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AIM: To investigate the proliferation regulatory effect of cone-rod homeobox (CRX) in retinal pigment epithelium (RPE) and retinoblastoma (RB) cells to explore the potential application and side effect (oncogenic potential) of CRX-based gene therapy in RPE-based retinopathies. METHODS: Adult human retinal pigment epithelial (ARPE)-19 and human retinal pigment epithelial (RPE)-1 cells and Y79 RB cell were used in the study. Genetic manipulation was performed by lentivirus-based technology. The cell proliferation was determined by a CellTiter-Glo Reagent. The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot assay. The transcriptional activity of the promoter was determined by luciferase reporter gene assay. The bindings between CRX and transcription factor 7 (TCF7) promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation (ChIP) assay. The transcription of the TCF7 was determined by a modified nuclear run-on assay. RESULTS: CRX overexpression and knockdown significantly increased (n=3, P

Objective Over-excavation in tunnel construction, mainly caused by inappropriate blasting,will affect the smooth progress and safety of tunnel excavation, increase construction cost and reduce economic benefits. In order to radically solve this problem, blasting design and blasting construction technology should be studied and optimized. Method Based on the shallow buried unsymmetrical pressured layered railway tunnel project for Chongqing Railway Hub East Ring Line(Chongqing East Ring Railway),the causes of vault, arch haunch and arch foot over-excavation are analyzed with theoretical method and modern computer technology. The drilling positions are designed with dynamic optimization, and control measures and solutions for over-excavation are put forward. Result & Conclusion Over-excavation at the tunnel vault is mainly caused by the secondary disturbance of the surrounding rock in smashed area by mechanical excavation after blasting, and over-excavation at the arch waist and arch foot is mainly caused by the improper amount of blasting explosive and improper drilling. In addition, the existence of rock cracks will also lead to significant decrease of the surrounding rock strength. Therefore, proper blasting and under-excavation should be done at the vault to reduce the disturbance of the surrounding rock, and then manual + mechanical excavation and trimming should be combined to reduce the amount of over-excavation. Secondly, according to the attributes of surrounding rock, and based on GA-SVR model and genetic algorithm, the blasthole spacing is properly optimized. On-site monitoring results show that in the initial stage without optimized blasthole spacing, the over-excavation in cracked stratum is about 40cm, which is reduced to about 9cm after the blasthole spacing optimization. The results indicate that optimizing the blasthole spacing can effectively control tunnel over-excavation. The above results can provide reference for similar projects.

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2).

The tuber of Coeloglossum viride var. bracteatum is a Tibetan medicine that has been used for generations as a tonic for Yang and Qi, tranquilizing, to enhance intelligence and to promote longevity. We have previously characterized the constituents of Coeloglossum viride var. bracteatum extract (CE) and investigated its anti-Alzheimer’s disease (AD) effect in mice models. However, the exact role of CE in Parkinson’s disease (PD), especially the neurotrophic and inflammatory pathways regulated by CE, remains unknown. In this study, we investigated the anti-PD effects of CE in an MPTP-induced acute mouse model and its underlying mechanisms, focusing on BDNF, FGF2 and their mediated signaling pathways and RIP1-driven inflammatory signaling axis. Pole test and traction test were performed for behavioral analysis. RT-PCR, IHC and Western blotting were performed to assay the mRNA, tissues, and protein, respectively. We found that CE improved dyskinesia in MPTP-intoxicated mice, which was confirmed by the pole test and traction test. Also, oxidative stress and astrocyte activation and inflammation were alleviated. MPTP-intoxication disrupted the levels of BDNF, FGF2 and their mediated signaling pathways, triggered elevation of pro-inflammatory factors such as TNF-α, IL-1β, and IL-6, and activated RIP1-driven inflammatory axis. However, CE restored the levels of BDNF, FGF2 and TrkB/Akt signaling pathways while inhibiting the RIP1-driven inflammatory signaling axis, thereby inhibiting apoptosis, preventing loss of nigrostriatal neurons, and maintaining cellular homeostasis. Thus, CE is a promising agent for the treatment of PD.

The neuroprotective effects of Coeloglossum viride var. bracteatum extract (CE) was investigated in a mouse model of AD. We found that CE improved cognitive deficits in 5xFAD mice in MWM and Y-maze behavioral tests. Also, antioxidant levels in serum and brain were normalized and peroxidation product MDA was reduced after CE treatment compared to untreated 5xFAD mice. Similarly, levels of pro-inflammatory factors such as TNF-α, IL-6 and IL-1β were reduced and anti-inflammatory factor IL-10 was increased. CE restored levels of BDNF and FGF2, as well as the signaling regulators Akt, TrkB and the apoptotic factors Bcl-2 and cleaved-Caspase-3. In addition, the RIP1/RIP3/MLKL inflammatory signaling pathway and necroptosis were inhibited, the RIP1 inhibitor TBK1 was restored and Aβ deposition was reduced in hippocampus and prefrontal cortex of 5xFAD mice. Thus, CE is effective in improving cognitive dysfunction in AD mouse models and may be a potential therapeutic agent.

Hemoptysis in children is caused by various factors, the most common of which is basic lung disease or heart disease. Aortopulmonary collateral arteries (APCAs) are blood vessels that originate from the aorta or its branches and provide blood flow to the pulmonary tissues. We herein report a rare case of APCAs without abnormal structures in the heart. The patient was a previously healthy boy with APCAs originating from the descending aorta. He had no history of congenital heart disease and developed repeated episodes of cryptogenic hemoptysis during his school-age years. Arteriography examination facilitated the diagnosis of APCAs. After embolization, the patient developed no further hemoptysis during 10 months of follow-up. Arteriography is of great significance in determining the cause of recurrent cryptogenic hemoptysis.