Science China Life Sciences最新文献

While FDA-approved liposomal drugs (e.g., Doxil®) have demonstrated improved toxicity profiles and targeted delivery, emerging evidence reveals paradoxical pro-angiogenic and immunosuppressive effects that compromise therapeutic outcomes. This review examines the critical yet underappreciated role of complement system activation in mediating these adverse effects. We present a comprehensive analysis of the dynamic interactions between liposomal formulations, complement proteins, and the tumor microenvironment. By elucidating these mechanisms, we identify key challenges and opportunities for optimizing nanocarrier design. Our synthesis provides a framework for developing next-generation liposomal therapeutics with enhanced efficacy and reduced immunogenic potential, offering important insights for translational cancer nanomedicine.

Cotton (Gossypium hirsutum), serving as a critical raw material for textile manufacturing, is highly vulnerable to drought stress during its growth cycle. Water deficit conditions directly impair boll development and ultimately reduce lint yield. As a crucial unsaturated fatty acid, linolenic acid (C18:3) plays a pivotal role in plant growth and drought response. However, the specific role of C18:3 in drought tolerance and the underlying regulatory network remain largely unelucidated. In this study, drought treatment significantly reduced C18:3 content in cotton leaves, while exogenous application of C18:3 enhanced drought tolerance. Gene expression analysis indicated that the fatty acid desaturase GhFAD3-2 may be involved in the drought-induced reduction of C18:3 content. Overexpression of GhFAD3-2 improved drought tolerance in cotton, whereas silencing GhFAD3-2 decreased drought tolerance, potentially by regulating C18:3, jasmonic acid, and flavonoid metabolism. Further investigation revealed that GhDREB1B acted as an upstream transcriptional activator of GhFAD3-2, directly binding to the promoter of GhFAD3-2 to activate its transcription in response to drought stress in cotton. The expression of GhDREB1B was significantly suppressed under drought stress, and silencing GhDREB1B resulted in decreased GhFAD3-2 expression, reduced C18:3 content, and consequently diminished drought tolerance in cotton. In conclusion, this study elucidates the role of the GhDREB1B-GhFAD3-2 module in regulating C18:3 biosynthesis in response to drought stress in cotton, providing new insights into the molecular mechanisms of drought response and potential breeding targets for cotton.

The Indo-Pacific humpback dolphin (Sousa chinensis; hereafter IPH dolphin), a coastal cetacean species primarily distributed in Chinese waters, serves as a flagship species for marine ecosystem conservation. Currently, this species faces sustained population declines and habitat degradation, and is listed as "Vulnerable" on the IUCN Red List. Herein, we de novo assembled a high-quality chromosome-level genome for the IPH dolphin and conducted conservation genomic analyses using whole-genome resequencing data from 82 individuals across four major geographic populations in Chinese waters (northern Beibu Gulf (NBG), eastern Zhanjiang (EZJ), Pearl River Estuary (PRE), and Xiamen (XM)) and one population from the Gulf of Thailand (THA). Our findings reveal that the four Chinese populations form three genetic clusters, with PRE and XM merging into one. Historical fluctuations in the effective population size (N_e) of IPH dolphins correlate with sea-level changes, while recent declines and critically low N_e now characterize all four Chinese populations. Gene flow was detected between NBG and EZJ, and between EZJ and PRE, indicating high historical population connectivity. Alarmingly, all four Chinese populations exhibited extremely low genetic diversity and elevated inbreeding levels. Genes carrying loss-of-function mutations in IPH dolphins were enriched in pathways related to DNA repair and cellular responses to organonitrogen compounds, potentially increasing cancer susceptibility and impairing the responses to aquatic organic pollutants. In conclusion, given the extremely low N_e and limited genetic evolutionary potential of IPH dolphins in Chinese waters, coupled with unfavorable marine environmental conditions, urgent conservation measures are warranted.

The associations between short-term exposure to PM_2.5 constituents and diabetes remain inconsistent and understudied. We conducted a nationwide case-crossover study across 153 hospitals in Chinese mainland. Daily average concentrations of five major PM_2.5 constituents, including black carbon (BC), organic matter (OM), sulfate (SO₄^2-), nitrate (NO₃^-), and ammonium (NH₄⁺), were assessed by satellite-based models. We applied single-constituent analysis and inverse-probability-of-treatment weighting (IPTW) to assess each constituent's independent effect. In addition, we developed a weighted quantile sum (WQS) regression for paired data with multiple controls to examine the joint impacts of the constituents and quantify each one's contribution. The single-constituent analysis suggested that an interquartile range increase in each of the five constituents was significantly associated with elevated risk of T2DM hospitalization, the effects ranging from 1.49%-2.14%. After adjusting for other constituents using IPTW methods, only OM and SO₄^2- remained significant associations with T2DM. The WQS analysis further confirmed SO₄^2- and OM as the dominant contributors. Our findings highlight the importance of targeted air pollution control measures for T2DM prevention.

Circulating sphingolipids, composed of a sphingoid backbone, a fatty acid chain, and a polar head group, exert important physiological effects and are dysregulated in various metabolic disorders. Ceramides and sphingomyelins (SM) may contribute to elevated cardiovascular risk via pathways that are independent of traditional lipid metabolism, playing an important role in identifying residual risk. However, the impacts of specific types of ceramides and sphingomyelins on cardiovascular outcomes remain uncertain. In this review, we (i) summarize the latest advances in prospective evidence linking circulating ceramides and sphingomyelins to cardiovascular diseases (CVD), (ii) discuss improvements in predicting adverse cardiovascular outcomes using comprehensive risk scores based on ceramides, and (iii) further illustrate potential modifiable factors influencing ceramides and sphingomyelins levels, such as diet, physical activity, and air pollutants. In conclusion, circulating ceramides and sphingomyelins are valuable cardiovascular risk biomarkers, serving as key factors in both primary and secondary prevention by identifying the additional risk of CVD independent of conventional lipid biomarkers, with distinct roles among different types of ceramides and sphingomyelins. Further studies are urgently needed to elucidate the causal relationships between specific types of circulating ceramides or sphingomyelins and subtypes of CVD and their underlying biological mechanisms. To advance the practical application of ceramides and other sphingolipids in the prevention and treatment of CVD, large-scale studies are required to determine the extent to which modifiable factors reduce cardiovascular risk by regulating ceramide and sphingomyelin levels, and continued efforts should be focused on targeted interventions and clinical translation in sphingolipid metabolism.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis, primarily due to late-stage diagnosis. This study aimed to elucidate the metabolic alterations associated with the development and early progression of ESCC and to identify potential biomarkers for its early diagnosis. Using two independent cohorts comprising 245 individuals in total, with 161 individuals in cohort 1 (a cross-sectional cohort) and 84 LGIN patients in cohort 2 (a follow-up cohort) at baseline, untargeted metabolomic profiling of 329 serum samples revealed 1,431 metabolites. Significant dysregulation was observed in steroid hormone biosynthesis, primary bile acid biosynthesis, and glycine, serine, and threonine metabolism. Combining metabolomics and transcriptomics data, multi-omics integration identified key metabolites and genes driving these pathways, particularly in early tumorigenesis. Furthermore, 9 blood-based metabolites were identified as potential non-invasive biomarkers for early ESCC detection and achieved high predictive accuracy. The findings provide critical insights into the metabolic underpinnings of ESCC progression and underscore the value of blood-based metabolite biomarkers for early diagnosis.

Orthoflaviviruses are recognized as significant emerging mosquito-borne pathogens globally. Members of the Japanese encephalitis (JE) serogroup can be distinguished from other orthoflaviviruses by the presence of an additional non-structural protein (NS1'). However, the role of the NS1' protein in the virus's life cycle and transmission remains incompletely understood. This study demonstrates that the acquisition of the secretory NS1' protein from JE serogroup viruses by mosquitoes from infected hosts significantly suppresses the antiviral effect of the RNA interference pathway, thereby facilitating viral infection in mosquitoes. Furthermore, immunization of mice with the NS1' protein showed considerable efficacy in preventing the transmission of orthoflaviviruses from mice to mosquitoes. These findings indicate that targeting the NS1' protein may represent a promising strategy for controlling the spread of JE serogroup viruses and other orthoflaviviruses between vertebrate hosts and mosquitoes.