Effect of icariin on depressive behaviour in rat pups. Evidences for its mechanism of action by integrating network pharmacology, metabolomics and gut microbiota composition.

BACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear. PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups. METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing. RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour. CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.

Inhibition of FLT1 Attenuates Neurodevelopmental Abnormalities and Cognitive Impairment in Offspring Caused by Maternal Prenatal Stress.

Fms-like tyrosine kinase 1 (FLT1) has been shown to regulate processes such as angiogenesis, neurogenesis, and cognitive impairment. However, the role of FLT1 in prenatal stress (PS) is unclear. The purpose of this study was to investigate the role of FLT1 in PS mothers and their offspring. Wire mesh restrainers were used to construct PS rat model. The levels of FLT1, IL-1ß, IL-6, and ROS in clinical samples and rat samples were detected by qRT-PCR, ELisa kit, and DCFH-DA fluorescence kit. Morris water maze assay and forced swimming assay were used to test the cognitive function of offspring young rats. The apoptosis level of hippocampal neurons and the expression of NMDARs were detected by MTT assay, TUNEL assay, and Western blot. The results showed that FLT1 was upregulated in PS mothers and positively correlated with PS degree. The level of FLT1 was elevated in PS model rats. Knockdown of FLT1 reduced maternal ROS and MDA levels and increased SOD levels in PS rats. Knockdown of FLT1 also reduced the secretion of IL-1ß, IL-6, and cortisol in PS rats. Inhibition of FTL1 alleviated cognitive impairment in PS offspring pups. Inhibition of FTL1 reduced hippocampal neuronal apoptosis and increased the expression of NMDARs in PS progeny. In conclusions, we demonstrated that knockdown of FLT1 inhibits maternal oxidative stress, inflammation, and cortisol secretion in PS rats. In addition, knockdown of FLT1 also alleviated cognitive dysfunction and neurodevelopmental abnormalities in PS offspring pups.

Electronic and thermal transport properties of the metallic antiferromagnet MnSn2.

We report the structure, magnetic and electrical/thermal transport properties of the antiferromagnet MnSn2. Importantly, the existence of the two antiferromagnetic states below TN2 (∼320 K) is confirmed by magnetism and electrical transport measurements. An unsaturated positive magnetoresistance up to 150% at ∼9 T was observed at 5 K, whereas the magnetoresistance becomes negative in the whole range at high temperatures (T > 74 K). Systematic investigations of the Hall transport and thermoelectric properties reveal that the hole-type carriers are the majority carriers in MnSn2. The kink around 320 K in the Seebeck coefficient originates from the effect of the antiferromagnetic phase on the band structure, while the pronounced peak around 231 K is attributed to the phonon-drag effect. The results suggest that the spin arrangement plays a vital role in the magnetic, electrical, and thermal transport properties in MnSn2.

Air travel demand forecasting based on big data: A struggle against public anxiety.

It is of great significance to accurately grasp the demand for air travel to promote the revival of long-distance travel and alleviate public anxiety. The main purpose of this study is to build a high-precision air travel demand forecasting framework by introducing effective Internet data. In the age of big data, passengers before traveling often look for reference groups in search engines and make travel decisions under their informational influence. The big data generated based on these behaviors can reflect the overall passenger psychology and travel demand. Therefore, based on big data mining technology, this study designed a strict dual data preprocessing method and an ensemble forecasting framework, introduced search engine data into the air travel demand forecasting process, and conducted empirical research based on the dataset composed of air travel volume of Shanghai Pudong International Airport. The results show that effective search engine data is helpful to air travel demand forecasting. This research provides a theoretical basis for the application of big data mining technology and data spatial information in air travel demand forecasting and tourism management, and provides a new idea for alleviating public anxiety.

Research on Government-Enterprise Regulation of Online Car-Hailing Based on Differential Game.

In the Internet era, with the widespread application of digital technology, the way people travel has changed. Compared with traditional taxis, more and more people prefer to choose online car-hailing. The rapid development of the online car-hailing industry has solved the problem of taxi-hailing to a certain extent, but it has also brought some new problems. To change the dilemma of the online car-hailing industry, it is necessary to strengthen the regulation of the online car-hailing industry. In this study, we consider the regulatory system composed of a local government and an enterprise and use the differential game to study the regulation of online car-hailing. In the Nash non-cooperative game, Stackelberg master-slave game, and cooperative game, we, respectively, investigate the indicators, such as the optimal regulatory effort of the government, the optimal regulatory effort of the enterprise, the optimal benefit function of the government, the optimal benefit function of the enterprise, the optimal benefit function of the system, the optimal trajectory of the service quality level for the enterprise, and the optimal trajectory of the goodwill for the enterprise. Moreover, we analyze the corresponding conclusions through examples. We obtained some important results. (i) In the Stackelberg master-slave game, the optimal ratio of the local government subsidy to the enterprise's regulatory cost is only related to the benefit distribution coefficient and has nothing to do with other factors. Moreover, when the benefit distribution coefficient is >1/3, the local government is willing to share the regulatory cost of the enterprise. Otherwise, the local government refuses to share the regulatory cost of the enterprise. (ii) Compared with the Nash non-cooperative game, the optimal regulatory effort of the local government remains unchanged in the Stackelberg master-slave game, but the optimal benefit of the local government increases. Moreover, when the benefit distribution coefficient is >1/3, both the optimal regulatory effort and the optimal benefit of the enterprise increase. (iii) Compared with the Stackelberg master-slave game, in the cooperative game, the optimal regulatory effort of both government and enterprise increases, and the system's optimal benefit also increases. (iv) From the Nash non-cooperative game to the Stackelberg master-slave game and then to the cooperative game when the benefit distribution coefficient is >1/3, the service quality level and goodwill of the enterprise all increase.

Do Internet Search Data Help Forecast Air Passenger Demand? Evidence From China's Airports.

Before making travel plans, people often use the Internet to collect relevant information to help themselves make better decisions. Among the numerous information search channels, Internet search engine is used by the vast number of travelers because of its low cost and high efficiency. To a large extent, Internet search behavior is the external manifestation of users' psychological activities, reflecting their concerns, needs and preferences. Therefore, Internet search data can reflect the air passenger demand information to a certain extent. In this manuscript, a novel decomposition ensemble model is proposed to discuss the role of Internet search data in air passenger demand forecasting. In the empirical study, the relevant data of Shanghai Pudong International Airport and Beijing Capital International Airport are taken as samples. The results show that the proposed forecasting model can integrate the advantages of decomposition-ensemble strategy and deep learning algorithm, and achieve more accurate and reliable prediction results than all benchmark models. This further indicates that adding Internet search data into the forecasting model can effectively improve the prediction performance of air passenger demand, and can provide scientific and reliable decision support for air transport management.

Research on Corporate Social Responsibility Coordination of Three-Tier Supply Chain Based on Stochastic Differential Game.

In the Internet era, consumers prefer products with the attributes of social responsibility. Supply chain enterprises strengthen corporate social responsibility (CSR) management for their own development. To improve CSR throughout the supply chain, it requires coordination and cooperation among the members of the supply chain. In this paper, we consider a three-tier supply chain system consisting of a supplier, a manufacturer, and a retailer and use stochastic differential game to study the CSR coordination of the supply chain. The following indicators are investigated under four decision situations, such as the optimal level of CSR effort for the supply chain members, the optimal value of profit for the supply chain members and the supply chain system, and the expectation and variance of CSR goodwill. Some important results are obtained. (i) Compared with decentralized decision-making, the optimal level of CSR effort increases for the supplier and the manufacturer under local alliance decision-making without cost sharing, whereas the optimal level of CSR effort remains unchanged for the retailer. (ii) Compared with local alliance decision-making without cost sharing, the optimal level of CSR effort remains unchanged for the supplier and the manufacturer under local alliance decision-making with cost sharing. When the sum of the marginal profit for the supplier and the manufacturer is greater than half of the marginal profit for the retailer, the optimal level of CSR effort increases for the retailer. (iii) Compared with local alliance decision-making with cost sharing, the optimal level of CSR effort increases for the supply chain members under overall alliance decision-making. (iv) From decentralized decision-making to local alliance decision-making without cost sharing, to local alliance decision-making with cost sharing, and then to overall alliance decision-making, the optimal value of profit increases for the supply chain members and the supply chain system. Also, the expectation and variance of CSR goodwill increase.

Different modulation effects of Tai Chi Chuan and Baduanjin on resting-state functional connectivity of the default mode network in older adults.

The default mode network (DMN) plays an important role in age-related cognitive decline. This study aims to explore the modulation effect of two mind-body interventions (Tai Chi Chuan and Baduanjin) on DMN in elderly individuals. Participants between 50 and 70 years old were recruited and randomized into a Tai Chi Chuan, Baduanjin or control group. The Wechsler Memory Scale-Chinese Revision and resting-state fMRI scans were administered at baseline and following 12 weeks of exercise. Seed-based resting-state functional connectivity (rsFC) was calculated. We found that (i) compared to the Baduanjin group, Tai Chi Chuan was significantly associated with increased rsFC between the medial prefrontal cortex (mPFC) and right putamen/caudate and (ii) compared to the control group, Tai Chi Chuan increased posterior cingulate cortex rsFC with the right putamen/caudate, while Baduanjin decreased rsFC between the mPFC and orbital prefrontal gyrus/putamen. Baseline mPFC rsFC with orbital prefrontal gyrus was negatively correlated with visual reproduction subscore. These results suggest that both Tai Chi Chuan and Baduanjin can modulate the DMN, but through different pathways. Elucidating the mechanisms underlying different mind-body interventions may shed light on the development of new methods to prevent age-related diseases as well as other disorders associated with disrupted DMN.

Effects of Tai Chi Yunshou exercise on community-based stroke patients: a cluster randomized controlled trial.

BACKGROUD: Tai Chi Chuan was used for stroke survivors with balance impairments. However, even a short-form of Tai Chi Chuan includes forms that make the exercise challenging for the stroke survivors. Tai Chi Yunshou (wave hands in the cloud) is the "mother" form and the fundamental form of all Tai Chi Chuan styles, which is considered more suitable and feasible for stroke survivors with balance impairments. So this study was designed to evaluate the effects of Tai Chi Yunshou exercise on community-based stroke patients with balance dysfunctions. METHODS: A total of 250 participants from 10 community health centers (5 per arm) were selected and randomly allocated into Tai Chi Yunshou exercise group (TC group) or a balance rehabilitation training group (control group) in an equal ratio. Participants in the TC group were received Tai Chi Yunshou exercise training five times per week for 12 weeks and those in control group were received balance rehabilitation training five times per week for 12 weeks. Outcome assessments including Berg Balance Scale (BBS), Time up to go test (TUGT), Modified Barthel Index (MBI) were measured at baseline, 4 weeks, 8 weeks, 12 weeks and followed-up 6 weeks (18 weeks), 12 weeks (24 weeks). Intention-to-treat analysis was performed. Analysis of variance of repeated measures was used to assess between-group differences. RESULTS: A total of 244 participants, 120 in the TC group and 124 in the rehabilitation group, were included in final analysis. There was no siginificant difference in Tai Chi Yunshou and balance rehabilitation training on the improvement of balance ability and mobility (P = 0.531 and P = 0.839, respectively) after adjustment for baseline. However, there was significant difference between two groups on improvement of motor funtion (P = 0.022), fear of falling (P < 0.001) and depression (P = 0.035) for the post stroke patients. No adverse events were reported during the study. CONCLUSION: Tai Chi Yunshou and balance rehabilitation training led to improved balance ability and functional mobility, and both are suitable community-based programs that may benefit for stroke recovery and community reintegration. Our data demonstrated that a 12-week Tai Chi Yunshou intervention was more effective in motor function, fear of falling and depression than balance rehabilitation training. Future studies examining the effectiveness of Tai Chi Yunahou as a balance ability improvement strategy for community-dwelling survivors of stroke are recommended. TRIAL REGISTRATION: Chinese Clinical Trail Registry: ChiCRT-TRC-13003641. Registration date: 22 August, 2013.