A typical acidic extracellular polysaccharide alludes to algae-bacteria-collaboration in microalgal-bacterial symbiosis.

Microalgal-bacterial symbioses are prevalent in aquatic ecosystems and play a pivotal role in carbon sequestration, significantly contributing to global carbon cycling. The understanding of the contribution of exopolysaccharides (EPSs), a crucial carbon-based component, to the structural integrity of microalgal-bacterial symbioses remains insufficiently elucidated. To address this gap, our study aims to enhance our comprehension of the composition and primary structure of EPSs within a specific type of granular microalgal-bacterial symbiosis named microalgal-bacterial granular sludge (MBGS). Our investigation reveals that the acidic EPSs characteristic of this symbiosis have molecular weights ranging from several hundred thousand to over one million Daltons, including components like glucopyranose, galactopyranose, mannose, and rhamnose. Our elucidation of the backbone linkage of a representative exopolysaccharide revealed a →3)-ß-D-Galp-(1→4)-ß-D-Glcp-(1→ glycosidic linkage. This linear structure closely resembles bacterial xanthan, while the branched chain structure bears similarities to algal EPSs. Our findings highlight the collaborative synthesis of acidic EPSs by both microalgae and bacteria, emphasizing their joint contribution in the production of macromolecules within microalgal-bacterial symbiosis. This collaborative synthesis underscores the intricate molecular interactions contributing to the stability and function of these symbiotic relationships.

Rationale and design of the GOLDEN BRIDGE II: a cluster-randomised multifaceted intervention trial of an artificial intelligence-based cerebrovascular disease clinical decision support system to improve stroke outcomes and care quality in China.

BACKGROUND: Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease. AIMS: To describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality. DESIGN: The GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations. CONCLUSIONS: Once the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China. TRIAL REGISTRATION NUMBER: NCT04524624.

Toward Accurate Simulation of Coupling between Protein Secondary Structure and Phase Separation.

Intrinsically disordered proteins (IDPs) frequently mediate phase separation that underlies the formation of a biomolecular condensate. Together with theory and experiment, efficient coarse-grained (CG) simulations have been instrumental in understanding the sequence-specific phase separation of IDPs. However, the widely used Cα-only models are limited in capturing the peptide nature of IDPs, particularly backbone-mediated interactions and effects of secondary structures, in phase separation. Here, we describe a hybrid resolution (HyRes) protein model toward a more accurate description of the backbone and transient secondary structures in phase separation. With an atomistic backbone and coarse-grained side chains, HyRes can semiquantitatively capture the residue helical propensity and overall chain dimension of monomeric IDPs. Using GY-23 as a model system, we show that HyRes is efficient enough for the direct simulation of spontaneous phase separation and, at the same time, appears accurate enough to resolve the effects of single His to Lys mutations. HyRes simulations also successfully predict increased ß-structure formation in the condensate, consistent with available experimental CD data. We further utilize HyRes to study the phase separation of TPD-43, where several disease-related mutants in the conserved region (CR) have been shown to affect residual helicities and modulate the phase separation propensity as measured by the saturation concentration. The simulations successfully recapitulate the effect of these mutants on the helicity and phase separation propensity of TDP-43 CR. Analyses reveal that the balance between backbone and side chain-mediated interactions, but not helicity itself, actually determines phase separation propensity. These results support that HyRes represents an effective protein model for molecular simulation of IDP phase separation and will help to elucidate the coupling between transient secondary structures and phase separation.

Accurate Simulation of Coupling between Protein Secondary Structure and Liquid-Liquid Phase Separation.

Intrinsically disordered proteins (IDPs) frequently mediate liquid-liquid phase separation (LLPS) that underlies the formation of membraneless organelles. Together with theory and experiment, efficient coarse-grained (CG) simulations have been instrumental in understanding sequence-specific phase separation of IDPs. However, the widely-used Cα-only models are severely limited in capturing the peptide nature of IDPs, including backbone-mediated interactions and effects of secondary structures, in LLPS. Here, we describe a hybrid resolution (HyRes) protein model for accurate description of the backbone and transient secondary structures in LLPS. With an atomistic backbone and coarse-grained side chains, HyRes accurately predicts the residue helical propensity and chain dimension of monomeric IDPs. Using GY-23 as a model system, we show that HyRes is efficient enough for direct simulation of spontaneous phase separation, and at the same time accurate enough to resolve the effects of single mutations. HyRes simulations also successfully predict increased beta-sheet formation in the condensate, consistent with available experimental data. We further utilize HyRes to study the phase separation of TPD-43, where several disease-related mutants in the conserved region (CR) have been shown to affect residual helicities and modulate LLPS propensity. The simulations successfully recapitulate the effect of these mutants on the helicity and LLPS propensity of TDP-43 CR. Analyses reveal that the balance between backbone and sidechain-mediated interactions, but not helicity itself, actually determines LLPS propensity. We believe that the HyRes model represents an important advance in the molecular simulation of LLPS and will help elucidate the coupling between IDP transient secondary structures and phase separation.

Relationship Between Carotid Artery Angle and Plaque Morphology in Acute Cerebral Infarction Patients.

BACKGROUND: High-resolution magnetic resonance imaging (HRMRI) can be used to clearly distinguish the luminal structure of the carotid artery (CA); measure the lumen, vessel wall, and total blood vessel area; and accurately describe the morphologic features of plaques. METHODS: This study used HRMRI to investigate the relationship between geometric features and volume and composition of carotid atherosclerotic plaques. Patients (n=81) who had experienced acute cerebral infarction (CI) within 7±3 days before admission to the Neurology Department of Beijing Tiantan Hospital between November 2011 and June 2012 were enrolled in the study. CA HRMRI was performed to analyze the geometry and morphology of plaques in 160 blood vessels. RESULTS: The median left and right internal carotid artery angles (ICAAs) were 32.79 and 31.00 degrees, respectively. Aside from the nonplanar external CA angle, plaque volume and angles did not differ significantly between the left and right sides. Age ( B =3.77; P =0.03) and nonplanar ICAA ( B =4.70; P =0.01) were predictors of left but not right carotid plaque volume. ICAA and bifurcation angle did not predict plaque volume. CONCLUSIONS: In this study, CA morphology in acute stroke patients is not associated with plaque volume or composition, but age and nonplanar ICAA can predict left carotid plaque volume.

Extracranial Carotid Plaque Hemorrhage Is Independently Associated With Poor 3-month Functional Outcome After Acute Ischemic Stroke-A Prospective Cohort Study.

Background and Purpose: Carotid plaque hemorrhage (IPH) is a critical plaque vulnerable feature. We aim to elucidate the association between symptomatic extracranial carotid atherosclerotic IPH and poor 3-month functional outcome after acute ischemic stroke by high-resolution vessel wall MRI (HRVMRI). Methods: We prospectively studied consecutive patients with a recent stroke or transient ischemic attack (TIA) of carotid atherosclerotic origin. All patients underwent a High-Resolution (HR) VWMRI scan of ipsilateral extracranial carotid within 1 week after admission. The patients recruited were interviewed by telephone after 3 months after stroke onset. The primary outcome was a 3-month functional prognosis of stroke, expressed as a modified Rankin Scale (mRS) score. A poor prognosis was defined as a 3-month modified Rankin Scale (mRS) score ≥ of 3. Univariate analysis was used to analyze the correlation between risk factors and IPH. The relation between IPH and 3-month functional outcome was analyzed by Logistic regression analysis. Results: A total of 156 patients (mean age, 61.18 ± 10.12 years; 108 males) were included in the final analysis. There were significant differences in the age, gender, smoking history, national institutes of health stroke scale (NIHSS) on admission, and diastolic blood pressure (DBP) on admission between the IPH group and the non-IPH group (all p < 0.05). During the follow-up, 32 patients (20.5%) had a poor functional outcome. According to the prognosis analysis of poor functional recovery, there was a significant difference between the two groups [36.7 vs. 16.7%; unadjusted odds ratio (OR), 2.32, 95% confidence interval (CI), 1.12-4.81, p = 0.024). Even after adjusting for confounding factors [such as age, gender, smoking history, National Institutes of Health Stroke Scale (NIHSS) on admission, DBP on admission, stenosis rate of carotid artery (CA), calcification, loose matrix, lipo-rich necrotic core (LRNC), and statins accepted at 3 months], IPH was still a strong predictor of poor 3-month outcome, and the adjusted OR was 3.66 (95% CI 1.68-7.94, p = 0.001). Conclusions: Extracranial carotid IPH is significantly associated with poor 3-month outcome after acute ischemic stroke and can predict the poor 3-month functional prognosis.

Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions.

Intrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for a mechanistic understanding of IDPs in biology, diseases, and therapeutics. Here, we provide an in-depth review of recent advances in the multi-scale simulation of disordered protein states, with a particular emphasis on the development and application of advanced sampling techniques for studying IDPs. These techniques are critical for adequate sampling of the manifold functionally relevant conformational spaces of IDPs. Together with dramatically improved protein force fields, these advanced simulation approaches have achieved substantial success and demonstrated significant promise towards the quantitative and predictive modeling of IDPs and their dynamic interactions. We will also discuss important challenges remaining in the atomistic simulation of larger systems and how various coarse-grained approaches may help to bridge the remaining gaps in the accessible time- and length-scales of IDP simulations.

Improvement of exhausted cerebral autoregulation in patients with idiopathic intracranial hypertension benefit of venous sinus stenting.

Objective.To evaluate the cerebral autoregulation (CA) in idiopathic intracranial hypertension (IIH) patients with transfer function analysis, and to explore its improvement after venous sinus stenting.Approach. In total, 15 consecutive IIH patients with venous sinus stenosis and 15 controls were recruited. All the patients underwent digital subtraction angiography and venous manometry. Venous sinus stenting was performed for IIH patients with a trans-stenosis pressure gradient ≥8 mmHg. CA was assessed before and after the operation with transfer function analysis, by using the spontaneous oscillations of the cerebral blood flow velocity in the bilateral middle cerebral artery and blood pressure.Main results. Compared with controls, the autoregulatory parameters, phase shift and rate of recovery, were both significantly lower in IIH patients [(57.94° ± 23.22° versus 34.59° ± 24.15°,p < 0.001; (39.87 ± 21.95) %/s versus (20.56 ± 46.66) %/s,p= 0.045, respectively). In total, six patients with bilateral transverse or sigmoid sinus stenosis received venous sinus stenting, in whom, the phase shift significantly improved after venous sinus stenting (39.62° ± 20.26° versus 22.79° ± 19.96°,p = 0.04).Significance. The study revealed that dynamic CA was impaired in IIH patients and was improved after venous sinus stenting. CA assessment has the potential to be used for investigating the hemodynamics in IIH patients.

Accelerating atomistic simulations of proteins using multiscale enhanced sampling with independent tempering.

Efficient sampling of the conformational space is essential for quantitative simulations of proteins. The multiscale enhanced sampling (MSES) method accelerates atomistic sampling by coupling it to a coarse-grained (CG) simulation. Bias from coupling to the CG model is removed using Hamiltonian replica exchange, such that one could benefit simultaneously from the high accuracy of atomistic models and fast dynamics of CG ones. Here, we extend MSES to allow independent control of the effective temperatures of atomistic and CG simulations, by directly scaling the atomistic and CG Hamiltonians. The new algorithm, named MSES with independent tempering (MSES-IT), supports more sophisticated Hamiltonian and temperature replica exchange protocols to further improve the sampling efficiency. Using a small but nontrivial ß-hairpin, we show that setting the effective temperature of CG model in all conditions to its melting temperature maximizes structural transition rates at the CG level and promotes more efficient replica exchange and diffusion in the condition space. As the result, MSES-IT drive faster reversible transitions at the atomic level and leads to significant improvement in generating converged conformational ensembles compared to the original MSES scheme.

Impaired Dynamic Cerebral Autoregulation in Cerebral Venous Thrombosis.

Background: Cerebral autoregulation is crucial in traumatic brain injury, which might be used for determining the optimal intracranial pressure. Cerebral venous thrombosis (CVT) is a cerebral vascular disease with features of high intracranial pressure. However, the autoregulatory mechanism of CVT remains unknown. We aimed to investigate the capacity of cerebral autoregulation in patients with CVT. Methods: This study consecutively enrolled 23 patients with CVT and 16 controls from December 2018 to May 2019. Cerebral autoregulation was assessed by transfer function analysis (rate of recovery/phase/gain) using the spontaneous oscillations of the cerebral blood flow velocity and arterial blood pressure. Results: In total, 76 middle cerebral arteries (MCAs) were investigated, including 44 MCAs in patients with CVT and 32 normal ones. The phase shift estimated in patients with CVT was significantly different from that of the controls (37.37 ± 36.53 vs. 54.00 ± 26.78, p = 0.03). The rate of recovery and gain in patients with CVT were lower than those in controls but without statistical significance. Conclusion: To our knowledge, this is the first time that a study has indicated that patients with CVT were more likely to have impaired cerebral autoregulation. Hence, cautious blood pressure control is required in such patients to prevent hyper- or hypoperfusion.

Application of Transcranial Color-coded Duplex Sonography in the Diagnosis and Management of Straight Sinus Thrombosis With Dural Arteriovenous Fistulae: A Case Report.

INTRODUCTION: Transcranial color-coded duplex sonography (TCCS) with and without ultrasound contrast agent has been used to diagnose cerebral venous thrombosis, however, no experience in the diagnosis of patients with cerebral venous thrombosis and with dural arteriovenous fistula (dAVF) by contrast-enhanced TCCS has been reported yet. CASE REPORT: The authors reported a 49-year-old male patient with straight sinus (StS) thrombosis and dAVF. Plain TCCS and contrast-enhanced TCCS demonstrated the direct presentation of the selected feeder and drainage veins of the dAVFs, arterialized venous flow waveform, and an enlarged optic nerve sheath diameter, indicating an increased intracranial pressure, and a filling defect in the StS even after administration of an ultrasound contrast agent. After intravascular thrombolysis and blockage of 2 feeders of the dAVF, TCCS still showed retrograde flow direction in the left basal vein and significantly elevated flow velocity in the StS, reflecting a high venous pressure caused by a high volume of arteriovenous shunt and severe stenosis in the StS. The patient's clinical manifestation did not substantially improve until 3 stents were implanted in the StS, and TCCS unveiled that the stents were well filled with flow signal, and the flow velocity in the StS dramatically decreased. CONCLUSIONS: TCCS could provide reliable data about the feeder and drainage veins of dAVF in our case. The extent of an increase in venous flow velocity may be closely associated with clinical manifestations, which may influence therapy. Moreover, TCCS possesses a unique advantage in terms of evaluating the patency of the stents compared with other neuroimaging techniques.

Cerebral Hemodynamic Changes After Endovascular Recanalization of Symptomatic Chronic Intracranial Artery Occlusion.

Objective: We performed this study to evaluate the hemodynamic changes over time after successful endovascular recanalization in patients with symptomatic chronic intracranial artery occlusion (CIAO). Materials and Methods: We included 20 patients with symptomatic CIAO in a high-volume stroke center from June 2014 to June 2019. All subjects were evaluated with CT perfusion (CTP) studies before and after the recanalization. The relative cerebral blood flows (rCBFs) in perforating artery territory (PAT) and cortical artery territory (CAT) of occluded arteries were compared before and after the recanalization. The patients were categorized into subgroups based on the time interval from revascularization to post-procedural CTP, occlusion sites, and restenosis status. The proportion of rCBF change (rCBFc%) was compared in variable subgroups. Results: The rCBF increased significantly from 0.52 to 0.71 in PAT (P < 0.001) and from 0.59 to 0.85 in CAT (P < 0.001) after recanalization, and there were also statistical differences in variable subgroups except for those with restenosis. The median and interquartile range (IQR) of rCBFc% were 35.2 and 18.6-56.6%. For patients with short-term follow-up (55.2%), the rCBFc% was relatively higher than that in patients with mid-term (35.4%) and long-term follow-up (32.7%), although without statistical difference (P = 0.273). For patients with restenosis, the rCBFc% was significantly lower than that in patients without restenosis (18.5 vs. 37.3%, P = 0.008). Conclusions: In patients with symptomatic CIAO, the CBF may increase and be relatively stable over time after successful recanalization except for restenosis.

Accelerating the Generalized Born with Molecular Volume and Solvent Accessible Surface Area Implicit Solvent Model Using Graphics Processing Units.

The generalized Born with molecular volume and solvent accessible surface area (GBMV2/SA) implicit solvent model provides an accurate description of molecular volume and has the potential to accurately describe the conformational equilibria of structured and disordered proteins. However, its broader application has been limited by the computational cost and poor scaling in parallel computing. Here, we report an efficient implementation of both the electrostatic and nonpolar components of GBMV2/SA on graphics processing unit (GPU) within the CHARMM/OpenMM module. The GPU-GBMV2/SA is numerically equivalent to the original CPU-GBMV2/SA. The GPU acceleration offers ~60- to 70-fold speedup on a single NVIDIA TITAN X (Pascal) graphics card for molecular dynamic simulations of both folded and unstructured proteins of various sizes. The current implementation can be further optimized to achieve even greater acceleration with minimal reduction on the numerical accuracy. The successful development of GPU-GBMV2/SA greatly facilitates its application to biomolecular simulations and paves the way for further development of the implicit solvent methodology. © 2019 Wiley Periodicals, Inc.

Transcranial Color-Coded Sonography for the Detection of Cerebral Veins and Sinuses and Diagnosis of Cerebral Venous Sinus Thrombosis.

This study aimed to determine the detection rate of transcranial color-coded sonography (TCCS) of cerebral veins and sinuses and to explore the diagnostic accuracy of TCCS for straight sinus (SS) and transverse sinus (TS) thromboses. The detection rates of cerebral veins and sinuses using TCCS and contrast-enhanced TCCS (CE-TCCS) were analyzed. The diagnostic accuracy of CE-TCCS was evaluated. Median time from symptoms to CE-TCCS was 10 (range, 1-150) d. The detection rate of bilateral basal veins of Rosenthal was 100% by CE-TCCS, followed by right TS (91.89%), SS (88.12%), left TS (74.59%) and vein of Galen (70.27%). Compared with magnetic resonance imaging/magnetic resonance venography, CE-TCCS showed 100% sensitivity and 96.3% specificity for SS thrombosis, 100% and 100% for right TS thrombosis and 100% and 94.4% for left TS thrombosis. In conclusion, CE-TCCS shows high identification rates of cerebral veins and sinuses and a high diagnostic accuracy for SS and TS thrombosis.

Hamiltonian Matrix Correction Based Density Functional Valence Bond Method.

In this work, a valence bond type multireference density functional theory (MRDFT) method, called the Hamiltonian matrix correction based density functional valence bond method (hc-DFVB), is presented. In hc-DFVB, the static electronic correlation is considered by the valence bond self-consistent field (VBSCF) strategy, while the dynamic correlation energy is taken into account by Kohn-Sham density functional theory (KS-DFT). Different from our previous version of DFVB (J. Chem. Theory Comput. 2012, 8, 1608), hc-DFVB corrects the dynamic correlation energy with a Hamiltonian correction matrix, improving the functional adaptability and computational accuracy. The method was tested for various physical and chemical properties, including spectroscopic constants, bond dissociation energies, reaction barriers, and singlet-triplet gaps. The accuracy of hc-DFVB matches that of KS-DFT and high level molecular orbital (MO) methods quite well. Furthermore, hc-DFVB keeps the advantages of VB methods, which are able to provide clear interpretations and chemical insights with compact wave functions.

The application of cholesky decomposition in valence bond calculation.

The Cholesky decomposition (CD) technique, used to approximate the two-electron repulsion integrals (ERIs), is applied to the valence bond self-consistent field (VBSCF) method. Test calculations on ethylene, C2 n H2 n +2 , and C2 n H4 n -2 molecules (n = 1-7) show that the performance of the VBSCF method is much improved using the CD technique, and thus, the integral transformation from basis functions to VB orbitals is no longer the bottleneck in VBSCF calculations. The errors of the CD-based ERIs and of the total energy are controlled by the CD threshold, for which a value of 10(-6) ensures to control the total energy error within 10(-6) Hartree. © 2016 Wiley Periodicals, Inc.

Apolipoprotein E ε4 Allele was Associated With Nonlesional Mesial Temporal Lobe Epilepsy in Han Chinese Population.

Apolipoprotein E (APOE) gene has been implicated as one of the genes susceptible to temporal lobe epilepsy (TLE), but the association is inconsistent. We carried out a study to investigate the association of APOEε4 allele with a subtype of TLE-nonlesional mesial temporal lobe epilepsy (NLMTLE) in Han Chinese people.T he study consisted of total 308 NLMTLE patients and 302 controls in Han Chinese. The APOE polymorphisms were genotyped using polymerase chain reaction (PCR) DNA sequencing. We compared the frequency of APOEε4 allele and carrying status between NLMTLE patients and control subjects to test for the association of APOEε4 allele with NLMTLE clinical status. Carrying status of APOEε4 allele was significantly associated with the risk of NLMTLE. No effect of APOEε4 allele was found on the age of onset, duration of epilepsy, or frequency of seizure. Moreover, there was no association between APOEε4 allele and hippocampal sclerosis (HS) or febrile convulsion (FC) history.O ur study provided an evidence that APOEε4 allele was a possible risk factor for NLMTLE, and further study with a larger sample is needed to warrant this finding.

The synergistic mechanism of graphene and MoS2 for hydrogen generation: insights from density functional theory.

The synergistic effect of graphene and MoS2 was investigated by using density functional theory (DFT) calculations on the enhanced photocatalytic H2 production activity of TiO2/graphene/MoS2 ternary nanoparticles. Our results indicate that it can form a weak covalent bond between the Ti atom of TiO2 nanocluster and the nearest C atom on graphene, which not only makes the original degenerate C(2p) orbital level of the graphene (part of the conduction band energy level) split, resulting in the production of a lower level of C(2p) that makes it easier to accept the excited electron from the Ti(3d) orbital, but also forms a +/- sequence electric field in the interface between them. It is conclusive that the electron moves from the TiO2 cluster to the graphene. In addition, we also find that the band gap of the TiO2 cluster can be doped by the graphene and MoS2, and the conduction band consists predominantly of C(2p), S(3p) and Mo(4d) orbital energy level near the Fermi level. These results illustrate that the excited electron will eventually accumulate in the graphene or MoS2 film, which can effectively enhance the separation between the excited electrons and the holes in the TiO2 clusters, thereby increasing the efficiency of hydrogen evolution. Our results are consistent with the experimental results, and can provide some valuable information for the design of photocatalytic composites.

Assessment of dynamic cerebral autoregulation in patients with basilar artery stenosis.

BACKGROUND AND AIMS: Previous studies have shown impaired cerebral autoregulation (CA) in carotid and middle cerebral artery (MCA) stenosis/occlusion. Little is known about CA in patients with basilar artery (BA) stenosis. We therefore investigated dynamic CA patterns in BA stenosis using transfer function analysis (TFA). METHODS: We measured spontaneous oscillations of blood flow velocity (CBFV) in the right posterior cerebral artery (PCA), and left MCA and mean arterial pressure (ABP) continuously in 25 patients with BA stenosis (moderate n=16 with 50-69% occlusion and severe n=9 with ≥ 70% occlusion) and 22 healthy volunteers in supine position during 6 circles per minute deep breath. Analysis was based on the 'black-box' model of transfer function deriving phase and gain in both PCA and MCA. RESULTS: Though changes of phase shift and gain between the patients and healthy controls were observed in MCA, the differences are however not significant. Phase shift in PCA was significantly decreased in severe stenosis when comparing with healthy controls and moderate stenosis (4.2 ± 34.2° VS 41.1 ± 40.4°, 4.2 ± 34.2° VS 34.2 ± 27.2°, both p<0.05), whilst the gain in PCA is increased for moderate BA stenosis and decreased for severe BA stenosis. Furthermore, we found that phase shift were almost abolished in patients with ischemic stroke who developed unfavorable clinical outcome (mRs>2) on the 90 days after stroke onset. CONCLUSION: Dynamic CA in PCA reduces in patients with severe BA stenosis and those with ischemic stroke who present poor outcome in 90 days after stroke onset. Phase shift might be a sensitive index prompting impaired CA in posterior circulation.