Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis.

Cuproptosis is a recently discovered programmed cell death pattern that affects the tricarboxylic acid (TCA) cycle by disrupting the lipoylation of pyruvate dehydrogenase (PDH) complex components. However, the role of cuproptosis in the progression of ischemic heart failure (IHF) has not been investigated. In this study, we investigated the expression of 10 cuproptosis-related genes in samples from both healthy individuals and those with IHF. Utilizing these differential gene expressions, we developed a risk prediction model that effectively distinguished healthy and IHF samples. Furthermore, we conducted a comprehensive evaluation of the association between cuproptosis and the immune microenvironment in IHF, encompassing infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes. Moreover, we identified two different cuproptosis-mediated expression patterns in IHF and explored the immune characteristics associated with each pattern. In conclusion, this study elucidates the significant influence of cuproptosis on the immune microenvironment in ischemic heart failure (IHF), providing valuable insights for future mechanistic research exploring the association between cuproptosis and IHF.

Structured illumination contrast transfer function for high resolution quantitative phase imaging.

We report a sub-diffraction resolution imaging of non-fluorescent samples through quantitative phase imaging. This is achieved through a novel application of structured illumination microscopy (SIM), a super-resolution imaging technique established primarily for fluorescence microscopy. Utilizing our contrast transfer function formalism with SIM, we extract the high spatial frequency components of the phase profile from the defocused intensity images, enabling the reconstruction of a quantitative phase image with a frequency spectrum that surpasses the diffraction limit imposed by the imaging system. Our approach offers several advantages including a deterministic, phase-unwrapping-free algorithm and an easily implementable, non-interferometric setup. We validate the proposed technique for high-resolution phase imaging through both simulation and experimental results, demonstrating a two-fold enhancement in resolution. A lateral resolution of 0.814 µm is achieved for the phase imaging of human cheek cells using a 0.42 NA objective lens and an illumination wavelength of 660 nm, highlighting the efficacy of our approach for high-resolution quantitative phase imaging.

"AMP plus": Immunostimulant-Inspired Design Based on Chemotactic Motif-(PhHAhPH)n.

Ability to stimulate antimicrobial immunity has proven to be a useful therapeutic strategy in treating infections, especially in the face of increasing antibiotic resistance. Natural antimicrobial peptides (AMPs) exhibiting immunomodulatory functions normally encompass complex activities, which make it difficult to optimize their therapeutic benefits. Here, a chemotactic motif was harnessed as a template to design a series of AMPs with immunostimulatory activities plus bacteria-killing activities ("AMP plus"). An amphipathic peptide ((PhHAhPH)n) was employed to improve the antimicrobial impact and expand the therapeutic potential of the chemotactic motif that lacked obvious bacteria-killing properties. A total of 18 peptides were designed and evaluated for their structure-activity relationships. Among the designed, KWH2 (1) potently killed bacteria and exhibited a narrow antimicrobial spectrum against Gram-negative bacteria and (2) activated macrophages (i.e., inducing Ca2+ influx, cell migration, and reactive oxygen species production) as a macrophage chemoattractant. Membrane permeabilization is the major antimicrobial mechanism of KWH2. Furthermore, the mouse subcutaneous abscess model supported the dual immunomodulatory and antimicrobial potential of KWH2 in vivo. The above results confirmed the efficiency of KWH2 in treating bacterial infection and provided a viable approach to develop immunomodulatory antimicrobial materials with desired properties.

Liver enzymes mediate the association between aldehydes co-exposure and hypertriglyceridemia.

Aldehydes are recognized environmental toxicants that may affect lipid metabolism. For instance, acrolein has been found to increase serum triglyceride (TG) levels exclusively. However, it remains unclear whether other aldehydes are also associated with hypertriglyceridemia (HTG), and what mechanisms may be involved. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2013-2014) to identify associations between serum aldehydes, liver enzymes, and HTG. Serum aldehydes included crotonaldehyde (CRAL), propanaldehyde (3AL), butyraldehyde (4AL), pentanaldehyde (5AL), isopentanaldehyde (I5AL), and heptanaldehyde (7AL). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). HTG was defined as fasting TG levels ≥ 1.7 mmol/L. Aldehyde co-exposure was quantified using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), while mediation analysis was performed to investigate the role of liver enzymes. Among 1474 participants (mean age 38.6 years, male 50.0%), 426 were diagnosed with HTG. 4AL, 5AL, I5AL, and 7AL were shown to be positively associated with HTG (all P values <0.05). Aldehydes co-exposure was also positively associated with HTG (OR 1.706, 95%CI 1.299-2.240), with 5AL contributing the highest weight (35.3%). Furthermore, aldehydes co-exposure showed positive associations with ALT, AST, and GGT (all P values <0.05), and all four liver enzymes were positively associated with HTG (all P values <0.05). Mediation analysis revealed that liver enzymes (ALT, AST, and GGT) may mediate the associations of 5AL and 7AL with HTG (all P values <0.05). This study identified a positive association between aldehyde co-exposure and HTG, which may be partially mediated by liver enzymes.

Endothelial FIS1 DeSUMOylation Protects Against Hypoxic Pulmonary Hypertension.

BACKGROUND: Hypoxia is a major cause and promoter of pulmonary hypertension (PH), a representative vascular remodeling disease with poor prognosis and high mortality. However, the mechanism underlying how pulmonary arterial system responds to hypoxic stress during PH remains unclear. Endothelial mitochondria are considered signaling organelles on oxygen tension. Results from previous clinical research and our studies suggested a potential role of posttranslational SUMOylation (small ubiquitin-like modifier modification) in endothelial mitochondria in hypoxia-related vasculopathy. METHODS: Chronic hypoxia mouse model and Sugen/hypoxia rat model were employed as PH animal models. Mitochondrial morphology and subcellular structure were determined by transmission electron and immunofluorescent microscopies. Mitochondrial metabolism was determined by mitochondrial oxygen consumption rate and extracellular acidification rate. SUMOylation and protein interaction were determined by immunoprecipitation. RESULTS: The involvement of SENP1 (sentrin-specific protease 1)-mediated SUMOylation in mitochondrial remodeling in the pulmonary endothelium was identified in clinical specimens of hypoxia-related PH and was verified in human pulmonary artery endothelial cells under hypoxia. Further analyses in clinical specimens, hypoxic rat and mouse PH models, and human pulmonary artery endothelial cells and human embryonic stem cell-derived endothelial cells revealed that short-term hypoxia-induced SENP1 translocation to endothelial mitochondria to regulate deSUMOylation (the reversible process of SUMOylation) of mitochondrial fission protein FIS1 (mitochondrial fission 1), which facilitated FIS1 assembling with fusion protein MFN2 (mitofusin 2) and mitochondrial gatekeeper VDAC1 (voltage-dependent anion channel 1), and the membrane tethering activity of MFN2 by enhancing its oligomerization. Consequently, FIS1 deSUMOylation maintained the mitochondrial integrity and endoplasmic reticulum-mitochondria calcium communication across mitochondrial-associated membranes, subsequently preserving pulmonary endothelial function and vascular homeostasis. In contrast, prolonged hypoxia disabled the FIS1 deSUMOylation by diminishing the availability of SENP1 in mitochondria via inducing miR (micro RNA)-138 and consequently resulted in mitochondrial dysfunction and metabolic reprogramming in pulmonary endothelium. Functionally, introduction of viral-packaged deSUMOylated FIS1 within pulmonary endothelium in mice improved pulmonary endothelial dysfunction and hypoxic PH development, while knock-in of SUMO (small ubiquitin-like modifier)-conjugated FIS1 in mice exaggerated the diseased cellular and tissue phenotypes. CONCLUSIONS: By maintaining endothelial mitochondrial homeostasis, deSUMOylation of FIS1 adaptively preserves pulmonary endothelial function against hypoxic stress and consequently protects against PH. The FIS1 deSUMOylation-SUMOylation transition in pulmonary endothelium is an intrinsic pathogenesis of hypoxic PH.

Preparation and identification of isoquinoline alkaloids with ATP citrate lyase inhibitory activity from Dactylicapnos scandens.

Three new isoquinoline alkaloids including a morphine derivative (1), two aporphine alkaloids (2-3), together with five known alkaloids (4-8) were obtained from the extract of Dactylicapnos scandens (D.Don) Hutch. (D. scandens). Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-8 were evaluated for ATP Citrate Lyase (ACLY) inhibitory activity through an enzymatic assay. Among them, 2 and 3 showed the high ACLY inhibitory activity with an IC50 value of 10.48 ± 1.59 and 10.89 ± 4.89 µM.

Physics-informed neural network for phase imaging based on transport of intensity equation.

Non-interferometric quantitative phase imaging based on Transport of Intensity Equation (TIE) has been widely used in bio-medical imaging. However, analytic TIE phase retrieval is prone to low-spatial frequency noise amplification, which is caused by the illposedness of inversion at the origin of the spectrum. There are also retrieval ambiguities resulting from the lack of sensitivity to the curl component of the Poynting vector occurring with strong absorption. Here, we establish a physics-informed neural network (PINN) to address these issues, by integrating the forward and inverse physics models into a cascaded deep neural network. We demonstrate that the proposed PINN is efficiently trained using a small set of sample data, enabling the conversion of noise-corrupted 2-shot TIE phase retrievals to high quality phase images under partially coherent LED illumination. The efficacy of the proposed approach is demonstrated by both simulation using a standard image database and experiment using human buccal epitehlial cells. In particular, high image quality (SSIM = 0.919) is achieved experimentally using a reduced size of labeled data (140 image pairs). We discuss the robustness of the proposed approach against insufficient training data, and demonstrate that the parallel architecture of PINN is efficient for transfer learning.

High strength and damage-tolerance in echinoderm stereom as a natural bicontinuous ceramic cellular solid.

Due to their low damage tolerance, engineering ceramic foams are often limited to non-structural usages. In this work, we report that stereom, a bioceramic cellular solid (relative density, 0.2-0.4) commonly found in the mineralized skeletal elements of echinoderms (e.g., sea urchin spines), achieves simultaneous high relative strength which approaches the Suquet bound and remarkable energy absorption capability (ca. 17.7 kJ kg-1) through its unique bicontinuous open-cell foam-like microstructure. The high strength is due to the ultra-low stress concentrations within the stereom during loading, resulted from their defect-free cellular morphologies with near-constant surface mean curvatures and negative Gaussian curvatures. Furthermore, the combination of bending-induced microfracture of branches and subsequent local jamming of fractured fragments facilitated by small throat openings in stereom leads to the progressive formation and growth of damage bands with significant microscopic densification of fragments, and consequently, contributes to stereom's exceptionally high damage tolerance.

Combined effects of physical activity and sedentary behavior on all-cause mortality in heart failure patients: A cohort study of national health and nutrition examination survey analysis.

Background: Physical activity and sedentary behavior are independently related to the risk of cardiovascular disease. Physical activity is recognized as having a protective effect, while being sedentary seems to be adverse. Nonetheless, the interactions between physical activity and sedentary behavior and the combined effect on the prognosis of heart failure patients remain unclear. Methods and results: This cohort study included 886 heart failure patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Physical activity and sedentary behavior were assessed by the NHANES questionnaires. The all-caused deaths of enrolled subjects were identified from National Death Index (NDI) database. During a median follow-up of 51 months, 321 (36.2%) deaths from any causes occurred. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) for the all-cause mortality in heart failure patients associated with physical activity and sedentary behavior. Physical activity was independently associated with lower mortality [HR = 0.51, 95% CI (0.38-0.68), p < 0.001] and sedentary behavior was associated with adverse prognosis [HR = 1.79, 95% CI (1.41-2.28), p < 0.001]. Kaplan-Meier survival curve showed that physical activity appeared to attenuate the negative consequences of SB, while sedentary behavior increased the all-cause mortality, particularly those without physical activity. Conclusion: Physical activity has a protective effect on HF patients' prognosis, particularly those with sedentary behavior. Sedentary behavior independently exhibited a negative association in populations without physical activity, while it does not increase mortality in those with moderate physical activity.

Toward a BT.2020 green emitter through a combined multiple resonance effect and multi-lock strategy.

Color-saturated green-emitting molecules with high Commission Internationale de L'Eclairage (CIE) y values have great potential applications for displays and imaging. Here, we linked the outer phenyl groups in multiple-resonance (MR)-type blue-emitting B (boron)-N (nitrogen) molecules through bonding and spiro-carbon bridges, resulting in rigid green emitters with thermally activated delayed fluorescence. The MR effect and multiple interlocking strategy greatly suppressed the high-frequency vibrations in the molecules, which emit green light with a full-width at half-maximum of 14 nm and a CIE y value of 0.77 in cyclohexane. These were the purest green molecules with quantum efficiency and color purity that were comparable with current best quantum dots. Doping these emitters into a traditional green-emitting phosphorescence organic light-emitting diode (OLED) endowed the device with a Broadcast Service Television 2020 color-gamut, 50% improved external quantum efficiency, and an extremely high luminescence of 5.1 × 105 cd/m2, making it the greenest and brightest OLED ever reported.

Association between electronic cigarettes use and whole blood cell among adults in the USA-a cross-sectional study of National Health and Nutrition Examination Survey analysis.

Electronic cigarettes (E-cigarettes) use is an emerging public health problem. Trying to assess the independent associations between E-cigarettes use and whole blood cell in a nationally representative sample of the US adults is very important for the smoking population. Using E-cigarettes data from NHANES (National Health and Nutrition Examination Survey) 2013-2018, 17,180 adults were included in this cross-sectional analysis. All participants were stratified into four different groups (non-smoke group N=10087, E-cigarettes group N=52, dual-smoke group N=249, cigarettes group N=6792) based on questions SMQ020 (smoked at least 100 cigarettes in life) and SMQ690H (used last 5 days E-cigarettes). Whole blood cell tests included white blood cell (WBC) with differentials, red blood cell (RBC) with characteristics, and platelet variables. With adjusted by age, gender, and race ethnicity, multivariate logistic regression analyses were used to assess independent associations between E-cigarettes group and other groups for different whole blood cell variables. A total of 17,180 participants were included in the study; 47.9% were males, with a mean age of 46.99 (±0.29). In WBC-related variables, non-smoke group had the lowest value in WBC counts (7.15±0.05), lymphocyte (2.15±0.02), and monocyte (0.57±0.01), among the four different groups. In RBC-related variables, non-smoke group had the lowest value in mean cell volume (MCV, 88.46±0.14, p<0.05) and mean cell hemoglobin (MCH, 29.73±0.06, p<0.05), among the four different groups. In adjusted analysis, WBC (OR = 0.97, 95% CI: 0.96-0.98, p<0.001), especially lymphocyte (OR = 0.97, 95% CI: 0.96-0.98, p<0.001) and monocyte (OR = 0.11, 95% CI: 0.02-0.66, p<0.001) of non-smoke group, showed negative significant effect for E-cigarettes group. Meanwhile, lower odds of MCV (OR = 0.91, 95% CI: 0.81-1.04, p<0.05) and MCH (OR = 0.81, 95% CI: 0.65-1.00, p<0.05) in non-smoke group were observed compared to E-cigarettes group. Conversely, for dual-smoke group and cigarette group, there was no significant results in all whole blood cell variables compared to E-cigarettes group. E-cigarettes use might be associated with a systemic response that could lead to an increase in WBC, especially lymphocytes and monocytes, in the US adults. Meanwhile, the properties of RBC might also be influenced simultaneously; MCV and MCH in E-cigarettes population were bigger than the non-smoke population.

FGFR1 SUMOylation coordinates endothelial angiogenic signaling in angiogenesis.

Angiogenesis contributes fundamentally to embryonic development, tissue homeostasis, and wound healing. Basic fibroblast growth factor (FGF2) is recognized as the first proangiogenic molecule discovered, and it facilitates angiogenesis by activating FGF receptor 1 (FGFR1) signaling in endothelial cells. However, the precise roles of FGFR and the FGF/FGFR signaling axis in angiogenesis remain unclear, especially because of the contradictory phenotypes of in vivo FGF and FGFR gene deficiency models. Our previous study results suggested a potential role of posttranslational small ubiquitin-like modifier modification (SUMOylation), with highly dynamic regulatory features, in vascular development and disorder. Here, we identified SENP1-regulated endothelial FGFR1 SUMOylation at conserved lysines responding to proangiogenic stimuli, while SENP1 functioned as the deSUMOylase. Hypoxia-enhanced FGFR1 SUMOylation restricted the tyrosine kinase activation of FGFR1 by modulating the dimerization of FGFR1 and FGFR1 binding with its phosphatase PTPRG. Consequently, it facilitated the recruitment of FRS2α to VEGFR2 but limited additional recruitment of FRS2α to FGFR1, supporting the activation of VEGFA/VEGFR2 signaling in endothelial cells. Furthermore, SUMOylation-defective mutation of FGFR1 resulted in exaggerated FGF2/FGFR1 signaling but suppressed VEGFA/VEGFR2 signaling and the angiogenic capabilities of endothelial cells, which were rescued by FRS2α overexpression. Reduced angiogenesis and endothelial sprouting in mice bearing an endothelial-specific, FGFR1 SUMOylation-defective mutant confirmed the functional significance of endothelial FGFR1 SUMOylation in vivo. Our findings identify the reversible SUMOylation of FGFR1 as an intrinsic fine-tuned mechanism in coordinating endothelial angiogenic signaling during neovascularization; SENP1-regulated FGFR1 SUMOylation and deSUMOylation controls the competitive recruitment of FRS2α by FGFR1 and VEGFR2 to switch receptor-complex formation responding to hypoxia and normoxia angiogenic environments.

Strategies employed in the design of antimicrobial peptides with enhanced proteolytic stability.

Due to the alarming developing rate of multidrug-resistant bacterial pathogens, the development and modification of antimicrobial peptides (AMPs) are unprecedentedly active. Despite the fact that considerable efforts have been expended on the discovery and design strategies of AMPs, the clinical translation of peptide antibiotics remains inadequate. A large number of articles and reviews credited the limited success of AMPs to their poor stability in the biological environment, particularly their poor proteolytic stability. In the past forty years, various design strategies have been used to improve the proteolytic stability of AMPs, such as sequence modification, cyclization, peptidomimetics, and nanotechnology. Herein, we focus our discussion on the progress made in improving the proteolytic stability of AMPs and the principle, successes, and limitations of various anti-proteolytic design strategies. It is of prospective significance to extend current insights into the degradation-related inactivation of AMPs and also alleviate/overcome the problem.

Effect of Lycopene on the Growth Performance, Antioxidant Enzyme Activity, and Expression of Gene in the Keap1-Nrf2 Signaling Pathway of Arbor Acres Broilers.

The objective of this study was to determine the effect of dietary lycopene supplementation on the growth performance, antioxidant enzyme activity of serum and liver, and gene expressions associated with Kelch-like ech-associated protein-1 (Keap1)/Nuclear Factor E2-related factor 2 (Nrf2) pathway in liver of Arbor Acres broilers. A total of 288 1-day-old male broilers were randomly divided into 4 treatments with 6 replicates and 12 chickens for each replicate. The control group was fed with the basal diet, while the treated groups were fed with the basal diet with 10, 20, and 30 mg/kg lycopene in powder. Feed and water were provided ad libitum for 42 days. Compared with the control group, (a) the average daily gain increased (p = 0.002 vs. p = 0.001) and the feed conversion ratio decreased (p = 0.017 vs. p = 0.023) in groups treated with lycopene in the grower and whole phases, and the average daily feed intake was quadratically affected (p = 0.043) by lycopene in the grower phase; (b) the serum superoxide dismutase content was linearly affected (p = 0.035) by lycopene at 21 days; (c) the serum glutathione peroxidase content, superoxide dismutase content, and total antioxidant capability were higher (p = 0.014, p = 0.003, and p = 0.016, respectively) in the 30 mg/kg lycopene group at 42 days; (d) the liver glutathione peroxidase and superoxide dismutase contents in groups treated with lycopene were higher (p ≤ 0.001 vs. p ≤ 0.001) at 21 days; (e) the liver glutathione peroxidase content was higher (p ≤ 0.001) in the 20 and 30 mg/kg lycopene groups, at 42 days; (f) the mRNA expression levels of Nrf2, superoxide dismutase 2, NAD(P)H quinone dehydrogenase 1, and heme oxygenase 1 genes were higher (21 days: p = 0.042, p = 0.021, p = 0.035, and p = 0.043, respectively; 42 days: p = 0.038, p = 0.025, p = 0.034, and p = 0.043, respectively) in the 20 and 30 mg/kg lycopene groups at 21 and 42 days. The 30 mg/kg lycopene concentration improved the growth performance, antioxidant enzyme activity in serum and liver, and gene expression in the Keap1-Nrf2 signaling pathway of Arbor Acres broilers.

Corybungines A-K: Isoquinoline alkaloids from Corydalis bungeana with dopamine D2 receptor activity.

Eleven undescribed isoquinoline alkaloids corybungines A-K including a protoberberine-type alkaloid, an isoquinoline alkaloid with a unique 6-norprotoberberine skeleton, one 13,14-seco-protoberberine-type alkaloid, two 1a,14-seco-protoberberine-type alkaloids with a 4-(hydroxymethyl)phenoxy moiety and six aporphine alkaloids, together with seven known alkaloids, have been isolated from the whole herb extract of Corydalis bungeana Turcz. Their structures and absolute configurations were elucidated based on an analysis of spectroscopic data and electronic circular dichroism (ECD) spectra. (R)-stephanine displayed high antagonistic activity against the dopamine D2 receptor with an IC50 value of 0.85 ± 0.09 µM in CHO-D2 cells. Additionally, corybungines D, F, H, (R)-roemerine, (R)-vireakine and (R)-tuduranine showed moderate D2 antagonism (IC50 5.20-26.07 µM). The preliminary structure-activity relationships (SARs) of aporphine alkaloids were discussed.

Biomaterial-Interrelated Bacterial Sweeper: Simplified Self-Assembled Octapeptides with Double-Layered Trp Zipper Induces Membrane Destabilization and Bacterial Apoptosis-Like Death.

Treatment of microbial-associated infections continues to be hampered by impaired antibacterial efficiency and the variability in nanomedicines. Herein, an octapeptide library with a double-layered zipper, constructed via a systematic arrangement, simplifying the sequence and optimizing the structure (diverse motifs including surfactant-like, central-bola, and end-bola), is assessed in terms of biological efficiency and self-assembly properties. The results indicate that peptides with double-layered Trp zipper exhibit significant antimicrobial activity. Extracellularly, affinity interactions between micelles and bacteria induce the lateral flow of the membrane and electric potential perturbation. Intracellularly, lead molecules cause apoptosis-like death, as indicated by excessive accumulation of reactive oxygen species, generation of a DNA ladder, and upregulation of mazEF expression. Among them, RW-1 performs the best in vivo and in vitro. The intersecting combination of Trp zipper and surfactants possesses overwhelming superiority with respect to bacterial sweepers (therapeutic index [TI] = 52.89), nanostructures (micelles), and bacterial damage compared to RW-2 (central-bola) and RW-3 (end-bola). These findings confirm that the combination of double-layered Trp zipper and surfactants has potential for application as a combined motif for combating microbial infection and connects the vast gap between antimicrobial peptides and self-assembly, such as Jacob's ladder.

Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum Disorder.

Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-ß, and IFN-γ when compared to healthy controls (FDR-adjusted p < 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p < 0.01) and Lachnospiraceae (FDR-adjusted p < 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p < 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p < 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p < 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.

Polymer Electrochemiluminescence Featuring Thermally Activated Delayed Fluorescence.

Electrochemiluminescence (ECL) based on conjugated polymers or oligomers is persistently being pursued owing to its huge application scope ranging from ultra-sensitive bioanalysis to ultra-resolution imaging and spectroscopy. Because of the theoretical limit in radiative exciton generation yield (typically ∼25 %) of those polymers or oligomers, the corresponding ECL efficiency is still limited, which hampers its ECL performance and its related applications. Herein, we report ECL based on a thermally activated delayed fluorescence (TADF) polymer scaffold, which is characteristic of all-exciton harvesting in the ECL process, and thus potentially capable of achieving ∼100 % ECL efficiency. These desired properties of the TADF polymer ECL is attributed to a fast and efficient up-conversion process from non-radiative triplet to radiative singlet states under thermal activation, which is absent in conventional fluorescent polymers/oligomers, such as F8BT. In this study, various ECL modes, including annihilation or co-reactant mode using TPrA or S2 O82- as co-reactant, are confirmed for our model TADF polymer ECL system, which was different from fluorescent polymer ECL counterpart. Furthermore, solid-state ECL sensing on L-cysteine (an important marker of disease) is also evaluated by using the model TADF polymer. Ultralow detection limit in combination with high sensitivity and good specificity are achieved for this model system, indicative of a high potential of the TADF polymer scaffold for applications in the broad field of ECL.