Fluidized Reduction Kinetics of Boron-Bearing Iron Concentrate by Hydrogen at Low Temperatures Based on Model-Fitting and Model-Free Methods.

Pyrometallurgy is the most effective way to comprehensively utilize boron-bearing iron concentrate, and there is an urgency for an environmentally friendly and efficient method to achieve the prereduction of boron-bearing iron concentrate. In this study, the mechanism and kinetics of isothermal hydrogen reduction of boron-bearing iron concentrate in a fluidized bed at 500-570 °C were discussed. The reduction degree was quantified in combination with the online gas composition analysis technique, and the phase and microstructure of the reduced products were characterized. The results exhibited that the apparent activation energy remained constant during the whole reduction process, with average values of 50.67 and 48.08 kJ/mol calculated by the model-free and model-fitting methods, respectively, and the reaction was controlled by the contracting sphere model. The formation of a microporous metallic iron facilitated the rapid penetration of hydrogen to the reaction interface. Therefore, the intrinsic chemical reaction at the interface determined the whole reaction process.

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

Lentinus edodes mycelium polysaccharide inhibits AGEs-induced HUVECs pyroptosis by regulating LncRNA MALAT1/miR-199b/mTOR axis and NLRP3/Caspase-1/GSDMD pathway.

A novel Lentinus edodes mycelia polysaccharide (LMP) prepared in our laboratory has been identified to be effective in inhibiting the damage of islet ß cells induced by glucose toxicity. However, whether it can effectively alleviate the pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by advanced glycation end products (AGEs) remains unclear. Bioinformatics and cell biology techniques were used to explore the mechanism of LMP inhibiting AGEs-induced HUVECs damage. The results indicated that AGEs significantly increased the expression of LncRNA MALAT1, decreased cell viability to 79.67 %, increased intracellular ROS level to 248.19 % compared with the control group, which further led to cell membrane rupture. The release of LDH in cellular supernatant was increased to 149.42 %, and the rate of propidium iodide staining positive cells increased to 277.19 %, indicating the cell pyroptosis occurred. However, the above trend was effectively retrieved after the treatment with LMP. LMP effectively decreased the expression of LncRNA MALAT1 and mTOR, promoted the expression of miR-199b, inhibited AGEs-induced HUVECs pyroptosis by regulating the NLRP3/Caspase-1/GSDMD pathway. LncRNA MALAT1 might be a new target for LMP to inhibit AGEs-induced HUVECs pyroptosis. This study manifested the role of LMP in improving diabetes angiopathy and broadens the application of polysaccharide.

Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (3-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B's favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the sequential organ failure assessment scores, the clustering results did not simply provide a recapitulation of previous acuity assessments. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.

Freeze-thaw aged polyethylene and polypropylene microplastics alter enzyme activity and microbial community composition in soil.

In cold regions, microplastics (MPs) in the soil undergo freeze-thaw (FT) aging process. Little is known about how FT aged MPs influence soil physico-chemical properties and microbial communities. Here, two environmentally relevant concentrations (50 and 500 mg/kg) of 50 and 500 µm polyethylene (PE) and polypropylene (PP) MPs treated soils were subjected to 45-day FT cycles (FTCs). Results showed that MPs experienced surface morphology, hydrophobicity and crystallinity alterations after FTCs. After 45-day FTCs, the soil urease (SUE) activity in control (MPs-free group that underwent FTCs) was 33.49 U/g. SUE activity in 50 µm PE group was reduced by 19.66 %, while increased by 21.16 % and 37.73 % in 500 µm PE and PP groups compared to control. The highest Shannon index was found in 50 µm PP-MPs group at 50 mg/kg, 2.26 % higher than control (7.09). Compared to control (average weighted degree=8.024), all aged MPs increased the complexity of network (0.19-1.43 %). Bacterial biomarkers of aged PP-MPs were associated with pollutant degradation. Aged PP-MPs affected genetic information, cellular processes, and disrupted the biosynthesis of metabolites. This study provides new insights into the potential hazards of MPs after FTCs on soil ecosystem in cold regions.

Probing the CRL4DCAF12 interactions with MAGEA3 and CCT5 di-Glu C-terminal degrons.

Damaged DNA-binding protein-1 (DDB1)- and CUL4-associated factor 12 (DCAF12) serves as the substrate recognition component within the Cullin4-RING E3 ligase (CRL4) complex, capable of identifying C-terminal double-glutamic acid degrons to promote the degradation of specific substrates through the ubiquitin proteasome system. Melanoma-associated antigen 3 (MAGEA3) and T-complex protein 1 subunit epsilon (CCT5) proteins have been identified as cellular targets of DCAF12. To further characterize the interactions between DCAF12 and both MAGEA3 and CCT5, we developed a suite of biophysical and proximity-based cellular NanoBRET assays showing that the C-terminal degron peptides of both MAGEA3 and CCT5 form nanomolar affinity interactions with DCAF12 in vitro and in cells. Furthermore, we report here the 3.17 Šcryo-EM structure of DDB1-DCAF12-MAGEA3 complex revealing the key DCAF12 residues responsible for C-terminal degron recognition and binding. Our study provides new insights and tools to enable the discovery of small molecule handles targeting the WD40-repeat domain of DCAF12 for future proteolysis targeting chimera design and development.

SFXN1-mediated immune cell infiltration and tumorigenesis in lung adenocarcinoma: A potential therapeutic target.

BACKGROUND: Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target. METHODS: We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD. RESULTS: SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth. CONCLUSIONS: Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.

Rheumatoid Arthritis Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

Comparison of midterm efficacy of Kirschner wires and elastic intramedullary nails after closed reduction of Judet type 3 radial neck fractures in children: a multicenter study.

Objective: The objective of this study was to compare the midterm efficacy of Kirschner wires and elastic intramedullary nails after the closed reduction treatment of Judet 3 radial neck fractures in children. Methods: This was a retrospective multicenter study of patients diagnosed with Judet type 3 radial neck fractures who underwent closed reduction and internal fixation at four tertiary hospitals from January 2019 to December 2021. Gender, age, fracture type, operation time, follow-up time, x-ray results and complications were collected. The recovery of elbow joint between the two internal fixation methods, elbow motion and complications at the last follow-up were compared. Results: The average operation time of EIN group was statistical significantly increased compared with KW group. There were no significant differences in MEPS score and ROM 3 months after surgery between the two groups, but the ROR Angle of EIN group was statistical significantly increased compared with KW group 3 months after surgery. There were no significant differences in MEPS score, ROM and ROR at the last follow-up. The incidence of complications in EIN group was significantly lower than that in KW group. Conclusion: The use of elastic intramedullary nails fixation or Kirschner wires fixation in the treatment of radial neck fractures in children can both achieve satisfactory fracture reduction and healing. Compared with elastic intramedullary nails, the operation time of Kirschner wires fixation is shorter, and the internal fixation does not need to be removed under anesthesia again, but the complication rate is higher.

Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.

Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.

Changes in the femoral trochlear induced with estradiol exposure, an experimental study on rats.

BACKGROUND: It is well known that estrogen is closely related to bone and joint tissue. Findings indicate that estradiol, injected during pregnancy, passes through the placental barrier and reaches the fetuses in utero where it exerts its action. Since trochlea appears well established in the prenatal period, however, whether trochlear dysplasia is related to estradiol exposure has not been confirmed, and the pathological process of estradiol exposure-induced trochlear dysplasia remains unclear. This study aimed to establish an estradiol exposure animal model in fetuses and to analyze the morphology of the femoral trochlear in neonatal rats. METHODS: 30 pregnant Wistar rats provided by the local Animal Center were assigned randomly into three groups, a high dose estradiol injection group, a low dose estradiol injection group and a blank control group. Gross, cross-sectional observation, histological staining measurement and microcomputed tomography of the rat offspring were conducted to evaluate the morphological changes of the femoral trochlea. RESULTS: The incidence of trochlear dysplasia increased with the concentration of estradiol injection. Gross and cross-sectional observation showed a shallower trochlea groove in two groups with estradiol injection. Histological staining measurement indicated that the trochlear sulcus angle and trochlear sulcus depth were significantly different between the two groups with estradiol injection and the blank control group at 0,5 and 10 days after birth. Subchondral bone loss was observed in the two estradiol injection groups by micro-CT, and the bone loss was found to deteriorate over time. CONCLUSION: In this study, estradiol exposure in fetuses had an adverse effect on intrauterine development and could induce trochlear dysplasia and bone loss in rat offspring. In addition, this study also showed that the higher concentration of estradiol injection in pregnant rats, the more incidence of trochlear dysplasia in rat offspring.

Identification and evolution of non-traditional nitrilase from Spirosoma linguale DSM 74 with high hydration activity.

Hydration, a secondary activity mediated by nitrilase, is a promising new pathway for amide production. However, low hydration activity of nitrilase or trade-off between hydration and catalytic activity hinders its application in the production of amides. Here, natural C-terminal-truncated wild-type nitrilase, mined from a public database, obtained a high-hydration activity nitrilase as a novel evolutionary starting point for further protein engineering. The nitrilase Nit-74 from Spirosoma linguale DSM 74 was successfully obtained and exhibited the highest hydration activity level, performing 50.7 % nicotinamide formation and 87.6 % conversion to 2 mM substrate 3-cyanopyridine. Steric hindrance of the catalytic activity center and the N-terminus of the catalytic cysteine residue helped us identify three key residues: I166, W168, and T191. Saturation mutations resulted in three single mutants that further improved the hydration activity of N-heterocyclic nitriles. Among them, the mutant T191S performed 72.7 % nicotinamide formation, which was much higher than the previously reported highest level of 18.7 %. Additionally, mutants I166N and W168Y exhibited a 97.5 % 2-picolinamide ratio and 97.7 % isonicotinamide ratio without any loss of catalytic activity, which did not indicate a trade-off effect. Our results expand the screening and evolution library of promiscuous nitrilases with high hydration activity for amide formation.

ETV7 promotes colorectal cancer progression through upregulation of IFIT3.

Members of the E26 transformation-specific (ETS) variant transcription factor family act as either tumor suppressors or oncogenic factors in numerous types of cancer. ETS variant transcription factor 7 (ETV7) participates in the development of malignant tumors, whereas its involvement in colorectal cancer (CRC) is less clear. In this study, The Cancer Genome Atlas (TCGA) and immunochemistry staining were applied to check the clinical relevance of ETV7 and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in CRC patients. Overexpression and knockdown of ETV7 and IFIT3 were conducted by transfecting the cells with pCDNA3.1 plasmids and siRNAs, respectively. Western blotting was used to detect the protein expression of ETV7 in CRC cells. Cell Counting Kit-8, cell colony formation, and Transwell assays, as well as flow cytometry, were used to evaluate the proliferation, migration, cell cycle, and apoptosis of CRC cells. Furthermore, western blotting, RT-qPCR, and luciferase assay were used to explore the regulation of ETV7 on IFIT3. Rescue assay was used to investigate the significance of ETV7/IFIT3 axis on CRC progression. We found that ETV7 was upregulated in CRC tissues and cells. Overexpression of ETV7 stimulated the proliferation, migration, and cell cycle amplification, and reduced the apoptosis of CRC cells. Downregulation of ETV7 exerted the opposite effect on CRC cell progression. Moreover, we demonstrated that ETV7 stimulated the transcription activity, the mRNA and protein expression of IFIT3 in CRC cells. There was a positive correlation between ETV7 and IFIT3 in CRC patients. IFIT3 knockdown reversed the promotive effect exerted by overexpression of ETV7 on the amplification and migration of CRC cells. By contrast, overexpression of IFIT3 blocked the inhibitory effect of ETV7-targeting siRNA. In summary, ETV7 induces progression of CRC by activating the transcriptional expression of IFIT3. The EVT7/IFIT3 axis may be a novel target for CRC therapy.

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition.

Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy due to its role in promoting an immunosuppressive tumor environment. A Cbl-b inhibitor, Nx-1607, is currently in phase I clinical trials for advanced solid tumor malignancies. Using a suite of biophysical and cellular assays, we confirm potent binding of C7683 (an analogue of Nx-1607) to the full-length Cbl-b and its N-terminal fragment containing the TKBD-LHR-RING domains. To further elucidate its mechanism of inhibition, we determined the co-crystal structure of Cbl-b with C7683, revealing the compound's interaction with both the TKBD and LHR, but not the RING domain. Here, we provide structural insights into a novel mechanism of Cbl-b inhibition by a small-molecule inhibitor that locks the protein in an inactive conformation by acting as an intramolecular glue.

Single-cell RNA sequencing revealed potential targets for immunotherapy studies in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a solid tumor prone to chemotherapy resistance, and combined immunotherapy is expected to bring a breakthrough in HCC treatment. However, the tumor and tumor microenvironment (TME) of HCC is highly complex and heterogeneous, and there are still many unknowns regarding tumor cell stemness and metabolic reprogramming in HCC. In this study, we combined single-cell RNA sequencing data from 27 HCC tumor tissues and 4 adjacent non-tumor tissues, and bulk RNA sequencing data from 374 of the Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) samples to construct a global single-cell landscape atlas of HCC. We analyzed the enrichment of signaling pathways of different cells in HCC, and identified the developmental trajectories of cell subpopulations in the TME using pseudotime analysis. Subsequently, we performed transcription factors regulating different subpopulations and gene regulatory network analysis, respectively. In addition, we estimated the stemness index of tumor cells and analyzed the intercellular communication between tumors and key TME cell clusters. We identified novel HCC cell clusters that specifically express HP (HCC_HP), which may lead to higher tumor differentiation and tumor heterogeneity. In addition, we found that the HP gene expression-positive neutrophil cluster (Neu_AIF1) had extensive and strong intercellular communication with HCC cells, tumor endothelial cells (TEC) and cancer-associated fibroblasts (CAF), suggesting that clearance of this new cluster may inhibit HCC progression. Furthermore, ErbB signaling pathway and GnRH signaling pathway were found to be upregulated in almost all HCC tumor-associated stromal cells and immune cells, except NKT cells. Moreover, the high intercellular communication between HCC and HSPA1-positive TME cells suggests that the immune microenvironment may be reprogrammed. In summary, our present study depicted the single-cell landscape heterogeneity of human HCC, identified new cell clusters in tumor cells and neutrophils with potential implications for immunotherapy research, discovered complex intercellular communication between tumor cells and TME cells.

Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning.

WD40 repeat-containing protein 91 (WDR91) regulates early-to-late endosome conversion and plays vital roles in endosome fusion, recycling, and transport. WDR91 was recently identified as a potential host factor for viral infection. We employed DNA-encoded chemical library (DEL) selection against the WDR domain of WDR91, followed by machine learning to predict ligands from the synthetically accessible Enamine REAL database. Screening of predicted compounds identified a WDR91 selective compound 1, with a KD of 6 ± 2 µM by surface plasmon resonance. The co-crystal structure confirmed the binding of 1 to the WDR91 side pocket, in proximity to cysteine 487, which led to the discovery of covalent analogues 18 and 19. The covalent adduct formation for 18 and 19 was confirmed by intact mass liquid chromatography-mass spectrometry. The discovery of 1, 18, and 19, accompanying structure-activity relationship, and the co-crystal structures provide valuable insights for designing potent and selective chemical tools against WDR91 to evaluate its therapeutic potential.

A novel deep learning-based algorithm combining histopathological features with tissue areas to predict colorectal cancer survival from whole-slide images.

BACKGROUND: Many methodologies for selecting histopathological images, such as sample image patches or segment histology from regions of interest (ROIs) or whole-slide images (WSIs), have been utilized to develop survival models. With gigapixel WSIs exhibiting diverse histological appearances, obtaining clinically prognostic and explainable features remains challenging. Therefore, we propose a novel deep learning-based algorithm combining tissue areas with histopathological features to predict cancer survival. METHODS: The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) dataset was used in this investigation. A deep convolutional survival model (DeepConvSurv) extracted histopathological information from the image patches of nine different tissue types, including tumors, lymphocytes, stroma, and mucus. The tissue map of the WSIs was segmented using image processing techniques that involved localizing and quantifying the tissue region. Six survival models with the concordance index (C-index) were used as the evaluation metrics. RESULTS: We extracted 128 histopathological features from four histological types and five tissue area features from WSIs to predict colorectal cancer survival. Our method performed better in six distinct survival models than the Whole Slide Histopathological Images Survival Analysis framework (WSISA), which adaptively sampled patches using K-means from WSIs. The best performance using histopathological features was 0.679 using LASSO-Cox. Compared to histopathological features alone, tissue area features increased the C-index by 2.5%. Based on histopathological features and tissue area features, our approach achieved performance of 0.704 with RIDGE-Cox. CONCLUSIONS: A deep learning-based algorithm combining histopathological features with tissue area proved clinically relevant and effective for predicting cancer survival.

Quantification of nanoplastics uptake and transport in lettuce by pyrolysis gas chromatography-mass spectrometry.

Nanoplastics (NPs) can enter the edible parts of crop and threaten human health, which attract widespread attention. However, the precise quantification of NPs in crop is still a tremendous challenge. Herein, a method with Tetramethylammonium hydroxide (TMAH) digestion, dichloromethane extraction combined with pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) quantification was present to quantify polystyrene (PS) NPs uptake in lettuce (Lactuca sativa). 25% of TMAH was optimized as extraction solvent and 590 °C was selected as pyrolysis temperature. Recoveries of 73.4-96.9% were obtained for PS-NPs at spiking level of 4-100 µg/g in control samples (RSD < 8.6%). The method exhibited good intra-day and inter-day reproducibility, detection limits of 34-38 ng/g and linearity with 0.998-0.999. The reliability of Py-GC/MS method was verified by europium-chelated PS using inductively coupled plasma mass spectrometry (ICP-MS). To simulate different environmental conditions, hydroponic culture and soil incubated lettuce were exposed to different concentrations of NPs. Higher levels of PS-NPs were detected in roots and very few was transferred to the shoots. NPs in lettuce were confirmed by laser scanning confocal microscopy (LSCM). The developed method provides new opportunities for the quantification of NPs in crops.

CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/ß-catenin/YAP1 axis.

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.