Autoantibody of interleukin-17A induced by recombinant Mycobacterium smegmatis attenuates airway inflammation in mice with neutrophilic asthma.

OBJECTIVE: Previous studies have shown Interleukin (IL)-17A as an important contributor to the development of severe asthma, which is mainly characterized by neutrophilic inflammation and less response to corticosteroids. Consequently, the IL-17A-neutrophil axis could be a potential therapeutic target. Previously, we constructed a recombinant Mycobacterium smegmatis (rMS) expressing fusion protein Ag85A-IL-17A, and confirmed it could induce production of IL-17A autoantibody in vivo. This study uses a murine model of neutrophilic asthma to further investigate the effects of rMS on airway inflammation. METHODS: DO11.10 mice were divided into four groups: phosphate buffered saline (PBS), asthma, rMS and MS. This murine model of neutrophilic asthma was established with ovalbumin (OVA) challenge, whereby PBS, rMS and MS were administered intranasally. Anti-inflammatory effects on inflammatory cell infiltration and expression of inflammatory mediators in bronchoalveolar lavage fluid (BALF) were evaluated, along with histopathological changes in lung tissues. RESULTS: A sustained high-titer IL-17A autoantibody was detected in sera of the rMS group. Compared to the asthma group, the number of neutrophils, IL-17A, CXCL-1 levels and MPO activity in the rMS group were all significantly reduced (p < 0.01). Histological analysis showed rMS remarkably suppressed inflammatory infiltration around bronchia. The inflammation score and the mucus score in the rMS group were both significantly lower than those in the asthma group (p < 0.001). CONCLUSION: rMS ameliorated airway inflammation in mice with neutrophilic asthma caused by inducing IL-17A autoantibody and regulating the IL-17A-neutrophil axis, thus offering a possible novel treatment for neutrophilic asthma.

Main-Group Elements Enhance Electrochemical Nitrogen Reduction Reaction of Vanadium-Based Single Atom Catalysts Through d-p Orbital Hybridization.

Developing active sites with flexibility and diversity is crucial for single atom catalysts (SACs) towards sustainable nitrogen fixation at ambient conditions. Herein, the effects of doping main group metal elements (MGM) on the stability, catalytic activity, and selectivity of vanadium-based SACs is systematically investigated based on density functional theory calculations. It is found that the catalytic activity of V site can be significantly enhanced by the synergistic effect between MGM and vanadium atoms. More importantly, a volcano curve between the catalytic activity and the adsorption free energy of NNH* can be established, in which V-Pb dimer embedded on N-coordinated graphene (VPb-NG) exhibits optimal NRR activity due to its location at the top of volcano. Further analysis of electronic structures reveals that the unoccupancy ratio (eg/t2g) of V site is dramatically increased by the strong d-p orbital hybridization between V and Pb atoms, subsequently, N2 is activated to a larger extent. These interesting findings may provide a new path for designing active sites in SACs with excellent performance.

Early differential diagnosis of pancytopenia related diseases based on serum surface-enhanced Raman spectroscopy.

Pancytopenia is a common blood disorder defined as the decrease of red blood cells, white blood cells and platelets in the peripheral blood. Its genesis mechanism is typically complex and a variety of diseases have been found to be capable of causing pancytopenia, some of which are featured by their high mortality rates. Early judgement on the cause of pancytopenia can benefit timely and appropriate treatment to improve patient survival significantly. In this study, a serum surface-enhanced Raman spectroscopy (SERS) method was explored for the early differential diagnosis of three pancytopenia related diseases, i.e., aplastic anemia (AA), myelodysplastic syndrome (MDS) and spontaneous remission of pancytopenia (SRP), in which the patients with those pancytopenia related diseases at initial stage exhibited same pancytopenia symptom but cannot be conclusively diagnosed through conventional clinical examinations. The SERS spectral analysis results suggested that certain amino acids, protein substances and nucleic acids are expected to be potential biomarkers for their early differential diagnosis. In addition, a diagnostic model was established based on the joint use of partial least squares analysis and linear discriminant analysis (PLS-LDA), and an overall accuracy of 86.67 % was achieved to differentiate those pancytopenia related diseases, even at the time that confirmed diagnosis cannot be made by routine clinical examinations. Therefore, the proposed method has demonstrated great potential for the early differential diagnosis of pancytopenia related diseases, thus it has significant clinical importance for the timely and rational guidance on subsequent treatment to improve patient survival.

Predictive and prognostic value of leptin status in asthma.

Asthma is closely associated with inflammation. We evaluated the predictive and prognostic value of leptin status in asthma. We searched the electronic databases for articles that determined the leptin level in asthma cases through May 2020. We compared the differences of leptin level between asthma and non-asthma controls, as well as between severe and mild asthma cases. We also investigated the impact of age and gender on these differences by using meta-regression analysis. 59 studies were included in our pooled analysis. Asthma cases demonstrated significantly higher leptin level than that in non-asthma controls among overall populations (SMD:1.061, 95% CI: 0.784-1.338, p < 10-4), Caucasians (SMD:0.287, 95% CI: 0.125-0.448, p = 0.001), Asians (SMD:1.500, 95% CI: 1.064-1.936, p < 10-4) and Africans (SMD: 8.386, 95% CI: 6.519-10.253, p < 10-4). Severe asthma cases showed markedly higher leptin level than that in mild asthma cases among overall populations (SMD:1.638, 95% CI: 0.952-2.323, p < 10-4) and Asians (SMD:2.600, 95% CI: 1.854-3.345, p < 10-4). No significant difference of leptin level between severe and mild asthma was observed in Caucasians (SMD:-0.819, 95% CI: -1.998-0.360, p = 0.173). Cumulative analyses yielded similar results regarding the difference of leptin status between asthma and non-asthma controls, as well as between severe and mild asthma cases among overall populations. Age and male/ female ratio were not associated with the difference of leptin status between asthma and non-asthma controls (coefficient:-0.031, 95% CI: -0.123-0.061, p = 0.495; coefficient:0.172, 95% CI: -2.445-2.789, p = 0.895), as well as between severe and mild asthma cases among overall populations (coefficient:-0.072, 95% CI: -0.208-0.063, p = 0.279; coefficient: 2.373, 95% CI: -0.414-5.161, p = 0.090). Asthma demonstrated significantly higher level of leptin than that in non-asthma controls among overall populations, Caucasians, Asians and Africans. Severe asthma cases showed markedly higher leptin level than that in mild cases among overall populations and Asians. Leptin may be a risk predictor and prognostic marker of asthma. Early monitoring and intervention of leptin may be needed for asthma.

The prognostic prediction of periodontal non-surgery therapy in periodontitis patients based on surface-enhanced Raman measurements of pre-treatment saliva.

Periodontitis is one of the most prevalent dental diseases, and the patients with periodontitis often suffer from refractory periodontitis or recurrence of disease due to improper or inadequate treatment. In clinical practice, the early and accurate assessment of post-treatment prognosis in periodontitis patients is always very important in order to implement timely interventions. In this study, a pre-treatment saliva SERS based prognostic protocol was explored to predict the prognosis of periodontal non-surgery therapy in periodontitis patients. According to the biomolecular analysis, significant differences in the levels of ascorbic acid, uric acid and glutathione are observed between good prognosis group and poor prognosis group, which are expected to serve as potential prognostic markers. Furthermore, high accuracy, sensitivity and specificity can also be achieved by using the proposed prognostic model. The excellent performance of the proposed method has demonstrated its potential for fast, accurate, and non-invasive prognostic prediction of periodontal non-surgery therapy in periodontitis patients, even at the time before implementing treatment, thus is expected to benefit timely and rational guidance on clinical interventions.

A prediction study of IL-18 and IFN-γ in glucocorticoid treatment response in infants and young children with severe Mycoplasma pneumoniae pneumonia.

Background: In infants and young children, the clinical decision to apply glucocorticoids to severe Mycoplasma pneumoniae pneumonia (SMPP) is more an empirical choice with reference to clinical symptoms, but the effect is not satisfying. We aimed to explore and identify early predictive indicators of ideal response to glucocorticoids treatment in SMPP in infants and young children. Methods: We retrospectively reviewed the data of 59 patients, which met the age range and diagnostic criteria, admitted to Department of Pediatrics, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, from January to December 2017. Patients were divided into a glucocorticoid treatment group and a normal treatment group according to whether glucocorticoid treatment was used, and the difference in therapeutic effectiveness was compared between two groups. The glucocorticoid treatment group was further subdivided into effective versus ineffective treatment groups dependent on the difference of glucocorticoid treatment effect in main clinical symptoms improvement. We obtained the test value of biomarkers by ELISA, and identified several specific indicators with significantly different expressions in the early stage by independent sample t-tests and calculated their cut-off values by ROC curve. Results: Thirty-one SMPP patients who received glucocorticoid treatment were divided into effective and ineffective treatment groups according to the clinical improvements shown on different days of glucocorticoid use. The expression of two markers, interleukin-18 (IL-18) and interferon-γ (IFN-γ), were significantly different in cases showing improvement in the early stage of SMPP (P<0.05), and the cut-off values for IL-18 (218.19 pg/mL, AUC =0.581, sensitivity =0.909, 1-specificity =0.786) and IFN-γ (11.24 pg/mL, AUC =0.566, sensitivity =0.905, 1-specificity =0.795) were identified. Conclusions: The expressions of IL-18 and IFN-γ in the early stage of SMPP might suggest their predictive effect of early application of glucocorticoid for effective treatment of SMPP in infants and young children. Further study with larger sample size will be carried on in the future.

Prediction of the postoperative prognosis in patients with non-muscle-invasive bladder cancer based on preoperative serum surface-enhanced Raman spectroscopy.

Non-muscle-invasive bladder cancer (NMIBC) is a common urinary tumor and has a high recurrence rate due to improper or inadequate conservative treatment. The early and accurate prediction of its recurrence can be helpful to implement timely and rational treatment. In this study, we explored a preoperative serum surface-enhanced Raman spectroscopy based prognostic protocol to predict the postoperative prognosis for NMIBC patients at the time even before treatment. The biochemical analysis results suggested that biomolecules related to DNA/RNA, protein substances, trehalose and collagen are expected to be potential prognostic markers, which further compared with several routine clinically used immunohistochemistry expressions with prognostic values. In addition, high prognostic accuracies of 87.01% and 89.47% were achieved by using the proposed prognostic models to predict the future postoperative recurrence and recurrent type, respectively. Therefore, we believe that the proposed method has great potential in the early and accurate prediction of postoperative prognosis in patients with NMIBC, which is with important clinical significance to guide the treatment and further improve the recurrence rate and survival time.

Blockade of NLRP3/Caspase-1/IL-1ß Regulated Th17/Treg Immune Imbalance and Attenuated the Neutrophilic Airway Inflammation in an Ovalbumin-Induced Murine Model of Asthma.

Asthma is a heterogeneous inflammatory disorder of the airways, and multiple studies have addressed the vital role of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1ß (IL-1ß) pathway in asthma, but its impact on ovalbumin- (OVA-) induced neutrophilic asthma remains unclear. Here, we explored this pathway's effect on airway inflammation in neutrophilic asthma to clarify whether blocking this signaling could alleviate asthmatic airway inflammation. Using an established OVA-induced neutrophilic asthma mouse model, we provided asthmatic mice with a highly selective NLRP3 inhibitor, MCC950, and a specific caspase-1 inhibitor, Ac-YVAD-cmk. Our results indicated that asthmatic mice exhibited increased airway hyperresponsiveness, neutrophil infiltration, and airway mucus hypersecretion, upregulated retinoid-related orphan receptor-γt (RORγt) mRNA expression, and downregulated fork head box p3 (Foxp3) mRNA expression, which was concurrent with NLRP3 inflammasome activation and upregulation of caspase-1, IL-1ß, and IL-18 expression in lung. Treatment of NLRP3 inflammasome inhibitors significantly attenuated airway hyperresponsiveness, airway inflammation, and reversed T helper 17 (Th17)/regulatory T (Treg) cell imbalance in asthmatic mice. We propose that the NLRP3/caspase-1/IL-1ß pathway plays an important role in the pathological process of neutrophilic asthma and provides evidence that blocking this pathway could potentially be a treatment strategy to ameliorate airway inflammation in asthma after validation with future experimental and clinical studies.

Early assessment of chemotherapeutic response in hepatocellular carcinoma based on serum surface-enhanced Raman spectroscopy.

In clinical practice, the transcatheter arterial chemoembolization (TACE) has been widely accepted as the first option for non-surgical hepatocellular carcinoma (HCC) treatment. However, patients with HCC often suffer from poor response to TACE therapy. This can be prevented if the chemotherapeutic response can be early and accurately assessed, which is essential to guide timely and rational management. In this study, the serum SERS technique was for the first time investigated as a potential prognostic tool for early assessment of HCC chemotherapeutic response. According to the SERS spectral analysis results, it is newly found that not only the absolute circulating nucleic acids and collagen levels in pre-therapeutic serum but also the changes in circulating nucleic acids and amino acids between pre-therapeutic and post-therapeutic serum are expected to be potential serum markers for HCC prognosis. By further applying chemometrics methods to establish prognostic models, excellent prognostic accuracies were achieved within only 3 days after TACE therapy. Thus, the proposed method is expected to provide guidance on timely and rational management of HCC to improve its survival rate.

Predicting prognosis in acute myeloid leukemia patients by surface-enhanced Raman spectroscopy.

Aim: To develop a timely and accurate method for predicting acute myeloid leukemia (AML) prognosis after chemotherapy treatment by surface-enhanced Raman spectroscopy (SERS). Methods: Biomolecular differences between AML patients with good and poor prognosis and individuals without AML were investigated based on SERS measurements of bone marrow supernatant fluid samples. Multivariate analysis was implemented on the SERS measurements to establish an AML prognostic model. Results: Significant differences in amino acid, saccharide and lipid levels were observed between AML patients with good and poor prognoses. The AML prognostic model achieved a prediction accuracy of 84.78%. Conclusion: The proposed method could be a potential diagnostic tool for timely and precise prediction of AML prognosis.

Lay abstract Acute myeloid leukemia (AML) is a disease in which too many immature white blood cells are found in the blood and bone marrow. Prognosis (the chance of recovery) for this disease is not favorable. However, if the disease can be quickly and precisely assessed, a personalized chemotherapy plan can be used. This could significantly improve the cure rate. In this study, a technique known as surface-enhanced Raman spectroscopy was used to analyze bone marrow samples from patients with and without AML. The samples were looked at to find biological molecules that could act as indicators for the disease and for disease prognosis. Using the collected data, models were established to predict whether a patient had AML and, if so, whether they had good or poor prognosis.

A predictive model for dilated cardiomyopathy with pulmonary hypertension.

AIMS: Dilated cardiomyopathy (DCM) is defined as a serious cardiac disorder caused by the presence of left ventricular dilatation and contractile dysfunction in the absence of severe coronary artery disease and abnormal loading conditions. The incidence of cardiac death is markedly higher in patients with DCM with pulmonary hypertension (PH) than in DCM patients without PH. No previous studies have constructed a predictive model to predict PH in patients with DCM. METHODS: Data from 218 DCM patients (68.3% man; mean age 57.33) were collected. Patients were divided into low, intermediate and high PH-risk groups based on the echocardiographic assessment at the tricuspid regurgitation peak velocity (TRV) in conjunction with the presence of echocardiographic signs from at least two different categories. Basic information, vital signs, comorbidities and biochemical data of each patient were determined. The impact of each parameter on PH probability was analysed by univariable and multivariable analyses, the data from which were employed to establish a predictive model. Finally, the discriminability, calibration ability and clinical efficacy of the model were verified for both the modelling group and the external validation group. RESULTS: We successfully applied a history of chronic obstructive pulmonary disease (COPD) or chronic bronchitis, systolic murmur (SM) at the tricuspid area, SM at the apex and brain natriuretic peptide (BNP) level to establish a model for predicting PH probability in DCM. The model was proven to have high accuracy and good discriminability (area under the receiver operating characteristic curve 0.889), calibration ability and clinical application value. CONCLUSIONS: A model for predicting PH probability in patients with DCM was successfully established. The new model is reliable for predicting PH probability in DCM and has good clinical applicability.

Visible-Light-Responsive Photocatalyst of Graphitic Carbon Nitride for Pathogenic Biofilm Control.

Pathogenic biofilms raise significant health and economic concerns, because these bacteria are persistent and can lead to long-term infections in vivo and surface contamination in healthcare and industrial facilities or devices. Compared with conventional antimicrobial strategies, photocatalysis holds promise for biofilm control because of its broad-spectrum effectiveness under ambient conditions, low cost, easy operation, and reduced maintenance. In this study, we investigated the performance and mechanism of Staphylococcus epidermidis biofilm control and eradication on the surface of an innovative photocatalyst, graphitic carbon nitride (g-C3N4), under visible-light irradiation, which overcame the need for ultraviolet light for many current photocatalysts (e.g., titanium dioxide (TiO2)). Optical coherence tomography and confocal laser scanning microscopy (CLSM) suggested that g-C3N4 coupons inhibited biofilm development and eradicated mature biofilms under the irradiation of white light-emitting diodes. Biofilm inactivation was observed occurring from the surface toward the center of the biofilms, suggesting that the diffusion of reactive species into the biofilms played a key role. By taking advantage of scanning electron microscopy, CLSM, and atomic force microscopy for biofilm morphology, composition, and mechanical property characterization, we demonstrated that photocatalysis destroyed the integrated and cohesive structure of biofilms and facilitated biofilm eradication by removing the extracellular polymeric substances. Moreover, reactive oxygen species generated during g-C3N4 photocatalysis were quantified via reactions with radical probes and 1O2 was believed to be responsible for biofilm control and removal. Our work highlights the promise of using g-C3N4 for a broad range of antimicrobial applications, especially for the eradication of persistent biofilms under visible-light irradiation, including photodynamic therapy, environmental remediation, food-industry applications, and self-cleaning surface development.