A nomogram to predict cryptococcal meningitis in patients with pulmonary cryptococcosis.

Background: The most serious manifestation of pulmonary cryptococcosis is complicated with cryptococcal meningitis, while its clinical manifestations lack specificity with delayed diagnosis and high mortality. The early prediction of this complication can assist doctors to carry out clinical interventions in time, thus improving the cure rate. This study aimed to construct a nomogram to predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis through a scoring system. Methods: The clinical data of 525 patients with pulmonary cryptococcosis were retrospectively analyzed, including 317 cases (60.38 %) with cryptococcal meningitis and 208 cases (39.62 %) without cryptococcal meningitis. The risk factors of cryptococcal meningitis were screened by univariate analysis, LASSO regression analysis and multivariate logistic regression analysis. Then the risk factors were incorporated into the nomogram scoring system to establish a prediction model. The model was validated by receiver operating characteristic (ROC) curve, decision curve analysis (DCA) and clinical impact curve. Results: Fourteen risk factors for cryptococcal meningitis in patients with pulmonary cryptococcosis were screened out by statistical method, including 6 clinical manifestations (fever, headache, nausea, psychiatric symptoms, tuberculosis, hematologic malignancy) and 8 clinical indicators (neutrophils, lymphocytes, glutamic oxaloacetic transaminase, T cells, helper T cells, killer T cells, NK cells and B cells). The AUC value was 0.978 (CI 96.2 %∼98.9 %), indicating the nomogram was well verified. Conclusion: The nomogram scoring system constructed in this study can accurately predict the risk of cryptococcal meningitis in patients with pulmonary cryptococcosis, which may provide a reference for clinical diagnosis and treatment of patients with cryptococcal meningitis.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Construction and validation of a nomogram model to predict the poor prognosis in patients with pulmonary cryptococcosis.

Background: Patients with poor prognosis of pulmonary cryptococcosis (PC) are prone to other complications such as meningeal infection, recurrence or even death. Therefore, this study aims to analyze the influencing factors in the poor prognosis of patients with PC, so as to build a predictive nomograph model of poor prognosis of PC, and verify the predictive performance of the model. Methods: This retrospective study included 410 patients (78.1%) with improved prognosis of PC and 115 patients (21.9%) with poor prognosis of PC. The 525 patients with PC were randomly divided into the training set and validation set according to the ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to screen the demographic information, including clinical characteristics, laboratory test indicators, comorbidity and treatment methods of patients, and other independent factors that affect the prognosis of PC. These factors were included in the multivariable logistic regression model to build a predictive nomograph. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to verify the accuracy and application value of the model. Results: It was finally confirmed that psychological symptoms, cytotoxic drugs, white blood cell count, hematocrit, platelet count, CRP, PCT, albumin, and CD4/CD8 were independent predictors of poor prognosis of PC patients. The area under the curve (AUC) of the predictive model for poor prognosis in the training set and validation set were 0.851 (95% CI: 0.818-0.881) and 0.949, respectively. At the same time, calibration curve and DCA results confirmed the excellent performance of the nomogram in predicting poor prognosis of PC. Conclusion: The nomograph model for predicting the poor prognosis of PC constructed in this study has good prediction ability, which is helpful for improving the prognosis of PC and further optimizing the clinical management strategy.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Relationship Between Systemic Immune-Inflammation Index and Risk of Respiratory Failure and Death in COPD: A Retrospective Cohort Study Based on the MIMIC-IV Database.

Purpose: Chronic obstructive pulmonary disease (COPD) concurrent with respiratory failure (RF) is devastating, and may result in death and disability. Systemic immune-inflammation index (SII) is a new prognostic biomarker linked to unfavorable outcomes of acute coronary syndrome, ischemic stroke, and heart failure. Nonetheless, its role in COPD is rarely investigated. Consequently, this study intends to assess the accuracy of SII in predicting the prognosis of COPD. Patients and Methods: The clinical information was retrospectively acquired from the Medical Information Mart for Intensive Care-IV database. The outcomes encompassed the incidence of RF and mortality. The relationship between different SII and outcomes was examined utilizing the Cox proportional-hazards model and restricted cubic splines. Kaplan-Meier analysis was employed for all-cause mortality. Results: The present study incorporated 1653 patients. During hospitalization, 697 patients (42.2%) developed RF, and 169 patients (10.2%) died. And 637 patients (38.5%) died during long-term follow-up. Higher SII increased the risk of RF (RF: HR: 1.19, 95% CI 1.12-1.28, P<0.001), in-hospital mortality (HR: 1.22, 95% CI 1.07-1.39, P=0.003), and long-term follow-up mortality (HR: 1.12, 95% CI 1.05-1.19, P<0.001). Kaplan-Meier analysis suggested a significantly elevated risk of all-cause death (log-rank P<0.001) in patients with higher SII, especially during the short-term follow-up period of 21 days. Conclusion: SII is closely linked to an elevated risk of RF and death in COPD patients. It appears to be a potential predictor of the prognosis of COPD patients, which is helpful for the risk stratification of this population. However, more prospective studies are warranted to consolidate our conclusion.

The Effect of Colloidal Nanoparticles on Phase Separation of Block and Heteroarm Star Copolymers Confined between Polymer Brushes.

The effect of colloidal nanoparticles on the phase changes of the amphiphilic AB linear diblock, A1A2B, and A2B heteroarm star copolymers confined between two polymer brush substrates was investigated by using a real-space self-consistent field theory. By changing the concentrations of nanoparticles and polymer brushes, the phase structure of the amphiphilic AB copolymer transforms from lamellar to core-shell hexagonal phase to cylinder phase. The pattern of A2B heteroarm star copolymer changes from core-shell hexagonal phases to lamellar phases and the layer decreases when increasing the density of the polymer brushes. The results showed that the phase behavior of the system is strongly influenced by the polymer brush architecture and the colloidal nanoparticle numbers. The colloidal nanoparticles and the soft confined surface of polymer brushes make amphiphilic AB copolymers easier to form ordered structures. The dispersion of the nanoparticles was also investigated in detail. The soft surfaces of polymer brushes and the conformation of the block copolymers work together to force the nanoparticles to disperse evenly. It will give helpful guidance for making some new functional materials by nano etching technology, nano photoresist, and nanoprinting.

Triphenylamine Spirofunctionalized Light-Emitting Conjugated Polymer with an Ultradeep-Blue Narrowband Emission for Large-Area Printed Display.

Emerging printed large-area polymer light-emitting diodes (PLEDs) are essential for manufacturing flat-panel displays and solid lighting devices. However, it is challenging to obtain large-area and stable ultradeep-blue PLEDs because of the lack of light-emitting conjugated polymers (LCPs) with robust deep-blue emissions, excellent morphological stabilities, and high charging abilities. Here, a novel unsymmetrically substituted polydiarylfluorene (POPSAF) is obtained with stable narrowband emission for large-area printed displays via triphenylamine (TPA) spirofunctionalization of LCPs. POPSAF films show narrowband and stable ultradeep-blue emission with a full width at half maximum (FWHM) of 36 nm, associated with their intrachain excitonic behavior without obvious polaron formation. Compared to controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF), excellent charge transport is observed in the POPSAF films because of the intrinsic hole transport ability of the TPA units. Large-area PLEDs are fabricated via blade-coating with an emission area of 9 cm2, which exhibit uniform ultradeep-blue emission with an FWHM of 36 nm and corresponding Commission internationale de l'éclairage (CIE) coordinates of (0.155, 0.072). These findings are attributed to the synergistic effects of robust emission, stable morphology, and printing capacity. Finally, preliminary printed passive matrix (PM) PLED displays with 20 × 20 pixels monochromes are fabricated, confirmed the effectiveness of spirofunctionalization in optoelectronics.

Hypoxia and Singlet Oxygen Dual-Responsive Micelles for Photodynamic and Chemotherapy Therapy Featured with Enhanced Cellular Uptake and Triggered Cargo Delivery.

Introduction: Combination therapy provides better outcomes than a single therapy and becomes an efficient strategy for cancer treatment. In this study, we designed a hypoxia- and singlet oxygen-responsive polymeric micelles which contain azo and nitroimidazole groups for enhanced cellular uptake, repaid cargo release, and codelivery of photosensitizer Ce6 and hypoxia-activated prodrug tirapazamine TPZ (DHM-Ce6@TPZ), which could be used for combining Ce6-mediated photodynamic therapy (PDT) and PDT-activated chemotherapy to enhance the therapy effect of cancer. Methods: The hypoxia- and singlet oxygen-responsive polymeric micelles DHM-Ce6@TPZ were prepared by film hydration method. The morphology, physicochemical properties, stimuli responsiveness, in vitro singlet oxygen production, cellular uptake, and cell viability were evaluated. In addition, the in vivo therapeutic effects of the micelles were verified using a tumor xenograft mice model. Results: The resulting dual-responsive micelles not only increased the concentration of intracellular photosensitizer and TPZ, but also facilitated photosensitizer and TPZ release for enhanced integration of photodynamic and chemotherapy therapy. As a photosensitizer, Ce6 induced PDT by generating toxic singlet reactive oxygen species (ROS), resulting in a hypoxic tumor environment to activate the prodrug TPZ to achieve efficient chemotherapy, thereby evoking a synergistic photodynamic and chemotherapy therapeutic effect. The cascade synergistic therapeutic effect of DHM-Ce6@TPZ was effectively evaluated both in vitro and in vivo to inhibit tumor growth in a breast cancer mice model. Conclusion: The designed multifunctional micellar nano platform could be a convenient and powerful vehicle for the efficient co-delivery of photosensitizers and chemical drugs for enhanced synergistic photodynamic and chemotherapy therapeutic effect of cancer.

LncRNA HCG11 enhances the chemosensitivity of non-small cell lung cancer cells to Gemcitabine via miR-17-5p/p21 axis.

BACKGROUND: This study investigated the inhibitory effects of lncRNA HLA Complex Group 11 (HCG11) on non-small cell lung cancer (NSCLC) and the molecular mechanisms. RESEARCH DESIGN AND METHODS: Bioinformatics analysis was conducted to determine the downstream targeted gene miR-17-5p/p21 and predict their binding sites. qRT-PCR and Western blot were used to detect expression levels, and dual luciferase and RIP assays were adopted to verify binding relationship. RESULTS: The lncRNA HCG11/miR-17-5p/p21 axis was found to regulate drug resistance, proliferation, apoptosis, and cell cycle of A549 and A549-Gemcitabine (GEM) cells. HCG11 acted as a ceRNA binding to miR-17-5p, which repressed p21 expression in turn. In vivo experiments demonstrated that HCG11 hindered tumor growth. Therefore, lncRNA HCG11, by targeting the miR-17-5p/p21 axis, suppressed GEM resistance and malignant progression of NSCLC cells. CONCLUSIONS: This study provides a reference for investigating the potential value of lncRNA HCG11 in the diagnosis of NSCLC and finding potential targets against clinical chemotherapeutic resistance in NSCLC.

Investigating alcohol consumption in China via wastewater-based epidemiology.

Alcohol abuse and addiction is a public health issue of global concern. Wastewater-based epidemiology (WBE) is a forceful and effective complementary tool for investigating chemical consumption. This study examined alcohol consumption in major cities of China via WBE and compared WBE estimates with other data sources. A simple and valid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of two alcohol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) in wastewater. The optimized method was applied to 62 sewage samples collected from wastewater treatment plants (WWTPs) in 31 provincial capital cities across China in the fourth quarter of 2020. The methodology established in this study was validated with the lower limit of quantification (LLOQ) up to 0.1 µg/L, good linearity in the range of 0.1-50 µg/L, intra-day and inter-day precision less than 5.58% and 5.55%, respectively, and the recoveries of the extracts were higher than 97.14%. The consumption range of alcohol estimated via WBE was 6.09 ± 4.56 ethanol/person/day (EPD) in the capital cities of China. Alcohol consumption varies significantly between cities in China, with WBE estimating lower alcohol consumption than WHO and lower than foreign countries. Investing in alcohol consumption based on WBE has great potential to accurately and efficiently estimate alcohol consumption.

The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study.

OBJECTIVE: To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. METHODS: This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. RESULTS: A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). CONCLUSION: Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.

Multi-feature concatenation and multi-classifier stacking: An interpretable and generalizable machine learning method for MDD discrimination with rsfMRI.

Major depressive disorder (MDD) is a serious and heterogeneous psychiatric disorder that needs accurate diagnosis. Resting-state functional MRI (rsfMRI), which captures multiple perspectives on brain structure, function, and connectivity, is increasingly applied in the diagnosis and pathological research of MDD. Different machine learning algorithms are then developed to exploit the rich information in rsfMRI and discriminate MDD patients from normal controls. Despite recent advances reported, the MDD discrimination accuracy has room for further improvement. The generalizability and interpretability of the discrimination method are not sufficiently addressed either. Here, we propose a machine learning method (MFMC) for MDD discrimination by concatenating multiple features and stacking multiple classifiers. MFMC is tested on the REST-meta-MDD data set that contains 2428 subjects collected from 25 different sites. MFMC yields 96.9% MDD discrimination accuracy, demonstrating a significant improvement over existing methods. In addition, the generalizability of MFMC is validated by the good performance when the training and testing subjects are from independent sites. The use of XGBoost as the meta classifier allows us to probe the decision process of MFMC. We identify 13 feature values related to 9 brain regions including the posterior cingulate gyrus, superior frontal gyrus orbital part, and angular gyrus, which contribute most to the classification and also demonstrate significant differences at the group level. The use of these 13 feature values alone can reach 87% of MFMC's full performance when taking all feature values. These features may serve as clinically useful diagnostic and prognostic biomarkers for MDD in the future.

Large-scale group-hierarchical DEMATEL method for complex systems.

Existing Decision-Making Trial and Evaluation Laboratory (DEMATEL) methods are mostly suitable for simple systems with fewer factors, and lack effective integration of expert knowledge and experience from large-scale group populations, resulting in a potential compromise of the quality of the initial direct relation (IDR) matrix. To make DEMATEL better suited for the identification of critical factors in complex systems, this paper proposes a hierarchical DEMATEL method for large-scale group decision-making. Considering the limitations of expert knowledge and experience, a method based on expert consistency network for constructing the expert weight matrix is designed. The expert consistency network is constructed for different elements, and the weights of experts in different elements are determined using the clustering coefficient. Following the principles of the classic DEMATEL method, the steps for identifying key elements in complex systems using the large-scale group-hierarchical DEMATEL method are summarized. To objectively test the effectiveness and superiority of the decision algorithm, the robustness of the algorithm is analyzed in an interference environment. Finally, the superiority of the proposed method and algorithm is verified through a case study, which demonstrating that the proposed decision-making method is suitable for group decision-making in complex systems, with high algorithm stability and low algorithm deviation.

The A53T mutation in α-synuclein enhances pro-inflammatory activation in human microglia.

Parkinson's disease (PD) is characterized by the aggregation of α-synuclein into Lewy bodies and Lewy neurites in the brain. Microglia-driven neuroinflammation may contribute to neuronal death in PD, however the exact role of microglia remains unclear and has been understudied. The A53T mutation in the gene coding for α-synuclein has been linked to early-onset PD, and exposure to A53T-mutant human α-synuclein increases the potential for inflammation of murine microglia. To date, its effect has not been studied in human microglia. Here, we used 2-dimensional cultures of human iPSC-derived microglia and transplantation of these cells into the mouse brain to assess the effects of the A53T mutation on human microglia. We found that A53T-mutant human microglia had an intrinsically increased propensity towards pro-inflammatory activation upon inflammatory stimulus. Additionally, A53T mutant microglia showed a strong decrease in catalase expression in non-inflammatory conditions, and increased oxidative stress. Our results indicate that A53T mutant human microglia display cell-autonomous phenotypes that may worsen neuronal damage in early-onset PD.

Effect of postoperative radiotherapy on survival in patients with completely resected and pathologically confirmed stage N2 non-small-cell lung cancer: a systematic review and meta-analysis.

Background: The role of postoperative radiotherapy (PORT) for patients with completely resected stage N2 non-small-cell lung cancer (NSCLC) has been controversial. This study aimed to investigate the efficacy of PORT and prognosis in these patients. Objectives: An updated meta-analysis was conducted in this study to investigate the efficacy of PORT and prognosis in patients with completely resected and pathologically confirmed stage N2 NSCLC. Design: This study is a systematic review and meta-analysis. Data source and methods: Databases were searched up to 2 March 2022. All trials on patients with completely resected and pathologically confirmed stage N2 NSCLC undergoing PORT were screened, and data indicators in the PORT and non-PORT groups were extracted, respectively. The effect of PORT on overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) was estimated. Subgroup and sensitivity analyses were performed. Results: In all, 20 studies involving 6340 patients were finally included. The PORT significantly increased OS [hazard ratio (HR) = 0.77, 95% CI: 0.71-0.84, p < 0.001), LRFS (HR = 0.63, 95% CI: 0.52-0.76, p < 0.001), and DFS (HR = 0.72, 95% CI: 0.63-0.82, p < 0.001) while it showed no significant difference in improving DMFS (HR = 0.86, 95% CI: 0.71-1.05, p = 0.14). Conclusion: Our results suggest that in the postoperative treatment of patients with completely resected and pathologically confirmed stage N2 NSCLC, the addition of PORT provides better local recurrence control and survival benefit, but no benefit for distant metastases. The PORT may be incorporated into the postoperative treatment options for some patients with high-risk factors. However, it needs to be validated by more prospective studies in the future. Trail registration: CRD42022314095.

Metal-Organic Framework for Hypoxia/ROS/pH Triple-Responsive Cargo Release.

Nanoparticulate antitumor photodynamic therapy (PDT) is suffering from a very short lifetime, limited diffusion distance of reactive oxygen species (ROS). Herein, a hypoxia/ROS/pH triple-responsive metal-organic framework (MOF) is designed to facilitate the on-demand release of photosensitizers and hence enhanced PDT efficacy. Tailored azo-containing imidazole ligand is coordinated with zinc to form MOF where photosensitizer (Chlorin e6/Ce6) is encapsulated. Azo can be reduced by overexpressed azoreductase in hypoxic tumor cells, resulting in depletion of glutathione (GSH) and thioredoxin (Trx) which are major antioxidants against ROS oxidative damage in PDT, resulting in rapid cargo release and additional efficacy amplification. The imidazole ionization causes a proton sponge effect to ensure the disintegration of the nanocarriers in acidic organelles, allowing the rapid release of Ce6 through lysosome escape. Under light irradiation, ROS produced by Ce6 may oxidize imidazole to urea, resulting in rapid cargo release. All of the triggers are expected to show interactive synergism. The pH- and hypoxia-responsiveness can improve the release rate of Ce6 for enhanced PDT therapy, whereas the consumption of oxygen by PDT may induce elevated hypoxia and hence in turn enhanced cargo release. This work highlights the role of triple-responsive nanocarriers for triggered photosensitizer release and improved antitumor PDT efficacy.

The association between exposure to volatile organic compounds and serum lipids in the US adult population.

BACKGROUND AND AIM: Epidemiological evidence on the relationship between exposure to volatile organic compounds (VOCs), both single and mixed, and serum lipid levels is limited, and their relationship remains unclear. Our study aimed to investigate the associations of exposure to VOCs with serum lipid levels in the US adult population. METHODS AND RESULTS: The study examined the association of 16 VOC levels (2-methylhippuric acid, 3- and 4-methylhippuric acid, N-acetyl-S-(2-carbamoylethyl)-L-cysteine, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine, 2-aminothiazoline-4-carboxylic acid, N-acetyl-S-(benzyl)-L-cysteine, N-acetyl-S-(n-propyl)-L-cysteine, N-acetyl-S-(2-carboxyethyl)-L-cysteine, N-acetyl-S-(2-cyanoethyl)-L-cysteine, N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine. N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, mandelic acid, N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, phenylglyoxylic acid and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) using data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2015, and a total of 1410 adults were enrolled. The association was evaluated by Bayesian kernel machine regression (BKMR), multiple linear regression and weighted quantile sum (WQS) regression. In BKMR analysis, exposure to VOCs is positively correlated with levels of TC, TG, and LDL-C. However, statistical significance was observed only for the impact on TG. Our linear regression analysis and WQS regression generally support the BKMR results. Several VOCs were positively associated with serum lipid profiles (e.g., the ln-transformed level of mandelic acid (MA) displayed an increase in estimated changes of 7.01 (95% CIs: 2.78, 11.24) mg/dL for TC level), even after the effective number of tests for multiple testing (P < 0.05). CONCLUSIONS: Exposure to VOCs was associated with serum lipids, and more studies are needed to confirm these findings.

Biologically Plausible Sparse Temporal Word Representations.

Word representations, usually derived from a large corpus and endowed with rich semantic information, have been widely applied to natural language tasks. Traditional deep language models, on the basis of dense word representations, requires large memory space and computing resource. The brain-inspired neuromorphic computing systems, with the advantages of better biological interpretability and less energy consumption, still have major difficulties in the representation of words in terms of neuronal activities, which has restricted their further application in more complicated downstream language tasks. Comprehensively exploring the diverse neuronal dynamics of both integration and resonance, we probe into three spiking neuron models to post-process the original dense word embeddings, and test the generated sparse temporal codes on several tasks concerning both word-level and sentence-level semantics. The experimental results show that our sparse binary word representations could perform on par with or even better than original word embeddings in capturing semantic information, while requiring less storage. Our methods provide a robust representation foundation of language in terms of neuronal activities, which could potentially be applied to future downstream natural language tasks under neuromorphic computing systems.

The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.

Intrinsically Stretchable and Efficient Fully Π-Conjugated Polymer via Internal Plasticization for Flexible Deep-Blue Polymer Light-Emitting Diodes with CIEy = 0.08.

Intrinsically stretchable polymeric semiconductors are essential to flexible polymer light-emitting diodes (PLEDs) owing to their excellent strain tolerance capacity under long-time deformation operation. Obtaining intrinsic stretchability, robust emission properties, and excellent charge-transport behavior simultaneously from fully π-conjugated polymers (FCPs) is difficult, particularly for applications in deep-blue PLEDs. Herein, an internal plasticization strategy is proposed to introduce a phenyl-ester plasticizer into polyfluorenes (PF-MC4, PF-MC6, and PF-MC8) for narrowband deep-blue flexible PLEDs. Compared with controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPFs) (2.5%), the freestanding PF-MC8 thin film shows a fracture strain of >25%. The three stretchable films exhibit stable and efficient deep-blue emission (PLQY > 50%) because of the encapsulation of π-conjugated backbone via pendant phenyl-ester plasticizers. The PF-MC8-based PLEDs show deep-blue emission, which corresponds to CIE and EQE values of (0.16, 0.10) and 1.06%, respectively. Finally, the narrowband deep-blue electroluminescence (FWHM of ≈25 nm; CIE coordinates: (0.15, 0.08)) and performance of the transferred PLEDs based on the PF-MC8 stretchable film are independent of the tensile ratio (up to 45%); however, they show a maximum brightness of 1976 cd m-2 at a ratio of 35%. Therefore, internal plasticization is a promising approach for designing intrinsically stretchable FCPs for flexible electronics.