Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

Microglia accumulation and activation after subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH) is a severe cerebrovascular disease accounting for a significant portion of young patients with stroke with high morbidity and mortality(van Gijn et al., 2007). Secondary brain injury resulting from neuroinflammation is considered to be a key pathological process(Zheng and Wong, 2017). Microglia, the resident immune cells of the brain, are implicated in numerous neurological diseases, such as Alzheimer's disease。

UNIQUENESS THEOREMS OF L-FUNCTIONS IN THE EXTENDED SELBERG CLASS

We establish uniqueness theorems of L-functions in the extended Selberg class,which show how an L-function and a meromorphic function are uniquely determined by their shared values in two finite sets.This can be seen as a new solution of a problem proposed by Gross.

RSPSSL:A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology.It is also an emerging omics technique for metabolic profiling to shape precision medicine.However,precisely attributing vibration peaks coupled with specific environmental,instrumental,and specimen noise is problematic.Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction.Here,we propose a novel Raman spectral preprocessing scheme based on self-supervised learning(RSPSSL)with high capacity and spectral fidelity.It can preprocess arbitrary Raman spectra without further training at a speed of~1900 spectra per second without human interference.The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88%reduction in root mean square error and a 60%reduction in infinite norm(L__(∞))compared to established techniques.With this advantage,it remarkably enhanced various biomedical applications with a 400%accuracy elevation(ΔAUC)in cancer diagnosis,an average 38%(few-shot)and 242%accuracy improvement in paraquat concentration prediction,and unsealed the chemical resolution of biomedical hyperspectral images,especially in the spectral fingerprint region.It precisely preprocessed various Raman spectra from different spectroscopy devices,laboratories,and diverse applications.This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput,cross-device,various analyte complexity,and diverse applications.

Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

Background and purpose Signal transducer and activator of transcription 3(STAT3)may contribute to the proinflammation in the central nervous system diseases by modulating the microglial responses.Thus,this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage(SAH).Methods The SAH model was established by endovascular perforation in the mouse.Real-time PCR(RtPCR)and western blot were used to examine the dynamic STAT3 signalling pathway responses after SAH.To clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH,the microglia-specific STAT3 knockout(KO)mice were generated by the Cre-LoxP system.The neurological functions were assessed by Catwalk and Morris water maze tests.Neuronal loss after SAH was determined by immunohistochemistry staining.Microglial polarisation status after STAT3 KO was then examined by RtPCR and immunofluorescence.Results The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after SAH.Downstream factors and related mediators altered dynamically and accordingly.Microglial STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after SAH.To investigate the underlying mechanism,we examined the microglial reaction after STAT3 KO.STAT3 deletion reversed the increase of microglia after SAH.Loss of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 polarisation.Functionally,microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early phase.Conclusions STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent neuroinflammation.Microglial STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inflammatory responses after SAH.STAT3 may serve as a promising therapeutic target to alleviate early brain injury after SAH.

Efficient simulation of a low-profile visualized intraluminal support device: a novel fast virtual stenting technique

Background: The low-profile visualized intraluminal support (LVIS) stent has become a promising endovascular option for treating intracranial aneurysms. To achieve better treatment of aneurysms using LVIS, we developed a fast virtual stenting technique for use with LVIS (F-LVIS) to evaluate hemodynamic changes in the aneurysm and validate its reliability. Methods: A patient-specific aneurysm was selected for making comparisons between the real LVIS (R-LVIS) and the F-LVIS. To perform R-LVIS stenting, a hollow phantom based on a patient-specific aneurysm was fabricated using a three-dimensional printer. An R-LVIS was released in the phantom according to standard procedure. F-LVIS was then applied successfully in this aneurysm model. The computational fluid dynamics (CFD) values were calculated for both the F-LVIS and R-LVIS models. Qualitative and quantitative comparisons of the two models focused on hemodynamic parameters. Results: The hemodynamic characteristics for R-LVIS and F-LVIS were well matched. Representative contours of velocities and wall shear stress (WSS) were consistently similar in both distribution and magnitude. The velocity vectors also showed high similarity, although the R-LVIS model showed faster and more fluid streams entering the aneurysm. Variation tendencies of the velocity in the aneurysm and the WSS on the aneurysm wall were also similar in the two models, with no statistically significant differences in either velocity or WSS. Conclusions: The results of the computational hemodynamics indicate that F-LVIS is suitable for evaluating hemodynamic factors. This novel F-LVIS is considered efficient, practical, and effective.