Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six a...Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.展开更多
The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression...The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression resistance, so the compression resistance of an explosive can be compared and analyzed quantificationally with the desensitization degree. The influence of an emulsifier on the pressure desensitization of EE was studied, including the content and category of emulsifiers. Three kinds of emulsifiers (Span-80, compound emulsifier, and T-152) were used in the tests. The experimental results show that both the content and category of emulsifiers make a great effect on the pressure desensitization of EE. The desensitization degree of EE reduces with the emulsifier content being increased, but there is an optimal content of an emulsifier for the compression resistance of EE. While the content of Span-80 reaches 4wt%, the desensitization degree of EE becomes a minimal value, and augments somewhat if the emulsifier content is increased more. That is to say, the compression resistance of EE becomes the highest while the content of Span-80 is 4wt%, and the compression resistance will decline if the content of Span-80 is increased more. The compression resistance of the explosive emulsified by compound emulsifier is the highest among all the explosives, when the content of the whole components and manufacturing engineering are kept invariable.展开更多
The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effec...The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (h=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=O.O33) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.展开更多
Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using stan...Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.展开更多
Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through ...Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.展开更多
BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric ...BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.展开更多
Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accident...Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accidents during its storage and usage in ammunition.In this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were synthesized.The products were characterized by FT-IR,Raman,XRD,SEM,elemental analysis,TGA,DSC,accelerating rate calorimeter analysis(ARC),and drop weight test to study their molecular structure,thermal characteristics and desensitization performance.Compared with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC curves.The H50values of the two kinds of LNC increased from 25.76 to 30.01 cm for low nitrogen content and from 18.02 to 21.84 cm for high nitrogen content,respectively.The results show that the ladder-structure of LNC which provides regular molecular arrangement and a soft buffer made with polyethylene glycol could affect the energy releasing process of LNC and reduce the sensitivity of LNC.Insensitive LNC provides an alternative to be used as a binder in insensitive propellants formulation.展开更多
The mechanical sensitivity, the critical thickness of detonation wave propagation and detonation velocity of desensitized PETN film were studied by experiments. The relationship between the mass of desensitizer paraff...The mechanical sensitivity, the critical thickness of detonation wave propagation and detonation velocity of desensitized PETN film were studied by experiments. The relationship between the mass of desensitizer paraffin wax and the friction sensitivity of desensitized PETN film was tested. According to the microstructure of film, the function of desensitizer was explained. It was proved that the explosive film could make explosive element micromation and kept its inherence properties by the result of testing the propagating critical dimension of the desensitized PETN film detonation wave. The explosive velocity of confined desensitized PETN film was tested by the multiplex optical fibre..展开更多
The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients w...The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.展开更多
Aim: This study determined whether prior brushing with desensitizing toothpastes (Sensodyne Rapid Relief and Colgate Pro-Relief) affected the shear bond strengths of composite to dentine surfaces after appropriate use...Aim: This study determined whether prior brushing with desensitizing toothpastes (Sensodyne Rapid Relief and Colgate Pro-Relief) affected the shear bond strengths of composite to dentine surfaces after appropriate use of two different dentine bonding agents (SingleBond and PQ-1). Materials and Methods: Sixty caries free molar teeth were cleaned, disinfected and embedded in individual cylinders of polymethylmethracyrlate. The occulsal surfaces were flattened to expose dentine and finished down with 600 grit silicone carbide paper. The teeth were randomly divided into six groups of 10 teeth each. Two groups served as control where dentine surfaces were brushed with pumice slurry. Of the remaining 4 groups, 2 groups were brushed with Sensodyne Rapid Relief and 2 groups brushed with Colgate Pro-Relief. The dentine surfaces were brushed to simulate 2 weeks of twice-daily toothpaste use. The specimens in each of the control groups and experimental groups were subjected to dentine bonding procedures (Single Bond or PQ-1), and application of hybrid composite resin (Z-250) according to the manufacturer’s instructions. A universal material testing machine, with a cross head speed of 0.05 mm/min was used to determine shear bond strengths. Results: Mean shear bond strengths ranged from 5.71 MPa (Colgate pretreatment, composite bonded with Single Bond) to 9.07 MPa (Sensodyne pretreatment, composite bonded with Single Bond). Results showed neither of the main effects, of toothpaste type or bonding agent were significant (p > 0.05) but their interaction was (F = 4.25, p = 0.02). Post hoc analysis showed that teeth brushed with the Sensodyne group, treated with the unfilled dentine bonding agent had a significantly higher bond strength than those treated with the filled dentine bonding agent. Conclusion: The desensitizing toothpastes that use the mechanism of occlusion of open dentinal tubules in the preliminary management of tooth sensitivity should not have an adverse effect on future restorative treatment modalities.展开更多
OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as e...OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.展开更多
Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensit...Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.展开更多
Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and ...Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.展开更多
Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization ast...Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization asthma model group.Asthma model was established,and on this basis,the method of atom-izing inhalation and intraperitoneal injections of salbutamol was used to prepareβ_(2)-AR desensitization asthma model.After the last stimulation on the 21st day of modeling,the airway resistance of mice was measured.ELISA was used to detect the content of serum IgE;HE staining was used to observe the lung organization degree of infla-mmatory cell infiltration;Western blot method was used to detect theβ_(2)-AR content in lung tissue,RT-PCR was used to detect theβ_(2)-ARmRNA expressionin lung tissue.Results:Compared with the blank group,as acetyl choline(Mch)levels increased,groups of OVA induced airway resistance increases;but theβ_(2)-AR desensitization asthma model group increased airway resistance was more significant(P<0.05);compared with the blank group,IgE levels of common asthma group andβ_(2)-AR desensitization asthma model group elevated(P<0.01).The pathological histology observation found theβ_(2)-AR desensitization asthma airway inflammation infiltration in mice,the excessive mucus secretion and collagen deposition,and the pathological performance obviously increase compared with the common asthma group;β_(2)-AR content in the lung tissue ofβ_(2)-AR desensitization asthma model in mice,β_(2)-AR mRNA expression level in the blank group and common asthma model group were significantly decreased(P<0.05).Conclusion:Theβ_(2)-AR desensitization asthma mouse model was successfully established,and the buildingcycle was short.展开更多
Arabidopsis seedlings undergo photomorphogenesis in the light and etiolation in the dark. HFR1, a bHLH transcription factor, is required for both phytochrome A (phyA)-mediated far-red and cryptochrome 1 (cry1)-mediate...Arabidopsis seedlings undergo photomorphogenesis in the light and etiolation in the dark. HFR1, a bHLH transcription factor, is required for both phytochrome A (phyA)-mediated far-red and cryptochrome 1 (cry1)-mediated blue light signaling. We report that HFR1 is a short-lived protein in darkness and is degraded through a 26S proteasome-dependent pathway. Light, irrespective of its quality, enhances HFR1 protein accumulation via promoting its stabilization. We demonstrate that HFR1 physically interacts with COP1 and that COP1 exhibits ubiquitin ligase activity toward HFR1 in vitro. In addition, we show that COP1 is required for degradation of HFR1 in vivo. Furthermore, plants overexpressing a C-terminal 161 amino acid fragment of HFR1 (CT161) display enhanced photomorphogenesis, suggesting an autonomous function of CT161 in promoting light signaling. This truncated HFR1 gene product is more stable than the full-length HFR1 protein in darkness, indicating that the COP1-interacting N-terminal portion of HFR1 is essential for COP1-mediated destabilization of HFR1. These results suggest that light enhances HFR1 protein accumulation by abrogating COP1-mediated degradation of HFR1, which is necessary and sufficient for promoting light signaling. Additionally, our results substantiate the E3 ligase activity of COP1 and its critical role in desensitizing light signaling.展开更多
Objective: The purpose of this study was to investigate the effects of desensitized nicotinic receptors(n ACh Rs) on striatal dopaminergic system in the hemiparkinsonian rats treated with 6-hydroxydopamine(6-OHDA). Me...Objective: The purpose of this study was to investigate the effects of desensitized nicotinic receptors(n ACh Rs) on striatal dopaminergic system in the hemiparkinsonian rats treated with 6-hydroxydopamine(6-OHDA). Methods: We examined the effects of desensitized n ACh Rs on the levels of dopamine(DA) and its metabolites, m RNA expression of dopamine receptor D1,D2 and monoamine oxidase B(MAO-B) in the striatum of 6-OHDA-lesioned rats using high-performance liquid chromatography and reverse transcription-polymerase chain reaction. Results: The results showed that n ACh Rs desensitization following repeated nicotine stimulation could reverse significantly the decrease of striatal DA and its metabolites levels and the increase in DA turnover in lesioned side striatum of hemiparkinsonian rats. Dopamine D1 receptor m RNA expression increased significantly, whereas dopamine D2 receptor m RNA expression remained unchanged in lesioned side striatum of nicotine-treated rats compared to 6-OHDA-lesioned rats when n ACh Rs were desensitized. Meanwhile, nicotine-treated rats displayed a significant decrease in MAO-B m RNA expression in lesioned side striatum compared to 6-OHDA-lesioned rats after n ACh Rs desensitization. Conclusion: These results suggest that n ACh Rs desensitization could promote DA level, upregulate dopamine D1 receptor expression and downregulate MAO-B expression in striatum of hemiparkinsonian rats.展开更多
文摘Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.
基金This work was financially supported by the National Natural Science Foundation of China (No.50574004).
文摘The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression resistance, so the compression resistance of an explosive can be compared and analyzed quantificationally with the desensitization degree. The influence of an emulsifier on the pressure desensitization of EE was studied, including the content and category of emulsifiers. Three kinds of emulsifiers (Span-80, compound emulsifier, and T-152) were used in the tests. The experimental results show that both the content and category of emulsifiers make a great effect on the pressure desensitization of EE. The desensitization degree of EE reduces with the emulsifier content being increased, but there is an optimal content of an emulsifier for the compression resistance of EE. While the content of Span-80 reaches 4wt%, the desensitization degree of EE becomes a minimal value, and augments somewhat if the emulsifier content is increased more. That is to say, the compression resistance of EE becomes the highest while the content of Span-80 is 4wt%, and the compression resistance will decline if the content of Span-80 is increased more. The compression resistance of the explosive emulsified by compound emulsifier is the highest among all the explosives, when the content of the whole components and manufacturing engineering are kept invariable.
基金This study was funded by the National Natural Science Foundation of China (No.30872175,No.81573236).
文摘The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (h=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=O.O33) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.
基金ThisresearchwassupportedbytheNationalNaturalScienceFoundationofChina (No .30 2 70 5 5 4No .39970 2 73) +1 种基金Doctonialsubject (No .2 0 0 10 6 980 34)keyItemofScientificTechnologyforministryofEducation (No .0 116 1) .
文摘Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.
文摘Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.
基金supported by a grant from the National Natural Science Foundation of China (30972920)
文摘BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.
基金supported in part by the National Natural Science Foundation of China(No.22075146)。
文摘Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accidents during its storage and usage in ammunition.In this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were synthesized.The products were characterized by FT-IR,Raman,XRD,SEM,elemental analysis,TGA,DSC,accelerating rate calorimeter analysis(ARC),and drop weight test to study their molecular structure,thermal characteristics and desensitization performance.Compared with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC curves.The H50values of the two kinds of LNC increased from 25.76 to 30.01 cm for low nitrogen content and from 18.02 to 21.84 cm for high nitrogen content,respectively.The results show that the ladder-structure of LNC which provides regular molecular arrangement and a soft buffer made with polyethylene glycol could affect the energy releasing process of LNC and reduce the sensitivity of LNC.Insensitive LNC provides an alternative to be used as a binder in insensitive propellants formulation.
文摘The mechanical sensitivity, the critical thickness of detonation wave propagation and detonation velocity of desensitized PETN film were studied by experiments. The relationship between the mass of desensitizer paraffin wax and the friction sensitivity of desensitized PETN film was tested. According to the microstructure of film, the function of desensitizer was explained. It was proved that the explosive film could make explosive element micromation and kept its inherence properties by the result of testing the propagating critical dimension of the desensitized PETN film detonation wave. The explosive velocity of confined desensitized PETN film was tested by the multiplex optical fibre..
文摘The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.
文摘Aim: This study determined whether prior brushing with desensitizing toothpastes (Sensodyne Rapid Relief and Colgate Pro-Relief) affected the shear bond strengths of composite to dentine surfaces after appropriate use of two different dentine bonding agents (SingleBond and PQ-1). Materials and Methods: Sixty caries free molar teeth were cleaned, disinfected and embedded in individual cylinders of polymethylmethracyrlate. The occulsal surfaces were flattened to expose dentine and finished down with 600 grit silicone carbide paper. The teeth were randomly divided into six groups of 10 teeth each. Two groups served as control where dentine surfaces were brushed with pumice slurry. Of the remaining 4 groups, 2 groups were brushed with Sensodyne Rapid Relief and 2 groups brushed with Colgate Pro-Relief. The dentine surfaces were brushed to simulate 2 weeks of twice-daily toothpaste use. The specimens in each of the control groups and experimental groups were subjected to dentine bonding procedures (Single Bond or PQ-1), and application of hybrid composite resin (Z-250) according to the manufacturer’s instructions. A universal material testing machine, with a cross head speed of 0.05 mm/min was used to determine shear bond strengths. Results: Mean shear bond strengths ranged from 5.71 MPa (Colgate pretreatment, composite bonded with Single Bond) to 9.07 MPa (Sensodyne pretreatment, composite bonded with Single Bond). Results showed neither of the main effects, of toothpaste type or bonding agent were significant (p > 0.05) but their interaction was (F = 4.25, p = 0.02). Post hoc analysis showed that teeth brushed with the Sensodyne group, treated with the unfilled dentine bonding agent had a significantly higher bond strength than those treated with the filled dentine bonding agent. Conclusion: The desensitizing toothpastes that use the mechanism of occlusion of open dentinal tubules in the preliminary management of tooth sensitivity should not have an adverse effect on future restorative treatment modalities.
文摘OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.
文摘Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.
文摘Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.
基金General Projects of National Natural Science Fund(81873338)Key Scientific and Technological Projects in Henan Province(202102310491)Training Subjects of Leading Talents in the Department of Traditional Chinese Medicine in Henan Province(Yuweizhongyihan[2021]No.8)。
文摘Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization asthma model group.Asthma model was established,and on this basis,the method of atom-izing inhalation and intraperitoneal injections of salbutamol was used to prepareβ_(2)-AR desensitization asthma model.After the last stimulation on the 21st day of modeling,the airway resistance of mice was measured.ELISA was used to detect the content of serum IgE;HE staining was used to observe the lung organization degree of infla-mmatory cell infiltration;Western blot method was used to detect theβ_(2)-AR content in lung tissue,RT-PCR was used to detect theβ_(2)-ARmRNA expressionin lung tissue.Results:Compared with the blank group,as acetyl choline(Mch)levels increased,groups of OVA induced airway resistance increases;but theβ_(2)-AR desensitization asthma model group increased airway resistance was more significant(P<0.05);compared with the blank group,IgE levels of common asthma group andβ_(2)-AR desensitization asthma model group elevated(P<0.01).The pathological histology observation found theβ_(2)-AR desensitization asthma airway inflammation infiltration in mice,the excessive mucus secretion and collagen deposition,and the pathological performance obviously increase compared with the common asthma group;β_(2)-AR content in the lung tissue ofβ_(2)-AR desensitization asthma model in mice,β_(2)-AR mRNA expression level in the blank group and common asthma model group were significantly decreased(P<0.05).Conclusion:Theβ_(2)-AR desensitization asthma mouse model was successfully established,and the buildingcycle was short.
文摘Arabidopsis seedlings undergo photomorphogenesis in the light and etiolation in the dark. HFR1, a bHLH transcription factor, is required for both phytochrome A (phyA)-mediated far-red and cryptochrome 1 (cry1)-mediated blue light signaling. We report that HFR1 is a short-lived protein in darkness and is degraded through a 26S proteasome-dependent pathway. Light, irrespective of its quality, enhances HFR1 protein accumulation via promoting its stabilization. We demonstrate that HFR1 physically interacts with COP1 and that COP1 exhibits ubiquitin ligase activity toward HFR1 in vitro. In addition, we show that COP1 is required for degradation of HFR1 in vivo. Furthermore, plants overexpressing a C-terminal 161 amino acid fragment of HFR1 (CT161) display enhanced photomorphogenesis, suggesting an autonomous function of CT161 in promoting light signaling. This truncated HFR1 gene product is more stable than the full-length HFR1 protein in darkness, indicating that the COP1-interacting N-terminal portion of HFR1 is essential for COP1-mediated destabilization of HFR1. These results suggest that light enhances HFR1 protein accumulation by abrogating COP1-mediated degradation of HFR1, which is necessary and sufficient for promoting light signaling. Additionally, our results substantiate the E3 ligase activity of COP1 and its critical role in desensitizing light signaling.
基金supported by a grant from the National Natural Science Foundations of China(30371641)
文摘Objective: The purpose of this study was to investigate the effects of desensitized nicotinic receptors(n ACh Rs) on striatal dopaminergic system in the hemiparkinsonian rats treated with 6-hydroxydopamine(6-OHDA). Methods: We examined the effects of desensitized n ACh Rs on the levels of dopamine(DA) and its metabolites, m RNA expression of dopamine receptor D1,D2 and monoamine oxidase B(MAO-B) in the striatum of 6-OHDA-lesioned rats using high-performance liquid chromatography and reverse transcription-polymerase chain reaction. Results: The results showed that n ACh Rs desensitization following repeated nicotine stimulation could reverse significantly the decrease of striatal DA and its metabolites levels and the increase in DA turnover in lesioned side striatum of hemiparkinsonian rats. Dopamine D1 receptor m RNA expression increased significantly, whereas dopamine D2 receptor m RNA expression remained unchanged in lesioned side striatum of nicotine-treated rats compared to 6-OHDA-lesioned rats when n ACh Rs were desensitized. Meanwhile, nicotine-treated rats displayed a significant decrease in MAO-B m RNA expression in lesioned side striatum compared to 6-OHDA-lesioned rats after n ACh Rs desensitization. Conclusion: These results suggest that n ACh Rs desensitization could promote DA level, upregulate dopamine D1 receptor expression and downregulate MAO-B expression in striatum of hemiparkinsonian rats.