Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children?

ObjectiveBy examining fractional exhaled nitric oxide (FeNO) levels and performing pulmonary function testing, this study explored whether the multicenter study on the normal range of FeNO in children in China can be used to evaluate standardized treatment efficacy in 6- to 12-year-old children with asthma.MethodsA total of 115 children aged 6–12 years old who were first diagnosed with asthma and received standardized asthma treatment from April 2018 to July 2022 were selected. According to the FeNO level at the first visit, the subjects were divided into different high- and low-FeNO groups according to the American Thoracic Society (ATS) guidelines and the Chinese multicenter study recommendations. The consistency of the two grouping methods and the differences between the high- and low-FeNO groups were compared after standardized treatment. The grouping method that was the most suitable for children in the cross group was discussed.Results(i) There was fair consistency between the Chinese multicenter study recommendations and the ATS guidelines regarding the classification of high- and low-FeNO groups (Kappa = 0.338). (ii) Repeated-measures ANOVA showed that the level of improvement in FVC%, FEV1%, FEF25%, FEF50%, and FeNO in the American high- and low-FeNO groups differed with the duration of therapy (P < 0.05), however, there was no significant difference between the Chinese groups. (iii) FEV1% and FeNO improved more after treatment in the fixed high-FeNO group than in the cross group (P < 0.05).ConclusionThe Chinese multicenter study on the normal range of FeNO in children in China has a limited role in evaluating standardized asthma treatment efficacy in 6- to 12-year-old children. The ATS guidelines are currently recommended for clinical assessment of asthma treatment efficacy

MicroRNA-155 Hallmarks Promising Accuracy for the Diagnosis of Various Carcinomas: Results from a Meta-Analysis

Background. Recent studies have shown that microRNAs (miRNAs) have diagnostic values in various cancers. This meta-analysis seeks to summarize the global diagnostic role of miR-155 in patients with a variety of carcinomas. Methods. Eligible studies were retrieved by searching the online databases, and the bivariate meta-analysis model was employed to generate the summary receiver operator characteristic (SROC) curve. Results. A total of 17 studies dealing with various carcinomas were finally included. The results showed that single miR-155 testing allowed for the discrimination between cancer patients and healthy donors with a sensitivity of 0.82 (95% CI: 0.73-0.88) and specificity of 0.77 (95% CI: 0.70-0.83), corresponding to an area under curve (AUC) of 0.85, while a panel comprising expressions of miR-155 yielded a sensitivity of 0.76 (95% CI: 0.68-0.82) and specificity of 0.82 (95% CI: 0.77-0.86) in diagnosing cancers. The subgroup analysis displayed that serum miR-155 test harvested higher accuracy than plasma-based assay (the AUC, sensitivity, and specificity were, resp., 0.87 versus 0.73, 0.78 versus 0.74, and 0.77 versus 0.70). Conclusions. Our data suggest that single miR-155 profiling has a potential to be used as a screening test for various carcinomas, and parallel testing of miR-155 confers an improved specificity compared to single miR-155 analysis

Real-projective-plane hybrid-order topological insulator realized in phononic crystals

The manifold of the fundamental domain of the Brillouin zone is always considered to be a torus. However, under the synthetic gauge field, the Brillouin manifold can be modified by the projective symmetries, resulting in unprecedented topological properties. Here, we realize a real-projective-plane hybrid-order topological insulator in a phononic crystal by introducing the Z_2 gauge field. Such insulator hosts two momentum-space non-symmorphic reflection symmetries, which change the Brillouin manifold from a torus to a real projective plane. These symmetries can simultaneously lead to Klein-bottle and quadrupole topologies in different bulk gaps. The non-symmorphic reflection symmetries on Brillouin real projective plane, edge states of Klein-bottle insulator, and corner states of quadrupole insulator are observed. These results evidence the hybrid-order topology on Brillouin manifold beyond the torus, and enrich the topological physics.Comment: 4 figure

Efficacy of guideline-directed medical treatment in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) has received increasing attention following the publication of the latest ESC guidelines in 2021. However, it remains unclear whether patients with HFmrEF could benefit from guideline-directed medical treatment (GDMT), referring the combination of ACEI/ARB/ARNI, β-blockers, and MRAs, which are recommended for those with reduced ejection fraction. This study explored the efficacy of GDMT in HFmrEF patients. This was a retrospective cohort study of HFmrEF patients admitted to The First Affiliated Hospital of Dalian Medical University between 1 September 2015 and 30 November 2019. Propensity score matching (1:2) between patients receiving triple-drug therapy (TT) and non-triple therapy (NTT) based on age and sex was performed. The primary outcome was all cause death, cardiac death, rehospitalization from any cause, and rehospitalization due to worsening heart failure. Of the 906 patients enrolled in the matched cohort (TT group, n = 302; NTT group, N = 604), 653 (72.08%) were male, and mean age was 61.1 ± 11.92. Survival analysis suggested that TT group experienced a significantly lower incidence of prespecified primary endpoints than NTT group. Multivariable Cox regression showed that TT group had a lower risk of all-cause mortality (HR 0.656, 95% CI 0.447-0.961, P = 0.030), cardiac death (HR 0.599, 95% CI 0.380-0.946, P = 0.028), any-cause rehospitalization (HR 0.687, 95% CI 0.541-0.872, P = 0.002), and heart failure rehospitalization (HR 0.732, 95% CI 0.565-0.948, P = 0.018). In patients with HFmrEF, combined use of neurohormonal antagonists produces remarkable effects in reducing the occurrence of the primary outcome of rehospitalization and death. Thus, the treatment of HFmrEF should be categorized as HFrEF due to the similar benefit of neurohormonal blocking therapy in HFrEF and HFmrEF. [Abstract copyright: © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

The ERAD Inhibitor Eeyarestatin I Is a Bifunctional Compound with a Membrane-Binding Domain and a p97/VCP Inhibitory Group

Protein homeostasis in the endoplasmic reticulum (ER) has recently emerged as a therapeutic target for cancer treatment. Disruption of ER homeostasis results in ER stress, which is a major cause of cell death in cells exposed to the proteasome inhibitor Bortezomib, an anti-cancer drug approved for treatment of multiple myeloma and Mantle cell lymphoma. We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib.Here we developed in vitro binding and cell-based functional assays to demonstrate that a nitrofuran-containing (NFC) group in EerI is the functional domain responsible for the cytotoxicity. Using both SPR and pull down assays, we show that EerI directly binds the p97 ATPase, an essential component of the ERAD machinery, via the NFC domain. An aromatic domain in EerI, although not required for p97 interaction, can localize EerI to the ER membrane, which improves its target specificity. Substitution of the aromatic module with another benzene-containing domain that maintains membrane localization generates a structurally distinct compound that nonetheless has similar biologic activities as EerI.Our findings reveal a class of bifunctional chemical agents that can preferentially inhibit membrane-bound p97 to disrupt ER homeostasis and to induce tumor cell death. These results also suggest that the AAA ATPase p97 may be a potential drug target for cancer therapeutics

A (Bi₂O₂)²⁺ layer as a significant carrier generator and transmission channel in CaBi₂Nb₂O₉ platelets for enhanced piezo-photo-catalytic performance

The low photocatalytic conversion efficiency, poor light absorption and high charge recombination rate of traditional semiconductor photocatalysts continues to be a significant research challenge. In this paper, by combining detailed experimental and modeling techniques, we report on the unique potential of CaBi2Nb2O9 (CBN) platelets that can couple both piezo- and photo- multi-field effects to overcome these issues and realize high-efficiency hydrogen production and dye degradation. The surface adsorption of OH− and dye molecules is improved as a result of the built-in electric field, thereby demonstrating an enhanced piezo- and photo-catalytic H2 production activity, with a high rate of 96.83 μmol g−1 h−1. The piezo-photocatalytic decomposition ratio for 100 mL RhB dye of 10 mg/L can reach up to 98.7 % in 32 min using only 0.05 mg of CBN platelets (k = 0.131 min−1). It is shown that the careful introduction of regularly arranged layers of (Bi2O2)2+ into the CBN platelet structure provides a high transport of photoelectrons via a pathway of (Bi2O2)2+ → (CaNb2O7)2− → CBN surface. The electron density distribution of Bi atoms is also found to be enriched on the facets of (020) and (200) crystal planes in the CBN platelets, which is beneficial to the oxidation reduction reaction. Furthermore, the large deformation of CBN platelet during the application of ultrasound leads to an increase of the piezo-induced built-in electric field to improve charge separation and migration. This work therefore provides a new perspective in the design and manufacture of advanced materials with enhanced piezo- and photo-catalytic performance by exploiting multi-field coupling effects.</p

A (Bi₂O₂)²⁺ layer as a significant carrier generator and transmission channel in CaBi₂Nb₂O₉ platelets for enhanced piezo-photo-catalytic performance

The low photocatalytic conversion efficiency, poor light absorption and high charge recombination rate of traditional semiconductor photocatalysts continues to be a significant research challenge. In this paper, by combining detailed experimental and modeling techniques, we report on the unique potential of CaBi2Nb2O9 (CBN) platelets that can couple both piezo- and photo- multi-field effects to overcome these issues and realize high-efficiency hydrogen production and dye degradation. The surface adsorption of OH− and dye molecules is improved as a result of the built-in electric field, thereby demonstrating an enhanced piezo- and photo-catalytic H2 production activity, with a high rate of 96.83 μmol g−1 h−1. The piezo-photocatalytic decomposition ratio for 100 mL RhB dye of 10 mg/L can reach up to 98.7 % in 32 min using only 0.05 mg of CBN platelets (k = 0.131 min−1). It is shown that the careful introduction of regularly arranged layers of (Bi2O2)2+ into the CBN platelet structure provides a high transport of photoelectrons via a pathway of (Bi2O2)2+ → (CaNb2O7)2− → CBN surface. The electron density distribution of Bi atoms is also found to be enriched on the facets of (020) and (200) crystal planes in the CBN platelets, which is beneficial to the oxidation reduction reaction. Furthermore, the large deformation of CBN platelet during the application of ultrasound leads to an increase of the piezo-induced built-in electric field to improve charge separation and migration. This work therefore provides a new perspective in the design and manufacture of advanced materials with enhanced piezo- and photo-catalytic performance by exploiting multi-field coupling effects.</p

Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly

Background: Whole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus. Results: A search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1. Conclusions: Our findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5′ stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother’s third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants