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OBJECTIVE: Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. METHODS: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-β, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. RESULTS: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = - 0.348) and asthma quality of life questionnaire scores (r = - 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. CONCLUSION: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.

Background Data on treatable traits (TTs) in different populations are limited. Objective To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. Methods We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. Results A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection–induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection–induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. Conclusions TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma.

Objective To assess the effectiveness, safety, and acceptability of post-placental insertion of GyneFix postpartum intrauterine device (PPIUD) in women undergoing cesarean section (C-section). Design Prospective cohort study. Setting Fourteen hospitals in four provinces of China. Population and sample Women who underwent C-section and consented to the post-placental insertion of GyneFix PPIUD. We enrolled 470 participants, and 400 completed the 12-month follow-up. Methods Participants were interviewed in the wards after delivery and followed up at 42 days, and months 3, 6, and 12 after delivery. Main outcome measures Pregnancy, PPIUD expulsion, serious adverse events, and continuation of PPIUD. Results Nine pregnancies were detected during the first year after GytneFix PPIUD insertion, 7 were due to device expulsion and 2 occurred with PPIUD in situ. The Pearl Indices (PI; pregnancy per 100 women-years) for overall 1-year pregnancy rate and pregnancies with IUD in situ were 2.32 (95% CI: 1.06–4.40) and 0.51 (95% CI: 0.06–1.86), respectively. The 1-year expulsion PI was 8.25 (95% CI: 5.63–11.63). The expulsion PI was significantly higher in the first 6 months (12.78, 95% CI: 8.42–18.60) than the second 6 months (2.82, 95% CI: 0.92–6.58). The cumulative 1-year continuation rate was 86.56% (95% CI: 83.32–89.79). We did not identify any patient with insertion failure, uterine perforation, pelvic infection, or excess bleeding due to GyneFix PPIUD insertion. Conclusions Post-placental insertion of GyneFix PPIUD is effective, safe, and acceptable for women undergoing C-section. An ultrasound scan during the first 6 months after PPIUD insertion is recommended to identify any unrecognized expulsions.

Background: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. Objectives: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25–75%), with clinical and inflammatory profile and treatment responsiveness in asthma. Method: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. Results: SAD subjects had more elevated ΔVAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (p < 0.05), and Spearman partial correlation found FEF25–75% significantly related to IFN-γ and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (p = 0.022 and p = 0.032). Conclusions: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy.

Background: Although studies have consistently linked obesity and asthma, the potential influence of visceral obesity on asthma has not been well investigated. Objective: To study the associations of visceral fat area (VFA) and clinical and inflammatory features of asthma and to further explore the effects of VFA on the future risk of asthma exacerbation. Methods: A 12-month prospective cohort study based on the Australasian Severe Asthma Network was designed to observe patients with stable asthma grouped by the median value of VFA. The clinical and inflammatory features of asthma were compared between the low VFA (VFAlow) and high VFA (VFAhigh) groups. Relationships between VFA and clinical and inflammatory features of asthma were analyzed by using correlation analysis. Univariate and multivariable negative binomial regression analyses were performed to investigate the association of VFA with exacerbations within a 12-month follow-up period. Results: The patients in the VFAhigh group were older and had a longer asthma duration. Interleukin (IL) 6 and IL-8 in sputum were higher, whereas fractional exhaled nitric oxide (FeNO) and blood eosinophils were lower in the VFAhigh group. Gender-differentiated correlations of VFA with clinical and inflammatory variables were observed in age, FeNO, immunoglobulin E, blood total white cells and neutrophils, and sputum IL-1β and IL-8. Furthermore, compared with the VFAlow group, the VFAhigh group was at significantly increased risk of moderate-to-severe exacerbations (adjusted incidence rate ratio [IRR] 1.55 [95% confidence interval {CI}, 1.06‐2.28; p = 0.025), severe exacerbations (adjusted IRR 2.25 [95% CI, 1.26‐4.04]; p = 0.007), and emergency visits (adjusted IRR 5.33 [95% CI, 1.78‐17.16]; p = 0.003). Conclusion: The level of VFA was associated with specific clinical and inflammatory characteristics of asthma. Furthermore, VFA, as an independent risk factor, was associated with an increased risk of exacerbations. It indicated that VFA would provide more potential clinical implications for asthma management.

BACKGROUND: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). METHODS: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. RESULTS: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/). CONCLUSION: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.

The Chinese white wax scale insect, Ericerus pela Chavannes (Hemiptera: Coccidae), is one of the scale insects with great economic value and has been dispersed and reared in China for over one thousand years. Its mitochondrial genome provides essential information for the molecular identification and genetic study of this species. We assembled the complete mitochondrial genome of E. pela based on PacBio sequencing and analyzed its genomic features. The genome was 17,766 bp in length with 13 protein-coding genes, 22 tRNAs, and two rRNA genes. The analysis results showed E. pela had significant gene rearrangements involving tRNAs compared with other Coccoidea species. Furthermore, E. pela’s nine tRNAs were identified to have obvious truncated structures. The phylogenetic tree compiled of the species showed a long branch of the Coccoidea lineage, which indicated the high evolutionary rate in this group. Our study revealed the mitochondrial characteristics of E. pela and enriched the mitochondrial genetic information on Coccoidea species. It also determined the occurrence of gene rearrangement for the species in this superfamily.

Insects encounter infection of microorganisms, and they also harbor endosymbiosis to participate in nutrition providing and act as a defender against pathogens. We previously found the Chinese white wax scale insect

The Chinese white wax scale, Ericerus pela, is an insect native to China. It harbors a variety of microbes. The Paraconiothyrium fungus was isolated from E. pela and genome sequenced in this study. A fungal cytotoxicity assay was performed on the Aedes albopictus cell line C6/36. The assembled Paraconiothyrium sp. genome was 39.55 Mb and consisted of 14,174 genes. The coding sequences accounted for 50.75% of the entire genome. Functional pathway analyses showed that Paraconiothyrium sp. possesses complete pathways for the biosynthesis of 20 amino acids, 10 of which E. pela lacks. It also had complementary genes in the vitamin B groups synthesis pathways. Secondary metabolism prediction showed many gene clusters that produce polyketide. Additionally, a large number of genes associated with ‘reduced virulence’ in the genome were annotated with the Pathogen–Host Interaction database. A total of 651 genes encoding carbohydrate-active enzymes were predicted to be mostly involved in plant polysaccharide degradation. Pan-specific genomic analyses showed that genes unique to Paraconiothyrium sp. were enriched in the pathways related to amino acid metabolism and secondary metabolism. GO annotation analysis yielded similar results. The top COG categories were ‘carbohydrate transport and metabolism’, ‘lipid transport and metabolism’, and ‘secondary metabolite biosynthesis, transport and catabolism’. Phylogenetic analyses based on gene family and pan genes showed that Paraconiothyrium sp is clustered together with species from the Didymosphaeriaceae family. A multi-locus sequence analysis showed that it converged with the same branch as P. brasiliense and they formed one group with fungi from the Paraconiothyrium genus. To validate the in vitro toxicity of Paraconiothyrium sp., a cytotoxicity assay was performed. The results showed that medium-cultured Paraconiothyrium sp. had no harmful effect on cell viability. No toxins were secreted by the fungus during growth. Our results imply that Paraconiothyrium sp. may establish a symbiotic relationship with the host to supply complementary nutrition to E. pela.

Optimizing the electrochemical carbon dioxide reduction reaction (CRR) to fuels is one of the most significant challenges in materials science and chemistry. Recently, single metal atom catalysts based on 2D materials have shown promise to improve the electroreduction performance of pristine 2D materials in the CRR. The physical origins of such performance enhancements are still poorly understood. Herein, we report the potential of a single Cu atom doped phosphorene catalyst for CO

Emerging evidence suggests that aging affects asthma outcomes, but the mechanism remains largely unexplored.To explore age-related clinical characteristics, inflammatory features, phenotypes, and treatment response in asthma.This was a prospective cohort study of asthmatic patients with a 12-month follow-up in a real-world setting. Clinical inflammatory and phenotypic characteristics, future risk for exacerbations, and treatment response were assessed across different age groups (young was defined as age 18 to 39 years; middle-aged, 40 to 64 years; and elderly, 65 years or older).Compared with young (n = 106) and middle-aged (n = 179) asthmatic patients, elderly patients (n = 55) had worse airway obstruction, more comorbidities including chronic obstructive pulmonary disease and diabetes, less atopy, and lower levels of IgE and FeNO, and were more likely to have late-onset and fixed airflow obstruction asthma and a reduced risk for having type 2 profile asthma. Levels of IFN-gamma, IL-17A, and IL-8 in induced sputum were significantly increased in elderly asthmatic patients (all P.05). Path analysis indicated that age directly and significantly led to future exacerbations in asthma, partially mediated by an upregulation of airway IFN-gamma. Moreover, elderly patients with asthma had a reduced treatment response (improvement in FEVThis study confirms that asthma in the elderly population represents a specific phenotype and indicates that aging can influence asthma in terms of clinical characteristics, inflammatory features, exacerbations, and treatment response.

The Chinese white wax scale insect, Ericerus pela, is an important resource insect in China. The rapid response of E. pela to decreasing temperatures plays key roles in the population distribution. In this study, we analyzed the gene expression of E. pela treated with low temperature using transcriptome analyses and weighted gene coexpression network analysis (WGCNA). The results showed that the cold resistance of E. pela involved changes in the expression of many genes. The genes were mainly involved in alcohol formation activity, lipid metabolism, membrane and structure, and oxidoreductase activity. According to the WGCNA results, some pathways related to cold resistance were found in the genes in the modules, such as cytoskeleton proteins, cytoskeleton protein pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, ether lipid metabolism, and thermogenesis. Some of the hub genes were nonspecific lipid-transfer proteins, DnaJ homolog subfamily C member 13, paramyosin, tropomodulin, and tubulin beta chain. In particular, the hub genes of the tan module included the heat shock protein (hsp) 10, hsp 60, hsp 70, and hsp 90 genes. Thirty-five antifreeze protein (afp) genes were identified according to the annotation results. Three afp genes were further identified among the hub genes. Six of these genes were selected for heterogeneous protein expression. One of them was expressed successfully. The thermal hysteresis activity (THA) analyses showed that the THA was 1.73°C. These results showed that the cytoskeleton, lipid metabolism, thermogenesis, HSPs and AFPs may play important roles in the cold resistance of E. pela.

Given that airway obstruction in asthma is not always fully reversible, reduced bronchodilator reversibility (BDR) may be a special asthma phenotype.To explore the characteristics of BDRAfter baseline assessments, all patients were classified into BDRSubjects with BDRWe identified that BDR

5526 Background: The study (NCT03676959) is an open-label, phase I study investigating the safety and efficacy of the recombinant, fully human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody socazolimab for recurrent or metastatic cervical cancer. Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. Primary endpoints of the dose-expansion phase were safety and overall response rate (ORR) of the 5mg/kg dose. Efficacy was assessed by a third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as the evaluation standard. Pharmacokinetics and pharmacodynamics were also studied. Results: One hundred four patients were enrolled. Twelve patients were included in the dose-escalation phase, with one complete and two partial responses in the 5mg/kg treatment group. Ninety-two patients (5mg/kg) were enrolled in the dose-expansion phase, with 54 patients (59.3%) expressing baseline PD-L1-positive tumors. ORR was 15.4% (95% CI, 8.7 to 24.5%). Median PFS was 4.44 months (95% CI, 2.37 to 5.75 months), and the median OS was 14.72 months (95% CI, 9.59 to NE months). ORRs for PD-L1-positive and PD-L1-negative patients were 16.7% and 17.9%, respectively. Treatment-related grade 3 to 4 adverse events occurred in 7.7% of patients. No treatment-related deaths had occurred. Conclusions: Our study demonstrates that socazolimab has remarkable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 monoclonal antibodies. Clinical trial information: NCT03676959. [Table: see text]

Background: Information on HIV-infected cervical cancer is very limited in China. The current study investigated long-term follow-up results of HIV-infected cervical cancer patients treated by different methods from an area in southwestern China in which HIV and cervical cancer are endemic.Methods: All HIV-infected cervical cancer patients registered in Yunnan Cancer Hospital from January 2015 to December 2017 were retrospective reviewed. Overall survival (OS) was the primary end-point.Results: A total of 47 patients entered into the study. 7 patients underwent radical surgery. 24 patients received radiotherapy with high palliative intent, including intensity modulated radiotherapy (IMRT)/volume modulated arc therapy (VMAT)/helical tomotherapy (TOMO) with simultaneous integrated boost (SIB) (SIB; n=15), IMRT/VMAT to the pelvis followed by late course boost (LCB) (LCB; n=9) to the gross tumor volume (GTV). 3 patients received simple external beam radiotherapy to the pelvis (EBRT) (SEBRT; n=3). 13 patients gave up anti-tumor therapy at the initial diagnosis.The 3-year OS for patients who received surgery, LCB, SIB, SEBRT, no anti-tumor treatment were 100%, 51.9%, 66.7%, 0%, and 0%. All of the deaths were attributed to cancer. The prognosis of HIV-infected cervical cancer patients was closely related to the treatment methods (p＜0.05).Conclusions: LCB and SIB are effective and safe modality for treatment of HIV-infected cervical cancer in a limited resource setting.

BACKGROUND Depressive symptoms worsen asthma outcomes; however, the mechanism remains largely unexplored. OBJECTIVE This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes. METHODS Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood sampling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Pre- and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1β, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected. RESULTS Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029). Levels of IL-1β, TNF-α and IFN-γ in the serum and those of IL-1β and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P

Background A pandemic of SARS‐CoV‐2 infection broke out all over the world, however, epidemiological data and viral shedding in pediatric patients are limited. Methods We conducted a retrospective, multi‐center study, and followed up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with RT‐PCR method, and epidemiological data between children and adults in the same families was compared. Effect of antiviral therapy was evaluated observationally and fecal viral excretion times among groups with different antiviral regiments were compared with Kaplan Meier plot. Results By February 29, 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had COVID‐19 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. Conclusion Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation and fecal viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine. This article is protected by copyright. All rights reserved.

With the rapid development of high-throughput sequencing technology and translatome studies, the translational ability of circular RNA (circRNA) has gradually attracted much attention. Previous studies have shown that circRNA itself can be translated into proteins, whose function is closely related to the occurrence and development of human diseases. And it is expected to become an ideal substitute for mRNA, which can be widely used in protein engineering in the future. In this review, we systematically summarize the sources, biogenesis and features of circRNA, the driving models of circRNA translation, identification and functional verification of circRNA translation. We also sum up the latest research progress of circRNA translation in human diseases and its application in protein engineering, and make prospective anticipations for future research directions, which may offer more theoretical references for related researches in this field.随着高通量测序技术和翻译组学研究的快速发展,对环状RNA (circular RNA, circRNA)翻译能力的研究日益成为热点。已有研究表明,circRNA自身可以翻译为蛋白,其蛋白功能与人类疾病发生发展有着密切联系,而且其有望成为mRNA的理想替代品,未来可被广泛地应用在蛋白质工程。本文系统综述了circRNA来源、形成方式和主要特征、翻译蛋白的方式、翻译能力的鉴定和功能验证,归纳了近年来circRNA翻译在人类疾病中的研究进展及其在蛋白质工程的应用,并对后续研究关注的问题进行了展望,以期为相关领域的研究提供参考。.

Insects encounter infection of microorganisms, and they also harbor endosymbiosis to participate in nutrition providing and act as a defender against pathogens. We previously found the Chinese white wax scale insect, Ericerus pela, was infected and killed by Cladosporium sp. (pathogen). We also found it harbored Cladosporium sp. (endogensis). In this study, we cultured these two Cladosporium fungi and sequenced their genome. The results showed Cladosporium sp. (endogensis) has a larger genome size and more genes than Cladosporium sp. (pathogen). Pan-genome analysis showed Cladosporium sp. (endogensis)-specific genes enriched in pathways related to nutrition production, such as amino acid metabolism, carbohydrate metabolism, and energy metabolism. These pathways were absent in that of Cladosporium sp. (pathogen). Gene Ontology analysis showed Cladosporium sp. (pathogen)-specific genes enriched in the biosynthesis of asperfuranone, emericellamide, and fumagillin. These terms were not found in that of Cladosporium sp. (endogensis). Pathogen Host Interactions analysis found Cladosporium sp. (endogensis) had more genes related to loss of pathogenicity and reduced virulence than Cladosporium sp. (pathogen). Cytotoxicity assay indicated Cladosporium sp. (pathogen) had cytotoxicity, while Cladosporium sp. (endogensis) had no cytotoxicity. These characters reflect the adaptation of endosymbiosis to host-restricted lifestyle and the invader of the entomopathogen to the host.

Photocatalytic microcompartments have attracted increasing interests in the field of photocatalytic degradation. This work focused on the construction and characterization of a novel photocatalytic microsystem comprising polydopamine-modified TiO2 nanoparticles (NPs) dispersed in clay-based colloidosomes, utilizing partially hydrophobic montmorillonite particles as building blocks for colloidosome membrane assembly. Assessment of photocatalytic activity was performed by photocatalytic degradation of methylene blue and rhodamine B, with the small molecule dyes decomposing within the compartmentalized microsystems. Encapsulation of TiO2 NPs within the clay colloidosomes enhanced the efficiency of photocatalytic degradation. The results showed a selective degradation of methylene blue in the presence of rhodamine B, with associated λMB/λRhB of 2.04. The present study indicates that photocatalytic semiconductor NPs encapsulated in clay colloidosomes form a promising microsystem with great potential for application in environmental remediation.

Aiming at the problem of the detecting difficulty and imaging the moving target submerged in clutter, a multi-channel Synthetic Aperture Radar (SAR) moving target detection and imaging method based on complex Convolutional Neural Network (CNN) is proposed. First, using Range Doppler algorithm (RDA) to image SAR data to obtain images with clutter, noise and defocused moving targets. Then, the SAR image is used as the input of complex CNN. A SAR image with the clutter and noise eliminated, and the moving target in focus is obtained after processing by neural network. The simulation experiment results show this method is effectiveness.

To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers. MIC-1/GDF15 decreased food intake and body weight of high-fat-fed and chow-fed mice compared with their vehicle-treated control mice. MIC-1/GDF15 reduced body weight, accompanied by greater reduction in fat mass in high-fat-fed mice compared to its effect on chow-fed mice. Further, whilst MIC-1/GDF15-treated chow-fed mice lost lean as well as fat mass, MIC-1/GDF15-treated high-fat-fed mice lost fat mass alone. This reduction in body weight and adiposity was due largely to reduced food intake, but MIC-1/GDF15-treated high-fat-fed mice also displayed increased energy expenditure that may be due to increased thermogenesis. MIC-1/GDF15-treated high-fat-fed mice also had higher circulating level of adiponectin and lower tissue expression, and circulating levels of leptin and inflammatory mediators associated with insulin resistance. Peripheral insulin and glucose intolerance were improved in both MIC-1/GDF15-treated high-fat-fed and chow-fed mice compared to that of their vehicle-treated control mice. MIC-1/GDF15 is highly effective in reducing adiposity and correcting the metabolic dysfunction of mice with high-fat fed. These studies suggest that MIC-1/GDF15 may be a candidate anti-obesity therapeutic.

Background Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. Objective To identify and prospectively validate asthma clusters in a Chinese population. Methods Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k -means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Results Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03–1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07–3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26–40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02–4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95–69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission ( P Conclusion We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries.

SummaryBackground Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15) concentration has been associated with colonic adenomas and carcinoma. Aims To determine whether circulating MIC-1/GDF15 serum concentrations are higher in the presence of adenomas and whether the level decreases after excision. Methods Patients were recruited prospectively from a single centre and stratified into five groups: no polyps (NP); hyperplastic polyps (HP); sessile serrated ademona (SSA); adenomas (AP); and colorectal carcinoma (CRC). Blood samples were collected immediately before and 4 weeks after colonoscopy. MIC-1/GDF15 serum levels were quantified using ELISA. Results Participants (n=301) were stratified as: NP; n=116 (52%), HP; n=37 (12%), SSA; n=19 (7%), AP; n=68 (23%); and CRC; n=3 (1%). Patients were excluded from the study due to nondiagnostic pathology (n=9, 3%) and exclusion criteria (n=20, 6%). In the 272 remaining subjects (M=149; F=123), age (P=.005), history of colonic polyps (P=.003) and family history of colonic polyps (P=.002) were associated with presence of adenomas. Baseline median MIC-1/GDF15 serum levels increased significantly from NP 609 (460-797) pg/mL, HP 582 (466-852) pg/mL, SSA 561 (446-837) pg/mL to AP 723 (602-1122) pg/mL and CRC 1107 (897-1107) pg/mL; (P

Our aim was to study the changes in bone age and serum osteocalcin levels before and after adenotonsillectomy (AT) in children with obstructive sleep apnea hypopnea syndrome (OSAHS). A total of 58 OSAHS children (37 males and 21 females) with the mean age of 6.68 ± 1.11 years were enrolled and assessed by x-ray-based bone age estimation and enzyme-linked immunosorbent assay-based measurement of serum osteocalcin levels, before surgery and 6 months after AT. SPSS 19.0 software was used for statistical analysis. Our results revealed that bone age and serum osteocalcin levels in OSAHS patients were significantly lower than normal controls before AT (P < 0.05). Within 6 months after surgery, the bone age and the serum osteocalcin levels were significantly elevated in OSAHS patients (P < 0.05), compared with those before surgery. Serum osteocalcin levels and bone age are negatively correlated with apnea-hypopnea index, oxygen desaturation index, the percentage of the total recorded time spent below 90% oxygen saturation, and Epworth sleepiness scale scores (all P < 0.05). Our findings suggested that bone age and serum osteocalcin levels may be correlated with the development of OSAHS in children. AT may improve bone age and serum osteocalcin levels in OSAHS children.

Background: The SARS-CoV-2 has been responsible for over 300,000 infections worldwide, however, epidemiological and clinical data of infected children are limit

Growth Differentiation Factor-15 (GDF15) is a divergent TGF-beta superfamily cytokine that is overexpressed by most cancers and is induced by anticancer therapy. Transgenic and induced animal models suggest that it protects from cancer development but the mechanisms are uncertain. We investigated the role of immunity in GDF15 induced reduction in prostate cancer (PCa) growth. The C57BL/6 transgenic TRAMP prostate cancer prone mice were bred with mice that were immunodeficient and/or systemically overexpressed GDF15. We developed a novel orthotopic TRAMP PCa model in which primary TRAMP tumor cells were implanted into prostates of mice to reduce the study time. These mice were administered recombinant mouse GDF15, antibody to CD8, PD1 or their respective controls. We found that GDF15 induced protection from tumor growth was reversed by lack of adaptive immunity. Flow cytometric evaluation of lymphocytes within these orthotopic tumors showed that GDF15 overexpression was associated with increased CD8 T cell numbers and an increased number and proportion of recently activated CD8+CD11c+ T cells and a reduced proportion of "exhausted" CD8+PD1+ T cells. Further, depletion of CD8 T cells in tumor bearing mice abolished the GDF15 induced protection from tumor growth. Infusion of GDF15 into mice bearing orthotopic TRAMP tumor, substantially reduced tumor growth that was further reduced by concurrent PD1 antibody administration. GDF15 overexpression or recombinant protein protects from TRAMP tumor growth by modulating CD8 T cell mediated antitumor immunity and augments the positive effects of anti-PD1 blockers.

Background and objective T lymphocytes, which are characterized by longevity and immune memory, play an important role in airway inflammation in asthma. Here, we assessed the association between immune memory and histone deacetylation and/or acetylation status. Methods CD4 + CD45RBlow cells (memory T (Tm)) obtained from the spleens of asthma mice models were co-cultured with glucocorticoids (GCs), trichostatin A (TSA) or anacardic acid (AA) and adoptively transferred to naive mice. Interleukin (IL)-4, 5 and 13 and IFN-γ concentrations were measured in culture supernatants and bronchoalveolar lavage fluid (BALF). Histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities and the expression of T-bet, GATA-3, HDACs 1–11 and alveolar eosinophilic inflammation index (AEII) were determined in lung tissues. Results Culture supernatants and the BALF showed similar cytokine profiles. AA and GCs significantly inhibited HAT activity (P = 0.002 and P = 0.018), whereas TSA inhibited and GCs promoted HDAC activity (P = 0.004 and P = 0.025). HDACs 7, 9 and 10 were upregulated by AA and GCs (all P

FeSiAl magnetic powder contains high cost-performance as inductance components, which is widely used in various fields. In the present investigation the structure, magnetic properties and properties of magnetic powder cores prepared by strip cast ingot process were studied, and then compared with FeSiAl magnetic powder prepared by ingot cast broken process. The results show that strip cast sheet contained much little grain which surround with big grain, while the ingot cast broken has big grain connect with each other. For FeSiAl magnetic powder prepared by strip cast ingot process, the bigger grains were strip, the smaller grains were irregular shape, the surface of the powder was coarse, the powder prepared by strip cast ingot process was good for keeping the insulation film perfectly. For FeSiAl magnetic powder prepared by ingot cast broken, much of the powder was irregular bulk shape, and the grain corner was sharp, which is not good for insulation coating. Compared the patterns of strip cast ingot powder with the patterns of ingot cast broken powder, the diffraction peak of the patterns of strip cast ingot process powder became broaden. The initial magnetization curves of FeSiAl were obtained by vibrating sample magnetometer (VSM), observing that the saturation magnetization of strip cast magnetic powder was greater than that of ingot cast broken.

Soft magnetic material FeCoV is sensitive to magnetic field and its cost is lower than giant magnetostriction materials (Terfenol-D et al.). In the present investigation Pb (Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) with different thickness and FeCoV laminate with 0.8mm thickness were assembled into layer structure to study the effect of the PMN-PT volume fraction on the magnetoelectric coefficient of PMN-PT/FeCoV laminate composites. The ME coefficients and voltages have been characterized in the longitudinally magnetized and transversely polarized mode. The measurement was conducted under a static magnetic field superimposed with an alternating magnetic field. The influences of the static and the alternating field strength were discussed. The peak ME coefficient was obtained at 430 Oe. With the volume fraction of PMN-PT increased, the ME coefficient decreased within the experiment fraction. It can be explained by the module of M.I.Bichurin. A linear relationship was observed between the magnetoelectric voltage and the alternating field strength under a static field of 400 Oe. The ME voltage decreased when the PMN-PT volume fraction increased in the experiment fraction.

Background Hospitalization due to acute asthma exacerbation (AE) is a highly detrimental situation requiring critical management to prevent further deterioration, including mechanical ventilation, intensive care unit (ICU) admission, and death. However, patients hospitalized for AEs are highly heterogeneous and remain largely unexplored. Objective To identify clinical and inflammatory phenotypes of AE requiring hospitalization associated with in-hospital outcomes. Methods We performed a hierarchical cluster analysis of 825 consecutively recruited patients hospitalized for AEs. Logistic regressions were conducted to quantify the independent associations of the identified phenotypes with in-hospital outcomes. Decision tree analysis was developed to predict cluster assignment. Results We identified 3 clusters of patients, which had significantly different characteristics associated with in-hospital adverse outcomes. Cluster 1 (n = 526, 63.8%) was a late-onset phenotype, cluster 2 (n = 97, 11.8%) was an early-onset phenotype, and cluster 3 (n = 202, 24.5%) was a phenotype with fewer eosinophils and more comorbidities. Clusters 2 and 3 had an elevated risk of death (relative ratio [RRadj], 18.10 and 19.17, respectively) and mechanical ventilation (RRadj, 2.56 and 5.71, respectively) than did cluster 1. Individuals in cluster 3 had an extended length of hospital stay (11 days), increased hospitalization direct costs (13,481.57 Chinese Yuan), and a higher risk of ICU admission (RRadj, 2.14) than individuals in clusters 1 and 2. The decision tree assigned 90.8% of the participants correctly. Conclusions We identified 3 phenotypes with differential clinical and inflammatory characteristics associated with in-hospital adverse outcomes. These new phenotypes might have important and clinically relevant implications for the management of patients hospitalized for AEs.

Asthma is a heterogeneous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored.To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma.In this cross-sectional study, adult participants with stable asthma (n = 522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles.Among the 522 participants, 73.4% (n = 383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n = 248). T2 POS was positively associated with eosinophils, IgE, and fractional exhaled nitric oxide (FeNO), and negatively with Asthma Quality of Life Questionnaire (AQLQ), sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with Asthma Control Questionnaire, neutrophils and sputum IL-8, and negatively with AQLQ, forced expiratory volume in 1 s, blood eosinophils, IgE, and FeNO (all P.05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P = .035) and non-T2 (adjusted β = 0.310, P.001) POS were significantly associated with severe exacerbations.Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.

Elevated circulating levels of the divergent transforming growth factor-beta (TGFb) family cytokine, growth differentiation factor 15 (GDF15), acting through its CNS receptor, glial-derived neurotrophic factor receptor alpha-like (GFRAL), can cause anorexia and weight loss leading to anorexia/cachexia syndrome of cancer and other diseases. Preclinical studies suggest that administration of drugs based on recombinant GDF15 might be used to treat severe obesity. However, the role of the GDF15-GFRAL pathway in the physiological regulation of body weight and metabolism is unclear. The critical site of action of GFRAL in the CNS has also not been proven beyond doubt. To investigate these two aspects, we have inhibited the actions of GDF15 in mice started on high-fat diet (HFD).The actions of GDF15 were inhibited using two methods: (1) Groups of 8 mice under HFD had their endogenous GDF15 neutralised by monoclonal antibody treatment, (2) Groups of 15 mice received AAV-shRNA to knockdown GFRAL at its hypothesised major sites of action, the hindbrain area postrema (AP) and the nucleus of the solitary tract (NTS). Metabolic measurements were determined during both experiments.Treating mice with monoclonal antibody to GDF15 shortly after commencing HFD results in more rapid gain of body weight, adiposity and hepatic lipid deposition than the control groups. This is accompanied by reduced glucose and insulin tolerance and greater expression of pro-inflammatory cytokines in adipose tissue. Localised AP and NTS shRNA-GFRAL knockdown in mice commencing HFD similarly caused an increase in body weight and adiposity. This effect was in proportion to the effectiveness of GFRAL knockdown, indicated by quantitative analysis of hindbrain GFRAL staining. We conclude that the GDF15-GFRAL axis plays an important role in resistance to obesity in HFD-fed mice and that the major site of action of GDF15 in the CNS is GFRAL-expressing neurons in the AP and NTS.

OBJECTIVE To determine whether anxiety and depression are associated with greater respiratory discomfort in asthma. METHODS Adults with asthma (n = 230) underwent methacholine (Mch) challenge. Anxiety and depression, asthma control, and quality of life were evaluated at study entry by using the Hospital Anxiety and Depression Scale, Asthma Control Test, and Asthma Quality of Life Questionnaire, respectively. Qualitative descriptors of breathlessness, dyspnea intensity (modified Borg scale and visual analog scale [VAS]), and other respiratory symptoms were evaluated before and after Mch challenge. RESULTS Patients were classified as neither anxiety nor depression (NAD), anxiety only, depression only (D), or both anxiety and depression (AD) according to the Hospital Anxiety and Depression Scale score. Asthma Control Test and Asthma Control Test, and Asthma Quality of Life Questionnaire scores were lowest in the AD group (both p < 0.001). VAS scores for dyspnea and wheezing before Mch challenge were highest in the AD group (both p < 0.05). The increase in the modified Borg scale score after Mch challenge was higher in the AD group (mean [standard deviation] 2.5 ± 2.0) than in the NAD (1.5 ± 1.5) and D (0.8 ± 0.9) groups (p = 0.006 and p = 0.003, respectively). Most descriptors of breathlessness were more prevalent in the anxiety only, D, and AD groups than in the NAD group. Multivariable logistic regression models indicated that anxiety increased the risk of dyspnea (odds ratio 1.10, p < 0.001 for the Borg score; odds ratio 3.84, p = 0.032 for the VAS score) but not for other respiratory symptoms. CONCLUSIONS Anxiety but not depression was associated with greater perceived dyspnea intensity but not other measures of respiratory discomfort in individuals with asthma. Anxiety may shape the quality and intensity of dyspnea at a given respiratory load.

Gardenia yellow and geniposide were separated simultaneously by employing isopropanol-salt aqueous two-phase system. Prior to separation, enrichment of geniposide and gardenia yellow in the same phase were obtained by aqueous two-phase system containing 2.0 mL isopropanol and 1.3 g of sodium citrate at room temperature with no pH adjustment. Their separation was achieved by multistage extraction in the same system at pH 3.2. At the end of the third extraction, the bottom phase had only geniposide, and the top phase had essentially gardenia yellow. Geniposide and gardenia yellow in the opposite phases were analyzed by the spectrophotometric method and HPLC.

As one of the first identified long non-coding RNAs (lncRNAs), H19 plays a wide range of roles in vivo, including not only as a tumor suppressor and oncogene involved in disease process, but also as a regulator of growth and development of multiple tissues in mammalian embryos. The function of H19 in muscles (both skeletal and cardiac muscle) draws widespread attention due to the following two reasons. On one hand, H19 promotes myogenic differentiation and myogenesis of skeletal muscle satellite cells (SMSCs) via regulating Igf2 in cis. On the other hand, H19 also modulates the target genes in trans, including sponging let-7, miR-106 or miR-29 to mediate myocyte glucose uptake, cardiomyocyte proliferation and tendon repair, as well as promote embryonic development and muscle regeneration through binding to MBD1 as a chromatin modifier. In this review, we summarize the role of H19 in mammalian muscles, which will provide a reference for further research to unveil the molecular mechanism of muscle growth and development.