RRL-only sources. This trend is consistent with the proposed evolutionary trend of HC3N under the assumption that our Maser-only, Maser-RRL, and RRL-only sources correspond to massive young stellar objects, ultracompact H ii regions, and normal classical H ii regions, respectively. Our detections enlarge the sample of HC3N in HMSFRs and support the idea that unsaturated complex organic molecules can exist in HMSFRs with a formed protostar. Furthermore, a statistical analysis of the integrated line intensity and column density of HC3N and shock-tracing molecules (SiO, H2CO) enabled us to find positive correlations between them. This suggests that HC3N may be another tracer of shocks, and should therefore be the subject of further observations and corresponding chemical simulations. Our results indirectly support the idea that the neutral-neutral reaction between C2H2 and CN is the dominant formation pathway of HC3N.

Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro

Adverse outcome pathways (AOPs) are organized sequences of key events (KEs) that are triggered by a xenobiotic-induced molecular initiating event (MIE) and summit in an adverse outcome (AO) relevant to human or ecological health. The AOP framework causally connects toxicological mechanistic information with apical endpoints for application in regulatory sciences. AOPs are very useful to link endophenotypic, cellular endpoints in vitro to adverse health effects in vivo. In the field of in vitro developmental neurotoxicity (DNT), such cellular endpoints can be assessed using the human “Neurosphere Assay,” which depicts different endophenotypes for a broad variety of neurodevelopmental KEs. Combining this model with large-scale transcriptomics, we evaluated DNT hazards of two selected Chinese herbal medicines (CHMs) Lei Gong Teng (LGT) and Tian Ma (TM), and provided further insight into their modes-of-action (MoA). LGT disrupted hNPC migration eliciting an exceptional migration endophenotype. Time-lapse microscopy and intervention studies indicated that LGT disturbs laminin-dependent cell adhesion. TM impaired oligodendrocyte differentiation in human but not rat NPCs and activated a gene expression network related to oxidative stress. The LGT results supported a previously published AOP on radial glia cell adhesion due to interference with integrin-laminin binding, while the results of TM exposure were incorporated into a novel putative, stressor-based AOP. This study demonstrates that the combination of phenotypic and transcriptomic analyses is a powerful tool to elucidate compounds’ MoA and incorporate the results into novel or existing AOPs for a better perception of the DNT hazard in a regulatory context.Graphical abstract

Pulse Profile Variations Associated with Two Glitches of PSR B1822–09

We reported two new glitches of PSR B1822−09 that were detected at the Shanghai Tian Ma Radio Telescope. The glitches occurred around MJD 58,025 and 58,474.5, respectively. The shapes of the integrated mean pulse profiles in both the radio-bright (B-mode) and the radio-quiet (Q-mode) modes changed after two glitches. Such changes are probably related to the trigger mechanisms of the glitches. According to the Gaussian fitting to the integrated mean pulse profiles, variations of the integrated mean pulse profiles can be attributed to variations of the Gaussian components. The fitting also indicates that there may be changes in only a part of the Gaussian components after glitches. We proposed an interpretation of the relation between the precursor and the interpulse of PSR B1822−09 according to variations of Gaussian components. We analyzed the cumulative distributions of the glitch sizes and the waiting times of all 14 glitches of PSR B1822−09. The cumulative distribution of the glitch sizes can be fitted well by a power law with an index α of 0.985 ± 0.005. The cumulative distribution of the waiting times follows a Poisson model with a mean waiting time λ of 466 ± 66 days. The correlation coefficient between the waiting times and the sizes of the corresponding preceding glitches is 0.906. In contrast, there is no apparent correlation between the waiting times and the sizes of the corresponding trailing glitches.

Ameliorative effect of Gastrodia elata Blume extracts on depression in zebrafish and cellular models through modulating reticulon 4 receptors and apoptosis

Ethnopharmacological relevanceGastrodia elata Blume (G. elata), a traditional Chinese herb, known as “Tian Ma”, is widely used as a common medicine and diet ingredient for treating or preventing neurological disorders for thousands of years in China. However, the anti-depressant effect of G. elata and the underlying mechanism have not been fully evaluated. Aim of the studyThe study is aimed to investigate the anti-depressant effect and the molecular mechanism of G. elata in vitro and in vivo using PC12 cells and zebrafish model, respectively. Material and methodsNetwork pharmacology was performed to explore the potential active ingredients and action targets of G. elata Blume extracts (GBE) against depression. The cell viability and proliferation were determined by MTT and EdU assay, respectively. TUNEL assay was used to examine the anti-apoptotic effect of GBE. Immunofluorescence and Western blot were used to detect the protein expression level. In addition, novel tank diving test was used to investigate the anti-depressant effect in zebrafish depression model. RT-PCR was used to analyze the mRNA expression levels of genes. ResultsG. elata against depression on the reticulon 4 receptors (RTN4R) and apoptosis-related targets, which were predicted by network pharmacology. Furthermore, GBE enhanced cell viability and inhibited the apoptosis in PC12 cells against CORT treatment. GBE relieved depression-like symptoms in adult zebrafish, included increase of exploratory behavior and regulation of depression related genes. Mechanism studies showed that the GBE inhibited the expression of RTN4R-related and apoptosis-related genes. ConclusionOur studies show the ameliorative effect of G. elata against depression. The mechanism may be associated with the inhibition of RTN4R-related and apoptosis pathways.