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Virtual reality (VR) technology has experienced a steady rise and has been widely applied in the field of rehabilitation. The integration of VR technology in rehabilitation has shown promising results in enhancing their motivation for treatment, thereby enabling patients to actively engage in rehab training. Despite the advancement, there is a dearth of comprehensive summary and analysis on the use of VR technology to enhance patient motivation in rehabilitation. Thus, this narrative review aims to evaluate the potential of VR technology in enhancing patient motivation during motor rehabilitation training. This review commences with an explanation of how enhancing motivation through the VR rehabilitation system could improve the efficiency and effectiveness of rehabilitation training. Then, the technology was analyzed to improve patient motivation in the present VR rehabilitation system in detail. Furthermore, these technologies are classified and summarized to provide a comprehensive overview of the state-of-the-art approaches for enhancing patient motivation in VR rehabilitation. Findings showed VR rehabilitation training utilizes game-like exercises to enhance the engagement and enjoyment of rehabilitation training. By immersing patients in a simulated environment with multisensory feedback, VR systems offer a unique approach to rehabilitation that can lead to improved patient motivation. Both ultimately lead to improved patient outcomes, which is not typically achievable with traditional rehabilitation methods. The review concludes that VR rehabilitation presents an opportunity to improve patient motivation and adherence to long-term rehabilitation training. However, to further enhance patient self-efficacy, VR rehabilitation should integrate psychology and incorporate methods. Moreover, it is necessary to build a game design theory for rehabilitation games, and the latest VR feedback technology should also be introduced.
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Motivação , Realidade Virtual , Humanos , Jogos de Vídeo/psicologia , Jogos de Vídeo/tendências , Reabilitação/métodos , Reabilitação/psicologia , Reabilitação/tendênciasRESUMO
Characterizing entanglement is central for quantum information science. Special observables which indicate entanglement, so-called entanglement witnesses, are a widely used tool for this task. The construction of these witnesses typically relies on the observation that quantum states with a high fidelity to some entangled target state are entangled, too. We introduce a general method to construct entanglement witnesses based on the Schmidt decomposition of observables. The method works for two-particle and multiparticle systems and is strictly stronger than fidelity-based constructions. The resulting witnesses can also be used to quantify entanglement and to characterize its dimensionality. Finally, we present experimentally relevant examples, where our approach improves entanglement detection significantly.
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Virtual reality (VR) Rehabilitation holds the potential to address the challenge that patients feel bored and give up long-term rehabilitation training. Despite the introduction of gaming elements by some researchers in rehabilitation training to enhance engagement, there remains a notable lack of in-depth research on VR rehabilitation serious game design methods, particularly the absence of a concrete design framework for VR rehabilitation serious games. Hence, we introduce the Clinical-Function-Interesting (CFI): a VR rehabilitation serious game design framework, harmonizing rehabilitation function and game design theories. The framework initiates with clinic information, defining game functions through the functional decomposition of rehabilitation training. Subsequently, it integrates gaming elements identified through the analysis and comparison of related literature to provide enduring support for long-term training. Furthermore, VR side-effect and enhancement are considered. Building upon this design framework, we have developed an upper limb VR rehabilitation serious game tailored for mild to moderate stroke patients and aligned our framework with another developed VR rehabilitation serious game to validate its practical feasibility. Overall, the proposed design framework offers a systematic VR rehabilitation serious game design methodology for the VR rehabilitation field, assisting developers in more accurately designing VR rehabilitation serious games that are tailored to specific rehabilitation goals.
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Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Jogos de Vídeo , Realidade Virtual , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/instrumentaçãoRESUMO
Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between ß-cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly(ε-caprolactone)-b-poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL-b-PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25â¯wt% (P1) and 20â¯wt% (P2) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1-based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1-based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.
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Antineoplásicos , Sistemas de Liberação de Medicamentos , Receptores de Hialuronatos , Ácido Hialurônico , Espécies Reativas de Oxigênio , beta-Ciclodextrinas , Ácido Hialurônico/química , Receptores de Hialuronatos/metabolismo , Humanos , beta-Ciclodextrinas/química , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Nanopartículas/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Doxorrubicina/farmacologia , Doxorrubicina/química , Células MCF-7RESUMO
Non-Hermitian quantum metrology, an emerging field at the intersection of quantum estimation and non-Hermitian physics, holds promise for revolutionizing precision measurement. Here, we present a comprehensive investigation of non-Hermitian quantum parameter estimation in the quantum regime, with a special focus on achieving Heisenberg scaling. We introduce a concise expression for the quantum Fisher information (QFI) that applies to general non-Hermitian Hamiltonians, enabling the analysis of estimation precision in these systems. Our findings unveil the remarkable potential of non-Hermitian systems to attain the Heisenberg scaling of 1/t, where t represents time. Moreover, we derive optimal measurement conditions based on the proposed QFI expression, demonstrating the attainment of the quantum Cramér-Rao bound. By constructing non-unitary evolutions governed by two non-Hermitian Hamiltonians, one with parity-time symmetry and the other without specific symmetries, we experimentally validate our theoretical analysis. The experimental results affirm the realization of Heisenberg scaling in estimation precision, marking a substantial milestone in non-Hermitian quantum metrology.
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Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.
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Uncertainty relations for Hermitian operators have been confirmed through many experiments. However, previous experiments have only tested the special case of non-Hermitian operators, i.e., uncertainty relations for unitary operators. In this study, we explore uncertainty relations for general non-Hermitian operators, which include Hermitian and unitary operators as special cases. We perform experiments with both real and complex non-Hermitian operators for qubit states, and confirm the validity of the uncertainty relations within the experimental error. Our results provide experimental evidence of uncertainty relations for non-Hermitian operators. Furthermore, our methods for realizing and measuring non-Hermitian operators are valuable in characterizing open-system dynamics and enhancing parameter estimation.
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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The oncogenic role of Matrin-3 (MATR3), an a nuclear matrix protein, in HCC remains largely unknown. Here, we document the biological function of MATR3 in HCC based on integrated bioinformatics analysis and functional studies. According to the TCGA database, MATR3 expression was found to be positively correlated with clinicopathological characteristics in HCC. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve displayed the diagnostic and prognostic potentials of MATR3 in HCC patients, respectively. Pathway enrichment analysis represented the enrichment of MATR3 in various molecular pathways, including the regulation of the cell cycle. Functional assays in HCC cell lines showed reduced proliferation of cells with stable silencing of MATR3. At the same time, the suppressive effects of MATR3 depletion on HCC development were verified by xenograft tumor experiments. Moreover, MATR3 repression also resulted in cell cycle arrest by modulating the expression of cell cycle-associated genes. In addition, the interaction of MATR3 with cell cycle-regulating factors in HCC cells was further corroborated with co-immunoprecipitation and mass spectrometry (Co-IP/MS). Furthermore, CIBERSORT and TIMER analyses showed an association between MATR3 and immune infiltration in HCC. In general, this study highlights the novel oncogenic function of MATR3 in HCC, which could comprehensively address how aberrant changes in the cell cycle promote HCC development. MATR3 might serve as a prognostic predictor and therapeutic target for HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Ciclo Celular/genética , Divisão Celular , Biomarcadores , Proteínas de Ligação a RNA , Proteínas Associadas à Matriz Nuclear/genéticaRESUMO
Decoding the user's natural grasp intent enhances the application of wearable robots, improving the daily lives of individuals with disabilities. Electroencephalogram (EEG) and eye movements are two natural representations when users generate grasp intent in their minds, with current studies decoding human intent by fusing EEG and eye movement signals. However, the neural correlation between these two signals remains unclear. Thus, this paper aims to explore the consistency between EEG and eye movement in natural grasping intention estimation. Specifically, six grasp intent pairs are decoded by combining feature vectors and utilizing the optimal classifier. Extensive experimental results indicate that the coupling between the EEG and eye movements intent patterns remains intact when the user generates a natural grasp intent, and concurrently, the EEG pattern is consistent with the eye movements pattern across the task pairs. Moreover, the findings reveal a solid connection between EEG and eye movements even when taking into account cortical EEG (originating from the visual cortex or motor cortex) and the presence of a suboptimal classifier. Overall, this work uncovers the coupling correlation between EEG and eye movements and provides a reference for intention estimation.
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Movimentos Oculares , Intenção , Humanos , Movimento , Eletroencefalografia , Força da MãoRESUMO
In natural waters, hydroxyl radical (OH) can initiate many free radical-induced reactions, oxidizing various inorganic and organic compounds through electron transfer reactions, dehydrogenation reactions, addition reactions, and self-quenching reactions. However, due to its extremely low concentration and short lifetime in natural waters, studies on the quantitative measurement of OH levels are insufficient. In this work, we developed the first quinolinium-based fluorescence probe containing fluoride substituted donor that could detect hydroxyl radicals in the water system. This probe exhibits excellent selectivity towards OH with a large Stokes shift (114 nm) and 23-fold enhancement in fluorescence. Additionally, this probe has been proven to be low toxicity and applied to detect OH in living cells, zebrafish, and natural water samples with good recovery (over 92 %).
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Sleep regularity is an essential part of the multidimensional sleep health framework. The phenomenon of irregular sleep patterns is widespread in contemporary lifestyles. This review synthesizes clinical evidence to summarize the measures of sleep regularity and discusses the role of different sleep regularity indicators in developing cardiometabolic diseases (coronary heart disease, hypertension, obesity, and diabetes). Existing literature has proposed several measurements to assess sleep regularity, mainly including the standard deviation (SD) of sleep duration and timing, sleep regularity index (SRI), interdaily stability (IS), and social jetlag (SJL). Evidence on associations between sleep variability and cardiometabolic diseases varies depending on the measure used to characterize variability in sleep. Current studies have identified a robust association between SRI and cardiometabolic diseases. In comparison, the association between other metrics of sleep regularity and cardiometabolic diseases was mixed. Meanwhile, the associations of sleep variability with cardiometabolic diseases differ across the population. SD of sleep characteristics or IS may be more consistently associated with HbA1c in patients with diabetes compared with the general population. The association between SJL and hypertension for patients with diabetes was more accordant than in the general population. Interestingly, the age-stratified association between SJL and metabolic factors was observed in the present studies. Furthermore, the relevant literature was reviewed to generalize the potential mechanisms through which irregular sleep increases cardiometabolic risk, including circadian dysfunction, inflammation, autonomic dysfunction, hypothalamic-pituitary-adrenal (HPA) axis disorder, and gut dysbiosis. Health-related practitioners should give more attention to the role of sleep regularity on human cardiometabolic in the future.
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Background: Excessive immune activation leads to secondary injury and impedes injured brain recovery after ischemic stroke. However, few effective methods are currently used for equilibrating immune balance. CD3+NK1.1-TCRß+CD4-CD8- double-negative T (DNT) cells which do not express NK cell surface markers are unique regulatory cells that maintain homeostasis in several immune-related diseases. However, the therapeutic potential and regulatory mechanism of DNT cells in ischemic stroke are still unknown. Methods: Mouse ischemic stroke is induced by occlusion of the distal branches of the middle cerebral artery (dMCAO). DNT cells were adoptively transferred intravenously into ischemic stroke mice. Neural recovery was evaluated by TTC staining and behavioral analysis. Using immunofluorescence, flow cytometry, and RNA sequencing, the immune regulatory function of DNT cells was investigated at different time points post ischemic stroke. Results: Adoptive transfer of DNT cells significantly reduces infarct volume and improves sensorimotor function after ischemic stroke. DNT cells suppress peripheral Trem1+ myeloid cell differentiation during the acute phase. Furthermore, they infiltrate the ischemic tissue via CCR5 and equilibrate the local immune balance during the subacute phase. During the chronic phase, DNT cells enhance Treg cell recruitment through CCL5, eventually developing an immune homeostatic milieu for neuronal recovery. Conclusions: DNT cell treatment renders the comprehensive anti-inflammatory roles in specific phases of ischemic stroke. Our study suggests that the adoptive transfer of regulatory DNT cells may be a potential cell-based therapy for ischemic stroke.
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AVC Isquêmico , Camundongos , Animais , AVC Isquêmico/terapia , Receptores de Antígenos de Linfócitos T alfa-beta , Linfócitos T Reguladores , Inflamação , Linfócitos T CD8-PositivosRESUMO
We herein report a 54-year-old man with eagle syndrome who presented with repeated episodes of syncope, especially after moving his head to a downward position. Computed tomography with contrast revealed a bilateral elongated styloid process. The left internal carotid artery was obviously compressed by the left elongated styloid processes. A transcranial Doppler examination detected a significantly decreased blood flow velocity in the left middle cerebral artery when the patient slightly lowered his head position. After surgery, the positional cerebral blood flow alteration disappeared. No further similar syncope episodes have been reported to date.
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Artéria Carótida Interna , Ossificação Heterotópica , Masculino , Humanos , Pessoa de Meia-Idade , Artéria Carótida Interna/diagnóstico por imagem , Ossificação Heterotópica/complicações , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/cirurgia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , Síncope/etiologiaRESUMO
BACKGROUND: Glucoside natural products have been showing great medicinal values and potentials. However, the production of glucosides by plant extraction, chemical synthesis, and traditional biotransformation is insufficient to meet the fast-growing pharmaceutical demands. Microbial synthetic biology offers promising strategies for synthesis and diversification of plant glycosides. RESULTS: In this study, the two efficient UDP-glucosyltransferases (UGTs) (UGT85A1 and RrUGT3) of plant origin, that are capable of recognizing phenolic aglycons, are characterized in vitro. The two UGTs show complementary regioselectivity towards the alcoholic and phenolic hydroxyl groups on phenolic substrates. By combining a developed alkylphenol bio-oxidation system and these UGTs, twenty-four phenolic glucosides are enzymatically synthesized from readily accessible alkylphenol substrates. Based on the bio-oxidation and glycosylation systems, a number of microbial cell factories are constructed and applied to biotransformation, giving rise to a variety of plant and plant-like O-glucosides. Remarkably, several unnatural O-glucosides prepared by the two UGTs demonstrate better prolyl endopeptidase inhibitory and/or anti-inflammatory activities than those of the clinically used glucosidic drugs including gastrodin, salidroside and helicid. Furthermore, the two UGTs are also able to catalyze the formation of N- and S-glucosidic bonds to produce N- and S-glucosides. CONCLUSIONS: Two highly efficient UGTs, UGT85A1 and RrUGT3, with distinct regioselectivity were characterized in this study. A group of plant and plant-like glucosides were efficiently synthesized by cell-based biotransformation using a developed alkylphenol bio-oxidation system and these two UGTs. Many of the O-glucosides exhibited better PEP inhibitory or anti-inflammatory activities than plant-origin glucoside drugs, showing significant potentials for new glucosidic drug development.
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Produtos Biológicos , Glucosiltransferases , Glucosídeos/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Preparações Farmacêuticas , Prolil Oligopeptidases , Difosfato de UridinaRESUMO
We report an experimental investigation of quantum correlations in a two-qutrit spin system in a single nitrogen-vacancy center in diamond at room temperatures. Quantum entanglement between two qutrits was observed at room temperature, and the existence of nonclassical correlations beyond entanglement in the qutrit case has been revealed. Our work demonstrates the potential of the NV centers as the multiqutrit system to execute quantum information tasks and provides a powerful experimental platform for studying the fundamental physics of high-dimensional quantum systems in the future.
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PURPOSE: The recognition of new diagnostic and prognostic biological markers for lung cancer is an essential and eager study. It's shown that ion channels play important roles in regulating various cellular processes and have been suggested to be associated with patient survival. However, tweety family member 3 (TTYH3), as a maxi-Cl- channel, its role in lung cancer remains elusive. METHODS: The expression, diagnostic and prognostic efficacy of TTYH3 were analyzed by public databases and clinical samples. Cell functional experiments were used to explore the effects of TTYH3 on cell viability. GO and KEGG enrichment analysis revealed underlying pathways that TTYH3 and its co-expressed genes were enriched in. TIMER, TIDE and R language analyses were used to detect the correlation between TTYH3 and immune infiltration cell and immunotherapy response. RESULTS: TTYH3 was up-regulated in lung cancer tissues compared to normal tissues and possessed a prominent diagnostic and prognostic value. TTYH3 knockdown significantly inhibited the proliferation of lung cancer cells. Enrichment analyses showed that TTYH3 and its co-expressed genes were mainly involved in immune related signaling pathways. Further investigation clarified that TTYH3 had a positive correlation with the infiltration of TAMs, Treg infiltration as well as T cell exhaustion and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment. CONCLUSION: This study not only revealed the diagnostic and prognostic value of TTYH3 but also provided TTYH3-based estimation of immunotherapy response for lung cancer patients, which might provide new strategies like anti-TTYH3 combined with immune therapy for the treatment of lung cancer.
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Neoplasias Pulmonares , Biomarcadores , Biomarcadores Tumorais/metabolismo , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , PrognósticoRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related mortality globally with a high risk of lymph node metastasis (LNM). In this study, weighted gene co-expression network analysis (WGCNA) showed the identification of 10 modules among which the significant module (turquoise), including 1352 genes, was correlated with LNM. A group 52 overlapping differentially expressed genes (DEGs) was identified based on the comparison of turquoise module with GSE23400 and GSE20347 datasets. Using Ctyohubba plugin, we identified 7 hub genes (ACTG2, SORBS1, MYH11, CXCL12, CNN1, IRS1 and CXCL8). IRS1 displayed significant correlation with metastasis. The decreased expression of IRS1 was also a predictor of poor OS of ESCC patients whereas the hub genes namely ACTG2, MYH11, CXCL8, CXCL12, IRS1 and CNN1 were associated with RFS of ESCC patients. These findings suggest that the altered expression of these hub genes are associated with prognosis and thus can be used as potential biomarkers for ESCC. Moreover, immunohistochemical staining and cell functional experiments displayed that the overexpression of IRS1 was negatively associated with metastasis in ESCC. In general, our research revealed several novel genes in ESCC especially the association of IRS1 with LNM in ESCC, which could provide novel insights into the initiation and progression of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Perfilação da Expressão Gênica , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Metástase LinfáticaRESUMO
Objective: At present, the use of particular radial hemostatic devices after coronary angiography (CAG) or percutaneous coronary intervention (PCI) has become the primary method of hemostasis. Most control studies are based on the products already on the market, while only a few studies are on the new hemostatic devices. The aim of this study is to compare a new radial artery hemostasis device which is transformed based on the invention patent (Application number: CN201510275446) with TR Band (Terumo Medical) to evaluate its clinical effects. Methods: In a prospective randomized clinical trial, 60 patients after CAG or PCI were randomly divided into two groups, patients in the trial group (CD group) using a new radial artery hemostasis device to stop bleeding and the control group (TR group) using the TR Band. The method is to collect relevant data of the two groups and compare the differences in hemostasis, local complications, and patient discomfort between the two groups. Results: The hemostatic devices in both groups achieved adequate hemostasis, and there was no failure to stop bleeding. The new radial artery hemostasis device was better than the TR band in pain and swelling (P < 0.05). There were no significant differences in bleeding, hematoma, ecchymosis, skin damage, and local infection between the two groups (P > 0.05). Conclusions: The sample of the new radial artery hemostasis device can stop bleeding effectively at the puncture site after CAG or PCI and is not inferior to the TR Band balloon hemostatic device in safety and is better in comfort.
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Hemostáticos , Intervenção Coronária Percutânea , Angiografia Coronária/efeitos adversos , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hemostasia , Técnicas Hemostáticas , Hemostáticos/uso terapêutico , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Artéria Radial , Resultado do TratamentoRESUMO
Perforin-mediated cytotoxicity plays a crucial role in microbial defense, tumor surveillance, and primary autoimmune disorders. However, the contribution of the cytolytic protein perforin to ischemia-induced secondary tissue damage in the brain has not been fully investigated. Here, we examined the kinetics and subpopulations of perforin-positive cells and then evaluated the direct effects of perforin-mediated cytotoxicity on outcomes after ischemic stroke. Using flow cytometry, we showed that perforin+CD45+ immune cells could be detected at 12 h and that the percentage of these cells increased largely until on day 3 and then significantly declined on day 7. Surprisingly, the percentage of Perforin+CD45+ cells also unexpectedly increased from day 7 to day 14 after ischemic stroke in Perforin1-EGFP transgenic mice. Our results suggested that Perforin+CD45+ cells play vital roles in the ischemic brain at early and late stages and further suggested that Perforin+CD45+ cells are a heterogeneous population. Surprisingly, in addition to CD8+ T cells, NK cells, and NKT cells, central nervous system (CNS)-resident immune microglia, which are first triggered and activated within minutes after ischemic stroke in mice, also secreted perforin during ischemic brain injury. In our study, the percentage of perforin+ microglia increased from 12 h after ischemic stroke, increased largely until on day 3 after ischemic stroke, and then moderately declined from days 3 to 7. Intriguingly, the percentage of perforin+ microglia also dramatically increased from days 7 to 14 after ischemic stroke. Furthermore, compared with wild-type littermates, Perforin 1-/- mice exhibited significant increases in the cerebral infarct volume, neurological deficits, and neurogenesis and inhibition of neurotoxic astrogliosis. Interestingly, the number of CD45+CD3+ T cells was significantly decreased in Perforin 1-/- mice compared with their wild-type littermates, especially the number of γδ T cells. In addition, Perforin 1-/- mice had lower levels of IL-17 than their wild-type littermates. Our results identified a critical function of perforin-mediated neurotoxicity in the ischemic brain, suggesting that targeting perforin-mediated neurotoxicity in brain-resident microglia and invading perforin+CD45+ immune cells may be a potential strategy for the treatment of ischemic stroke.
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The novel coronavirus (COVID-19) has induced unprecedented improvements of air quality due to drastic shrinking of human activities during the pandemic lockdown in 2020. While declines of most air pollutants have been globally evidenced in most cities worldwide, there is few detailed spatial knowledge at local scale. Therefore, we present here a high resolution mapping of the 2018-2020 evolution of human activities and air pollutants in Wuhan. Human activities were assessed by nighttime light radiance. We measured the air quality index (AQI) as the maximum value among air quality sub-indices of SO2, NO2, CO, O3 and particulate matter. We also compared mean monthly pollutant concentration during January-April in 2018, 2019 and 2020. Mapping results show that variations of nighttime light radiance were heterogenous at local scale, showing both rises and declines in the same district. The radiance decreased in eight districts located mostly in the city center, as a result of lower human activity, but the radiance increased in the five surrounding districts, as a consequence of people staying at home. AQI was low during lockdown, averaging at 57, but showed strong daily variations with a slight pollution around February 5 with AQI rising to 126. During this pollution event, particulate matter, SO2, NO2 and CO levels were positively correlated, suggesting common sources, but were not correlated with ozone; and particulate matter, SO2, NO2 and CO decreased with relative humidity, suggesting removal by precipitation. Comparison of 2020 data with previous years shows that particulate matter and NO2 were highly reduced, CO was less reduced due to ongoing power industries, SO2 first declined then increased to exceed 2018-19 values due to coal combustion, and ozone levels was more abundant due both to less NOx pollution and the weekend effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10311-021-01222-x.