Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.

The Status and Influencing Factors of COVID-19 Vaccination for 3-7-Year-Old Children Born Prematurely.

Objective: To explore the status and influencing factors of COVID-19 vaccination for 3-7-year-old children born prematurely. Methods: A questionnaire was administered to parents of preterm infants born between 1 January 2016 and 31 December 2019 in Gansu Maternal and Child Health Hospital using convenience sampling. Results: It was found that 96.81% of 282 parents had known about COVID-19 vaccines and acquired COVID-19- and vaccine-related knowledge primarily through WeChat (104/282, 36.88%) and TikTok (91/282, 32.27%). Most parents of the group whose children were vaccinated with a COVID-19 vaccine believed that this approach was effective in preventing COVID-19 (49.75%), whereas most parents of the group whose children were not vaccinated were worried about the adverse reaction and safety of the vaccine (45.88%). According to the regression analysis, the risk factors of children born prematurely receiving a COVID-19 vaccine were no vaccination against COVID-19 in the mothers (odds ratio [OR]=48.489, 95% CI: 6.524-360.406) and in younger children (OR=12.157, 95% CI: 6.388-23.139). Previous history of referral (OR=0.229, 95% CI: 0.057-0.920), history of diseases (OR=0.130, 95% CI: 0.034-0.503) and high educational level of guardians (OR=0.142, 95% CI: 0.112-0.557) were protective factors for children born prematurely to receive COVID-19 vaccination. Conclusion: There is a relatively high proportion of children born prematurely receiving COVID-19 vaccination, but some people still have concerns. Publicity in the later stage can be conducted through WeChat, TikTok and other social media platforms, with special attention paid to the populations with lower education levels.

Plasma neurofilament light as a promising biomarker in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable biomarkers. This study investigates plasma protein levels as potential biomarkers of disease severity and progression in NIID. In this study, we enrolled 30 NIID patients and 36 age- and sex-matched controls, following them for 1-2 years. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and tau were measured using ultrasensitive single molecule array (Simoa) assays. Disease severity was evaluated with the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), and CNS symptom counts, in addition to neuroimaging data. Our study revealed that NIID patients has significantly higher plasma NfL (median, 35.2 vs. 8.61 pg/mL, p < 0.001) and GFAP (102 vs. 79.0 pg/mL, p = 0.010) levels compared to controls, with NfL emerging as a robust diagnostic marker (AUC = 0.956). NfL levels were notably higher in acute-onset NIID (77.5 vs. 28.8 pg/mL, p = 0.001). NfL correlated strongly with disease severity, including MMSE (ρ = - 0.687, p < 0.001), MoCA (ρ = - 0.670, p < 0.001), ADL (ρ = 0.587, p = 0.001), CNS symptoms (ρ = 0.369, p = 0.045), and white matter hyperintensity volume (ρ = 0.620, p = 0.004). Higher baseline NfL (≥ 35.2 pg/mL) associated with increased ADL scores, CNS symptoms, and white matter hyperintensity at follow-up. UCH-L1 and total tau levels showed no significant differences. Our results suggested the potential of NfL as a promising biomarker of disease severity and progression in NIID.

Real-World COVID-19 Vaccine Protection Rates against Infection in the Delta and Omicron Eras.

The real-world vaccine protection rates (VPRs) against the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection are critical in formulating future vaccination strategies against the virus. Based on a varying coefficient stochastic epidemic model, we obtain 7 countries' real-world VPRs using daily epidemiological and vaccination data, and find that the VPRs improved with more vaccine doses. The average VPR of the full vaccination was 82% (SE: 4%) and 61% (SE: 3%) in the pre-Delta and Delta-dominated periods, respectively. The Omicron variant reduced the average VPR of the full vaccination to 39% (SE: 2%). However, the booster dose restored the VPR to 63% (SE: 1%) which was significantly above the 50% threshold in the Omicron-dominated period. Scenario analyses show that the existing vaccination strategies have significantly delayed and reduced the timing and the magnitude of the infection peaks, respectively, and doubling the existing booster coverage would lead to 29% fewer confirmed cases and 17% fewer deaths in the 7 countries compared to the outcomes at the existing booster taking rates. These call for higher full vaccine and booster coverage for all countries.

Better strategies for containing COVID-19 pandemic: a study of 25 countries via a vSIADR model.

We study epidemiological characteristics of 25 early COVID-19 outbreak countries, which emphasizes on the reproduction of infection and effects of government control measures. The study is based on a vSIADR model which allows asymptomatic and pre-diagnosis infections to reflect COVID-19 clinical realities, and a linear mixed-effect model to analyse the association between each country's control measures and the effective reproduction number R t . It finds significant effects of higher stringency measures in lowering the reproduction, and a significant shortening effect on the time to the epidemic turning point by applying stronger early counter measures. Epidemic projections under scenarios of the counter measures (China and Korea, the USA and the UK) show substantial reduction in the epidemic size and death by taking earlier and forceful actions. The governments' response before and after the start of the second wave epidemics were alarmingly weak, which made the average duration of the second wave more than doubled that of the first wave. We identify countries which urgently need to restore to at least the maximum stringency measures implemented so far in the pandemic in order to avoid even higher infection size and death.