Search

Abstract Background Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)‐driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen‐like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS‐mutated cancer. Methods The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes‐associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A‐directed transcriptional program. Results Upregulation of FGL1 expression in KRAS‐mutated cancer was inversely correlated with the infiltration of CD8+ T cells. Mechanistically, KRAS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A‐mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap‐induced transcription of FGL1 and immune evasion in KRAS‐driven LUAD. Notably, dual blockade of programmed cell death‐1 (PD‐1) and FGL1 further increased the therapeutic efficacy of anti‐PD‐1 immunotherapy in LUAD patients. Conclusion FGL1 could be used as a diagnostic biomarker of KRAS‐mutated lung cancer, and targeting the Yap‐FGL1 axis could increase the efficacy of anti‐PD‐1 immunotherapy.

Evaluation of ecological asset quality is a prerequisite for resource management and ecological protection, and objective, timely, and quantitative assessment of ecological asset quality is of great significance for ecological construction and sustainable development strategies. In this study, we synthesized soil, topography, and perpendicular indicators, based on Sen + MK trend analysis, Hurst index analysis, and Pearson correlation analysis methods, combined with climate and socio-economic data, and took the municipal scale of Agro-pastoral Ecotone of China as the study unit to quantitatively assess the spatial and temporal changes of ecological asset quality in the study area from 2000 to 2020, and to identify the influencing factors that generate spatial heterogeneity. The results show that: (1) The overall ecological asset quality of the zone was between 0.35 and 0.5 from 2000 to 2020, which was located at a medium grade and accounted for 47.08 % of the total area. The spatial heterogeneity was obvious, showing a distribution pattern of high in the northeast-southwest and low in the middle, and it was mainly concentrated in the high-elevation zone of 2968–6702 m and the low-elevation zone of −3–785 m. The distribution pattern of the ecological assets was also obvious, showing a distribution pattern of high in the northeast and low in the middle. (2) The effects of altitude and latitude/longitude on the quality of ecological assets in the study area were mainly characterized by a decreasing trend in the quality of ecological assets with decreasing altitude from west to east, and a decreasing and then increasing trend in the quality of ecological assets with increasing altitude from south to north. (3) The quality of ecological assets has a complex correlation with climate and socio-economic factors, among which, temperature and precipitation are significantly positively correlated in the middle altitude (785–2968 m) and low altitude northwest; socio-economic factors are significantly positively correlated with large and medium-sized agricultural tractors, agricultural, forestry, animal husbandry and fishery population and rural population in the high altitude area, significantly positively correlated with GDP of the primary industry in the middle altitude area, and significantly positively correlated with agricultural population and animal husbandry and fishery population in the low altitude area. (4) The construction of a comprehensive assessment system that introduces soil and terrain indices mainly shows an increase in the proportion of medium and low grades of ecological asset quality and a decrease in the proportion of excellent, good, and poor grades, compared with the quality of ecological assets using only the perpendicular index as the assessment system. This study reveals the relationship between the spatial distribution characteristics of ecological asset quality and climatic-socio-economic factors in Agro-pastoral Ecotone of China and further reflects the quality of regional ecological assets objectively by introducing more comprehensive assessment indicators. The results of the study not only provide a scientific basis for the effective monitoring and improvement of the quality of regional ecological assets, but also provide theoretical support for the formulation of relevant ecological environmental protection policies, as well as data support and decision-making reference for future ecological management and sustainable development strategies.

Seasonal influenza remains a significant public health concern globally, with annual vaccinations as the most effectively preventive measure. This study examines influenza vaccination coverage rates across different age groups in Pudong New Area, Shanghai, China, from 2013 to 2023. This study extracted influenza vaccination data from the Shanghai Immunization Planning Information System (SIPIS) of the Center for Disease Control and Prevention Shanghai’s Pudong New Area from 2013 to 2023. The analysis utilized weighted linear regression to compare vaccination rates over the study period. From 2013 to 2023, a cumulative total of 1,421,295 influenza vaccinations were administered in Pudong New Area, with the quadrivalent inactivated influenza vaccines (IIV4) and trivalent inactivated influenza vaccines (IIV3) comprising 56.8% and 42.9%, respectively. The overall average influenza vaccine coverage rate was 2.27% (95% CI: 2.26, 2.28). The 0–4 years group exhibited the highest average annual coverage rate of 22.52% (95% CI: 22.47, 22.57) among different age groups, in stark contrast to that of the 20–24 years age group, which had the lowest at 0.32% (95% CI: 0.31, 0.33). In terms of repeat vaccinations, a significant majority (86.87%) of recipients received only 1–2 doses, while just 13.13% received 3 or more doses. Although influenza vaccination coverage among preschool children in Pudong New Area is relatively high, it falls significantly short of WHO recommendations. Enhance the level of awareness of influenza vaccine among adults and provide a free influenza vaccination strategy for specific groups such as doctors, which is helpful to increase influenza vaccination rates among populations.

The aim of this study was to investigate the level of inactivated A71 (EV-A71) vaccination in Pudong New Area of Shanghai and its effects on the epidemiology and pathogen spectrum of hand–foot–mouth disease (HFMD) in this area, as well as to provide a basis for improving the prevention and control strategy of HFMD in this area. Data were collected from the “Comprehensive Management Cloud Platform for Immunization Program” system from December 2016 to December 2022. The data on HFMD cases from January 2012 to December 2022 were extracted from the “China Information System for Disease Control and Prevention”. A total of 484,056 doses were administered. The vaccination rate of the first dose was 14.03%, and the full vaccination rate was 13.33%. There were significant differences between the first dose and the full vaccination rate in different years (χ2 = 46,538.831, p < 0.001, χ2 = 50,013.946, p < 0.001). A total of 91625 cases of HFMD were reported, including 58 severe cases, and no deaths. Before and after the administration of the inactivated EV-A71 vaccine, there were statistical differences in the distribution of HFMD cases in terms of gender, household registration, occupation, and age (p < 0.001). The etiological surveillance results showed that the rate of enterovirus positivity was 84.15%, with 9.85% being EV-A71, 23.74% CV-A16, and 50.56% non-EV-A71 and non-CV-A16. The coverage rate of the inactivated EV-A71 vaccine in Pudong New Area was not high, and the incidence of HFMD showed a downward trend after the postmarketing of the vaccine. The majority of HFMD infections were non-EV-A71 and non-CV-A16, with CV-A6 accounting for the highest proportion. It is recommended to accelerate the development of combined vaccines to provide more antibody protection.

ObjectiveTo examine vaccination status of recombinant coronavirus disease 2019 (COVID-19) vaccine (adenovirus type 5 vector) (Ad5-nCoV) and to evaluate the safety of Ad5-nCoV vaccination in Pudong New Area of Shanghai during a period of COVID-19 epidemic for providing evidence to Ad5-nCoV mass vaccination. MethodsThe data on Ad5-nCoV mass vaccination and on reported adverse events following immunization (AEFI) related to the vaccination in Pudong New Area of Shanghai from May 2021 through February 2022 were extracted from Shanghai Municipal Vaccination Registry Information System and from China Information System for Disease Control and Prevention. Descriptive statistics was performed on the data collected. ResultsDuring the 10-month period in the district, totally 246 913 doses of Ad5-nCoV were administrated and 198 AEFI were registered, with a reported AEFI incidence rate of 80.190/100 000 doses. Of all the reported AEFI, 151 (76.26%) were common adverse reactions, followed by 36 (18.18%) of coincidental events and 9 (4.55%) of psychogenic reactions, and only 2 (1.01%) rare adverse reactions were reported. The reported AEFI incidence rate was the lowest among the vaccinees aged 50 – 92 years. Higher reported AEFI rate was observed among the female vaccinees than that among the male vaccinees (112.29 vs. 66.47 per 100 000 doses) and the reported AEFI rate was higher in the vaccinees having the first dose Ad5-nCoV than that in those having the booster dose (89.03 vs. 25.10 per 100 000 doses). Almost all (93.94% , n =186) of the reported AEFI occurred during the day of the vaccination. ConclusionThe reported incidence of Ad5-nCoV-related AEFI was higher than that of inactivated COVID-19 vaccine but lower than that of influenza vaccine in the mass vaccination during a COVID-19 epidemic in a district of Shanghai city, suggesting that the AEFI incidence of recombinant novel coronavirus vaccination was within the safety range.

Alzheimer’s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid–donepezil–rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC50 values of 0.91 μM and 0.57 μM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aβ1–42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aβ1–40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu2+-induced Aβ1–42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.