Dynamics of respiratory infectious diseases under rapid urbanization and COVID-19 pandemic in the subcenter of Beijing during 2014-2022.

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China. Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases. Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 (r = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread. Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control.

Epidemiological change of influenza virus in hospitalized children with acute respiratory tract infection during 2014-2022 in Hubei Province, China.

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.

Total Syntheses of (-)-Deoxoapodine, (-)-Kopsifoline D, and (-)-Beninine.

The total syntheses of Aspidosperma and Kopsia alkaloids (-)-deoxoapodine, (-)-kopsifoline D, and (-)-beninine are described through a domino deprotection-Michael addition-nucleophilic substitution protocol to assemble the core framework in efficient steps. Corey-Bakshi-Shibata reduction was employed to afford the enantioenriched intermediate for the total syntheses of the aforementioned alkaloids. The chirality was shown to completely transfer to the backbone using Johnson-Claisen rearrangement. The enantioselective total syntheses of (-)-kopsifoline D and (-)-beninine were accomplished for the first time. Our strategy opens up practical avenues for the total synthesis of structurally similar alkaloids.

An overactive neddylation pathway serves as a therapeutic target and MLN4924 enhances the anticancer activity of cisplatin in pancreatic cancer.

The survival rate of patients with pancreatic cancer is between 3 and 5%. The neddylation pathway is overactive in multiple cancer types and is associated with poor prognosis. In recent years, the neddylation process has become a popular research target for the development of novel cancer therapies. However, the activation level of the pathway, and whether its targeting sensitizes pancreatic cancer cells to cisplatin treatment is currently unclear. In the present study, using reverse transcription-quantitative PCR and western blot analyses, the neddylation pathway was observed to be overactivated at the protein, but not the mRNA level. In addition, by analyzing The Cancer Genome Atlas data, it was demonstrated that high expression levels of NEDD8 activating enzyme E1 subunit 1 were observed to be a predictor of poor prognosis for patients with pancreatic cancer. Cisplatin enhanced the cytotoxic effects of MLN4924 both in vitro and in vivo according to Cell Counting kit-8 assays and an in vivo tumor model. Further mechanistic studies, including western blotting and immunohistochemistry assays, revealed that combined MLN4924 and cisplatin treatment induced higher levels of DNA damage by increasing the accumulation of well-defined cullin-ring ligase substrates, such as chromatin licensing and DNA replication factor 1, origin recognition complex subunit 1, p21, p27 and phosphorylated IκBα. The results of the present study support the clinical use of combined neddylation inhibitor and cisplatin treatment, which may improve the survival of, and impart other benefits for patients with pancreatic cancer.

Dissociated brain organization for two-digit addition and subtraction: an fMRI investigation.

The present study compared the patterns of brain activation elicited by two-digit addition and subtraction problems. Thirty-two Chinese undergraduates of the same educational background and of similar age were asked to assess whether arithmetic operations were true or false during functional magnetic resonance imaging. Results showed that both complex addition and subtraction were supported by the broad neural system that involved regions within the inferior parietal lobule, the precuneus, and the inferior occipital gyrus, as well as some subcortical structures. Nevertheless, complex problems involving addition elicited more activation mainly in the bilateral medial frontal gyrus, whereas problems involving subtraction had more activation in the precentral gyrus and the thalamus in the right hemisphere, as well as the inferior parietal lobule in the left hemisphere. This pattern of dissociated activation suggests that partially separate neuronal networks might support these different operations. It also suggests that complex addition has a greater reliance on the fronto-parietal cortical circuit and subtraction on the parieto-subcortical circuit.