Heme oxygenase-1 alleviates allergic airway inflammation by suppressing NF-κB-mediated pyroptosis of bronchial epithelial cells.

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase-1 (HO-1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO-1-mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)-induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO-1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO-1 restrained GSDMD-mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor-Kappa B (NF-κB) p65 RHD domain and thus controlling NF-κB-dependent pyroptosis. These data provide new therapeutic indications for purposing HO-1 to counteract inflammation, which contributes to allergic inflammation control.

Coupled Poly(ethylenimine) Coreactant to Enhance Electrochemiluminescence of Polymer Dots for Array Imaging of Protein Biomarkers.

Traditional electrochemiluminescent (ECL) bioanalysis suffers from the demand for excessive external coreactants and the damage of reaction intermediates. In this work, a poly(ethylenimine) (PEI)-coupled ECL emitter was proposed by covalently coupling tertiary amine-rich PEI to polymer dots (Pdots). The coupled PEI might act as a highly efficient coreactant to enhance the ECL emission of Pdots through intramolecular electron transfer, reducing the electron transfer distance between emitter and coreactant intermediates and avoiding the disadvantages of traditional ECL systems. Through modification of the PEI-Pdots with tDNA, a sequence partially complementary to cDNA that was complementary to the aptamer of target protein biomarker (aDNA), tDNA-PEI-Pdots were obtained. The biosensors were produced using Au/indium tin oxide (ITO) with an aDNA/cDNA hybrid, and an ECL imaging biosensor array was constructed for ultrasensitive detection of protein biomarkers. Using vascular endothelial growth factor 165 (VEGF165) as a protein model, the proposed ECL imaging method containing two simple incubations with target samples and then tDNA-PEI-Pdots showed a detectable range of 1 pg mL-1 to 100 ng mL-1 and a detection limit of 0.71 pg mL-1, as well as excellent performance such as low toxicity, high sensitivity, excellent selectivity, good accuracy, and acceptable fabrication reproducibility. The PEI-coupled Pdots provide a new avenue for the design of ECL emitters and the application of ECL imaging in disease biomarker detection.

Adaptive imaging through dense dynamic scattering media using transfer learning.

Imaging through scattering media is a long-standing challenge in optical imaging, holding substantial importance in fields like biology, transportation, and remote sensing. Recent advancements in learning-based methods allow accurate and rapid imaging through optically thick scattering media. However, the practical application of data-driven deep learning faces substantial hurdles due to its inherent limitations in generalization, especially in scenarios such as imaging through highly non-static scattering media. Here we utilize the concept of transfer learning toward adaptive imaging through dense dynamic scattering media. Our approach specifically involves using a known segment of the imaging target to fine-tune the pre-trained de-scattering model. Since the training data of downstream tasks used for transfer learning can be acquired simultaneously with the current test data, our method can achieve clear imaging under varying scattering conditions. Experiment results show that the proposed approach (with transfer learning) is capable of providing more than 5dB improvements when optical thickness varies from 11.6 to 13.1 compared with the conventional deep learning approach (without transfer learning). Our method holds promise for applications in video surveillance and beacon guidance under dense dynamic scattering conditions.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Mechanism of scutellarin inhibition of astrocyte activation to type A1 after ischemic stroke.

OBJECTIVE: The aim of this study was to investigate the effects of scutellarin on the activation of astrocytes into the A1 type following cerebral ischemia and to explore the underlying mechanism. METHODS: In vivo, a mouse middle cerebral artery wire embolism model was established to observe the regulation of astrocyte activation to A1 type by scutellarin, and the effects on neurological function and brain infarct volume. In vitro, primary astrocytes were cultured to establish an oxygen-glucose deprivation model, and the mRNA and protein expression of C3, a specific marker of A1-type astrocytes pretreated with scutellarin, were examined. The neurons were cultured in vitro to detect the toxic effects of ischemia-hypoxia-activated A1 astrocyte secretion products on neurons, and to observe whether scutellarin could reduce the neurotoxicity of A1 astrocytes. To validate the signaling pathway-related proteins regulated by scutellarin on C3 expression in astrocytes. RESULTS: The results showed that scutellarin treatment reduced the volume of cerebral infarcts and attenuated neurological deficits in mice caused by middle cerebral artery embolism. Immunofluorescence and Western blot showed that treatment with scutellarin down-regulated middle cerebral artery embolism and OGD/R up-regulated A1-type astrocyte marker C3. The secretory products of ischemia-hypoxia-activated A1-type astrocytes were toxic to neurons and induced an increase in neuronal apoptosis, and astrocytes treated with scutellarin reduced the toxic effects on neurons. Further study revealed that scutellarin inhibited the activation of NF-κB signaling pathway and thus inhibited the activation of astrocytes to A1 type.

A Practical Method for Synthesizing Iptacopan.

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.

Engineered ATG8-binding motif-based selective autophagy to degrade proteins and organelles in planta.

Protein-targeting technologies represent essential approaches in biological research. Protein knockdown tools developed recently in mammalian cells by exploiting natural degradation mechanisms allow for precise determination of protein function and discovery of degrader-type drugs. However, no method to directly target endogenous proteins for degradation is currently available in plants. Here, we describe a novel method for targeted protein clearance by engineering an autophagy receptor with a binder to provide target specificity and an ATG8-binding motif (AIM) to link the targets to nascent autophagosomes, thus harnessing the autophagy machinery for degradation. We demonstrate its specificity and broad potentials by degrading various fluorescence-tagged proteins, including cytosolic mCherry, the nucleus-localized bZIP transcription factor TGA5, and the plasma membrane-anchored brassinosteroid receptor BRI1, as well as fluorescence-coated peroxisomes, using a tobacco-based transient expression system. Stable expression of AIM-based autophagy receptors in Arabidopsis further confirms the feasibility of this approach in selective autophagy of endogenous proteins. With its wide substrate scope and its specificity, our concept of engineered AIM-based selective autophagy could provide a convenient and robust research tool for manipulating endogenous proteins in plants and may open an avenue toward degradation of cytoplasmic components other than proteins in plant research.

DeepSCI: scalable speckle correlation imaging using physics-enhanced deep learning.

In this Letter we present a physics-enhanced deep learning approach for speckle correlation imaging (SCI), i.e., DeepSCI. DeepSCI incorporates the theoretical model of SCI into both the training and test stages of a neural network to achieve interpretable data preprocessing and model-driven fine-tuning, allowing the full use of data and physics priors. It can accurately reconstruct the image from the speckle pattern and is highly scalable to both medium perturbations and domain shifts. Our experimental results demonstrate the suitability and effectiveness of DeepSCI for solving the problem of limited generalization generally encountered in data-driven approaches.

Prognostic Implication of Pulmonary Arterial Pressure in Surgical Repair of Predominantly Congenital Mitral Valve Regurgitation-Based Intracardiac Abnormalities.

INTRODUCTION: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. METHODS: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. RESULTS: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively. CONCLUSIONS: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP.

Assessment of association between the carotid web and dissection in spontaneous internal carotid artery dissection patients using vessel wall MRI.

BACKGROUND: Internal carotid artery dissection (ICAD) is the major cause of ischemic stroke in young to middle-aged people. Recognition of predisposing factors may facilitate in early individual risk prediction and expand treatment. PURPOSE: To evaluate the association between a carotid web and dissection in patients with ICAD using vessel wall magnetic resonance imaging (VW-MRI). MATERIAL AND METHODS: A retrospective study was conducted of 223 patients who underwent VW-MRI. Of these patients, 58 patients with craniocervical artery dissection (CCAD) (33 ICAD and 25 vertebrobasilar artery dissection [VBAD]) were included. The control group (n = 165) consisted of patients without arterial dissection who had undergone VW-MRI . The presence of a carotid web in the posterior aspect of carotid bulb was recorded. The distance between the carotid web and start of dissection in ICA was recorded. RESULTS: The presence of a carotid web showed a significant difference between the ICAD, VBAD, and control groups (19 [57.6%] vs. 5 [20%] vs. 36 [21.8%], respectively; P < 0.001). In multi-nominal analysis, the presence of a carotid web showed a significant difference between the ICAD and VBAD groups and the ICAD and control groups (P < 0.05), with odds ratios of 5.41 (95% confidence interval [CI]=1.634-17.973) and 4.81 (95% CI=2.176-10.651), respectively. Out of 19 ICAD patients with carotid web, 16 had occurrence of dissection in the C1 segment of the ICA with a mean distance of 1.91 ± 1.71 cm from the carotid web. CONCLUSION: Presence of a carotid web was more frequent in patients with ICAD. The carotid web may be one of the predisposing factors for development of dissection in patients with ICAD.

Does the Message Frame Promote People's Willingness to Vaccinate when they Worry about Side Effects from the COVID-19 Vaccine? Evidence from an Online Survey Experiment in China.

Vaccination is an effective strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. However, worrying about side effects (WSE) from the COVID-19 vaccine is the leading concern making people hesitant to get vaccinated. Regrettably, there are few studies on alleviating the negative impacts of WSE on COVID-19 vaccination. This study aimed to assess whether message framing (gain- and loss-framed) can moderate the impacts of WSE on the willingness to vaccinate. We conducted an online self-administered survey experiment with three groups: control group (non-framed group), gain-framed groups, and loss-framed groups. In total, 981 participants were randomly assigned to one of the three groups, and their willingness to vaccinate themselves, their children, and elderly members was recorded. People with a higher level of WSE exhibited a lower willingness to vaccinate against COVID-19. However, the gain- and loss-framed messages increased people's willingness to vaccinate themselves, their children, and the elderly. Compared to the gain-framed messages, the loss-framed messages had a greater impact on enhancing people's willingness to self-vaccinate, but not on vaccinating their children and the elderly. Although the gain- and loss-framed messages weakened the negative impacts of WSE on the willingness to be vaccinated, their buffer effect was non-significantly different. The findings in this study suggest that a loss-framed messaging strategy could be a valuable tool in disseminating information on vaccination against COVID-19.

Hypotension from afatinib in epidermal growth factor receptor-mutated non-small cell lung cancer: a case report and literature review.

Side effects of afatinib are a problem in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the occurrence of afatinib-induced hypotension. An 81-year-old man with NSCLC had an epidermal growth factor receptor-positive genotype with the p.L861Q mutation in exon 21. He was administered afatinib (40 mg/day) as anticancer therapy. Hypotension occurred twice after afatinib initiation. He suffered from dizziness and nausea. Blood pressure gradually returned to normal after afatinib cessation. Clinicians should be aware of hypotension in patients with NSCLC after afatinib initiation.

What Strategy Is Better for Promoting COVID-19 Vaccination? A Comparison Between Gain-Framed, Loss-Framed, and Altruistic Messages.

BACKGROUND/OBJECTIVE: Vaccination is an efficient public health strategy for controlling infectious diseases like the COVID-19 pandemic. Therefore, this study evaluates the effect of gain-framed, loss-framed, and altruism messages on willingness to get a COVID-19 vaccine and confirms the best strategy for promoting vaccination. METHODS: Herein, we designed an online survey experiment, including a control (exposure to non-framed information) and three experimental (exposure to gain-framed, loss-framed, or altruistic messages) groups, to assess the vaccination willingness. All participants (n = 1316) were randomly assigned into one of the four groups. RESULTS: The individuals exposed to gain-framed, loss-framed, or altruism messages exhibited a higher willingness to get a COVID-19 vaccine than those exposed to non-framed information. Moreover, the loss-framed information effect on vaccination willingness was more substantial than the other two messages. However, no significant difference was observed between the gain-framed and altruism messages. CONCLUSION: This study suggests that a loss-framed information dissemination strategy could be preferable to motivate vaccination willingness against COVID-19.

The intrinsic relevance of nitrogen removal pathway to varying nitrate loading rate in a polycaprolactone-supported denitrification system.

Up to date, the intrinsic association of nitrate loading rate (NLR) with treatment performance of solid-phase denitrification (SPD) systems is still ambiguous. To address this issue, three continuous up-flow bioreactors were configured. They were packed with polycaprolactone (PCL) under a filling ratio of 30%, 60% or 90% and were operated under a varying NLR of 0.34 ± 0.01-3.99 ± 0.12 gN/(L·d). Results showed that the denitrification efficiency was high (RE > 96%) and stable except the case with the highest NLR, which was mainly attributed to the lack of available carbon sources. At the phylum or genus level, most of the detected dominant bacterial taxa were either associated with organics degradation or nitrogen metabolism. The difference in bacterial community structure among the three stages was mainly caused by NLR rather than the filling ratio. Moreover, as the NLR got higher, the Bray-Curtis distance between samples from the same stage became shorter. By the results of gene or enzyme prediction performed in PICRUSt2, the main nitrogen metabolism pathways in these reactors were denitrification, dissimilatory nitrate reduction to ammonium (DNRA), assimilatory nitrate reduction to ammonium (ANRA) and nitrogen fixation. Moreover, aerobic and anaerobic nitrate dissimilation coexisted in the systems with the latter playing a dominant role. Finally, denitrification and DNRA occurred under both high and low NLR conditions while nitrogen fixation and ANRA preferred to occur under low NLR environments. These findings might help guide practical applications.

Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model.

Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin (PTx), a G-protein blocker, is known to suppress intracellular calcium accumulation. We hypothesize that PTx can protect against stroke by blocking calcium influx. In a permanent middle cerebral artery occlusion model, PTx (1000 ng) was given intraperitoneally 30 min after inducing stroke. Magnetic Resonance Imaging of perfusion and T2-weighted brain scans were obtained to evaluate cerebral blood flow (CBF) and infarct volume. Primary neuronal culture was used to test glutamate induced excitotoxicity and calcium influx. We established a non-linear exponential curve model to minimize variations in animal cerebrovasculature. A reduction of 40-60% in relative CBF was a critical window where infarct volume started to increase as rCBF reduced. PTx showed maximal effects in reducing infarct volume at this window. In vitro studies further demonstrated PTx increased neuronal cell survival by decreasing glutamate-induced calcium influx into neurons and preventing neurons from apoptosis. PTx salvages the ischemic penumbra by blocking calcium influx. This provides us a new mechanism upon which experimental therapies can be explored to treat ischemic stroke. In ischemic stroke, excessive glutamate binds to AMPA receptor that depolarizes calcium channel and/ or NMDA receptor. Both of them allow calcium to enter the cell. The overload of calcium triggers cellular cascade that includes Caspase activation and release, leading to pre-mature cell death. We have demonstrated that PTx, a G-protein inhibitor, blocks calcium entry which in turn prevents further cellular damage.

Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic interstitial lung disease with poor survival. Previous reports suggested the contributory effect of receptor for advanced glycation end products (RAGE) to the pathogenesis of IPF. But the findings are controversial. The present in vivo study with RAGE null mice, we further confirmed the evidence that lack of RAGE evolves worse bleomycin-induced pulmonary fibrosis compared with control mice. Moreover, RAGE null mice spontaneously developed similar pathogenesis of lung fibrosis via immunohistochemical staining. In addition, we investigated the negative roles of RAGE on epithelial-mesenchymal transition (EMT) indicated by elevated α-smooth muscle actin (α-SMA) and collagen-I (Col-I) deposition in A549 cell treated with transforming growth factor-ß (TGF-ß), all of which were blocked by sRAGE, a decoy receptor. Furthermore, interacting with the specific ligand as AGE, RAGE blocked TGF-ß-induced activation of Smad2, ERK and JNK signals in A549 cells, which were also challenged by sRAGE administration. This present study confirmed an important role of RAGE in vivo and vitro models of pulmonary fibrosis and suggested the therapeutic possibility for pulmonary fibrosis via RAGE regulation.

CX3CR1 deficiency suppresses activation and neurotoxicity of microglia/macrophage in experimental ischemic stroke.

BACKGROUND: Chemokine (C-X3-C motif) ligand 1 (CX3CL1)/ CX3C chemokine receptor 1 (CX3CR1) signaling is important in modulating the communication between neurons and resident microglia/migrated macrophages in the central nervous system (CNS). Although CX3CR1 deficiency is associated with an improved outcome following ischemic brain injury, the mechanism of this observation is largely unknown. The aim of this study was to investigate how CX3CR1 deficiency influences microglia/macrophage functions in the context of its protection following brain ischemia. METHODS: Wild-type (WT) and CX3CR1-deficient (CX3CR1⁻/⁻) mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion. The ischemic brain damage was monitored by rodent high-field magnetic resonance imaging. Neurological deficit was assessed daily. Neuronal apoptotic death and reactive oxygen species (ROS) production were analyzed by immunostaining and live imaging. Activation/inflammatory response of microglia/macrophage were assessed using immunohistochemistry, flow cytometry, 5-bromo-2-deoxyuridine labeling, cytokine ELISA, and real-time PCR. RESULTS: CX3CR1⁻/⁻ mice displayed significantly smaller infarcts and less severe neurological deficits compared to WT controls, following MCAO. In addition, CX3CR1⁻/⁻ MCAO mice displayed fewer apoptotic neurons and reduced ROS levels. Impaired CX3CR1 signaling abrogated the recruitment of monocyte-derived macrophages from the periphery, suppressed the proliferation of CNS microglia and infiltrated macrophage, facilitated the alternative activation (M2 state) of microglia/macrophages, and attenuated their ability to synthesize and release inflammatory cytokines. CONCLUSION: Our results suggest that inhibition of CX3CR1 signaling could function as a therapeutic modality in ischemic brain injury, by reducing recruitment of peripheral macrophages and expansion/activation of CNS microglia and macrophages, resulting in protection of neurological function.

The design and implementation of postprocessing for depth map on real-time extraction system.

Depth estimation becomes the key technology to resolve the communications of the stereo vision. We can get the real-time depth map based on hardware, which cannot implement complicated algorithm as software, because there are some restrictions in the hardware structure. Eventually, some wrong stereo matching will inevitably exist in the process of depth estimation by hardware, such as FPGA. In order to solve the problem a postprocessing function is designed in this paper. After matching cost unique test, the both left-right and right-left consistency check solutions are implemented, respectively; then, the cavities in depth maps can be filled by right depth values on the basis of right-left consistency check solution. The results in the experiments have shown that the depth map extraction and postprocessing function can be implemented in real time in the same system; what is more, the quality of the depth maps is satisfactory.

Long-term outcomes of trapping vertebral artery-posterior inferior cerebellar artery dissecting aneurysms after revascularization.

OBJECTIVE: This study is designed to evaluate the long-term outcome of trapping vertebral artery-posterior inferior cerebellar artery (VA-PICA) dissecting aneurysms after revascularization. MATERIALS AND METHODS: Five patients with VA-PICA dissecting aneurysms were treated surgically between 2007 and 2010. All the aneurysms were trapped through a far-lateral approach after revascularization of the PICAs by occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. All patients were scheduled for clinical follow-up in the out-patient department at 3 months, 6 months, then annually. Computed tomography (CT) scan and CT angiography, or magnetic resonance (MR) imaging and MR angiography were performed to assess the anastomosis and cerebral blood supply. RESULTS: Among the five patients, two of them did not have any neurological deficit after surgery, the other three had post-operative lower cranial nerve palsy but recovered completely within 6 months. Post-operative cerebral angiography (received by two patients) and CT angiography (received by the other three patients) showed patent bypasses in all patients and there was no reappearance of the aneurysms. After following-up from 47 to 74 months (61 month is the median follow-up period), all patients showed excellent outcomes. CONCLUSION: Trapping the aneurysms after revascularization of PICAs by OA-PICA bypass is a safe method to treat the VA-PICA dissecting aneurysms.

CX3CR1 mediates motor dysfunction in mice through 5-HTR2a.

CX3CR1 knockout could induce motor dysfunction in several neurological disease models mainly through regulating microglia's function. While CX3CR1 was expressed on neurons in a few reports, whether neuronal CX3CR1 could affect the function of neurons and mediate motor dysfunction under physiological conditions is unknown. To elucidate the roles of neuronal CX3CR1 on motor dysfunction, CX3CR1 knockout mice were created. Rotarod test and Open field test found that the CX3CR1-/- mice's motor capacity was reduced. Immunofluorescence staining detected the expression of CX3CR1 in neurons both in vivo and in vitro. Immunohistochemistry and West blot found that knockout of CX3CR1 did not affect the neurons' number in both spinal cord and brain of mice. While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function. Further investigation revealed that CX3CR1 regulated the expression of HTR2a through the NF-κB pathway. For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction.