Zhejiang Center for Disease Control and Prevention

Intestinal aging characterized by imbalance between cell senescence and mucosal self-renewal, increases susceptibility to the elderly-onset ulcerative colitis (UC), while the underlying mechanisms remain elusive. Here, we identify mRNA N4-acetylcytidine (ac4C) modification and its specific writer, N-acetyltransferase 10 (NAT10), as critical regulators of human colonic epithelial cell senescence. Knockdown of NAT10 significantly alleviates human colonic epithelial cell senescence in vitro and colonoid and intestinal aging in vivo in aged mice. Using ac4C-modified transcriptome sequencing, we reveal that NAT10 stabilizes DYRK1A mRNA through ac4C modification, thereby driving colon epithelial senescence. Moreover, NAT10 and DYRK1A are markedly upregulated in ulcerative colitis tissues from elderly patients and positively correlate with disease severity. Knockdown of NAT10, treatment with Nat10 or Dyrk1a inhibitor, alleviates colitis in aged mice. Collectively, these findings suggest that modulating NAT10-mediated RNA ac4C modification could rejuvenate intestinal aging and provide a novel therapeutic strategy for elderly-onset colitis.

Refractory wounds are complicated multistep biological processes that can lead to severe complications in patients. Selective autophagy plays a crucial role in precisely controlling the quality of intracellular components and regulating biological behavior. This review explores the features and underlying mechanisms of various types of selective autophagy and highlights their implications in burn injury and wound healing. In-depth studies have underscored the critical role of selective autophagy, including mitophagy, endoplasmic reticulum (ER)-phagy, pexophagy, xenophagy, lysophagy, ferritinophagy, and lipophagy, in effectively controlling the quality of intracellular components and regulating biological behavior, which may enhance wound-healing process. Autophagy is a housekeeping and self-renewal process that utilizes lysosomal machinery to degrade and recycle cellular components, thereby enhancing cellular adaptability to stressful conditions. In addition to nonselective bulk degradation, autophagy selectively recycles specific cell constituents, including mitochondria, ER, peroxisomes, pathogens, lysosomes, lipid droplets, and ferritin. The effective management of the quality of cellular components during wound healing remains a challenge in clinical practice. Understanding the basic mechanisms and intricate crosstalk underlying selective autophagy may facilitate the development of comprehensive strategies and therapeutic targets for wound healing.

Severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has emerged as a significant global public health threat. Infected patients may present with gastrointestinal, neurological, and cardiovascular ribavirin and favipiravir are currently used in clinical practice, their efficacy remains controversial, and treatment primarily relies on symptomatic and supportive care. To date, there is no standard treatment regimen for SFTSV infection, nor are there any approved vaccines. However, recent advances in SFTSV research and the application of novel technologies have opened new pathways for the development of antiviral drugs and vaccines. This review summarizes the latest progress in the development of therapeutic agents and vaccines against SFTSV, aiming to provide valuable insights for drug development and countermeasure strategies for SFTS.

Preeclampsia (PE) is closely associated with alterationsin placental extracellular vesicles (pEVs), but the mechanisms and their role in PE pathogenesis remain unclear. This study reveals that nicotinamide (NAM) levels in PE-derived pEVs (PE-EVs) are lower than in pEVs from normal pregnancies, correlating with disease severity. Functionally, NAM in pEVs inhibits Th1 differentiation via SIRT1 suppression and Th17 differentiation via macrophages. NAM-deficient pEVs exhibit reduced capacity to inhibit Th1 and Th17 cell differentiation both in vitro and in vivo, leading to PE-like symptoms. NAM is enriched in pEVs compared to placental villous tissue and maternal serum. The lower NAM in PE-EVs is due to decreased hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) expression in trophoblasts, which loads NAM into the cargo of multivesicular bodies (MVBs) via binding to the tryptophan-115 residue of HRS. Furthermore, the reduction of HRS in PE trophoblasts results from ubiquitination and degradation by elevated HSP27. Collectively, these findings indicate that elevated HSP27 in PE trophoblasts leads to the degradation of HRS, a reduction in pEV NAM levels, and diminished Th1 and Th17 inhibitory effects, thereby contributing to the development of PE.

Objectives This study aimed to investigate the effects of meteorological factors on mosquito density by using a generalized additive model (GAM), and provide a scientific basis for the surveillance and early warnings of mosquito-borne diseases in Zhejiang Province. Methods Data on adult mosquito and larvae density were collected through ecological surveys conducted across Zhejiang Province, China, from 2017 to 2023. Meteorological data were obtained from the National Tibetan Plateau Data Center. The Kruskal-Wallis H-test and Chi-square test were used for the descriptive analysis of mosquito distribution characteristics, and Spearman rank correlation was used for the correlation of density indices. GAMs were developed to analyze the influence of meteorological factors on mosquito density. A value of p < 0.05 was considered statistically significant. Results The average adult mosquito density was 10.16 per light night from 2017 to 2023 in Zhejiang Province, which exhibited a unimodal curve, peaking at 21.76 per light night in July. The average Breteau Index (BI) was 12.45. GAMs revealed that adult mosquito density and BI with or without a time lag were positively correlated with average air pressure, average monthly relative humidity, monthly sunshine hours, and average monthly temperature (all p < 0.05). Adult mosquito density and BI increased sharply below 17 °C, plateaued from 17 °C to 23 °C, and declined above 23 °C. Adult mosquito density and BI were both increased with rising humidity, and increased with monthly sunshine up to 220 h, then declined slightly above 220 h. Adult mosquito density increased with the growth of air pressure, while BI was highest when the air pressure was 970 hPa. The monthly precipitation had no contemporaneous effect on adult mosquito density or BI, yet it exerted a lagged effect on BI. Conclusion Certain meteorological factors significantly influenced both adult mosquito density and the larvae density, with or without a time lag. It is crucial to incorporate the impact of meteorological factors into the ongoing processes of mosquito control, monitoring, and early warning systems.

On the basis of 2017 dengue fever outbreak data from Shangcheng District, this study developed a dynamic transmission model to analyze the epidemiological characteristics of dengue fever at a district scale, quantitatively evaluated the effectiveness of different intervention measures, and provided evidence-based support for optimizing outbreak control strategies. The outbreak data were obtained from the China Information Network System of Disease Prevention and Control. Some transmission parameters were initially estimated via Berkeley Madonna 8.3.18 software. An SEIAR epidemic model incorporating host-vector bidirectional transmission dynamics was established to evaluate the effectiveness of case isolation, health education, and vector control. With no intervention, the outbreak would last 225 days, resulting in 8420 cumulative cases, which were both significantly higher than the actual outbreak data (CC = 278 cases, DO = 79 days). Case isolation was the least effective intervention for epidemic control, reducing the cumulative number of cases by only about 71% compared to the estimated incidence without intervention. Vector control was the most effective single intervention. Even a 5% daily vector density reduction intervention could reduce cumulative cases by about 97% and shorten the outbreak duration to 87 days. Increasing the coverage rate and the behavior formation rate of health education could also effectively reduce the number of cumulative cases and shorten the duration of an outbreak. The combined strategy of low-frequency mosquito control (every 3 days) and health education (60% coverage, 50% behavior adoption) and 100% case isolation performed only slightly worse than sustained low-intensity mosquito control alone. However, they were both relatively close to the actual prevention and control effectiveness observed in 2017. For dengue control in high-density urban areas, we suggested a three-tiered synergistic prevention system: a foundation tier of strict case isolation coupled with intelligent monitoring and early-warning systems; a core tier of sustained high-intensity mosquito control to rapidly suppress vector density during the early epidemic stage; and an optimization tier integrated pulsed mosquito control, health education, and case isolation, thereby addressing the limitations of single interventions and minimizing costs.

Abstract The role of the cAMP/PKA pathway in antiviral innate immunity, including during coronavirus infections, remains unclear. We discovered coronavirus N proteins initiate cAMP-ADCY10-PKA cascade. Cytoplasmic PKA activates STAT1 independently of canonical JAK/TYR2 signaling. Coronavirus N proteins, via a conserved arginine (e.g., PEDV R58, SARS-CoV-2 R92), directly bind and sequester PKA Cα into the nucleus to evade STAT1 activation. Using PEDV as a model, mutant viruses with N mutNLS and N R58A were generated. Wildtype PEDV infection suppressed STAT1 activation in cells expressing PKA Cα/PKA Cα S339A deficient in STAT1 phosphorylation. However, in rXS0101 mutNLS - or rXS0101 R58A -infected cells, only PKA Cα S339A expression inhibited STAT1 activation. Downregulation of STAT1 activation is accompanied with increased viral replication. This study first elaborates that PKA Cα activates STAT1 in the cytoplasm of infected cells distinctly from canonical JAK/STAT1 signaling, while coronaviruses evade this antiviral response by sequestering PKA Cα into the nucleus via direct N protein interaction.