Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis.

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Association between Baseline Cognitive Function and Longitudinal Functional Outcome Change after Ischemic Stroke.

INTRODUCTION: Ischemic stroke can cause impairment of daily function and cognitive function. Higher cognitive function is reported in many studies to be associated with better functional outcomes; however, evidence from longitudinal study is lacking. Therefore, in the present study, the association between cognitive function and longitudinal changes of functional outcome was investigated based on stroke severity. Furthermore, whether the effect of cognitive function remained consistent after controlling for depression was investigated. METHODS: The data of 423 stroke patients (292 minor strokes, 93 moderate strokes, and 38 severe strokes) were collected. Baseline Mini-Mental State Examination (MMSE) score was considered a predictor, and change of modified Rankin Scale (mRS) score during 12 months of follow-up was the outcome. First, the association between the baseline MMSE score and longitudinal change in the mRS score was analyzed using linear mixed-effects models. Fixed effects were MMSE score group, time, and MMSE score group × time interaction. Additional adjustment was made for the Geriatric Depression Scale (GDS) score. RESULTS: Among the 423 subjects, the mean age was 73.5 years, and 43.4% were female. In the minor stroke group, the high MMSE score group had a decreased mRS score, and the low MMSE score group had an increased mRS score (p < 0.001). This association remained after additional adjustment of the GDS score. Association was not observed between cognitive function and functional recovery in the moderate or severe stroke group. CONCLUSION: After ischemic stroke, higher baseline global cognitive function was a predictive factor for better functional recovery regardless of depression symptoms in the minor stroke group.

Health-related quality of life using WHODAS 2.0 and associated factors 1 year after stroke in Korea: a multi-centre and cross-sectional study.

BACKGROUND: Little is known about the self-perceived level of disability of stroke survivors in the community. We aimed to characterise Health-related quality of life (HRQoL) 1 year after stroke and investigate how sociodemographic and stroke-related factors and medical adherence explain the self-perceived level of disability in a Korean stroke population. METHODS: This was a multicentre cross-sectional study. A total of 382 ischaemic stroke survivors at 1 year after onset from 11 university hospitals underwent a one-session assessment, including socioeconomic variables, the modified Rankin Scale (mRS), various neurological sequelae, the Morisky, Green and Levin-Medication Adherence Questionnaire (MGL), and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) 36-items. The relationship between disability and different variables was analysed using ordinal logistic regression. RESULTS: The prevalence of disability based on global WHODAS 2.0 was 62.6% (mild, 41.6%; moderate, 16.0%; severe, 5.0%). The prevalence of severe disability was higher in participation in society (16.8%) and getting around (11.8%) than in other domains. Low MGL- motivation was the only factor determining a significant association between all six domains of disability after adjustment. Different predictors for specific domains were age, mRS, dysarthria, trouble seeing, cognition problems, and MGL-motivation for understanding and communicating; age, recurrent stroke, mRS, hemiplegia, facial palsy, general weakness, and MGL-motivation for getting around; age, education, mRS, hemiplegia, and MGL-motivation for self-care; education, recurrent stroke, hemiplegia, dysarthria, and MGL-motivation for getting along with people; age, education, income, mRS, hemiplegia, dysarthria, MGL-knowledge, and MGL-motivation for life activities; living without a spouse, mRS, hemiplegia, dysarthria, trouble seeing, cognition problems, general weakness, and MGL-motivation for participation in society. CONCLUSIONS: Self-perceived disability according to the WHODAS 2.0 at 1 year after stroke was highly prevalent. Each disability domain showed a different prevalence and associated factors. Interventions promoting medical adherence to motivation seemed to help achieve high HRQoL in all domains.

Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea.

BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Topological Control of 2D Perovskite Emission in the Strong Coupling Regime.

Momentum space topology can be exploited to manipulate radiation in real space. Here we demonstrate topological control of 2D perovskite emission in the strong coupling regime via polaritonic bound states in the continuum (BICs). Topological polarization singularities (polarization vortices and circularly polarized eigenstates) are observed at room temperature by measuring the Stokes parameters of photoluminescence in momentum space. Particularly, in symmetry-broken structures, a very large degree of circular polarization (DCP) of ∼0.835 is achieved in the perovskite emission, which is the largest in perovskite materials to our knowledge. In the strong coupling regime, lower polariton modes shift to the low-loss spectral region, resulting in strong emission enhancement and large DCP. Our reciprocity analysis reveals that DCP is limited by material absorption at the emission wavelength. Polaritonic BICs based on 2D perovskite materials combine unique topological features with exceptional material properties and may become a promising platform for active nanophotonic devices.

Post-Stroke Depressive Symptoms: Varying Responses to Escitalopram by Individual Symptoms and Lesion Location.

OBJECTIVE: The efficacy of antidepressants in post-stroke depressive symptoms (PSD) varies. We aimed to examine whether the effect of escitalopram on PSD differs according to individual depressive symptoms and stroke lesion location. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram on depression in acute stroke patients (237 with placebo, 241 with escitalopram). Depressive symptoms were evaluated with the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Changes in MADRS and individual item scores at 12 weeks were compared between the treatment groups and among the stroke lesion location groups. Stroke lesion locations were grouped according to the anatomical distribution of serotonin fibers that originate from the midbrain/pons and spread to the forebrain via subcortical structures: "Midbrain-Pons," "Frontal-Subcortical," and "Others." Least-squares means were calculated to demonstrate the independent effect of lesion location. RESULTS: Total MADRS scores decreased more significantly in the escitalopram than in the placebo group, while a significant effect of escitalopram was observed in only 3 items: apparent sadness, reported sadness, pessimistic thoughts. In the lesion location analyses, escitalopram users in the Frontal-Subcortical group showed significant improvement in total MADRS scores (placebo [n = 130] vs. escitalopram [n = 148], least-square mean [95% CI]: -2.3 [-3.5 to -0.2] vs. -4.5 [-5.5 to -3.4], p = .005), while those in the Midbrain-Pons and Others groups did not. CONCLUSIONS: The effect of escitalopram on PSD may be more prominent in patients with particular depressive symptoms and stroke lesion locations, suggesting the need for tailored treatment strategies.

Removal of potentially toxic metal by biochar derived from rendered solid residue with high content of protein and bone tissue.

The purpose of this study was to produce rendering animal carcass residue char (RACR-C) by pyrolyzing the solid residues of low-recyclable rendered pig carcasses and to evaluate their cadmium (Cd) adsorption characteristics and mechanisms. As the pyrolysis temperature increased, the inorganic content of RACR-C increased, while the carbon content decreased. In particular, the surface structure and chemistry of RACR-Cs prepared at different pyrolysis temperatures were well described by SEM-EDS, XRD, XRF, TGA, and FTIR. The Cd adsorption characteristics of RACR-C were in good agreement with the Langmuir isotherm and pseudo-second-order models, and the Cd adsorption capacities of RACR-Cs prepared at various pyrolysis temperatures were in the order of RACR-C500 (73.5 mg/g)> RACR-C600 (53.8 mg/g)> RACR-C400 (41.5 mg/g) " RACR-C250 (15.9 mg/g). The intraparticle diffusion model suggested that the adsorption of Cd by RACR-C is greatly influenced by internal diffusion as well as external boundary. Since the Cd adsorption capacity of RACR-C is greatly influenced by the initial dosage, pH, and co-existing metals, it is necessary to manage these influencing factors when treating wastewater containing heavy metals. Our results suggest that Cd adsorption by RACR-C is a complex adsorption phenomenon by various mechanisms such as adsorption by functional group (CË­C and C-O), precipitation of Cd-P and ion exchange reaction by exchangeable cation occurring rather than by a single specific mechanism.

Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.

Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Depressive Symptoms in Stroke Patients: Are There Sex Differences?

BACKGROUND: We aimed to examine sex differences in symptom characteristics and pharmacological responses in post-stroke depressive (PSD) symptoms. METHODS: This is a post hoc analysis of EMOTION (ClinicalTrials.gov, NCT01278498), a randomized, placebo-controlled, double-blind trial that examined the efficacy of escitalopram for 3 months on depression in patients with acute stroke. Depressive symptoms were evaluated using the 10-item Montgomery-Åsberg Depression Rating Scale (MADRS). Baseline characteristics, clinical variables, and treatment responses to escitalopram were compared between male and female patients. Treatment responses were defined as changes in MADRS (total score and its components) between baseline and 3 months and were compared between the escitalopram and placebo groups within each sex group. The least square mean was calculated to determine the independent effect of escitalopram, of which interaction was evaluated with patient sex. RESULTS: Of the 478 patients (intention-to-treat population), 187 (39%) were female. Female patients were significantly older than male patients and demonstrated more severe depressive symptoms at baseline (male vs. female, MADRS score, mean [SD]: 9.7 ± 8.0 vs. 12.2 ± 8.4, p = 0.001), especially in apparent sadness, reported sadness, and reduced appetite items. These differences were significant after adjustment for age and the severity of neurologic deficits. The female escitalopram group showed a significant 3-month improvement in MADRS scores (placebo [n = 86] vs. escitalopram [n = 101], least square mean [95% CI] -2.7 [-4.1 to -1.2] vs. -5.0 [-6.4 to -3.6], p = 0.007), and this efficacy was prominent in apparent sadness, reported sadness, and pessimistic thoughts items. However, there was no significant effect of escitalopram on depressive symptoms in the male group. The treatment responses of escitalopram tended to be more pronounced in the female group, particularly in alleviating a subset of depressive symptoms such as apparent sadness (p for interaction = 0.009). CONCLUSION: PSD may differ according to sex in its symptom characteristics and treatment responses to escitalopram, and tailored treatment strategies for PSD may therefore be needed.

Lead sorption characteristics of various chicken bone part-derived chars.

Recycling food waste for beneficial use is becoming increasingly important in resource-limited economy. In this study, waste chicken bones of different parts from restaurant industry were pyrolyzed at 600 °C and evaluated for char physicochemical properties and Pb sorption characteristics. Lead adsorption isotherms by different chicken bone chars were carried out with initial Pb concentration range of 1-1000 mg L-1 at pH 5. The Pb adsorption data were better described by the Langmuir model (R2 = 0.9289-0.9937; ARE = 22.7-29.3%) than the Freundlich model (R2 = 0.8684-0.9544; ARE = 35.4-72.0%). Among the chars derived from different chicken bone parts, the tibia bone char exhibited the highest maximum Pb adsorption capacity of 263 mg g-1 followed by the pelvis (222 mg g-1), ribs (208 mg g-1), clavicle (179 mg g-1), vertebrae (159 mg g-1), and humerus (135 mg g-1). The Pb adsorption capacities were significantly and positively correlated with the surface area, phosphate release amount, and total phosphorus content of chicken bone chars (r ≥ 0.9711). On the other hand, approximately 75-88% of the adsorbed Pb on the chicken bone chars was desorbable with 0.1 M HCl, indicating their recyclability for reuse. Results demonstrated that chicken bone char could be used as an effective adsorbent for Pb removal in wastewater.

Adsorption of Cd, Cu and Zn from aqueous solutions onto ferronickel slag under different potentially toxic metal combination.

Adsorption characteristics of potentially toxic metals in single- and multi-metal forms onto ferronickel slag were evaluated. Competitive sorption of metals by ferronickel slag has never been reported previously. The maximum adsorption capacities of toxic metals on ferronickel were in the order of Cd (10.2 mg g(-1)) > Cu (8.4 mg g(-1)) > Zn (4.4 mg g(-1)) in the single-metal adsorption isotherm and Cu (6.1 mg g(-1)) >> Cd (2.3 mg g(-1)) > Zn (0.3 mg g(-1)) in the multi-metal adsorption isotherm. In comparison with single-metal adsorption isotherm, the reduction rates of maximum toxic metal adsorption capacity in the multi-metal adsorption isotherm were in the following order of Zn (93%) > Cd (78%) >> Cu (27%). The Freundlich isotherm provides a slightly better fit than the Langmuir isotherm equation using ferronickel slag for potentially toxic metal adsorption. Multi-metal adsorption behaviors differed from single-metal adsorption due to competition, based on data obtained from Freundlich and Langmuir adsorption models and three-dimensional simulation. Especially, Cd and Zn were easily exchanged and substituted by Cu during multi-metal adsorption. Further competitive adsorption studies are necessary in order to accurately estimate adsorption capacity of ferronickel slag for potentially toxic metals in natural environments.

Competitive adsorption and selectivity sequence of heavy metals by chicken bone-derived biochar: Batch and column experiment.

The objective of this research was to evaluate adsorption of heavy metals in single- and ternary-metal forms onto chicken bone biochar (CBB). Competitive sorption of heavy metals by CBB has never been reported previously. The maximum adsorption capacities of metals by CBB were in the order of Cu (130 mg g(-1)) > Cd (109 mg g(-1)) > Zn (93 mg g(-1)) in the single-metal adsorption isotherm and Cu (108 mg g(-1)) >> Cd (54 mg g(-1)) ≥ Zn (44 mg g(-1)) in the ternary-metal adsorption isotherm. Cu was the most retained cation, whereas Zn could be easily exchanged and substituted by Cu. Batch experimental data best fit the Langmuir model rather than the Freundlich isotherms. In the column experiments, the total adsorbed amounts of the metals were in the following order of Cu (210 mg g(-1)) > Cd (192 mg g(-1)) > Zn (178) in single-metal conditions, and Cu (156) > Cd (123) > Zn (92) in ternary-metal conditions. Results from both the batch and column experiments indicate that competitive adsorption among metals increases the mobility of these metals. Especially, Zn in single-metal conditions lost it adsorption capacity most significantly. Based on the 3D simulation graphs of heavy metals, adsorption patterns under single adsorption condition were different than under competitive adsorption condition. Results from both the batch and column experiments show that competitive adsorption among metals increases the mobility of these metals. The maximum metal adsorption capacity of the metals in the column experiments was higher than that in the batch experiment indicating other metal retention mechanisms rather than adsorption may be involved. Therefore, both column and batch experiments are needed for estimating retention capacities and removal efficiencies of metals in CBB.

Establishment of government-initiated comprehensive stroke centers for acute ischemic stroke management in South Korea.

BACKGROUND AND PURPOSE: In 2008, the Ministry of Health and Welfare of South Korea initiated the Regional Comprehensive Stroke Center (CSC) program to decrease the incidence and mortality of stroke nationwide. We evaluated the performance of acute ischemic stroke management after the Regional CSC program was introduced. METHODS: The Ministry of Health and Welfare established 9 Regional CSCs in different provinces from 2008 to 2010. All Regional CSCs have been able to execute the critical processes independently for stroke management since 2011. The Ministry of Health and Welfare was responsible for program development and financial support, the Regional CSC for program execution, and the Korea Centers for Disease Control and Prevention for auditing the execution. We analyzed prospectively collected data on the required indices from 2011 and repeated the analysis the following year for comparison. RESULTS: After the Regional CSCs were established, the first brain image was taken within 1 hour from arrival at the emergency room for all patients with stroke; the length of hospital stay decreased from 14 to 12 days; for the rapid execution of thrombolysis, the first brain image was taken within 12 minutes; intravenous and intra-arterial thrombolysis were started within 40 and 110 minutes, respectively, after emergency room arrival; and the hospital stay of thrombolytic patients decreased from 19 to 15 days. CONCLUSIONS: The Regional CSC program has improved the performance of acute stroke management in South Korea and can be used as a model for rapidly improving stroke management.

The effects of salinity on the growth and biochemical properties of Chlamydomonas mexicana GU732420 cultivated in municipal wastewater.

A freshwater microalga Chlamydomonas mexicana was grown on municipal wastewater with different levels of salinity up to 400 mmol/L NaCl, and the biochemical properties were characterized after 10 days of cultivation. C. mexicana showed the higher specific growth rates for 100 and 200mmol/L NaCl. Nitrogen was completely removed within 10 days as a result of algal growth promoted by the addition of 200-400 mmol/L NaCl. Phosphorus removal increased from 77-84% as the concentration of NaCI increased from 100 to 400 mmol/L. The highest removal of total inorganic carbon (66%) was obtained with the addition of 200 mmol/L NaCl. The lipid content increased from 17% to 38% as the concentration of NaCl increased from 0 to 400mmol/L. The total fatty acid content and glycerol yield of C. mexicana increased 1.8- and 4-fold in wastewater amended with NaCl, respectively. Fatty acids accumulated in the algal biomass were mainly composed of palmitic (27-29%), y-linolenic (27-30%), and linolelaidic acids (16-18%). The optimal condition for fatty acids production in C. mexicana was observed when the municipal wastewater was amended with 100-200 mmol/L NaCl with a simultaneous removal of nutrients.

Enrichment of infection-associated bacteria in the low biomass brain bacteriota of Alzheimer's disease patients.

Alzheimer's disease (AD) is a neurodegenerative disease accompanied by neuroimmune inflammation in the frontal cortex and hippocampus. Recently, the presence of bacteria in AD-affected brains has been documented, prompting speculation about their potential role in AD-associated neuroinflammation. However, the characterization of bacteriota in human brains affected by AD remains inconclusive. This study aimed to investigate potential associations between specific bacteria and AD pathology by examining brain tissues from AD-associated neurodegenerative regions (frontal cortex and hippocampus) and the non-AD-associated hypothalamus. Employing 16S rRNA gene sequencing, 30 postmortem brain tissue samples from four individuals with normal brain histology (N) and four AD patients were analyzed, along with three blank controls. A remarkably low biomass characterized the brain bacteriota, with their overall structures delineated primarily by brain regions rather than the presence of AD. While most analyzed parameters exhibited no significant distinction in the brain bacteriota between the N and AD groups, the unique detection of Cloacibacterium normanense in the AD-associated neurodegenerative regions stood out. Additionally, infection-associated bacteria, as opposed to periodontal pathogens, were notably enriched in AD brains. This study's findings provide valuable insights into potential link between bacterial infection and neuroinflammation in AD.

Biomass, lipid content, and fatty acid composition of freshwater Chlamydomonas mexicana and Scenedesmus obliquus grown under salt stress.

Two freshwater microalgae including Chlamydomonas mexicana and Scenedesmus obliquus were grown on Bold Basal Medium (BBM) with different levels of salinity up to 100 mM NaCl. The dry biomass and lipid content of microalgae were improved as the concentration of NaCl increased from 0 to 25 mM. Highest dry weight (0.8 and 0.65 g/L) and lipid content (37 and 34 %) of C. mexicana and S. obliquus, respectively, were obtained in BBM amended with 25 mM NaCl. The fatty acid composition of the investigated species was also improved by the increased NaCl concentration. At 50 mM, NaCl palmitic acid (35 %) and linoleic acid (41 %) were the dominant fatty acids in C. mexicana, while oleic acid (41 %) and α-linolenic acid (20 %) were the major fractions found in S. obliquus.

Chiral electroluminescence from thin-film perovskite metacavities.

Chiral light sources realized in ultracompact device platforms are highly desirable for various applications. Among active media used for thin-film emission devices, lead-halide perovskites have been extensively studied for photoluminescence due to their exceptional properties. However, up to date, there have been no demonstrations of chiral electroluminescence with a substantial degree of circular polarization (DCP) based on perovskite materials, being critical for the development of practical devices. Here, we propose a concept of chiral light sources based on a thin-film perovskite metacavity and experimentally demonstrate chiral electroluminescence with a peak DCP approaching 0.38. We design a metacavity created by a metal and a dielectric metasurface supporting photonic eigenstates with a close-to-maximum chiral response. Chiral cavity modes facilitate asymmetric electroluminescence of pairs of left and right circularly polarized waves propagating in the opposite oblique directions. The proposed ultracompact light sources are especially advantageous for many applications requiring chiral light beams of both helicities.

Synthesis and SAR of geminal substitutions at the C5' carbosugar position of pyrimidine-derived HCV inhibitors.

The installation of geminal substitution at the C5' position of the carbosugar in our pyrimidine-derived hepatitis C inhibitor series is reported. SAR studies around the C5' position led to the installation of the dimethyl group as the optimal functionality. An improved route was subsequently designed to access these substitutions. Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species.

Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors.

Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R(1), R(2) or R(3) positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in all species studied, and cross genotype activity.