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Objective Renal interstitial fibrosis (RIF) is the common pathological feature of Chronic kidney disease (CKD). The diagnosis of RIF requires kidney biopsy, while non-invasive methods are still lacking. Given the association between (Pro)renin receptor (PRR) and organ fibrosis, and the secrete nature of soluble (pro)renin receptor (soluble PRR), we postulate that serum soluble PRR may serve as a potential biomarker of renal fibrosis in CKD patients.Methods 90 CKD patients received kidney biopsy were included, 75 of them were followed up for 1 year. Serum soluble PRR concentration was determined by ELISA kits. Masson staining and PRR immunohistochemical staining were performed on their renal biopsy specimens.Results (1) Serum soluble PRR was statistically significant in patients with different degrees of RIF (P = 0.002). Multivariate analysis showed that serum soluble PRR could independently predict the risk of RIF (P = 0.046). (2) Serum soluble PRR was positively correlated with serum creatinine (r = 0.282, P = 0.007) and negatively correlated with eGFR (r=-0.321, P = 0.002). With the progression of CKD, the serum soluble PRR level was increased significantly (P = 0.010). (3) PRR expression in renal tissues was positively correlated with the area of RIF (r = 0.836, P Conclusions Serum soluble PRR and renal PRR expression in CKD patients were positively correlated with the degree of RIF. Serum soluble PRR can independently predict the risk of RIF and the progression of CKD.

Objective: Through the method of network analysis, the acupuncture prescriptions recorded in Essential Prescriptions Worth A Thousand Gold (EPWATG) were investigated, and the laws of acupuncture point use were discussed. Methods: Literatures, including acupuncture prescriptions in EPWATG, were collected and screened, according to the method of differentiating prescriptions based on the diseased part. Microsoft Excel 2010 was used to establish a database of prescriptions for head and neck diseases, chest and flank diseases, abdomen diseases, lumbosacral diseases and limbs diseases, and a network of acupoint compatibilities was constructed using the Cytoscape software. Using the network analysis method, the commonly used acupoint compatibilities and core acupoints of acupuncture and moxibustion treatment for various parts of diseases and syndromes in EPWATG were excavated. Results: The commonly used acupoint compatibilities in EPWATG prescriptions for the treatment of head and neck diseases are Tianzhu and Taodao, Hanyan and Houding, and Baihui and Xinshu, and the core acupoints are Tianzhu, Benshen, Kunlun, Zhongzhu, Zutonggu, Fengchi and Shangguan. The commonly used acupoint compatibilities for the treatment of chest and flank diseases are Ququan and Xiangu, Rangu and Taixi, and Yanggu and carpal bone, and the core acupoints are Zhangmen, Feishu, Tanzhong, Yunmen, Jimen and Zhongfu. The commonly used acupoint compatibilities for the treatment of abdominal diseases are Gongsun and Taibai, Shuigou and Dazhui, and Dazhui and Shixuan, and the core acupoints are Tanzhong, zhangmen, Pishu, Ganshu, Laogong and Taixi. The commonly used acupoint compatibilities for the treatment of lumbosacral diseases are Xialiao and Shangliao, Danshu and Geshu, and Dazhu and Shentao, and the core acupoints are Dachangshu, Weizhong, Weiyang, Chengfu and Eight-liao. The commonly used acupoint compatibilities for the treatment of four limbs diseases are Dubi and Shanglian, Dubi and Xialian, and Shanglian and Xialian, and the core acupoints are Xuanzhong, Zusanli, Fuliu, Sanyinjiao, Shanglian, Xialian and Shugu. Conclusion: The selection of acupuncture points in EPWATG follows the law of acupoint selection based on the meridians and diseased parts. This also focuses on the selection of acupoints of the bladder meridian of foot Taiyang and specific acupoints. This provides a scientific basis for clinical acupuncture and moxibustion treatment.

As the increasing number of the individuals suffering from AIDs, chemotherapy, and radiotherapy, pathogenic fungi, which may rapidly grow and invade the host tissues in these immune-compromised patients, is becoming great threat to human health. In this study, we constructed a novel fungal pathogen-responsive assembly of cuprous oxide (Cu2O) nanoparticles (NPs) for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen, Candida albicans ( C. albicans ). This assembly was formed by coating the initial Cu2O NPs with both phosphatidylethanolamine (PE) and bovine serum albumin (BSA), followed by hydrophobic/electrostatic interaction-driven formation of the Cu2O-PE-BSA microaggregates. The formed microaggregates could be induced for disassembly by the fungal pathogen C. albicans , leading to close binding of the NPs to the cell wall of the pathogen. Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen, but had extreme low toxicity to mammalian cells. In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues. This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.

Background: Studies have found that autophagy could promote the clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer's disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. Objective: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. Methods: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris water maze (MWM) test, Nissl’s staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and autophagy related proteins. Results: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.0080.05), while Caspase3 expression in YHD group was significantly lower (P=0.044 Conclusions: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby to regulate autophagy, thereby to promote the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.

In this paper we present a method of zero-padding temporal auto-correlation imaging (ztDCI) for imaging blood flows. Compared with temporal auto-correlation imaging (tDCI), ztDCI effectively slows down the decorrelation speed of speckle frames, so it has wider applicable speed range. We also prove that the combination of tDCI and ztDCI can compensate the non-monotonous trend of ztDCI VS speed and provides higher relative signal to noise rate (rSNR) for slow flows and short exposure times than laser speckle contrast imaging (LSCI). It captures both slow and fast flows independent of camera exposure time which will be an advantage for in vivo or clinical applications.

Background & Objective: NSCs therapy is considered one of the most potential methods for spinal cord injury (SCI). Methods: We build the SCI model rats to investigate the therapeutic effect of fire needle acupuncture in improving the locomotor function of SCI rats and its possible mechanism. BBB scale was used for the motor ability of rats. The expression of Nestin, NSE, Gal-C, and GFAP was detected by immunohistochemistry. Wnt, GSK3β, β-catenin, ERK1/2, CyclinD1, and ngn1 were detected by western blot and PCR. The BBB score of both model group (1.20±0.94, 3.12±0.67, 5.34±1.57, 7.12±1.49) and fire needle group (1.70±0.58, 4.50±1.63, 7.53±2.41, 9.24±0.63) gradually increased after SCI. Furthermore, at d10 and d14, the fire needle group showed a significantly high score compared with that in model group at the same time (P Conclusion: In conclusion, fire needle could improve lower limb locomotor function of SCI rats. Also, fire needles could promote endogenous NSCs proliferation differentiating into neurons, and the mechanism might be mediated by promoting the activation of Wnt/β-catenin and inhibiting the overexpression of ERK.

The vacuolar-type H+-ATPase (V-ATPase) is a highly conserved protein complex among the eukaryotic cells. We previously revealed that both the V-ATPase and the transient receptor potential (TRP) channel Yvc1 are involved in oxidative stress response (OSR). However, the relationship between V-ATPase and Yvc1 during OSR remains unknown. In this study, disruption of the V-ATPase-encoding genes VPH2 and TFP1, similar with disruption of YVC1, caused H2O2 hypersensitivity and enhancement of vacuolar membrane permeability (VMP) under oxidative stress. Further investigations showed that unlike the wild type strain with vacuole membrane-localized Yvc1, both vph2Δ/Δ and tfp1Δ/Δ had Yvc1 localization in the vacuole cavity, indicating that disruption of VPH2 or TFP1 impaired normal vacuolar membrane-localization of Yvc1. Interestingly, addition of CaCl2 alleviated the growth defect of vph2Δ/Δ and tfp1Δ/Δ under oxidative stress, leading to prevention of VMP, decrease in ROS levels and activation of OSR. In contrast, addition of the Ca2+ chelating agent glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) aggravated H2O2 hypersensitivity of the mutants. These results showed that the V-ATPase plays an important role in maintenance of normal Yvc1 localization, which contributes to Ca2+ transport from the vacuoles to the cytosol for activation of OSR. This work sheds a novel light on the interaction between V-ATPase and Ca2+ transport for regulation of OSR in C. albicans.

Studies have found that autophagy could promote the clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer's Disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD.To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model.Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris Water Maze (MWM) test, Nissl's staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and autophagy related proteins.The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.0080.05), and the number of crossing platform in YHD group increased significantly (P=0.020.05). Nissl's staining showed that the number of neurons in YHD group increased significantly (P0.0001). TEM showed in YHD group that the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.0930.05), while Caspase3 expression in YHD group was significantly lower (P=0.0440.05). YHD could promote the clearance of Aβ1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins.YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.

Introduction The functional magnetic resonance imaging (fMRI) Stroop task could be used to study brain activity changes during treatment for Alzheimer’s disease(AD). The aim was to observe the brain functional activity changes during the treatment for AD patients with Yishen Huazhuo Decoction (YHD) using an fMRI Stroop task. Methods Thirty-five mild AD patients were randomized into either a treatment group or a control group in order to observe the brain activity before and after the treatment. Results Before the treatment, the activated regions were bilateral cerebellar hemispheres and bilateral frontal occipital lobe. After the treatment, the activated regions of bilateral cerebellar hemispheres and bilateral frontal occipital lobes decreased for patients in control group, but the activated regions were larger than that in treatment group, and there appeared deactivated regions in the bilateral prefrontal lobes, left orbitofrontal gyrus and right inferior parietal lobule; the activated state of bilateral anterior cingulate gyri, bilateral superior, middle, and medial frontal gyri, left middle-superior frontal gyrus, right middle-superior frontal gyrus, and bilateral posterior cingulate gyri significantly decreased after treatment compared with before treatment in control group. Regions of higher brain functional activity changes in YHD treatment group were observed in the control group were; left anterior central gyrus, left middle-inferior frontal gyrus, bilateral medial frontal gyri, left anterior cingulate gyrus, bilateral superior frontal gyri, left middle frontal gyrus, left superior-middle frontal gyrus. Conclusions We used an fMRI Stroop task to investigate the brain functional activity changes during the treatment of AD patients by YHD, and we found that YHD could improve brain activity of AD patients.

Candida albicans is an important opportunistic fungal pathogen, and hyphal polarized growth is critical for its invasive infection to the host. Both the vacuolar transient receptor potential (TRP) Ca

Candida albicans is an important opportunistic fungal pathogen, and hyphal polarized growth is critical for its invasive infection to the host. Both the vacuolar transient receptor potential (TRP) Ca2+ channel Yvc1 and the NADPH oxidase Fre8-governed reactive oxygen species (ROS) gradient are involved in hyphal development, but the relationship between Yvc1 and Fre8 during hyphal polarized growth remains to be investigated. Herein, we found that deletion of YVC1 led to dispersed distribution of ROS along the germ tube, while it was concentrated at the hyphal tip in WT cells. Moreover, Fre8 localization was altered as YVC1 was disrupted. Besides, similar to deletion of YVC1, addition of the Ca2+ chelating agent EGTA caused depolarization of Fre8-GFP in the wild-type cells, indicating the critical role of Yvc1-maintained Ca2+ gradient in polarized distribution of Fre8-GFP and consequent disruption of tip ROS gradient. By constructing a series of GFP-tagged polarized growth-related proteins, including Bud6, Exo70 and Lifeact, we found that these proteins, similar to Fre8 and ROS, had depolarized localization in yvc1Δ/Δ. Thus, our work provides a mechanic explanation of Yvc1-governed and ROS-related hyphal polarized growth, and shed a novel light on the role of Ca2+ signaling in maintenance of redox homeostasis and morphogenesis in the fungal pathogens.

Background: Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer’s disease (AD). Objective: To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism. Methods: Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured. Results: The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group. Conclusion: The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.