血小板生成素抑制TGFβ1诱导的肺成纤维细胞向肌成纤维细胞转化的研究

目的:探讨血小板生成素处理对TGFβ1介导的肺成纤维细胞向肌成纤维细胞转化的影响。方法:CCK8法测定血小板生成素及TGFβ1组合处理后细胞生长的抑制率,采用荧光实时定量PCR及免疫荧光染色分别检测不同处理组细胞αSMA、COL1A2基因及蛋白的表达水平,应用免疫荧光染色检测细胞增殖相关蛋白Ki-67的表达水平,应用荧光实时定量PCR检测HO-1基因的表达水平。结果:TGFβ1处理能够诱导肺成纤维细胞分化为肌成纤维细胞,细胞形态发生显著变化且增殖速度提高,肌成纤维细胞标志基因/蛋白αSMA及COL1A2的表达水平随诱导时间延长显著提高(P<0.01)。在TGFβ1处理同时添加血小板生成素(TPO),αSMA、COL1A2基因和蛋白的表达水平均显著下调(P<0.01)。此外,TPO显著抑制TGFβ1诱导的细胞增殖,且增殖相关蛋白Ki-67的表达水平较TGFβ1处理组显著降低(P<0.05)。此外,发现TGFβ1处理导致HO-1的表达水平下降,而添加TPO能够挽救该基因的表达水平(P<0.05)。结论:血小板生成素能够抑制TGFβ1诱导的肺成纤维细胞向肌成纤维细胞的转化,这一发现对肺纤维化的对症治疗具有潜在的应用价值。

New framework of low-carbon city development of China:Underground space based integrated energy systems

Cities play a vital role in social development,which contribute to more than 70%of global carbon emission.Low-carbon city construction and decarbonization of the energy sector are the critical strategies to cope with the increasingly serious climate change problems,and low-carbon technologies have attracted extensive attention.However,the potential of such technologies to reduce carbon emissions is constrained by various factors,such as space,operational environment,and safety concerns.As an essential territorial natural resource,underground space can provide large-scale and stable space support for existing low-carbon technologies.Integrating underground space and low-carbon technologies could be a promising approach towards carbon neutrality,and hence,warrants further exploration.First,a comprehensive review of the existing low-carbon technologies including the technical bottlenecks is presented.Second,the features of underground space and its low carbon potential are summarized.Moreover,a framework for the underground space based integrated energy system is proposed,including system configuration,operational mechanisms,and the resulting benefits.Finally,the research prospect and key challenges required to be settled are highlighted.

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive type of breast cancer.Immune checkpoint inhibitors(ICIs)have been widely used to treat various tumors and have changed the landscape of tumor management,but the data from real-world studies of ICIs for TNBC treatment remain limited.The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.Methods:The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army(PLA)General Hospital were collected.Treatment responses,outcomes and adverse events(AEs)were assessed.Results:Eighty-one patients were included in the study.The confirmed objective response rate(ORR)was 32.1%,and the disease control rate(DCR)was 64.2%.The median progression-free survival(PFS)was 4.2 months,and the median overall survival(OS)was 11.0 months.PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation;specifically,patients with higher TILs had longer PFS.Overall AEs were tolerable.Conclusions:ICIs are effective in the treatment of advanced TNBC,and the adverse reactions are tolerable.A panel of biomarkers including LDH,ALP,and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

Online demand peak shaving with machine-learned advice in digital twins

As the use of physical instruments grows,control algorithms are being increasingly deployed to enhance efficiency and reliability through digital twin technology.Demand load management is central to energy systems within digital twins,which significantly impacts operational costs.Peak demand loads can lead to substantial monthly utility expenses without proper management.AMPAMOD,a randomised online algorithm incorporating machine-learned insights is introduced to optimise battery operations and mitigate peak demand loads.AMPAMOD leverages limited-bit information from ma-chine learning models to inform its online decision-making process for cost-effective load management.We provide theoretical evidence demonstrating that AMPAMOD maintains minimal advice complexity,has a linear computational cost,and achieves a bounded competitive ratio.Extensive trace-driven experiments with real-world household data reveal that AMPAMOD successfully reduces peak loads by over 90%,outperforming other benchmarks by at least 50%.These experimental findings align with our theoretical assertions,showcasing the effectiveness of AMPAMOD.

Synergistic effect of additional anlotinib and immunotherapy as second‐line or later‐line treatment in pancreatic cancer:A retrospective cohort study

Background:Pancreatic ductal adenocarcinoma(PDAC)is in urgent need of a second‐line or later‐line treatment strategy.We aimed to analyze the efficacy and safety of additional anlotinib,specifically anlotinib in combination with immunotherapy,in patients with PDAC who have failed first‐line therapy.Methods:Patients with pathological diagnosis of PDAC were additionally treated with anlotinib,and some patients were treated with anti‐PD‐1 agents at the same time,which could be retrospectively analyzed.The efficacy and safety of additional anlotinib were evaluated.Results:A total of 23 patients were included.In patients treated with additional anlotinib,the overall median progression‐free survival(PFS)was 1.8 months and the median overall survival(OS)was 6.3 months,regardless of anti‐PD‐1 agents.Among patients receiving additional anlotinib in combination with anti‐PD‐1 agents,median PFS and OS were 1.8 and 6.5 months,respectively.Adverse events(AEs)were observed in 16 patients(69.6%).In patients treated with additional anlotinib,the majority of AEs were grade 1–3.Univariate analysis revealed that patients with baseline red blood cell distribution width(RDW)<14%treated with additional anlotinib plus anti‐PD‐1 agents had significantly longer OS than patients with baseline RDW≥14%(p=0.025).Patients with additional anlotinib plus anti‐PD‐1 agents as second‐line therapy had a longer OS than those treated as later‐line therapy(p=0.012).Multivariate analysis showed that baseline RDW was the only independent risk factor for OS(p=0.042).Conclusion:The combination of anlotinib and immunotherapy represents an effective add‐on therapy with tolerable AEs as second‐or later‐line therapy in patients with PDAC,particularly in patients with baseline RDW<14%.