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ObjectiveCarotid artery stenosis, primarily caused by atherosclerosis, is a major risk factor for ischemic stroke. Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are established interventions to reduce stroke risk and restore cerebral blood flow. However, the effect of these treatments on circadian rhythms, and their influence on stroke recovery, remains underexplored. This study aims to assess how disruptions in circadian rhythms—specifically sleep quality and blood pressure variability—impact recovery in patients undergoing CEA or CAS.MethodsWe conducted a prospective study involving 177 patients with carotid artery stenosis, all treated with either CEA or CAS. Patients were followed for 90 days post-treatment, with neurological outcomes evaluated using the NIHSS Stroke Scale (NIHSS). Circadian rhythm-related factors, including sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and blood pressure variability (daytime systolic and nighttime diastolic BP), were assessed pre-and post-treatment. Stepwise regression was used to identify predictors of stroke recovery.ResultsIn a cohort of 177 patients with symptomatic carotid atherosclerotic stenosis, stepwise regression identified post-treatment changes in PSQI, nighttime diastolic blood pressure, and the presence of coronary heart disease as significant independent predictors of poor neurological outcomes (p

With the progress of communication technology, the cost of optical fiber and 5G continues to decrease, and data transmission becomes more convenient and fast, making it possible to realize differential protection of distribution network by various intelligent algorithms using signal waveforms. Aiming at the problem that the traditional relay protection device can not meet the actual demand when the single-phase ground fault occurs in the distribution network with distributed generation, this paper proposes a new differential protection scheme. The characteristic mode decomposition improved by the whale optimization algorithm is used to decompose the zero-sequence current waveform collected at both ends of the line. Based on the basic principle of current differential protection, the derivative dynamic time warping of the component with the largest fault feature can effectively solve the problem that the grounding current of the distribution network cannot meet the working requirements of the differential protection device, and ensure the safe and stable operation of the system. Finally, based on MATLAB software, the performance of this method is comprehensively evaluated by simulating different fault conditions, so as to ensure the feasibility and accuracy of this method in the case of diversified faults when the distributed generation is used as part of the power supply.

Abstract Oncolytic viruses (OVs) represent a new class of multi-modal immunotherapies for cancer, with OV-elicited antitumor immunity being key to their overall therapeutic efficacy. Currently, the clinical effectiveness of OV as monotherapy remains limited, and thus investigators have been exploring various combinations with other anti-cancer agents and demonstrated improved therapeutic efficacy. As cancer cells have evolved to alter key signaling pathways for enhanced cell proliferation, cancer progression and metastasis, these cellular and molecular changes offer promising targets for rational cancer therapy design. In this regard, key molecules in relevant signaling pathways for cancer cells or/and immune cells, such as EGFR-KRAS (e.g., KRASG12C), PI3K-AKT-mTOR, ERK-MEK, JAK-STAT, p53, PD-1-PD-L1, and epigenetic, or immune pathways (e.g., histone deacetylases, cGAS-STING) are currently under investigation and have the potential to synergize with OV to modulate the immune milieu of the tumor microenvironment (TME), thereby improving and sustaining antitumor immunity. As many small molecule modulators of these signaling pathways have been developed and have shown strong therapeutic potential, here we review key findings related to both OV-mediated immunotherapy and the utility of small molecule modulators of signaling pathways in immuno-oncology. Then, we focus on discussion of the rationales and potential strategies for combining OV with selected modulators targeting key cellular signaling pathways in cancer or/and immune cells to modulate the TME and enhance antitumor immunity and therapeutic efficacy. Finally, we provide perspectives and viewpoints on the application of novel experimental systems and technologies that can propel this exciting branch of medicine into a bright future.

In response to the deformation resistance deficiency and poor toughness characteristics of soil after microbial curing, a combination of fibre reinforcement technology and microbial curing technology was used to conduct microbial curing tests using basalt fibres and denitrifying bacteria. In this paper, the effects of fibre on the strength and toughness of soil consolidation were analysed by unconfined compressive strength test and direct shear test, and the stability of reinforced slope was analysed by numerical simulation. The results show the following. (1) Basalt fibre can effectively improve the characteristics of brittle damage of microbially consolidated soil while increasing the compressive and shear strength. (2) Fibre dosing and fibre length have important effects on the mechanical properties of microbially consolidated soil. (3) The appropriate amount of basalt fibre can promote the generation of calcium carbonate. (4) The plastic strain area of the slope decreases after microbial reinforcement and the maximum equivalent plastic stress decreases by 65 kPa.

The COVID-19 outbreak has been a public health crisis of international concern, causing huge impact on people’s lives. As an important part of social public crisis management, how to quickly and effectively raise resources to participate in emergency relief in the era of self-media is a common challenge faced by global charitable organizations. This article attempts to use empirical evidence from Tencent charitable crowdfunding platform, the largest charitable crowdfunding platform in China, to answer this question. We consider 205 COVID-19 charitable projects and 11,177,249 donors to assess the process by which non-profit organizations raise funds through the information about project descriptions. Based on the effects of information and emotional framing, we explore the effects of the readability (i.e., complexity and understandability) and negative tone of the project description on fundraising amount. We then investigate the mediating role of forwarding times, as affective response to the text might explain forwarding times, which in turn affects money raised by increasing the visibility of the campaign. On this basis, the moderating role of recipient’s crisis involvement is tested during this process. The empirical results indicate that the complexity of the description will reduce the fundraising amount, while understandability and negative tone help to improve it. Furthermore, we found that forwarding times played an important mediating role in this process. Then the buffer effect of crisis involvement on the negative effect of complexity was validated, and its amplification on the positive effects of understandability was also verified.

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas.Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association.Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III.Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs.

Abstract Background Treatment of giant basilar aneurysms is extremely challenging, especially recurrences after previous coiling. Case presentation A 20-year-old male was referred for a recurrent giant proximal basilar aneurysm 3 months after coiling, with headache, blurred vision, and brainstem compression symptoms. Angiography showed that the previously placed coils were compacted within the caudal portion of the 43 mm × 31 mm aneurysm, with spontaneous occlusion of the right vertebral artery and absence of the posterior communicating arteries. The diameter of the aneurismal neck, the afferent and efferent arteries was 6 mm, 3.5 mm and 4.1 mm, respectively. A balloon-expandable covered-stent of 3.5 mm × 10 mm was selected, matching the above 3 measurements; and deployed precisely across the aneurismal neck, immediately creating the “sub-complete reconstruction with intentional endoleak distal to aneurismal neck”. Subsequently, 2 self-expanding 4.5 mm × 37 mm stents were telescopically implanted within the covered-stent to adjust the angulation of the proximal basilar artery. After the procedure, the patient’s symptoms gradually disappeared. Catheter angiography at 18 days, 3 months and 15 months demonstrated complete aneurismal exclusion from the patent vertebrobasilar artery, with dramatic elimination of aneurismal volume and reconfiguration of the compacted coils. The patient was asymptomatic at 15-month follow-up. Conclusions Sub-complete reconstruction with intentional endoleak distal to aneurismal neck can be safely achieved after implantation of a covered-stent and conventional stents in the case of a recurrent post-coiling proximal giant basilar aneurysm, with complete vascular reconstruction subsequently.

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.

Constructing vascular scaffolds is important in tissue engineering. However, scaffolds with characteristics such as multiple layers and a certain degree of spatial morphology still cannot be readily constructed by current vascular scaffolds fabrication techniques. This paper presents a three-layered bifurcated vascular scaffold with a curved structure. The technique combines 3D printed molds and casting hydrogel and fugitive ink to create vessel-mimicking constructs with customizable structural parameters. Compared with other fabrication methods, the technique can create more native-like 3D geometries. The diameter and wall thickness of the fabricated constructs can be independently controlled, providing a feasible approach for vascular scaffold construction. Enzymatically-crosslinked gelatin was used as the scaffold material. The morphology and mechanical properties were evaluated. Human umbilical cord derived endothelial cells (HUVECs) were seeded on the scaffolds and cultured for 72 h. Cell viability and morphology were assessed. The results showed that the proposed process had good application potentials, and will hopefully provide a feasible approach for constructing vascular scaffolds.

Constructing tissue engineered vascular grafts (TEVG) is of great significance for cardiovascular research. However, most of the fabrication techniques are unable to construct TEVG with a bifurcated and curved structure. This paper presents multilayered biodegradable TEVGs with a curved structure and multi-branches. The technique combined 3D printed molds and casting hydrogel and sacrificial material to create vessel-mimicking constructs with customizable structural parameters. Compared with other fabrication methods, the proposed technique can create more native-like 3D geometries. The diameter and wall thickness of the fabricated constructs can be independently controlled, providing a feasible approach for TEVG construction. Enzymatically-crosslinked gelatin was used as the material of the constructs. The mechanical properties and thermostability of the constructs were evaluated. Fluid-structure interaction simulations were conducted to examine the displacement of the construct’s wall when blood flows through it. Human umbilical vein endothelial cells (HUVECs) were seeded on the inner channel of the constructs and cultured for 72 h. The cell morphology was assessed. The results showed that the proposed technique had good application potentials, and will hopefully provide a novel technological approach for constructing integrated vasculature for tissue engineering.

The extended time window and theoretic reduction in hemorrhage make mechanical strategies an attractive approach for the treatment of patients with ischemic stroke. However, a limited availability of suitable animal models of cerebrovascular thrombosis has hampered the study of novel endovascular interventions. The aim of the present study was to develop a new technique for site-specific placement of a thrombus in a canine model that would allow for the evaluation of mechanical thrombectomy and clot retrieval methods and the visualization of thrombus dislocation or fragmentation during angiographic manipulation.Angiography and embolization with a preformed thrombus were performed in 12 canines. Under fluoroscopic guidance, an embolism protection device (EPD) was anchored to the middle segment of the left vertebral artery (VA) via the left femoral arterial sheath. A preformed radiopaque clot was injected through the guide catheter into the left VA, via the contralateral femoral artery, proximal to the EPD. After 15 min of occlusion, the EPD was removed and persistent occlusion of the VA was documented angiographically.Angiography performed during the observation period confirmed the persistence of VA occlusion in each case, and displacement of the radiopaque clots did not occur during the 3-hour observation period. The technique allowed selective embolization of targeted vessels without thrombus fragmentation.This study demonstrates, for the first time, a canine model of post-circulation embolism induced by autologous blood clot placement. This model can be rapidly formed and easily operated, and the site of thrombosis can be readily controlled.

As a special class of short non-coding RNAs, microRNAs (a.k.a. miRNAs or miRs) have been reported to perform important roles in various biological processes by regulating respective target genes. However, significant barriers exist during biologists' conventional miR knowledge discovery. Emerging semantic technologies, which are based upon domain ontologies, can render critical assistance to this problem. Our previous research has investigated the construction of a miR ontology, named Ontology for MIcroRNA Target Prediction (OMIT), the very first of its kind that formally encodes miR domain knowledge. Although it is unavoidable to have a manual component contributed by domain experts when building ontologies, many challenges have been identified for a completely manual development process. The most significant issue is that a manual development process is very labor-intensive and thus extremely expensive. Therefore, we propose in this paper an innovative ontology development methodology. Our contributions can be summarized as: (i) We have continued the development and critical improvement of OMIT, solidly based on our previous research outcomes. (ii) We have explored effective and efficient algorithms with which the ontology development can be seamlessly combined with machine intelligence and be accomplished in a semi-automated manner, thus significantly reducing large amounts of human efforts. A set of experiments have been conducted to thoroughly evaluate our proposed methodology.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways. [ABSTRACT FROM AUTHOR]

Under the background of the shortage of traditional energy and the increasingly serious environmental problems, this paper proposes a bi-level optimization configuration method for microgrids based on stepped carbon trading and price-based demand response. The stepped carbon trading mechanism is introduced into the planning model to clarify the impact of construction processes on land carbon emissions. Simultaneously, price-based demand response during system operation is introduced, guiding users to change the electricity consumption strategies to promote the consumption of renewable energy. Then, a bi-level optimal configuration framework is constructed. The upper level is optimized to allocate the capacity of the microgrid, with the lowest annual equivalent comprehensive cost as the objective function. The lower level is optimized for microgrid operation, with the minimum sum of the microgrid operation cost and carbon emission cost as the objective function. In view of the advantages of enhanced whale optimization algorithm (E-WOA) in solving multidimensional feature selection problems, E-WOA and CPLEX solver are combined to solve the bi-level optimization model for the first time. Simulation results show that after introducing a stepped carbon trading mechanism, the system carbon emissions decreased by 23.09%. Considering price-based demand response under the premise of introducing a stepped carbon trading mechanism, the total cost decreased by 3.57% and the carbon emissions decreased by 19.83%. [ABSTRACT FROM AUTHOR]

Background: We describe use of a canine model to evaluate physiological effects and neuroprotective strategies in the setting of cerebral ischemia and endovascular neurosurgery training. Methods: We performed transfemoral digital subtraction cerebral and cervical angiography on eight anesthetized dogs. Angiographic images of cerebral arteries were obtained following cannulation of the femoral artery. Cerebral ischemia models were made after angiography. Results: The canine cerebral vasculature exhibited extensive tortuosity of the carotid and vertebral arteries. Conversely, the bilateral anterior spinal arteries were easily catheterized using microcatheters and microguidewires. The basilar artery and its branches were facilely cannulable. Circle of Willis continuity sans hypoplasia or aplasia of its constitutive segments was appreciated in all animals. The middle cerebral arteries could be easily accessed via the posterior communicating arteries. We generated an empirically evaluable therapeutically interventional experimental animal model of cerebral ischemia by occluding the middle cerebral artery using small coils for a duration between 15 and 60 min. Conclusion: Unique amenability of the canine intracranial vasculature to selective and microcatheter cannulation renders experimentally induced cerebral, cerebellar, and brainstem via occlusion of the supratentorial and infratentorial arteries a simple matter. The neural vasculature irrigating the canine cerebrum, brainstem, and cerebellum may consequently prove useful in helping young and nascent endovascular neurosurgeons in developing and refining their skills of microcatheter navigation and manipulation and deployment of therapeutic devices to achieve effective occlusion of aneurysms, arteriovenous malformations, arteriovenous fistulas, and neoplasms of the intracranial cavity. [ABSTRACT FROM AUTHOR]

Objective To evaluate the recanalization efficacy and safety of a novel stent retriever in a swine model of acute arterial occlusion. Methods The JRecan thrombectomy device, a stent retriever with a weaving stent design, was evaluated in 18 occluded cervicocerebral vessels of swine. The flow restoration effect immediately upon deployment, the reperfusion rate after retrieval, thromboembolic events, and complications were assessed. The histologic structure of the renal arteries after retriever passage was measured to further assess the safety of JRecan. Results Immediate flow restoration was achieved in 66.7% of occlusions (12/18). The reperfusion rate was 94.4% (two Thrombolysis in Cerebral Infarction (TICI) 2b and 15 TICI 3). Distal thromboembolic events did not occur. Microscopic examination of the arteries after retrieval showed mild degrees of endothelial loss in 96.6% (29/30), fibrin or platelet deposition in 53.3% (16/30), and disruption of the internal elastic lamina in 10% (3/30), without severe pathologic lesions. Conclusions The JRecan is highly effective at clot removal with a favorable safety profile and merits further development as a stent retriever for the treatment of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background Neural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown. Results We ablated ILK specifically in neural crest by Wnt1-Cre. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of Ncam and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced TGFß2 but increased BMP signaling. Consistent with these observations, microarray analysis of FACS sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis. Conclusions Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell-matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants. [ABSTRACT FROM AUTHOR]

Not uncommonly, differentiating multiple sclerosis (MS) from ischemic cerebral vascular disease is difficult based on conventional magnetic resonance imaging (MRI). We aim to determine whether preferential occult injury in the normal-appearing corpus callosum (NACC) is more severe in patients with MS than symptomatic carotid occlusion by comparing fractional anisotropy (FA) from diffusion tensor imaging (DTI). Eighteen patients (eight men, ten women; mean age, 38.6 years) with MS and 32 patients (24 men, eight women; mean age, 64.0 years) with symptomatic unilateral internal carotid occlusion were included. DTI (1.5 T) were performed at corpus callosum which were normal-appearing on fluid-attenuated inversion recovery MRI. Mean FA was obtained from the genu, anterior body, posterior body, and splenium of NACC. Independent-sample t test statistical analysis was performed. The FA values in various regions of NACC were lower in the MS patients than symptomatic carotid occlusion patients, which was statistically different at the anterior body (0.67 ± 0.12 vs 0.74 ± 0.06, P = 0.009), but not at genu, posterior body, and splenium (0.63 ± 0.09 vs 0.67 ± 0.07, P = 0.13; 0.68 ± 0.09 vs 0.73 ± 0.05, P = 0.07; 0.72 ± 0.09 vs 0.76 ± 0.05, P = 0.13). MS patients have lower FA in the anterior body of NACC compared to patients with symptomatic carotid occlusion. It suggests that DTI has potential ability to differentiate these two conditions due to the more severe preferential occult injury at the anterior body of NACC in MS. [ABSTRACT FROM AUTHOR]

The Brillouin equations with strong nonlinearity are solved using a perturbation technique. The calculated results agree quite well with the published experimental results [1, 2]. In addition some new conclusions are obtained from our analysis. [ABSTRACT FROM AUTHOR]

The article focuses on endovascular middle cerebral arterial occlusion in a chronic cerebral ischemia model. For this study, endovascular intervention was used in order to establish cerebral infarction models in rhesus monkeys. Pronounced paralysis at the acute phase and long-term upper extremity dysfunction at the chronic phase were observed. This study found that there is a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion.

Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulation of the protein phosphatase PP2A-B55β. PP2A-B55β targets the N- and C-terminal phosphodegrons of cyclin E1 for dephosphorylation, thus protecting it from degradation mediated by the SCFFbxw7 ubiquitin ligase. Augmented B55b expression stabilizes cyclin E1 and promotes its overexpression in cancer-derived cell lines and breast tumors. Conversely, B55β ablation enforces the degradation of cyclin E1 and inhibits cancer cell proliferation in vitro and tumor formation in vivo. Therefore, PP2A-B55β promotes cyclin E1 overexpression by antagonizing its degradation and its inhibition could represent a therapeutic mechanism for abrogating cyclin E1 function in cancers. [ABSTRACT FROM AUTHOR]