The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we disco...The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we discovered that the activated NLRP3 inflammasome complex(disc-NLRP3)and the activating mutation L351P exhibited resistance to MCC950.Through investigations using the small-molecule compound polydatin,HSP90αwas found to stabilize both the resting(cage-NLRP3)and activated state(disc-NLRP3)of NLRP3 complexes,sustaining its activation.Our mechanistic studies revealed that polydatin specifically targets HSP90α,binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction.This disruption leads to the dissipation of cage-NLRP3,disc-NLRP3 complexes and NLRP3 L351P.Importantly,genetic and pharmacological inactivation of HSP90αeffectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis.These therapeutic effects highlight the clinical potential of HSP90αinhibition.Our findings demonstrate that HSP90αis crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation,and targeting HSP90αrepresents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.展开更多
We classify all the indecomposable modules of dimension ≤ 5 over the quantum exterior algebra k(x, y)/(x^2, y^2, xy + qyx) in two variables, and all the indecomposable modules of dimension ≤3 over the quantum comple...We classify all the indecomposable modules of dimension ≤ 5 over the quantum exterior algebra k(x, y)/(x^2, y^2, xy + qyx) in two variables, and all the indecomposable modules of dimension ≤3 over the quantum complete intersection k(x,y)/(x^m,y^n,xy + qyx) in two variables, where m or n ≥3, by giving explicitly their diagram presentations.展开更多
Bit-interleaved coded modulation (BICM) is suitable to bandwidth-efficient communication systems. Hybrid automatic repeat request (HARQ) can provide more reliability to high-speed wireless data transmission. A new pat...Bit-interleaved coded modulation (BICM) is suitable to bandwidth-efficient communication systems. Hybrid automatic repeat request (HARQ) can provide more reliability to high-speed wireless data transmission. A new path weight complementary convolutional (PWCC) code used in the type-Ⅱ BICM-HARQ system is proposed. The PWCC code is composed of the original code and the complimentary code. The path in trellis with large hamming weight of the complimentary code is designed to compensate for the path in trellis with small hamming weight of the original code. Hence, both of the original code and the complimentary code can achieve the performance of the good code criterion of corresponding code rate. The throughput efficiency of the BICM-HARQ system wit PWCC code is higher than repeat code system, a little higher than puncture code system in low signal-to-noise ratio (SNR) values and much higher than puncture code system, the same as repeat code system in high SNR values. These results are confirmed by the simulation.展开更多
目的探讨血清半乳糖缺陷型IgA1(galactose-deficient IgA1,Gd-IgA1)、补体C4、补体因子H(complement factor H,CFH)和补体因子H相关蛋白(complement factor H related proteins,CFHRP)1、3、5在IgA肾病(IgA nephropathy,IgAN)中的诊断...目的探讨血清半乳糖缺陷型IgA1(galactose-deficient IgA1,Gd-IgA1)、补体C4、补体因子H(complement factor H,CFH)和补体因子H相关蛋白(complement factor H related proteins,CFHRP)1、3、5在IgA肾病(IgA nephropathy,IgAN)中的诊断价值。方法本研究为回顾性研究,收集2021年11月1日至2023年12月31日在雅安市人民医院行肾穿刺活检诊断为原发性IgAN的患者58例,同期其他肾小球疾病患者48例和健康志愿者20名作为对照,采用酶联免疫吸附分析法检测上述对象血清IgA、补体C4、Gd-IgA1、CFH、CFHRP1、3、5浓度并行组间比较,绘制受试者工作特征曲线评估血清Gd-IgA1、Gd-IgA1/CFH、CFHRP1/CFH、CFHRP5/CFH在IgAN中的诊断价值,筛选出受试者工作特征曲线的曲线下面积较大的指标Gd-IgA1、CFHRP1/CFH、CFHRP5/CFH,重点研究Gd-IgA1分别联合检测CFHRP1/CFH、CFHRP5/CFH对IgAN的诊断价值。结果原发性IgAN组患者血清IgA[1.568(1.344,1.705)g/L比1.177(0.618,1.893)g/L、0.538(0.433,0.732)g/L]、补体C4[0.547(0.494,0.643)g/L比0.396(0.312,0.515)g/L、0.289(0.186,0.356)g/L]、Gd-IgA1[0.003(0.002,0.004)g/L比0.002(0.001,0.003)g/L、0.0017(0.0010,0.0020)g/L]、CFHRP1[0.013(0.011,0.015)g/L比0.010(0.009,0.013)g/L、0.011(0.009,0.012)g/L]水平及Gd-IgA1/CFH[0.023(0.017,0.030)比0.012(0.009,0.021)mmol/L、0.005(0.004,0.007)mmol/L]、CFHRP1/CFH[0.115(0.091,0.161)比0.093(0.061,0.108)、0.038(0.028,0.043)]比值明显高于其他肾小球疾病组和健康组(P<0.05),血清CFH[0.000109(0.000089,0.000110)g/L比0.000285(0.000259,0.000347)g/L]浓度低于健康组(P<0.05);血清Gd-IgA1联合CFHRP1/CFH、CFHRP5/CFH诊断原发性IgAN的曲线下面积分别为0.946(95%CI:0.908~0.985)、0.926(95%CI:0.874~0.978),灵敏度分别为80%、90%,特异度分别为93.9%、86.3%。结论Gd-IgA1联合检测CFHRP1/CFH、CFHRP5/CFH对于诊断原发性IgAN具有较好价值,或可作为诊断IgAN的潜在无创性生物标志物。展开更多
基金supported by the National Natural Science Foundation of China(82273933,82073856,82230116,and 82473929)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(no.ZYYCXTD-C-202208)Fundamental Research Funds for the Central Universities(020814380199).
文摘The NLRP3 inflammasome plays a critical role in various inflammatory conditions.However,despite extensive research in targeted drug development for NLRP3,including MCC950,clinical success remains elusive.Here,we discovered that the activated NLRP3 inflammasome complex(disc-NLRP3)and the activating mutation L351P exhibited resistance to MCC950.Through investigations using the small-molecule compound polydatin,HSP90αwas found to stabilize both the resting(cage-NLRP3)and activated state(disc-NLRP3)of NLRP3 complexes,sustaining its activation.Our mechanistic studies revealed that polydatin specifically targets HSP90α,binding to it directly and subsequently interfering with the HSP90α-NLRP3 interaction.This disruption leads to the dissipation of cage-NLRP3,disc-NLRP3 complexes and NLRP3 L351P.Importantly,genetic and pharmacological inactivation of HSP90αeffectively reduced NLRP3 inflammasome activation and alleviated cerulein-induced acute pancreatitis.These therapeutic effects highlight the clinical potential of HSP90αinhibition.Our findings demonstrate that HSP90αis crucial for the stability of both the resting and activated states of the NLRP3 inflammasome during its sustained activation,and targeting HSP90αrepresents a promising therapeutic strategy for diseases driven by the NLRP3 inflammasome.
文摘We classify all the indecomposable modules of dimension ≤ 5 over the quantum exterior algebra k(x, y)/(x^2, y^2, xy + qyx) in two variables, and all the indecomposable modules of dimension ≤3 over the quantum complete intersection k(x,y)/(x^m,y^n,xy + qyx) in two variables, where m or n ≥3, by giving explicitly their diagram presentations.
基金the National Natural Science Foundation of China(Nos. 60302006 and 60462002)
文摘Bit-interleaved coded modulation (BICM) is suitable to bandwidth-efficient communication systems. Hybrid automatic repeat request (HARQ) can provide more reliability to high-speed wireless data transmission. A new path weight complementary convolutional (PWCC) code used in the type-Ⅱ BICM-HARQ system is proposed. The PWCC code is composed of the original code and the complimentary code. The path in trellis with large hamming weight of the complimentary code is designed to compensate for the path in trellis with small hamming weight of the original code. Hence, both of the original code and the complimentary code can achieve the performance of the good code criterion of corresponding code rate. The throughput efficiency of the BICM-HARQ system wit PWCC code is higher than repeat code system, a little higher than puncture code system in low signal-to-noise ratio (SNR) values and much higher than puncture code system, the same as repeat code system in high SNR values. These results are confirmed by the simulation.
文摘目的探讨血清半乳糖缺陷型IgA1(galactose-deficient IgA1,Gd-IgA1)、补体C4、补体因子H(complement factor H,CFH)和补体因子H相关蛋白(complement factor H related proteins,CFHRP)1、3、5在IgA肾病(IgA nephropathy,IgAN)中的诊断价值。方法本研究为回顾性研究,收集2021年11月1日至2023年12月31日在雅安市人民医院行肾穿刺活检诊断为原发性IgAN的患者58例,同期其他肾小球疾病患者48例和健康志愿者20名作为对照,采用酶联免疫吸附分析法检测上述对象血清IgA、补体C4、Gd-IgA1、CFH、CFHRP1、3、5浓度并行组间比较,绘制受试者工作特征曲线评估血清Gd-IgA1、Gd-IgA1/CFH、CFHRP1/CFH、CFHRP5/CFH在IgAN中的诊断价值,筛选出受试者工作特征曲线的曲线下面积较大的指标Gd-IgA1、CFHRP1/CFH、CFHRP5/CFH,重点研究Gd-IgA1分别联合检测CFHRP1/CFH、CFHRP5/CFH对IgAN的诊断价值。结果原发性IgAN组患者血清IgA[1.568(1.344,1.705)g/L比1.177(0.618,1.893)g/L、0.538(0.433,0.732)g/L]、补体C4[0.547(0.494,0.643)g/L比0.396(0.312,0.515)g/L、0.289(0.186,0.356)g/L]、Gd-IgA1[0.003(0.002,0.004)g/L比0.002(0.001,0.003)g/L、0.0017(0.0010,0.0020)g/L]、CFHRP1[0.013(0.011,0.015)g/L比0.010(0.009,0.013)g/L、0.011(0.009,0.012)g/L]水平及Gd-IgA1/CFH[0.023(0.017,0.030)比0.012(0.009,0.021)mmol/L、0.005(0.004,0.007)mmol/L]、CFHRP1/CFH[0.115(0.091,0.161)比0.093(0.061,0.108)、0.038(0.028,0.043)]比值明显高于其他肾小球疾病组和健康组(P<0.05),血清CFH[0.000109(0.000089,0.000110)g/L比0.000285(0.000259,0.000347)g/L]浓度低于健康组(P<0.05);血清Gd-IgA1联合CFHRP1/CFH、CFHRP5/CFH诊断原发性IgAN的曲线下面积分别为0.946(95%CI:0.908~0.985)、0.926(95%CI:0.874~0.978),灵敏度分别为80%、90%,特异度分别为93.9%、86.3%。结论Gd-IgA1联合检测CFHRP1/CFH、CFHRP5/CFH对于诊断原发性IgAN具有较好价值,或可作为诊断IgAN的潜在无创性生物标志物。
