Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized th...Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized through the kinesin-microtubule interaction.The binding site of kinesin on the microtubule surface is fixed.For most of the kinesin-family members,the binding site on microtubule is in the groove betweenα-tubulin andβ-tubulin in a protofilament.The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear.Using the molecular dynamics simulation method,we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin's different nucleotide-binding states are listed.The differences of the amino-acid sequences betweenα-andβ-tubulins make kinesin-1 binding to theα–βgroove much more favorable than to theβ–αgroove.From these results,a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed.Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule,the mechanism may also be shared by other family members of kinesin.展开更多
The most recognized and employed model of the solvation equilibration in the ionic solutions was proposed by Eigen and Tamm, in which there are four major states for an ion pair in the solution: the completely solvat...The most recognized and employed model of the solvation equilibration in the ionic solutions was proposed by Eigen and Tamm, in which there are four major states for an ion pair in the solution: the completely solvated state, 2SIP (double solvent separate ion pair), SIP (single solvent separate ion pair), and CIP (contact ion pair). Eigen and Tamm suggested that the transition from SIP to CIP is always the slowest step during the whole pairing process, due to a high free energy barrier between these two states. We carried out a series of potential of mean force calculations to study the pairing free energy profiles of two sets of model mono- atomic 1:1 ion pairs 2.0:x and x:2.0. For 2.0:x pairs the free energy barrier between the SIP and CIP states is largely reduced due to the salvation shell water structure. For these pairs the SIP to CIP transition is thus not the slowest step in the ion pair formation course. This is a deviation from the Eigen-Tamm model.展开更多
To the Editor:Schwannoma is an infrequent tumor originating from Schwann cells of the peripheral nerve sheath and was first reported as a true neoplasm originating from Schwann cells in 1910 [1] . The ma- jority of sc...To the Editor:Schwannoma is an infrequent tumor originating from Schwann cells of the peripheral nerve sheath and was first reported as a true neoplasm originating from Schwann cells in 1910 [1] . The ma- jority of schwannomas are detected as a solitary tumor from the peripheral nerves of the face, neck, trunk, extremities, or retroperi- toneal region. Based on a previous study [2] , merely 3% of schwan- nomas are retroperitoneal, accounting for approximately 4% of all retroperitoneal tumors. Furthermore, pancreatic schwannomas that stem from either parasympathetic or sympathetic fibers of the pancreas are especially rare. Schwannomas are generally encapsu- lated, and over 90% are benign [3] . Considering its benign biolog- ical behavior, it is essential to accurately diagnose schwannomas in order to apply reasonable surgical methods and postoperative surveillance. Herein, we report four cases of pancreatic schwan- noma in our center to update the data on the clinicopathological traits about this type of tumor.展开更多
High-performance nonlinear optical(NLO)crystals are crucial devices to convert wavelength of solid-state lasers.Chalcogenides play an indispensable role in the research of infrared NLO materials.In this work,ternary c...High-performance nonlinear optical(NLO)crystals are crucial devices to convert wavelength of solid-state lasers.Chalcogenides play an indispensable role in the research of infrared NLO materials.In this work,ternary chalcogenide ZnGa_(2)S_(4) with defect diamond-like structure was screened out and synthesized by chemical vapor transport method.展开更多
Background:Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis.Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD.In r...Background:Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis.Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD.In recent years,numerous case-control studies have investigated the relationship ofAPOE polymorphism with CHD risk.However,the results are confusing.Methods:To clarify this point,we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP,College Station,TX,USA).Results:Overall,the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs.ε3 allele:OR =0.82,95% CI:0.75-0.90,P 〈 0.001;ε2 carriers vs.ε3 carriers:OR =0.81,95% CI:0.73-0.89,P 〈 0.001),compared with those carrying ε3 allele,especially in Caucasian population.However,those with ε4 allele had a significant increased risk for CHD (ε4 allele vs.ε3 allele:OR =1.34,95% CI:1.15-1.57,P 〈 0.001),especially in Mongoloid population.Potential publication bias was observed in the genetic model of ε4 versus ε3,but the results might not be affected deeply by the publication bias.When we accounted for publication bias using the trim and fill method,the results were not materially alerted,suggesting the stability of our results.Conclusions:Taken together,our meta-analysis supported a genetic association between APOE gene and CHD.ε4 increased the risk of CHD,whereas ε2 decreased the risk of CHD展开更多
基金supported by the Natural Science Foundation of Hebei Province of China(Grant No.A2020202007)the National Natural Science Foundation of China(Grant No.11605038)。
文摘Microtubule catalyzes the mechanochemical cycle of kinesin,a kind of molecular motor,through its crucial roles in kinesin's gating,ATPase and force-generation process.These functions of microtubule are realized through the kinesin-microtubule interaction.The binding site of kinesin on the microtubule surface is fixed.For most of the kinesin-family members,the binding site on microtubule is in the groove betweenα-tubulin andβ-tubulin in a protofilament.The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear.Using the molecular dynamics simulation method,we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin's different nucleotide-binding states are listed.The differences of the amino-acid sequences betweenα-andβ-tubulins make kinesin-1 binding to theα–βgroove much more favorable than to theβ–αgroove.From these results,a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed.Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule,the mechanism may also be shared by other family members of kinesin.
文摘The most recognized and employed model of the solvation equilibration in the ionic solutions was proposed by Eigen and Tamm, in which there are four major states for an ion pair in the solution: the completely solvated state, 2SIP (double solvent separate ion pair), SIP (single solvent separate ion pair), and CIP (contact ion pair). Eigen and Tamm suggested that the transition from SIP to CIP is always the slowest step during the whole pairing process, due to a high free energy barrier between these two states. We carried out a series of potential of mean force calculations to study the pairing free energy profiles of two sets of model mono- atomic 1:1 ion pairs 2.0:x and x:2.0. For 2.0:x pairs the free energy barrier between the SIP and CIP states is largely reduced due to the salvation shell water structure. For these pairs the SIP to CIP transition is thus not the slowest step in the ion pair formation course. This is a deviation from the Eigen-Tamm model.
基金supported by a grant from the Youth Start-up Fund Project of Changhai Hospital(CH201823).
文摘To the Editor:Schwannoma is an infrequent tumor originating from Schwann cells of the peripheral nerve sheath and was first reported as a true neoplasm originating from Schwann cells in 1910 [1] . The ma- jority of schwannomas are detected as a solitary tumor from the peripheral nerves of the face, neck, trunk, extremities, or retroperi- toneal region. Based on a previous study [2] , merely 3% of schwan- nomas are retroperitoneal, accounting for approximately 4% of all retroperitoneal tumors. Furthermore, pancreatic schwannomas that stem from either parasympathetic or sympathetic fibers of the pancreas are especially rare. Schwannomas are generally encapsu- lated, and over 90% are benign [3] . Considering its benign biolog- ical behavior, it is essential to accurately diagnose schwannomas in order to apply reasonable surgical methods and postoperative surveillance. Herein, we report four cases of pancreatic schwan- noma in our center to update the data on the clinicopathological traits about this type of tumor.
基金financially supported by the National Natural Science Foundation of China(Nos.52072109,21975062 and 22101069)the Science and Technology Project of Hebei Education Department(Nos.BJK2023029 and QN2023234)。
文摘High-performance nonlinear optical(NLO)crystals are crucial devices to convert wavelength of solid-state lasers.Chalcogenides play an indispensable role in the research of infrared NLO materials.In this work,ternary chalcogenide ZnGa_(2)S_(4) with defect diamond-like structure was screened out and synthesized by chemical vapor transport method.
文摘Background:Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis.Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD.In recent years,numerous case-control studies have investigated the relationship ofAPOE polymorphism with CHD risk.However,the results are confusing.Methods:To clarify this point,we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP,College Station,TX,USA).Results:Overall,the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs.ε3 allele:OR =0.82,95% CI:0.75-0.90,P 〈 0.001;ε2 carriers vs.ε3 carriers:OR =0.81,95% CI:0.73-0.89,P 〈 0.001),compared with those carrying ε3 allele,especially in Caucasian population.However,those with ε4 allele had a significant increased risk for CHD (ε4 allele vs.ε3 allele:OR =1.34,95% CI:1.15-1.57,P 〈 0.001),especially in Mongoloid population.Potential publication bias was observed in the genetic model of ε4 versus ε3,but the results might not be affected deeply by the publication bias.When we accounted for publication bias using the trim and fill method,the results were not materially alerted,suggesting the stability of our results.Conclusions:Taken together,our meta-analysis supported a genetic association between APOE gene and CHD.ε4 increased the risk of CHD,whereas ε2 decreased the risk of CHD