Discrimination and quantification of volatile compounds in beer by FTIR combined with machine learning approaches.

The composition of volatile compounds in beer is crucial to the quality of beer. Herein, we identified 23 volatile compounds, namely, 12 esters, 4 alcohols, 5 acids, and 2 phenols, in nine different beer types using GC-MS. By performing PCA of the data of the flavor compounds, the different beer types were well discriminated. Ethyl caproate, ethyl caprylate, and phenylethyl alcohol were identified as the crucial volatile compounds to discriminate different beers. PLS regression analysis was performed to model and predict the contents of six crucial volatile compounds in the beer samples based on the characteristic wavelength of the FTIR spectrum. The R2 value of each sample in the prediction model was 0.9398-0.9994, and RMSEP was 0.0122-0.7011. The method proposed in this paper has been applied to determine flavor compounds in beer samples with good consistency compared with GC-MS.

Design of urban innovation space system using artificial intelligence technology and internet of things.

The goal of this paper is to integrate artificial intelligence (AI) and Internet of things (IoT) technology into urban innovation space systems while expediting the construction of urban informatization. The core of the paper is to build an innovation space system, which is developed around three key components: innovation elements, innovation networks and innovation bases. First, the definition of innovation space is investigated in detail, and the essence of innovation space is understood to ensure that the key elements in the innovation process can be accurately captured and analyzed in the follow-up research. Second, it is clear that Chengdu is a representative city in Sichuan Province. Through the research in this area, people can deeply understand the specific background and characteristics of urban innovation space system. Then, the innovation space system is constructed, which is supported by innovation elements, innovation networks and innovation bases. These three components are intertwined, which together constitute the key elements of urban innovation space. Furthermore, the Internet worm technology is integrated with the IoT technology, and the system is visually inspected with the help of AI. The application of IoT technology helps to realize the automation and information sharing of the system, while the use of AI provides a deep insight into the system structure and operation. Through this research process, people can fully understand the construction process of Chengdu innovation space system, and provide deeper insight and support for urban innovation through the application of IoT and AI technology. The results show that while Chengdu's entrepreneurship and innovation enterprises are dispersed throughout all of the city's districts and counties, the city's academic talent and the bulk of its higher education institutions are concentrated in the city's core. There are 275 entrepreneurship and innovation enterprises in the High-tech District of Chengdu, which is the most densely distributed area. An urban innovation space network is being built by eight distinct research and higher education establishments. As urban innovation spaces are being built, emphasis should be given to the regional aggregation features of talents, higher education and research institutions, as well as entrepreneurship and innovation business enterprises. The innovation space system based on Internet worm technology of the IoT shows excellent performance in real-time identification of innovation elements, network connection quality, sensor monitoring, AI visual monitoring and so on. The system performs well in real-time monitoring of new enterprises and projects, and the real-time recognition rate reaches 98 %. The communication quality of the innovation network is relatively stable, and the connection quality reaches 92 %. The accuracy of sensor status monitoring in the IoT is high, reaching 99 %. The coverage of AI vision monitoring system reaches 96 %, effectively monitoring the areas involved in innovative space systems. Generally speaking, through the combination of theory and practice, this paaper provides comprehensive and specific guidance for the construction of urban innovation space system, promotes the research progress in this field, and makes beneficial contributions to the sustainable development of urban innovation and informatization.

Retinoic acid-inducible gene-1 knockdown induces immature properties in dendritic cells and prolongs the survival time of allograft mice.

BACKGROUND: The mature state of dendritic cells (DCs) determines their ability to regulate immune responses. Retinoic acid-inducible gene-1 (RIG-1) plays a critical role in DC activation and maturation. RIG-1 activation triggers mitogen-activated protein kinase and nuclear factor-kappa B signal transduction. In this study, we aimed to investigate the effects of inhibiting RIG-1 expression in DCs and its potential in inducing immune tolerance. METHODS: DCs were transduced with the recombinant lentiviral vector (Lv) to inhibit RIG-1 expression. A murine islet and skin transplantation model were constructed to find out whether DC-DDX58-RNAi could prolong allograft survival. The phenotypes of DCs and T-cells were analyzed using flow cytometry. Cytokines in serum were detected by the enzyme-linked immunosorbent assay. Protein levels were determined by Western blot. RESULTS: RIG-1-deficient DCs had low expression of costimulatory molecules and major histocompatibility complex and a strong phagocytic ability. DC-DDX58-RNAi induced regulatory T cell differentiation in the transplant recipient spleens. The DC-DDX58-RNAi-treated recipients showed satisfactory islet allograft function and longer survival time. CONCLUSION: Inhibition of RIG-1 with DDX58-RNAi prevented the activation and maturation of the DCs, affected T cell differentiation, protected the biological function of the allograft, and prolonged graft survival. These findings may have important therapeutic implications for new immunomodulatory regimens.

Immune-Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults.

Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status. However, the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed. Here, we analysed T and natural killer (NK) cell subsets, the phenotype and cell differentiation states in 43,096 healthy individuals, aged 20-88 years, without known diseases. Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals. The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis. Our initial analysis and machine modelling prediction showed that naïve T cells decreased with ageing, whereas central memory T cells (Tcm) and effector memory T cells (Tem) increased cluster of differentiation (CD) 28-associated T cells. This is the largest study to investigate the correlation between age and immune cell function in a Chinese population, and provides insightful differences, suggesting that healthy adults might be considerably influenced by age and sex. The age of a person's immune system might be different from their chronological age. Our immune-ageing modelling study is one of the largest studies to provide insights into 'immune-age' rather than 'biological-age'. Through machine learning, we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction. Our research not only reveals the impact of age on immune parameter differences within the Chinese population, but also provides new insights for monitoring and preventing some diseases in clinical practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00106-0.

Risk factors for neck pain in college students: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 epidemic, the prevalence of neck pain among college students has increased due to the shift from offline to online learning and increasing academic and employment pressures. Therefore, this systematic review aimed to identify the personal, occupational, and psychological factors associated with the development of neck pain to promote the development of preventive strategies and early intervention treatment. METHODS: Seven electronic databases were searched from inception to December 2022 for cross-sectional studies, cohort studies, case----control studies, and randomized controlled trials (RCTs) on neck pain. The quality of the selected studies were assessed by American Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the effects of the included risk factors on neck pain. RESULTS: Thirty studies were included, including 18,395 participants. And a total of 33 potentially associated risk factors were identified. Ultimately, 11 risk factors were included in the meta-analysis after assessing, and all results were statistically significant (P < 0.05). The factors supported by strong evidence mainly include the improper use of the pillow (OR = 2.20, 95% CI: 1.39 to 3.48), lack of exercise (OR = 1.88, 95% CI: 1.53 to 2.30), improper sitting posture (OR = 1.97, 95% CI: 1.39 to 2.78), history of neck and shoulder trauma (OR = 2.32, 95% CI: 1.79 to 3.01), senior grade (OR = 2.86, 95% CI: 2.07 to 3.95), staying up late (OR = 1.80, 95% CI: 1.35 to 2.41), long-time electronic product usage daily (OR = 1.53, 95% CI: 1.33 to 1.76), long-time to bow head (OR = 2.04, 95% CI: 1.58 to 2.64), and emotional problems (OR = 2.09; 95% CI: 1.66  to 2.63). Risk factors supported by moderate evidence were high stress (OR = 1.61, 95% CI: 1.02 to 2.52) and female gender (OR = 1.69, 95% CI: 1.52 to 1.87). CONCLUSION: This study obtained 11 main risk factors affecting college students neck pain, including improper use of the pillow, lack of exercise, improper sitting posture, history of neck and shoulder trauma, senior grade, staying up late, long-term electronic product usage daily, long time to bow head, high stress, emotional problems and female gender.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

BACKGROUND: Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. OBJECTIVE: We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP. METHODS: Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils. RESULTS: Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+ MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation. CONCLUSIONS: MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

Interferon-gamma FlowSpot assay for the measurement of the T-cell response to cytomegalovirus.

Objectives: We describe a new method, FlowSpot, to assess CMV-specific T-cell response by quantification of interferon-gamma (IFN-γ). CMV-specific, T-cell-released IFN-γ was captured by flow beads and measured via flow cytometry. In the present study, we used FlowSpot to assess CMV-specific T-cell response in healthy individuals. The FlowSpot results were compared with those of serological analysis and enzyme-linked immunospot (ELISpot) assay. Methods: Experimental results and parameter analysis were investigated by using serological, ELISpot, and FlowSpot assays. Results: The levels of IFN-γ, which is released from CMV-specific T-cells, were measured, and the results and parameter analysis showed a good correlation between FlowSpot and ELISpot. However, FlowSpot was more sensitive and better reflected the strength of IFN-γ secretion than did ELISpot. Conclusions: Compared to ELISpot, FlowSpot has a high sensitivity and is cost and time effective. Thus, this method can be used in wider clinical and scientific applications.

Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

Chinese medicinal herbs for reducing endocrine therapy-induced side effects in patients with hormone receptor-positive breast cancer: a systematic review and meta-analysis.

CONTEXT: Chinese medicinal herbs (CMH) have been considered a potentially efficacious approach for patients with breast cancer that experience adverse effects from endocrine treatment. OBJECTIVE: To investigate the impact of CMH on endocrine therapy-induced side effects in patients with hormone receptor-positive (HR+) breast cancer. METHODS: Ten databases (e.g., PubMed, Web of Science, Cochrane Library, China National Knowledge Information Database and other databases) were searched up to 20 May 2022. The search terms included Chinese herb, breast cancer, endocrine therapy, clinical trial and their mesh terms. The study selection and data extraction were performed by two independent reviewers. The risk of bias was evaluated using the Cochrane risk of bias method. RESULTS: A total of 31 studies with 2288 patients were included. There were significant improvements in bone mineral density (BMD) [lumbar BMD (MD 0.08, 95% CI 0.07 to 0.09, p < 0.00001) and femoral neck BMD (MD 0.08, 95% CI 0.07 to 0.10, p < 0.00001)] and bone gal protein (BGP) (MD 0.24, 95% CI 0.17 to 0.31, p < 0.00001), with a significant reduction in triglycerides (MD -0.53, 95% CI -1.00 to -0.07, p < 0.05) and no effect on estradiol levels (MD 0.90, 95% CI -0.31 to 2.12, p = 0.15). CONCLUSIONS: CMH combined with complementary therapy can moderately reduce endocrine therapy-induced side effects, including bone loss and dyslipidemia in patients with HR + breast cancer, revealing the potential role of CMH in treating (HR+) breast cancer. More high-quality RCTs are warranted to further validate the effectiveness and safety of CMH.

Target Density Effects on Charge Transfer of Laser-Accelerated Carbon Ions in Dense Plasma.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1 mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis.

Introduction: The risk of alcoholic cirrhosis increases in a dose- and time-dependent manner with alcohol consumption and ethanol metabolism in the liver. Currently, no effective antifibrotic therapies are available. We aimed to obtain a better understanding of the cellular and molecular mechanisms involved in the pathogenesis of liver cirrhosis. Methods: We performed single-cell RNA-sequencing to analyze immune cells from the liver tissue and peripheral blood form patients with alcoholic cirrhosis and healthy controls to profile the transcriptomes of more than 100,000 single human cells and yield molecular definitions for non-parenchymal cell types. In addition, we performed single-cell RNA-sequencing analysis to reveal the immune microenvironment related to alcoholic liver cirrhosis. Hematoxylin and eosin, Immunofluorescence staining and Flow cytometric analysis were employed to study the difference between tissues and cells with or without alcoholic cirrhosis. Results: We identified a fibrosis-associated M1 subpopulation of macrophages that expands in liver fibrosis, differentiates from circulating monocytes, and is pro-fibrogenic. We also define mucosal-associated invariant T (MAIT) cells that expand in alcoholic cirrhosis and are topographically restricted to the fibrotic niche. Multilineage modeling of ligand and receptor interactions between the fibrosis-associated macrophages, MAIT, and NK cells revealed the intra-fibrotic activity of several pro-fibrogenic pathways, including responses to cytokines and antigen processing and presentation, natural killer cell-mediated cytotoxicity, cell adhesion molecules, Th1/Th2/Th17 cell differentiation, IL-17 signaling pathway, and Toll-like receptor signaling pathway. Discussion: Our work dissects unanticipated aspects of the cellular and molecular basis of human organ alcoholic fibrosis at the single-cell level and provides a conceptual framework for the discovery of rational therapeutic targets in liver alcoholic cirrhosis.

Novel preparation of red fluorescent carbon dots for tetracycline sensing and its application in trace determination.

The controllable design of red-emitting carbon dots and further exploration of their application in the trace determination of environmental pollutants remains a tremendous challenge. Herein, the novel strategy for red fluorescent carbon dots (R-CDs) with a higher quantum yield of 58.9% was proposed by doping small-molecule urea into the bio-dye of resazurin for the first time, which can retain the luminophore of precursors and exhibit exceptional optical, advantageous reversibility and outstanding photostability. Importantly, the R-CDs exhibit a remarkable fluorescence reduction towards tetracyclines (TCs) accompanied by a noticeable color change of R-CDs solution from red to yellow, which can realize the trace detection of TCs at strelatively low levels, including tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC). The linear range of TC, CTC, and OTC are 3-40 µM, 4-50 µM, and 2-50 µM, and the corresponding detection limits are 38.5 nM, 64.6 nM, and 45.4 nM, respectively (S/N = 3). Furthermore, the R-CDs demonstrate sensitivity to the physiological pH in the linear range of 4.0-5.0 and 5.0-6.2 with a pKa of 5.61. As a multifunctional fluorescent sensor, R-CDs can provide a new perspective for the preparation of long-wavelength CDs, and further realize the trace determination of environmental pollutants.

One-pot synthesis of efficient multifunctional nitrogen-doped carbon dots with efficient yellow fluorescence emission for detection of hypochlorite and thiosulfate.

CD-based ratiometric fluorescence probes are of great significance for visual detection, but accomplishing this goal is still a particularly challenging task. Herein, nitrogen-doped carbon dots (NCDs) with bright yellow fluorescence were easily manufactured via a one-pot hydrothermal method for visual detection of hypochlorite (ClO-) and thiosulfate (S2O32-) under UV light irradiation. The as-prepared NCDs demonstrate favorable water solubility, excellent biocompatibility, superior optical properties and low cytotoxicity. Strikingly, the fluorescence of the NCDs could be quenched with ClO-. Based on these results, an original fluorescent nanoprobe was constructed for the highly discriminating recognition of ClO- by oxidation of the amino groups on their surface to nitro groups. The assay covered the ranges from 0.067 to 19.33 µM and 24 to 98 µM with a limit of detection (S/N = 3) of as low as 0.013 µM. Remarkably, a growing peak appears at 537 nm and the emission at 492 nm shrinks with the introduction of S2O32-, which demonstrates ratiometric fluorescence emission characteristics (F537nm/F492nm) in the range of 6.6-100 µM with a limit of detection (S/N = 3) of as low as 0.78 µM. In addition, the fluorescence color of the NCDs also changes (yellow-green-blue) after adding various ClO- concentrations. The fluorescence color of the NCDs-ClO- also changes (blue-green-yellow) after adding various S2O32- concentrations. This excellent ratiometric fluorescence probe was successfully further used for nuclear imaging. Accordingly, an easy-to-prepare paper-based sensor to identify ClO- and S2O32- was fabricated, which demonstrated their adaptability for in situ on-site testing. This research further opens up new opportunities for the development of efficient yellow fluorescent probes based on NCDs nanomaterials for visual detection, biomarking, and biomedical optical imaging.

Sex differences in factors associated with neck pain among undergraduate healthcare students: a cross-sectional survey.

BACKGROUND: Neck pain is widespread among students in healthcare-related fields. Although neck pain is more prevalent in females, since most research involves mixed-sex samples we know very little about sex differences in contributors to neck pain. Thus, this study sought to explore sex differences in the risk factors for neck pain in this high-risk population. METHODS: This cross-sectional study was conducted in China in 2021 and included a sample of 1921 undergraduate healthcare students (693 males, 1228 females) from 7 health professional schools at Fujian Medical University. We collected data on neck pain symptoms, demographics, behavioral and psychological factors. Multiple regression analysis was conducted to examine sex differences in the risk factors of neck pain. RESULTS: The overall prevalence of neck pain was 41.6% with female students having a higher prevalence than male students (44.4% vs. 36.7%, respectively). The adjusted analyses showed that self-study time ≥ 6 h/day (OR = 1.44, 95% CI:1.13-1.83), flexed neck posture >20 degrees (OR = 2.19, 95% CI: 1.28-3.74), static duration posture >2 h (OR = 1.42, 95% CI: 1.02-1.97), and psychological distress (high: OR = 2.04, 95% CI:1.42-2.94; very high: OR = 2.50, 95% CI:1.57-3.74; respectively) were independent factors for neck pain in females. Among males, self-study time ≥ 6 h/day (OR = 1.43, 95% CI: 1.02-2.01) and psychological distress (moderate: OR = 2.04, 95% CI:1.28-3.25; high: OR = 2.37, 95% CI:1.49-3.79; very high: OR = 2.97, 95% CI:1.75-5.02; respectively) were significant risk factors for neck pain. CONCLUSIONS: These findings suggest that the risk profiles of neck pain differ between females and males. The modifiable risk factors for neck pain, such as prolonged self-study time and elevated psychological distress, as well as poor posture among females, could be targeted through health promotion interventions in university settings.

The Influencing Factors of Art Graduates' Entrepreneurship by Logistic Regression Analysis From the Perspective of Entrepreneurial Mentality.

The purpose of this study was to understand the influence mechanism of college students' entrepreneurial intention in view of the increasing number of college students at present to alleviate college students' employment competition. The psychological factors that influence the entrepreneurial tendency of art graduates were analyzed and studied. First, venture capital and factors affecting entrepreneurial performance were analyzed. Second, the coefficient calculation is carried out for college students majoring in art through the regression analysis of the logistic model. Finally, a team entrepreneurial performance questionnaire was designed, and team reward levels were discussed. The results show that the logistic model can well reflect the real situation of the respondents. The significance level of the entrepreneurial team was 0.02, which was correlated. Additionally, corresponding suggestions were put forward according to the questionnaire results. Clear team goals, assignment of tasks to members, good pressure resistance, and psychological quality of members are necessary qualities for successful entrepreneurship. This conclusion provides a certain theoretical basis for the current college students' entrepreneurial learning and a reliable inspiration for helping college students to successfully start a business.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

Serum Soluble B Cell-Activating Factor Is a Non-Invasive Biomarker of Antibody-Mediated Rejection in Kidney Allograft With Satisfactory Risk Stratification Performance But Negligible Diagnostic Value.

Objectives: B cell-activating factor (BAFF), which is critical in the activation and differentiation of B cells, is a candidate diagnostic and predictive biomarker for antibody-mediated rejection (ABMR). We aimed to investigate the value of serum soluble BAFF (sBAFF) for the diagnosis and risk stratification of ABMR after kidney transplantation. Methods: In the diagnostic study, sBAFF level among ABMR (n = 25), T cell-mediated rejection (TCMR) (n = 14), 4 other pathological lesions (n = 21), and stable allograft function group (n = 15) were compared. In the nested case-control study, kidney allograft recipients with de novo donor-specific antibody (DSA) or ABMR (n = 16) vs. stable allograft function (n = 7) were enrolled, and sBAFF was measured preoperatively, at D7, M1, M3, M6, M9, M12, M18 posttransplant and at allograft biopsy. Results: There was no significant difference in sBAFF level at biopsy between ABMR and non-ABMR groups. Longitudinal study showed that the sBAFF levels decreased dramatically at D7 in both groups. The sBAFF level in the DSA group started to increase within M1, while in the stable group, it maintained a low level until M3 and M6. The sBAFF levels of the DSA group were significantly higher than that of the stable group at M1 [1,013.23 (633.97, 1,277.38) pg/ml vs. 462.69 (438.77, 586.48) pg/ml, P = 0.005], M3 [1,472.07 (912.79, 1,922.08) pg/ml vs. 561.63 (489.77, 630.00) pg/ml, P = 0.002], and M6 [1,217.95 (965.25, 1,321.43) pg/ml vs. 726.93 (604.77, 924.60) pg/ml, P = 0.027]. sBAFF levels at M3 had the best predictive value for the DSA/ABMR with the area under the receiver operating characteristic (AUROC) curve value of 0.908. The predictive performance of the maximum (max) change rate from D7 to the peak within M3 was also excellent (AUROC 0.949, P = 0.580). Conclusion: We clarified by a diagnostic study that sBAFF is not a diagnostic biomarker for ABMR in kidney transplantation and revealed by a nested case-control study that sBAFF values at M3 posttransplant and dynamic changes in sBAFF within M3 posttransplant have a good predictive value for the DSA/ABMR. It provides a useful tool for early screening of low-risk patients with negative preoperative DSA for the risk of developing postoperative DSA in kidney allograft recipients.

Hepatocellular carcinoma-infiltrating γδ T cells are functionally defected and allogenic Vδ2+ γδ T cell can be a promising complement.

In hepatocellular carcinoma (HCC), γδ T cells participate in mediating the anti-tumour response and are linked with a positive prognosis. However, these cells can become pro-tumoural in the tumour microenvironment (TME). We aimed to decipher the immune landscape and functional states of HCC-infiltrating γδ T cells to provide fundamental evidence for the adoptive transfer of allogeneic Vδ2+ γδ T cells in HCC immunotherapy. We performed single-cell RNA sequencing (scRNA-seq) on γδ T cells derived from HCC tumours and healthy donor livers. Confocal microscopy, flow cytometry and a Luminex assay were applied to validate the scRNA-seq findings. The γδ T cells in the HCC TME entered G2/M cell cycle arrest, and expressed cytotoxic molecules such as interferon-gamma and granzyme B, but were functionally exhausted as indicated by upregulated gene and protein LAG3 expression. The γδ T cells in the HCC TME were dominated by the LAG3+ Vδ1+ population, whereas the Vδ2+ γδ T population was greatly depleted. Moreover, glutamine metabolism of γδ T cells was markedly upregulated in the glutamine-deficient TME. Both in vitro and in vivo experiments showed that glutamine deficiency upregulated LAG3 expression. Finally, our results indicated that ex vivo-expanded Vδ2+ γδ T cells from healthy donor could complement the loss of T cell receptor clonality and effector functions of HCC-derived γδ T cells. This work deciphered the dysfunctional signatures of HCC-infiltrating γδ T cells in the HCC TME, providing scientific support for the use of allogeneic Vδ2+ γδ T cells in HCC cellular therapy.

Aqueous extracts of tree peony petals: renin and angiotensin I-converting enzyme inhibitory activities in different colours and flowering stages.

Tree peony (Paeonia suffruticosa Andr.) is an ornamental and medicinal plant from China. Previous studies have detected novel blood pressure-regulating substances in this species, which potentiate its value of utilization. To explore these substances, the aqueous extracts of 7 different colours of tree peony petals were assessed for inhibitory activity on renin and angiotensin-converting enzyme (ACE). The results showed that the activity of dark-coloured samples was significantly stronger than that of light-coloured ones. Furthermore, the inhibitory activity of the red tree peony petals 'Hong TaiYang' on renin and ACE indicated a downward trend from bud compaction to the full opening stage. The antioxidant activities of the aqueous extracts, on one side, and the correlations between phenolics and flavonoids functionalities and total contents, on the other, were also evaluated. In this regard, the extracts of different samples had ABTS free radical scavenging capacities of 17.28-210.41 mg TE per g DW, DPPH radical scavenging capacities of 35.45-150.78 mg TE per g DW, iron ion reduction capacities of 16.66-150.77 mg TE per g DW, and total phenolic content of 23.94-150.78 mg GAE per g DW. Correlation analysis revealed that the renin and ACE inhibitory activities, the DPPH and ABTS free radical scavenging capacities, and the iron reduction ability of different sample extracts were positively correlated with total phenolic contents (p < 0.01). Finally, the aqueous phenolic compounds in the sample extracts tended to show strong renin and ACE inhibitory activities and therefore exhibit a potential auxiliary blood pressure control prospect.

Dual inhibition of the renin and angiotensin converting enzyme activities of aqueous extracts of 22 edible flower petals.

In order to explore novel blood pressure-regulating substances and fulfill the high-value utilization of various edible flowers, the inhibitory activities of aqueous solutions of 22 edible flower petals extracts on renin and angiotensin converting enzyme (ACE) were investigated. The results showed that almost all the aqueous sample extracts demonstrated an inhibition of renin and/or ACE. The Rosa rugosa Thunb. (IC50 = 25.13 and 60.00 µg mL-1) and Paeonia suffruticosa Andr. (IC50 = 50.54 and 292.47 µg mL-1) extracts showed prominent dual inhibitory activity against renin and ACE. The antioxidant activities and content of total phenols and flavonoids of the aqueous sample extracts were tested, because the oxidative damage of blood vessels is closely related to the occurrence and development of hypertension. The correlation between the contents of total phenolic substances and flavonoids, and the functional activities was analyzed. Renin and ACE inhibitory activities, DPPH and ABTS free radical scavenging capacity, and iron reduction ability of different sample extracts were significantly positively correlated with the total phenolic content (p <0.01), whereby the correlation coefficients were 0.87, 0.83, 0.93, 0.95, and 0.93 respectively. It was indicated that the aqueous phenolic compounds in Rosa rugosa Thunb and Paeonia suffruticosa Andr extracts tended to show stronger renin and ACE inhibitory activities, and exhibited a potential prospect for auxiliary blood pressure control.