Zhejiang Entry-Exit Inspection and Quarantine Bureau

Global expansion of cyanobacterial harmful algal blooms, driven by anthropogenic nutrient loading and climate change, poses escalating threats to water security. While altered precipitation regimes are recognized as critical climate multipliers, their hierarchical controls on cyanobacterial harmful algal bloom dynamics remain poorly quantified, particularly in stratified reservoirs. Here, we integrate a 60-yr (1961-2020) trend analysis of rainfall extremes with 4 yr (2017-2020) of high-frequency monitoring of hydrology, nutrients, and phytoplankton through manual sampling and autonomous buoys in Lake Qiandaohu, a deep subtropical reservoir vital for drinking water in eastern China. Using Mann-Kendall trend analysis, random forest, and partial least squares path modeling, we elucidate the hierarchical mechanisms linking altered rainfall regimes to phytoplankton community shifts, with a focus on cyanobacterial harmful algal blooms. Our results reveal significant increases in both annual rainfall and rainstorm frequency over the past six decades, with peak events coinciding notably with early summer agricultural fertilization. Intensified early summer rainstorms triggered disproportionate phosphorus loading, significantly lowering N/P ratios and transiently suppressing cyanobacterial dominance. However, a critical approximately 20-d lag period followed these events, wherein rapid thermal stratification recovery, combined with persistent legacy nutrients, selectively favored cyanobacterial proliferation. Furthermore, subsequent continuous dry-hot spells amplified cyanobacterial dominance by enhancing water column stability and elevating temperatures. These findings reveal a paradoxical post-storm vulnerability window that facilitates bloom formation in climate-sensitive reservoirs. Given projected intensification of rainfall extremes under climate change, this study highlights the urgent need for integrated management strategies combining watershed nutrient control, meteorological forecasting, and adaptive reservoir operation to mitigate cyanobacterial harmful algal bloom risks.

Previous research has indicated that the exopolysaccharide galactosaminogalactan (GAG) from Aspergillus fumigatus plays a pivotal role in the pathogenesis of experimental invasive aspergillosis by promoting virulence. However, it remains unclear whether the exopolysaccharide is directly virulent to host cells. In this study, we established a co-incubation system using human THP-1-derived macrophages and GAG extracted from A. fumigatus ATCC 1022 to assess the capacity of GAG to induce necroptosis in THP-1 cells, as well as to elucidate the underlying mechanisms of this process. Our findings indicate that the proportion of N-acetylgalactosamine in the GAG fraction derived from strain ATCC 1022 was lower, while GAG demonstrated a significantly greater ability to induce the production of the pro-inflammatory cytokines TNF-α and IL-1β, which was accompanied by the induction of necroptosis. Western blotting analysis revealed a significant increase in the phosphorylation of RIP1, RIP3, and MLKL proteins in GAG-treated THP-1 cells, and RIP1-RIP3-MLKL signaling activation and GAG-induced caspase activity-independent cell death were effectively inhibited by the TNF-α receptor-1 (TNFR1) inhibitor R-7050, the neutralizing antibody against TNF-α or necroptosis inhibitor Necrostatin-1. It's worth noting that the expression of CLEC4E, the gene encoding the Mincle receptor in macrophages, was elevated in the co-incubation system, potentially enhancing TNF-α-mediated necroptotic cell death. In addition to the RIP1-RIP3-MLKL axis, BAX, cleaved PARP, and JNK were also activated following GAG treatment, warranting further investigation into their roles in the regulation of necroptosis. Our findings demonstrate that GAG produced by A. fumigatus conidia during germination triggers necroptotic cell death in human THP-1 cells via TNF-α-mediated RIP1-RIP3-MLKL signaling.

Gram-negative Burkholderia bacteria are known for causing diseases in humans, animals, and plants, and high intrinsic resistance to antibiotics. Phage therapy is a promising alternative to control multidrug-resistant bacterial pathogens. Here, we present an overview of Burkholderia phage characteristics, host specificity, genomic classification, and therapeutic potentials across medical, veterinary, and agricultural systems. We evaluate the efficacy and limitations of current phage candidates, the biological and environmental barriers of phage applications, and the phage cocktail strategy. We highlight the innovations on the development of targeted phage delivery systems and the transition from the exploration of clinical phage therapy to plant disease management, advocating integrated disease control strategies.

Introduction and Objective: An increasing number of individuals with normal weight are attempting weight loss through caloric restriction. However, most weight loss attempts are followed by weight regain, leading to weight cycling. Whether weight cycling poses metabolic risks, especially in normal-weight individuals, remains debated. This study aims to evaluate the effects of weight cycling on glucose and lipid metabolism in normal-weight mice using an animal model. Methods: C57BL/6J mice underwent a weight-cycling protocol for 24 weeks, consisting of a 3-week period of 60% CR followed by 3 weeks of ad libitum (AL) feeding, with this 6-week cycle repeated four times. Subsequently, the mice were fed a HFD ad libitum to assess the potential metabolic risks associated with weight cycling. Throughout the study, body weight, food intake, and fasting blood glucose levels were monitored regularly. Glucose metabolism was evaluated periodically using GTT and ITT., Western blot, qPCR,ELISA and biochemical assays were employed to assess fasting insulin levels, hepatic insulin resistance, hepatic inflammation, and hepatic and circulating lipid content. Results: In C57BL/6J mice, weight cycling led to impaired glucose tolerance in normal-weight mice, which was associated with downregulation of mRNA expression for glucose transporters and metabolic enzymes involved in glucose oxidative utilization. However, this impairment in glucose tolerance could be slowly compensated for over time, accompanied by the disappearance of related molecular phenotypes. When the weight-cycling mice were subsequently fed a high-fat diet, glucose tolerance was again impaired, with a significant increase in hepatic triglyceride content and a higher weight of epididymal white adipose tissue. Conclusion: In summary, our study underscore the potential metabolic risks associated with weight cycling and the potential hazards of weight loss in normal-weight individuals. Disclosure J. Lin: None. M. Ren: None. L. Yan: None. W. Wang: None. X. Hong: None.

Introduction and Objective: To assess metabolic profiles and medication prescription patterns in patients with diabetes in Guangdong province. Methods: Data of 1621 patients with diabetes in Guangdong province were collected from the China National Diabetic Chronic Complications Survey conducted between March 2018 and January 2020. Questionnaires for medical history and blood tests for metabolic indices were collected. Results: The patients characteristics included: males 47.6%, urban residents 51.1%, medium diabetes duration 6.5 years, average BMI 24.8 kg/m², and average HbA1c 7.1%. The prevalences of hypertension and dyslipidemia were 55.5% and 92.7%, respectively, with the corresponding awarenesses of 37.9% and 23.3%. 79.6% of the patients received diabetes medications, with 48.2% on monotherapy. Only 42.6% of the patients met the glycemic target. The status of the prescriptions of hypoglycemic agents were shown in Figure 1. 59.1% of the patients with hypertension and 8.7% of the patients with dyslipidemia were on medical treatments, with 16.7% and 7.1% of the patients met the targets of blood pressure and lipid profiles. Among all the patients, only 1.7% of the patients achieved all the targets of blood glucose, blood pressure and lipid profiles. Conclusion: The control rates of medical disorders in patients with diabetes in Guangdong were still very low. Promising strategies to improve this status should be implemented. Disclosure X. Chen: None. Y. Yang: None. W. Jiang: None. W. Xu: None. L. Zeng: None.

Introduction and Objective: Silent myocardial infarction (SMI) is a severe cardiovascular disease among patients with DM. Our previous study confirmed that concomitant cardiac autonomic neuropathy (CAN) was an independent predictor of the risk of SMI in patients with T2DM. However, whether CAN increases the risk of HF in T2DM patients with SMI is still unclear. Therefore, we aimed to assess the effect of CAN on prognosis of HF in T2DM patients with SMI. Methods: This is a hospital-based observational study. 1015 T2DM patients who were screened for CAN by Holter monitoring were investigated. Q-waves SMI was detected by ECG. Coronary artery stenosis was examined by multislice computed tomographic (MSCT) coronary angiograph. We conducted a follow-up of up to 180 days for patients who underwent MSCT to assess the incidence of hospitalization due to HF events. Results: A total of 14070 patients were screened. At last, we included 1015 patients with T2DM and 133 of them underwent MSCT. In these 133 T2DM patients, patients with CAN had a higher risk of occurring obstructive coronary artery disease (CAD) than those without CAN (66.7% vs. 33.3%, p<0.001). Besides, they were more likely to have multivessel stenosis (p=0.007) and the stenosis extent of all affected vessels was more serious in this group of patients. At 180 days of follow-up, a total of 27 (20.3%) patients with T2DM developed HF. Multivariate Cox proportional risk models showed that T2DM patients with SMI had significantly higher risk of HF (HR=6.26, 95%CI 2.53-15.51, p<0.001). Conclusion: In asymptomatic T2DM patients, the occurrence of SMI was independently associated with CAN and CAN increased the risk of HF among T2DM patients with SMI. Therefore, we should pay attention to the possibility of SMI in asymptomatic T2DM patients clinically and strengthen the follow-up on cardiac function. In particular, the monitoring should be intensified when patients have concurrent diabetic CAN. Disclosure Q. Luo: None. Y. Fu: None. L. Wu: None. B. Qin: None. X. Wang: None. Y. Chen: None. Y. Zhu: None.

Introduction and Objective: Triple-negative breast cancer (TNBC), an aggressive subtype lacking targeted therapies, exhibits compromised CD8+ cytotoxic T lymphocyte (CTL) infiltration, particularly in obese patients. While obesity exacerbates TNBC progression through metabolic dysregulation, the mechanisms linking obesity-driven free fatty acids (FFAs) to CTL exclusion remain unknown. Methods: We conducted survival analysis to compare the prognosis of obese and non-obese TNBC patients. In vitro experiments were performed to investigate the effects of FFAs on TNBC cell lines. Flow cytometry was used to analyze CD8+T cell infiltration. Additionally, gene expression profiling and signaling pathway analyses were carried out to elucidate the underlying molecular mechanisms. Results: Obese TNBC patients exhibited elevated serum FFAs, reduced intratumoral CD8+ T cells, and poor survival (HR = 4.13, p<0.05). Palmitate, the predominant circulating FFA in obesity, upregulated CPT1A in TNBC cells, driving fatty acid oxidation and acetyl-CoA accumulation. This metabolic shift suppressed STAT1 activation through promoting deacetylation and attenuating phosphorylation. Consequently, CPT1A knockdown or pharmacological inhibition restored STAT1 activity and chemokine secretion, enhancing CTL infiltration and suppressing tumor growth exclusively in obese mice. Clinically, TNBCs with high CPT1A expression showed dismal prognosis. Conclusion: Our study demonstrates that obesity-related FFAs promote the progression of TNBC by modulating the CPT1A-STAT1 signaling axis and reducing CD8+T cell infiltration. These findings provide novel insights into the complex interaction between obesity and TNBC and may offer potential therapeutic targets for improving the prognosis of TNBC patients. Disclosure L. Li: None. L. Yan: None.

Salt-tolerant and halophilic microorganisms are critical drivers of ecosystem stability and biogeochemical cycling in athalassohaline environments. Lake Barkol, a high-altitude inland saline lake, provides a valuable natural setting for investigating microbial community dynamics and adaptation mechanisms under extreme salinity. In this study, we employed high-throughput metagenomic sequencing to characterize the taxonomic composition, metabolic potential, and ecological functions of microbial communities in both water and sediment samples from Lake Barkol. We reconstructed 309 metagenome-assembled genomes (MAGs), comprising 279 bacterial and 30 archaeal genomes. Notably, approximately 97% of the MAGs could not be classified at the species level, indicating substantial taxonomic novelty in this ecosystem. Dominant bacterial phyla included Pseudomonadota, Bacteroidota, Desulfobacterota, Planctomycetota, and Verrucomicrobiota, while archaeal communities were primarily composed of Halobacteriota, Thermoplasmatota, and Nanoarchaeota. Metabolic reconstruction revealed the presence of diverse carbon fixation pathways, including the Calvin-Benson-Bassham (CBB) cycle, the Arnon-Buchanan reductive tricarboxylic acid (rTCA) cycle, and the Wood-Ljungdahl pathway. Autotrophic sulfur-oxidizing bacteria, alongside members of Cyanobacteria and Desulfobacterota, were implicated in primary production and carbon assimilation. Nitrogen metabolism was predominantly mediated by Gammaproteobacteria, with evidence for both nitrogen fixation and denitrification processes. Sulfur cycling was largely driven by Desulfobacterota and Pseudomonadota, contributing to sulfate reduction and sulfur oxidation pathways. Microbial communities exhibited distinct osmoadaptation strategies. The “salt-in” strategy was characterized by ion transport systems such as Trk/Ktr potassium uptake and Na+/H+ antiporters, enabling active intracellular ion homeostasis. In contrast, the “salt-out” strategy involved the biosynthesis and uptake of compatible solutes including ectoine, trehalose, and glycine betaine. These strategies were differentially enriched between water and sediment habitats, suggesting spatially distinct adaptive responses to local salinity gradients and nutrient regimes. Additionally, genes encoding microbial rhodopsins were widely distributed, suggesting that rhodopsin-based phototrophy may contribute to supplemental energy acquisition under osmotic stress conditions. The integration of functional and taxonomic data highlights the metabolic versatility and ecological roles of microbial taxa in sustaining biogeochemical processes under hypersaline conditions. Overall, this study reveals extensive taxonomic novelty and functional plasticity among microbial communities in Lake Barkol and underscores the influence of salinity in structuring microbial assemblages and metabolic pathways in athalassohaline ecosystems.