Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.

Rationale: Tripeptidyl peptidase II (TPP2) has been proven to be related to human immune and neurological diseases. It is generally considered as a cytosolic protein which forms the largest known protease complex in eukaryotic cells to operate mostly downstream of proteasomes for degradation of longer peptides. However, this canonical function of TPP2 cannot explain its role in a wide variety of biological and pathogenic processes. The mechanistic interrelationships and hierarchical order of these processes have yet to be clarified. Methods: Animals, cells, plasmids, and viruses established and/or used in this study include: TPP2 knockout mouse line, TPP2 conditional knockout mouse lines (different neural cell type oriented), TRE-TPP2 knockin mouse line on the C57BL/6 background; 293T cells with depletion of TPP2, ATF6, IRE1, PERK, SYVN1, UCHL1, ATG5, CEPT1, or CCTα, respectively; 293T cells stably expressing TPP2, TPP2 S449A, TPP2 S449T, or CCTα-KDEL proteins on the TPP2-depleted background; Plasmids for eukaryotic transient expression of rat CYP19A1-Flag, CYP19A1 S118A-Flag, CYP19A1 S118D-Flag, Sac I ML GFP Strand 11 Long, OMMGFP 1-10, G-CEPIA1er, GCAMP2, CEPIA3mt, ACC-GFP, or SERCA1-GFP; AAV2 carrying the expression cassette of mouse CYP19A1-3 X Flag-T2A-ZsGreen. Techniques used in this study include: Flow cytometry, Immunofluorescence (IF) staining, Immunohistochemical (IHC) staining, Luxol fast blue (LFB) staining, ß-galactosidase staining, Lipid droplet (LD) staining, Calcium (Ca2+) staining, Stimulated emission depletion (STED) imaging, Transmission electron microscopic imaging, Two-photon imaging, Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end Labeling (TUNEL) assay, Bromodeoxyuridine (BrdU) assay, Enzymatic activity assay, Proximity ligation assay (PLA), In vivo electrophysiological recording, Long-term potentiation (LTP) recording, Split-GFP-based mitochondria-associated membrane (MAM) detection, Immunoprecipitation (IP), Cellular fractionation, In situ hybridization, Semi-quantitative RT-PCR, Immunoblot, Mass spectrometry-based lipidomics, metabolomics, proteomics, Primary hippocampal neuron culture and Morris water maze (MWM) test. Results: We found that TPP2, independent of its enzymatic activity, plays a crucial role in maintaining the homeostasis of intracellular Ca2+ and phosphatidylcholine (PC) in the central nervous system (CNS) of mice. In consistence with the critical importance of Ca2+ and PC in the CNS, TPP2 gene ablation causes presenile dementia in female mice, which is closely associated with Ca2+/PC dysregulation-induced endoplasmic reticulum (ER) stress, abnormal autophagic degradation of CYP19A1 (aromatase), and estrogen depletion. This work therefore uncovers a new role of TPP2 in lipogenesis and neurosteroidogenesis which is tightly related to cognitive function of adult female mice. Conclusion: Our study reveals a crucial role of TPP2 in controlling homeostasis of Ca2+ and lipids in CNS, and its deficiency causes sexual dimorphism in dementia. Thus, this study is not only of great significance for elucidating the pathogenesis of dementia and its futural treatment, but also for interpreting the role of TPP2 in other systems and their related disorders.

Five-week of solution-focused group counseling successfully reduces internet addiction among college students: A pilot study.

Background and Aims: In the digital age, Internet addiction (IA) was deemed an epidemic and few treatments had been effectively developed for it. Here, we proposed a solution-focused group counseling (SFGC) as a potentially solution to reduce Internet addiction among college students. The present study examined the short- and long-term effect of a five-week solution-focused group counseling intervention on Internet addiction. Methods: Thirty-two participants were recruited and randomly assigned to either the experimental or control group, and twenty-six participants completed the whole intervention. The experimental group (n = 14) received the intervention, while control group (n = 12) did not. The revised version of the Chinese Internet Addiction Scale (CIAS-R), the Future Time Perspective, and resting-state EEG were administered pre-intervention, post-intervention, and at two follow-up tests (one month and six months after intervention). Results: The results showed that the scores of the CIAS-R in the experimental group were significantly decreased after intervention, and these effects could be sustained for one month and six months follow-ups. Additionally, the intervention conducted an increase in future time perspective. EEG results further suggested that the alpha, beta, and gamma absolute power decreased after the intervention. Conclusion: These results from the pilot-study primarily suggested that solution-focused group counseling could be an effective intervention for Internet addiction.

Spontaneous brain microstates correlate with impaired inhibitory control in internet addiction disorder.

The prevalence of the Internet addiction disorder (IAD) has been on the rise, making it increasingly imperative to explore the neurophysiological markers of it. Using the whole-brain imaging approach of EEG microstate analysis, which treats multichannel EEG recordings as a series of quasi-steady states, similar as the resting-state networks found by fMRI, the present study aimed to investigate the specificity of the IAD in class C of the four canonical microstates. The existing EEG data of 40 participants (N = 20 for each group) was used, and correlation between the time parameters of microstate C and the performance of the Go/NoGo task was analyzed. Results suggested that the duration and coverage of class C were significantly reduced in the IAD group as compared to the healthy control (HC) group. Furthermore, the duration of class C had a significant inverse correlation with Go RTs in the IAD group. These results implied that class C might serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanism of inhibitory control in IAD.

From fears of evaluation to social anxiety: The longitudinal relationships and neural basis in healthy young adults

Background: Social anxiety disorder (SAD) is a common mental health problem, and its core cognitive manifestation is the persistent fear of being evaluated, including both negatively (FNE) and positively (FPE). This study aimed to examine the longitudinal relationships of FNE, FPE and SAD and explore their neural basis. Methods: Three samples were retrieved in this study. First, the data of 649 college students who completed a survey and fMRI scan were used to explore the neural basis of FNE, FPE, and SAD symptoms. Next, the data of 450 participants who completed the same survey twice were used to examine the longitudinal relationships of the variables. Finally, the overlapping of the two samples (N = 288) who completed two surveys and the fMRI scan were used to establish a brain-behavior model. Results: Both FNE and FPE predicted SAD, and SAD also predicted FPE. The neural signals of subregions in prefrontal cortex were correlated with the scores of FNE, FPE and SAD. Abnormal prefrontal signals influenced SAD symptoms via fears of evaluation. Conclusions: Our findings explain the behavioral and neural underpinnings of social anxiety from a fear of evaluation angle. This contributes to a better theorical understanding of SAD and clinical practice. (AU)

Can financial efficiency and environmental regulation promote R&D innovation? From the perspective of value chain decomposition.

There is a plethora of current research on economic or financial resources for fostering innovation. These studies lack the micro-analysis and, more importantly, disregard the effect of environmental control. This study will offer a new analytical paradigm by linking financial growth, environmental regulation, and innovation growth throughout the value chain. Using the information on 30 Chinese provinces collected between 1990 and 2020, we develop a dynamic panel data model to examine the interplay between financial effectiveness, ecological regulation, and research and development (R&D) innovation. We assess the impact that the efficiency of financial organizations and the stock market have on R&D's ability to influence R&D innovation. There are positive spillover effects for stock market efficiency, which boosts the development and conversion of R&D innovation; there are positive spillover effects for financial institution efficiency, which hurts the conversion of R&D innovation, and there is an adverse effect on environmental regulation efficiency. To what extent environmental rules affect the commercialization of research and development innovation is unclear; human capital is an effective motivator for the advancement of R&D innovation, and the volume of FDI may increase the commercialization of R&D innovation.

The C-terminal domains of ADAMTS1 contain exosites involved in its proteoglycanase activity.

A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1) is a protease involved in fertilization, cancer, cardiovascular development, and thoracic aneurysms. Proteoglycans such as versican and aggrecan have been identified as ADAMTS1 substrates, and Adamts1 ablation in mice typically results in versican accumulation; however, previous qualitative studies have suggested that ADAMTS1 proteoglycanase activity is weaker than that of other family members such as ADAMTS4 and ADAMTS5. Here, we investigated the functional determinants of ADAMTS1 proteoglycanase activity. We found that ADAMTS1 versicanase activity is approximately 1000-fold lower than ADAMTS5 and 50-fold lower than ADAMTS4 with a kinetic constant (kcat/Km) of 3.6 × 103 M-1 s-1 against full-length versican. Studies on domain-deletion variants identified the spacer and cysteine-rich domains as major determinants of ADAMTS1 versicanase activity. Additionally, we confirmed that these C-terminal domains are involved in the proteolysis of aggrecan as well as biglycan, a small leucine-rich proteoglycan. Glutamine scanning mutagenesis of exposed positively charged residues on the spacer domain loops and loop substitution with ADAMTS4 identified clusters of substrate-binding residues (exosites) in ß3-ß4 (R756Q/R759Q/R762Q), ß9-ß10 (residues 828-835), and ß6-ß7 (K795Q) loops. This study provides a mechanistic foundation for understanding the interactions between ADAMTS1 and its proteoglycan substrates and paves the way for development of selective exosite modulators of ADAMTS1 proteoglycanase activity.

From fears of evaluation to social anxiety: The longitudinal relationships and neural basis in healthy young adults.

Background: Social anxiety disorder (SAD) is a common mental health problem, and its core cognitive manifestation is the persistent fear of being evaluated, including both negatively (FNE) and positively (FPE). This study aimed to examine the longitudinal relationships of FNE, FPE and SAD and explore their neural basis. Methods: Three samples were retrieved in this study. First, the data of 649 college students who completed a survey and fMRI scan were used to explore the neural basis of FNE, FPE, and SAD symptoms. Next, the data of 450 participants who completed the same survey twice were used to examine the longitudinal relationships of the variables. Finally, the overlapping of the two samples (N = 288) who completed two surveys and the fMRI scan were used to establish a brain-behavior model. Results: Both FNE and FPE predicted SAD, and SAD also predicted FPE. The neural signals of subregions in prefrontal cortex were correlated with the scores of FNE, FPE and SAD. Abnormal prefrontal signals influenced SAD symptoms via fears of evaluation. Conclusions: Our findings explain the behavioral and neural underpinnings of social anxiety from a fear of evaluation angle. This contributes to a better theorical understanding of SAD and clinical practice.

Influence of China's Carbon Emissions Trading Scheme on Green Innovation of Enterprises.

China's economic growth has entered "new normal," and the task of reducing carbon emissions has become more onerous. Hence, this study aimed to explore whether China's carbon emissions trading pilot policy stimulated corporate green innovation capabilities. The data pertained to the green patent data of the listed companies in Shanghai and Shenzhen stock exchanges during 2008-2018. Using a difference-in-difference-in-differences (DDD) method, the study took advantage of the variations across regions, across enterprises, and across years and obtained several novel findings. First, the pilot carbon emissions trading policy significantly stimulated the green innovation capabilities of emission control companies in the pilot areas compared with enterprises in nonpilot areas and the nonemission control list. Second, the effect of the policy on the improvement in corporate green innovation capabilities might be driven by the improvement in corporate input factor allocation efficiency and the additional benefits that could be obtained from the carbon trading market. Third, the positive effect of the policy on the green innovation capabilities of state-owned enterprises was more significant. Therefore, the establishment and promotion of a unified national carbon emissions trading market and supporting mechanisms should be accelerated to achieve the balance of stable economic growth and carbon emission task.

A Random Forest Method for Identifying the Effectiveness of Innovation Factor Allocation.

This paper makes a new attempt to identify the effectiveness of innovation factor allocation with a random forest method. This method avoids the evaluation bias of the relative effectiveness caused by the noneffective selection of production frontier in the nonparametric DEA method. It does not refer to other optimal subjects but shifts the focus to the judgment of its own effectiveness. In addition, it also gets rid of the constraints of the model and variables in the parameter SFA method, ensuring the reliability of the measurement results by resampling thousands of times. The data is collected from 30 provinces in China from 2009 to 2018. The findings show the innovation factor allocation in more than half of the provinces is not fully effective. It indicates that how to make use of innovation factor inputs to achieve the actual innovation output higher than own optimal levels is currently still in a period of exploration in China. To further improve innovation factor allocation efficiency, it deeply analyzes the impacts of innovation factor inputs and finds out the important innovation factor inputs. Furthermore, this study presents the nonlinear characteristics and optimal combination of important innovation factor inputs. According to this, it offers the detailed suggestions about how to adjust current important innovation factor inputs for each province in order to greatly enhance the effectiveness of innovation factor allocation in the future.

Slow-Wave EEG Activity Correlates with Impaired Inhibitory Control in Internet Addiction Disorder.

Impaired inhibitory control is a core feature of internet addiction disorder (IAD). It is therefore of interest to determine the neurophysiological markers associated with it. The present study aimed to find such biomarkers with a resting-state electroencephalogram (EEG). We specifically used scores on the Chinese Internet Addiction Scale revised edition (CIAS-R) to divide 46 participants into two groups: the IAD group (>53, n = 23) and control group (<46, n = 23). Both behavioral aspects (Go/NoGo responses and impulsivity) and EEG were measured in the lab. The results suggest that the IAD group presented a decreased slow-wave (1−8 Hz) absolute power across the whole brain. The slow-wave activities in the frontal areas were also correlated with the commission error rate in the Go/NoGo task in the IAD group. These results imply that the frontal slow-wave EEG activity may serve as a neurophysiological marker of IAD, helping to understand the underlying neural mechanisms of inhibitory control deficits in IAD and point to possible interventions.

Carbon Transfer Decision Model Based on LMDI Method.

Establishing a coordinated governance mechanism for regional carbon emissions is an essential way to achieve carbon peak and carbon neutrality, while the study of interprovincial carbon emissions transfer is one of the important foundations of regional carbon emissions coordinated governance research. Based on the multiregional input-output (MRIO) model, this study calculated the carbon emissions from both the producers' perspective and the consumers' perspective and analyzed the interprovincial net carbon emissions transfer decision. Furthermore, the logarithmic mean Divisia index (LMDI) method was adopted to decompose the factors that affect the province's net carbon emissions into technological effect, structural effect, input-output effect, and scale effect. It was revealed that the input-output effect was the primary influencing factor of the net carbon transfer at the provincial level.

Resveratrol derivative excited postsynaptic potentiation specifically via PKCß-NMDA receptor mediation.

Several decades have passed since resveratrol (RSV) was first identified in red wine. Researchers have reported the pleiotropic anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, and neuronal protective effects of resveratrol and its glycosylated derivative. However, few studies have distinguished the minute differences in the properties between resveratrol and its glycosylated derivative in terms of synaptic plasticity. As an abundant natural product of glycosylated resveratrol, the derivative 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been determined to be a better option for long-term potentiation (LTP) in the hippocampus under physiological and pathological conditions than resveratrol. TSG, as well as its parent molecule RSV, could elicit early-LTP and recover fast excitatory postsynaptic potentials (EPSPs) in the hippocampus. Using various modalities, including pre- and post-whole-cell patch clamping techniques in the calyx of Held, pharmacological inhibition of the N-methyl-d-aspartic acid receptor (NMDAr) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAr) as well as protein kinase C (PKC) activation, we demonstrated that TSG, unlike RSV, could merely promote NMDA-mediated EPSC via PKCß cascade. Our results provide new knowledge that glycosylation of resveratrol could significantly improve its specificity in promoting sole NMDAr mediation of EPSPs, in addition to improving solubility and resistance against oxidation in vivo. These observations could contribute to further exploration of pharmaceutical evaluation of glycosylated stilbene in the future.

Enzymatic activity of palmitoyl-protein thioesterase-1 in serum from schizophrenia significantly associates with schizophrenia diagnosis scales.

Genome-wide association studies have confirmed that schizophrenia is an inheritable multiple-gene mental disorder. Longitudinal studies about depression, first episode psychosis (FEP) and acute psychotic relapse have mostly searched for brain imaging biomarkers and inflammatory markers from the blood. However, to the best of our knowledge, the association between enzymatic activities with diagnosis or prediction of treatment response in people with schizophrenia has barely been validated. Under the Longitudinal Study of National Mental Health Work Plan (2015-2020), we have studied a subsample of approximately 36 individuals from the cohort with data on palmitoyl-protein thioesterase-1 enzymatic activity from FEP and performed a bivariate correlation analysis with psychiatric assessment scores. After adjusting for sex, age, body mass index (BMI) and total serum protein, our data demonstrated that PPT1 enzymatic activity is significantly associated with schizophrenia and its Positive and Negative Syndrome Scale (PANSS) scores. This longitudinal study compared the PPT1 enzymatic activity in FEP schizophrenia patients and healthy volunteers, and the former exhibited a significant 1.5-fold increase in PPT1 enzymatic levels (1.79 mmol/L/h/mL, and 1.18 mmol/L/h/mL; P < 0.05; 95% CI, 2.3-2.9 and 1.4-1.8). The higher PPT1 enzymatic levels in FEP schizophrenia patients were positively associated with larger PANSS scaling scores (r = 0.32, P = 0.0079 for positive scaling; r = 0.41, P = 0.0006 for negative scaling; r = 0.45, P = 0.0001 for general scaling; and r = 0.34, P = 0.0048 for PNASS-S scaling). Higher enzymatic PPT1 in FEP schizophrenia patients is significantly associated with increased PANSS scaling values, indicating more serious rates of developing psychosis. Enzymatic activity of PPT1 may provide an important new view for schizophrenia disorders.

A novel nanofiltration membrane with simultaneously enhanced antifouling and antibacterial properties.

A novel nanofiltration membrane prepared by modification of a commercial membrane surface is fabricated using polydopamine (PDA) and hydroxyl propyl trimethyl ammonium chloride chitosan (HACC) mixed with chitosan (CN) and chelated silver (Ag) nanoparticles. The surface chemical composition, cross-sectional morphology, hydrophilicity and surface structure of the prepared membranes were examined by scanning electron microscopy, water contact angle measurements, and atomic force microscopy, respectively. The membrane performance was evaluated in terms of volumetric flux and protein rejection. In addition, the antifouling and antibacterial properties of the membranes were also explored. The results demonstrated that the prepared membranes exhibited an excellent antifouling property due to their three-layer architecture and it provided a special layer to promote the antibacterial property. According to the results, the modified membrane has a significantly improved flux recovery rate (over 96%). Besides, the antibacterial activity tests showed that the proposed three-layer architecture modification extensively prevented bacterial growth on the membrane surface.

Advanced glycation end products inhibit testosterone secretion by rat Leydig cells by inducing oxidative stress and endoplasmic reticulum stress.

Diabetes severely impairs male reproduction. The present study assessed the effects and mechanisms of action of advanced glycation end products (AGEs), which play an important role in the development of diabetes complications, on testosterone secretion by rat Leydig cells. Primary rat Leydig cells were cultured and treated with AGEs (25, 50, 100 and 200 µg/ml). Testosterone production induced by human chorionic gonadotropin (hCG) was determined by ELISA. The mRNA and protein expression levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), which are involved in testosterone biosynthesis, were measured by reverse transcription-quantitative PCR and western blot analyssi, respectively. Reactive oxygen species (ROS) production in Leydig cells was measured using the dichlorofluorescein diacetate (DCFH-DA) probe. The expression levels of endoplasmic reticulum stress-related proteins [C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78)] in the Leydig cells were measured by western blot analysis. We found that the AGEs markedly suppressed testosterone production by rat Leydig cells which was induced by hCG in a concentration-dependent manner compared with the control (P<0.01). The mRNA and protein expression levels of StAR, 3ß-HSD and P450scc were downregulated by the AGEs in a dose-dependent manner compared with the control (P<0.01). The antioxidant agent, N-acetyl­L­cysteine (NAC), and the endoplasmic reticulum stress inhibitor, tauroursodeoxycholic acid (TUDCA), reversed the inhibitory effects of AGEs. In addition, the content of ROS in Leydig cells treated with AGEs increased significantly. The expression levels of CHOP and GRP78 were markedly upregulated by the AGEs in the Leydig cells. From these findings, it can be concluded that AGEs inhibit testosterone production by rat Leydig cells by inducing oxidative stress and endoplasmic reticulum stress.

Tissue Inhibitor of Matrix Metalloproteinases-1 Knockdown Suppresses the Proliferation of Human Adipose-Derived Stem Cells.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional matrix metalloproteinase, and it is involved in the regulation of cell proliferation and apoptosis in various cell types. However, little is known about the effect of TIMP-1 expression on the proliferation of adipose-derived stem cells (ADSCs). Therefore, TIMP-1 expression in the ADSCs was firstly detected by western blotting, and TIMP-1 gene was knocked down by lentivirus-mediated shRNA. Cell proliferation was then evaluated by MTT assay and Ki67 staining, respectively. Cell cycle progression was determined by flow cytometry. The changes of p51, p21, cyclin E, cyclin-dependent kinase 2 (CDK2), and P-CDK2 caused by TIMP-1 knockdown were detected by western blotting. The results indicated that ADSCs highly expressed TIMP-1 protein, and the knockdown of TIMP-1 inhibited cell proliferation and arrested cell cycle progression at G1 phase in the ADSCs possibly through the upregulation of p53, p21, and P-CDK2 protein levels and concurrent downregulation of cyclin E and CDK2 protein levels. These findings suggest that TIMP-1 works as a positive regulator of cell proliferation in ADSCs.

Vitamin C promotes the proliferation of human adipose-derived stem cells via p53-p21 pathway.

Although adipose-derived stem cells (ADSCs) have demonstrated a promising potential for the applications of cell-based therapy and regenerative medicine, excessive reactive oxygen species (ROS) are harmful to ADSCs cell survival and proliferation. Vitamin C is an important antioxidant, and is often added into culture media as an essential micronutrient. However, its roles on the proliferation of human ADSCs have not been studied. Therefore, in this study, human ADSCs were isolated, and detected by flow cytometry for the analysis of their cell surface antigens. Cell proliferation and cell cycle progression were measured with cell counting kit-8 assay and flow cytometry, respectively. Western blotting was used to detect the expression levels of cyclin E1, p53, p21, and CDK2 proteins. The effect of vitamin C pretreatment on the production of hydrogen peroxide (H2O2)-mediated ROS in the ADSCs was evaluated by flow cytometry. Our results indicated that vitamin C treatment significantly increased cell proliferation, and changed the cell cycle distribution of ADSCs by decreasing the percentage of G1 phase, and concurrently increased the percentage of S and G2/M phase. Western blot analysis indicated that vitamin C treatment up-regulated the expression levels of cyclin E1 and CDK2, but down-regulated p53 and p21 proteins expression, which contributed to cell proliferation and cell cycle progression. Vitamin C pretreatment significantly reduced the production of H2O2-induced ROS in the ADSCs. These findings suggest that vitamin C can promote the proliferation and cell cycle progression in the ADSCs possibly through regulation of p53-p21 signal pathway.

Xenotransplantation of human adipose-derived stem cells in zebrafish embryos.

Zebrafish is a widely used animal model with well-characterized background in developmental biology. The fate of human adipose-derived stem cells (ADSCs) after their xenotransplantation into the developing embryos of zebrafish is unknown. Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral vector system carrying a green fluorescent protein (GFP) reporter gene, and followed by detection of their cell viability and the expression of cell surface antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish embryos at 3.3-4.3 hour post-fertilization (hpf). Green fluorescent signal, the proliferation and differentiation of human ADSCs in recipient embryos were respectively examined using fluorescent microscopy and immunohistochemical staining. The results indicated that human ADSCs did not change their cell viability and the expression levels of cell surface antigens after GFP transduction. Microscopic examination demonstrated that green fluorescent signals of GFP expressed in the transplanted cells were observed in the embryos and larva fish at post-transplantation. The positive staining of Ki-67 revealed the survival and proliferation of human ADSCs in fish larvae after transplantation. The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31 expression was undetectable. Therefore, our results indicate that human ADSCs xenotransplanted in the zebrafish embryos not only can survive and proliferate at across-species circumstance, but also seem to maintain their undifferentiation status in a short term. This xenograft model of zebrafish embryos may provide a promising and useful technical platform for the investigation of biology and physiology of stem cells in vivo.

[Advanced glycation end products inhibit testosterone production in rat Leydig cells].

OBJECTIVE: To study the expression of the receptor for advanced glycation end products (RAGE) and the inhibitory effect of advanced glycation end products (AGEs) on testosterone production in rat Leydig cells. METHODS: Rat Leydig cells were primarily cultured and the expression of RAGE in the Leydig cells was detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively, and the testosterone content was determined by ELISA. RESULTS: RT-PCR and immunofluorescence staining exhibited the expression of RAGE in the rat Leydig cells. AGEs remarkably suppressed hCG-induced testosterone production in the Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml groups as compared with the control (P < 0.01). CONCLUSION: RAGE exists in rat Leydig cells and AGEs can significantly inhibit the secretion of testosterone in primarily cultured rat Leydig cells.