



To explore the inhibitory effect and molecular mechanism of diosmetin on the invasion and mi-gration of breast cancer cells, MCF7 and MDA-MB-231 cells were treated with different doses (5 mg/L, 10 mg/L, 20 mg/L) of diosmetin for 24 h, and then the changes in the invasion and migration abilities of breast cancer cells were detected using the Transwell assay and cell scratch healing assay. The effect of diosmetin on the expression of metastasis-related proteins was further determined by Western-blot. The Gene Expression Om-nibus (GEO) database was used to analyze differentially expressed genes in breast cancer tissues, and the HERB database was used to obtain the regulatory targets of diosmetin. The effect of diosmetin on the ex-pression of phosphatidylinositol 3-kinase, regulatory subunit 1 (PIK3R1) was confirmed by real-time fluores-cent quantitative PCR (qRT-PCR) and Western-blot experiments. Finally, actinomycin D was used to deter-mine the effect of diosmetin on the stability of PIK3R1 mRNA. The results showed that diosmetin signifi-cantly inhibited the invasion and migration ability of breast cancer cells in a dose-dependent manner (P<0.05). Furthermore, in a dose-dependent manner, diosmetin significantly increased the levels of E-cadherin and significantly decreased the levels of N-cadherin and matrix metallopeptidase 2 (MMP2). Additionally, PIK3R1 was both a differentially expressed gene in breast cancer and a target of diosmetin. Breast cancer patients with low levels of PIK3R1 had a worse disease-free survival (P<0.05). Treatment with diosmetin significantly up-regulated the levels of PIK3R1 mRNA and protein (P<0.05), and also significantly improved the stability of PIK3R1 mRNA. These results indicate that diosmetin can inhibit the invasion and migration of breast cancer cells, which may be achieved by increasing the stability of PIK3R1 mRNA.
E3 ubiquitin ligases, as core components of the ubiquitin-proteasome system, play crucial roles in maintaining intracellular protein homeostasis by mediating the ubiquitination of target proteins. In recent years, the abnormal regulatory mechanisms of E3 ubiquitin ligases in tumor initiation and progression have emerged as a research hotspot. However, the specific functions and regulatory mechanisms of E3 ubiquitin ligases with different structural types in tumors still need to be systematically elucidated. Therefore, under-standing the mechanisms of different types of E3 ubiquitin ligases in tumorigenesis has important theoretical and clinical significance for clarifying the molecular pathological mechanisms of cancers and developing novel targeted therapeutic strategies. This review first describes the classification and structural characteristics of E3 ubiquitin ligases, focusing on the domain composition and ubiquitin transfer mechanisms of the homolo-gous to E6AP carboxyl-terminus (HECT), really interesting new gene (RING), RING-between-RING (RBR), and U-box families. Next, the dual functions, targeted proteins, and related signaling pathways of several typical E3 ubiquitin ligases in four common high-incidence malignant tumors (lung cancer, liver cancer, co-lorectal cancer, and breast cancer) are extensively discussed, and the molecular mechanisms by which E3 ubi-quitin ligases regulate tumor progression and drug resistance are elucidated. Finally, the latest research progress and potential therapeutic strategies targeting E3 ubiquitin ligases in cancer treatment are summa-rized, and the challenges including the efficacy and safety risks of such strategies are discussed. Future ef-forts should further integrate multidisciplinary approaches, such as structural biology, high-throughput screen-ing, and artificial intelligence-assisted drug design, to promote the application of E3 ubiquitin ligases in cancer diagnosis and treatment, offering new prospects for improving the prognosis and therapeutic outcomes of cancer patients.
To analyze the immunophenotypic and functional characteristics of natural killer (NK) cells in the peripheral blood of patients with secondary bloodstream infection of Klebsiella pneumoniae liver abscess (KPLABSI), and to explore the role of NK cells in the immune response to infection as well as the impact of diabetes mellitus on NK cells, this study included 18 patients diagnosed with KPLABSI at Peking University Third Hospital during the period October 2022 to May 2024. Blood samples and clinical data were collected from the patients, and flow cytometry was used to detect the immunophenotypes and functional markers of NK cells. Blood samples from 10 healthy individuals collected during the same period served as controls. Correlations between NK cell indicators and laboratory test results were analyzed, and differences between KPLABSI patients with and without diabetes mellitus were compared. The results showed that KPLABSI pa-tients exhibited significant hyperinflammatory responses, liver parenchymal damage, and impaired liver syn-thetic function. Meanwhile, NK cells in these patients exhibited remarkable immunophenotypic and func-tional changes: CD158e expression was significantly lower than that in the healthy control group (P<0.000 1), and perforin (PFN) expression was significantly reduced in KPLABSI patients with diabetes mellitus compared with those without (P=0.023). Further correlation analysis revealed that NK cells are involved in the complex immune-metabolic interactions during the occurrence and development of KPLABSI. This study preliminarily suggests that NK cells play a crucial role in the anti-infective immunity among KPLABSI patients, and that hyperglycemia promotes the occurrence and progression of KPLABSI by affecting the expression level of PFN in NK cells.
To investigate the inhibitory effect of early intervention with curcumin (Cur)-loaded GelMA (Cur/GelMA) hydrogel on hypertrophic scarring, a 25 μmol/L Cur/GelMA hydrogel was prepared. Its internal structure and mean pore size were characterized by scanning electron microscope (SEM), and the release ki-netics of curcumin were evaluated by drug release assays. Biocompatibility of the Cur/GelMA hydrogel was assessed by CCK-8 assay and live/dead staining. Reverse transcription quantitative PCR (RT-qPCR) was employed to analyze the effects of Cur/GelMA on the gene expression of transforming growth factor-β1 (TGF-β1), Smad2, and Smad3 in hypertrophic scar fibroblasts (HSFBs). Then Cur/GelMA hydrogel was ap-plied to the hypertrophic scars for early intervention in an established rabbit ear scar model. Gross observa-tion and hematoxylin-eosin (HE) staining were performed at 7, 14, and 28 days after treatment to evaluate wound healing and scar formation, and immunofluorescence and immunohistochemical staining were con-ducted at 28 days to assess expression levels of platelet-endothelial cell adhesion molecule (CD31) and α-smooth muscle actin (α-SMA). The results showed that the prepared Cur/GelMA hydrogel exhibited a porous structure with appropriate pore size, an adequate sustained-release profile for curcumin, and good biocom-patibility. Cur/GelMA significantly reduced TGF-β1, Smad2, and Smad3 gene expression in HSFBs, markedly improved the color, texture, smoothness, and healing rate of regenerated skin in the rabbit ear scar model, inhibited fibroblast proliferation and excessive collagen deposition, and promoted relatively organized colla-gen fiber arrangement. Expression levels of CD31 and α-SMA were significantly decreased. In summary, early application of Cur/GelMA hydrogel effectively attenuates hypertrophic scar formation in rabbit ears, likely via inhibition of fibroblast hyperproliferation and neovascularization, as well as promotion of myofi-broblast apoptosis.
Glucolipid metabolic disorders (GLMD) refer to a group of diseases caused by glucose and/or lipid metabolism disturbances such as diabetes mellitus, hyperlipidemia, and obesity. These diseases interact with each other, have a large affected population, and pose a serious threat to human health. In addition, the pathogenesis of GLMD is complex, and current therapeutic approaches mainly focus on symptom control and disease progression delay, with a lack of effective early diagnostic methods and treatment strategies. Multiple studies have shown that hypoxia is involved in the occurrence and development of various GLMD. Based on a comprehensive review of domestic and international literature, this article provides an in-depth analysis of the relationship between hypoxia and GLMD, with the aim of better understanding the pathogenesis of diffe-rent types of GLMD and offering insights for disease prevention, therapy improvement, and new treatment de-velopment.
Fluorescence imaging is a common technique for investigating the subcellular localization of tar-get proteins and protein-protein interactions within the biomedical domain. However, the fluorescence imaging resolution of many cells is often suboptimal due to their thickness and volume. Expansion microscopy imaging technology represents a sophisticated solution to this problem, but the current protocol is characterized by operational complexity, limited stability, and necessity for relatively high concentrations of immunofluores-cence antibodies. Our previous studies found that Reniformin A, a compound isolated from Isodon excisoi-des, has a magnifying effect on tumor cells. In this study, a low-cost and easily operationally convenient method was explored to improve the resolution of fluorescence imaging. Firstly, the effects of the aqueous extract of I. excisoides on three tumor cell lines A549, MDA-MB-231, and HeLa were investigated across different concentrations and treatment durations. The results indicated that the aqueous extract of I. exci-soides induced a significant volumetric enlargement in A549 and MDA-MB-231 cells, effectively enhan-cing the fluorescence imaging resolution. The optimal treatment time and concentration were identified as 24 h and 8 mg/mL, respectively. Conversely, the extract showed no such effect on HeLa cells, suggesting its cell-specific mechanism of action. Secondly, morphological analysis of key organelles and the cytoskeleton was investigated after treatment with the aqueous extract. The results revealed that the extract did not influence the fundamental cytoskeletal structures (α-tubulin, F-actin) or the morphology and distribution characteristics of key organelles (lysosomes, mitochondria) in A549 and MDA-MB-231 cells. Thirdly, subcellular localization was performed with three proteins of known subcellular localization information (METTL6, SLC38A7 and MYH9) in A549 cells. The results showed that treatment with the aqueous extract did not alter the original localization characteristics of the three proteins and did not induce any nonspecific co-localization. Finally, using A549 cells as a model, immunofluorescence assays were conducted to preliminarily investigate the po-tential mechanism by which the aqueous extract enhances fluorescence imaging resolution in tumor cells. It is hypothesized that the extract may enhance integrin function, stabilize focal adhesions, and optimize focal adhesion dynamics, thereby providing improved structural support for increased cell volume. These results indicate that the aqueous extract at a high concentration (8 mg/mL) exerts an enlarging effect on certain tumor cells without affecting the morphology and distribution of the original cellular structure, thereby effectively improving the convenience and resolution of fluorescence imaging. The aqueous extract of I. excisoides has broad application potential in biomedical research.
Sepsis is a systemic inflammatory response syndrome caused by infection. It is often complicated by organ dysfunction, which is a major contributor to mortality of patients with severe infections. Heparin-binding protein (HBP), a multifunctional mediator derived from neutrophils, exhibits levels closely correlated with the severity of sepsis and has great potential as a biomarker for early diagnosis and prognosis of sepsis. Herein, after vector construction and prokaryotic expression, the purified recombinant HBP was used as an immunogen to immunize mice. Following this, four stable cell lines secreting anti-HBP monoclonal antibodies were selected through cell fusion technology. The properties of the antibodies were analyzed by indirect en-zyme-linked immunosorbent assay (ELISA). Finally, a colloidal gold immunochromatographic assay for HBP was established using mAb 11 as the labeling antibody and mAb 18 as the capture antibody. This study suc-cessfully generated monoclonal antibodies against HBP using the recombinant HBP, and preliminarily estab-lished a rapid detection method for HBP. This method is of significant importance in resource-limited areas or scenarios where rapid assessment of infection severity is required.
Through literature review and comparative studies of plant morphology, two newly recorded species of Brassicaceae in Xinjiang were identified: Didymophysa aucheri Boiss. and Bunias orientalis L.. Among them, D. aucheri is a newly recorded species for China, while Bunias represents a newly recorded genus for Xinjiang. Additionally, B. orientalis is classified as a quarantine weed. Herein, morphologies of the two newly recorded species are described, accompanied by color photographs and distribution information. Meanwhile, the biogeographic significance of their discovery, as well as the diversity and particularity of plants in their distribution area, are discussed. Suggestions for further investigation and protection are also proposed. The voucher specimens are deposited in the Herbarium of Grassland General Station of Xinjiang Uygur Auto-nomous Region (XJCYZZ).
Based on field survey, specimen identification and a review of published literature, nine species are documented as new records for Jiangsu Province, China: Dactyloctenium aegyptium (L.) Willd., Miscanthus lutarioriparius L.Liu ex Renvoize & S.L.Chen, Pilea peploides (Gaudich.) Hook. & Arn., Allium ramosum L., Oenanthe linearis Wall. ex DC., Ipomoea pes-caprae (L.) R. Br., Canavalia rosea (Sw.) DC., Xanthium chi-nense Mill., and Asystasia neesiana (Wall.) Nees. Among them, Dactyloctenium Willd. is a newly recorded genus from Jiangsu Province, and X. chinense Mill. is a new record of an alien naturalized plant in the province. All voucher specimens are deposited in the Herbarium of the Institute of Botany, Jiangsu Province and Chinese Academy of Sciences (NAS).
Under the strategic blueprint for building China into an agricultural powerhouse, biotechnology, as the core driver of modern agriculture, is generating an increasingly imperative demand for multidisci-plinary professionals. Owing to the swift emergence and continual iteration of knowledge in fields such as gene editing, synthetic biology, and artificial intelligence, urgent reform is necessitated for traditional talent cultivation models. This paper focuses on the educational reform practices of the biotechnology major at Hunan University, taking the curriculum development of the cellular signal transduction course as a starting point. It explores optimized implementation strategies for the talent cultivation system under the new agricul-tural science framework, aiming to cultivate interdisciplinary agricultural biotechnology professionals who possess innovative capabilities, practical skills, and a strong sense of national commitment.
The paper analyzes the common problems in the cultivation of life science graduate students in China, as well as the prominent issues faced by the discipline of life sciences at the Beijing Institute of Technology. It proposes a “Four-in-One” response strategy for cultivating outstanding biopharmaceutical pro-fessionals, which consists of demand-driven guidance, interdisciplinary innovation, cultural empowerment, and integration of industry and research. The main operational measures include: 1) Augment foundational theoretical knowledge through the curriculum, and harness interdisciplinary approaches to foster innovation; 2) Underscore the role of cultural empowerment in the cultivation process, and strengthen the integration of industry and research; 3) Conduct in-depth pedagogical research, and pursue bold reforms in teaching metho-dologies. This cultivation model has the sturdy theoretical foundation, with its four aspects designed for in-cremental progression and logical coherence. Furthermore, it demonstrates strong practicality and high poten-tial for broader application. It can not only enhance the innovative capability and sense of service among graduate students but also foster research awareness among undergraduates. The idea for culturing graduate students mentioned in this paper is valuable to refer to specialized talent cultivation in other majors or colleges.
