On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated ...On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.展开更多
<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternativ...<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">which </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.</span>展开更多
The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of ...The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of an open pit slope.For this purpose,spatially conditioned DFN models were developed for the pit walls at Tasiast mine using comprehensive structural data from the mine.Using Sequential Gaussian Simulation(SGS),volumetric fracture intensities(P32)were modeled across the entire mine site in the form of 3D block models.The simulated P32 block models were used as the input constraints for conditional DFN fracture generation,where the DFN grid dimension is the same as the SGS 3D blocks.The spatially constrained DFN models were further calibrated using aerial fracture intensities(P21)data from the pit walls,obtained by a survey of the pit walls using an unmanned aerial vehicle(UAV)and measured traces of joints from 3D point cloud data.The final DFN model is expected to honor the fracture intensities gathered through different means with optimal model accuracy.Finally,bench-scale and interramp scale rock wedge slope stability analyses were conducted using the calibrated conditional DFN models.This work proves the significance of conditioned DFN models in rock wedge stability analysis.Such models provide detailed information regarding rock wedge stability so that site monitoring and prevention plans can be conducted with higher efficiency.展开更多
In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→...In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→∞)x′(t)e^(t)=0,where t_(0) and ψ_(0) are real constants,φ(s)=s/√1−s^(2),s∈R with s∈(−1,1),f:[t_(0),∞)×R→R satisfies the Lipschitz or Osgood-type conditions.展开更多
In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary c...In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.展开更多
Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of...Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.展开更多
Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of ...Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).展开更多
This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are glob...This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are globally convergent for general convex functions.展开更多
Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain la...Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.展开更多
The changes in the physical characteristics of unconditioned and conditioned anaerobic digested sludge （ADS） biosolids, such as capillary suction time （CST）, yield stress, average size and fractal dimensions, were...The changes in the physical characteristics of unconditioned and conditioned anaerobic digested sludge （ADS） biosolids, such as capillary suction time （CST）, yield stress, average size and fractal dimensions, were investigated through a CST test, transient and dynamic rheological test and image analysis. The results showed that the optimum polymer dose range was observed when CST or its reciprocal value was employed as an indicator. There were good correlations between the yield stresses determined from both a controlled shear stress test and a strain amplitude sweep test. The yield stress and storage modulus （G＇） increased as the polymer dose increased in most cases. A frequency sweep test revealed that polymer conditioning could extend the frequency sweep ranges for their elastic behaviors over viscous behaviors as well as the gel-like structure in the linear viscoelastic range. These results implied that more deformation energy was stored in this rigid structure, and that elastic behavior became increasingly dominant with the addition of the polymer in most cases, In addition, both the average sizes and two-dimensional fractal dimensions for conditioned ADS biosolids presented a similar up-climax-down variation trend as the polymer doses increased, whereas the critical polymer doses at the highest average sizes or two-dimensional fractal dimensions, were different. Correlation analysis revealed that the conditioned ADS dewaterability was not correlated with the yield stresses, while the average sizes or the two-dimensional fractal dimensions for conditioned ADS biosolids could be taken as the indication parameters for ADS dewaterability.展开更多
In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curve...In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curves of conditioned rubber specimens under di?erent conditioned strains are obtained. Test results show di?erences between these curves. Based on an analysis of the classical constitutive models, a new modi?ed eight-chain model is proposed, which takes account of both the locking stretch of chains and the interaction e?ect in the network. Fitting test data shows that the modi?ed model well characterizes the incompressible hyperelastic mechanical behavior of conditioned rubbers under the moderate ?nite deformation as well as under the large deformation.展开更多
The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned sti...The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned stimulus （CS）. In the experiment, 36 participants were trained in differential DEC with a soft tone （60 dB） or a loud tone （85 dB） as the CS, paired with a corneal air-puff as the unconditioned stimulus （US）. After conditioning, awareness of the relationship between assessed with a 17-item the CS and the US was true/false questionnaire. Interestingly, during differential DEC with a soft-tone CS, a higher proportion of differential conditioned responses （CRs） was evident in participants who were aware than those who were unaware. In contrast, when a loud tone was used as the CS, the proportion of differential CRs of the aware participants did not differ significantly from those who were unaware over any of the blocks of 20 trials. In unaware participants, the percentage of differential CRs with a loud-tone CS was significantly higher than that with a soft-tone CS; however in participants classified as aware, the percentage of differential CRs with a loud-tone CS did not differ significantly from that with a soft-tone CS. The present findings suggest that awareness is critical for differential DEC when the delay task is rendered more difficult.展开更多
Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progeni...Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments. After primary culture of bone marrow-derived macrophages, lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype. These cells were then treated with endothelial progenitor cell-conditioned medium or control medium. Polymerase chain reaction was used to determine mR NA expression levels of related inflammatory factors. Afterwards, primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2and either endothelial progenitor cell-conditioned medium or control medium. Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis. Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis. Compared with control medium, endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site, suppressed apoptosis, and promoted angiogenesis. Next, we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo. The rats were randomly administered intraperitoneal injection of PBS, control medium or endothelial progenitor cell-conditioned medium, once a day, for 6 consecutive weeks. Immunohistochemistry was used to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter. The Basso, Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury. Compared with the other two groups, the number of axons was increased, cavities in the spinal cord were decreased, the proportion of apoptotic neurons in the gray matter was reduced, and the Basso, Beattie and Bresnahan score was higher in the endothelial progenitor cell-conditioned medium group. Taken together, the in vivo and in vitro results suggest that endothelial progenitor cell-conditioned medium suppresses inflammation, promotes angiogenesis, provides neuroprotection, and promotes functional recovery after spinal cord injury.展开更多
Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction ...Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.展开更多
Animals learn to avoid particular food when some of its sensory properties are associated with gastrointestinal discomfort. Twenty rats were exposed to free access to food and a sugar solution for ten days in first ph...Animals learn to avoid particular food when some of its sensory properties are associated with gastrointestinal discomfort. Twenty rats were exposed to free access to food and a sugar solution for ten days in first phase. During second phase, experimental group received a dose of LiCl. Control group received an injection without LiCl. Both groups had free access to a sugar solution and food restriction for three days. In the final phase, both groups returned to the conditions of first phase. Results showed a significant decrease in sugar intake after aversive conditioning regarding the intake registered in the initial phase in experimental group. Control group did not show any differences in its sugar intake before and after the experimental manipulation. The procedure carried out is discussed as a means to decrease sugar intake.展开更多
Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to...Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin’s role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30-300 pmol) and cocaine (0.625-10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pretreatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds.展开更多
A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fi...A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fibroblastlike cells to maintain culture homeostasis by producing TGF-β and insulin-like growth factor-lI （IGF-Ⅱ） in response to basic fibroblast growth factor （bFGF）. Although the importance of TGF-β family members in the maintenance of pluripotency of hESCs is widely established, very little is known about the role of IGF-Ⅱ. In order to ease hESC cul- ture conditions and to reduce xenogenic components, we sought （i） to determine whether hESCs can be maintained stable and pluripotent using CM from human foreskin fibroblasts （HFFs） and human mesenchymal stem cells （hM- SCs） rather than MEF-CM, and （ii） to analyze whether the cooperation of bFGF with TGF-β and IGF-Ⅱ to maintain hESCs in MEF-CM may be extrapolated to hESCs maintained in allogeneic mesenchymal stem cell （MSC）-CM and HFF-CM. We found that MSCs and HFFs express all FGF receptors （FGFR1-4） and specifically produce TGF-β in response to bFGF. However, HFFs but not MSCs secrete IGF-Ⅱ. Despite the absence of IGF-Ⅱ in MSC-CM, hESC pluripotency and culture homeostasis were successfully maintained in MSC-CM for over 37 passages. Human ESCs derived on MSCs and hESCs maintained in MSC-CM retained hESC morphology, euploidy, expression of surface markers and transcription factors linked to pluripotency and displayed in vitro and in vivo multilineage developmental potential, suggesting that IGF-Ⅱ may be dispensable for hESC pluripotency. In fact, IGF-Ⅱ blocking had no effect on the homeostasis of hESC cultures maintained either on HFF-CM or on MSC-CM. These data indicate that hESCs are successfully maintained feeder-free with IGF-Ⅱ-lacking MSC-CM, and that the previously proposed paracrine mechanism by which bFGF cooperates with TGF-β and IGF-Ⅱ in the maintenance of hESCs in MEF-CM may not be fully extrapolated to hESCs maintained in CM from human MSCs.展开更多
BACKGROUND： Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE： It has been suggested that activated astrocytes alter the expression of the estrogen recept...BACKGROUND： Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE： It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium. DESIGN AND SETTING： This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China. MATERIAL： Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS： Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium （10 μ L） was injected into rat lateral ventricle in the control group （n = 8）. Coriaria lactone-activated, astrocyte-conditioned medium （10 μL） was infused into the rat lateral ventricle in the coriaria lactone group （n = 32）. At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point. MAIN OUTCOME MEASURES： Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry. RESULTS： Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group （P 〈 0.05）. Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group （P 〈 0.05）. Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours. CONCLUSION： Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.展开更多
Rheological tests for raw and conditioned activated sludge （AS） or anaerobic digested sludge （ADS） show that power-law relationships can be used to describe the evolution of several rheological parameters, i.e., l...Rheological tests for raw and conditioned activated sludge （AS） or anaerobic digested sludge （ADS） show that power-law relationships can be used to describe the evolution of several rheological parameters, i.e., limiting viscosity （η∞）, yield stress （τy）, cohesion energy of the sludge network （Ec）, and storage modulus （G＇）, with total suspended solid （TSS） content in raw and conditioned sludge. A gel-like structure that behaves similar to weak-link flocs/aggregates was observed in AS and ADS. As derived from the double-logarithmic plots of G＇-TSS content, the mass fractal dimensions of the raw and conditioned AS or ADS flocs/aggregates were 2.70 and 2.53 or 2.85 and 2.79, respectively. The theological tests also indicate that both polymer conditioning and increased TSS content led to improved elastic behavior, cohesion energy, and yield stress of the sludge network, as well as expanded the corresponding linear viscoelastic range. The porosity of AS or ADS flocs/aggregates will be improved by polymer conditioning.展开更多
文摘On September 23, 2020, in order “To address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines”. With this announcement, the FDA proclaimed that much more needs to be known about the initiation, continuation, and discontinuation of these widely-used drugs. Unfortunately, relevant information is lacking, since for many years, there has been a notable sparsity in the funding and conduct of basic and clinical research on these drugs. In order to begin to fill the void, it is valuable to (re)examine animal models. We here describe a model of conditioned place-preference (CPP) for rats and for the first time, to our knowledge, show that the representative benzodiazepine alprazolam induces positive place-preference in male rats.
文摘<span lang="EN-US" style="white-space:normal;font-family:Verdana;">The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">the </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">us</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">e of</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> these widely-used drugs with publication of the announcement </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">“</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">”</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;"> Because for many years</span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">, </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">there has been a sparsity </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">of </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place</span><span lang="EN-US" style="white-space:normal;" "=""> </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">preference (CPP) </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">which </span><span lang="EN-US" style="white-space:normal;font-family:Verdana;">suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.</span>
基金Kinross Gold and MITACS for their financial support(Grant No.FR42880).
文摘The goal of this research is to develop mine-scale discrete fracture network(DFN)models in which the influence of the spatial heterogeneity of fracture distributions may be investigated on the rock wedge stability of an open pit slope.For this purpose,spatially conditioned DFN models were developed for the pit walls at Tasiast mine using comprehensive structural data from the mine.Using Sequential Gaussian Simulation(SGS),volumetric fracture intensities(P32)were modeled across the entire mine site in the form of 3D block models.The simulated P32 block models were used as the input constraints for conditional DFN fracture generation,where the DFN grid dimension is the same as the SGS 3D blocks.The spatially constrained DFN models were further calibrated using aerial fracture intensities(P21)data from the pit walls,obtained by a survey of the pit walls using an unmanned aerial vehicle(UAV)and measured traces of joints from 3D point cloud data.The final DFN model is expected to honor the fracture intensities gathered through different means with optimal model accuracy.Finally,bench-scale and interramp scale rock wedge slope stability analyses were conducted using the calibrated conditional DFN models.This work proves the significance of conditioned DFN models in rock wedge stability analysis.Such models provide detailed information regarding rock wedge stability so that site monitoring and prevention plans can be conducted with higher efficiency.
基金Supported by the National Natural Science Foundation of China(Grant Nos.12361040,12061064)the National Science Foundation of Gansu Province(Grant No.22JR5RA264)State Scholarship Fund(Grant No.20230862021).
文摘In this article,we show the existence,uniqueness and stability of bounded solutions to the following quasilinear problems with mean curvature operator(φ'(x′(t)))′=f(t,x),t≥t_(0),lim_(t→∞)x(t)=ψ_(0),lim_(t→∞)x′(t)e^(t)=0,where t_(0) and ψ_(0) are real constants,φ(s)=s/√1−s^(2),s∈R with s∈(−1,1),f:[t_(0),∞)×R→R satisfies the Lipschitz or Osgood-type conditions.
文摘In this paper,we study the asymptotic behavior of the micropolar fluid flow through a thin domain,assuming zero Dirichlet boundary condition on the top boundary,which is rapidly oscillating,and non-standard boundary conditions on the flat bottom.Assuming“Reynolds roughness regime”,in which the thickness of the domain is very small compared to the wavelength of the roughness(i.e.a very slight roughness),we rigorously derive a generalized Reynolds equation for pressure,clearly showing the roughness-induced effects.Moreover,we give expressions for the average velocity and microrotation.
基金supported by the Chung-Ang University Research Grants in 2023.Alsothe work is supported by the ELLIIT Excellence Center at Linköping–Lund in Information Technology in Sweden.
文摘Recommending personalized travel routes from sparse,implicit feedback poses a significant challenge,as conventional systems often struggle with information overload and fail to capture the complex,sequential nature of user preferences.To address this,we propose a Conditional Generative Adversarial Network(CGAN)that generates diverse and highly relevant itineraries.Our approach begins by constructing a conditional vector that encapsulates a user’s profile.This vector uniquely fuses embeddings from a Heterogeneous Information Network(HIN)to model complex user-place-route relationships,a Recurrent Neural Network(RNN)to capture sequential path dynamics,and Neural Collaborative Filtering(NCF)to incorporate collaborative signals from the wider user base.This comprehensive condition,further enhanced with features representing user interaction confidence and uncertainty,steers a CGAN stabilized by spectral normalization to generate high-fidelity latent route representations,effectively mitigating the data sparsity problem.Recommendations are then formulated using an Anchor-and-Expand algorithm,which selects relevant starting Points of Interest(POI)based on user history,then expands routes through latent similarity matching and geographic coherence optimization,culminating in Traveling Salesman Problem(TSP)-based route optimization for practical travel distances.Experiments on a real-world check-in dataset validate our model’s unique generative capability,achieving F1 scores ranging from 0.163 to 0.305,and near-zero pairs−F1 scores between 0.002 and 0.022.These results confirm the model’s success in generating novel travel routes by recommending new locations and sequences rather than replicating users’past itineraries.This work provides a robust solution for personalized travel planning,capable of generating novel and compelling routes for both new and existing users by learning from collective travel intelligence.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
基金This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No.002p1503).
文摘Objective: To find out a method of extraction and purification of bone morphogenetic protein (BMP) from osteosarcoma cell conditioned medium, and evaluate the biological activity of BMP.Methods: Conditioned medium of osteosarcoma cell lines (MG-63) was collected, concentrated and dialyzed. The concentrated protein was purified through gel chromatography on Sephcryl-S-100. The purified protein was tested by BMP monoclonal antibody (McAb), its molecular weight (MW) was determined by SDS-PAGE and its biological activity was demonstrated by heterotopic ossification.Results: The purified protein was proved to be BMP by BMP McAb, had a satisfactory heterotopic ossification, and its MW was about 21 kD.Conclusion: BMP existed in the conditioned medium of osteosarcoma cell and had a satisfactory biological activity after purification. Because osteosarcoma cell can be cultured and grew for a long timein vitro, this method will be helpful to a vast extraction of BMP and clinical application. Key words osteosarcoma cell - conditioned medium - bone morphogenetic protein - protein purification This project was a key scientific and technological program of Hubei Provicial Scientific and Technological Committee (No. 002p1503).
文摘This paper explores the convergence of a class of optimally conditioned self scaling variable metric (OCSSVM) methods for unconstrained optimization. We show that this class of methods with Wolfe line search are globally convergent for general convex functions.
基金supported by grants from the National Natural Science Foundation of China (31671091 and 81771197)the Natural Science Foundation of Jiangsu Province, China (BK20171255)the Science and Technology Planning Project of Nantong Municipality, China (MS12017023-9)
文摘Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
基金supported by the National Natural Science Foundation of China (No. 51078035, 20977008)the Fundamental Research Funds for the Central Universities (No. BLJC200902, TD2010-5)+1 种基金the High-Tech Research and Development Program (863) of China (No. 2007AA06Z301)the Major Projects on Control and Rectification of Water Body Pollution (No. 2008ZX07422-002-004, 2008ZX07314-006)
文摘The changes in the physical characteristics of unconditioned and conditioned anaerobic digested sludge （ADS） biosolids, such as capillary suction time （CST）, yield stress, average size and fractal dimensions, were investigated through a CST test, transient and dynamic rheological test and image analysis. The results showed that the optimum polymer dose range was observed when CST or its reciprocal value was employed as an indicator. There were good correlations between the yield stresses determined from both a controlled shear stress test and a strain amplitude sweep test. The yield stress and storage modulus （G＇） increased as the polymer dose increased in most cases. A frequency sweep test revealed that polymer conditioning could extend the frequency sweep ranges for their elastic behaviors over viscous behaviors as well as the gel-like structure in the linear viscoelastic range. These results implied that more deformation energy was stored in this rigid structure, and that elastic behavior became increasingly dominant with the addition of the polymer in most cases, In addition, both the average sizes and two-dimensional fractal dimensions for conditioned ADS biosolids presented a similar up-climax-down variation trend as the polymer doses increased, whereas the critical polymer doses at the highest average sizes or two-dimensional fractal dimensions, were different. Correlation analysis revealed that the conditioned ADS dewaterability was not correlated with the yield stresses, while the average sizes or the two-dimensional fractal dimensions for conditioned ADS biosolids could be taken as the indication parameters for ADS dewaterability.
文摘In this paper, the automated grid method is applied to test for the mechanical properties of conditioned rubbers under the moderate ?nite deformation (not exceeding 100%). More accurate stress-strain curves of conditioned rubber specimens under di?erent conditioned strains are obtained. Test results show di?erences between these curves. Based on an analysis of the classical constitutive models, a new modi?ed eight-chain model is proposed, which takes account of both the locking stretch of chains and the interaction e?ect in the network. Fitting test data shows that the modi?ed model well characterizes the incompressible hyperelastic mechanical behavior of conditioned rubbers under the moderate ?nite deformation as well as under the large deformation.
基金supported by the National Natural Science Foundation of China (81171249)
文摘The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned stimulus （CS）. In the experiment, 36 participants were trained in differential DEC with a soft tone （60 dB） or a loud tone （85 dB） as the CS, paired with a corneal air-puff as the unconditioned stimulus （US）. After conditioning, awareness of the relationship between assessed with a 17-item the CS and the US was true/false questionnaire. Interestingly, during differential DEC with a soft-tone CS, a higher proportion of differential conditioned responses （CRs） was evident in participants who were aware than those who were unaware. In contrast, when a loud tone was used as the CS, the proportion of differential CRs of the aware participants did not differ significantly from those who were unaware over any of the blocks of 20 trials. In unaware participants, the percentage of differential CRs with a loud-tone CS was significantly higher than that with a soft-tone CS; however in participants classified as aware, the percentage of differential CRs with a loud-tone CS did not differ significantly from that with a soft-tone CS. The present findings suggest that awareness is critical for differential DEC when the delay task is rendered more difficult.
基金supported by the National Natural Science Foundation of China,No.81171173 and 81672161
文摘Endothelial progenitor cells secrete a variety of growth factors that inhibit inflammation, promote angiogenesis and exert neuroprotective effects. Therefore, in this study, we investigated whether endothelial progenitor cell-conditioned medium might have therapeutic effectiveness for the treatment of spinal cord injury using both in vitro and in vivo experiments. After primary culture of bone marrow-derived macrophages, lipopolysaccharide stimulation was used to classically activate macrophages to their proinflammatory phenotype. These cells were then treated with endothelial progenitor cell-conditioned medium or control medium. Polymerase chain reaction was used to determine mR NA expression levels of related inflammatory factors. Afterwards, primary cultures of rat spinal cord neuronal cells were prepared and treated with H2O2and either endothelial progenitor cell-conditioned medium or control medium. Hoechst 33258 and propidium iodide staining were used to calculate the proportion of neurons undergoing apoptosis. Aortic ring assay was performed to assess the effect of endothelial progenitor cell-conditioned medium on angiogenesis. Compared with control medium, endothelial progenitor cell-conditioned medium mitigated the macrophage inflammatory response at the spinal cord injury site, suppressed apoptosis, and promoted angiogenesis. Next, we used a rat model of spinal cord injury to examine the effects of the endothelial progenitor cell-conditioned medium in vivo. The rats were randomly administered intraperitoneal injection of PBS, control medium or endothelial progenitor cell-conditioned medium, once a day, for 6 consecutive weeks. Immunohistochemistry was used to observe neuronal morphology. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was performed to detect the proportion of apoptotic neurons in the gray matter. The Basso, Beattie and Bresnahan Locomotor Rating Scale was used to evaluate the recovery of motor function of the bilateral hind limbs after spinal cord injury. Compared with the other two groups, the number of axons was increased, cavities in the spinal cord were decreased, the proportion of apoptotic neurons in the gray matter was reduced, and the Basso, Beattie and Bresnahan score was higher in the endothelial progenitor cell-conditioned medium group. Taken together, the in vivo and in vitro results suggest that endothelial progenitor cell-conditioned medium suppresses inflammation, promotes angiogenesis, provides neuroprotection, and promotes functional recovery after spinal cord injury.
基金supported by grants from the National Basic Research Development Program (973 Program) of China (2011CB707802,2011CB707800)the National Natural Science Foundation of China (81171302)
文摘Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.
文摘Animals learn to avoid particular food when some of its sensory properties are associated with gastrointestinal discomfort. Twenty rats were exposed to free access to food and a sugar solution for ten days in first phase. During second phase, experimental group received a dose of LiCl. Control group received an injection without LiCl. Both groups had free access to a sugar solution and food restriction for three days. In the final phase, both groups returned to the conditions of first phase. Results showed a significant decrease in sugar intake after aversive conditioning regarding the intake registered in the initial phase in experimental group. Control group did not show any differences in its sugar intake before and after the experimental manipulation. The procedure carried out is discussed as a means to decrease sugar intake.
文摘Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin’s role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30-300 pmol) and cocaine (0.625-10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pretreatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds.
文摘A paracrine regulation was recently proposed in human embryonic stem cells （hESCs） grown in mouse embryonic fibroblast （MEF）-conditioned media （MEF-CM）, where hESCs spontaneously differentiate into autologous fibroblastlike cells to maintain culture homeostasis by producing TGF-β and insulin-like growth factor-lI （IGF-Ⅱ） in response to basic fibroblast growth factor （bFGF）. Although the importance of TGF-β family members in the maintenance of pluripotency of hESCs is widely established, very little is known about the role of IGF-Ⅱ. In order to ease hESC cul- ture conditions and to reduce xenogenic components, we sought （i） to determine whether hESCs can be maintained stable and pluripotent using CM from human foreskin fibroblasts （HFFs） and human mesenchymal stem cells （hM- SCs） rather than MEF-CM, and （ii） to analyze whether the cooperation of bFGF with TGF-β and IGF-Ⅱ to maintain hESCs in MEF-CM may be extrapolated to hESCs maintained in allogeneic mesenchymal stem cell （MSC）-CM and HFF-CM. We found that MSCs and HFFs express all FGF receptors （FGFR1-4） and specifically produce TGF-β in response to bFGF. However, HFFs but not MSCs secrete IGF-Ⅱ. Despite the absence of IGF-Ⅱ in MSC-CM, hESC pluripotency and culture homeostasis were successfully maintained in MSC-CM for over 37 passages. Human ESCs derived on MSCs and hESCs maintained in MSC-CM retained hESC morphology, euploidy, expression of surface markers and transcription factors linked to pluripotency and displayed in vitro and in vivo multilineage developmental potential, suggesting that IGF-Ⅱ may be dispensable for hESC pluripotency. In fact, IGF-Ⅱ blocking had no effect on the homeostasis of hESC cultures maintained either on HFF-CM or on MSC-CM. These data indicate that hESCs are successfully maintained feeder-free with IGF-Ⅱ-lacking MSC-CM, and that the previously proposed paracrine mechanism by which bFGF cooperates with TGF-β and IGF-Ⅱ in the maintenance of hESCs in MEF-CM may not be fully extrapolated to hESCs maintained in CM from human MSCs.
基金Supported by:the Key Construction Program Foundation of Shandong Province during the 11~(th) Five-Year Development Plan Period
文摘BACKGROUND： Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE： It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium. DESIGN AND SETTING： This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China. MATERIAL： Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS： Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium （10 μ L） was injected into rat lateral ventricle in the control group （n = 8）. Coriaria lactone-activated, astrocyte-conditioned medium （10 μL） was infused into the rat lateral ventricle in the coriaria lactone group （n = 32）. At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point. MAIN OUTCOME MEASURES： Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry. RESULTS： Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group （P 〈 0.05）. Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group （P 〈 0.05）. Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours. CONCLUSION： Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.
基金supported by the Fundamental Research Funds for the Central Universities (No. JC2011-1,TD2010-5)the National Natural Science Foundation of China (No. 51078035,21177010)+2 种基金the Ph.D. Programs Foundation of the Ministry of Education of China (No.20100014110004)the High-Tech Research and Development Program (863) of China (No. 2007AA06Z301)the Major Projects on the Control and Rectificationof Water Body Pollution (No. 2008ZX07422-002-004,2008ZX07314-006)
文摘Rheological tests for raw and conditioned activated sludge （AS） or anaerobic digested sludge （ADS） show that power-law relationships can be used to describe the evolution of several rheological parameters, i.e., limiting viscosity （η∞）, yield stress （τy）, cohesion energy of the sludge network （Ec）, and storage modulus （G＇）, with total suspended solid （TSS） content in raw and conditioned sludge. A gel-like structure that behaves similar to weak-link flocs/aggregates was observed in AS and ADS. As derived from the double-logarithmic plots of G＇-TSS content, the mass fractal dimensions of the raw and conditioned AS or ADS flocs/aggregates were 2.70 and 2.53 or 2.85 and 2.79, respectively. The theological tests also indicate that both polymer conditioning and increased TSS content led to improved elastic behavior, cohesion energy, and yield stress of the sludge network, as well as expanded the corresponding linear viscoelastic range. The porosity of AS or ADS flocs/aggregates will be improved by polymer conditioning.
