Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 352
Filter
1.
ACS Omega ; 9(17): 18777-18785, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38708220

ABSTRACT

The solution of wellbore multiphase flow models has an important position in oil-gas field development. However, the solution of multiphase flow models often involves a series of complicated situations such as interphase mass and energy transfer, surface problems, and so on. Foam carrying sand particles in the wellbore is a solid, liquid, and gas three-phase cylinder flow problem. To solve this problem, we developed a computational fluid dynamics-discrete element method model based on the traditional N-S equations to track the streamline of the foam fluid and sand particles in the wellbore. On this basis, we investigated the influence of three factors, i.e., foam and sand properties and wellbore parameters, on the sand carrying rate of foam. The results show that whether the sand mound at the bottom of wells that can be dispersed is mainly affected by the properties of foam. The location of sand deposition in the wellbore and the effectiveness of foam in sand transportation are mainly influenced by the wellbore parameters and sand properties.

2.
Adv Mater ; : e2401838, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748700

ABSTRACT

The advent of 2D ferroelectrics, characterized by their spontaneous polarization states in layer-by-layer domains without the limitation of a finite size effect, brings enormous promise for applications in integrated optoelectronic devices. Comparing with semiconductor/insulator devices, ferroelectric devices show natural advantages such as non-volatility, low energy consumption and high response speed. Several 2D ferroelectric materials have been reported, however, the device implementation particularly for optoelectronic application remains largely hypothetical. Here, the linear electro-optic effect in 2D ferroelectrics is discovered and electrically tunable 2D ferroelectric metalens is demonstrated. The linear electric-field modulation of light is verified in 2D ferroelectric CuInP2S6. The in-plane phase retardation can be continuously tuned by a transverse DC electric field, yielding an effective electro-optic coefficient rc of 20.28 pm V-1. The CuInP2S6 crystal exhibits birefringence with the fast axis oriented along its (010) plane. The 2D ferroelectric Fresnel metalens shows efficacious focusing ability with an electrical modulation efficiency of the focusing exceeding 34%. The theoretical analysis uncovers the origin of the birefringence and unveil its ultralow light absorption across a wide wavelength range in this non-excitonic system. The van der Waals ferroelectrics enable room-temperature electrical modulation of light and offer the freedom of heterogeneous integration with silicon and another material system for highly compact and tunable photonics and metaoptics.

3.
ACS Appl Mater Interfaces ; 16(17): 22166-22176, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38648115

ABSTRACT

We propose an atomically resolved approach to capture the spatial variations of the Schottky barrier height (SBH) at metal-semiconductor heterojunctions. This proposed scheme, based on atom-specific partial density of states (PDOS) calculations, further enables calculation of the effective SBH that aligns with conductance measurements. We apply this approach to study the variations of SBH at MoS2@Au heterojunctions, in which MoS2 contains conducting and semiconducting grain boundaries (GBs). Our results reveal that there are significant variations in SBH at atoms in the defected heterojunctions. Of particular interest is the fact that the SBH in some areas with extended defects approaches zero, indicating Ohmic contact. One important implication of this finding is that the effective SBH should be intrinsically dependent on the defect density and character. Remarkably, the obtained effective SBH values demonstrate good agreement with existing experimental measurements. Thus, the present study addresses two long-standing challenges associated with SBH in MoS2-metal heterojunctions: the wide variation in experimentally measured SBH values at MoS2@metal heterojunctions and the large discrepancy between density-functional-theory-predicted and experimentally measured SBH values. Our proposed approach points out a valuable pathway for understanding and manipulating SBHs at metal-semiconductor heterojunctions.

4.
Nano Lett ; 24(17): 5206-5213, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38647212

ABSTRACT

Single Atoms Catalysts (SACs) have emerged as a class of highly promising heterogeneous catalysts, where the traditional bottom-up synthesis approaches often encounter considerable challenges in relation to aggregation issues and poor stability. Consequently, achieving densely dispersed atomic species in a reliable and efficient manner remains a key focus in the field. Herein, we report a new facile electrochemical knock-down strategy for the formation of SACs, whereby the metal Zn clusters are transformed into single atoms. While a defect-rich substrate plays a pivotal role in capturing and stabilizing isolated Zn atoms, the feasibility of this novel strategy is demonstrated through a comprehensive investigation, combining experimental and theoretical studies. Furthermore, when studied in exploring for potential applications, the material prepared shows a remarkable improvement of 58.21% for the Li+ storage and delivers a capacity over 300 Wh kg-1 after 500 cycles upon the transformation of Zn clusters into single atoms.

5.
Brain Circ ; 10(1): 67-76, 2024.
Article in English | MEDLINE | ID: mdl-38655441

ABSTRACT

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

6.
Langmuir ; 40(15): 7843-7859, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38557084

ABSTRACT

Two-dimensional materials have shown immense promise for gas-sensing applications due to their remarkable surface-to-volume ratios and tunable chemical properties. However, despite their potential, the utilization of ReSe2 as a gas-sensing material for nitrogen-containing molecules, including NO2, NO, and NH3, has remained unexplored. The choice of doping atoms in ReSe2 plays a pivotal role in enhancing the gas adsorption and gas-sensing capabilities. Herein, the adsorption properties of nitrogen-containing gas molecules on metal and non-metal single-atom (Au, Pt, Ni, P, and S)-doped ReSe2 monolayers have been evaluated systematically via ab initio calculations based on density functional theory. The findings strongly suggest that intrinsic ReSe2 has better selectivity toward NO2 than toward NO and NH3. Moreover, our results provide compelling evidence that all of the dopants, with the exception of S, significantly enhance both the adsorption strength and charge transfer between ReSe2 and the investigated molecules. Notably, P-decorated ReSe2 showed the highest adsorption energy for NO2 and NO (-1.93 and -1.52 eV, respectively) with charge transfer above 0.5e, while Ni-decorated ReSe2 exhibited the highest adsorption energy for NH3 (-0.76 eV). In addition, on the basis of transition theory, we found that only Au-ReSe2 and Ni-ReSe2 can serve as reusable chemiresisitve gas sensors for reliable detection of NO and NH3, respectively. Hence, our findings indicate that gas-sensing applications can be significantly improved by utilizing a single-atom-doped ReSe2 monolayer.

7.
Neurocrit Care ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480608

ABSTRACT

BACKGROUND: In this study, we aimed to investigate the risk factors and impact of poststroke pneumonia (PSP) on mortality and functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). METHODS: This was a post hoc analysis of a prospective randomized trial (Direct intraarterial thrombectomy in order to revascularize AIS patients with large-vessel occlusion efficiently in Chinese tertiary hospitals: a multicenter randomized clinical trial). Patients with AIS who completed EVT were evaluated for the occurrence of PSP during the hospitalization period and their modified Rankin Scale (mRS) scores at 90 days after AIS. Logistic regression analysis was conducted to investigate the independent predictors of PSP. Propensity score matching was conducted for the PSP and non-PSP groups by using the covariates resulting from the logistic regression analysis. The associations between PSP and outcomes were analyzed. The outcomes included 90-day poor functional outcome (mRS scores > 2), 90-day mortality, and early 2-week mortality. RESULTS: A total of 639 patients were enrolled, of whom 29.58% (189) developed PSP. Logistic regression analysis revealed that history of chronic heart failure (unadjusted odds ratio [OR] 2.011, 95% confidence interval [CI] 1.026-3.941; P = 0.042), prethrombectomy reperfusion on initial digital subtraction angiography (OR 0.394, 95% CI 0.161-0.964; P = 0.041), creatinine levels at admission (OR 1.008, 95% CI 1.000-1.016; P = 0.049), and National Institutes of Health Stroke Scale at 24 h (OR 1.023, 95% CI 1.007-1.039; P = 0.004) were independent risk factors for PSP. With propensity scoring matching, poor functional outcome (mRS > 2) was more common in patients with PSP than in patients without PSP (81.03% vs. 71.83%, P = 0.043) at 90 days after EVT. The early 2-week mortality of patients with PSP was lower (5.74% vs. 12.07%, P = 0.038). But there was no statistically significant difference in 90-day mortality between the PSP group and non-PSP group (22.41% vs. 14.94%, P = 0.074). The survivorship curve also shows no statistical significance (P = 0.088) between the two groups. CONCLUSIONS: Nearly one third of patients with AIS and EVT developed PSP. Heart failure, higher creatinine levels, prethrombectomy reperfusion, and National Institutes of Health Stroke Scale at 24 h were associated with PSP in these patients. PSP was associated with poor 90-day functional outcomes in patients with AIS treated with EVT.

8.
Ground Water ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38517231

ABSTRACT

Tianjin, a coastal metropolis in north China, has grappled with land subsidence for nearly a century. Yet, emerging evidence suggests a notable decrease in subsidence rates across Tianjin since 2019. This trend is primarily attributed to the importation of surface water from the Yangtze River system via the South-to-North Water Diversion Project, initiated in December 2014. Utilizing Sentinel-1A Interferometric Synthetic Aperture Radar (InSAR) data (2014-2023), this study reveals that one-third of the Tianjin plain has either halted subsidence or experienced land rebound. As a result, the deep aquifer system (~-200 to -450 m) beneath one third of the Tianjin plain has completed a consolidation cycle, leading to the establishment of new, locally specific preconsolidation heads. The identification of the newly established preconsolidation head seeks to answer a crucial question: How can we prevent the reoccurrence of subsidence in areas where it has already ceased? In essence, subsidence will stop when the local hydraulic head elevates to the new preconsolidation head (NPCH), and permanent subsidence will not be reinitiated as long as hydraulic head remains above the NPCH. The difference of the depth between current hydraulic head and the NPCH defines the safe pumping buffer (SPB). This study outlines detailed methods for identifying the NPCHs in the deep aquifer system from long-term InSAR and groundwater-level datasets. Determining NPCHs and ascertaining SPBs are crucial for estimating how much groundwater can be safely extracted without inducing permanent subsidence, and for developing sustainable strategies for long-term groundwater management and conservation.

9.
Int J Biol Macromol ; 265(Pt 2): 131165, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38547941

ABSTRACT

Garlic is a common vegetable and spice in people's daily diets, in which garlic polysaccharide (GP) is one of the most important active components with a variety of benefits, such as antioxidant, immune-enhancing, anti-inflammatory, liver-protective and bowel-regulating properties. >20 types of GPs, mainly crude polysaccharides, have been identified. However, the exact chemical composition of GPs or the mechanism underlying their pharmacological activity is still not fully understood. The extraction and purification methods of GPs are compared in this review while providing detailed information on their structural features, identification methods, major biological activities, mechanisms of actions, structural modifications, structure-activity relationships as well as potential applications. Finally, the limitations of GP research and future issues that need to be addressed are discussed in this review. GPs are widely recognized as substances with great potential in the pharmaceutical and food industries. Therefore, this review aims to provide a comprehensive summary of the latest research progresses in the field of GPs, together with scientific insights and a theoretical support for the development of GPs in research and industrialization.


Subject(s)
Biological Products , Garlic , Humans , Antioxidants/pharmacology , Vegetables , Structure-Activity Relationship , Polysaccharides/pharmacology
10.
JAMA ; 331(9): 764-777, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38324409

ABSTRACT

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.


Subject(s)
Brain Ischemia , Fibrinolytic Agents , Ischemic Stroke , Thrombectomy , Thrombolytic Therapy , Aged , Female , Humans , Male , Middle Aged , Administration, Intravenous , Brain Ischemia/drug therapy , Brain Ischemia/surgery , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Randomized Controlled Trials as Topic , Recovery of Function , Stroke/drug therapy , Stroke/complications , Thrombolytic Therapy/methods , Time-to-Treatment , Treatment Outcome
11.
Inorg Chem ; 63(8): 3974-3985, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38346714

ABSTRACT

Designing transition-metal oxides for catalytically removing the highly toxic benzene holds significance in addressing indoor/outdoor environmental pollution issues. Herein, we successfully synthesized ultrathin LayCoOx nanosheets (thickness of ∼1.8 nm) with high porosity, using a straightforward coprecipitation method. Comprehensive characterization techniques were employed to analyze the synthesized LayCoOx catalysts, revealing their low crystallinity, high surface area, and abundant porosity. Catalytic benzene oxidation tests demonstrated that the La0.029CoOx-300 nanosheet exhibited the most optimal performance. This catalyst enabled complete benzene degradation at a relatively low temperature of 220 °C, even under a high space velocity (SV) of 20,000 h-1, and displayed remarkable durability throughout various catalytic assessments, including SV variations, exposure to water vapor, recycling, and long time-on-stream tests. Characterization analyses confirmed the enhanced interactions between Co and doped La, the presence of abundant adsorbed oxygen, and the extensive exposure of Co3+ species in La0.029CoOx-300 nanosheets. Theoretical calculations further revealed that La doping was beneficial for the formation of oxygen vacancies and the adsorption of more hydroxyl groups. These features strongly promoted the adsorption and activation of oxygen, thereby accelerating the benzene oxidation processes. This work underscores the advantages of doping rare-earth elements into transition-metal oxides as a cost-effective yet efficient strategy for purifying industrial exhausts.

12.
AJNR Am J Neuroradiol ; 45(3): 296-301, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38388688

ABSTRACT

BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Thrombosis , Humans , Tissue Plasminogen Activator/therapeutic use , Stroke/surgery , Thrombolytic Therapy , Brain Ischemia/therapy , Treatment Outcome , Thrombectomy , Thrombosis/drug therapy , Fibrinolytic Agents/therapeutic use
13.
Nanomicro Lett ; 16(1): 121, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38372805

ABSTRACT

The conventional computing architecture faces substantial challenges, including high latency and energy consumption between memory and processing units. In response, in-memory computing has emerged as a promising alternative architecture, enabling computing operations within memory arrays to overcome these limitations. Memristive devices have gained significant attention as key components for in-memory computing due to their high-density arrays, rapid response times, and ability to emulate biological synapses. Among these devices, two-dimensional (2D) material-based memristor and memtransistor arrays have emerged as particularly promising candidates for next-generation in-memory computing, thanks to their exceptional performance driven by the unique properties of 2D materials, such as layered structures, mechanical flexibility, and the capability to form heterojunctions. This review delves into the state-of-the-art research on 2D material-based memristive arrays, encompassing critical aspects such as material selection, device performance metrics, array structures, and potential applications. Furthermore, it provides a comprehensive overview of the current challenges and limitations associated with these arrays, along with potential solutions. The primary objective of this review is to serve as a significant milestone in realizing next-generation in-memory computing utilizing 2D materials and bridge the gap from single-device characterization to array-level and system-level implementations of neuromorphic computing, leveraging the potential of 2D material-based memristive devices.

14.
Cerebrovasc Dis ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38377964

ABSTRACT

BACKGROUND: Although guidelines recommend a target blood pressure 185-180/105-110 mmHg after mechanical thrombectomy for acute ischemic stroke (AIS), there is limited randomized evidence to support this level. We surveyed candidate institutions about the approach to blood pressure management in this patient group in preparation for inviting them to participate in the Enhanced Blood Pressure Control after Endovascular Thrombectomy for the Acute Ischemic Stroke Trial (ENCHANTED2/MT). METHODS: Physicians from a professional network of institutions that met mechanical thrombectomy qualification requirements were invited to participate in an online questionnaire covering basic clinical information as well as questions on blood pressure management. RESULTS: We invited 88 sites to participate with 44 (50%) ultimately joining the trial, and a total of 88 physicians finished the survey. The median number of annual mechanical thrombectomy cases performed per site was 89 [IQR 65-150]. Only 38 (43%) institutions strictly adhere to guidelines when managing the blood pressure of mechanical thrombectomy patients. The most popular blood pressure target for reperfusion patients was 140-160 mmHg (n=47, 53%), and <120 mmHg (n=28, 32%). Fewer hospital stroke beds (40 [21-57] vs. 60 [39-110], p = 0.01) and lower proportion of elevated blood pressure after mechanical thrombectomy (25% [10%-50%] vs. 50% [20%-70%], p = 0.02) were related to a more aggressive blood pressure target (<120 mmHg). Urapidil (n=82, 93%) and calcium channel blockers (CCBs) (n = 87, 99%), were the most widely used antihypertensive drugs, respectively. CONCLUSIONS: According to the survey, unstandardized blood pressure management protocols are performed in mechanical thrombectomy patients at institutions across China, which is different from prior survey from another country. More high-quality studies are needed to guide clinical practice.

15.
ACS Sens ; 9(5): 2372-2382, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38401047

ABSTRACT

Rapid and ultrasensitive detection of toxic gases at room temperature is highly desired in health protection but presents grand challenges in the sensing materials reported so far. Here, we present a gas sensor based on novel zero dimensional (0D)/two dimensional (2D) indium oxide (In2O3)/titanium carbide (Ti3C2Tx) Schottky heterostructures with a high surface area and rich oxygen vacancies for parts per billion (ppb) level nitrogen dioxide (NO2) detection at room temperature. The In2O3/Ti3C2Tx gas sensor exhibits a fast response time (4 s), good response (193.45% to 250 ppb NO2), high selectivity, and excellent cycling stability. The rich surface oxygen vacancies play the role of active sites for the adsorption of NO2 molecules, and the Schottky junctions effectively adjust the charge-transfer behavior through the conduction tunnel in the sensing material. Furthermore, In2O3 nanoparticles almost fully cover the Ti3C2Tx nanosheets which can avoid the oxidation of Ti3C2Tx, thus contributing to the good cycling stability of the sensing materials. This work sheds light on the sensing mechanism of heterojunction nanostructures and provides an efficient pathway to construct high-performance gas sensors through the rational design of active sites.


Subject(s)
Indium , Nitrogen Dioxide , Temperature , Titanium , Nitrogen Dioxide/analysis , Nitrogen Dioxide/chemistry , Titanium/chemistry , Indium/chemistry , Porosity
16.
Brain ; 147(5): 1784-1798, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38387080

ABSTRACT

The Huntington's disease mutation is a CAG repeat expansion in the huntingtin gene that results in an expanded polyglutamine tract in the huntingtin protein. The CAG repeat is unstable and expansions of hundreds of CAGs have been detected in Huntington's disease post-mortem brains. The age of disease onset can be predicted partially from the length of the CAG repeat as measured in blood. Onset age is also determined by genetic modifiers, which in six cases involve variation in DNA mismatch repair pathways genes. Knocking-out specific mismatch repair genes in mouse models of Huntington's disease prevents somatic CAG repeat expansion. Taken together, these results have led to the hypothesis that somatic CAG repeat expansion in Huntington's disease brains is required for pathogenesis. Therefore, the pathogenic repeat threshold in brain is longer than (CAG)40, as measured in blood, and is currently unknown. The mismatch repair gene MSH3 has become a major focus for therapeutic development, as unlike other mismatch repair genes, nullizygosity for MSH3 does not cause malignancies associated with mismatch repair deficiency. Potential treatments targeting MSH3 currently under development include gene therapy, biologics and small molecules, which will be assessed for efficacy in mouse models of Huntington's disease. The zQ175 knock-in model carries a mutation of approximately (CAG)185 and develops early molecular and pathological phenotypes that have been extensively characterized. Therefore, we crossed the mutant huntingtin allele onto heterozygous and homozygous Msh3 knockout backgrounds to determine the maximum benefit of targeting Msh3 in this model. Ablation of Msh3 prevented somatic expansion throughout the brain and periphery, and reduction of Msh3 by 50% decreased the rate of expansion. This had no effect on the deposition of huntingtin aggregation in the nuclei of striatal neurons, nor on the dysregulated striatal transcriptional profile. This contrasts with ablating Msh3 in knock-in models with shorter CAG repeat expansions. Therefore, further expansion of a (CAG)185 repeat in striatal neurons does not accelerate the onset of molecular and neuropathological phenotypes. It is striking that highly expanded CAG repeats of a similar size in humans cause disease onset before 2 years of age, indicating that somatic CAG repeat expansion in the brain is not required for pathogenesis. Given that the trajectory for somatic CAG expansion in the brains of Huntington's disease mutation carriers is unknown, our study underlines the importance of administering treatments targeting somatic instability as early as possible.


Subject(s)
Huntingtin Protein , Huntington Disease , Trinucleotide Repeat Expansion , Huntington Disease/genetics , Huntington Disease/therapy , Animals , Humans , Trinucleotide Repeat Expansion/genetics , Mice , Huntingtin Protein/genetics , MutS Homolog 3 Protein/genetics , Disease Models, Animal , Nerve Tissue Proteins/genetics , Brain/pathology , Brain/metabolism
17.
J Neurointerv Surg ; 16(2): 204-208, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-37185108

ABSTRACT

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of ischemic stroke. Conventional anatomical analysis by CT angiography, MRI, or digital subtraction angiography can provide valuable information on the anatomical changes of stenosis; however, they are not sufficient to accurately evaluate the hemodynamic severity of ICAS. The goal of this study was to assess the diagnostic performance of the pressure ratio across intracranial stenoses (termed as fractional flow (FF)) derived from cerebral angiography for the diagnosis of hemodynamically significant ICAS defined by pressure wire-derived FF. METHODS: This retrospective study represents a feasible and reliable method for calculating the FF from cerebral angiography (AccuFFicas). Patients (n=121) who had undergone wire-based measurement of FF and cerebral angiography were recruited. The accuracy of the computed pressure ratio was evaluated using wire-based FF as the reference standard. RESULTS: The mean value of wire-based FF was 0.78±0.19, while the computed AccuFFicas had an average value of 0.79±0.18. Good correlation (Pearson's correlation coefficient r=0.92, P<0.001) between AccuFFicas and FF was observed. Bland-Altman analysis showed that the mean difference between AccuFFicas and FF was -0.01±0.07, indicating good agreement. The area under the curve (AUC) of AccuFFicas in predicting FF≤0.70, FF≤0.75, and FF≤0.80 was 0.984, 0.986, and 0.962, respectively. CONCLUSION: Angiography-based FF computed from cerebral angiographic images could be an effective computational tool for evaluating the hemodynamic significance of ICAS.


Subject(s)
Hemodynamics , Intracranial Arteriosclerosis , Humans , Constriction, Pathologic , Retrospective Studies , Angiography, Digital Subtraction , Intracranial Arteriosclerosis/diagnostic imaging
18.
J Neuroradiol ; 51(1): 52-58, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37120144

ABSTRACT

BACKGROUND: The DIRECT-MT trial showed that endovascular thrombectomy (EVT) alone was noninferior to EVT preceded by intravenous alteplase. However, the infusion of intravenous alteplase was uncompleted before the initiation of EVT in most cases of this trial. Therefore, the additional benefit and risk of over 2/3-dose intravenous alteplase pretreatment remain to be assessed. METHODS: We assessed patients with acute anterior circulation ischemic stroke who received EVT alone or with over 2/3-dose intravenous alteplase pretreatment from the DIRECT-MT trial. Patients were assigned to the thrombectomy-alone group and the alteplase pretreatment group. The primary outcome was the distribution of modified Rankin Scale (mRS) at 90 days. The interaction of treatment allocation and collateral capacity was assessed. RESULTS: A total of 393 patients (thrombectomy alone: 315; alteplase pretreatment: 78) were identified. The thrombectomy alone was comparable with alteplase pretreatment prior to the thrombectomy on the distribution of mRS at 90 days without significant effect modification by collateral capacity (adjusted common odds ratio (acOR), 1.12; 95% CI, 0.72-1.74; adjusted P for interaction = 0.83). Successful reperfusion before thrombectomy and the number of passes in the thrombectomy alone group differed significantly from the alteplase pretreatment group (2.6% vs. 11.5%; corrected P = 0.02 and 2 vs. 1; corrected P = 0.003). There was no interaction between treatment allocation and collateral capacity on all outcomes. CONCLUSIONS: EVT alone and EVT preceded by over 2/3-dose intravenous alteplase might have equal efficacy and safety for patients with acute anterior circulation large vessel occlusion, except for successful perfusion before thrombectomy and the number of passes.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Stroke/drug therapy , Stroke/surgery , Brain Ischemia/therapy , Endovascular Procedures/adverse effects , Thrombectomy/adverse effects , Thrombolytic Therapy/adverse effects , Treatment Outcome
19.
Cerebrovasc Dis ; 53(2): 176-183, 2024.
Article in English | MEDLINE | ID: mdl-37598670

ABSTRACT

INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.


Subject(s)
Endovascular Procedures , Ischemic Stroke , Thrombectomy , Humans , Endovascular Procedures/methods , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Thrombectomy/methods , Thrombolytic Therapy/methods , Treatment Outcome , Time Factors
20.
Ann Biomed Eng ; 52(2): 282-291, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38042765

ABSTRACT

Postoperative adhesion is a very common and serious complication that occurs frequently in cardiac surgery. The purpose of this study was to evaluate the efficacy of a fibrin hydrogel layer-anchored decellularized pericardial matrix in preventing pericardial adhesions in a miniature pig model with a myocardial injury. Fibrin hydrogel layer-anchored decellularized pericardial matrix was prepared by spraying a mixture of fibrinogen and thrombin on a fibrinogen-doped decellularized pericardium. Cardiac injury was generated by abrading and desiccating the epicardial surface of a miniature pig to induce severe postoperative adhesions. The adhesion between the epicardial surface and fibrin hydrogel layer-anchored decellularized pericardial matrix in three different regions (left outer, front, and right outer) was evaluated macroscopically one month after surgery. The fibrin hydrogel layer-anchored decellularized pericardial matrix showed significantly less adhesion than an autologous pericardium (0.2 ± 0.7 in DPM-FHG0.5 and 0.4 ± 0.8 in DPM-FHG1, p < 0.01) and expanded polytetrafluoroethylene (ePTFE) (1.6 ± 0.5, p < 0.05). The fibrin hydrogel concentration had no effect on preventing postoperative adhesion. A thinner fibrin hydrogel layer was observed on the decellularized pericardial matrix one month after surgery; however, the inside of the matrix was filled with fibrin hydrogel. Fibrin hydrogel layer-anchored decellularized pericardial matrix prevented postoperative epicardial adhesions in a miniature pig model. Our findings suggest that pericardial closure using a fibrin hydrogel layer-anchored decellularized pericardial matrix is a promising method for preventing adverse outcomes in reoperative surgeries.


Subject(s)
Fibrin , Hydrogels , Animals , Swine , Swine, Miniature , Pericardium , Fibrinogen
SELECTION OF CITATIONS
SEARCH DETAIL
...