Interaction between baseline BMI and baseline disease severity predicts greater improvement in negative symptoms in first-episode schizophrenia.

Several studies have reported that baseline symptom severity in patients with schizophrenia (SCZ) is associated with the efficacy of antipsychotic medication. Overweight/obesity is common in SCZ and has also been reported to be correlated with therapeutic response to antipsychotics. This study aimed to evaluate whether baseline body mass index (BMI) and disease severity were associated with improvements in negative symptoms in patients with first-episode and medication-naïve (FEMN) SCZ. A total of 241 FEMN patients were recruited in this study and treated with oral risperidone over 3 months. Clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) and BMI was assessed at baseline and 3-month follow-up. We found that baseline BMI was correlated with the baseline severity of symptoms. Baseline BMI or baseline disease severity was associated with improvement in negative symptoms after 3 months of treatment. Linear regression analysis indicated that the interaction of BMI and disease severity at baseline was associated with improvement in negative symptoms in the early stage of SCZ after controlling for sex, age, and dose of risperidone. Our study suggests that the interaction of baseline BMI and disease severity may play a role in predicting negative symptom improvement after 3 months of risperidone treatment.

Vector-guided Fourier single-pixel imaging.

The Fourier single-pixel imaging technique exhibits great potential for compressive imaging. However, the utilization of low sampling ratio can introduce unwanted ringing artifacts, thereby compromising the fidelity of reconstructed image detail. To address this issue, Vector guided Fourier single-pixel imaging (V-FSI) has been proposed. We analyze the statistical properties in the edge vector field derived from images with low sampling ratio. Based on this information, a tailored sampling map is designed to acquire the significant high-frequency components for image reconstruction. Experimental results demonstrate the remarkable effectiveness of the proposed V-FSI method in enhancing image quality. Notably, V-FSI exhibits exceptional capabilities in perceiving and preserving the details of the objects, particularly for objects characterized by pronounced periodicity and directionality.

Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy.

Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO2 (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O2) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.

Effects of renal denervation on cardiac function after percutaneous coronary intervention in patients with acute myocardial infarction.

Objective: To observe the effect of renal artery denervation (RDN) on cardiac function in patients with acute myocardial infarction after percutaneous coronary intervention (AMI-PCI). Methods: This is a single-centre, prospective randomized controlled study. A total of 108 AMI-PCI patients were randomly assigned to the RDN group or the control group at 1:1 ratio. All patients received standardized drug therapy after PCI, and patients in the RDN group underwent additional RDN at 4 weeks after the PCI. The follow-up period was 6 months after RDN. Echocardiography-derived parameters, cardiopulmonary exercise testing (CPET) data, Holter electrocardiogram, heart rate variability (HRV) at baseline and at the 6 months-follow up were analyzed. Results: Baseline indexes were similar between the two groups (all P > 0.05). After 6 months of follow-up, the echocardiography-derived left ventricular ejection fraction was significantly higher in the RDN group than those in the control group. Cardiopulmonary exercise test indicators VO2Max, metabolic equivalents were significantly higher in the RDN group than in the control group. HRV analysis showed that standard deviation of the normal-to-normal R-R intervals, levels of square root of the mean squared difference of successive RR intervals were significantly higher in the RDN group than those in the control group. Conclusions: RDN intervention after PCI in AMI patients is associated with improved cardiac function, improved exercise tolerance in AMI patients post PCI. The underlying mechanism of RDN induced beneficial effects may be related to the inhibition of sympathetic nerve activity and restoration of the sympathetic-vagal balance in these patients.

Viral and Atypical Pathogen's Epidemiology of a Large Cohort of Patients with Acute Respiratory Tract Infections in Shaanxi Province, Northwest China.

Purpose: To analyze and summarize the etiological and epidemiological characteristics of acute respiratory tract infections (ARIs) in northwest China to improve the clinical management and prevention of local ARIs. Methods: Patients with ARIs in Shaanxi Province, from January 2014 to December 2018, were retrospectively analyzed. Indirect immunofluorescence assay (IFA) was used to detect the IgM antibody of eight respiratory pathogens. Results: A total of 15,543 eligible patients were included in this study. Overall, 36.01% of the patients (5597/15543) were positive for at least one of eight pathogens, among which single and mixed infections accounted for 74.65% (4178/5597) and 25.35% (1419/5597), respectively. Mycoplasma (MP) showed the highest detection rate (18.12%), followed by influenza virus B (Flu B, 11.65%), chlamydia (CP, 7.00%), respiratory syncytial virus (RSV, 4.18%), parainfluenza virus (PIV, 2.83%), influenza virus A (Flu A, 1.69%), legionella (LP, 1.00%) and adenovirus (ADV, 0.70%). Flu B (17.54%, 759/4327) was the most prevalent virus in patients aged less than 18 years. In addition, common respiratory infections with higher detection rates were found in autumn (39.65%), followed by winter (37.37%), summer (36.21%) and spring (30.91%). There were significant differences in the detection rates of pathogens in different seasons (P < 0.001). Conclusion: These findings serve as a reference for local health authorities to develop further plans for the prevention and control of ARIs.

Labeling Assembly of Hydrophilic Methionine into Nanoparticle for Mild-Heat Mediated Immunometabolic Therapy.

Methionine metabolism has a significant impact on T cells' survival and activation even in comparison to arginine, a well-documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild-heat mediated immunometabolic therapy. The strategy is to first label methionine with protocatechualdehyde (as the tag) via reversible Schiff-base bond, and then drive nanoassembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photothermal characteristics can be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor-selective aggregation in acidic TME. A mild heat of 43 °C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8+ T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2-fold of tumor-infiltrating INF-γ+ CD8+ T cells, leading to an inhibition ratio of 27.3-fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids.

Effects and mechanism of renal denervation on ventricular arrhythmia after acute myocardial infarction in rats.

BACKGROUND: Renal denervation (RDN) can reduce ventricular arrhythmia after acute myocardial infarction (AMI), but the mechanism is not clear. The purpose of this study is to study its mechanism. METHODS: Thirty-two Sprague-Dawley rats were divided into four groups: control group, AMI group, RDN-1d + AMI group, RDN-2w + AMI group. The AMI model was established 1 day after RDN in the RDN-1d + AMI group and 2 weeks after RDN in the RDN-2w + AMI group. At the same time, 8 normal rats were subjected to AMI modelling (the AMI group). The control group consisted of 8 rats without RDN intervention or AMI modelling. RESULTS: The study confirmed that RDN can reduce the occurrence of ventricular tachycardia in AMI rats, reduce renal sympathetic nerve discharge, and inhibit the activity of local sympathetic nerves and cell growth factor (NGF) protein expression in the heart after AMI. In addition, RDN decreased the expression of norepinephrine (NE) and glutamate in the hypothalamus,and NE in cerebrospinal fluid, and increased the expression level of γ aminobutyric acid (GABA) in the hypothalamus after AMI. CONCLUSION: RDN can effectively reduce the occurrence of ventricular arrhythmia after AMI, and its main mechanism may be via the inhibition of central sympathetic nerve discharge.

Dual Closed-Loop of Catalyzed Lactate Depletion and Immune Response to Potentiate Photothermal Immunotherapy.

Lactate accumulation in the solid tumor is highly relevant to the immunosuppressive tumor microenvironment (TME). Targeting lactate metabolism significantly enhances the efficacy of immunotherapy. However, lactate depletion by lactate oxidase (LOX) consumes oxygen and results in the aggravated hypoxia situation, counteracting the benefit of lactate depletion. Beyond the TME regulation, it is necessary to initiate the effective immunity cycle for therapeutic purposes. In this fashion, dual close-loop of catalyzed lactate depletion and immune response by a rational material design are established to address this issue. Here, we constructed PEG-modified mesoporous polydopamine nanoparticles with Cu2+ chelation and LOX encapsulation (denoted as mCuLP). After mCuLP nanosystems targeting into the tumor sites, released LOX consumes lactate to H2O2. Subsequently, the produced H2O2 is further catalyzed by Cu2+-chelated mPDA to produce oxygen, supplying the oxygen source for the closed-loop of lactate depletion. Meanwhile, the mild PTT caused by the photothermal mPDA induces ICD of tumor cells to promote DC maturation and then T lymphocyte infiltration to kill tumor cells, which forms another closed-loop for cancer immunity. Therefore, this dual closed-loop strategy of mCuLP nanosystems effectively inhibits tumor growth, providing a promising treatment modality to cancer immunotherapy.

Remotely boosting hyaluronidase activity to normalize the hypoxic immunosuppressive tumor microenvironment for photothermal immunotherapy.

Tumor hyaluronan (HA) accumulation is closely associated with the formation of a hypoxic microenvironment that is highly immunosuppressive and severely hinders the efficacy of antitumor therapeutics. To address this problem, we develop an effective HA attenuation strategy that uses an integrated nanosystem based on mesoporous polydopamine (mPDA) with excellent photothermal conversion efficiency to boost hyaluronidase (HAase) activity remotely. Upon light irradiation, the thermal effect generated by mPDA not only directly kills tumor cells that produces an in situ vaccine effect, but also significantly boosts HAase activity (∼5 folds), leading to marked HA break down. Photoheat and HA degradation synergistically reduce tumor HIF-1α expression and reverse immunosuppressive responses. Using the synergistic treatment in a breast cancer model, we find decreased infiltration of immunosuppressive cells, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, increased immune-activated cells, such as mature dendritic cells and CD8+ T cells, and reduced immune checkpoint PD-L1 expression. The resulting relief from tumor microenvironment immunosuppression significantly contributes to an enhanced antitumor effect. This study provides an effective strategy to improve the hypoxic tumor microenvironment and simultaneously promote immune-mediated tumor regression.

Targeting the Negative Feedback of Adenosine-A2AR Metabolic Pathway by a Tailored Nanoinhibitor for Photothermal Immunotherapy.

The metabolite adenosine plays an important immunosuppressive role in the tumor microenvironment (TME) through its ligation with the metabolic checkpoint adenosine 2A receptor (A2AR). Here, an adenosine-A2AR negative feedback pathway is highlighted during photothermal-induced immunogenic cell death (ICD). Adenosine, hydrolyzed from ATP, is amplified during the photothermal-induced ICD process. It is possible to achieve a robust ICD-based immunotherapy via targeting the adenosine-A2AR metabolic pathway. In this regard, an A2AR inhibitor-loaded polydopamine nanocarrier masked by an acid-sensitive PEG shell is designed to enable tumor-specific delivery and photothermal-induced ICD simultaneously. Upon reaching the acidic TME, the PEG shell selectively detaches and exposes the adhesive polydopamine layer, causing the inhibitors to accumulate at the tumor tissue. The accumulated inhibitors attenuate adenosine's metabolically suppressive effect and strengthen the ICD immune response. It occurs through promoting dendritic cell (DC) activation, increasing CD8+ T lymphocyte infiltration, and reducing the myeloid-derived suppressor cell (MDSC) population. Furthermore, this synergistic therapy significantly regresses the primary tumor, inhibits distal tumor growth, and prevents lung metastasis. The study highlights a strategy to enhance the immunotherapy efficacy of ICD by blocking the metabolic checkpoint A2AR using advanced nanomaterials.

Organocatalytic cycloaddition of alkynylindoles with azonaphthalenes for atroposelective construction of indole-based biaryls.

The axially chiral indole-aryl motifs are present in natural products and biologically active compounds as well as in chiral ligands. Atroposelective indole formation is an efficient method to construct indole-based biaryls. We report herein the result of a chiral phosphoric acid catalyzed asymmetric cycloaddition of 3-alkynylindoles with azonaphthalenes. A class of indole-based biaryls were prepared efficiently with excellent yields and enantioselectivities (up to 98% yield, 99% ee). Control experiment and DFT calculations illustrate a possible mechanism in which the reaction proceeds via a dearomatization of indole to generate an allene-iminium intermediate, followed by an intramolecular aza-Michael addition. This approach provides a convergent synthetic strategy for enantioselective construction of axially chiral heterobiaryl backbones.

Nanotechnology-Based Approaches to Promote Lymph Node Targeted Delivery of Cancer Vaccines.

Vaccines are a promising immunotherapy that awakens the human immune system to inhibit and eliminate cancer with fewer side effects compared with traditional radiotherapy and chemotherapy. Although cancer vaccines have shown some efficacy, there are still troublesome bottlenecks to expand their benefits in the clinic, including weak immune effects and limited therapeutic outcomes. In the past few years, in addition to neoantigen screening, a main branch of the efforts has been devoted to promoting the lymph nodes (LNs) targeting of cancer vaccines and the cross-presentation of antigens by dendritic cells (DCs), two cardinal stages in effective initiation of the immune response. Especially, nanomaterials have shown hopeful biomedical applications in the improvement of vaccine effectiveness. This Review briefly outlines the possible mechanisms by which nanoparticle properties affect LN targeting and antigen cross-presentation and then gives an overview of state-of-the-art advances in improving these biological outcomes with nanotechnology.

Clinical observation of sacubitril valsartan sodium in the treatment of resistant hypertension: A randomized clinical trial.

Objective: To investigate the effectiveness and safety of sacubitril valsartan sodium in the treatment of resistant hypertension (RH). Methods: This study is a single-center, prospective, randomized controlled study. According to the inclusion and exclusion criteria, patients with RH who met the criteria were screened, and all patients adjusted their drug treatment (valsartan 80 mg, amlodipine 5 mg, and hydrochlorothiazide 12.5 mg). After 4 weeks of drug elution, the random envelope method was used for random grouping. The treatment group took sacubitril valsartan sodium 200 mg, amlodipine 5 mg, hydrochlorothiazide 12.5 mg, and the control group took valsartan 80 mg, amlodipine 5 mg, and hydrochlorothiazide 12.5 mg for 8 weeks. The 24 h ambulatory blood pressure (BP) and the echocardiography index using the office sphygmomanometer were observed in the patients. Results: A total of 100 patients with RH were included in the two groups, with 50 cases in each group. There were no significant differences in sex, age, or comorbid diseases between the two groups. During the 8-week follow-up, the office BP of the research group were significantly decreased (24.78/17.86 mmHg) compared with those of the control group. In the research group the 24 h average BP, daytime average BP, and nighttime average BP were 144.84/79.82, 147.10/82.06, and 138.67/76.31 mmHg at baseline, and reduced to 128.96/73.32, 131.50/74.94, and 122.11/69.27 mmHg at week 8, which were significantly decreased (P < 0.05 or P < 0.01), and the left ventricular ejection fraction was significantly increased (P < 0.05), compared with the control group. Conclusion: Sacubitril valsartan sodium can effectively reduce BP and improve cardiac function in RH.

Nanofactory for metabolic and chemodynamic therapy: pro-tumor lactate trapping and anti-tumor ROS transition.

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a "lactate treatment plant" (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.

Adaptive Fourier single pixel imaging based on the radial correlation in the Fourier domain.

Fourier single-pixel imaging (FSI) can directly measure the Fourier coefficients of an object and reconstruct its image, and the technique has attracted attention recently. However, with the current spectrum sampling methods of FSI it is difficult to balance image details and noise suppression within a limited sampling number and a short reconstruction time. To address this problem, the method of adaptive Fourier single-pixel imaging (A-FSI) is proposed to measure the coefficients of the key spectra adaptively. First we examine radial correlation between low-frequency and high-frequency components in the Fourier domain. Based on this correlation, we estimate the positions of significant high-frequency components through the chosen low-frequency components, measure the corresponding Fourier coefficients and form the image. Importantly, the proposed A-FSI only uses the inverse Fourier transform for reconstruction, which is much faster than the algorithm of compressed sensing under the given conditions. Both the simulations and experiments show that the proposed method can keep details of the image and reduce the noise of reconstruction at same time with a limited sampling number and a short reconstruction time. This technology can promote the practical development of single-pixel imaging.

Nanovaccine biomineralization for cancer immunotherapy: a NADPH oxidase-inspired strategy for improving antigen cross-presentation via lipid peroxidation.

Current efforts to develop novel vaccine nanotechnologies to increase cytotoxic T lymphocytes have met the challenges of the limited efficacy of antigen cross-presentation. Recent studies have uncovered a unique biological mechanism by which activation of the NADPH oxidase 2 (NOX2) complex, a major source of reactive oxygen species (ROS), enhances the cross-presentation by antigen-presenting cells (APCs). Inspired by the NOX2 mechanism, we devise biomineralized nanovaccines named NVscp, which are developed by in situ growth of calcium peroxide on nanovaccines self-assembled with the model antigen ovalbumin. The ~80 nm NVscp efficiently flow to the draining lymph nodes, where they accumulate within APC endo-/lysosomes, and generate a rapid burst of ROS in response to the acidic endo-/lysosomal environment with the subsequent endo-/lysosomal lipid peroxidation. Accompanied by the process, NVscp stimulate distinct APCs maturation and antigen presentation to T lymphocytes. Notably, high levels of antigen-specific CD8+ T cell responses, accompanied by the induction of CD4+ T helper cells, are achieved. More importantly, NVscp significantly increase the ratios of intratumoral CD8+ T/regulatory T cells and achieve prominent tumor therapy effects. The NOX2-inspired biomineralized NVscp represent an effective and easily applicable strategy that enables the strong cross-presentation of exogenous vaccine antigens.

Block Matching Pyramid Algorithm-Based Analysis on Efficacy of Shexiang Baoxin Pills Guided by Echocardiogram (ECG) on Patients with Angina Pectoris in Coronary Heart Disease.

This paper was aimed to explore the application of the block matching pyramid (BMP) algorithm in echocardiographic spot tracking in patients with coronary heart disease (CHD) and angina pectoris, as well as the effect of Shexiang Baoxin pills (a kind of drug containing musk, which is good for cardiac diseases) on blood lipids, cardiac function, and curative effect. 206 patients with CHD angina pectoris in the hospital from July 2018 to May 2020 were selected as the research subjects and were enrolled into the control (Ctrl) group (conventional treatment, n = 103) and the observation group (the Shexiang Baoxin pill was given on the basis of conventional treatment, n = 103) in random. Then, the patients' echocardiograms were obtained, and the BMP algorithm was used to track the echocardiograms. At 12 months after treatment, the total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were compared. Besides, the differences between left ventricular end-systolic volume (LVESV), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic dimension (LVEDD), cardiac index (CI), cardiac output (CO), and LVEF were observed. Finally, the efficacy of angina pectoris and electrocardiogram was calculated. It was found that the BMP algorithm can track the echocardiograms and display the movement and displacement of the patients' left ventricle. After treatment, in contrast with the Ctrl, the levels of TC, TG, and LDL-C in the observation group were obviously lower (P < 0.05); the LVESV, LVEDV, and LVEF were obviously lower (P < 0.05), the LVESD, LVEDD, CO, and CI were obviously higher (P < 0.05), the total score of angina after treatment was obviously lower (P < 0.05), and the total effective rates of angina pectoris and echocardiogram were obviously higher (P < 0.05). In conclusion, echocardiographic spot tracking can realize the diagnosis of patients with CHD angina pectoris, and Shexiang Baoxin pill can regulate the blood lipid level and improve the echocardiographic indicators and the clinical efficacy is obvious.

Photosensitizer-Laden Neutrophils Are Controlled Remotely for Cancer Immunotherapy.

By incorporating an artificial reactive oxygen species (ROS) generation mechanism, a biotic/abiotic integration is designed to improve the anti-tumor effect of neutrophils by artificially potentiating their ROS effector mechanism in a remotely controlled route. Specifically, the photosensitizer Ce6 is nano-packaged by the albumin BSA to achieve biocompatible and efficient integration with neutrophils (NEs). Reinfusion of the engineered NEs into 4T1 tumor-bearing mice led to more Ce6 accumulation in tumors relative to Ce6 nanoformulation. At the peak of accumulation, tumor illumination activates the embedded Ce6 for ROS generation and NETosis formation. Because of the ROS-intensified cytolytic effect, the growth of 4T1 tumors is inhibited significantly. The photo-controlled process largely avoids the off-target effects observed frequently in current cell therapies. The strategy directly generates ROS effector molecules with spatiotemporal precision. This engineering approach is able to potentiate the native capacity of immune cells independent of the tumor microenvironment.

The Value of Inflammatory Biomarkers in Differentiating Asthma-COPD Overlap from COPD.

Purpose: To evaluate the accuracy of inflammatory biomarkers in differentiating patients with asthma-COPD overlap (ACO) from those with COPD alone. Methods: Clinical data of 134 patients with COPD and 48 patients with ACO admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 were retrospectively analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the best cut-off values of fractional exhaled nitric oxide (FeNO), blood eosinophil counts (EOS), and neutrophil to lymphocyte ratio (NLR) for differentiating between ACO and COPD alone. Spearman correlation analysis was conducted to evaluate the relationships between these inflammatory biomarkers and the forced expiratory volume in one second/prediction (FEV1%pred). Results: FeNO and EOS in the ACO patients were significantly higher than those in the COPD patients (FeNO: median 37.50 vs 24.50 ppb, P < 0.001; EOS: median 0.20 vs 0.10 ×109/L, P = 0.004). FeNO was positively correlated with FEV1%pred (r = 0.314, P = 0.030), while NLR was negatively correlated with FEV1%pred (r = -0.372, P = 0.009) in patients with ACO. In addition, a positive correlation between FeNO and EOS was also found in ACO, especially in patients without history of inhaled corticosteroids (ICS) use (r = 0.682, P < 0.001). The optimal cut-off value of FeNO was 31.5 ppb (AUC = 0.758, 95% CI = 0.631-0.886) in patients with smoking history, with 70.0% sensitivity and 89.9% specificity for differentiating ACO from COPD. In patients without history of ICS use, the best cut-off value of FeNO was 39.5 ppb (AUC = 0.740, 95% CI = 0.610-0.870), with 58.3% sensitivity and 84.9% specificity. Among patients without history of ICS use and smoking, 27.5 ppb was optimal cut-off level for FeNO (AUC = 0.744, 95% CI = 0.579-0.908) to diagnose ACO, with 81.8% sensitivity and 60.7% specificity, and the sensitivity was improved to 91.7% when FeNO was combined with EOS. Conclusion: The inflammatory biomarkers FeNO and EOS can be used as indicators for differentiating between ACO and COPD alone.

Development of EST-SSR markers and association mapping with floral traits in Syringa oblata.

BACKGROUND: Lilac (Syringa oblata) is an important woody plant with high ornamental value. However, very limited genetic marker resources are currently available, and little is known about the genetic architecture of important ornamental traits for S. oblata, which is hindering its genetic studies. Therefore, it is of great significance to develop effective molecular markers and understand the genetic architecture of complex floral traits for the genetic research of S. oblata. RESULTS: In this study, a total of 10,988 SSRs were obtained from 9864 unigene sequences with an average of one SSR per 8.13 kb, of which di-nucleotide repeats were the dominant type (32.86%, 3611). A set of 2042 primer pairs were validated, out of which 932 (45.7%) exhibited successful amplifications, and 248 (12.1%) were polymorphic in eight S. oblata individuals. In addition, 30 polymorphic EST-SSR markers were further used to assess the genetic diversity and the population structure of 192 cultivated S. oblata individuals. Two hundred thirty-four alleles were detected, and the PIC values ranged from 0.23 to 0.88 with an average of 0.51, indicating a high level of genetic diversity within this cultivated population. The analysis of population structure showed two major subgroups in the association population. Finally, 20 significant associations were identified involving 17 markers with nine floral traits using the mixed linear model. Moreover, marker SO104, SO695 and SO790 had significant relationship with more than one trait. CONCLUSION: The results showed newly developed markers were valuable resource and provided powerful tools for genetic breeding of lilac. Beyond that, our study could serve an efficient foundation for further facilitate genetic improvement of floral traits for lilac.