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1.
Artigo em Inglês | MEDLINE | ID: mdl-32621959

RESUMO

Functional dysconnectivity has been widely reported in bipolar disorder during depressive episodes (BDD). However, the frequency-specific alterations of functional connectivity (FC) in BDD remain poorly understood. To address this issue, the FC patterns across slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) bands were computed using resting-state functional magnetic resonance imaging data from 37 BDD patients and 56 healthy controls (HCs). Short-range (local) FC density (lfcd) and long-range FC density (lrfcd) were calculated, and two-way analysis of variance was performed to ascertain the main effect of diagnosis and interaction effects between diagnosis and frequency. The BDD patients showed increased lfcd in the midline cerebelum. Meanwhile, the BDD patients showed increased lrfcd in the left supplementary motor cortex and right striatum and decreased lrfcd in the bilateral inferior temporal gyrus and left angular gyrus (AG) compared with the HCs. A significant frequency-by-diagnosis interaction was observed. In the slow-4 band, the BDD patients showed increased lfcd in the left pre-/postcentral gyrus and left fusiform gyrus (FG) and increased lrfcd in the left lingual gyrus (LG). In the slow-5 band, the BDD patients showed decreased lrfcd in the left LG. Moreover, the increased lfcd in the left FG in the slow-4 band was correlated with clinical progression and decreased lrfcd in the left AG was correlated with depressive severity. These results suggest that the presence of aberrant communication in the default mode network, sensory network, and subcortical and limbic modulating regions (striatum and midline cerebelum), which may offer a new framework for the understanding of the pathophysiological mechanisms of BDD.

2.
Neural Regen Res ; 16(1): 179-185, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788474

RESUMO

Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H2O2) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2. Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People's Hospital, China (approval No. 2018PHC081) on December 18, 2018.

3.
Pediatr Surg Int ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040172

RESUMO

PURPOSE: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders. METHODS: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. RESULTS: The mean follow-up was 26.6 months. The liver function and ammonia remained in the normal range at the end of the follow-up in all recipients. One D-APOLT patient experienced portal vein thrombosis 2 days after transplantation and required reoperation, this patient presented an imbalance of portal blood perfusion between the native and the domino liver at 8 months after liver transplant. The imbalance was improved by interventional radiology treatment. Two LDLT patients experienced early mild acute rejection. CONCLUSIONS: The non-cirrhotic livers from pediatric patients with metabolic liver disease can be used as domino donor grafts for selected pediatric patients with different metabolic liver disease. D-APOLT achieves ideal recipient outcomes and provides a strategy to expand donor source for children.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33043389

RESUMO

Several quorum sensing systems occurring in Bacillus subtilis, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in Bacillus velezensis NAU-B3. We found that the rapA4 and phrA4 genes were co-transcribed in NAU-B3. When rapA4 was expressed in the heterologous host Bacillus subtilis OKB105, surfactin production and sporulation were severely inhibited. However, when the phrA4 was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase srfA gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the srfA operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment. KEY POINTS: •Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42. •RapA4-PhrA4 regulates surfactin production and sporulation. •RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.

5.
Bioorg Chem ; 104: 104314, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33011538

RESUMO

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.

6.
J Vis Exp ; (163)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33044461

RESUMO

Type 1 fimbriae are important virulence determinants of some Gram-negative pathogens, which promote bacterial colonization. The fimbrial rod is primarily composed of multiple copies of the major fimbrial subunit FimA. FimH adhesin, however, is present as a fibrillar tip structure that drive bacteria binding to host cellular mannose containing receptor. Here, we provide protocols to evaluate and compare the function of type 1 fimbrial subunits in F18ab fimbriae+ Shiga toxin-producing Escherichia coli (STEC). We found that both FimA and FimH are required for bacterial adhesion, invasion, and biofilm formation. Deleting fimA gene showed much more reduction in bacterial adhesion and invasion to porcine intestinal columnar epithelial cells IPEC-J2, than that of fimH mutant. Biofilm formation was significantly reduced in both mutants with an equal level. In addition, qPCR demonstrated that either fimA or fimH deletion down-regulated the bacterial flagella and F18 fimbriae genes expression, while up-regulated adhesin was involved in diffuse adherence-I (AIDA-I) gene expression, suggesting the co-regulation of cell surface-localized adhesins in F18ab fimbriae+ STEC.

7.
Int J Biochem Cell Biol ; : 105862, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045372

RESUMO

During the orthodontic tooth movement, cells in periodontal ligament could differentiate into osteoblasts to synthesize alveolar bone as well as affect the proliferation, migration and differentiation of mesenchymal stem cells, which also contribute to bone remodeling. However, the mechanism is still largely elusive. Here, we evaluated the expression of CREB at the tension site of mouse periodontal ligament under orthodontic mechanical strain and in the cyclic tension strain treated human periodontal ligament cells. Then, through gain and loss of function analysis, we revealed that CREB in PDLCs promotes SDF-1 and FGF2 secretion, which enhance the migration and osteoblastic differentiation of BMSCs. We further discovered that CREB transcriptionally activates FGF2 and SDF-1 expressions by binding to the promoter regions. In conclusion, this study confirms that CREB is an upregulated gene in periodontal ligament under orthodontic tension strain stimulation and plays an important role in regulating BMSCs' physiological activity in orthodontic tension strain-induced bone formation.

8.
Euro Surveill ; 25(40)2020 10.
Artigo em Inglês | MEDLINE | ID: covidwho-841040

RESUMO

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.


Assuntos
Infecções por Coronavirus/transmissão , Coronavirus/patogenicidade , Período de Incubação de Doenças Infecciosas , Pneumonia Viral/transmissão , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Criança , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Estudos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Adulto Jovem
11.
Can Respir J ; 2020: 2379814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082890

RESUMO

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.

12.
World J Clin Cases ; 8(19): 4565-4571, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083419

RESUMO

BACKGROUND: Angiosarcoma is a rare disease with a poor prognosis. Its occurrence in the small intestine is low, and gastrointestinal bleeding caused by small intestinal angiosarcoma is unusual. CASE SUMMARY: Here, we report the case of a 57-year-old man who presented with hematochezia for 1 mo. The patient had a medical history of chronic viral hepatitis B for 15 years. The causes of gastrointestinal bleeding were initially diagnosed as esophagogastric variceal bleeding or portal hypertensive gastropathy before endoscopy. However, after a complicated diagnostic and therapeutic process, including gastroendoscopy, colonoscopy, contrast-enhanced computed tomographic (CT), positron emission computed tomography/CT, capsule endoscopy, and pathological and immunohistochemical examinations, small intestinal angiosarcoma was diagnosed. Arrest of bleeding was achieved after surgical treatment. Furthermore, the patient had lung cancer with bone and adrenal metastases. At the follow-up 10 mo after the operation, the patient was alive. CONCLUSION: Gastroenterologists should maintain strong vigilance to small intestinal angiosarcoma, which is necessary for the early identification of this infrequent but fatal disease.

13.
Structure ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: covidwho-872505

RESUMO

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) resulted from the outbreak of SARS-CoV-2 in December 2019. Currently, multiple efforts are being made to rapidly develop vaccines and treatments to fight COVID-19. Current vaccine candidates use inactivated SARS-CoV-2 viruses; therefore, it is important to understand the architecture of inactivated SARS-CoV-2. We have genetically and structurally characterized ß-propiolactone-inactivated viruses from a propagated and purified clinical strain of SARS-CoV-2. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are found, most spikes appear nail shaped, thus resembling a postfusion state, where the S1 protein of the spike has disassociated from S2. Cryoelectron tomography and subtomogram averaging of these spikes yielded a density map that closely matches the overall structure of the SARS-CoV postfusion spike and its corresponding glycosylation site. Our findings have major implications for SARS-CoV-2 vaccine design, especially those using inactivated viruses.

14.
J Colloid Interface Sci ; 583: 157-165, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-33002688

RESUMO

Lithium-sulfur (Li-S) battery has been considered a promising next-generation electrochemical energy storage device due to its high theoretical capacity and high energy density. However, the dissolution and shuttling problems of lithium polysulfides (LiPSs) are major obstacles hindering the performance and application of Li-S batteries. To address these issues, we report the rapid preparation of porous TiO2 nanoparticles (p-TiO2-NPs) as an effective sulfur host for Li-S batteries using a facile, scalable, and green one-step air oxidation strategy. Experimental results reveal that the p-TiO2-NPs have a mesopores-rich structure and strong chemical adsorption capability against LiPSs, which effectively mitigates the dissolution and shuttling of LiPSs by way of physical and chemical adsorptions. Incorporating highly conductive multi-wall carbon nanotubes to interconnect with the active materials, the p-TiO2-NPs-based cathode delivers a high discharge capacity of 1276 mAh g-1 at 0.2 C and stable cycling performance with an ultralow capacity decay rate of 0.0526% per cycle at 1 C over 1200 cycles. This green and facile fabrication strategy can also be extended to other metal carbides to endow an environmentally friendly route for the sustainable development of high-performance Li-S batteries.

15.
Water Res ; 188: 116473, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33038718

RESUMO

Sand biofilters (SBFs) are commonly used to remove manganese (Mn(II)) from drinking water. Mn(II) load variation frequently occurs in SBFs due to fluctuating influent Mn(II) concentrations or flow rates. Therefore, it is important to understand the responses of microbial biofilms in SBFs to environmental disturbances and how they affect Mn(II) oxidation efficiency. Here, the responses of microbial ecological networks and Mn(II) removal in SBFs to increasing Mn(II) load were investigated. The Mn(II) removal efficiency in two SBFs remained at 99.8% despite an increase in influent Mn(II) from 2 mg/L to 4 mg/L, but significantly deteriorated (50.1-58.5%) upon increasing the filtration rate. A canonical correlation analysis of the microbial communities indicated that the local Mn(II) concentration and biofilter depth impacted community compositions of biofilms. The dominant species within the biofilms exhibited clear stratification, with simple associations in the upper layer of the SBFs and more complex interspecies interactions in the bottom layers. Putative manganese-oxidizing bacteria Hyphomicrobium and Pedomicrobium dominated the microbiomes in different layers of SBFs, and changed relatively little in abundance when Mn(II) and filtration rate increased. The community networks showed that biofilm microbiomes in SBFs were resilient to the disturbance of Mn(II) load, primarily via regulating microbial interactions. High manganese loads negatively affected the functional modules for Mn(II) removal. Furthermore, the relatively rare species Candidatus Entotheonella palauensis was identified as a module hub, implying taxa with low abundances can have important roles in ecosystem function. These results shed new light on the ecological rules guiding responses of microbiomes in sand biofilters to environmental stress.

16.
Anal Chem ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048522

RESUMO

The mitochondrial outer membrane protein, mitoNEET (mNT), is an iron-sulfur protein containing an Fe2S2(His)1(Cys)3 cluster with a unique single Fe-N bond. Previous studies have shown that this Fe(III)-N(His) bond is essential for metal cluster transfer and protein function. To further understand the effect of this unique Fe-N bond on the metal cluster and protein, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to investigate the mechanical unfolding mechanism of an mNT monomer, focusing on the rupture pathway and kinetic stability of the cluster. We found that the Fe-N bond was the weakest point of the cluster, the rupture of which occurred first, and could be independent of the cluster break. Moreover, this Fe-N bond enabled a dynamic and labile iron-sulfur cluster, as multiple unfolding pathways of mNT with a unique Fe2S2(Cys)3 intermediate were observed accordingly.

17.
Sci Total Environ ; 755(Pt 2): 142712, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33049531

RESUMO

Black carbon (BC) can mitigate or worsen air pollution by perturbing meteorological conditions. BC aging processes strongly influence the evolution of the particle size, concentration, and optical properties of BC, which determine its influence on meteorology. Here, we use the online coupled Weather Research and Forecasting-Chemistry (WRF-Chem) model to quantify the role of BC aging processes, including physical processes (PP) and absorption enhancement (AE), in causing BC-induced meteorological changes and their associated feedbacks to PM2.5 (particulate matter less than 2.5 µm in diameter) and O3 concentrations during a severe haze event in the Beijing-Tianjin-Hebei (BTH) region during 21-27 February 2014. Our results show that, compared to those from the simulation without PP, the simulated near-surface BC concentration and BC mass loading in the BTH region decreased by 6.6% and 12.1%, respectively, when PP were included. PP increased the proportion of large BC (particle diameter greater than 0.312 µm) below 1000 m from 28 to 33% to 59-64% in the BTH region. When both PP and AE were included in the simulation, the reduction in PBL height due to the BC-PBL interaction was 116.3 m (20.7%), compared to reductions of 75.7 m (13.5%) without AE and 66.6 m (11.9%) without PP and AE. However, during this haze event, anomalous northeasterly winds were produced by the direct radiative effect of BC, which further affected aerosol mixing and transport. Due to their combined impacts on multiple meteorological factors, the direct radiative effects of BC without PP and AE, without AE, and with PP and AE increased the surface concentrations of PM2.5 by 8.3 µg m-3 (by 6.1% relative to the mean value), 6.1 µg m-3 (4.5%) and 9.6 µg m-3 (7.0%), respectively, but decreased the surface O3 concentrations by 2.8 ppbv (7.4%), 4.0 ppbv (9.0%) and 5.0 ppbv (10.8%) on average in the BTH region during 21-27 February 2014.

18.
PLoS One ; 15(10): e0239890, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064719

RESUMO

Mushroom-forming fungi are complex multicellular organisms that form the basis of a large industry, yet, our understanding of the mechanisms of mushroom development and its responses to various stresses remains limited. The winter mushroom (Flammulina filiformis) is cultivated at a large commercial scale in East Asia and is a species with a preference for low temperatures. This study investigated fruiting body development in F. filiformis by comparing transcriptomes of 4 developmental stages, and compared the developmental genes to a 200-genome dataset to identify conserved genes involved in fruiting body development, and examined the response of heat sensitive and -resistant strains to heat stress. Our data revealed widely conserved genes involved in primordium development of F. filiformis, many of which originated before the emergence of the Agaricomycetes, indicating co-option for complex multicellularity during evolution. We also revealed several notable fruiting-specific genes, including the genes with conserved stipe-specific expression patterns and the others which related to sexual development, water absorption, basidium formation and sporulation, among others. Comparative analysis revealed that heat stress induced more genes in the heat resistant strain (M1) than in the heat sensitive one (XR). Of particular importance are the hsp70, hsp90 and fes1 genes, which may facilitate the adjustment to heat stress in the early stages of fruiting body development. These data highlighted novel genes involved in complex multicellular development in fungi and aid further studies on gene function and efforts to improve the productivity and heat tolerance in mushroom-forming fungi.

19.
Gen Comp Endocrinol ; : 113645, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058908

RESUMO

Reproductive activity is closely related to the development and function of the brain and liver in teleosts, particularly in seasonal breeding teleosts. This study measured the involvement of the insulin-like growth factor (IGF) system in controlling the reproduction of the silver pomfret Pampus argenteus, a seasonal breeding tropical to temperate commercial fish. We cloned and characterized the cDNAs of igfs (igf2 and igf3) and igfrs (igf1ra, igf1rb, and igf2r) and examined their transcript levels in relation to seasonal reproduction. Phylogenetic analyses revealed that two types of IGFs (IGF-1 and IGF-2) and three types of IGFRs (IGF1RA, IGF1RB, and IGF2R) of the silver pomfret were clustered with those of teleosts; however, IGF-3 was a transmembrane protein different with the IGF-3 of other teleosts. The expression of IGF-3 was gonad-specific in the silver pomfret. The transcript levels of igf1 in the female brain were the highest, and the levels of igfrs in both sexes' brains increased during gametogenesis. Meanwhile, igfs and igfrs maintained high transcript levels in both sexes' liver and gonad during vitellogenesis and spermatogonia proliferation. We concluded that the development and activities of brain, liver, and gonad were related to the IGF system (IGFs and IGFRs). And the IGFs were mainly expressed in the liver. Nevertheless, gonadal development, especially vitellogenesis and spermatogonia proliferation, were related with IGFs in this species.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1125-1130, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059812

RESUMO

OBJECTIVE: To study the continuous expression and potential function of circular RNA (circRNA), circ4:150439343|150477468 and circ15:73330849|73343359, in mouse lung development. METHODS: According to the stage of lung development, lung tissue samples were collected from mice on embryonic day 16.5 (E16.5), embryonic day 18.5 (E18.5), and postnatal day 2 (P2). Hematoxylin and eosin staining was performed to observe the morphology of lung tissue. Quantitative real-time PCR (qRT-PCR) was used to measure the mRNA expression of circ4:150439343|150477468 and circ15:73330849|73343359 during late lung development; miRanda and TargetScan were used to predict the target miRNAs of circRNAs, and then GO and KEGG analysis was performed for the target genes to predict the potential function of circRNAs. RESULTS: Type II alveolar epithelial cells were observed in the lung slices of E16.5 mice, with a gradual increase in number. On P2, the pulmonary alveoli expanded rapidly, the pulmonary interstitium became thinner, and the alveolar structure gradually became mature. The results of qRT-PCR showed that the relative expression of circ4:150439343|150477468 was continuously upregulated over time and the relative expression of circ15:73330849|73343359 was first downregulated and then upregulated (P<0.05). The KEGG and GO analysis showed that circRNAs were involved in the Notch, PI3K-Akt, and NF-κB signaling pathways. CONCLUSIONS: Circ4:150439343|150477468 and circ15:73330849|73343359 can participate in lung development through the Notch signaling pathway.

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