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OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.
Subject(s)
Acquired Immunodeficiency Syndrome , Coinfection , Tuberculosis , Humans , BCG Vaccine , Coinfection/epidemiology , Prevalence , Risk Factors , Tuberculosis/epidemiology , China/epidemiologyABSTRACT
INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.
Subject(s)
Dementia , Encephalitis , Glioma , Hyponatremia , Limbic Encephalitis , Status Epilepticus , Female , Humans , Limbic Encephalitis/diagnostic imaging , Limbic Encephalitis/complications , Hyponatremia/complications , Leucine/therapeutic use , Autoantibodies , Intracellular Signaling Peptides and Proteins/therapeutic use , Encephalitis/complications , Neuroimaging , Glioma/complications , Status Epilepticus/complicationsABSTRACT
BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.
Subject(s)
Aspartate Aminotransferases/blood , Bilirubin/blood , COVID-19/mortality , Hospital Mortality , Liver Diseases/complications , SARS-CoV-2 , Aged , Female , Hepatitis B/complications , Humans , Male , Middle Aged , Propensity Score , Retrospective StudiesABSTRACT
Direct C-H bond functionalization catalyzed by non-precious transition metals is an attractive strategy in synthetic chemistry. Compared with the precious metals rhodium, palladium, ruthenium, and iridium commonly used in this field, catalysis based on non-precious metals, especially the earth-abundant ones, is appealing due to the increasing demand for environmentally benign and sustainable chemical processes. Herein, developments in iron- and cobalt-catalyzed C(sp3)-H bond functionalization reactions are described, with an emphasis on their applications in organic synthesis, i.e., the synthesis of natural products and pharmaceuticals and/or their modification.
Subject(s)
Biological Products/chemical synthesis , Cobalt/chemistry , Coordination Complexes/chemistry , Iron/chemistry , Amination , Catalysis , Chemistry Techniques, Synthetic , Electrochemical Techniques , Hydrogen Bonding , Hydroxylation , Ligands , Molecular Structure , Oxidation-Reduction , Photochemical ProcessesABSTRACT
Photoinduced hydroarylation of alkenes is an appealing synthetic strategy for arene functionalization. Herein, we demonstrated that aryl radicals generated from electron-deficient aryl chlorides/bromides could be trapped by an array of terminal/internal aryl alkenes in the presence of [Pt(O^N^C^N)] under visible-light (410â nm) irradiation, affording anti-Markovnikov hydroarylated compounds in up to 95 % yield. Besides, a protocol for [Pt(O^N^C^N)]-catalyzed intramolecular photocyclization of acrylanilides to give structurally diverse 3,4-dihydroquinolinones has been developed.
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A model based on carrier rate equations is proposed to evaluate the gain saturation and predict the dependence of the output power of a terahertz master-oscillator power-amplifier quantum cascade laser (THz-MOPA-QCL) on the material and structure parameters. The model reveals the design rules of the preamplifier and the power extractor to maximize the output power and the wall-plug efficiency. The correction of the model is verified by its agreement with the experiment results. The optimized MOPA devices exhibit single-mode emission at â¼ 2.6 THz with a side mode suppression ratio of 23 dB, a pulsed output power of 153 mW, a wall-plug efficiency of 0.22%, and a low divergence angle of â¼6°×16°, all measured at an operation temperature of 77 K. The model developed here is helpful for the design of MOPA devices and semiconductor optical amplifiers, in which the active region is based on intersubband transitions.
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BACKGROUND: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. METHODS: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. RESULTS: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = - 1.44, 95% CI = (- 1.68,- 1.19)] and acute migraine-specific medication days [WMD = - 1.28, 95% CI = (- 1.66,- 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. CONCLUSIONS: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Calcitonin Gene-Related Peptide/immunology , Migraine Disorders/prevention & control , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
BACKGROUND/OBJECTIVES: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome. METHODS: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis. RESULTS: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis. CONCLUSION: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.
Subject(s)
Cerebral Hemorrhage , Hematoma , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Humans , Prevalence , Prognosis , Prospective StudiesABSTRACT
BACKGROUND: Noncontrast computed tomography (CT) markers are increasingly used for predicting hematoma expansion. The aim of our study was to investigate the predictive value of expansion-prone hematoma in predicting hematoma expansion and outcome in patients with intracerebral hemorrhage (ICH). METHODS: Between July 2011 and January 2017, ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. Expansion-prone hematoma was defined as the presence of one or more of the following imaging markers: blend sign, black hole sign, or island sign. The diagnostic performance of blend sign, black hole sign, island sign, and expansion-prone hematoma in predicting hematoma expansion was assessed. Predictors of hematoma growth and poor outcome were analyzed using multivariable logistical regression analysis. RESULTS: A total of 282 patients were included in our final analysis. Of 88 patients with early hematoma growth, 69 (78.4%) had expansion-prone hematoma. Expansion-prone hematoma had a higher sensitivity and accuracy for predicting hematoma expansion and poor outcome when compared with any single imaging marker. After adjustment for potential confounders, expansion-prone hematoma independently predicted hematoma expansion (OR 28.33; 95% CI 12.95-61.98) and poor outcome (OR 5.67; 95% CI 2.82-11.40) in multivariable logistic model. CONCLUSION: Expansion-prone hematoma seems to be a better predictor than any single noncontrast CT marker for predicting hematoma expansion and poor outcome. Considering the high risk of hematoma expansion in these patients, expansion-prone hematoma may be a potential therapeutic target for anti-expansion treatment in future clinical studies.
Subject(s)
Cerebral Hemorrhage/pathology , Disease Progression , Hematoma/pathology , Outcome Assessment, Health Care , Adult , Aged , Aged, 80 and over , Cerebral Hemorrhage/diagnostic imaging , Female , Follow-Up Studies , Hematoma/diagnostic imaging , Humans , Male , Middle Aged , Tomography, X-Ray ComputedABSTRACT
In this study, variety of statistical methods were performed to reveal the spatiotemporal distribution characteristics of pollutants and parsing pollution sources of the coastal water in Hong Kong. The temporal-spatial distribution characteristics of the water pollution were various among the three distinct areas, which might be ascribed to the different dominant pollution sources. Cluster and network analysis showed preliminary pollution sources in these areas, and also indicated the temporal characteristics of Deep Bay water pollution, which could divided into two parts before and after 2010. According to the principal component analysis/factor analysis results, three factors in Deep Bay, Tolo Harbour and Victoria Harbour could explained 68.72%, 54.87% and 72.28% of the total variances, respectively. The contribution rate of different pollution source on water quality variables in each area had calculated by absolute principal component score-multiple linear regression model. The contribution rate was roughly ranked as: point source pollutionâ¯>â¯non-point source pollutionâ¯>â¯overland runoffâ¯>â¯river input. It is the first time to combine multivariate statistical methods, network analysis and regression model to profoundly analyze spatiotemporal variation of seawater quality and parsing the pollution sources. This novel analysis method can provide reference for the water quality evaluation and management of other water bodies.
Subject(s)
Environmental Monitoring , Water Pollutants, Chemical , Hong Kong , Models, Statistical , Rivers , Water PollutionABSTRACT
A terahertz master-oscillation power-amplifier quantum cascade laser (THz-MOPA-QCL) is demonstrated where a grating coupler is employed to efficiently extract the THz radiation. By maximizing the group velocity and eliminating the scattering of THz wave in the grating coupler, the residue reflectivity is reduced down to the order of 10-3. A buried DFB grating and a tapered preamplifier are proposed to improve the seed power and to reduce the gain saturation, respectively. The THz-MOPA-QCL exhibits single-mode emission, a single-lobed beam with a narrow divergence angle of 18° × 16°, and a pulsed output power of 136 mW at 20 K, which is 36 times that of a second-order DFB laser from the same material.
ABSTRACT
To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.
Subject(s)
Aging/metabolism , Beclin-1/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , NF-kappa B/metabolism , Plant Extracts/therapeutic use , Aging/drug effects , Aging/genetics , Animals , Beclin-1/agonists , Cognitive Dysfunction/genetics , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Dose-Response Relationship, Drug , Ginkgo biloba , Male , Maze Learning/drug effects , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/antagonists & inhibitors , Plant Extracts/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
Ligand cooperativity provides (transition) metal complexes with new reactivities in substrate activation and catalytic reactions, but usually the ligand acts as an internal (Brønsted) base, while the metal acts as a (Lewis) acid. We describe the synthesis and stepwise activation of a new phosphane-pyridine-amide ligand PNN(H2) in combination with Rh(I) . The ligand is susceptible to stepwise proton and hydride loss from the nitrogen arm (imine formation) and deprotonation at the pyridylphosphine arm (dearomatization), giving rise to amine complex 1, amido species 2, imine complex 3 and dearomatized compound 4. Complex 4 bears a dual-mode cooperative PNN' ligand containing both a (nucleophilic) basic methine fragment and a reactive (electrophilic) imine moiety. The basic ligand arm enables substrate deprotonation while the imine ligand arm enables reversible "storage" of the activated (nucleophilic) form of a sulfonamide substrate at the ligand. In combination with metal-based reactivity, this allows for the mono-alkylation of o-toluenesulfonamide with iodomethane. Compounds 1, 3 and 4 are structurally characterized. We also report the first structurally characterized example of an aminal in the coordination sphere of rhodium, complex 5, [Rh(CO)(PNN'')], formed by sequential NH activation of sulfonamide by the dearomatized ligand PNN' and follow-up nucleophilic attack of anionic sulfonamide onto the imine fragment.
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The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.
Subject(s)
Brain Edema/drug therapy , Cerebral Hemorrhage/drug therapy , Tissue Plasminogen Activator/administration & dosage , Adult , Aged , Brain Edema/mortality , Brain Edema/pathology , Brain Edema/surgery , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/surgery , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
Roots are essential for acquiring water and nutrients to sustain and support plant growth and anchorage. However, they have been studied less than the aboveground traits in phenotyping and plant breeding until recent decades. In modern times, root properties such as morphology and root system architecture (RSA) have been recognized as increasingly important traits for creating more and higher quality food in the "Second Green Revolution". To address the paucity in RSA and other root research, new technologies are being investigated to fill the increasing demand to improve plants via root traits and overcome currently stagnated genetic progress in stable yields. Artificial intelligence (AI) is now a cutting-edge technology proving to be highly successful in many applications, such as crop science and genetic research to improve crop traits. A burgeoning field in crop science is the application of AI to high-resolution imagery in analyses that aim to answer questions related to crops and to better and more speedily breed desired plant traits such as RSA into new cultivars. This review is a synopsis concerning the origins, applications, challenges, and future directions of RSA research regarding image analyses using AI.
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Neurexophilin 1 (nxph1) has been considered a potential candidate marker for sperm storage in chicken sperm storage tubules. In this work, one mutation of chicken nxph1 was detected. We analyzed 18 nxph1 gene sequences from 18 species. The coding sequence length of the zebra fish nxph1 gene is 819 bp; that of the other species is 816 bp. Amino acid alignment analysis revealed that the gene product is a conserved protein, especially in mammals. The sequences of mammals are highly conserved. We found 202 conserved amino acids (70-271), and there were only eight mutations in the remaining 69 amino acids. That level of conservation could be due to the nxph1 gene having been subjected to substantial constraints or strong purifying selection during millions of years of evolution.
Subject(s)
Chickens/genetics , Glycoproteins/genetics , Neuropeptides/genetics , Polymorphism, Genetic , Alleles , Amino Acid Sequence , Animals , Base Sequence , Codon , Molecular Sequence Data , Mutation , Phylogeny , Sequence Alignment , Sequence Homology, Amino Acid , Species SpecificityABSTRACT
Ischemic stroke is one of the most common causes of mortality and disability worldwide. However, treatment efficacy and the progress of research remain unsatisfactory. As the critical support system and essential components in neurovascular units, glial cells and blood vessels (including the blood-brain barrier) together maintain an optimal microenvironment for neuronal function. They provide nutrients, regulate neuronal excitability, and prevent harmful substances from entering brain tissue. The highly dynamic networks of this support system play an essential role in ischemic stroke through processes including brain homeostasis, supporting neuronal function, and reacting to injuries. However, most studies have focused on postmortem animals, which inevitably lack critical information about the dynamic changes that occur after ischemic stroke. Therefore, a high-precision technique for research in living animals is urgently needed. Two-photon fluorescence laser-scanning microscopy is a powerful imaging technique that can facilitate live imaging at high spatiotemporal resolutions. Two-photon fluorescence laser-scanning microscopy can provide images of the whole-cortex vascular 3D structure, information on multicellular component interactions, and provide images of structure and function in the cranial window. This technique shifts the existing research paradigm from static to dynamic, from flat to stereoscopic, and from single-cell function to multicellular intercommunication, thus providing direct and reliable evidence to identify the pathophysiological mechanisms following ischemic stroke in an intact brain. In this review, we discuss exciting findings from research on the support system after ischemic stroke using two-photon fluorescence laser-scanning microscopy, highlighting the importance of dynamic observations of cellular behavior and interactions in the networks of the brain's support systems. We show the excellent application prospects and advantages of two-photon fluorescence laser-scanning microscopy and predict future research developments and directions in the study of ischemic stroke.
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Objective: To investigate the association between cerebral small vessel disease (SVD) and hematoma volume in primary intracerebral hemorrhage (ICH). Methods: Patients from a prospective ICH cohort were enrolled. Admission and follow-up CT scan within 72 h after onset were reviewed to calculate the final hematoma volume. We evaluated cortical superficial siderosis and the global SVD score, including white matter hyperintensities, lacunes, enlarged perivascular space, and cerebral microbleeds on MRI. We conducted the multivariate logistic regression analyses to explore the association between SVD markers and small ICH, as well as hematoma volume. Hematoma location was stratified into lobar and non-lobar for subgroup analysis. Results: A total of 187 patients with primary ICH (mean age 62.4 ± 13.4 years, 67.9% male) were enrolled. 94 (50.2%) patients had small ICH. The multivariate logistic regression analysis showed an association between global SVD score and small ICH [adjusted odds ratio (aOR) 1.27, 95% CI 1.03-1.57, p = 0.027] and a trend of higher global SVD score towards non-lobar small ICH (aOR 1.23, 95% CI 0.95-1.58, p = 0.122). In the multivariate linear regression analysis, global SVD score was inversely related to hematoma volume of all ICH (ß = -0.084, 95% CI -0.142 to -0.025, p = 0.005) and non-lobar ICH (ß = -0.112, 95% CI -0.186 to -0.037, p = 0.004). Lacune (ß = -0.245, 95% CI -0.487 to -0.004, p = 0.046) was associated with lower non-lobar ICH volume. Conclusion: Global SVD score is associated with small ICH and inversely correlated with hematoma volume. This finding predominantly exists in non-lobar ICH.
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Alfalfa is the most widely cultivated forage legume, with approximately 30 million hectares planted worldwide. Genetic improvements in alfalfa have been highly successful in developing cultivars with exceptional winter hardiness and disease resistance traits. However, genetic improvements have been limited for complex economically important traits such as biomass. One of the major bottlenecks is the labor-intensive phenotyping burden for biomass selection. In this study, we employed two alfalfa fields to pave a path to overcome the challenge by using UAV images with fully automatic field plot segmentation for high-throughput phenotyping. The first field was used to develop the prediction model and the second field to validate the predictions. The first and second fields had 808 and 1025 plots, respectively. The first field had three harvests with biomass measured in May, July, and September of 2019. The second had one harvest with biomass measured in September of 2019. These two fields were imaged one day before harvesting with a DJI Phantom 4 pro UAV carrying an additional Sentera multispectral camera. Alfalfa plot images were extracted by GRID software to quantify vegetative area based on the Normalized Difference Vegetation Index. The prediction model developed from the first field explained 50-70% (R Square) of biomass variation in the second field by incorporating four features from UAV images: vegetative area, plant height, Normalized Green-Red Difference Index, and Normalized Difference Red Edge Index. This result suggests that UAV-based, high-throughput phenotyping could be used to improve the efficiency of the biomass selection process in alfalfa breeding programs.
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Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor (P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079 (100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079 (100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126 (2 µg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23 (3.5 µg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039 (100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China (approval No. TJ-A20160805) on August 26, 2016.