Self-delivery nanodrug to manipulate tumor microenvironment for boosting photodynamic cancer immunotherapy.

Immunotherapy has captured attention for its high clinical efficacy. However, its efficacy is limited by inadequate immune activation. Therefore, a platform to activate the immune system and amplify the host's immune response against tumors is urgently needed. Herein, a self-delivery photodynamic nanodrug (VAC@HSA) is reported as inducing immunogenic cell death (ICD), promoting the recruitment of dendritic cells (DCs), and normalizing tumor blood vessels. Firstly, verteporfin with laser assistance releases tumor-associated antigen to induce ICD, while celecoxib downregulates prostaglandin E2 and releases CCL5 to activate DC recruitment. Moreover, vasculature is normalized through axitinib, which contributes to reducing tumor hypoxia and reversing the immunosuppressive effects of vascular endothelial growth factor. This joint action promotes the infiltration of immune effector cells into the tumor. Therefore, the amplified photodynamic nanodrug with excellent biocompatibility effectively inhibits tumor growth and lung metastasis and produces a cascade of immune responses. Our study demonstrates a practically innovative strategy for activating cancer immunotherapy, which can alter the "cold" properties of tumors.

Gender Impacted Gut Microbiota and Growth Performance in the Blotched Snakehead (Channa maculata).

The blotched snakehead Channa maculata is an important economical freshwater species in East Asia. However, there has been relatively little research conducted on the correlation between gender and gut microbes. In this study, 36 of 1000 blotched snakeheads were randomly selected for growth performance measurement and gut microbiota high-throughput sequencing. Results showed that microbial diversity, composition, and metabolic functions were altered by gender and growth performance except the microbial network. In our study, Proteobacteria were the most abundant phylum, with Fusobacteria showing enrichment in males and Bacteroidetes in females. Notably, phylum Deinococcus-Thermus was identified as a significant biomarker. The Cetobacterium was the most abundant genus-level taxon. Furthermore, gut microbes specializing in the production of gut-healthy substances, such as coenzymes and vitamins, were identified as biomarkers in the fast-growing group. Our investigation highlighted the impact of gender on the composition and abundance of gut microbial biomarkers in both males and females, thereby influencing differential growth performance through the modulation of specific metabolic functions.

Incidence of community-acquired pneumonia among children under 5 years in Suzhou, China: a hospital-based cohort study.

OBJECTIVES: To depict the seasonality and age variations of community-acquired pneumonia (CAP) incidence in the context of the COVID-19 impact. DESIGN: Retrospective cohort study. PARTICIPANTS: The observational cohort study was conducted at Soochow University Affiliated Children's Hospital from January 2017 to June 2021 and involved 132 797 children born in 2017 or 2018. They were followed and identified CAP episodes by screening on the Health Information Systems of outpatients and inpatients in the same hospital. OUTCOME: The CAP episodes were defined when the diagnoses coded as J09-J18 or J20-J22. The incidence of CAP was estimated stratified by age, sex, birth year, health status group, season and month, and the rate ratio was calculated and adjusted by a quasi-Poisson regression model. Stratified analysis of incidence of CAP by birth month was conducted to understand the age and seasonal variation. RESULTS: The overall incidence of CAP among children aged ≤5 years was 130.08 per 1000 person years. Children aged ≤24 months have a higher CAP incidence than those aged >24 months (176.84 vs 72.04 per 1000 person years, p<0.001). The CAP incidence increased from October, peaked at December and January and the highest CAP incidence was observed in winter (206.7 per 1000 person years, 95% CI 204.12 to 209.28). A substantial decline of CAP incidence was observed during the COVID-19 lockdown from February to August 2020, and began to rise again when the communities reopened. CONCLUSIONS: The burden of CAP among children is considerable. The incidence of CAP among children ≤5 years varied by age and season and decreased during COVID-19 lockdown.

The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis.

BACKGROUND: Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden. METHODS: The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I2 , Egger's and Begg's tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data. RESULTS: A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%-11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%-7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae ( S. pneumoniae ), with a positive rate of 33.52% (95% CI: 26.55%-41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533-12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901-6,277,862) cases of OM were caused by S. pneumoniae . CONCLUSIONS: The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.

Disease Burden of Meningitis Caused by Streptococcus pneumoniae Among Under-Fives in China: A Systematic Review and Meta-analysis.

INTRODUCTION: Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. METHODS: A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. RESULTS: A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. CONCLUSIONS: Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.

Drug Self-Delivery Nanocubes Enhance O2 -Economized Photodynamic-Immunotherapy of Triple-Negative Breast Cancer by Downregulating Wnt/ß-catenin Signaling.

Although the combination of chemotherapy and immune checkpoint inhibitors (ICIs) can treat triple-negative breast cancer (TNBC), the severe effects of chemotherapy on immune cells significantly reduce the efficacy of the ICIs. Photodynamic therapy (PDT) with high selectivity is an alternative to chemotherapy that can also effectively treat hypoxic TNBC. However, high levels of immunosuppressive cells, and low infiltration of cytotoxic T lymphocytes (CTLs) limit the efficacy of PDT combined with ICIs. This study aims to evaluate the role of drug self-delivery nanocubes (ATO/PpIX-SMN) combined with anti-PD-L1 in TNBC treatment. Anti-malarial atovaquone (ATO) enhances protoporphyrin IX (PpIX)-mediated PDT-induced immunogenic cell death and downregulates tumor Wnt/ß-catenin signaling. Furthermore, the nanocubes combined with anti-PD-L1, which synergistically induce maturation of dendritic cells, promote infiltration of CTLs, reduce regulatory T cells, and significantly activate the host immune system, thus treating primary and distal tumors. This work demonstrates that ATO/PpIX-SMN can enhance the response rate of anti-PD-L1 in TNBC treatment via O2 -economized photodynamic-downregulating Wnt/ß-catenin signaling.

Antibacterial activity of positively charged carbon quantum dots without detectable resistance for wound healing with mixed bacteria infection.

Widespread bacterial infection and the spread of antibiotic resistance exhibit increasing threat to the public and thus require new antibacterial strategies. Carbon quantum dots (CQDs) have been extensively investigated to play fluorescent, catalytic roles and even potential biomedical functions containing sterilization. However, synthetic understanding of the interaction of CQDs and bacteria, the exhibition of antibacterial ability, and the risk of resistance evolution remain lacking. Herein, a simple one-pot method was fabricated to prepare positively charged CQDs (PC-CQDs) as a broad-spectrum antibacterial agent. PC-CQDs possessed effective antibacterial activity against all tested Gram-positive, Gram-negative, and drug-resistant bacteria. Investigation of the antibacterial mechanism of PC-CQDs indicated that small-sized PC-CQDs functionalized with -NH2 and -NH induced strong adherence behavior on the bacterial cell membrane. Moreover, the entry of PC-CQDs caused conformational changes in the genes and generation of reactive oxygen species in the bacteria. Safety evaluation illustrated that PC-CQDs did not trigger detectable drug resistance or hemolysis. Furthermore, PC-CQDs effectively promoted the antibacterial treatment of mixed Staphylococcus aureus and Escherichia coli infected wound in rats with low in vivo toxicity. These results suggested that PC-CQDs are a potential antibacterial candidate for real wound healing applications in complex bacterial infections and even resistant bacteria-caused infections.