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Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

Normal aging is accompanied by hippocampus-dependent cognitive impairment and act as a risk factor of Alzheimer’s disease (AD). The study aims to investigate the effect of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on hippocampus-dependent learning and memory in aged mice and to explore the underlying mechanisms. Forty-five male Kunming mice (15-month-old) were randomly divided into 3 aged groups: aged sham, 5Hz rTMS and 25Hz rTMS group. Two sessions of 5Hz or 25Hz rTMS comprising of 1000 pulses in 10 trains were delivered once a day for consecutive 14 days. Aged sham group were treated by the reverse side of the coil. In adult sham group, fifteen male Kunming mice (3-month-old) were treated the same way as aged sham group. Morris water maze (MWM) was conducted following the stimulation. The synaptic ultrastructure was observed by transmission electron microscope (TEM). HF-rTMS improved the spatial learning and memory impairment in aged mice and 5Hz was more significant than 25Hz. Synaptic plasticity associated gene profiles were modified by HF-rTMS, especially neurotrophin signaling pathway and cyclic adenosine monophosphate response element binding protein (CREB) cofactors. Compared to aged sham group Synaptic plasticity associated proteins, i.e. synaptophysin (SYN) and post synaptic density (PSD) 95 were increased, brain derived neurotrophic factor (BDNF) and phosphorylated CREB (pCERB) were significantly increased after 5Hz HF-rTMS treatment. Collectively, our results suggest that HF-rTMS ameliorated the cognitive deficits in natural aged mice. 5Hz rTMS treatment significantly enhances synaptic structural plasticity and actives BDNF / CREB pathway in hippocampus. Therefore, HF-rTMS may serve as an effective noninvasive, nonsurgical method for enhancing cognitive functions and may translate into novel treatments to alleviate cognitive decline in normal aging in the future.

In Western medicine, therapeutic drugs for the treatment of diseases are required to have a well-defined pure molecular target （one protein or one gene） because the understanding of molecular mechanisms for diseases are largely based on the principle of phenotype-genotype relationship, ie, ＂one gene encoding one protein and responsible for one phenotype＂.

Targeting modules or signalings may open a new path to understanding the complex pharmacological mechanisms of reversing disease processes. However, determining how to quantify the structural alteration of these signalings or modules in pharmacological networks poses a great challenge towards realizing rational drug use in clinical medicine. Here, we explore a novel approach for dynamic comparative and quantitative analysis of the topological structural variation of modules in molecular networks, proposing the concept of allosteric modules (AMs). Based on the ischemic brain of mice, we optimize module distribution in different compound-dependent modular networks by using the minimum entropy criterion and then calculate the variation in similarity values of AMs under various conditions using a novel method of SimiNEF. The diverse pharmacological dynamic stereo-scrolls of AMs with functional gradient alteration, which consist of five types of AMs, may robustly deconstruct modular networks under the same ischemic conditions. The concept of AMs can not only integrate the responsive mechanisms of different compounds based on topological cascading variation but also obtain valuable structural information about disease and pharmacological networks beyond pathway analysis. We thereby provide a new systemic quantitative strategy for rationally determining pharmacological mechanisms of altered modular networks based on topological variation.

The natural and ecologically safe control of stored product insects has gained considerable attention in modern society. In this study of further searching for botanical pesticides from wild-growing plant, the contact toxicity and repellency towards Tribolium castaneum and Liposcelis bostrychophila were assessed for the essential oil (EO) from Ostericum viridiflorum . The EO was distilled from aboveground parts of O. viridiflorum and checked by gas chromatography-mass spectrometry. Twenty-two compounds were identified and the main components were β -caryophyllene (24.3%), α -humulene (21.0%), apiol (10.2%), and carotol (2.5%). For bioactivity tests, results indicated that the EO and its two main compounds ( β -caryophyllene and α -humulene) all showed potent contact toxicity towards L. bostrychophila with LD 50 values of 44.52 μg/cm 2 , 74.11 μg/cm 2 , and 118.56 μg/cm 2 , respectively. The EO and the two main compounds also exhibited comparable repellency towards T. castaneum and L. bostrychophila . The results evidenced the EO of O. viridiflorum aboveground parts and its major compounds could be considered for the development of eco-friendly botanical insecticides and repellents in controlling stored product insects.

After rocks are damaged under stress loading, the changes of their microstructural and mechanical properties are major factors that affect construction safety in geotechnical engineering projects. Studying the microstructures and mechanical behaviors of stress-damaged rocks can help better guide construction and reduce construction risks for geotechnical engineering projects. In this study, a sandstone was first artificially predamaged and then subsequently subjected to scanning electron microscopy (SEM) analysis, computed tomography (CT) scanning, and uniaxial compression testing. Afterwards, the rock microstructures were three-dimensionally (3D) reconstructed, and the pores were classified and characterized based on their diameters. Moreover, the microstructural and mechanical parameters of the rock were subjected to significance analysis. The results showed that as the stress-induced damage (σi) increased, the uniaxial compressive strength (σc) of the soft rock decreased by 13.7–31.8%; as σi increased from 11.2 to 19.6 MPa, the elastic modulus (E) of the soft rock increased by up to 28.8%; and as σi increased beyond 19.6 MPa, there was a significant (22.3%) decrease in E. Stress-induced damage significantly affected the spatial distribution of the pores’ structure of the soft rock. Changes in the spatial structure of the pores led to the formation of cracks. The microstructural parameters of the stress-damaged soft rock were correlated with its mechanical parameters.

This work aimed to investigate chemical composition of essential oils obtained from Zanthoxylum dissitum leaves and roots and their insecticidal activities against several stored product pests, namely the cigarette beetle (Lasioderma serricorne), red flour beetle (Tribolium castaneum) and black carpet beetle (Attagenus piceus). The analysis by GC-MS of the essential oils allowed the identification of 28 and 22 components, respectively. It was found that sesquiterpenoids comprised a fairly high portion of the two essential oils, with percentages of 74.0% and 80.9% in the leaves and roots, respectively. The main constituents identified in the essential oil of Z. dissitum leaves were δ-cadinol (12.8%), caryophyllene (12.7%), β-cubebene (7.9%), 4-terpineol (7.5%) and germacrene D-4-ol (5.7%), while humulene epoxide II (29.4%), caryophyllene oxide (24.0%), diepicedrene-1-oxide (10.7%) and Z,Z,Z-1,5,9,9-tetramethyl-1,4,7-cycloundecatriene (8.7%) were the major components in the essential oil of Z. dissitum roots. The insecticidal activity results indicated that the essential oil of Z. dissitum roots exhibited moderate contact toxicity against three species of storage pests, L. serricorne,T. castaneum and A. piceus, with LD50 values of 13.8, 43.7 and 96.8 µg/adult, respectively.

Refined Qing-Kai-Ling (QKL), a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid), plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA) and principal component analysis (PCA) to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5) could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4) were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM), emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.

In the early February, 2020, we called up an experts’ committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.