Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice: Through ERK/GATA3 signaling pathway.

Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.

Nerolidol attenuates airway inflammation and airway remodeling and alters gut microbes in ovalbumin-induced asthmatic mice.

Asthma is a common respiratory disease associated with airway inflammation. Nerolidol is an acyclic sesquiterpenoid with anti-inflammatory properties. BALB/C mice were sensitized with ovalbumin (OVA) to induce asthma symptoms and given different doses of Nerolidol. We found that Nerolidol reduced OVA-induced inflammatory cell infiltration, the number of goblet cells and collagen deposition in lung tissue. Nerolidol reduced the OVA-specific IgE levels in serum and alveolar lavage fluid in an asthma model. Immunohistochemical staining of α-SMA (the marker of airway smooth muscle) showed that Nerolidol caused bronchial basement membrane thinning in asthmatic mice. The hyperplasia of airway smooth muscle cells (ASMCs) is an important feature of airway remodeling in asthma. ASMCs were treated with 10 ng/mL TGF-ß to simulate the pathological environment of asthma in vitro and then treated with different doses of Nerolidol. Nerolidol inhibited the activity of TGF-ß/Smad signaling pathway both in the lung tissue of OVA-induced mouse and TGF-ß-stimulated ASMCs. 16s rRNA sequencing was performed on feces of normal mice, the changes of intestinal flora in OVA-induced asthmatic mice and Nerolidol-treated asthmatic mice were studied. The results showed that Nerolidol reversed the reduced gut microbial alpha diversity in asthmatic mice. Nerolidol changed the relative abundance of gut bacteria at different taxonomic levels. At the phylum level, the dominant bacteria were Bacteroidota, Firmicutes, and Proteobacteria. At the genus level, the dominant bacteria were Lactobacillus, Muribaculaceae, Bacteroides, and Lachnospiraceae. We conclude that Nerolidol attenuates OVA-induced airway inflammation and alters gut microbes in mice with asthma via TGF-ß/Smad signaling.

Efficacy and safety of macrolides in the treatment of children with bronchiectasis: a meta-analysis.

BACKGROUND: This study summarized the available randomized controlled trials (RCTs) to assess the efficacy and safety of macrolides on pathogens, lung function, laboratory parameters, and safety in children with bronchiectasis. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for available papers published up to June 2021. The outcomes were the pathogens, adverse events (AEs), and the forced expiratory volume in one second (FEV1%) predicted. RESULTS: Seven RCTs (633 participants) were included. The long-term use of macrolides reduced the risk of the presence of Moraxella catarrhalis (RR = 0.67, 95% CI: 0.30-1.50, P = 0.001; I2 = 0.0%, Pheterogeneity = 0.433), but not Haemophilus influenza (RR = 0.19, 95% CI: 0.08-0.49, P = 0.333; I2 = 57.0%, Pheterogeneity = 0.040), Streptococcus pneumonia (RR = 0.91, 95% CI: 0.61-1.35, P = 0.635; I2 = 0.0%, Pheterogeneity = 0.515), Staphylococcus aureus (RR = 1.01, 95% CI: 0.36-2.84, P = 0.986; I2 = 61.9%, Pheterogeneity = 0.033), and any pathogens present (RR = 0.61, 95% CI: 0.29-1.29, P = 0.195; I2 = 80.3%, Pheterogeneity = 0.006). Long-term macrolides had no effect on FEV1% predicted (WMD = 2.61, 95% CI: -1.31, 6.53, P = 0.192; I2 = 0.0%, Pheterogeneity = 0.896). Long-term macrolides did not increase the risk of AEs or serious AEs. CONCLUSION: Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) or increase FEV1% predicted among children with bronchiectasis. Moreover, macrolides were not associated with AEs. Considering the limitations of the meta-analysis, further larger-scale RCTs are needed to confirm the findings. IMPACT: Macrolides do not significantly reduce the risk of pathogens present (except for Moraxella catarrhalis) among children with bronchiectasis. Macrolides do not significantly increase FEV1% predicted among children with bronchiectasis. This meta-analysis reports on the efficacy and safety of macrolides in the treatment of children with bronchiectasis, providing evidence for the management of children with bronchiectasis. This meta-analysis does not support the use of macrolides in the management of children with bronchiectasis unless the presence of Moraxella catarrhalis is provenor suspected.

Reconstructing the earliest known composite-tiled roofs from the Chinese Loess Plateau.

The origins of composite tiles, one of the oldest forms of roofing, are still unclear. This study is based on a set of over 5000 clay tile fragments excavated from a single context in the Qiaocun site on the Chinese Loess Plateau, dated to ~ 2400-2200 BCE (Early Longshan Period). By combining morphological measurement statistics, 3D modeling, computer-based simulations, and reference to historical and archaeological records, we reconstruct the earliest known composite-tile roofing techniques and demonstrate that tile production was under a low-level standardization, with manual control forming a key agent during the roofing process. The quantitative study of the composite roof tiles from Qiaocun was then placed in its archaeological context and compared with other sites on the Loess Plateau. It was found that tile-roofed buildings were, by necessity, community projects. Such structures served as nodes in larger social communication networks; additionally, their appearance was linked to intensified social complexity in public affairs during the Longshan Period. The invention of clay tiles was associated with the inception of thick rammed-earth walls which had sufficient strength to serve as load-bearing structures for heavy tiled roofs. The roof tiles excavated from Qiaocun site indicate that the Loess Plateau was a key center for the origin and spread of composite tiles and related roofing and construction methods, suggesting a Longshan-Western Zhou tradition of roofing techniques in East Asia.

2-Undecanone alleviates asthma by inhibiting NF-κB pathway.

Asthma is characterized by airway inflammation and remodeling. 2-Undecanone (methyl nonyl ketone), a volatile organic compound originating from Houttuynia cordata, has the potential to ameliorate inflammatory diseases. This study aimed to explore potential benefits of 2-undecanone in asthma. 2-Undecanone (100, 200, or 400 mg/kg) was administered intragastrically to ovalbumin (OVA)-challenged BALB/c mice. Lung tissues were collected to observe histopathological changes, and bronchoalveolar lavage fluid (BALF) was collected for the detection of inflammatory cells and cytokine production. The results showed that 2-undecanone ameliorated OVA-induced pathologic changes of lungs, including reducing inflammatory cell infiltration, goblet cell hyperplasia, and airway smooth muscle thickness. The number of inflammatory cells and the levels of IL-4, IL-5, IL-13, and IgE in BALF were decreased by 2-undecanone in asthmatic mice. Furthermore, abnormal activation of NF-κB pathway in lung tissues of asthmatic mice was impeded by 2-undecanone. In vitro, 2-undecanone (12.5, 25, or 50 µM) suppressed platelet-derived growth factor-BB-induced proliferation and migration of primary airway smooth muscle cells (ASMCs), and inhibited the switching of ASMCs from contractile phenotype to synthetic phenotype. Consistently, 2-undecanone blocked NF-κB activation in ASMCs. Collectively, 2-undecanone relieves asthma through alleviating airway inflammation and remodeling, and this beneficial effect is achieved by inhibiting NF-κB pathway.

[Design and development of the multi-dimensional ultrasonic reconstruction and visualization system].

The design and development of multi-dimensional ultrasonic reconstruction and visualization system (MURVS) have been described in the present paper. This system is basically composed of four modules: the data input/output module, image segmentation and arrangement module, multi-dimensional reconstruction module, and the dynamic visualization module. At first, some algorithms used in the system are introduced by the authors, including the AVI segmentation algorithm, three-dimensional interpolation algorithm, and volume rendering algorithms. Then the key questions of techniques to be discussed are: how to design the main modules, how to solve the dynamic visualization problem, and how to implement the system. The experiments indicate that MURVS is able to reconstruct all three-dimensional data fields in one cardiac cycle of a patient within 4 seconds, and dynamically display the motion of the heart. It allows the medical professionals to select different parameters when observing the reconstructed results. This is very helpful for medical professionals to reach more accurate diagnoses of their patients' diseases.

[Quantitative functional evaluation on right ventricle with auto-segmentation and three-dimensional reconstruction].

The authors first segment the right ventricle regions from the echocardiographics by introducig a seeded region growth algorithm. Then they reconstrunct the three dimensional data field of right ventricle by using rotary scanning interpolation algorithm. And then, the authors propose a layer-by-layer, row-by-row, and voxel-by-voxel approach based on the interpolation results to estimate the volume of right ventricle. Finally, some right ventricle functional parameters such as EDV (End-diastolic volume), ESV (End-systolic volume), and RVEF (Right ventricular ejection fraction) are computed according to the volume results. The volume variation curves of several patients during a cardiac cycle have been successfully plotted out. The obtained results are compared with those from Tomtec medial image workstation. The comparison indicates the proposed approach is practical and meaningful.