BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective To analyze the topological characteristics of the brain structural network in primary angle-closure glaucoma (PACG) patients by applying graph theoretical approaches.Methods From October 2015 to April 2017, nineteen PACG patients and nineteen gender-and age-matched healthy controls (HCs) were enrolled to undergo MRI scan. The whole brain was parceled into 90 regions by automated anatomical labeling template, and the brain structural network was constructed by the fiber distribution of continuous tracking method.Both the weighted and unweighted network analyses were performed.The global and regional properties were computed by graph theoretical analysis.To compare the brain network regional properties between two groups, two-sample t-test was utilized.The correlations between the brain structural network properties and clinical parameters were further analysed. Results Both two groups were found to follow the efficient small-world characteristics. Compared to HCs, the brain structural network in PACG patients showed no statistical significance in the small-worldness, average shortest path, clustering coefficient, global efficiency and local efficiency(P＞0.05). Compared to the HCs, the PACG patients showed decreased nodal efficiency in the right superior frontal gyrus, right inferior frontal gyrus, left median cingulate and paracingulate gyri, left amygdala and left cuneus(P＜0.05). Compared to HCs, the PACG patients showed decreased node degree in left superior frontal gyrus, medial orbital, right inferior frontal gyrus, left amygdala, left cuneus and left lingual gyrus(P＜0.05). Compared with the hub regions in healthy controls'network, we found that two hub regions disappeared.Those hubs were right inferior parietal lobule and left middle temporal gyrus. Node degree in left amygdala showed negatively correlated with visual ability (r=-0.679, P=0.001). Node degree in left lingual gyrus showed negatively correlated with vertical CDR(r=-0.791, P=0.001),which showed positively correlated with visual acuity(r=0.538, P=0.018).Conclusions The brain structural network in PACG patients showed small-worldness properties as HCs group. The alterations of local properties in visual, emotion-cognition brain regions were observed, manifesting that PACG can affect the topology properties of the structural brain network.

China Three Gorges University(CTGU) started undergraduate medical education for foreign students since 2004. Over the years,through continuous interaction with coordinators,CTGU grad-ually transited from passive teaching to active teaching. Firstly we determined basic principles,objectives and requirements of talent training programme. Secondly,we strengthen Chinese language teaching, reasonably adjusted professional curriculum and teaching content,added basic medical courses and rea-sonably arranged clinical practice based on the concrete situation in our country. in order to make the cur-riculum system consistent with the require-ments of talent training.

It has become a hotspot and keystone in gene engineering and bioengineering to produce recombinant proteins through heterologous expression systems. Unfortunately, not all the genes could be successfully and effectively expressed in heterologous hosts. The role of gene itself in regulating translation process through its intrinsic sequence characteristics such as codon bias, codon pair bias, GC content, mRNA secondary structure and mRNA stability, has been gradually elucidated. Here we review these factors that influence the translation processes and their corresponding optimization methods in the process of gene design. We emphatically discussed codon bias and codon pair bias and their optimization methods. In particular, the latest theories of codon harmonization and codon pair harmonization were discussed and compared with the traditional codon and codon pair optimization strategies in gene design.
Codon ; genetics ; DNA, Bacterial ; genetics ; Escherichia coli ; genetics ; Genes, Synthetic ; genetics ; Protein Biosynthesis ; genetics ; Protein Engineering ; methods ; trends ; RNA Stability ; genetics ; Recombinant Proteins ; biosynthesis ; genetics

Objective To observe the change of liver sinusoid in BALB/c mice infected with Schistosoma japonicum and explore its relationship between the degree of hepatic fibrosis and liver function. Methods A model was established in BALB/c mice infected with cercariae of Schistosoma japonicum. The liver specimens of mice were used for pathological examination with routine and picric acid-sirius red staining to know the degree of hepatic fibrosis by semi-quantity. The expressions of C-IV and vWF in liver sinusoid were assayed through the immuhistochemistry staining. The serum ALT and AST were detected by the automatic biochemistry analyzer, and the ultramicrostructure of the liver tissue was observed by a transmission electron microscope. Results The number and diameter of fenestrations in SEC reduced 4 weeks after the infection. The fenestrations were disappeared and the base membrane established 8 weeks after the infection. The expressions of C-IV and vWF in liver sinusoid and the degree of hepatic fibrosis increased with the time after infection. The levels of serum ALT and AST were not correlated with the infection time. Conclusions The phenotype alteration of the hepatic sinusoidal endothelium may be a vital issue triggering the liver fibrosis induced by Schistosoma japoncium.