Jinan University

Atorvastatin (ATV), a commonly prescribed lipid-lowering drug, has been widely detected in various aquatic environments due to its large use and low degradation rate. Since the target gene inhibited by ATV is highly conserved in organisms, many studies have shown that ATV can interfere with lipid metabolism in aquatic non-target organisms. However, studies on mitochondria, energy metabolism, and developmental toxicity of ATV on non-target organisms are limited. In this study, Mugilogobius chulae embryos were exposed to ATV (0.5 and 50 µg/L) until 96 h post fertilization (hpf). The results confirmed that the environmental concentrations of ATV caused toxic effects including developmental malformations, pathological damage, hepatotoxicity, and oxidative stress in M. chulae larvae. Both transcriptomic and metabolomic analyses showed that ATV exposure interfered the normal processes of oxidative phosphorylation and TCA cycle, resulting in energy metabolic disorder. In addition, ATV exposure also damaged the mitochondrial structure of M. chulae larvae. Thus, M. chulae could regulate PI3K/AMPK/FoxO proteins to promote mitochondrial regeneration, support autophagy, and even initiate apoptosis to maintain metabolism homeostasis. Taken together, our findings suggested that mitochondrial dysfunction and metabolic disorder were involved in ATV-induced toxicity which may cause developmental malformations and abnormalities, providing novel insight into the toxic mechanisms of ATV.

The ubiquitous occurrence of organic UV stabilizers (OUVs) poses a potential threat to marine fish, but the metabolism of OUVs in the body remains a missing piece of the puzzle in their ecotoxicology. This study investigated the in vitro metabolism of six OUVs in the liver microsomes of an economically valuable marine fish (Lateolabrax japonicus). The depletion of the six OUVs follows first-order kinetics in the microsomes, with in vitro depletion rate constants (kdepl) ranging from 0.23 to 0.40/h. The intrinsic clearance (CLint) of 1H-benzotriazole (BT) was estimated to be 0.0026 μL/(min·mg·protein). The enzyme inhibition experiments and molecular docking results highlight the importance of cytochrome P450 enzyme (CYP) 3A4 in OUVs metabolism. Among the 4 metabolizable compounds, some metabolites from hydroxylation, methylation, acetylation and conjugation were tentatively identified. In addition, the in vitro transformation rates can more accurately predict the whole-body bioconcentration potential via an in vitro to in vivo extrapolation (IVIVE) model.

Longifolene (C15H24) is a tricyclic sesquiterpene widely utilized in the cosmetics and fragrances due to its versatile applications. Traditional extraction methods from plants suffer from low titer and lengthy production cycles, while chemical synthesis is hampered by the compound's complex structure, leading to high costs and insufficient market supply. This study aimed to develop a microbial cell factory for enhanced longifolene production. The strategy involved integrating longifolene synthase from Pinus sylvestris (PsTPS) into Yarrowia lipolytica and employing multiple metabolic engineering approaches. Initially, key genes in the mevalonate (MVA) pathway were overexpressed to enhance longifolene precursor availability for longifolene biosynthesis. Subsequently, protein engineering techniques were applied to optimize PsTPS (tPsTPS) for improved catalytic efficiency. Furthermore, co-expression of molecular chaperones was implemented to enhance the synthesis and secretion of PsTPS. The introduction of the isopentenol utilization pathway (IUP) further augmented the supply of C5 substrate. By optimizing the culture conditions, including a reduction in culture temperature, the efflux of longifolene was increased, and the dissolved oxygen levels were enhanced to promote the growth of the strain. These collective efforts resulted culminated in the engineered strain Z03 achieving a noteworthy production level of 34.67 mg/L of longifolene in shake flasks. This study not only demonstrates the feasibility of enhancing sesquiterpene production in Y. lipolytica but also highlights the potential of microbial platforms in meeting industrial demands for complex natural products.

A facile and efficient electrochemical strategy for reduction of various aryl alkenes/alkynes to aryl alkyl derivatives was achieved. The protocol was also suitable to dehalogenation of structural versatile aryl/alkyl halides. This strategy has good functional group compatibility to gain the desired products in good yields under mild reaction condition and air atmosphere with simple undivided electrolysis cell. The preliminary study of the reaction mechanism was carried out. Gram‐scale experiment exhibited the potential application of this method in practical synthesis.

Background Circulating linoleic acid (LA) levels have been reported to be associated with various metabolic outcomes. However, the role of LA and its interplay with gut microbiota in gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate the longitudinal association between circulating LA levels during pregnancy and the risk of GDM, and the potential role of gut microbiota. Methods A nested case–control study was conducted within the ongoing Tongji-Huaxi-Shuangliu Birth Cohort in Chengdu, China. Blood and fecal samples were collected during early and middle pregnancy from 807 participants. GDM was diagnosed in middle pregnancy using the International Association of Diabetes and Pregnancy Study Groups criteria. Plasma LA levels were measured using gas chromatography-mass spectrometry, and gut microbiota was analyzed through 16S rRNA gene sequencing and shotgun metagenomic sequencing. A two-sample Mendelian randomization study was conducted using data from the IEU OpenGWAS database and the FinnGen consortium. Results Elevated plasma LA levels were associated with a lower risk of GDM in both early (P for trend = 0.002) and middle pregnancy (P for trend = 0.02). Consistently, Mendelian randomization analysis revealed that each unit increase in LA was associated with a 16% reduction in GDM risk (odds ratio: 0.84, 95% confidence interval: 0.72, 0.95). In early pregnancy, higher plasma LA levels were correlated with higher adiponectin levels (P < 0.001) and lower levels of triglycerides (P < 0.001), HbA1c (P = 0.04), and C-peptide (P = 0.04). The LA-accociated microbiota mediated the relationship between LA and C-peptide (P = 0.01). Additionally, the inverse association between LA and GDM was modified by Bilophila (P for interaction = 0.03), with a stronger association observed in participants with lower Bilophila levels in early pregnancy. Metagenomic analyses further showed that the LA-associated pathway (D-galacturonate degradation I) and its key enzyme (EC 4.2.1.7) were associated with metabolic traits. Conclusions Our study provides evidence for an inverse causal association between plasma LA levels during pregnancy and GDM risk, which is both mediated and modified by gut microbiota.

Breast cancer (BRCA) is a complex disease influenced by the tumor microenvironment, where interactions between immune cells and cancer cells play a crucial role in tumor progression and response to therapy. Understanding the intricacies of these interactions requires detailed analysis at the single-cell level, enabling the identification of specific immune cell subpopulations and their functional roles within the tumor milieu. This study comprehensively analyzed immune cell subpopulations and macrophage subtypes in BRCA using single-cell RNA sequencing technology and various computational tools. Initially, Sc-Type software accurately identified and annotated immune cell subpopulations, followed by CNV analysis using infercnv software, revealing significant CNV variations in epithelial cells. Subsequently, macrophages were re-clustered into 5 clusters, and their biological significance and functional features were assessed. CellChat analysis elucidated potential interactions between macrophage subtypes and BRCA cells, primarily through SPP1-CD44 and LGALS9-CD44 signaling networks. Additionally, CytoTRACE and Monocle were employed to analyze cellular plasticity and differentiation trajectories of macrophage subtypes. Furthermore, efferocytosis-related gene set scoring, transcription factor analysis, and risk score development were conducted, followed by immune infiltration and tumor mutation burden analysis, revealing increased immune infiltration and higher TMB levels in the high-risk group. These findings offer crucial insights into the interaction mechanisms of immune cells and macrophage subtypes within the BRCA tumor microenvironment, aiding in the understanding of tumor progression and therapeutic interventions.

Introduction Cuproptosis has emerged as a potential therapeutic target for colorectal cancer (CRC). This study investigated the role of ferredoxin 1 (FDX1) in regulating cuproptosis under hypoxic conditions and explored the impact of autophagy on this process in CRC. Methods CRC patient samples and cell lines were used in this study. Cells were exposed to hypoxia and treated with Es-Cu (a copper supplement) and rapamycin, an autophagy inducer. FDX1 expression in clinical tissues was assessed in clinical tissues using qPCR and Western blot. The CCK8 assay, EdU staining, and Transwell assay were employed to evaluate the malignant behavior of tumor cells. Copper content and DLAT oligomerization were measured. A nude mouse xenograft model was used to explore the role of FDX1 under hypoxic conditions. Results Compared with adjacent normal tissues, elevated FDX1 expression was observed in CRC tissues. In vitro, hypoxia or Es-Cu treatment upregulated FDX1 expression in CRC cell lines, resulting in reduced cell proliferation and increased cellular damage. FDX1 overexpression under hypoxic conditions suppressed migration, invasion, and proliferation while promoting cellular damage and DLAT oligomerization. Rapamycin-induced autophagy reversed the inhibitory effects of FDX1 overexpression on CRC cells. In vivo, rapamycin treatment attenuated the tumor-suppressive effects of FDX1 overexpression in nude mouse xenograft models. Discussion This study demonstrated that hypoxia-induced autophagy inhibits FDX1-mediated cuproptosis, leading to resistance to copper-induced cell death in CRC cells. Targeting the autophagy pathway may provide a novel therapeutic strategy to overcome resistance to cuproptosis and improving CRC treatment outcomes.

Self‐assembled monolayers (SAMs) play a crucial role in high‐performance perovskite solar cells (PSCs). However, the incompatibility between the nonpolar head groups of SAMs and the polar perovskite precursor solutions leads to SAM assembly defects and wettability issues, consequently impacting device efficiency. Moreover, the uneven distribution of hydroxyl groups on the surface of conventional transparent conductive oxide substrates is detrimental to SAMs onto them. Here, a dual‐sided passivation strategy is reported based on a co‐adsorbed approach, in which (4‐(3,6‐dimethyl‐9H‐carbazole‐9‐yl)butyl)phosphonic acid (Me‐4PACz) is doped with phaclofen (PLF) self‐assembly on the NiOx substrate. By compensating for the unanchored sites of Me‐4PACz, the phosphonic acid groups in PLF adsorb onto the NiOx surface, enabling more uniform and ordered anchoring of SAMs as well as improved wettability for perovskite deposition. This leads to optimized surface morphology and enhanced interface contact. Additionally, the amino groups in PLF passivate the defects at the buried perovskite interface, suppressing non‐radiative recombination during charge transport. The champion PSC fabricated using this co‐adsorbed strategy achieves a high fill factor of 84.92%, a power conversion efficiency of 24.04%, and excellent long‐term stability under ISOS‐D‐1I and ISOS‐T‐1I protocols, maintaining over 85% of the initial efficiency after >1000 h under thermal cycling conditions.

Aging induces significant alterations in the immune system, with immunosenescence contributing to age‐related diseases. Peripheral blood mononuclear cells (PBMCs) offer a convenient and comprehensive snapshot of the body's immune status. In this study, we performed an integrated analysis of PBMCs using both bulk‐cell and single‐cell RNA‐seq data, spanning from children to frail elderlies, to investigate age‐related changes. We observed dynamic changes in the PBMC transcriptome during healthy aging, including dramatic shifts in inflammation, myeloid cells, and lymphocyte features during early life, followed by relative stability in later stages. Conversely, frail elderly individuals exhibited notable disruptions in peripheral immune cells, including an increased senescent phenotype in monocytes with elevated inflammatory cytokine expression, heightened effector activation in regulatory T cells, and functional impairment of cytotoxic lymphocytes. Overall, this study provides valuable insights into the complex dynamics of immunosenescence, elucidating the mechanisms driving abnormal inflammation and immunosuppression in frailty.

Intravenous injection of thrombolytic drugs is the prevailing strategy for the treatment of thrombotic disease. However, its applications are limited due to hemorrhagic risk and thrombus microenvironment. In pursuit of visualized thrombolysis and inspired by the excessive reactive oxygen species (ROS) and inflammatory factors within the thrombus site, an ultrasmall nanobubble (CeO2/MnOX@UK@PFP) for integration of imaging and therapy by low intensity pulse ultrasound (LIPUS) trigger is designed, which achieved the visual delivery of Urokinas (UK) and ROS scavenging agents to adjust thrombus microenvironment. In this study, CeO2/MnOX with ROS scavenging activity are prepared and wrapped with UK and perfluoropentane (PFP) by lipid layer, forming a CeO2/MnOX@UK@PFP. Under LIPUS, PFP undergoes phase transition from liquid to gas for real‐time imaging, meanwhile, CeO2/MnOX@UK@PFP is burst to release UK and CeO2/MnOX. UK is delivered to the side of the clot avoiding hemorrhagic risk. CeO2/MnOX@UK@PFP not only can detect the progression of thrombolytic treatment through ultrasound imaging (US) in real‐time but also play an important role in the elimination of excessive ROS at the thrombus microenvironment for protecting endangium. Taken together, the in vitro and in vivo experiments illustrated that CeO2/MnOX@UK@PFP displayed excellent efficiency in thrombolysis visual, anti‐inflammation, and ROS scavenging.

Background This study aimed to assess the effectiveness of an integrated Team-Based Learning (TBL) and Peer Teaching (PT) model in enhancing theoretical knowledge, clinical competencies, and engagement among dental residents, offering insights for improving stomatology education. Methods This study was conducted at the affiliated stomatology hospital of Guangzhou medical university between 2021 and 2023. The 2021–22 cohort (n = 39) students received a traditional teacher-centered approach, whereas the 2022–23 cohort (n = 43) underwent a combined TBL and PT approach. Following a three-month training period, theoretical exams and OSCE were administered. Student engagement was evaluated using the SCEQ, and satisfaction was assessed through SSS. Data were analyzed using independent t-tests, Mann-Whitney U tests, and χ² tests, with statistical significance set at p < 0.05. Results No significant baseline differences were observed in demographics. TBL + PT cohort demonstrated significantly higher theoretical test scores and OSCE performance in most assessed skills, including pulpotomy, tooth preparation, incision and suturing, and patient intake. Engagement scores were also significantly higher in the domains of emotional engagement and participation/interaction, and overall student satisfaction improved, particularly regarding teaching quality and student-centric learning methods. Word cloud analyses of student feedback revealed a stronger emphasis on collaboration, participation, and innovation in the TBL + PT cohort compared to the traditional group. Conclusions Incorporating Team-Based Learning and Peer Teaching into standardized dental residency training markedly enhanced theoretical knowledge, clinical proficiencies, and learner engagement. This instructional strategy improved residents’ technical competencies and cultivated stronger team collaboration, communication, and higher satisfaction levels, offering a promising alternative to traditional teaching for residency training in oral medicine.

Background and aim The ability of geriatric nurses to cope with death affects both their physical and mental health, as well as the quality of the hospice services they provide. The aim of this study was to investigate the death coping ability, death attitude, and professional quality of life of geriatric nurses, analyse the influencing factors of death coping ability, and explore the correlations among them. Design A multicentre cross-sectional study design was used and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Methods From October to November 2024, a convenience sampling method was used to survey 357 geriatric nurses from 9 hospitals in 8 provinces and cities, including Guangdong and Hubei, China, as the research subjects. The general information questionnaire, Coping With Death Scale (CDS), Death Attitude Profile-Revised (DAP-R), and Nurse Professional Quality of Life Scale were used for the investigation. Results The death coping ability score of the geriatric nurses was 135.23 ± 33.04 points, the total death attitude score was 96.65 ± 21.04 points, and the total raw professional quality of life score was 90.00 ± 11.91 points. Pearson correlation analysis revealed that the death coping ability of geriatric nurses was positively correlated with death attitudes, negatively correlated with secondary trauma and occupational burnout, and positively correlated with compassion satisfaction. Regression analysis revealed that age, frequency of sharing experiences of caring for terminally ill patients with others, participation in death-related courses or training, attitude towards death, and professional quality of life were factors influencing geriatric nurses’ ability to cope with death (P < 0.05). Conclusion The death coping ability of geriatric nurses is moderate and is related to death attitude and professional quality of life. Nursing managers are encouraged to enhance death education or training for geriatric nurses to help them develop a positive attitude towards death, pay attention to the quality of professional life of geriatric nurses and improve their ability to cope with death.