Impacts of a highly pathogenic ovine Eimeria ovinoidalis on the growth of Hu lambs.

The apicomplexan Eimeria ovinoidalis is distributed worldwide. It can cause clinical coccidiosis, which is one of the most pathogenic species in sheep, reducing growth rates and resulting in significant economic losses in the industry. Its principal clinical sign is profuse diarrhoea in young animals. In this study, we established a model of E. ovinoidalis infection in lambs to understand its pathogenicity and evaluate the gut microbiota and fecal metabolite profiles. Specifically, we observed a significant shift in the abundance of bacteria and disrupted metabolism in lambs. Especially during the peak period of excrete oocysts, it promoted the reproduction of some harmful bacteria in Proteobacteria and Actinobacteriota, and reduced the abundance of beneficial bacteria such as Lachnospiraceae and Rikenellaceae. In the later stage of the patent period, the abundance of harmful bacteria in the intestine decreased, the abundance of beneficial bacteria which could produce anti-inflammatory substances began to increase, and the abundance and diversity of intestinal flora also tended to parallel with the control group. Coccidia infection could lead to the increase of differential metabolites and metabolic pathways between infected and control group, but the difference decreased with time. During the peak period of excrete oocysts, although the antimicrobial metabolites such as Lividamine were up-regulated, the excess of these metabolites could still induce the production of endotoxin, while Butanoic acid and other anti-inflammatory metabolites decreased significantly. A metabolomics analysis showed that E. ovinoidalis infection altered metabolites and metabolic pathways, with biosynthesis of unsaturated fatty acids, Teichoic acid biosynthesis and Butanoate metabolism as the major disrupted metabolic pathways. Details of the gut microbiota and the metabolome after infection with E. ovinoidalis may aid in the discovery of specific diagnostic markers and help us understand the changes in parasite metabolic pathways.

Advancements in defect engineering of two-dimensional nanomaterial-based membranes for enhanced gas separation.

The advent of two-dimensional nanomaterials, a revolutionary class of materials, is marked by their atomic-scale thickness, superior aspect ratios, robust mechanical attributes, and exceptional chemical stability. These materials, producible on a large scale, are emerging as the forefront candidates in the domain of membrane-based gas separation. The concept of defect engineering in 2D nanomaterials has introduced a novel approach in their application for membrane separation, offering an effective technique to augment the performance of these membranes. Nonetheless, the development of customized microstructures in gas separation membranes via defect engineering remains nascent. Hence, this review is designed to serve as a comprehensive guide for the application of defect engineering in 2D nanomaterial-based membranes. It delves into the most recent developments in this field, encompassing the synthesis methodologies of defective 2D nanomaterials and the mechanisms underlying gas transport. Special emphasis is placed on the utilization of defect-engineered 2D nanomaterial-based membranes in gas capture applications. Furthermore, the paper encapsulates the burgeoning challenges and prospective advancements in this area. In essence, defect engineering emerges as a promising avenue for enhancing the efficacy of 2D nanomaterial-based membranes in gas separation, offering significant potential for advancements in membrane-based gas separation technologies.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Novel fluorescence strategy based on G-quadruplex structure-switching aptamer for enrofloxacin detection in food and environmental samples.

Enrofloxacin (ENR) is widely used in the prevention and treatment of animal infectious diseases, so it is necessary to strengthen the residue detection of this drug in animal-derived food and water environments. In this work, for the first time, we engineered assembly a split ENR aptamer into the G-quadruplex (G4) region to form a new aptamer (G4-ENRA) that provides a more sensitive signal-reporting function while retaining target-specific recognition ability of the aptamer. This rational design effectively overcomes the issue of difficulty in identification probe development. Under the optimized conditions, a response range of 0.05-20 µM and limit of detection of 26.7 nM were obtained by directly detecting fluorescence signals, displaying a comparative advantage over the previously reported methods. Moreover, this method demonstrated satisfactory performance for the ENR detection in various real food and environmental samples, with the detection recoveries ranging from 95.87 % to 104.36 %, illustrating promising applicability prospects.

Is the incident of once chronic obstructive pulmonary disease related admission a high risk for readmission in the future?

Background: Although it is known that a history of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most important predictor of future risk of AECOPD and readmission to hospitals, there is no scientific evidence that an event of only one chronic obstructive pulmonary disease (COPD)-related admission is a high risk of future readmission. We retrospectively analyzed the association of an incident of one COPD-related admission with future readmission risk. Methods: This is a retrospective study. The data of AECOPD-related admissions and readmissions during 5 years were obtained and analyzed for the admission frequencies of patients with AECOPD and an association of the admission history with a future readmission risk. Results: The admission frequency of patients with frequent admission (3 or more admissions within 5 years) was 4.1 times that of those with non-frequent admission (0.95 vs. 0.23 times per person per year). In each calendar year during the 5-year study period, most patients (88.2%) were hospitalized only once, and 11.8% had two or more admissions. Nevertheless, their average number of admissions in each calendar year was 3.3 times that of those who only had one admission each year (3.33 vs. 1.00 times per person per year). More importantly, the positive predictive value for future readmission due to AECOPD was only 14.8% in those who had one admission in the previous year. The patients with the greater readmission risk were those with two or more admissions due to AECOPD in the previous year [crude odds ratio (OR): 4.10, 95% confidence interval (CI): 1.24-13.58 and 7.51, 95% CI: 3.81-16.68]. Conclusions: There is a subtype of frequent admission due to AECOPD, and it can be distinguished by having three or more admissions in the past 5 years or two or more admissions in the previous year. Nevertheless, an incident of admission once a year is not a good predictor of future readmission.

Ag microlabyrinth/nanoparticles coated large-area thin PDMS films as flexible and transparent SERS substrates for in situ detection.

Flexible and transparent surface-enhanced Raman scattering (SERS) substrates haveattractedmuchattention as a fast, sensitive and in situ detection platform for practical applications. However, the large-area fabrication of flexible and transparent SERS substrates with high performance is still challenging. Here, a flexible and transparent SERS substrate based on large-area thin PDMS film decorated with Ag microlabyrinth/nanoparticles hierarchical structures (denoted as ALNHS@PDMS) is fabricated by using the floating-on-water method and magnetron sputtering technology. By optimizing the sputtering time, the ALNHS with multiple hot spots are uniformly distributed on the PDMS surface. Based on characterizing the rhodamine 6G (R6G) with a portable Raman spectrometer, the optimal ALNHS@PDMS film exhibits a high enhancement factor (5.2 × 106), excellent uniformity and reproducibility, as well as superior mechanical stability. In addition, thanks to the good sticky feature and bi-directional activation property of the thin ALNHS@PDMS film, the prepared flexible and transparent SERS substrate can achieve in situ detection of malachite green residues (10-6 M) on apple and tomato skins. This large-area, thin, mechanically robust, flexible and transparent ALNHS@PDMS film, integrated with a portable Raman spectrometer, shows great potential for point-of-care testing (POCT)in practical applications.

Ag NPs@PDMS nanoripple array films as SERS substrates for rapid in situ detection of pesticide residues.

The large-area fabrication of flexible and transparent surface-enhanced Raman scattering (SERS) substrates with high performance by a facile and efficient method is still challenging. Here, we demonstrated a large-scale, flexible and transparent SERS substrate composed of PDMS nanoripple array film decorated with silver nanoparticles (Ag NPs@PDMS-NR array film) prepared by a combination of plasma treatment and magnetron sputtering. The performances of SERS substrates were characterized by rhodamine 6G (R6G) using a handheld Raman spectrometer. The optimal Ag NPs@PDMS-NR array film exhibited high SERS sensitivity, with a detection limitation of R6G reaching 8.20 × 10-8 M as well as excellent uniformity (RSD = 6.8%) and batch-to-batch reproducibility (RSD = 2.3%). In addition, the substrate showed outstanding mechanical stability and good SERS enhancement by backside illumination, thus it was suitable for in situ SERS detection on curved surfaces. The detection limit of malachite green on apple and tomato peels was 1.19 × 10-7 and 1.16 × 10-7 M, respectively, and quantitative analysis of pesticide residues could be realized. These results demonstrate that the Ag NPs@PDMS-NR array film has great practical potential in rapid in situ detection of pollutants.

GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling.

Glutamate receptor, ionotropic, kainate 5 (GRIK5) is a member of glutamate receptors participating, and the kainate receptor family has been proved to regulate cell proliferation and transformation. Our study aimed at exploring the role of GRIK5 in colon tumor progression. Three hundred and ninety eight colon cancer patients in The Cancer Genome Atlas Program (TCGA) data set and 26 clinical colon cancer patients were included for GRIK5 expression and prognosis analysis. GRIK5 overexpressed HCT116 and CT26 cell lines were established for cell proliferation and Transwell assay. Western blot analysis and immunostaining assay was conducted to evaluate the activation of activation of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cell adhesion molecular 3 (CADM3) signaling in cell lines and tumor tissues. Subcutaneous CT26-bearing mice model was established to examine GRIK5-induced tumor growth and metastasis in vivo. Our study identified GRIK5 to be upregulated in patients with colon cancer, and higher GRIK5 levels correlated with the poor overall survival in patients. In vitro, GRIK5 overexpression markedly enhanced the proliferative properties and aggressive behaviors of colon cancer cells. Mechanistically, GRIK5 induced the activation of cAMP/PKA signaling, proceeded with augmented CADM3 expression, eventually resulting in sustained tumor growth. GRIK5 was a crucial scaffold in enabling colon cancer growth and metastasis, which offered a promising target for therapeutic manipulation of colon cancer.

A label-free G-quadruplex aptamer fluorescent aptasensor for visual and real-time kanamycin detection in lake and human samples.

Antibiotic abuse is considered a serious problem affecting human health, necessitating that great attention be paid to explore robust, simple and sensitive methods for rapid evaluation. In this paper, we developed a fluorescent aptasensor for visual and real-time kanamycin detection by taking advantage of the label-free strategy based on H-aggregate disassembly of a chiral cyanine dye induced by a G-quadruplex aptamer. The good sensitivity and selectivity enabled this aptasensor to have a detection limit as low as 43 nM and have high specificity for kanamycin recognition. Furthermore, this assay was successfully applied for the detection of kanamycin in lake water and urine with excellent recoveries.

Texting in a crisis-using SMS for information and emotional support during COVID-19: A mixed methods research study.

In the era of new media, short message service (SMS) is no longer seen as advantageous and it is no longer used very much by the Chinese public. However, as a traditional media, local governments managing public health crises used SMS as a way of meeting the public's need for emotional support during the COVID-19 pandemic. Our study examined 108 SMS texts pushed to phones in Chongqing between January and December 2020, and carried out in-depth interviews with ten interviewees. This mixed research method of descriptive and grounded theory analysis was designed to investigate how SMS was used to communicate prevention guidelines and give emotional support during COVID-19. The results show that Chongqing Municipal Health and Health Commission gained the public's attention with SMS messages consisting of neutral, objective advice, and guidance to reduce people's anxiety and panic. However, with the stabilization of COVID-19, SMS has once again been discarded by users, including the public health sector. The study found that the emotional support offered by SMS was limited to the elderly, a subset of the population considered to be weak users of the internet. SMS has been replaced by other technologies, but along with other media, such as official media and social media, it has shaped the media communication environment and served as an emotional support channel for the public. Undoubtedly,the use of SMS during COVID-19 presents a research opportunity for exploring its capacity for prevention, control and emotional support.

3D Flexible SERS Substrates Integrated with a Portable Raman Analyzer and Wireless Communication for Point-of-Care Application.

With the development of flexible surface-enhanced Raman spectroscopy (SERS) substrates that can realize rapid in situ detection, the SERS technique accompanied by miniaturized Raman spectrometers holds great promise for point-of-care testing (POCT). For an in situ detection strategy, constructing high-performance flexible and transparent SERS substrates through a facile and cost-effective fabrication method is critically important. Herein, we present a simple method for fabricating a large-area flexible and transparent SERS substrate consisting of a silver-nanoparticle-grafted wrinkled polydimethylsiloxane (Ag NPs@W-PDMS) film, using a surface-wrinkling technique and magnetron sputtering technology. By characterizing rhodamine 6G as a probe molecule with a portable Raman spectrometer, the flexible SERS substrate shows a low detection limit (10-7 M), a high enhancement factor (6.11 × 106), and excellent spot-spot and batch-batch reproducibilities (9.0% and 4.2%, respectively). Moreover, the Ag NPs@W-PDMS substrate maintains high SERS activity under bending and twisting mechanical deformations of over 100 cycles, as well as storage in air for 30 days. To evaluate its practical feasibility, in situ detection of malachite green on apple and tomato peels is performed with a detection limit of 10-6 M. In addition, for point-of-care analysis, we develop a wireless transmission system to transmit the collected SERS spectral data to a computer in real time for signal processing and analysis. Therefore, the proposed Ag NPs@W-PDMS SERS substrate fabricated through a simple and mass-producible method, combined with the utilization of a portable Raman spectrometer and wireless communication, offers a promising opportunity to extend the SERS technique from the laboratory to POCT applications.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing.

Helicobacter pylori infection is a prevalent infectious disease, associated with many gastric diseases, including gastritis, gastric ulcer, and gastric cancer. To reveal the characteristics of the gastric microbiome in patients infected with H. pylori, we performed metagenomic shotgun sequencing of stomach swab samples from 96 patients and then conducted metagenomic association analyses between alterations in the gastric microbiome and H. pylori infection status. The overall composition of the gastric microbiota in H. pylori-infected individuals was distinctly different from the negative controls; H. pylori became the dominant species after colonizing the human stomach and significantly decreased the α-diversity of the gastric community (P < 0.05, Wilcoxon rank-sum test). We also identified 6 HPI-associated microbial species (FDR < 0.05, Wilcoxon rank-sum test): Stenotrophomonas maltophilia, Stenotrophomonas unclassified, Chryseobacterium unclassified, Pedobacter unclassified, Variovorax unclassified, and Pseudomonas stutzeri. Furthermore, 55 gastric microbial pathways were enriched in the H. pylori-positive group, whereas only 2 pathways were more abundant in the H. pylori-negative group: dTDP-L-rhamnose biosynthesis and tetrapyrrole biosynthesis (FDR < 0.05, Wilcoxon rank-sum test). Gastritis was not associated with non-H. pylori species in the stomach (P > 0.05, Wilcoxon rank-sum test). This study revealed alterations in gastric microbial taxa and function associated with HPI in the Chinese population, which provides an insight into gastric microbial interactions and their potential role in the pathological process of gastric diseases.

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.