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Depression is a common psychiatric disorder comorbid with diabetes and may lead to high morbidity, disability, and mortality. However, the underlying mechanism behind their association remains unknown. Cytokine-mediated inflammation in brain may play important roles in the pathogenesis of depression and insulin resistance. In the present study, we subjected the rats to chronic unpredictable mild stress (CUMS) for 3 to 8 weeks. The tests to ascertain depression-like behaviors including open field test (OFT) and forced swimming test (FST) were performed, and levels of morning fasting blood glucose, triglyceride (TG), total cholesterol (CHOL), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C), body weight, food intake, histopathological examinations of liver, adipose tissues and hypothalamus, hypothalamic GLUT4 as well as the IL-6-mediated glucose homeostasis signaling pathway were measured. The results showed that CUMS exposure resulted in the depression-like behavior at various time points in rats. Moreover, the rats exhibited increased peripheral glucose levels, impaired hepatocytes and hippocampal neurons, and decreased hypothalamic GLUT4 levels after 6 weeks of CUMS exposure. Meanwhile, activated IL-6 but suppressed IL-6-mediated glucose homeostasis signaling was observed in the hypothalamus. Markers of lipid metabolism including TG, CHOL, HDL-C and LDL-C were dysregulated, and body weight and food intake were decreased in the CUMS-exposed rats. Our results show that depressed rats induced by 6-week CUMS stimulation display susceptibility to hyperglycemia, which is associated with IL-6-mediated inhibition of glucose homeostasis signaling in the hypothalamus.

Babesia microti, the main pathogen causing human babesiosis, has been reported to exhibit resistance to the traditional treatment of azithromycin + atovaquone and clindamycin + quinine, suggesting the necessity of developing new drugs. The methylerythritol 4-phosphate (MEP) pathway, a unique pathway in apicomplexan parasites, was shown to play a crucial function in the growth of Plasmodium falciparum. In the MEP pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a rate-limiting enzyme and fosmidomycin (FSM) is a reported inhibitor for this enzyme. DXR has been shown as an antimalarial drug target, but no report is available on B. microti DXR (BmDXR). Here BmDXR was cloned, sequenced, analyzed by bioinformatics, and evaluated as a potential drug target for inhibiting the growth of B. micorti in vitro. Drug assay was performed by adding different concentrations of FSM in B. microti in vitro culture. Rescue experiment was done by supplementing 200 μM isopentenyl pyrophosphate (IPP) or 5 μM geranylgeraniol (GG-ol) in the culture medium together with 5 μM FSM or 10 μM diminazene aceturate. The results indicated that FSM can inhibit the growth of B. microti in in vitro culture with an IC50 of 4.63 ± 0.12 μM, and growth can be restored by both IPP and GG-ol. Additionally, FSM is shown to inhibit the growth of parasites by suppressing the DXR activity, which agreed with the reported results of other apicomplexan parasites. Our results suggest the potential of DXR as a drug target for controlling B. microti and that FSM can inhibit the growth of B. microti in vitro.

Clinical studies and basic science experiments have widely demonstrated the antidepressant and anxiolytic effects of the herbal formula Xiao-Yao-San (XYS). However, the system mechanism of these effects has not been fully characterized. The present study conducted a comprehensive network pharmacological analysis of XYS and sorted all pharmacologically active components (149) through the TCMSP webserver. Then, all potential molecular targets (449) were predicted, of which there were 99 genes clearly related to depression. To further investigate the mechanism of antidepressant effects of XYS, a compound-depression targets (C-DTs) network was constructed, and Gene Ontology (GO) functional and KEGG pathway enrichment analyses were performed for the 99 targets. Enrichment results revealed that XYS could regulate multiple aspects of depression through these targets, related to metabolism, neuroendocrine function, and neuroimmunity. Prediction and analysis of protein–protein interactions resulted in selection of three hub genes (AKT1, TP53, and VEGFA). In addition, a total of seven ingredients from XYS could act on these hub genes and they were identified through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), including paeoniflorin, quercetin, luteolin, acacetin, aloe-emodin, Glyasperin C, kaempferol. Hereafter, we investigated the effects of paeoniflorin and its predicted target, the results suggest that it can reverse the neurotoxicity produced by CORT and could be a neuroprotective effect by promoting the phosphorylation of Akt. Overall, our research revealed the complicated antidepressant mechanism of XYS, and also provided a rational strategy for revealing the complex composition and function of Chinese herbal formula.

Background: The theory of pulse diagnosis is to assess the physiological condition of the human body using radial pulse. However, pulses can vary markedly from person to person. Further, pulse diagnosis is difficult to learn and requires one-on-one teaching. Methods: To address this problem, we built a home-made pulse diagnoser and measured human pulses for studying the standardization of pulse diagnosis. Our pulse diagnoser was composed of a piezoelectric transducer, differential amplifier, data acquisition instrument, and a Matlab analysis program. The measured pulses were converted into electronic signals by a piezoelectric transducer and saved on a computer. The digitalized data were then refined and analyzed by fast Fourier transform for frequency analysis. Simulations were performed to assess the factors that affected the pulse, including phase shifts of reflected pulse waves (generate sub-peaks in pulses), inconsistent heart rates (deform pulse waves), the vessel stiffness (alter harmonic frequencies of the pulses), and the wave amplitudes (determined by the pulse strength). Results: By comparing a published report and our simulation findings, we characterized the pulse types and the effects of various factors, and then applied the findings to study actual pulses in patients. Three types of pulses were determined from the frequency spectrum—choppy pulse (Se mai) without apparent harmonic peaks, the harmonic frequencies of wiry pulse (Xian mai) that are non-integer multiples of the fundamental frequency, and surging pulse (Hong mai) that exhibit strong amplitudes in the spectrum of frequency. A normal pulse and a slippery pulse were differentiated by a phase shift, but not by assessing the frequency spectrum. Conclusion: These findings confirm that frequency domain analysis can avoid ambiguity arising in assessing the three types of pulses in the time domain. Further studies of other pulses in the frequency domain are required to develop a precise electronic pulse diagnoser.

Objective: To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (CIS). Methods: Rats were divided into control, model, and treatment groups. The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days, during which they were administered Xiaoyao San decoction [3.854 g/(kg·d)] or vehicle by gavage, and their body weight gain, food intake and water intake were monitored. The rats were subsequently subjected to the open field test (OFT) and d-xylose absorption test, and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA), radioimmune analysis, or real-time fluorescence quantitative polymerase chain reaction. Gastric mucosal morphology was also assessed. Results: The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS, abnormalities signified by decreases in food intake, reductions in digestive absorption, decreases in body weight, decreases in the total distances traveled and increases in the time in the central zone during the OFT, gastric mucosal lesion development and decreases in gastrointestinal hormone secretion. These changes were reversed after treatment with Xiaoyao San, which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides. Specifically, the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5, which are secreted by the hypothalamus and promote digestive function, were increased in the Xiaoyao San-treated group compared with the model group. Furthermore, the levels of pro-opiomelanocortin (POMC) and its receptor, melanocortin-4 receptor (MC4R), which are secreted by the hypothalamus and inhibit digestive function, were significantly decreased in the treatment group compared with the model group. However, the levels of ghrelin (GHRL), gastrin (GAS) and motilin (MTL), which are secreted by the stomach, were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P

Background: Chronic stress is an important risk factor for depression. The nesfatin-1 (NES1)–oxytocin (OT)–proopiomelanocortin (POMC) neural pathway, which is involved in the stress response, was recently shown to have an anorectic effect in the hypothalamus. Our previous study showed that Xiaoyaosan, a well-known antidepressant used in traditional Chinese medicine, effectively relieved appetite loss induced by chronic immobilization stress (CIS). However, whether Xiaoyaosan ameliorates depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway remains unclear.Objective: To investigate whether the antidepressant-like and anti-anorexia effects of Xiaoyaosan are related to the NES1-OT-POMC neural pathway in the hypothalamus.Methods: Rats were randomly divided into control, CIS, Xiaoyaosan treatment, and fluoxetine treatment groups. The rats in the CIS, Xiaoyaosan treatment, and fluoxetine treatment groups were subjected to CIS for 21 consecutive days, during which they were administered distilled water, a Xiaoyaosan decoction [3.854 g/(kg·d)] or fluoxetine [1.76 mg/(kg·d)], respectively, by gavage, and their body weights and food intake were monitored daily. The rats were subsequently subjected to the open field test and sucrose preference test. Then, the expression levels of corticosterone and NES1 in the serum and the expression levels of NES1, OT, POMC, and melanocortin-4 receptor (MC4R) in the hypothalamus were determined by real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunochemistry. Furthermore, immunofluorescence double staining was used to determine whether related proteins in the hypothalamic NES1-OT-POMC neural pathway were co-expressed.Results: Compared to control rats, rats exposed to CIS exhibited gradually less food intake and lower body weights and significantly increased concentrations of NES1 in the serum and paraventricular nucleus. Moreover, the expression levels of POMC, OT, and MC4R in the hypothalamus were significantly higher in the CIS group than those in the control group. However, these changes were reversed by pretreatment with Xiaoyaosan and fluoxetine. Specifically, the expression levels of members of the NES1-OT-POMC neural pathway were lower in the Xiaoyaosan-treated group than in the CIS group.Conclusion: Xiaoyaosan ameliorates CIS-induced depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway in the hypothalamus.

Babesia microti, an intraerythrocytic protozoa, can cause an emerging tick-borne disease—Human babesiosis. The parasite can successfully invade host red blood cells owing to the assistance of molecules expressed by babesia. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the housekeeping intracellular glycolytic enzyme, can also be expressed in the external of cells, where contributes to binding to several molecules such as plasminogen and actin. In the present study, we identified B. microti GAPDH (BmGAPDH) and generated the recombinant BmGAPDH (rBmGAPDH) via an E. coli expression system. Furthermore, we confirmed its catalytic dehydration activity in vitro. Moreover, we also demonstrated that rBmGAPDH could bind to human plasminogen and mouse α-actin. In addition, we demonstrated that rBmGAPDH could recognize anti-B. microti mouse serum. In conclusion, BmGAPDH is a multifunctional glycolytic enzyme, which can bind to host plasminogen and α-actin.

The cause of diphyllobothriosis in 5 persons in Harbin and Shanghai, China, during 2008–2011, initially attributed to the tapeworm Diphyllobothrium latum, was confirmed as D. nihonkaiense by using molecular analysis of expelled proglottids. The use of morphologic characteristics alone to identify this organism was inadequate and led to misidentification of the species.

Background: Long-term exposure to chronic stress is thought to be a factor closely correlated with the development of metabolic disorders, such as diabetes mellitus and metabolic syndrome. Xiaoyaosan, a Chinese herbal formula, has been described in many previous studies to exert anxiolytic-like or antidepressant effects in chronically stressed rats. However, few studies have observed the effects of Xiaoyaosan on the metabolic disorders induced by chronic stress. Objective: We sought to investigate the effective regulation of Xiaoyaosan on 21-day chronic immobility stress (CIS, which is 3 h of restraint immobilization every day)-induced behavioural performance and metabolic responses and to further explore whether the effects of Xiaoyaosan were related to SHIP2 expression in the liver. Methods: Sixty male Sprague Dawley rats were randomly divided into a control group, a CIS group, a Xiaoyaosan group and a rosiglitazone group. The latter three groups were subjected to 21 days of CIS to generate the stress model. After 21 days of CIS, the effects of Xiaoyaosan on body weight, food intake, and behaviour in the open field test, the sucrose preference test and the forced swimming test were observed following chronic stress. Plasma insulin, cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) concentrations and blood glucose were examined, and the protein and mRNA expression levels of SHIP2, p85 and Akt in the liver were measured using RT-qPCR and immunohistochemical staining. Results: Rats exposed to CIS exhibited depression-like behaviours, decreased levels of plasma insulin, CHOL, LDL-C, TG and HDL-C, and increased blood glucose. Increased SHIP2 expression and reduced Akt, p-Akt and p85 expression were also observed in the liver. Xiaoyaosan exerted antidepressant effects and effectively reversed the changes caused by CIS. Conclusions: These results suggest that Xiaoyaosan attenuates depression-like behaviours and ameliorates stress-induced abnormal levels of insulin, blood glucose, CHOL, LDL-C and HDL-C in the plasma of stressed rats, which may be associated with the regulation of SHIP2 expression to enhance PI3K/Akt signalling activity in the liver.

Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG), progesterone (PROG) and alloprognanolone (ALLO) in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), cholesterol side-chain cleavage enzyme (P450scc) and 5α-reductase (5a-R) in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3β-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.

Wireless sensor networks (WSNs) have wide applications in many fields sharing common grounds as their major technical challenges. This paper focuses on a high-level information association issue and designs an efficient routing protocol accordingly for delay tolerant mobile sensor networks (DTMSNs). In this paper, after making an analysis about the effect of social network theory on forwarding scheme and node mobility, we exploit landmark, a new social-aware metric indicating the geographical location corresponding to a node interest or a node community. To the best of our knowledge, this is the first work in which landmark is utilized to assist message forwarding in DTMSNs. Additionally, we propose the landmark-centric routing protocol utilizing the metric to accurately predict node mobility geographically. We can take full advantage of node mobility in our protocol while preserving the positive effects of existing social-aware metrics on protocol performance. Simulation results show that the proposed protocol achieves the highest packet delivery ratio outperforming SocialCast and doubling SGBR with more than 50% delivery cost reducing.

Human mobility modeling has increasingly drawn the attention of researchers working on wireless mobile networks such as delay tolerant networks (DTNs) in the last few years. So far, a number of human mobility models have been proposed to reproduce people’s social relationships, which strongly affect people’s daily life movement behaviors. However, most of them are based on the granularity of community. This paper presents interest-oriented human contacts (IHC) mobility model, which can reproduce social relationships on a pairwise granularity. As well, IHC provides two methods to generate input parameters (interest vectors) based on the social interaction matrix of target scenarios. By comparing synthetic data generated by IHC with three different real traces, we validate our model as a good approximation for human mobility. Exhaustive experiments are also conducted to show that IHC can predict well the performance of routing protocols.

The calculation scale of simulating wind farm dynamic radar echo is gradually growing with the increasing scale of wind farms, which can hardly meet the requirements of real-time radar echo simulation. Considering that the method of surface element division can greatly influence the result of simulation, uniform surface element division is applied to accelerate the traditional simulation algorithm based on the refined 3D scattering point model and enhance the main characteristics of the radar echo. The solution time of dynamic radar echoes from 1-8 wind turbines is calculated to test the average speed that the uniform 3D scattering point model can increase. The radar echo and Doppler spectrum of 4 wind turbines are simulated and analyzed as an example to verify the accuracy of the proposed model. The proposed model is demonstrated to accelerate the traditional 3D scattering point model simulation speed by 1.4 times without reducing much accuracy. [ABSTRACT FROM AUTHOR]