Excitotoxicity and neuronal cell death:Glutamate is the main excitatory neurotransmitter of the central nervous system and functionally involved in most brain activities,including brain development,synaptic plasticity...Excitotoxicity and neuronal cell death:Glutamate is the main excitatory neurotransmitter of the central nervous system and functionally involved in most brain activities,including brain development,synaptic plasticity,learning and memory.Exc让atory synaptic transmission is primarily mediated by ligana-gated ion channels,including a-amino-3-hydroxy-5-methylisoxazoIe-4-propionic acid(AMPA),N-methyl-D-aspartate(NMDA)and kainate receptors.Activation of glutamate receptors,particularly NMDA receptors,usually leads to calcium influx,whicn can act as a second messenger for several processes to mediate synaptic activity and brain function.Nevertheless,excessive release of glutamate neurotransmitter may produce intracellular calcium overload,leading to a cascade of events mediating cytoskeleton damage accompanied w让h reactive oxygen species(ROS)generation,mitochondrial dysfunction and ultimately neuronal cell death.These toxic effects of glutamate are known as excitotoxicity.Neuronal excitotoxicity has been linked to several acute and chronic brain diseases,such as stroke/ischemia,epilepsy and a range of neurodegenerative disorders,including Alzheimer's disease(AD),Huntingtons disease,amyotrophic lateral sclerosis(ALS)and Parkinsons disease(PD),contributing to the neuronal lost in different brain regions.Unfortunately,treating nervous system disorders with general glutamate receptor blockers has been associated with undesirable side effects,becoming increasingly necessary to unravel downstream effectors in the excitotoxicity-dependent cell death pathway in order to develop novel therapeutic strategies.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
The Hedgehog(Hh)signaling is one of the essential signaling pathways during embryogenesis and in adults.Hh signal transduction relies on primary cilium,a specialized cell surface organelle viewed as the hub of cell si...The Hedgehog(Hh)signaling is one of the essential signaling pathways during embryogenesis and in adults.Hh signal transduction relies on primary cilium,a specialized cell surface organelle viewed as the hub of cell signaling.Protein kinase A(PKA)has been recognized as a potent negative regulator of the Hh pathway,raising the question of how such a ubiquitous kinase specifically regulates one signaling pathway.We reviewed recent genetic,molecular and biochemical studies that have advanced our mechanistic understanding of PKA’s role in Hh signaling in vertebrates,focusing on the compartmentalized PKA at the centrosome and in the primary cilium.We outlined the recently developed genetic and optical tools that can be harvested to study PKA activities during the course of Hh signal transduction.展开更多
Background:Endovascular coiling for wide-neck aneurysms with a branch arising from the aneurysmal sac is challenging and sometimes considered impossible.This study aims to present our experience in treating wide-neck ...Background:Endovascular coiling for wide-neck aneurysms with a branch arising from the aneurysmal sac is challenging and sometimes considered impossible.This study aims to present our experience in treating wide-neck internal carotid artery(ICA)aneurysms with a posterior communicating artery(PComA)arising from the sac using a strategy of stenting the ICA and intentional compartmentalization to preserve the flow in the PComA.Methods:Eight consecutive cases of wide-neck ICA aneurysms with a fetal-type PComA arising from the aneurysmal sac were embolized from January 2015 to June 2018 at the First Affiliated Hospital,College of Medicine,Zhejiang University.Demographics,angiographic technique,procedural complications and clinical outcomes were reviewed.Results:There were 2 men and 6 women ranging from 56 to 81 years of age.Of the 8 cases,3 were ruptured and 5 were unruptured aneurysms.Stents were successfully deployed in all 8 cases.Near-complete occlusion was achieved in 3 cases(37.5%),neck remnant in 4(50%)and sac remnant in one(12.5%)of the cases.One case suffered transient ischemic attack after procedure completion.The clinical outcome was favorable in all 8 cases(modified Rankin scale 0-1).No rebleeding occurred during clinical follow-up.Conclusion:Stent-assisted compartmentalized embolization is feasible and safe in the treatment of wide-neck ICA aneurysm with a PComA arising from the sac.展开更多
Cellular metabolism in multiple organelles utilizes compartmentalized multienzyme efficient catalysis to realize substance metabolism, energy conversion and immune defenses. The convenient and biomimetic design of art...Cellular metabolism in multiple organelles utilizes compartmentalized multienzyme efficient catalysis to realize substance metabolism, energy conversion and immune defenses. The convenient and biomimetic design of artificial multienzymes has become an emerging research topic. Herein, we employ a facile enzyme-initiated radical polymerization to self-anchor multienzyme in cell-like hydrogels with mesoscale compartments. The dynamic assembly of glucose oxidase/cytochrome c(GOx/Cyt c) with methacrylate-modified hyaluronic acid can form nanoaggregates, where only the bound enzyme pairs with the adjacent position can catalyze the polymerization to compartmentalize multienzymes within hydrogel. Consequently, the cascade enzymes within hydrogel display 33.9 times higher activity compared to free enzymes, as well as excellent thermostability and multiple recyclability. The mechanism study indicates that the compartmental effect of the hydrogel and the anchoring effect of Cyt c synergistically enhance GOx/Cyt c activity. According to the density functional theory(DFT) calculation, Cyt c activity increment originates from its ligand changes of Fe(Ⅲ) porphyrin, which has a smaller energy barrier of the catalytic reaction.This study provides a promising strategy for autonomous colocalization of multienzyme in biocompatible hydrogels which can be potentially applied in cascade enzyme induced catalysis applications.展开更多
The muzzle blast overpressure induces disturbances in the flow field inside the crew compartment(FFICC)of a truck-mounted howitzer during the artillery firing.This overpressure is the primary factor preventing personn...The muzzle blast overpressure induces disturbances in the flow field inside the crew compartment(FFICC)of a truck-mounted howitzer during the artillery firing.This overpressure is the primary factor preventing personnel from firing artillery within the cab.To investigate the overpressure characteristics of the FFICC,a foreign trade equipment model was used as the research object,and a numerical model was established to analyze the propagation of muzzle blast from the muzzle to the interior of the crew compartment under extreme firing condition.For comparative verification,the muzzle blast experiment included overpressure data from both the flow field outside the crew compartment(FFOCC)and the FFICC,as well as the acceleration data of the crew compartment structure(Str-CC).The research findings demonstrate that the overpressure-time curves of the FFICC exhibit multi-peak characteristics,while the pressure wave shows no significant discontinuity.The enclosed nature of the cab hinders the dissipation of pressure wave energy within the FFICC,leading to sustained high-amplitude overpressure.The frameskin structure helps attenuate the impact of muzzle blast on the FFICC.Conversely,local high overpressure caused by the convex or concave features of the cab's exterior significantly amplifies the overpressure amplitude within the FFICC.展开更多
Acute compartment syndrome(ACoS)involves a complex pathological process in which rising pressures within an enclosed muscle space ultimately result in anoxia and cell death.The most common etiologies include long bone...Acute compartment syndrome(ACoS)involves a complex pathological process in which rising pressures within an enclosed muscle space ultimately result in anoxia and cell death.The most common etiologies include long bone fractures,crush injuries,and burns.[1,2]While rare,ACoS can also occur in atraumatic settings following periods of prolonged limb compression,such as intoxication.[3]Atraumatic ACoS is easily overlooked,resulting in diagnostic delay and poor patient outcomes.Prompt recognition and surgical management is essential to prevent critical sequelae.展开更多
Salinity is a major hazard to crop plant growth and significantly reduces grain yield.When subjected to high salinity,plants maintain ion homeostasis through Na^(+)compartmentalization and exclusion,enabling them to m...Salinity is a major hazard to crop plant growth and significantly reduces grain yield.When subjected to high salinity,plants maintain ion homeostasis through Na^(+)compartmentalization and exclusion,enabling them to mitigate salt stress.In this study,we revealed the role of rice(Oryza sativa)MYB9(OsMYB9)in regulating salt stress tolerance.OsMYB9 was expressed in the vascular bundles of roots and leaves,particularly in the parenchyma cells.The null mutation of OsMYB9 resulted in increased sodium ion accumulation in shoot tissues under salt stress,leading to salt-sensitive phenotypes.Real-Time Quantitative Reverse Transcription PCR analysis indicated the OsMYB9 mutation led to decreased expression of several genes associated with vacuolar Na^(+)/H^(+)antiporters(OsNHX1,OsNHX2,OsNHX3,OsNHX4,and OsNHX5),high-K^(+)affinity transporters(OsHKT1;5),and SALT OVERLY SENSITIVE proteins(OsSOS2 and OsSOS3).Among these,OsMYB9 upregulated the expression of OsNHX1 and OsNHX2 by directly binding to their promoter regions.Furthermore,GIGANTEA(OsGI)interacted with OsMYB9,suggesting that OsGI negatively acts upstream of OsMYB9 and regulates the expression levels of OsNHX1.Collectively,OsMYB9 alleviates the excess accumulation of Na^(+)ions in the xylem by retrieving Na^(+)ions from xylem parenchyma cells and compartmentalizing them into vacuoles.These regulatory mechanisms mediated by OsMYB9 are crucial for minimizing Na^(+)toxicity in photosynthetic tissues and enhancing salt stress tolerance in rice.展开更多
Crush syndrome demands an integrated multidisciplinary approach that spans acute surgical decisions and long-term functional recovery.In response to Khan et al’s recent systematic review,we propose complementary pers...Crush syndrome demands an integrated multidisciplinary approach that spans acute surgical decisions and long-term functional recovery.In response to Khan et al’s recent systematic review,we propose complementary perspectives that address two underrepresented dimensions:Vascular surgical decision-making and psychiatric rehabilitation.We emphasize the use of intraoperative technologies such as indocyanine green fluorescence angiography and compartment pressure monitoring to guide limb salvage strategies and reperfusion management.Additionally,we advocate for the systematic integration of mental health screening and trauma-informed psychiatric care to address the high prevalence of psychological distress in survivors.Embedding these domains into standardized protocols could enhance both short-and long-term outcomes,particularly in highimpact trauma and disaster settings.展开更多
BACKGROUND Hypoganglionosis is a rare gastrointestinal acquired motility disorder that res-embles Hirschsprung’s disease and can manifest in the adult life.Abdominal compartment syndrome,a condition characterized by ...BACKGROUND Hypoganglionosis is a rare gastrointestinal acquired motility disorder that res-embles Hirschsprung’s disease and can manifest in the adult life.Abdominal compartment syndrome,a condition characterized by an increase in intra-abdo-minal pressure with physiological disturbance can be caused by severe massive fecal impaction.CASE SUMMARY A 33-year-old female presented to the emergency room with massive abdominal distension that rapidly progressed to abdominal compartment syndrome.The pa-tient was diagnosed with hypoganglionosis.Life-saving emergent proctoco-lectomy was performed to save the patient.CONCLUSION Abdominal compartment syndrome can develop secondary to excessive colonic distension.This extreme but rare situation must be addressed immediately.Hypo-ganglionosis is a potential cause of severe constipation that may present in adu-lthood.展开更多
The residence-time distribution （RTD） and the compartment model were applied to characterizing the flow regions in red mud separation thickener’s feedwells. Combined with the experimental work, validated mathematic...The residence-time distribution （RTD） and the compartment model were applied to characterizing the flow regions in red mud separation thickener’s feedwells. Combined with the experimental work, validated mathematical model as well as three-dimensional computational fluid dynamics （CFD） model was established to analyze the flow regions of feedwells on an industrial scale. The concept of RTD, although a well-known method for the characterization of mixing behavior in conventional mixers and reactors, is still a novel measure for the characterization of mixing in feedwells. Numerical simulation results show that the inlet feed rate and the aspect ratio of feedwells are the most critical parameters which affect the RTD of feedwell. Further simulation experiments were then carried out. Under the optimal operation conditions, the volume fraction of dead zone can reduce by10.8% and an increasement of mixing flow volume fraction by 6.5% is also observed. There is an optimum feed inlet rate depending on the feedwell design. The CFD model in conjunction with the RTD analysis then can be used as an effective tool in the design, evaluation and optimization of thickener feedwell in the red mud separation.展开更多
The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was ...The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.展开更多
Glycine soja Sieb. et Zucc. plants living in saline soil in three provinces of China were treated with different salinity concentrations under different laboratory culture conditions (including solution, sand and fiel...Glycine soja Sieb. et Zucc. plants living in saline soil in three provinces of China were treated with different salinity concentrations under different laboratory culture conditions (including solution, sand and field cultivation). The attachment shape and distribution on the surface of stalk and leaf of G. soja plants were observed with scanning electron microscopy (SEM), and the ultrastructure of glandular hair with transmission electron microscopy (TEM). Na+ and Cl- contents in the secretion of the leaf surface and inside the leaf of G. soja subjected to different treatments were measured. The Na+ relative contents in glandular cells, epidermal cells and mesophyllous cells of leaves under different salinities were determined by X-ray microanalysis. Results show that only glandular and epidermal hair exist on the surface attachments of leaves and stalks of G. soja plants. These glandular hair were similar in shape to some salt glands of Gramineae halophytes, and they attached to the vein on the leaf surface. The cell structure of the glandular hair showed the characteristics of common salt glands, such as big vacuoles, dense cytoplasm, a great deal of mitochondria, chloroplast, plasmodesmata and thicker cell walls, etc. The results of Na+ and Cl- contents in the leaf secretion and inside the leaf showed that the glandular hair executed the function of salt-secretion, and when treated with the salt gland inhibitor the salt-secretion process was inhibited. As a result, Na+ and Cl- were mainly accumulated inside G. soja leaves. The results of Na+ X-ray microanalysis under different salinities proved that the three cells of the glandular hair, especially the top cell, possessed strong competence for Na+ accumulation. Above all, the glandular hair were the salt gland, and no other kind of salt glands were found on G. soja plants. The secreting mechanism of the salt gland was also discussed.展开更多
The gene encoded for tryptophan decarboxylase (TDC), which is the key enzyme in terpenoil indole alkaloids pathway, was targeted to different subcellular compartments and stably expressed in transgenic tobacco (Nicoti...The gene encoded for tryptophan decarboxylase (TDC), which is the key enzyme in terpenoil indole alkaloids pathway, was targeted to different subcellular compartments and stably expressed in transgenic tobacco (Nicotiana tabacum L.) plants at the levels detected by Western blot and tryptamine accumulation analysis. It was shown that the TDC was located in subcellular compartments, the chloroplasts and cytosol. The recombinant TDC targeted to chloroplasts and cytosol in tobacco plants was effectively expressed as soluble protein by Western blot analysis and enzymatic assay. The level of tryptamine accumulation in chloroplast was higher than that in cytosol and very low in vacuole and endoplasmic reticulum (ER) to be hardly detected by Western blot analysis. It was indicated that the highest amount of tryptamine was in chloroplasts, lower in endoplasmic reticula and the lowest in vacuoles as compared to those in wild type plants. The TDC targeted to different subcellular compartments of tobacco plants and its expression level were studied by different nucleotide sequences coding signal peptides at 5'-end of tdc gene in order to know the effects of the TDC in compartmentation on its functionality.展开更多
The two compartment model with variable extracellular volume is presented and solved by using both perturbation and analytical method. The computation for both creatinine and urea show that the perturbation solution ...The two compartment model with variable extracellular volume is presented and solved by using both perturbation and analytical method. The computation for both creatinine and urea show that the perturbation solution is not only simple but also accurate enough and is a good substitute for the more exact analytical solution.展开更多
Strictosidine synthase (STR) is a key enzyme involved in the biosynthesis of terpenoid indole alkaloids (TIA) by condensing tryptamine and secologanin into strictosidine. The transgenic tobacco plants targeting STR to...Strictosidine synthase (STR) is a key enzyme involved in the biosynthesis of terpenoid indole alkaloids (TIA) by condensing tryptamine and secologanin into strictosidine. The transgenic tobacco plants targeting STR to subcellular compartments were established to express STR in chloroplast, vacuole and endoplasmic reticulum (ER) by the tobacco stable transformation. It was shown that STR was effectively expressed in the above subcellular compartments by Western blot analysis and STR enzymatic assay. In vitro , STR enzymatic assay was measured indirectly by fluorimetrically detecting depletion of tryptamine feeding on secologanin in the reaction mixture. The tryptamine were completely depleted by STR in the crude extract of leaves of transgenic tobacco plants targeting and expressing STR in the chloroplast, vacuole and ER, which ascertained the STR functionally targeted to the three subcellular compartments. To confirm STR correct targeting and expressing in chloroplast, the chloroplasts were isolated and the fractions of purified chloroplasts were analyzed by Western blot. The hypothesis of STR correct targeting to the chloroplast was tested. The results have implications on our understanding of the complex intracellular trafficking in metabolic intermediates of TIA biosynthesis.展开更多
The clustering behavior of a mono-disperse granular gas is experimentally studied in an asymmetric two-compartment setup. Unlike the random clustering in either compartment in the case of symmetric configuration when ...The clustering behavior of a mono-disperse granular gas is experimentally studied in an asymmetric two-compartment setup. Unlike the random clustering in either compartment in the case of symmetric configuration when lowering the shaking strength to below a critical value, the directed clustering is observed, which corresponds to an imperfect pitchfork bifurcation. Numerical solutions of the flux equation using a modified simple flux function show qualitative agreements with the experimental results. The potential application of this asymmetric structure is discussed.展开更多
In recent years,due to excessive emission of industrial waste,wastewater irrigation,and unreasonable utilization of fertilizers,pesticides and plastic sheeting,heavy metal pollution is increasing rapidly,resulting in ...In recent years,due to excessive emission of industrial waste,wastewater irrigation,and unreasonable utilization of fertilizers,pesticides and plastic sheeting,heavy metal pollution is increasing rapidly,resulting in many environmental problems.Silicon(Si),as the second most abundant element in the soil,can not only stimulate plant growth,but alleviate various biotic and abiotic stresses,including heavy metal stress.Here,we reviewed recent advances in the mechanisms for Si-mediated heavy metal tolerance in plants.These mechanisms included reducing active heavy metal ions in growth media,reducing heavy metal transport to the shoot,stimulating enzymatic and non-enzymatic antioxidants,chelation,compartmentation,regulation of the expression of metal transport genes,and structural changes in plants.Further research orientation is also discussed.展开更多
AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on phys...AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on physiological functions, and the association of the presence of IAH/ACS and outcome. METHODS: Patients (n = 74) with AP recruited in this study were divided into two groups according to intra-abdominal pressure (IAP) determined by indirect measurement using the transvesical route via Foley bladder catheter during the first week after admission. Patients (n = 44) with IAP ≥ 12 mmHg were assigned in IAH group, and the remaining patients (n = 30) with IAP < 12 mmHg in normal IAP group. For analysis of the influence of IAH/ACS on organ function and outcome, the physiological parameters and the occurrence of organ dysfunction during intensive care unit (ICU) stay were recorded, as were the incidences of pancreatic infection and in-hospital mortality. RESULTS: IAH within the first week after admission was found in 44 patients (59.46%). Although the APACHE Ⅱ scores on admission and the Ranson scores within 48 h after hospitalization were elevated in IAH patients in early stage, they did not show the statistically significant differences from patients with normal IAP within a week after admission (16.18 ± 3.90 vs 15.70 ± 4.25, P = 0.616; 3.70 ± 0.93 vs 3.47 ± 0.94, P = 0.285, respectively). ACS in early AP was recorded in 20 patients (27.03%). During any 24-h period ofthe first week after admission, the recorded mean IAP correlated significantly with the Marshall score calculated at the same time interval in IAH group (r = 0.635, P < 0.001). Although ACS patients had obvious amelioration in physiological variables within 24 h after decompression, the incidences of pancreatitic infection, septic shock, multiple organ dysfunction syndrome (MODS) and death in the patients with ACS were significantly higher than that in other patients without ACS (pancreatitic infection: 60.0% vs 7.4%, P < 0.001; septic shock: 70.0% vs 11.1%, P < 0.001; MODS: 90.0% vs 31.5%, P < 0.001; mortality: 75.0% vs 3.7%, P < 0.001). CONCLUSION: IAH/ACS is a frequent finding in patients admitted to the ICU because of AP. Patients with IAP at approximately 10-12 mmHg and early signs of changes in physiologic variables should be seriously considered for urgent decompression to improve survival.展开更多
基金funded by grants from Geroscience Center for Brain Health and Metabolism(FONDAP-15150012,to FC)Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT,1150766,to FC)Comisión Nacional de Investigación Científica y Tecnológica,Fondecyt de Postdoctorado Project(3180313,to MA)
文摘Excitotoxicity and neuronal cell death:Glutamate is the main excitatory neurotransmitter of the central nervous system and functionally involved in most brain activities,including brain development,synaptic plasticity,learning and memory.Exc让atory synaptic transmission is primarily mediated by ligana-gated ion channels,including a-amino-3-hydroxy-5-methylisoxazoIe-4-propionic acid(AMPA),N-methyl-D-aspartate(NMDA)and kainate receptors.Activation of glutamate receptors,particularly NMDA receptors,usually leads to calcium influx,whicn can act as a second messenger for several processes to mediate synaptic activity and brain function.Nevertheless,excessive release of glutamate neurotransmitter may produce intracellular calcium overload,leading to a cascade of events mediating cytoskeleton damage accompanied w让h reactive oxygen species(ROS)generation,mitochondrial dysfunction and ultimately neuronal cell death.These toxic effects of glutamate are known as excitotoxicity.Neuronal excitotoxicity has been linked to several acute and chronic brain diseases,such as stroke/ischemia,epilepsy and a range of neurodegenerative disorders,including Alzheimer's disease(AD),Huntingtons disease,amyotrophic lateral sclerosis(ALS)and Parkinsons disease(PD),contributing to the neuronal lost in different brain regions.Unfortunately,treating nervous system disorders with general glutamate receptor blockers has been associated with undesirable side effects,becoming increasingly necessary to unravel downstream effectors in the excitotoxicity-dependent cell death pathway in order to develop novel therapeutic strategies.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
基金supported by the National Institutes of Health(CA235749)。
文摘The Hedgehog(Hh)signaling is one of the essential signaling pathways during embryogenesis and in adults.Hh signal transduction relies on primary cilium,a specialized cell surface organelle viewed as the hub of cell signaling.Protein kinase A(PKA)has been recognized as a potent negative regulator of the Hh pathway,raising the question of how such a ubiquitous kinase specifically regulates one signaling pathway.We reviewed recent genetic,molecular and biochemical studies that have advanced our mechanistic understanding of PKA’s role in Hh signaling in vertebrates,focusing on the compartmentalized PKA at the centrosome and in the primary cilium.We outlined the recently developed genetic and optical tools that can be harvested to study PKA activities during the course of Hh signal transduction.
基金supported by the grant from the Zhejiang Province Scientific Fund(LY12F02035).
文摘Background:Endovascular coiling for wide-neck aneurysms with a branch arising from the aneurysmal sac is challenging and sometimes considered impossible.This study aims to present our experience in treating wide-neck internal carotid artery(ICA)aneurysms with a posterior communicating artery(PComA)arising from the sac using a strategy of stenting the ICA and intentional compartmentalization to preserve the flow in the PComA.Methods:Eight consecutive cases of wide-neck ICA aneurysms with a fetal-type PComA arising from the aneurysmal sac were embolized from January 2015 to June 2018 at the First Affiliated Hospital,College of Medicine,Zhejiang University.Demographics,angiographic technique,procedural complications and clinical outcomes were reviewed.Results:There were 2 men and 6 women ranging from 56 to 81 years of age.Of the 8 cases,3 were ruptured and 5 were unruptured aneurysms.Stents were successfully deployed in all 8 cases.Near-complete occlusion was achieved in 3 cases(37.5%),neck remnant in 4(50%)and sac remnant in one(12.5%)of the cases.One case suffered transient ischemic attack after procedure completion.The clinical outcome was favorable in all 8 cases(modified Rankin scale 0-1).No rebleeding occurred during clinical follow-up.Conclusion:Stent-assisted compartmentalized embolization is feasible and safe in the treatment of wide-neck ICA aneurysm with a PComA arising from the sac.
基金supported by the National Science Fund for Distinguished Young Scholars (52125305)the National Natural Science Foundation of China (51873156,52173289)+1 种基金the Shanghai Science and Technology Committee (20dz1101200)the key project of the first demonstration project (Artificial Intelligence) of interdisciplinary joint research of Tongji University (ZD-11-202151)
文摘Cellular metabolism in multiple organelles utilizes compartmentalized multienzyme efficient catalysis to realize substance metabolism, energy conversion and immune defenses. The convenient and biomimetic design of artificial multienzymes has become an emerging research topic. Herein, we employ a facile enzyme-initiated radical polymerization to self-anchor multienzyme in cell-like hydrogels with mesoscale compartments. The dynamic assembly of glucose oxidase/cytochrome c(GOx/Cyt c) with methacrylate-modified hyaluronic acid can form nanoaggregates, where only the bound enzyme pairs with the adjacent position can catalyze the polymerization to compartmentalize multienzymes within hydrogel. Consequently, the cascade enzymes within hydrogel display 33.9 times higher activity compared to free enzymes, as well as excellent thermostability and multiple recyclability. The mechanism study indicates that the compartmental effect of the hydrogel and the anchoring effect of Cyt c synergistically enhance GOx/Cyt c activity. According to the density functional theory(DFT) calculation, Cyt c activity increment originates from its ligand changes of Fe(Ⅲ) porphyrin, which has a smaller energy barrier of the catalytic reaction.This study provides a promising strategy for autonomous colocalization of multienzyme in biocompatible hydrogels which can be potentially applied in cascade enzyme induced catalysis applications.
基金supported by the National Natural Science Foundation of China(Grant No.U2341269)。
文摘The muzzle blast overpressure induces disturbances in the flow field inside the crew compartment(FFICC)of a truck-mounted howitzer during the artillery firing.This overpressure is the primary factor preventing personnel from firing artillery within the cab.To investigate the overpressure characteristics of the FFICC,a foreign trade equipment model was used as the research object,and a numerical model was established to analyze the propagation of muzzle blast from the muzzle to the interior of the crew compartment under extreme firing condition.For comparative verification,the muzzle blast experiment included overpressure data from both the flow field outside the crew compartment(FFOCC)and the FFICC,as well as the acceleration data of the crew compartment structure(Str-CC).The research findings demonstrate that the overpressure-time curves of the FFICC exhibit multi-peak characteristics,while the pressure wave shows no significant discontinuity.The enclosed nature of the cab hinders the dissipation of pressure wave energy within the FFICC,leading to sustained high-amplitude overpressure.The frameskin structure helps attenuate the impact of muzzle blast on the FFICC.Conversely,local high overpressure caused by the convex or concave features of the cab's exterior significantly amplifies the overpressure amplitude within the FFICC.
文摘Acute compartment syndrome(ACoS)involves a complex pathological process in which rising pressures within an enclosed muscle space ultimately result in anoxia and cell death.The most common etiologies include long bone fractures,crush injuries,and burns.[1,2]While rare,ACoS can also occur in atraumatic settings following periods of prolonged limb compression,such as intoxication.[3]Atraumatic ACoS is easily overlooked,resulting in diagnostic delay and poor patient outcomes.Prompt recognition and surgical management is essential to prevent critical sequelae.
基金support of the Cooperative Research Program for Agriculture Science and Technology Development(RS-2022-RD010386 to Nam-Chon Paek)Rural Development Administration and the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00343929 and RS-2024-00452677 to Kiyoon Kang)Basic Science Research Program through the National Research Foundation of Korea(NRF)grant(RS-2023-00247376 to Sung-Hwan Cho and 2021R1I1A1A01044569 to Hyeryung Yoon),Republic of Korea.
文摘Salinity is a major hazard to crop plant growth and significantly reduces grain yield.When subjected to high salinity,plants maintain ion homeostasis through Na^(+)compartmentalization and exclusion,enabling them to mitigate salt stress.In this study,we revealed the role of rice(Oryza sativa)MYB9(OsMYB9)in regulating salt stress tolerance.OsMYB9 was expressed in the vascular bundles of roots and leaves,particularly in the parenchyma cells.The null mutation of OsMYB9 resulted in increased sodium ion accumulation in shoot tissues under salt stress,leading to salt-sensitive phenotypes.Real-Time Quantitative Reverse Transcription PCR analysis indicated the OsMYB9 mutation led to decreased expression of several genes associated with vacuolar Na^(+)/H^(+)antiporters(OsNHX1,OsNHX2,OsNHX3,OsNHX4,and OsNHX5),high-K^(+)affinity transporters(OsHKT1;5),and SALT OVERLY SENSITIVE proteins(OsSOS2 and OsSOS3).Among these,OsMYB9 upregulated the expression of OsNHX1 and OsNHX2 by directly binding to their promoter regions.Furthermore,GIGANTEA(OsGI)interacted with OsMYB9,suggesting that OsGI negatively acts upstream of OsMYB9 and regulates the expression levels of OsNHX1.Collectively,OsMYB9 alleviates the excess accumulation of Na^(+)ions in the xylem by retrieving Na^(+)ions from xylem parenchyma cells and compartmentalizing them into vacuoles.These regulatory mechanisms mediated by OsMYB9 are crucial for minimizing Na^(+)toxicity in photosynthetic tissues and enhancing salt stress tolerance in rice.
文摘Crush syndrome demands an integrated multidisciplinary approach that spans acute surgical decisions and long-term functional recovery.In response to Khan et al’s recent systematic review,we propose complementary perspectives that address two underrepresented dimensions:Vascular surgical decision-making and psychiatric rehabilitation.We emphasize the use of intraoperative technologies such as indocyanine green fluorescence angiography and compartment pressure monitoring to guide limb salvage strategies and reperfusion management.Additionally,we advocate for the systematic integration of mental health screening and trauma-informed psychiatric care to address the high prevalence of psychological distress in survivors.Embedding these domains into standardized protocols could enhance both short-and long-term outcomes,particularly in highimpact trauma and disaster settings.
文摘BACKGROUND Hypoganglionosis is a rare gastrointestinal acquired motility disorder that res-embles Hirschsprung’s disease and can manifest in the adult life.Abdominal compartment syndrome,a condition characterized by an increase in intra-abdo-minal pressure with physiological disturbance can be caused by severe massive fecal impaction.CASE SUMMARY A 33-year-old female presented to the emergency room with massive abdominal distension that rapidly progressed to abdominal compartment syndrome.The pa-tient was diagnosed with hypoganglionosis.Life-saving emergent proctoco-lectomy was performed to save the patient.CONCLUSION Abdominal compartment syndrome can develop secondary to excessive colonic distension.This extreme but rare situation must be addressed immediately.Hypo-ganglionosis is a potential cause of severe constipation that may present in adu-lthood.
基金Project (50876116) supported by the National Natural Science Foundation of China
文摘The residence-time distribution （RTD） and the compartment model were applied to characterizing the flow regions in red mud separation thickener’s feedwells. Combined with the experimental work, validated mathematical model as well as three-dimensional computational fluid dynamics （CFD） model was established to analyze the flow regions of feedwells on an industrial scale. The concept of RTD, although a well-known method for the characterization of mixing behavior in conventional mixers and reactors, is still a novel measure for the characterization of mixing in feedwells. Numerical simulation results show that the inlet feed rate and the aspect ratio of feedwells are the most critical parameters which affect the RTD of feedwell. Further simulation experiments were then carried out. Under the optimal operation conditions, the volume fraction of dead zone can reduce by10.8% and an increasement of mixing flow volume fraction by 6.5% is also observed. There is an optimum feed inlet rate depending on the feedwell design. The CFD model in conjunction with the RTD analysis then can be used as an effective tool in the design, evaluation and optimization of thickener feedwell in the red mud separation.
文摘The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.
文摘Glycine soja Sieb. et Zucc. plants living in saline soil in three provinces of China were treated with different salinity concentrations under different laboratory culture conditions (including solution, sand and field cultivation). The attachment shape and distribution on the surface of stalk and leaf of G. soja plants were observed with scanning electron microscopy (SEM), and the ultrastructure of glandular hair with transmission electron microscopy (TEM). Na+ and Cl- contents in the secretion of the leaf surface and inside the leaf of G. soja subjected to different treatments were measured. The Na+ relative contents in glandular cells, epidermal cells and mesophyllous cells of leaves under different salinities were determined by X-ray microanalysis. Results show that only glandular and epidermal hair exist on the surface attachments of leaves and stalks of G. soja plants. These glandular hair were similar in shape to some salt glands of Gramineae halophytes, and they attached to the vein on the leaf surface. The cell structure of the glandular hair showed the characteristics of common salt glands, such as big vacuoles, dense cytoplasm, a great deal of mitochondria, chloroplast, plasmodesmata and thicker cell walls, etc. The results of Na+ and Cl- contents in the leaf secretion and inside the leaf showed that the glandular hair executed the function of salt-secretion, and when treated with the salt gland inhibitor the salt-secretion process was inhibited. As a result, Na+ and Cl- were mainly accumulated inside G. soja leaves. The results of Na+ X-ray microanalysis under different salinities proved that the three cells of the glandular hair, especially the top cell, possessed strong competence for Na+ accumulation. Above all, the glandular hair were the salt gland, and no other kind of salt glands were found on G. soja plants. The secreting mechanism of the salt gland was also discussed.
文摘The gene encoded for tryptophan decarboxylase (TDC), which is the key enzyme in terpenoil indole alkaloids pathway, was targeted to different subcellular compartments and stably expressed in transgenic tobacco (Nicotiana tabacum L.) plants at the levels detected by Western blot and tryptamine accumulation analysis. It was shown that the TDC was located in subcellular compartments, the chloroplasts and cytosol. The recombinant TDC targeted to chloroplasts and cytosol in tobacco plants was effectively expressed as soluble protein by Western blot analysis and enzymatic assay. The level of tryptamine accumulation in chloroplast was higher than that in cytosol and very low in vacuole and endoplasmic reticulum (ER) to be hardly detected by Western blot analysis. It was indicated that the highest amount of tryptamine was in chloroplasts, lower in endoplasmic reticula and the lowest in vacuoles as compared to those in wild type plants. The TDC targeted to different subcellular compartments of tobacco plants and its expression level were studied by different nucleotide sequences coding signal peptides at 5'-end of tdc gene in order to know the effects of the TDC in compartmentation on its functionality.
文摘The two compartment model with variable extracellular volume is presented and solved by using both perturbation and analytical method. The computation for both creatinine and urea show that the perturbation solution is not only simple but also accurate enough and is a good substitute for the more exact analytical solution.
文摘Strictosidine synthase (STR) is a key enzyme involved in the biosynthesis of terpenoid indole alkaloids (TIA) by condensing tryptamine and secologanin into strictosidine. The transgenic tobacco plants targeting STR to subcellular compartments were established to express STR in chloroplast, vacuole and endoplasmic reticulum (ER) by the tobacco stable transformation. It was shown that STR was effectively expressed in the above subcellular compartments by Western blot analysis and STR enzymatic assay. In vitro , STR enzymatic assay was measured indirectly by fluorimetrically detecting depletion of tryptamine feeding on secologanin in the reaction mixture. The tryptamine were completely depleted by STR in the crude extract of leaves of transgenic tobacco plants targeting and expressing STR in the chloroplast, vacuole and ER, which ascertained the STR functionally targeted to the three subcellular compartments. To confirm STR correct targeting and expressing in chloroplast, the chloroplasts were isolated and the fractions of purified chloroplasts were analyzed by Western blot. The hypothesis of STR correct targeting to the chloroplast was tested. The results have implications on our understanding of the complex intracellular trafficking in metabolic intermediates of TIA biosynthesis.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 11034010 and 11274354)the Chinese Academy of Sciences "Strategic Priority Research Program - SJ-10" (Grant No. XDA04020200)the Special Fund for Earthquake Research of China (Grant No. 201208011)
文摘The clustering behavior of a mono-disperse granular gas is experimentally studied in an asymmetric two-compartment setup. Unlike the random clustering in either compartment in the case of symmetric configuration when lowering the shaking strength to below a critical value, the directed clustering is observed, which corresponds to an imperfect pitchfork bifurcation. Numerical solutions of the flux equation using a modified simple flux function show qualitative agreements with the experimental results. The potential application of this asymmetric structure is discussed.
基金Supported by the Program for New Century Excellent Talents in University of China(No.NCET-11-0441)the Chinese Universities Scientific Fund(No.QN2011092)the Talent Introduction Startup Fund of Northwest A&F University,China(No.Z111021003)
文摘In recent years,due to excessive emission of industrial waste,wastewater irrigation,and unreasonable utilization of fertilizers,pesticides and plastic sheeting,heavy metal pollution is increasing rapidly,resulting in many environmental problems.Silicon(Si),as the second most abundant element in the soil,can not only stimulate plant growth,but alleviate various biotic and abiotic stresses,including heavy metal stress.Here,we reviewed recent advances in the mechanisms for Si-mediated heavy metal tolerance in plants.These mechanisms included reducing active heavy metal ions in growth media,reducing heavy metal transport to the shoot,stimulating enzymatic and non-enzymatic antioxidants,chelation,compartmentation,regulation of the expression of metal transport genes,and structural changes in plants.Further research orientation is also discussed.
文摘AIM: To study retrospectively the influence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in patients with early acute pancreatitis (AP) (during the first week after admission) on physiological functions, and the association of the presence of IAH/ACS and outcome. METHODS: Patients (n = 74) with AP recruited in this study were divided into two groups according to intra-abdominal pressure (IAP) determined by indirect measurement using the transvesical route via Foley bladder catheter during the first week after admission. Patients (n = 44) with IAP ≥ 12 mmHg were assigned in IAH group, and the remaining patients (n = 30) with IAP < 12 mmHg in normal IAP group. For analysis of the influence of IAH/ACS on organ function and outcome, the physiological parameters and the occurrence of organ dysfunction during intensive care unit (ICU) stay were recorded, as were the incidences of pancreatic infection and in-hospital mortality. RESULTS: IAH within the first week after admission was found in 44 patients (59.46%). Although the APACHE Ⅱ scores on admission and the Ranson scores within 48 h after hospitalization were elevated in IAH patients in early stage, they did not show the statistically significant differences from patients with normal IAP within a week after admission (16.18 ± 3.90 vs 15.70 ± 4.25, P = 0.616; 3.70 ± 0.93 vs 3.47 ± 0.94, P = 0.285, respectively). ACS in early AP was recorded in 20 patients (27.03%). During any 24-h period ofthe first week after admission, the recorded mean IAP correlated significantly with the Marshall score calculated at the same time interval in IAH group (r = 0.635, P < 0.001). Although ACS patients had obvious amelioration in physiological variables within 24 h after decompression, the incidences of pancreatitic infection, septic shock, multiple organ dysfunction syndrome (MODS) and death in the patients with ACS were significantly higher than that in other patients without ACS (pancreatitic infection: 60.0% vs 7.4%, P < 0.001; septic shock: 70.0% vs 11.1%, P < 0.001; MODS: 90.0% vs 31.5%, P < 0.001; mortality: 75.0% vs 3.7%, P < 0.001). CONCLUSION: IAH/ACS is a frequent finding in patients admitted to the ICU because of AP. Patients with IAP at approximately 10-12 mmHg and early signs of changes in physiologic variables should be seriously considered for urgent decompression to improve survival.
