We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a the...We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a theoretical framework for the biphasic Ca^(2+)dependence of IP_(3)Rs and accurately reproduces their experimentally observed state distribution under saturating IP_(3) conditions.By integrating receptor dynamics with cytoplasmic and endoplasmic reticulum(ER)calcium exchange,we simulate IP_(3)R-mediated Ca^(2+)oscillations governed by six key conformational states.A pivotal finding is that IP_(3)regulates these oscillations in a switch-like manner:once a critical IP_(3) concentration is reached,the system abruptly transitions to sustained,constant-amplitude oscillations that quickly terminate when the concentration exceeds a secondary threshold.These results underscore the crucial role of the pre-activated state in modulating calcium signaling.展开更多
Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and...Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and environmental factors influencing its distribution in the semi-arid Karamoja sub-region, Uganda. We surveyed 388 plots (5 m radius) at different altitudes, recording life stages, stem diameters, and regeneration patterns, and analyzed soil samples. Multivariate analyses, including Canonical Correspondence Analysis (CCA), Detrended Correspondence Analysis (DCA), Non-metric Multidimensional Scaling (NMDS), and Multiple Regression Modeling (MRM), identified key environmental factors affecting its distribution. Findings show that O. lanceolata populations in Moroto, Nakapiripirit, and Amudat districts are severely degraded due to overexploitation. The species is primarily regenerating through coppicing rather than seedlings, with an exploitation intensity of 56.6%. Population densities are low, distribution is irregular, and sustainable harvesting is not viable. Soil properties, particularly Ca2+, N, P, K+, Na+, and organic matter, significantly influence its abundance. Conservation efforts should focus on identifying suitable provenances for genetic preservation and plantation establishment. Areas with at least 9 trees per hectare in Moroto, Nakapiripirit, and Amudat could serve as potential sites for ex-situ plantations. Further research should explore how biotic interactions, genetic diversity, and morphology affect oil yield and quality to support restoration, breeding, and domestication initiatives.展开更多
Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a cor...Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.展开更多
Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of lo...Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.展开更多
Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabb...Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.12475080)。
文摘We present a novel nonlinear state transition model for inositol 1,4,5-trisphosphate receptors(IP_(3)Rs)that incorporates a pre-activated state,as suggested by electron microscopy observations.Our model provides a theoretical framework for the biphasic Ca^(2+)dependence of IP_(3)Rs and accurately reproduces their experimentally observed state distribution under saturating IP_(3) conditions.By integrating receptor dynamics with cytoplasmic and endoplasmic reticulum(ER)calcium exchange,we simulate IP_(3)R-mediated Ca^(2+)oscillations governed by six key conformational states.A pivotal finding is that IP_(3)regulates these oscillations in a switch-like manner:once a critical IP_(3) concentration is reached,the system abruptly transitions to sustained,constant-amplitude oscillations that quickly terminate when the concentration exceeds a secondary threshold.These results underscore the crucial role of the pre-activated state in modulating calcium signaling.
文摘Osyris lanceolata is heavily and illegally exploited in East Africa for its essential oils, yet little is known about its population status and ecological requirements. This study examined its population structure and environmental factors influencing its distribution in the semi-arid Karamoja sub-region, Uganda. We surveyed 388 plots (5 m radius) at different altitudes, recording life stages, stem diameters, and regeneration patterns, and analyzed soil samples. Multivariate analyses, including Canonical Correspondence Analysis (CCA), Detrended Correspondence Analysis (DCA), Non-metric Multidimensional Scaling (NMDS), and Multiple Regression Modeling (MRM), identified key environmental factors affecting its distribution. Findings show that O. lanceolata populations in Moroto, Nakapiripirit, and Amudat districts are severely degraded due to overexploitation. The species is primarily regenerating through coppicing rather than seedlings, with an exploitation intensity of 56.6%. Population densities are low, distribution is irregular, and sustainable harvesting is not viable. Soil properties, particularly Ca2+, N, P, K+, Na+, and organic matter, significantly influence its abundance. Conservation efforts should focus on identifying suitable provenances for genetic preservation and plantation establishment. Areas with at least 9 trees per hectare in Moroto, Nakapiripirit, and Amudat could serve as potential sites for ex-situ plantations. Further research should explore how biotic interactions, genetic diversity, and morphology affect oil yield and quality to support restoration, breeding, and domestication initiatives.
文摘Following the publication of Zeng et al.(2023),an inadvertent error was recently identified in Figure 1B and Supplementary Figure S3.To ensure the accuracy and integrity of our published work,we formally request a correction to address this issue and apologize for any confusion this error may have caused.For details,please refer to the modified Supplementary Materials.
基金supported by NIH/NIDCR grant R01DE025664 to IPC.
文摘Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.
文摘Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. Conclusion: The “lytic circle' method is a simple, practical and reliable method to determine the plasma level of r SAK, and the pharmacokinetics of native r SAK infusion fits in two compartment model in rabbit's femoral artery thrombosis model.
