Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

Systemic Type 2 Inflammation-Associated Atopic Dermatitis Exacerbates Periodontitis.

INTRODUCTION: Atopic dermatitis (AD) is a prevalent and chronic inflammatory skin disease characterized by Th2 cell-mediated type 2 inflammation. Emerging evidence indicated that AD patients exhibit an increased incidence of oral disorders. In the present study, we sought mechanistic insights into how AD affects periodontitis. METHODS: Onset of AD was induced by 2,4-dinitrochlorobenzene (DNCB). Furthermore, we induced periodontitis (P) in AD mice. The effect of AD in promoting inflammation and bone resorption in gingiva was evaluated. Hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, immunofluorescence assay, and flow cytometry were used to investigate histomorphology and cytology analysis, respectively. RNA sequencing of oral mucosa is used tissues to further understand the dynamic transcriptome changes. 16S rRNA microbial analysis is used to profile oral microbial composition. RESULTS: Compared to control group, mice in AD group showed inflammatory signatures and infiltration of a proallergic Th2 (Th2A)-like subset in oral mucosa but not periodontitis, as identified by not substantial changes in mucosa swelling, alveolar bone loss, and TRAP+ osteoclasts infiltration. Similarly, more Th2A-like cell infiltration and interleukin-4 levels were significantly elevated in the oral mucosa of DNCB-P mice compared to P mice. More importantly, AD exacerbates periodontitis when periodontitis has occurred and the severity of periodontitis increased with aggravation of dermatitis. Transcriptional analysis revealed that aggravated periodontitis was positively correlated with more macrophage infiltration and abundant CCL3 secreted. AD also altered oral microbiota, indicating the re-organization of extracellular matrix. CONCLUSIONS: These data provide solid evidence about exacerbation of periodontitis caused by type 2 dermatitis, advancing our understanding in cellular and microbial changes during AD-periodontitis progression.

Improved visual outcomes of central retinal artery occlusion with local intra-arterial fibrinolysis beyond the conventional time window.

Local intra-arterial fibrinolysis (LIF) is a promising therapeutic option for CRAO. However, the narrow time window of 6 h has greatly limited the application of LIF. In this study, we explored the efficacy of LIF beyond the conventional time windows and compared the result with conservative therapy. This prospective study included 179 CRAO patients with baseline visual acuity (VA) ≤ 20/400 treated at Renmin Hospital of Wuhan University. The mean time from vision loss to presentation was 5.5 days. 58 patients received conventional standard therapy (CST) alone.121 patients underwent LIF. Main outcome was VA improvement ≥ 0.3 logMAR. Secondary outcome was a favorable VA outcome of 20/200 or better. Logistic regressions were performed to identify predictors of visual improvement. 43% patients in the LIF group experienced VA improvement versus 19% with CST (P = 0.002). LIF was associated with 4.0-fold higher likelihood of visual improvement compared to CST (P = 0.001). Poor baseline VA (light perception or no light perception) and shortened prothrombin time (PT) were associated with greater chance of visual improvement with LIF. However, LIF showed no significant advantage over CST for favorable VA outcomes. No major complications occurred. LIF beyond the therapeutic time window improved vision in functionally blind CRAO patients and showed better efficacy when compared with CST. PT may be a potential predictor of visual outcome after LIF. Our findings could complement existing time-based treatment guidelines and potentially allow for personalized decisions on the use of LIF beyond time windows.

Handedness Inversion of Chiral 3-Aminophenol Formaldehyde Resin Nanotubes Mediated by Metal Coordination.

Precise adjustment of microstructure and handedness of chiral nanomaterials is important to regulate their properties and performance. Herein, helical 3-aminophenol formaldehyde resin (APF) nanotubes and corresponding carbonaceous nanotubes with controllable handedness and optical activity were obtained via an external metal ion-mediated supramolecular co-templating method in an enantiomerically pure template system, in which an appropriate amount of Mn2+ (Co2+ or Ni2+ ) with moderate coordination abilities can reverse the spatial arrangement of the phenylglycine-based amphiphilic template molecules through metal coordination. Different stacking modes of coordination complexes in disparate metal ion systems lead to diverse helical senses (diameter and pitch) of the obtained helical APF. In addition, this coordination mode of metal intervention can be applied to other amine-based helical polymer synthesis systems, which paves the way for the design of high-quality chiral nanomaterials with satisfactory physical parameters and properties.

Fiber organic electrochemical transistors based on multi-walled carbon nanotube and polypyrrole composites for noninvasive lactate sensing.

Multi-walled carbon nanotubes (MWCNT) play a synergistic role with conducting polymer in practical applications such as biological sensing. In this paper, multi-walled carbon nanotube and polypyrrole (PPy) composites were prepared on a fiber surface for the first time, and their morphology and electrical properties were characterized. Compared with PPy-coated fiber, the presence of carbon nanotubes induced the growth of large areas of PPy nanowires. In addition, fiber organic electrochemical transistors (FECTs) based on PPy and MWCNT were assembled, showing a higher on/off ratio, better stability, and greater flexibility. The lactate biosensor based on FECTs exhibits high sensitivity, with a correlation coefficient of R = 0.9889, quick response time of 0.6-0.8 s, a wide linear response range of 1 nM-1 mM, and excellent selectivity for lactate. Furthermore, the lactate concentration in human sweat was successfully detected by a FECT-based sensor. The hybrid fibers can be easily woven and placed on fabric simply by stitching. This favorable performance of the FECT-based sensor makes it suitable for noninvasive sensing of lactate. Therefore, it provides a promising platform for future use in healthcare and detection applications. Graphical abstract.

Influence of critical thinking disposition on the learning efficiency of problem-based learning in undergraduate medical students.

BACKGROUND: Problem-based learning (PBL), a pedagogical approach, is widely accepted in medical education. Manipulated by many factors, the internal motivation of learner is the most crucial determinant that affects the nature of the outcome, in which the influences of critical thinking (CT) remained elusive. METHODS: One hundred two third-year undergraduate medical students at Peking University were involved in this study. A Chinese version of the Critical Thinking Disposition Inventory (CTDI-CV) was used to assess the CT disposition, and the performance scores of students in PBL tutorials were compiled. A parametric bivariate correlation analysis was performed between the students' CT scores and their PBL average scores. The PBL scores were compared between the strong and weak CT disposition groups using independent t-test. The analysis of numerical data was conducted using SPSS 16.0. RESULTS: CT disposition of third-year undergraduate medical students at Peking University was at a positive level, with an average score of 297.72. The total CT scores had a positive correlation with the scores of the PBL performance and its five dimensions significantly. In the majority, students with Strong-CT disposition obtained higher scores in PBL tutorials compared with students with Weak-CT disposition. The performance of these two groups was significantly different in the Late-Half but not in the Early-Half PBL tutorials. Furthermore, a significant improvement was observed in the students with strong CT but not weak CT dispositions. CONCLUSION: CT disposition positively correlates to a students' PBL performance. Students with stronger CT dispositions perform better in the PBL process and obtain higher scores. Our work suggested that the open-mindedness of the CT disposition is the primary factor that determines the improvement of the preparation dimensions in the PBL process.

Hierarchically Three-Dimensional Nanofiber Based Textile with High Conductivity and Biocompatibility As a Microbial Fuel Cell Anode.

Microbial fuel cells (MFCs) encompass complex bioelectrocatalytic reactions that converting chemical energy of organic compounds to electrical energy. Improving the anode configuration is thought to be a critical step for enhancing MFCs performance. In present study, a hierarchically structured textile polypyrrole/poly(vinyl alcohol-co-polyethylene) nanofibers/poly(ethylene terephthalate) (referred to PPy/NFs/PET) is shown to be excellent anode for MFCs. This hierarchical PPy/NFs/PET anode affords an open porous and three-dimensional interconnecting conductive scaffold with larger surface roughness, facilitating microbial colonization and electron transfer from exoelectrogens to the anode. The mediator-less MFC equipped with PPy/NFs/PET anode achieves a remarkable maximum power density of 2420 mW m(-2) with Escherichia coli as the microbial catalyst at the current density of 5500 mA m(-2), which is approximately 17 times higher compared to a reference anode PPy/PET (144 mW m(-2)). Considering the low cost, low weight, facile fabrication, and good winding, this PPy/NFs/PET textile anode promises a great potential for high-performance and cost-effective MFCs in a large scale.

Ion sensors based on novel fiber organic electrochemical transistors for lead ion detection.

Fiber organic electrochemical transistors (FECTs) based on polypyrrole and nanofibers have been prepared for the first time. FECTs exhibited excellent electrical performances, on/off ratios up to 10(4) and low applied voltages below 2 V. The ion sensitivity behavior of the fiber organic electrochemical transistors was investigated. It exhibited that the transfer curve of FECTs shifted to lower gate voltage with increasing cations concentration, the sensitivity reached to 446 µA/dec in the 10(-5)-10(-2) M Pb(2+) concentration range. The ion selective properties of the FECTs have also been systematically studied for the detection of potassium, calcium, aluminum, and lead ions. The devices with different cations showed great difference in response curves. It was suitable for selectively monitoring Pb(2+) with respect to other cations. The results indicated FECTs were very effective for electrochemical sensing of lead ion, which opened a promising perspective for wearable electronics in healthcare and biological application. Graphical Abstract The schematic diagram of fiber organic electrochemical transistors based on polypyrrole and nanofibers for ion sensing.

Evaluation of the Nano-TiO2 as a Novel Deswelling Material.

Nano-TiO2 is widely applied in the automobile exhaust hose reels as a catalyst to reduce oxynitride emissions, including nitric oxide (NO). In the biomedicine field, NO plays an important role in vasodilation and edema formation in human bodies. However, the deswelling activity of nano-TiO2 has not been reported. Here, we demonstrated that nano-TiO2 can significantly degrade the production of NO in LPS-induced RAW264.7 mouse macrophages. Further study indicated that nano-TiO2 exhibited an effect on vascular permeability inhibition, and prevented carrageenan-induced footpad edema. Therefore, we prepared a nano-TiO2 ointment and observed similar deswelling effects. In conclusion, nano-TiO2 might act as a novel deswelling agent related with its degradation of NO, which will aid in our ability to design effective interventions for edema involved diseases.

Comparisons of ultrafine and fine particles in their associations with biomarkers reflecting physiological pathways.

Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics compared to before and after the Olympics, we conducted the current study to compare ultrafine particles (UFPs) and fine particles (PM2.5) in their associations with biomarkers reflecting multiple pathophysiological pathways linking exposure and cardiorespiratory events. Number concentrations of particles (13.0-764.7 nm) and mass concentrations of PM2.5 were measured at two locations within 9 km from the residence and workplace of 125 participating Beijing residents. Each participant was measured 6 times for biomarkers of autonomic function (heart rate, systolic and diastolic blood pressures), hemostasis (von Willebrand factor, soluble CD40 ligand, and P-selectin), pulmonary inflammation and oxidative stress (exhaled nitric oxide and exhaled breath condensate pH, malondialdehyde, and nitrite), and systemic inflammation and oxidative stress (urinary malondialdehyde and 8-hydroxy-2'-deoxyguanosine, plasma fibrinogen, and white blood cells). Linear mixed models were used to estimate associations of biomarkers with UFPs and PM2.5 measured 1-7 days prior to biomarker measurements (lags). We found that the correlation coefficient for UFPs at two locations (∼ 9 km apart) was 0.45, and at the same location, the correlation coefficient for PM2.5 vs UFPs was -0.18. Changes in biomarker levels associated with increases in UFPs and PM2.5 were comparable in magnitude. However, associations of certain biomarkers with UFPs had different lag patterns compared to those with PM2.5, suggesting that the ultrafine size fraction (≤ 100 nm) and the fine size fraction (∼ 100 nm to 2.5 µm) of PM2.5 are likely to affect PM-induced pathophysiological pathways independently.

Role of berberine in anti-bacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor.

BACKGROUND: Berberine is an isoquinoline alkaloid mainly extracted from Rhizoma Coptidis and has been shown to possess a potent inhibitory activity against bacterial. However, the role of berberine in anti-bacterial action has not been extensively studied. METHODS: The animal model was established to investigate the effects of berberine on bacterial and LPS infection. Docking analysis, Molecular dynamics simulations and Real-time RT-PCR analysis was adopted to investigate the molecular mechanism. RESULTS: Treatment with 40 mg/kg berberine significantly increased the survival rate of mice challenged with Salmonella typhimurium (LT2), but berberine show no effects in bacteriostasis. Further study indicated that treatment with 0.20 g/kg berberine markedly increased the survival rate of mice challenged with 2 EU/ml bacterial endotoxin (LPS) and postpone the death time of the dead mice. Moreover, pretreatment with 0.05 g/kg berberine significantly lower the increasing temperature of rabbits challenged with LPS. The studies of molecular mechanism demonstrated that Berberine was able to bind to the TLR4/MD-2 receptor, and presented higher affinity in comparison with LPS. Furthermore, berberine could significantly suppressed the increasing expression of NF-κB, IL-6, TNFα, and IFNß in the RAW264.7 challenged with LPS. CONCLUSION: Berberine can act as a LPS antagonist and block the LPS/TLR4 signaling from the sourse, resulting in the anti-bacterial action.

Peripheral blood transcriptomic analysis identifies potential inflammation and immune signatures for central retinal artery occlusion.

Central retinal artery occlusion (CRAO) is an acute retinal ischaemic disease, but early diagnosis is challenging due to a lack of biomarkers. Blood samples were collected from CRAO patients and cataract patients. Gene expression profiles were distinct between arterial/venous CRAO blood (A-V group) and venous CRAO/control blood (V-C group) samples. Differentially expressed genes (DEGs) were subjected to GO and KEGG enrichment analyses. Hub genes were identified by Cytoscape and used to predict gene interactions via GeneMANIA. Immune cell infiltration was analysed by CIBERSORT. More than 1400 DEGs were identified in the A-V group and 112 DEGs in the V-C group compared to controls. The DEGs in both groups were enriched in the ribosome pathway, and those in the V-C group were also enriched in antigen processing/MHC pathways. Network analysis identified ribosomal proteins (RPS2 and RPS5) as the core genes of the A-V group and MHC genes (HLA-F) as the core genes of the V-C group. Coexpression networks showed ribosomal involvement in both groups, with additional immune responses in the V-C group. Immune cell analysis indicated increased numbers of neutrophils and T cells. Ribosomal and MHC-related genes were identified as potential CRAO biomarkers, providing research directions for prevention, diagnosis, treatment and prognosis.

Clinical application of multicolor scanning laser ophthalmology in diagnosis and grading of central retinal artery occlusion.

Purpose: To characterize features of central retinal artery occlusion (CRAO) using multicolor (MC) imaging and to assess the differences in CRAO grading between color fundus photography (CFP) and MC image qualitatively and quantitatively. Methods: We conducted a prospective, cross-sectional study in the Department of Ophthalmology of Renmin Hospital of Wuhan University. In total, 86 acute CRAO patients were included. Spectral-domain optical coherence tomography (SD-OCT), CFP, and MC examinations were taken at baseline. Based on the findings of these three examinations, CRAO was divided into three grades (incomplete, subtotal, and total). Based on OCT grading criteria, we qualitatively compared the ability of grading CRAO by CFP and MC. CRAO patient's visual acuity (VA) was obtained from the initial visit. The retinal thickness was measured by SD-OCT. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained from optical coherence tomography angiography (OCTA) examinations. Quantitative data were compared across the three acute CRAO subgroups and against three examination findings. Results: MC image had significantly higher power of acute CRAO detection than CFP (P = 0.03). In the same group of CRAO patients, there was no significant difference in VA when comparing OCT with the MC grading system or with the CFP grading system (all P > 0.05). Significant differences in VA were found between the three CRAO subgroups only under MC grading (P = 0.016). In incomplete CRAO patients, significant differences were found in central fovea thickness (CFT) when comparing OCT with the CFP grading system (P = 0.019). In the same group of CRAO patients, there was no significant difference in retinal thickness when comparing OCT with the MC grading system (All P > 0.05). Significance differences in CFT (P < 0.001), innermost retinal layer (IMRL; P < 0.01), middle retinal layer (MRL; P < 0.001), and outer retinal layer (ORL; P = 0.021) were found between the three CRAO subgroups by MC grading. Vessel density of SCP showed a statistically increased as the severity of three CRAO subgroups (P = 0.03), whereas DCP did not have significant differences (P = 0.745). Comparisons were made between the OCT grading method and the MC and CFP grading methods; there is no significant difference in vessel density of SCP and DCP (All P > 0.05). Conclusion: The images obtained by MC are superior to those obtained by CFP in CRAO grading, retinal thickness, and vessel density measurement. MC imaging may be more capable of CRAO grading than OCT. We recommend MC imaging to determine CRAO severity to guide disease treatment and predict visual prognosis.

Plasmalogens and Octanoylcarnitine Serve as Early Warnings for Central Retinal Artery Occlusion.

Central retinal artery occlusion (CRAO) is a kind of ophthalmic emergency which may cause loss of functional visual acuity. However, the limited treatment options emphasize the significance of early disease prevention. Metabolomics has the potential to be a powerful tool for early identification of individuals at risk of CRAO. The aim of the study was to identify potential biomarkers for CRAO through a comprehensive analysis. We employed metabolomics analysis to compare venous blood samples from CRAO patients with cataract patients for the venous difference, as well as arterial and venous blood from CRAO patients for the arteriovenous difference. The analysis of metabolites showed that PC(P-18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PC(P-18:0/20:4(5Z,8Z,11Z,14Z)) and octanoylcarnitine were strongly correlated with CRAO. We also used univariate logistic regression, random forest (RF), and support vector machine (SVM) to screen clinical parameters of patients and found that HDL-C and ApoA1 showed significant predictive efficacy in CRAO patients. We compared the predictive performance of the clinical parameter model with combined model. The prediction efficiency of the combined model was significantly better with area under the receiver operating characteristic curve (AUROC) of 0.815. Decision curve analysis (DCA) also exhibited a notably higher net benefit rate. These results underscored the potency of these three substances as robust predictors of CRAO occurrence.

Inflammatory and oxidative stress responses of healthy young adults to changes in air quality during the Beijing Olympics.

RATIONALE: Unprecedented pollution control actions during the Beijing Olympics provided a quasi-experimental opportunity to examine biologic responses to drastic changes in air pollution levels. OBJECTIVES: To determine whether changes in levels of biomarkers reflecting pulmonary inflammation and pulmonary and systemic oxidative stress were associated with changes in air pollution levels in healthy young adults. METHODS: We measured fractional exhaled nitric oxide, a number of exhaled breath condensate markers (H(+), nitrite, nitrate, and 8-isoprostane), and urinary 8-hydroxy-2-deoxyguanosine in 125 participants twice in each of the pre- (high pollution), during- (low pollution), and post-Olympic (high pollution) periods. We measured concentrations of air pollutants near where the participants lived and worked. We used mixed-effects models to estimate changes in biomarker levels across the three periods and to examine whether changes in biomarker levels were associated with changes in pollutant concentrations, adjusting for meteorologic parameters. MEASUREMENTS AND MAIN RESULTS: From the pre- to the during-Olympic period, we observed significant and often large decreases (ranging from -4.5% to -72.5%) in levels of all the biomarkers. From the during-Olympic to the post-Olympic period, we observed significant and larger increases (48-360%) in levels of these same biomarkers. Moreover, increased pollutant concentrations were consistently associated with statistically significant increases in biomarker levels. CONCLUSIONS: These findings support the important role of oxidative stress and that of pulmonary inflammation in mediating air pollution health effects. The findings demonstrate the utility of novel and noninvasive biomarkers in the general population consisting largely of healthy individuals.

Cardiorespiratory biomarker responses in healthy young adults to drastic air quality changes surrounding the 2008 Beijing Olympics.

Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents' biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics. To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2'-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matter < or = 2.5 microm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification. We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by -36%, TPN by -22%, SO2 by -60%, CO by -48%, and NO2 by -43% (P < 0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by -27%), sulfate (SO4(2-)) (by -13%), and organic carbon (OC) (by -23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO4(2-) and O3) increased to levels similar to or higher than pre-Olympics levels. Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (P < or = 0.05) or marginally significant (0.05 < P < 0.1) decreases in HR (-1 bpm or -1.7% [95% CI, -3.4 to -0.1]), SBP (-1.6 mmHg or -1.8% [95% CI, -3.9 to 0.4]), 8-OHdG (-58.3% [95% CI, -72.5 to -36.7]), FeNO (-60.3% [95% CI, -66.0 to -53.6]), EBC nitrite (-30.0% [95% CI, -39.3 to -19.3]), EBC nitrate (-21.5% [95% CI, -35.5 to -4.5]), EBC nitrite+nitrate (-17.6% [95% CI, -28.4 to -5.1]), EBC hydrogen ions (-46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (-34% [95% CI, -38.4 to -29.2]), sCD40L (-5.7% [95% CI, -10.5 to -0.7]), and vWF (-13.1% [95% CI, -18.6 to -7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, -1.7 to 10.2), neutrophil count (4.7% [95% CI, -7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or -4.8% in EBC pH [95% CI, -9.4 to -0.21), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, -3.7 to 23.5]). Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations. Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution.

Identifying biomarkers associated with the diagnosis of ulcerative colitis via bioinformatics and machine learning.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic inflammatory disease with an increasing incidence. This study aimed to identify potential UC biomarkers and associated immune infiltration characteristics. METHODS: Two datasets (GSE87473 and GSE92415) were merged to obtain 193 UC samples and 42 normal samples. Using R, differentially expressed genes (DEGs) between UC and normal samples were filtered out, and their biological functions were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Promising biomarkers were identified using least absolute shrinkage selector operator regression and support vector machine recursive feature elimination, and their diagnostic efficacy was evaluated through receiver operating characteristic (ROC) curves. Finally, CIBERSORT was used to investigate the immune infiltration characteristics in UC, and the relationship between the identified biomarkers and various immune cells was examined. RESULTS: We found 102 DEGs, of which 64 were significantly upregulated, and 38 were significantly downregulated. The DEGs were enriched in pathways associated with interleukin-17, cytokine-cytokine receptor interaction and viral protein interactions with cytokines and cytokine receptors, among others. Using machine learning methods and ROC tests, we confirmed DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 to be essential diagnostic genes for UC. Immune cell infiltration analysis revealed that all five diagnostic genes were correlated with regulatory T cells, CD8 T cells, activated and resting memory CD4 T cells, activated natural killer cells, neutrophils, activated and resting mast cells, activated and resting dendritic cells and M0, M1 and M2 macrophages. CONCLUSIONS: DUOX2, DMBT1, CYP2B7P, PITX2 and DEFB1 were identified as prospective biomarkers for UC. A new perspective on understanding the progression of UC may be provided by these biomarkers and their relationship with immune cell infiltration.

ApoB, non-HDL-C, and LDL-C Are More Prominent in Retinal Artery Occlusion Compared to Retinal Vein Occlusion.

PURPOSE: To evaluate and compare the blood lipid profile in retinal artery occlusion (RAO) and retinal vein occlusion (RVO). METHODS: We included 82 RAO patients and 95 RVO patients in this retrospective case-control study. Controls were matched to RAO or RVO patients at a 1:1 ratio, respectively. Associated lipid variates were analyzed in multivariable logistic regression models. RESULTS: LDL-C (OR = 1.69), non-HDL-C (OR = 1.87), and ApoB (OR = 11.72) individually significantly increased the risk of RAO. ApoA1 was associated with RVO (OR = 0.02), and with 75.8% sensitivity and 67.4% specificity. TG (OR = 1.61), LDL-C (OR = 1.69), non-HDL-C (OR = 1.91), and ApoB (OR = 12.12) each significantly increased the risk of RAO when compared with RVO. CONCLUSIONS: ApoB, non-HDL-C, and LDL-C may be potential biomarkers in RAO patients. Low ApoA1 is an independent risk factor for the development of RVO.

Dual-Analyte Sensing with a Molecularly Imprinted Polymer Based on Enhancement-Mode Organic Electrochemical Transistors.

Novel enhancement-mode organic electrochemical transistors (OECTs) have been prepared by poly(3, 4-ethylenedioxythiophene)-poly(styrenesulfonate) de-doped polyethylenimine on the multi-walled carbon nanotube-modified viscose yarn. The fabricated devices exhibit low power consumption with a high transconductance of 6.7 mS, rapid response time < 2 s, and excellent cyclic stability. In addition, the device has washing durability and bending and long-term stability suitable for wearable applications. Biosensors based on enhancement-mode OECTs for the selective detection of adrenaline and uric acid (UA) are developed by using molecularly imprinted polymer (MIP)-functionalized gate electrodes. The detection limits of adrenaline and UA analysis are as low as 1 pM, with the linear ranges of 0.5 pM to 10 µM and 1 pM to 1 mM, respectively. Moreover, the sensor based on enhancement-mode transistors can efficiently amplify the current signals according to the modulation of the gate voltage. The MIP-modified biosensor has high selectivity in the presence of interferents and desirable reproducibility. Additionally, due to the wearable nature of the developed biosensor, this sensing tool has the capability of being integrated with fabrics. Therefore, it has successfully been applied in textiles for the determination of adrenaline and UA in artificial urine samples. The excellent recoveries and rsds are 90.22-109.05% and 3.97-6.94%, respectively. Ultimately, these sensitive, low-power, wearable, and dual-analyte sensors help to develop non-laboratory tools for early disease diagnosis and clinical research.

Polypharmacology of ambroxol in the treatment of COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still underway. Due to the growing development of severe symptoms, it is necessary to promote effective therapies. Ambroxol [2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine] has long been used as one of the over-the-counter mucolytic agents to treat various respiratory diseases. Therefore, we focused on the mechanism of action of ambroxol in COVID-19 treatment. In vitro and in silico screening revealed that ambroxol may impede cell entry of SARS-CoV-2 by binding to neuropilin-1. Ambroxol could also interact with multiple inflammatory factors and signaling pathways, especially nuclear factor kappa B (NF-κB), to interfere cytokines cascade activated by SARS-CoV-2 internalization. Furthermore, multipathways and proteins, such as the cell cycle and matrix metalloproteinases (MMPs), were identified as significant ambroxol-targeting pathways or molecules in PBMC and lung of severe COVID-19 patients by bioinformatics analysis. Collectively, these results suggested that ambroxol may serve as a promising therapeutic candidate for the treatment of severe SARS-CoV-2 infection.