Modulating secondary growth of perovskite grains through residual solvent evaporation.

Over the past decade, perovskite solar cells (PSCs) have attracted enormous attention due to their high performance. One key to fabricating high-quality perovskite films lies in controlling the volatilization rate of residual solvents during the annealing process. This study systematically investigates how different protective substrates affect the volatilization rate of residual solvent in perovskite films. By adjusting the direction and rate of evaporation, the supersaturation time of the solution was precisely controlled, leading to effective recrystallization of the grains. Concurrently, the annealing time was optimized to enhance film quality further. This optimization aimed to increase crystallinity, reduce defects, and thereby minimize non-radiative recombination centers. Implementing these methodologies, particularly the use of filter paper as a protective substrate during a 2-minute annealing process, significantly improved the fill factor (FF) and open-circuit voltage (VOC) of the PSCs. This led to a remarkable 5.26% improvement in power conversion efficiency (PCE) compared to control devices. The strategies employed in this work demonstrate significant potential in improving PSC film quality. This approach not only advances our understanding of film formation dynamics but also provides a practical guideline for future PSC fabrication.

A unique Ca2+-inhibited C-type lectin in shrimp Fenneropenaeuschinensis.

C-type lectins (CTLs) are glycan-binding pattern recognition receptors (PRRs) that can bind to carbohydrates on pathogen surfaces, triggering immune responses in shrimp innate immunity. In this study, a unique Ca2+-inhibited CTL named FcLec was identified and characterized in Chinese shrimp Fenneropenaeus chinensis. The full-length cDNA sequence of FcLec was 976 bp (GenBank accession number KU361826), with a 615 bp open reading frame (ORF) encoding 204 amino acids. FcLec possesses a C-type lectin-like domain (CTLD) containing four conserved cysteines (Cys105, Cys174, Cys192, and Cys200) and two sugar-binding site structures (QPD and LNP). The tertiary structure of FcLec deduced revealed three α-helices and eight ß-pleated sheets. The mRNA expression levels of FcLec in hemocytes and the hepatopancreas were markedly elevated after stimulation with Vibrio anguillarum and white spot syndrome virus (WSSV). The recombinant FcLec protein exhibited Ca2+-independent hemagglutination and bacterial agglutination, but these activities were observed only in the presence of EDTA to chelate metal ions. These findings suggest that FcLec plays important and functionally distinct roles in the shrimp's innate immune response to bacteria and viruses, enriching the current understanding of the relationship between CTL activity and Ca2+ in invertebrates.

Elucidating the mechanism and origin of stereoselectivity in the activation/transformation of an acetic ester catalyzed by an N-heterocyclic carbene.

The activation of an ester by N-heterocyclic carbene (NHC) organocatalysis is an efficient and important approach for generating an NHC-bound enolate intermediate, an important active intermediate in the transformation of carbonyl compounds. Herein, we perform a theoretical study on the NHC-catalyzed activation and transformation reaction of an acetic ester in which the NHC-bound enolate intermediate is a key intermediate. Multiple activation and transformation pathways are proposed and analyzed to identify an energetically favorable pathway. The use of different substrates for the reaction is considered. When a chalcone substrate is used, [4+2] cycloaddition between the enolate intermediate and the chalcone is identified to be both the rate- and stereoselectivity-determining step for the reaction, with the R-configured product being generated as the major isomer. Noncovalent interaction (NCI) and atoms-in-molecules (AIM) analyses are performed to identify the origin of the stereoselectivity of the reaction, and a local reactivity analysis is conducted to explore substrate and catalyst effects on the reaction.

Slow Auger Recombination in Ag2Se Colloidal Quantum Dots.

Efficient Auger recombination (AR) presents a significant challenge for the advancement of colloidal quantum dot (QD)-based devices involving multiexcitons. Here, the AR dynamics of near-infrared Ag2Se QDs were studied through transient absorption experiments. As the QD radius increases from 0.9 to 2.5 nm, the biexciton lifetime (τ2) of Ag2Se QDs increases from 35 to 736 ps, which is approximately 10 times longer than that of comparable-sized CdSe and PbSe QDs. A qualitative analysis based on observables indicates that the slow Auger rate is primarily attributed to the low density of the final states. The biexciton lifetime and triexciton lifetime (τ3) of Ag2Se QDs follow R3 and R2.6 dependence, respectively. Moreover, the ratio of τ2/τ3 is ∼2.3-3.2, which is markedly lower than the value expected from statistical scaling (4.5). These findings suggest that environmentally friendly Ag2Se QDs can serve as excellent candidates for low-threshold lasers and third-generation photovoltaics utilizing carrier multiplication.

A Generalized Approach to Photon Avalanche Upconversion in Luminescent Nanocrystals.

Photon avalanching nanoparticles (ANPs) exhibit extremely nonlinear upconverted emission valuable for subdiffraction imaging, nanoscale sensing, and optical computing. Avalanching has been demonstrated with Tm3+-, Pr3+-, or Nd3+-doped nanocrystals, but their emission is limited to a few wavelengths and materials. Here, we utilize Gd3+-assisted energy migration to tune the emission wavelengths of Tm3+-sensitized ANPs and generate highly nonlinear emission from Eu3+, Tb3+, Ho3+, and Er3+ ions. The upconversion intensities of these spectrally discrete ANPs scale with nonlinearity factor s = 10-17 under 1064 nm excitation at power densities as low as 7 kW cm-2. This strategy for imprinting avalanche behavior on remote emitters can be extended to fluorophores adjacent to ANPs, as we demonstrate with CdS/CdSe/CdS core/shell/shell quantum dots. ANPs with rationally designed energy transfer networks provide the means to transform conventional linear emitters into a highly nonlinear ones, expanding the use of photon avalanching in biological, chemical, and photonic applications.

Exploring the potential link between MitoEVs and the immune microenvironment of periodontitis based on machine learning and bioinformatics methods.

BACKGROUND: Periodontitis is a chronic inflammatory condition triggered by immune system malfunction. Mitochondrial extracellular vesicles (MitoEVs) are a group of highly heterogeneous extracellular vesicles (EVs) enriched in mitochondrial fractions. The objective of this research was to examine the correlation between MitoEVs and the immune microenvironment of periodontitis. METHODS: Data from MitoCarta 3.0, GeneCards, and GEO databases were utilized to identify differentially expressed MitoEV-related genes (MERGs) and conduct functional enrichment and pathway analyses. The random forest and LASSO algorithms were employed to identify hub MERGs. Infiltration levels of immune cells in periodontitis and healthy groups were estimated using the CIBERSORT algorithm, and phenotypic subgroups of periodontitis based on hub MERG expression levels were explored using a consensus clustering method. RESULTS: A total of 44 differentially expressed MERGs were identified. The random forest and LASSO algorithms identified 9 hub MERGs (BCL2L11, GLDC, CYP24A1, COQ2, MTPAP, NIPSNAP3A, FAM162A, MYO19, and NDUFS1). ROC curve analysis showed that the hub gene and logistic regression model presented excellent diagnostic and discriminating abilities. Immune infiltration and consensus clustering analysis indicated that hub MERGs were highly correlated with various types of immune cells, and there were significant differences in immune cells and hub MERGs among different periodontitis subtypes. CONCLUSION: The periodontitis classification model based on MERGs shows excellent performance and can offer novel perspectives into the pathogenesis of periodontitis. The high correlation between MERGs and various immune cells and the significant differences between immune cells and MERGs in different periodontitis subtypes can clarify the regulatory roles of MitoEVs in the immune microenvironment of periodontitis. Future research should focus on elucidating the functional mechanisms of hub MERGs and exploring potential therapeutic interventions based on these findings.

A Cox Nomogram for Assessing Recurrence Free Survival in Hepatocellular Carcinoma Following Surgical Resection Using Dynamic Contrast-Enhanced MRI Radiomics.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) is difficult to predict and carries high mortality. This study utilized radiomic techniques with clinical examinations to assess recurrence in HCC. PURPOSE: To develop a Cox nomogram to assess the risk of postoperative recurrence in HCC using radiomic features of three volumes of interest (VOIs) in preoperative dynamic contrast-enhanced MRI (DCE-MRI), along with clinical findings. STUDY TYPE: Retrospective. SUBJECTS: 249 patients with pathologically proven HCCs undergoing surgical resection at three institutions were selected. FIELD STRENGTH/SEQUENCE: Fat saturated T2-weighted, Fat saturated T1-weighted, and DCE-MRI performed at 1.5 T and 3.0 T. ASSESSMENT: Three VOIs were generated; the tumor VOI corresponds to the area from the tumor core to the outer perimeter of the tumor, the tumor +10 mm VOI represents the area from the tumor perimeter to 10 mm distal to the tumor in all directions, finally, the background liver parenchyma VOI represents the hepatic tissue outside the tumor. Three models were generated. The total radiomic model combined information from the three listed VOI's above. The clinical-radiological model combines physical examination findings with imaging characteristics such as tumor size, margin features, and metastasis. The combined radiomic model includes features from both models listed above and showed the highest reliability for assessing 24-month survival for HCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) Cox regression, univariable, and multivariable Cox regression, Kmeans clustering, and Kaplan-Meier analysis. The discrimination performance of each model was quantified by the C-index. A P value <0.05 was considered statistically significant. RESULTS: The combined radiomic model, which included features from the radiomic VOI's and clinical imaging provided the highest performance (C-index: training cohort = 0.893, test cohort = 0.851, external cohort = 0.797) in assessing the survival of HCC. CONCLUSION: The combined radiomic model provides superior ability to discern the possibility of recurrence-free survival in HCC over the total radiomic and the clinical-radiological models. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Ion recognition properties of 2,2'-bibenzimidazole regulated by ammonium-modified pillar[5]arenes.

With the increasing issues of environmental degradation and health problem, the selective detection of toxic ions has attracted considerable attention from researchers. Chemical fluorescent sensors with the advantages of facile operation, high sensitivity, rapid response, and easy visualization are emerging as powerful detection tools towards ions. However, the selective recognition of ions is always hindered by the presence of other interfering substances. Herein, we show that supramolecular host-guest interaction based on a pillar[5]arene provides a new opportunity to regulate the ionic recognition properties of guest molecules. A pillar[5]arene-based host-guest complex HG was constructed through the host-guest interaction between ammonium functionalized pillar[5]arene (HAP5) and 2,2'-bibenzimidazole (G). The host-gust complex HG can realize the successive, highly selective, and sensitive detection of specific ions. It was found that only in the presence of HAP5, the sensitivity towards cations was evidently enhanced, and selective successive recognition for I- and HSO4- was achieved. Those results indicate that the introduction of HAP5 can effectively improve the ion recognition performance of 2,2'-bibenzimidazole, so it is a feasible strategy using supramolecular host-guest interaction to regulate the ionic recognition properties of guest molecules.

Concomitant aortic regurgitation predicts better left ventricular reverse remodeling after transcatheter aortic valve replacement.

BACKGROUND: We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). METHODS: We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. RESULTS: A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69-78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression. CONCLUSIONS: Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR.

Interpretable machine-learning model for Predicting the Convalescent COVID-19 patients with pulmonary diffusing capacity impairment.

INTRODUCTION: The COVID-19 patients in the convalescent stage noticeably have pulmonary diffusing capacity impairment (PDCI). The pulmonary diffusing capacity is a frequently-used indicator of the COVID-19 survivors' prognosis of pulmonary function, but the current studies focusing on prediction of the pulmonary diffusing capacity of these people are limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting PDCI in the COVID-19 patients using routinely available clinical data, thus assisting the clinical diagnosis. METHODS: Collected from a follow-up study from August to September 2021 of 221 hospitalized survivors of COVID-19 18 months after discharge from Wuhan, including the demographic characteristics and clinical examination, the data in this study were randomly separated into a training (80%) data set and a validation (20%) data set. Six popular machine learning models were developed to predict the pulmonary diffusing capacity of patients infected with COVID-19 in the recovery stage. The performance indicators of the model included area under the curve (AUC), Accuracy, Recall, Precision, Positive Predictive Value(PPV), Negative Predictive Value (NPV) and F1. The model with the optimum performance was defined as the optimal model, which was further employed in the interpretability analysis. The MAHAKIL method was utilized to balance the data and optimize the balance of sample distribution, while the RFECV method for feature selection was utilized to select combined features more favorable to machine learning. RESULTS: A total of 221 COVID-19 survivors were recruited in this study after discharge from hospitals in Wuhan. Of these participants, 117 (52.94%) were female, with a median age of 58.2 years (standard deviation (SD) = 12). After feature selection, 31 of the 37 clinical factors were finally selected for use in constructing the model. Among the six tested ML models, the best performance was accomplished in the XGBoost model, with an AUC of 0.755 and an accuracy of 78.01% after experimental verification. The SHAPELY Additive explanations (SHAP) summary analysis exhibited that hemoglobin (Hb), maximal voluntary ventilation (MVV), severity of illness, platelet (PLT), Uric Acid (UA) and blood urea nitrogen (BUN) were the top six most important factors affecting the XGBoost model decision-making. CONCLUSION: The XGBoost model reported here showed a good prognostic prediction ability for PDCI of COVID-19 survivors during the recovery period. Among the interpretation methods based on the importance of SHAP values, Hb and MVV contributed the most to the prediction of PDCI outcomes of COVID-19 survivors in the recovery period.

Evaluation of pyrrolidine-based analog of jaspine B as potential SphK1 inhibitors against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitise, and its pathogenesis is complicated. Sphingosine-1-phosphate (S1P) is a lipid produced by sphingosine kinase 1 and 2 (SphK1/2), which participate in some of most-spread skeletal diseases such as rheumatoid arthritis or osteoarthritis. To explore the anti-inflammatory activity of 2-epi-jaspine B analogs as SphKs inhibitors, we used LPS-induced rheumatoid arthritis fibroblast-like synovial cells (HFLS-RA) as the research object to evaluate the anti-inflammatory activity of 16 2-epi-jaspine B analogs and the newly synthesized salt CHJ01. We found that 2-epi-jaspine B analog CHJ01 in hydrochloride salt form has excellent SphK1 inhibitory effect and better anti-RA effect. CHJ01 showed an anti-inflammatory effect similar to that of MTX in vitro, its IC50 value is 8.64 µM. Moreover, the anti-RA effect of CHJ01 was also studied by using a Complete Freund's Adjuvant (CFA)-induced arthritis (AIA) in a rat mode. Pharmacological experiments show that CHJ01 can help to significantly improve the symptoms of rheumatoid arthritis by reducing the swelling volume, arthritis score, spleen index and the level of IL-1ß, TNF-α, IL-6 of AIA rats. Therefore, CHJ01 holds high potential for the treatment of RA.

Simultaneous Determination of 6 Antiretroviral Drugs in Human Hair Using an LC-ESI+-MS/MS Method: Application to Adherence Assessment.

BACKGROUND: The determination of antiretroviral drugs in hair is receiving considerable research interest to assess long-term adherence to antiretroviral therapy (ART). Currently in China, lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir are combined as first-line and second-line free therapy regimens and are recommended for people living with HIV (PLWH). Simultaneous determination of the 6 antiretroviral drugs in human hair is important for accurately and widely assessing long-term adherence in Chinese PLWH receiving different ART regimens. METHODS: Six drugs were extracted from 10-mg hair samples incubated in methanol for 16 hours at 37°C and then analyzed by liquid chromatography with tandem mass spectrometry using a mobile phase of 95% methanol, with an electrospray ionization source in multiple reaction monitoring and positive mode. RESULTS: The LC-ESI+-MS/MS method exhibited a linear range (R2 > 0.99) within 6-5000, 10-5000, 6-50,000, 12-50,000, 8-5000, and 8-12,500 pg/mg for lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir. For all 6 drugs, the limits of quantification ranged between 6 and 12 pg/mg. The intraday and interday coefficients of variation were within 15%, and the recoveries ranged from 91.1% to 113.7%. Furthermore, the other validation parameters (ie, selectivity, matrix effect, stability, and carryover) met the acceptance criteria stipulated by guidelines of the US Food and Drug Administration and European Medicines Agency. Significant intergroup differences were observed between high-adherence and low-adherence groups, with high intercorrelations in the hair content of the 6 drugs. CONCLUSIONS: The developed method demonstrated good reliability, to comprehensively and accurately assess adherence in PLWH receiving different ART regimens.

Age-related changes in endogenous glucocorticoids, gonadal steroids, endocannabinoids and their ratios in plasma and hair from the male C57BL/6 mice.

Age-related level changes of hormones, endocannabinoids and their ratios are of pathophysiological significance for understanding functions, activities and interactions of the endocrine systems, including the hypothalamic-pituitaryadrenal (HPA), hypothalamic-pituitary-gonadal (HPG) axes and endogenous cannabinoid system (ECS). The present study aimed to investigate the age-dependent fluctuations of glucocorticoids, gonadal steroids, endocannabinoids and their ratios from 21 days to 10 months in both plasma and hair from the male C57BL/6 mice. A novel framework based on the liquid chromatography-tandem mass spectrometry was developed to simultaneously determine ten hormones and two endocannabinoids in plasma and hair. Results showed that glucocorticoids, corticosterone (CORT), aldosterone (ALD), 11-dehydrocorticosterone (11-DHC), gonadal steroids, progesterone (P), dehydroepiandrosterone (DHEA), testosterone (T) and dihydrotestosterone (DHT) in plasma were unimodally fluctuated (ps < 0.001) along age with the maximum value at 2.7-month-old. In contrast, the other two gonadal steroids, estrone (E1) and estradiol (E2) were declined with age (ps < 0.001). Differently, endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 1-arachydonoyl glycerol (1-AG) showed nadir and zenith values at 2.7-month-old and 3.4-month-old, respectively (ps < 0.001). Additionally, the ratios of CORT to 11-DHC and ALD in plasma were dropped similarly with age (ps < 0.001). The ratios of 1-AG to AEA, and of T to A4 and DHT, and of DHEA to A4 were unimodally changed (ps < 0.001) along age with maximum value at 2.7- or 3.4-month-old. In contrast, the ratios of E2 to T and E1 to A4 were decreased with age (ps < 0.05). The rest six ratios that reflected the interactions among the three endocrine systems, were similar age-dependent and showed nadir and zenith values at 2.7-month-old and 3.4-month-old, respectively (ps < 0.05). Most importantly, these findings in light of age-related changing patterns in plasma were repeated in hair, suggesting that the fi41-ndings in the two matrices were mutually validated. However, it was worth noting that their magnitude of levels in the two bio-matrices were markedly different. The current findings could provide reliable hormone and endocannabinoid signatures with age on neuroendocrine profiles as well as their ratios for the male C57BL/6 mice.

Impacts of the COVID-19 pandemic on fish trade and the coping strategies: An initial assessment from China's perspective.

The outbreak of the COVID-19 pandemic in 2020 has posed unprecedented challenges for fish trade worldwide. This study examines these challenges through an observation of China's fish import and export activities and a qualitative study on evolving policies in the first nine months of 2020. The results indicate that control measures responding to uncertainty regarding the source of the disease and transmission path, the pressing need for restriction of the movement of people and goods, and fear of a second wave of outbreaks have substantially disrupted fish trade. To meet these challenges, certain coping measures are adopted to offset negative effects in the short term. These measures indicate the government's pivotal role in stabilizing the supply chain and striking a balance between control requirements and efficiency required in trading activities, as well as the importance to find alternative markets to mitigate risks brought by the delayed supply and the plummeting consumption market. It concludes with some suggestions on improving international cooperation and domestic regulation for building resilience in long run.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Parametric upconversion of Ince-Gaussian modes.

The Ince-Gaussian (IG) mode, a recently discovered type of structured Gaussian beam, corresponds to eigenfunctions of the paraxial wave equation in elliptical coordinates. This propagation-invariant mode is of significance in various domains, in particular, its nonlinear transformation; however, there have been few relevant studies to date. In this Letter, we report the parametric upconversion of IG modes and associated full-field selection rule for the first time, to the best of our knowledge. We demonstrate that IG signals can be perfectly upconverted by a flattop-beam pump; in contrast, significant mode distortion occurred when using the most common Gaussian pump. Particular attention was given to the origin of the distortion, i.e., radial-mode degeneration induced by the sum-frequency generation excited by a Gaussian pump. This proof-of-principle demonstration has great significance in relevant areas, such as high-dimensional quantum frequency interfacing and upconversion imaging.

Electroencephalographic abnormalities are correlated with cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes: A clinical study of 61 cases.

OBJECTIVE: The objective of this study was to explore the effect of spikes on cognition in patients with benign childhood epilepsy with centrotemporal spikes (BECTS) and to identify electroencephalography (EEG) markers enabling early detection of cognitive impairment. METHODS: Sixty-one children with BECTS diagnoses and 60 age- and education-matched healthy controls were enrolled. Four-hour EEG recordings were analyzed for each patient to check for interictal spikes, high-frequency oscillations (HFOs), nondipole spikes, and other atypical EEG features and to examine the spike-wave index of nonrapid eye movement (NREM) sleep. All 121 children underwent a series of neuropsychological tests to assess cognitive function. RESULTS: Patients with a high NREM sleep discharge index (≥55%) in the first sleep cycle exhibited significantly lower scores for arithmetic calculation, executive function, and attention and memory tests than patients with a low discharge index (<55%). Eight patients with HFOs exhibited even poorer performance than HFO-negative patients for arithmetic calculation, executive function, vocabulary comprehension, visual perception, vocal perception, spatial memory ability, and response ability. Children with bilateral discharge exhibited poorer ability in three-dimensional spatial imaging test, poorer memory, and slower response than did those with unilateral discharge (P < .05). Nondipole spikes, multiple asynchronous discharges, and generalized spike-wave discharges respectively had an impact on calculation ability, memory, and reaction ability respectively (P < .05). CONCLUSIONS: Spike frequencies in stage 3 and 4 sleep varied from those observed in stage 1 and 2 sleep; the highest spike frequency was in stage 2 sleep. High NREM sleep discharge index (i.e., ≥55%) and HFOs were linked to the highest risk for cognitive deficit, while bilateral discharges, nondipole spikes, multiple asynchronous discharges, and generalized spike-wave discharges were less indicative of cognitive impairment.

Synthesis and biological evaluation of 2-epi-jaspine B analogs as selective sphingosine kinase 1 inhibitors.

2-Epi-jaspine B is an isomer of the natural product jaspine B and shows certain selectivity for SphK1 and potent antitumor activity. Based on the crystal structure of SphK1, we transformed the structure of 2-epi-jaspine B and modified the hydrophobic side chain to obtain a series of 2-epi-jaspine B analogs. The MTT assay was used to examine the antitumor activities of these analogs. We identified a novel 2-epi-jaspine B analog YHR17, which has potent antiproliferative activities for tested cell lines with IC50 values that ranged from 0.68 to 5.68 µM and inhibited the proliferation of the A375 cell line by affecting the cell cycle and apoptosis. Furthermore, YHR17 inhibited SphK1 with more than 125-fold selectivity over SphK2.

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence.

The adherence assessment based on the combination of nevirapine (NVP) and its two metabolites (2-hydroxynevirapine and 3-hydroxynevirapine) would more comprehensively and accurately reflect long-term adherence than that of a single prototype. This study aimed to develop a specific, sensitive and selective method for simultaneous detection of the three compounds in hair and explore whether there was consistency among the three compounds in assessing long-term adherence. Furthermore, 75 HIV-positive patients who were taking the NVP drug were randomly recruited and divided into two groups (high-and low-adherence group). All participants self-reported their days of oral drug administration per month and provided their hair strands closest to the scalp at the region of posterior vertex. The concentrations of three compounds in the hair were determined using a developed LC-MS/MS method in multiple reaction monitoring. This method showed good performances in limit of quantification and accuracy with the recoveries from 85 to 115% and in precision with the intra-day and inter-day coefficients of variation within 15% for the three compounds. The population analysis revealed that patients with high-adherence showed significantly higher concentrations than those with low-adherence for all three compounds. There were significantly moderate correlations of nevirapine with 2-hydroxynevirapine and 3-hydroxynevirapin and high correlation between 2-hydroxynevirapine and 3-hydroxynevirapin. The two NVP's metabolites showed high consistency with NVP in evaluating long-term adherence.

MicroRNA-mediated regulation of T helper type 17/regulatory T-cell balance in autoimmune disease.

T helper type 17 (Th17) cells and regulatory T (Treg) cells are two distinct T-cell subsets with opposite effects on immune functions. While Th17 cells are a key effector in the immune response and play critical roles in the development of autoimmunity and inflammation, Treg cells orchestrate the overall immune response and maintain peripheral immune tolerance by regulating the activity of the effector T cells. However, the developmental pathways for Th17 and Treg cells are reciprocally interconnected and there is a significant amount of plasticity between them. Disturbed Th17/Treg balance contributes to the development of autoimmune diseases, like experimental autoimmune encephalomyelitis and multiple sclerosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Recently, emerging evidence demonstrates that miRNAs play an important role in regulating the pathogenesis of autoimmune diseases through the modulation of Th17/Treg balance. This review will provide an overview of the dysregulated miRNAs and their functions in modulating the Th17/Treg balance in autoimmune diseases.