Occurrence and characterization of NDM-5-producing Escherichia coli from retail eggs

The New Delhi Metallo-β-lactamase (NDM) producing Enterobacterales has been detected from diverse sources but has rarely been reported in retail eggs. In this study, 144 eggshell and 96 egg content samples were collected in 2022 from Guangdong province and were screened for NDM-producing strains. Four Escherichia coli strains (ST3014, ST10, ST1485, and ST14747) recovered from two (1.39%, 2 of 144) eggshells and two (2.08%, 2 of 96) egg content samples were identified as blaNDM−5-positive strains. Oxford Nanopore MinION sequencing and conjugation assays revealed that the blaNDM−5 gene was carried by IncX3 (n = 1), IncI1 (n = 1), and IncHI2 (n = 2). The IncI1-plasmid-carrying blaNDM−5 displayed high homology with one plasmid pEC6563-NDM5 from the human clinic, while the IncHI2 plasmid harboring blaNDM−5 shared highly similar structures with plasmids of animal origin. To the best of our knowledge, this is the first report on the identification of blaNDM−5-positive bacteria in retail eggs. NDM-producing E. coli could be transmitted to humans by the consumption of eggs or direct contact, which could pose a potential threat to human health

A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse

Asthma and mouse models of allergic respiratory inflammation are invariably associated with a pulmonary eosinophilia; however, this association has remained correlative. In this report, a causative relationship between eosinophils and allergen-provoked pathologies was established using eosinophil adoptive transfer. Eosinophils were transferred directly into the lungs of either naive or OVA-treated IL-5-/- mice. This strategy resulted in a pulmonary eosinophilia equivalent to that observed in OVA-treated wild-type animals. A concomitant consequence of this eosinophil transfer was an increase in Th2 bronchoalveolar lavage cytokine levels and the restoration of intracellular epithelial mucus in OVA-treated IL-5-/- mice equivalent to OVA-treated wild-type levels. Moreover, the transfer also resulted in the development of airway hyperresponsiveness. These pulmonary changes did not occur when eosinophils were transferred into naive IL-5-/- mice, eliminating nonspecific consequences of the eosinophil transfer as a possible explanation. Significantly, administration of OVA-treated IL-5-/- mice with GK1.5 (anti-CD4) Abs abolished the increases in mucus accumulation and airway hyperresponsiveness following adoptive transfer of eosinophils. Thus, CD4+ T cell-mediated inflammatory signals as well as signals derived from eosinophils are each necessary, yet alone insufficient, for the development of allergic pulmonary pathology. These data support an expanded view of T cell and eosinophil activities and suggest that eosinophil effector functions impinge directly on lung function

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), which often progresses to end-stage renal disease (ESRD) and ultimately leads to death. At present, there are no definitive therapies towards LN, so that illuminating the molecular mechanism behind the disease has become an urgent task for researchers. Bioinformatics has become a widely utilized method for exploring genes related to disease. This study set out to conduct weighted gene co-expression network analysis (WGCNA) and screen the hub gene of LN. We performed WGCNA on the microarray expression profile dataset of GSE104948 from the Gene Expression Omnibus (GEO) database with 18 normal and 21 LN samples of glomerulus. A total of 5,942 genes were divided into 5 co-expression modules, one of which was significantly correlated to LN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the LN-related module, and the module was proved to be associated mainly with the activation of inflammation, immune response, cytokines, and immune cells. Genes in the most significant GO terms were extracted for sub-networks of WGNCA. We evaluated the centrality of genes in the sub-networks by Maximal Clique Centrality (MCC) method and CD36 was ultimately screened out as a hub candidate gene of the pathogenesis of LN. The result was verified by its differentially expressed level between normal and LN in GSE104948 and the other three multi-microarray datasets of GEO. Moreover, we further demonstrated that the expression level of CD36 is related to the WHO Lupus Nephritis Class of LN patients with the help of Nephroseq database. The current study proposed CD36 as a vital candidate gene in LN for the first time and CD36 may perform as a brand-new biomarker or therapeutic target of LN in the future

A study protocol for an open‐label, single‐arm, single‐center phase I clinical study on tolerability, safety, and efficacy of dalpiciclib combined with apatinib in the treatment of patients with advanced or metastatic sarcoma

Abstract Introduction The prognosis of patients with advanced or metastatic sarcoma is very poor, and a new strategy for patients who fail systemic treatment is urgently required. Apatinib is a small molecule tyrosine kinase inhibitor of VEGFR‐2, which can exert an antitumor effect by blocking downstream PI3K/AKT and VEGFR2/STAT3 signaling pathways of sarcoma. Dysregulation of the cyclin D (CCND)‐cyclin‐dependent kinase 4/6 (CDK4/6)‐retinoblastoma 1 (Rb) pathway is highly prevalent in sarcoma. Thus, blocking VEGFR2 and CDK4/6 may exert a synergistic effect. We hypothesize that a combination of apatinib and dalpiciclib, an oral, highly effective, and selective small molecule CDK4/6 inhibitor, may result in higher antitumor efficacy in patients with refractory sarcoma. Methods In this open‐label, single‐arm, single‐center phase I trial, participants diagnosed with sarcoma who failed standard systemic treatment will be enrolled. Dose escalation will be conducted into three groups according to traditional 3 + 3 principle: dose 1, dalpiciclib 100 mg once daily oral d1‐21+ apatinib 250 mg once daily oral d1‐28, every 28 days as one cycle; dose 2, dalpiciclib 100 mg d1‐21+ apatinib 500 mg d1–28; dose 3, dalpiciclib 150 mg d–21+ apatinib 500 mg d1–28. The primary endpoint is the safety and tolerability of combined treatment. The secondary endpoint is to evaluate the initial efficacy, including objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and progression‐free survival (PFS). Discussion This trial will provide evidence of the tolerability, safety, and efficacy of dalpiciclib in combination with apatinib in metastatic sarcoma patients who have failed first‐line systemic treatment

Is the High-Speed Rail Opening Environmentally Friendly? Taking the Difference-in-Differences Test in Jiangsu, China

In view of rapid development of high-speed rail, the relationship between high-speed rail and air pollution needs to be tested and determined. Most research studies focused on the impact of high-speed rail on environmental pollution and just viewed high-speed rail as a control variable, which lacked a direct study on this relationship. Also, these rarely involved regional research, which is short of pertinence and insufficient understanding of regional issues. Therefore, based on the difference-in-differences (DID) model which is a natural experiment evaluation method, this study examined the impact of high-speed rail opening on air pollution by using the panel data of Jiangsu province, China, from the year of 2000 to 2017. The empirical results showed that the opening of Jiangsu high-speed rail, which increases cities’ good day significantly by 21.5%, has inhibitory effect on air pollution. Among control variables, there is no inverted “U” relationship between the economic development level and air pollution. Personal income and urbanization significantly improve air pollution, whereas foreign direct investment exacerbates it. And the results are still valid after robustness tests, including trend test and counterfactual test. Moreover, this study explores the relationship between the degree of reducing pollution caused by high-speed rail and the location of cities, which found that the opening of high-speed rail can greatly improve air pollution of areas in central city circle. Finally, it is found that when high-speed rail and other possible pollution items coexist, the improved effect of high-speed rail on air pollution is still obvious. Therefore, in order to exert the mitigating effect of high-speed rail on air pollution, it is necessary to rationally plan high-speed railway lines and develop the high-speed railways in cities closer to Shanghai

Effects of fancy job titles and pictures in recruitment advertisements.

This study postulates that the presence of a Fancy job title or a Picture in a recruitment advertisement has a greater impact on a job seeker’s Job Attitude and Intention to Apply for a job favourably. We used a questionnaire, simulating a recruitment print advertisement page for a Marketing position in the newspapers. The experiment was carried out in a controlled environment on 373 graduating Marketing majors. Participants read a scenario and answered questions regarding Job Attitude and Intention to Apply for four advertisements

A dielectrophoresis-assisted adsorption approach significantly facilitates the removal of cadmium species from wastewater

A newly designed apparatus and process, including dielectrophoresis and adsorption to efficiently remove cadmium species from wastewater, is reported in this study. With this technique, cadmium ions are firstly adsorbed by shell powder particles, which are subsequently trapped and concentrated by a dielectrophoresis process. The factors affecting the metal removal efficiency are systematically investigated, which allows us to determine the optimal operation conditions. Our experimental data indicate that via the adsorption and dielectrophoresis steps, cadmium can be almost completely removed from wastewater as evidenced by the very high removal efficiency of 99.4%. This suggests that our dielectrophoresis-assisted adsorption approach is highly effective for the removal of cadmium, and the technique could be extended to the removal of other heavy metal ions from wastewater as well

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P &lt; 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P &lt; 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P &lt; 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P &lt; 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines