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Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD [ABSTRACT FROM AUTHOR]

Purpose: Growing evidence reported that patients with comitant exotropia (CE) were accompanied by static cerebral neural activity changes. However, whether the dynamic time-varying of neural activity changes in patients with CE remains unknown. Methods: A total of 36 patients with CE (25 men and 11 women) and 36 well-matched healthy controls are enrolled in the study. The dynamic amplitude of low-frequency fluctuation (dALFF) combined with the sliding window method was used to assess the dynamic neural activity changes in patients with CE. Results: Compared with HCs, patients with CE had decreased dALFF values in the right superior parietal lobule (SPL) and right precuneus gyrus (PreCUN). Moreover, we found that the dALFF maps showed an accuracy of 48.61% and an area under the curve of.54 for distinguishing the patients with CE from HCs. Conclusion: Our study demonstrated that patients with CE showed altered dynamic neural activity changes in the right SPL and right PreCUN, which might indicate the neuropathological mechanism of stereoscopic dysfunction in patients with CE. [ABSTRACT FROM AUTHOR]

Background: We know little about the changes of brain activity in patients with normal-tension glaucoma (NTG). Purpose: To investigate the altered spontaneous brain activity in patients with NTG through the resting state functional magnetic resonance imaging-fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF) technique, and to explore the relationship with optical coherence tomography (OCT) and field of vision. Material and Methods: Twenty patients with NTG and 20 healthy controls (HCs) (matched for sex, age, and level of education) were enrolled. Spontaneous cerebral activity variations were investigated using the rsfMRI-fALFF technique in all individuals. The average fALFF values of patients with NTG and HCs were compared. Results: Compared with HCs, patients with NTG had significantly lower fALFF values in the right angular gyrus and precuneus; however, higher fALFF values in the brain regions were not observed. The values showed statistically significant negative correlation with those of the retinal nerve fiber layer (right angular gyrus: r = -0.607, P = 0.010; right precuneus: r = -0.504, P = 0.020). There was no significant correlation between the fALFF value and cup-disc ratio (right angular gyrus: r = 0.158, P = 0.494; right precuneus: r = -0.087, P = 0.706), mean deviation (right angular gyrus: r = 0.096, P = 0.468; right precuneus: r = 0.026, P = 0.845), and pattern SD value (right angular gyrus: r = 0.064, P = 0.626; right precuneus: r =-0.145, P = 0.268). Conclusion: Abnormal spontaneous activities were detected in numerous brain regions of patients with NTG, which may provide useful information for understanding the dysfunction in NTG. These activity changes in brain regions may be used as effective clinical indicators for NTG. [ABSTRACT FROM AUTHOR]

Rationale: Platelets are generated in the capillaries of the lung, control hemostasis, and display immunological functions. Tuberculosis primarily affects the lung, and patients show platelet changes and hemoptysis. A role of platelets in immunopathology of pulmonary tuberculosis requires careful assessment.Objectives: To identify the dynamics and interaction partners of platelets in the respiratory tissue and establish their impact on the outcome of pulmonary tuberculosis.Methods: Investigations were primarily performed in murine models of primary progressive pulmonary tuberculosis, by analysis of mouse strains with variable susceptibility to Mycobacterium tuberculosis infection using platelet depletion and delivery of antiplatelet drugs.Measurements and Main Results: Platelets were present at the site of infection and formed aggregates with different myeloid subsets during experimental tuberculosis. Such aggregates were also detected in patients with tuberculosis. Platelets were detrimental during the early phase of infection, and this effect was uncoupled from their canonical activation. Platelets left lung cell dynamics and patterns of antimycobacterial T-cell responses unchanged but hampered antimicrobial defense by restricting production of reactive oxygen species in lung-residing myeloid cells.Conclusions: Platelets are detrimental in primary progressive pulmonary tuberculosis, orchestrate lung immunity by modulating innate immune responsiveness, and may be amenable to new interventions for this deadly disease. [ABSTRACT FROM AUTHOR]

The demands of cooling, heating and electricity in residential buildings are varied with seasons. This article presented a seasonal solar combined cooling heating and power (CCHP) system based on evacuated flat-plate collectors and organic Rankine cycle. The heat collected by evacuated flat-plate collectors is used to drive the organic Rankine cycle unit in spring, autumn and winter, and drive the double-effect lithium bromide absorption chiller in summer. The organic Rankine cycle condensation heat is used to yield hot water in spring and autumn, whereas supply heating in winter. The system thermodynamic performance was analyzed. The results show that the system thermal efficiency in spring, autumn and winter, ηsys,I, increases as organic Rankine cycle evaporation temperature, T6, and evacuated flat-plate collectors outlet temperature, T2, decrease. The maximum ηsys,I of 67.0% is achieved when T6 = 80 °C and T2 =100 °C. In summer, the system thermal efficiency, ηsys,II, increases first and then decreases with the increment of T2. The maximum ηsys,II of 69.9% is obtained at T2 =136 °C. The system output performance in Beijing and Lanzhou is better than that in Hefei. The average output power, heating capacity, hot water and cooling capacity are 50-72 kWh per day, 989-1514 kWh per day, 49-57 ton per day and 1812-2311 kWh per day, respectively. The system exergy efficiency increases from 17.8-40.8% after integrating the organic Rankine cycle unit. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-b (Ab) plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity. In this study, we demonstrated that naringin dihydrochalcone (NDC), a widely used dietary sweetener with strong antioxidant activity, improved the cognitive function of transgenic AD mice. Pathologically, NDC attenuated Ab deposition in AD mouse brain. Furthermore, NDC reduced periplaque activated microglia and astrocytes, indicating the inhibition of neuroinflammation. It also enhanced neurogenesis as investigated by BrdU/NeuN double labeling. Additionally, the inhibition of Ab level and neuroinflammation by NDC treatment was also observed in an AD cell model or a microglia cell line. Taken together, our study indicated that NDC might be a potential therapeutic agent for the treatment of AD against multiple targets that include Ab pathology, neuroinflammation and neurogenesis. [ABSTRACT FROM AUTHOR]

Wickless loop thermosyphon solar water heating (LT-SWH) systems, which working under the passive and active cycle modes, were designed and experimental setup, systems' performance were comparative studied. The results showed that pump made the active cycle system overcharged, a small hydraulic head was observed most of time; because of that, there was a worse photothermal performance under the active cycle mode, no matter in the comparison of the instantaneous photothermal efficiency or the collector and system performance linear fitting; at the same time, there was also a worse isothermality of the solar evaporator under the active cycle mode. [ABSTRACT FROM AUTHOR]

To compare the difference in white matter volume (WMV) and gray matter volume (GMV) between the comitant strabismus (CS) patients and health controls by voxel-based morphometry (VBM) and the relationship with behavioral performance. A total of 20 patients with comitant strabismus (10 males and 10 females), and 20 healthy subjects (10 males and 10 females) with matched age, sex status underwent magnetic resonance examination. The authors analyzed the original 3D T1 brain images using the VBM module. The comitant strabismus groups were compared with the control groups for the GMW and WMV of the entire brain. Correlation analysis was performed to investigate the relationship between the GMV and WMV altered areas and the behavioral performance in comitant strabismus. CS patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic curves. Results of the VBM analysis demonstrated that the CS groups had decreased GMV in the brain regions of the left middle temporal pole, left cerebellum posterior lobe, right posterior cingulate cortex, left cuneus and right premotor cortex. Meanwhile, the WMV was significantly decreased in the brain regions of the left middle temporal gyrus, right middle temporal gyrus, left middle temporal gyrus, right precuneus and right premotor cortex in the comitant strabismus patients compared with HCs. Furthermore, the duration of CS was negatively correlated with the GMV values of the left middle temporal pole (r=-0.486, P=0.030). CS caused GMV and WMV atrophy in many brain regions, which may indicate the neural mechanisms of the ocular motility disorders in CS patients. [ABSTRACT FROM AUTHOR]

We studied the clinical efficacy of Bevacizumab combined with argon green laser in treating fundus macular edema. From May 2009 to April 2013, 78 patients seeking treatment for macular edema in the First Affiliated Hospital of Nanchang University were enrolled in this study. Patients were randomly divided into two groups: i) The experimental group (n=39) and the control group (n=39). Patients in the experimental group were treated with Bevacizumab (Avastin®) combined with argon green laser, and those in the control group were treated exclusively with argon green laser. Therapeutic effects were compared, and postoperative adverse reactions caused by both treatment methods were compared. Our results showed that, after treatment, the macular foveal thickness was reduced noticeably in both groups, while the therapeutic effect of combined treatment was more prominent. Patients in the experimental group gained the best-corrected visual acuity after one month of treatment, while patients in the control group achieved that after three months of treatment. We concluded that the use of Avastin® combined with argon green laser was safe and effective. Visual acuity was improved obviously with minimum adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia.Methods: The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta42 (Aβ42) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain.Results: Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions.Conclusions: Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses. [ABSTRACT FROM AUTHOR]

α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 µM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis. [ABSTRACT FROM AUTHOR]

With the development of the energy demands, solar energy medium-temperature applications (>80°C) for refrigeration, building heating, seawater desalination, thermal power generation etc. has become popular research fields. The article presents an investigation on a static low-concentration evacuated tube (LCET) solar collector for medium-temperature applications. Ray trace outcome at the incident angles between 0 and 60° shows that the average optical efficiency can reach 76.9%. The experimental testing was conducted in the medium temperature range of 80 and 140°C which indicates the instantaneous thermal efficiency is still larger than about 30.0%, and the instantaneous exergetic efficiency is >5.92%. The results comprehensively indicate the good performance of LCET solar collector for medium-temperature applications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the underlying regional homogeneity (ReHo) in brain-activity deficit in patients with optic neuritis (ON) and its relationship with behavioral performance. Materials and methods: In total, twelve patients with ON (four males and eight females) and twelve (four males and eight females) age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess the local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ReHo values of the different brain areas and the visual evoked potential (VEP) in patients with ON. Results: Compared with the healthy controls, patients with ON showed lower ReHo in the left cerebellum, posterior lobe, left middle temporal gyrus, right insula, right superior temporal gyrus, left middle frontal gyrus, bilateral anterior cingulate cortex, left superior frontal gyrus, right superior frontal gyrus, and right precentral gyrus, and higher ReHo in the cluster of the left fusiform gyrus and right inferior parietal lobule. Meanwhile, we found that the VEP amplitude of the right eye in patients with ON showed a positive correlation with the ReHo signal value of the left cerebellum posterior lobe (r=0.701, P=0.011), the right superior frontal gyrus (r=0.731, P=0.007), and the left fusiform gyrus (r=0.644, P=0.024). We also found that the VEP latency of the right eye in ON showed a positive correlation with the ReHo signal value of the right insula (r=0.595, P=0.041). Conclusion: ON may involve dysfunction in the default-mode network, which may reflect the underlying pathologic mechanism. [ABSTRACT FROM AUTHOR]

Objective: To use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the local features of spontaneous brain activity in optic neuritis (ON) and their relationship with behavioral performance. Materials and methods: Twelve patients with ON (four male, eight female) and twelve age-, sex-, and education status-matched healthy controls (HCs) (four male, eight female) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. The ALFF technique was used to assess local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ALFF values of the different areas and visual evoked potentials (VEPs) in patients with ON. Results: Compared with HCs, patients with ON had significantly decreased ALFF values in the posterior and anterior lobes of the right cerebellum, right putamen, right inferior frontal gyrus, right insula, right supramarginal gyrus, right inferior parietal lobule, left medial frontal gyrus, left superior temporal gyrus, bilateral anterior cingulate/medial frontal gyrus, and bilateral precuneus, and significantly increased ALFF values in the posterior lobes of the left and right cerebellum, right inferior temporal gyrus, right inferior temporal/fusiform gyrus, left parahippocampal gyrus, left fusiform gyrus, left calcarine fissure, left inferior parietal lobule, and left cuneus. We found negative correlations between the mean ALFF signal value of the left parahippocampal gyrus and the VEP amplitude of the right eye in ON (r=-0.584, P=0.046), and a positive correlation between the mean ALFF signal value of the bilateral precuneus and the best-corrected visual acuity of the left eye (r=0.579, P=0.048) in patients with ON. Conclusion: ON mainly seems to involve dysfunction in the default-mode network, cerebellum, and limbic system, which may reflect the underlying pathologic mechanism of ON. [ABSTRACT FROM AUTHOR]

Interferon-γ (IFN-γ) has been shown to regulate phagosome trafficking and function in macrophages, but the molecular mechanisms involved are poorly understood. Here, we identify Rab20as part of the machinery by which IFN-γ controls phagosome maturation. We found that IFN-γ stimulates the association of Rab20 with early phagosomes in macrophages. By using imaging of single phagosomes in live cells, we found that Rab20 induces an early delay in phagosome maturation and extends the time for which Rab5a and phosphatidylinositol 3-phosphate (PI3P) remain associated with phagosomes. Moreover, Rab20 depletion in macrophages abrogates the delay in phagosome maturation induced by IFN-γ. Finally, we demonstrate that Rab20 interacts with the Rab5a guanine nucleotide exchange factor Rabex-5 (also known as RABGEF1) and that Rab20 knockdown impairs the IFN-γ-dependent recruitment of Rabex-5 and Rab5a into phagosomes. Taken together, here, we uncover Rab20 as a key player in the Rab cascade by which IFN-γ induces a delay in phagosome maturation in macrophages. [ABSTRACT FROM AUTHOR]

Different from the semitransparent building integrated photovoltaic/thermal (BIPV/T) system with air cooling, the semitransparent BIPV/T system with water cooling is rare, especially based on the silicon solar cells. In this paper, a semitransparent photovoltaic/thermal system (SPV/T) with water cooling was set up, which not only would provide the electrical power and hot water, but also could attain the natural illumination for the building. The PV efficiency, thermal efficiency, and exergy analysis were all adopted to illustrate the performance of SPV/T system. The results showed that the PV efficiency and the thermal efficiency were about 11.5% and 39.5%, respectively, on the typical sunny day. Furthermore, the PV and thermal efficiencies fit curves were made to demonstrate the SPV/T performance more comprehensively. The performance analysis indicated that the SPV/T system has a good application prospect for building. [ABSTRACT FROM AUTHOR]

This paper presents a global optimization algorithm for solving globally the generalized nonlinear multiplicative programming (MP) with a nonconvex constraint set. The algorithm uses a branch and bound scheme based on an equivalently reverse convex programming problem. As a result, in the computation procedure the main work is solving a series of linear programs that do not grow in size from iterations to iterations. Further several key strategies are proposed to enhance solution production, and some of them can be used to solve a general reverse convex programming problem. Numerical results show that the computational efficiency is improved obviously by using these strategies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (TH17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator β-arrestin1 was significantly up-regulated in peripheral and synovial CD4+ T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of β-arrestin1 ameliorated disease with decreased TH17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that β-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for TH17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for β-arrestin1 in the pathogenesis of collagen-induced arthritis and TH17 cell differentiation and suggest β-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA. [ABSTRACT FROM AUTHOR]

This study aims to determine the necessity of applying a mirror coating on the side of a truncated solid dielectric CPC (compound parabolic concentrator) since ray tracing analysis has revealed that part of the incoming rays do not undergo total internal reflection, even within the half acceptance angle of the CPC. An experiment was designed and conducted indoors and outdoors to study the effect of mirror coating on the optical performance of a solid dielectric CPC. Ray tracing was also employed for the detailed analysis and its results are compared with the measurements. Based on these, a concept of partial coating is proposed and verified through simulation. The results show that a partly coated solid dielectric CPC may have a better optical efficiency than a solid CPC without coating for a certain range of incidence angles. [ABSTRACT FROM AUTHOR]

Evacuated tube solar water heater systems are widely used in China due to their high thermal efficiency, simple construction requirements, and low manufacturing costs. CPC evacuated tube solar water heaters with a geometrical concentration ratio C of less than one are rare. A comparison of the experimental rig of evacuated tube solar water heater systems with and without a mini-CPC reflector was set up, with a series of experiments done in Hefei (31°53'N, 117°15'E), China. The first and second laws of thermodynamics were used to analyze and contrast their thermal performance. The water in the tank was heated from 26.9 to 55, 65, 75, 85, and 95 °C. Two types of solar water heater systems were used, and the data gathered for two days were compared. The results show that when attaining low temperature water, the evacuated tube solar water heater system without a mini-CPC reflector has higher thermal and exergy efficiencies than the system with a mini-CPC reflector, including the average and immediate values. On the other hand, when attaining high temperature water, the system with a mini-CPC reflector has higher thermal and exergy efficiencies than the other one. The comparison presents the advantages of evacuated tube solar water heater systems with and without a mini-CPC reflector, which can be offered as a reference when choosing which solar water system to use for actual applications. [ABSTRACT FROM AUTHOR]

The low efficiency of reprogramming and genomic integration of virus vectors obscure the potential application of induced pluripotent stem (iPS) cells; therefore, identification of chemicals and cooperative factors that may improve the generation of iPS cells will be of great value. Moreover, the cellular mechanisms that limit the reprogramming efficiency need to be investigated. Through screening a chemical library, we found that two chemicals reported to upregulate K-cadhcrin considerably increase the reprogramminj; efficiency. Further study of the process indicated that E-cadherin is upregulated during reprogramming and the established iPS cells possess Ecadherin- mediated cell-cell contact, morphologically indistinguishable from embryonic stem (ES) cells. Our experiments also demonstrate that overexpression of E-cadherin significantly enhances reprogramming efficiency, whereas knockdown of endogenous E-cadherin reduces the efficiency. Consistently, abrogation of cell-cell contact by the inhibitory peptide or the neutralizing antibody against the extracellular domain of E-cadherin compromises iPS cell generation. Further mechanistic study reveals that adhesive binding activity of E-cadherin is required. Our results highlight the critical role of K-cadherin-mediated cell-cell contact in reprogramming and suggest new routes for more efficient iPS cell generation. [ABSTRACT FROM AUTHOR]

Dysregulation of β-site APP-cleaving enzyme (BACE) and/or γ-secretase leads to anomalous production of amyloid-β peptide (Aβ) and contributes to the etiology of Alzheimer's disease (AD). Since these secretases mediate proteolytic processing of numerous proteins, little success has been achieved to treat AD by secretase inhibitors because of inevitable undesired side effects. Thus, it is of importance to unravel the regulatory mechanisms of these secretases. Here, we show that δ-opioid receptor (DOR) promotes the processing of Aβ precursor protein (APP) by BACE1 and γ-secretase, but not that of Notch, N-cadherin or APLP. Further investigation reveals that DOR forms a complex with BACE1 and γ-secretase, and activation of DOR mediates the co-endocytic sorting of the secretases/receptor complex for APP endoproteolysis. Dysfunction of the receptor retards the endocytosis of BACE1 and γ-secretase and thus the production of Aβ. Consistently, knockdown or antagonization of DOR reduces secretase activities and ameliorates Aβ pathology and Aβ-dependent behavioral deficits, but does not affect the processing of Notch, N-cadherin or APLP in AD model mice. Our study not only uncovers a molecular mechanism for the formation of a DOR/secretase complex that regulates the specificity of secretase for Aβ production but also suggests that intervention of either formation or trafficking of the GPCR/secretase complex could lead to a new strategy against AD, potentially with fewer side effects. [ABSTRACT FROM AUTHOR]

Interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) are increasingly recognized as key participants in various autoimmune diseases, including multiple sclerosis. Although sets of transcription factors and cytokines are known to regulate TH-17 differentiation, the role of noncoding RNA is poorly understood. Here we identify a TH-17 cell–associated microRNA, miR-326, whose expression was highly correlated with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis (EAE). In vivo silencing of miR-326 resulted in fewer TH-17 cells and mild EAE, and its overexpression led to more TH-17 cells and severe EAE. We also found that miR-326 promoted TH-17 differentiation by targeting Ets-1, a negative regulator of TH-17 differentiation. Our data show a critical role for microRNA in TH-17 differentiation and the pathogenesis of multiple sclerosis. [ABSTRACT FROM AUTHOR]

The role of Yamanaka factors as the core regulators in the induction of pluripotency during somatic cell reprogramming has been discovered recently. Our previous study found that Yamanaka factors regulate a developmental signaling network in maintaining embryonic stem (ES) cell pluripotency. Here, we established completely reprogrammed induced pluripotent stem (iPS) cells and analyzed the global promoter occupancy of Yamanaka factors in these cells by ChIP-chip assays. We found that promoters of 565 genes were co-bound by four Yamanaka factors in iPS cells, a 10-fold increase when compared with their binding in ES cells. The promoters occupied by a single Yamanaka factor distributed equally in activated and repressed genes in iPS cells, while in ES cells Oct4, Sox2, or Klf4 distributed mostly in repressed genes and c-Myc in activated ones. Pathway analysis of the ChIP-chip data revealed that Yamanaka factors regulated 16 developmental signaling pathways in iPS cells, among which 12 were common and 4 were unique compared to pathways regulated in ES cells. We further analyzed another recently published ChIP-chip dataset in iPS cells and observed similar results, showing the power of ChIP-chip plus pathway analysis for revealing the nature of pluripotency maintenance and regeneration. Next, we experimentally tested one of the repressive signaling pathways and found that its inhibition indeed improved efficiency of cell reprogramming. Taken together, we proposed that there is a core developmental signaling network necessary for pluripotency, with TGF-β, Hedgehog, Wnt, p53 as repressive (Yin) regulators and Jak-STAT, cell cycle, focal adhesion, adherens junction as active (Yang) ones; and Yamanaka factors synergistically regulate them in a Yin-Yang balanced way to induce pluripotency. [ABSTRACT FROM AUTHOR]

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to the efficiency of human embryonic stem (ES) cells.

β-arrestins (β-Arrs) are known to be associated with tumor signaling pathways such as transforming growth factor-]31 (TGF-[31), P53/Murine double minute (MDM2) and NF-κB. To investigate the role of β-Arr in tumor progression in vivo, we generated β-Arr transgenic mice by subcutaneously inoculating tumor cells in them. We found that the xenograft tumor initiated earlier and grew more rapidly in β-Arr1 transgenic mice than in both the β-Arr2 transgenic and wild-type mice after inoculating murine liver cancer Hepal-6 cells or lymphoma EL4 cells. Moreover, matrix metalloproteinase 9 (MMP9) activity, vascular endothelial growth factor (VEGF) concentration in plasma and new small blood vessel formation in tumor tissues were enhanced in β-Arr1 transgenic mice compared with those in control mice. In addition, injection of MMP9 inhibitors in β-Arr1 transgenic mice abrogated all these effects and suppressed rapid Runor progression. Similar results were observed in human microvascular endothelial cells, where overexpressed β-Arr1 did increase MMP9 activity and small blood vessel formation. Furthermore, phosphatidylinositol 3-kinase (PI3K) inhibitors could suppress β-Arr1-enhanced MMP9 activity and the C-terminal 181-418 amino acids (aa) of β-Arr1 was largely responsible for this effect. Our data reveal a functional role for β-arrestin 1 in tumor progression in vivo, in which overexpression of β-Arr1 promotes MMP9 activity and tumor angiogenesis by providing a suitable microenvironment for tumor progression. [ABSTRACT FROM AUTHOR]

Addictive drugs have been shown to severely influence many neuronal functions, which are considered as the underlying mechanisms for physiological and psychological dependences. We previously showed that in vivo LTP in rat hippocampal CA1 region is significantly reduced during withdrawal following chronic opiates treatment, and the reduced LTP can be restored by re-exposure of animals to corresponding drugs. Here, we further demonstrated that during opiates withdrawal, the re-exposure of morphine either systemically (subcutaneously) or locally (intracerebroventricularly) could restore the reduced LTP in heroin-dependent rats, but heroin could not restore the reduced LTP, in morphine-dependent rats, indicating differential modulations of hippocampal functions by those two opiates. In contrast, DAMGO, a mu-opioid receptor (MOR) agonist, could restore the reduced LTP, and CTOP, a MOR antagonist, could block the restoration in rats dependent on both opiates, showing that MOR is functional under such conditions. However, the upregulation of hippocampal PKA activity during morphine withdrawal could be suppressed by re-exposure of morphine but not that of heroin, suggesting a likely underlying mechanism of the differential modulation of LTP by two opiates. Taken together, our study clearly demonstrates that chronic abuse of opiates inevitably leads to severe alteration of hippocampal LTP, and reveals the interesting differences between morphine and heroin in their effects on the differential modulation of hippocampal synaptic plasticity.Neuropsychopharmacology (2007) 32, 1738–1749; doi:10.1038/sj.npp.1301308; published online 24 January 2007 [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) peptide, the primary constituent of senile plaques in Alzheimer's disease (AD), is generated by β-secretase- and γ-secretase-mediated sequential proteolysis of the amyloid precursor protein (APP). The aspartic protease, β -site APP cleavage enzyme (BACE), has been identified as the main β-secretase in brain but the regulation of its activity is largely unclear. Here, we demonstrate that both BACE activity and subsequent Aβ production are enhanced after stimulation of receptor tyrosine kinases (RTKs), such as the receptors for epidermal growth factor (EGF) and nerve growth factor (NGF), in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also induces BACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and Aβ production upon RTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src with RNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominant negative form of Rab5 also abolished the enhancement of BACE activity and Aβ production, indicating the requirement of BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity and Aβ production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, and suggests that an aberration of such regulation might contribute to pathogenic Aβ production.Cell Research (2007) 17:389–401. doi: 10.1038/cr.2007.5; published online 27 February 2007 [ABSTRACT FROM AUTHOR]

The performance of photovoltaic/thermal (PV/T) solar collector had been studied theoretically and experimentally for some years. Air and water streams were used as the heat carriers for space heating or services hot water systems. The cooling effect allows the PV module to work at lower temperature and its PV efficiency is therefore improved. However, such an advantage diminishes when the solar irradiance is high. To improve the situation a new type of PV/T collector is proposed. It works as the evaporator of a heat pump, in that refrigerant evaporates in the tubing at the back of the flat-plate collector and the PV module is adhered to the front surface. Mathematical models were developed to simulate the complex energy conversion processes. Numerical analysis was then performed based on the distributed parameters approach. An experimental rig was also built to test its real performance. Our results showed that the PV/T evaporator had an overall efficiency in the range of 0.64–0.87, thermal efficiency 0.53–0.64 and PV efficiency 0.124–0.135. The simulation results were found in good agreement with the experiment measurements. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The evolution of new gene families subsequent to gene duplication may be coupled to the fluctuation of population and environment variables. Based upon that, we presented a systematic analysis of the animal transmembrane gene duplication events on a macroevolutionary scale by integrating the palaeontology repository. The age of duplication events was calculated by maximum likelihood method, and the age distribution was estimated by density histogram and normal kernel density estimation. We showed that the density of the duplicates displays a positive correlation with the estimates of maximum number of cell types of common ancestors, and the oxidation events played a key role in the major transitions of this density trace. Next, we focused on the Phanerozoic phase, during which more macroevolution data are available. The pulse mass extinction timepoints coincide with the local peaks of the age distribution, suggesting that the transmembrane gene duplicates fixed frequently when the environment changed dramatically. Moreover, a 61-million-year cycle is the most possible cycle in this phase by spectral analysis, which is consistent with the cycles recently detected in biodiversity. Our data thus elucidate a strong coupling of duplication events and macroevolution; furthermore, our method also provides a new way to address these questions. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor–associated factor 6 (TRAF6) is critical for mediating Toll-like receptor (TLR)–interleukin 1 receptor (IL-1R) signaling and subsequent activation of NF-κB and AP-1, transcriptional activators of innate immunity. Here we show that β-arrestins, a family of multifunctional proteins, directly interacted with TRAF6 after TLR–IL-1R activation. Formation of the β-arrestin–TRAF6 complex prevented autoubiquitination of TRAF6 and activation of NF-κB and AP-1. Endotoxin-treated β-arrestin 2–deficient mice had higher expression of proinflammatory cytokines and were more susceptible to endotoxic shock. Thus, β-arrestins are essential negative regulators of innate immune activation via TLR–IL-1R signaling. [ABSTRACT FROM AUTHOR]

NF-κB activation is an important mechanism of mammalian UV response to protect cells. UV-induced NF-κB activation depends on the casein kinase II (CK2) phosphorylation of IκBα at a cluster of C-terminal sites, but how it is regulated remains unclear. Here we demonstrate that β-arrestin2 can function as an effective suppressor of UV-induced NF-κB activation through its direct interaction with IκBα. CK2 phosphorylation of β-arrestin2 blocks its interaction with IκBα and abolishes its suppression of NF-κB activation, indicating that the β-arrestin2 phosphorylation is critical. Moreover, stimulation of β2-adrenergic receptors, a representative of G-protein-coupled receptors in epidermal cells, promotes dephosphorylation of β-arrestin2 and its suppression of NF-κB activation. Consequently, the β-arrestin2 suppression leads to promotion of UV-induced cell death, which is also under regulation of β-arrestin2 phosphorylation. Thus, β-arrestin2 is identified as a phosphorylation-regulated suppressor of UV response and this may play a functional role in the response of epidermal cells to UV. [ABSTRACT FROM AUTHOR]

1. Feitai, a Chinese medicine formulation, has been shown to protect against lung fibrosis induced by bleomycin (BLM). In the present study, we investigated the effect of Feitai on transforming growth factor (TGF)-β1 and monocyte chemoattractant protein-1 (MCP-1), which play important roles in the pathogenesis of BLM-induced lung fibrosis. 2. The results demonstrated that Feitai could significantly attenuate BLM-induced acute lung inflammation and subsequent lung fibrosis. Meanwhile, the expression of MCP-1 and TGF-β1 mRNA in the lungs increased in the BLM-treated group compared with the saline-instilled control group and Feitai treatment significantly decreased cytokine expression in BLM-treated mice. In addition, Feitai diminished the accumulation of MCP-1- and TGF-β1-positive cells in lung tissues at the time of peak mRNA levels. 3. In summary, the results of the present study indicate that treatment with Feitai ameliorates BLM-induced lung fibrosis, at least in part via the inhibition of MCP-1 and TGF-β1 expression. [ABSTRACT FROM AUTHOR]

Presents a study that investigated morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. Materials and methods; Results; Discussion.

Extra-adrenal pheochromocytomas are rare tumors that originate from the chromaffin tissue of the sympathetic nervous system. Ovarian extra-adrenal pheochromocytoma is even more rare. The present study reports a rare case of an extra-adrenal pheochromocytoma that was localized to the right ovary, but was gynecologically asymptomatic. Computed tomography angiography (CTA) detected the tumor and indicated that it was well defined, highly vascularized and obtained its blood supply from the right ovarian artery. This is the second case of ovarian extra-adrenal pheochromocytoma reported in the literature, and the first description of the CTA manifestations in the ovary. Gynecologists and radiologists should consider the possibility that an ovarian mass could be an extra-adrenal pheochromocytoma, which would allow time to prepare appropriately for the surgical removal of the mass. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one by Dániel Kirilly and Ting Xie on a review of the stem cell community in Drosophila ovary and another by Jinhua Wen and Lingsong on the use of neural stem cells.

β-arrestin 1 and β-arrestin 2 are well-known negative regulators of G-protein-coupled receptor (GPCR) signaling. Upon GPCR activation, β-arrestins translocate to the cell membrane and bind to the agonist-occupied receptors. This uncouples these receptors from G proteins and promotes their internalization, thus causing desensitization. However, accumulating evidence indicates that β-arrestins also function as scaffold proteins that interact with several cytoplasmic proteins and link GPCRs to intracellular signaling pathways such as MAPK cascades. Recent work has also revealed that, in response to activation of certain GPCRs, β-arrestins translocate from the cytoplasm to the nucleus and associate with transcription cofactors such as p300 and cAMP-response element-binding protein (CREB) at the promoters of target genes to promote transcription. They also interact with regulators of transcription factors, such as IκBα and MDM2, in the cytoplasm and regulate transcription indirectly. This β-arrestin-mediated regulation of transcription appears to play important roles in cell growth, apoptosis and modulation of immune functions. [ABSTRACT FROM AUTHOR]

The neuronal glutamate transporter, excitatory amino-acid carrier 1 (EAAC1), plays an important role in the modulation of neurotransmission and contributes to synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and to epileptogenesis. However, the mechanisms that regulate EAAC1 endocytic sorting and function remain largely unknown. Here, we first demonstrate that EAAC1 undergoes internalization through the clathrin-mediated pathway and further show that syntaxin 1A, a key molecule in synaptic exocytosis, potentiates EAAC1 internalization, thus leading to the functional inhibition of EAAC1. In the presence of the transmembrane domain of syntaxin 1A, its H3 coiled-coil domain of syntaxin 1A is necessary and sufficient for the inhibition of EAAC1. Furthermore, specific suppression of endogenous syntaxin 1A significantly blocked EAAC1 endocytic sorting and lysosomal degradation promoted by kainic acid, a drug for kindling the animal model of human temporal lobe epilepsy in rat, indicating a potential role of syntaxin 1A in epileptogenesis. These findings provide new evidence that syntaxin 1A serves as an intrinsic enhancer to EAAC1 endocytic sorting and further suggest that syntaxin 1A is conversant with both 'ins' and 'outs' of synaptic neurotransmission. [ABSTRACT FROM AUTHOR]