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Abstract Nanomaterials offer considerable benefits in improving plant growth and nutritional status owing to their inherent stability, and efficiency in essential nutrient absorption and delivery. Cerium oxide nanoparticles (CeO2 NPs) at optimum concentration could significantly influence plant morpho-physiology and nutritional status. However, it remains unclear how elevated CO2 and CeO2 NPs interactively affect plant growth and quality. Accordingly, the ultimate goal was to reveal whether CeO2 NPs could alter the impact of elevated CO2 on the nutrient composition of spinach. For this purpose, spinach plant morpho-physiological, biochemical traits, and nutritional contents were evaluated. Spinach was exposed to different foliar concentrations of CeO2 NPs (0, 25, 50, 100 mg/L) in open-top chambers (400 and 600 CO2 μmol/mol). Results showed that elevated CO2 enhanced spinach growth by increasing photosynthetic pigments, as evidenced by a higher photosynthetic rate (Pn). However, the maximum growth and photosynthetic pigments were observed at the highest concentration of CeO2 NPs (100 mg/L) under elevated CO2. Elevated CO2 resulted in a decreased stomatal conductance (gs) and transpiration rate (Tr), whereas CeO2 NPs enhanced these parameters. No significant changes were observed in any of the measured biochemical parameters due to increased levels of CO2. However, an increase in antioxidant enzymes, particularly in catalase (CAT; 14.37%) and ascorbate peroxidase (APX; 10.66%) activities, was observed in high CeO2 NPs (100 mg/L) treatment under elevated CO2 levels. Regarding plant nutrient content, elevated CO2 significantly decreases spinach roots and leaves macro and micronutrients as compared to ambient CO2 levels. CeO2 NPs, in a dose-dependent manner, with the highest increase observed in 100 mg/L CeO2 NPs treatment and increased roots and shoots magnesium (211.62–215.49%), iron (256.68–322.77%), zinc (225.89–181.49%), copper (21.99–138.09%), potassium (121.46–138.89%), calcium (118.22–91.32%), manganese (133.15–195.02%) under elevated CO2. Overall, CeO2 NPs improved spinach growth and biomass and reverted the adverse effects of elevated CO2 on its nutritional quality. These findings indicated that CeO2 NPs could be used as an effective approach to increase vegetable growth and nutritional values to ensure food security under future climatic conditions.

Abstract Background During the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators. Methods A total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD. Results A comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process of tumor antigen generation and loading, antigen drainage to lymph nodes (LNs), antigen internalization by dendritic cells (DCs), DC maturation, and antigen cross-presentation to activate T-cells. However, tumor vaccines are often unable to satisfy all the steps, leading to the limitation of their application and efficacy. Herein, based on a smart nanogel system, an in situ nano-vaccine (CpG@Man-P/Tra/Gel) targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer. The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib (Tra) and nano-adjuvant CPG@Man-P, which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P. Benefiting from mannose (Man) modification, the nano-vaccines targeted to LNs, promoted the uptake of antigens by DCs, further inducing the maturation of DCs and activation of T cells. Moreover, CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo. Notably, combined with PD-1 blocking, the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

Abstract Mercury (Hg), a potent neurotoxin posing risks to human health, is cycled through vegetation uptake, which is susceptible to climate change impacts. However, the extent and pattern of these impacts are largely unknown, obstructing predictions of Hg’s fate in terrestrial ecosystems. Here, we evaluate the effects of climate change on vegetation elemental Hg [Hg(0)] uptake using a state-of-the-art global terrestrial Hg model (CLM5-Hg) that incorporates plant physiology. In a business-as-usual scenario, the terrestrial Hg(0) sink is predicted to decrease by 1870 Mg yr−1 in 2100, that is ~60% lower than the present-day condition. We find a potential decoupling between the trends of CO2 assimilation and Hg(0) uptake process by vegetation in the 21st century, caused by the decreased stomatal conductance with increasing CO2. This implies a substantial influx of Hg into aquatic ecosystems, posing an elevated threat that warrants consideration during the evaluation of the effectiveness of the Minamata Convention.

With the continuous increase of depth in underground engineering, rock bursts or rock explosions can cause instantaneous shock load and result in rock engineering disasters. To solve these problems, a novel high strength and high toughness (HSHT) bolt steel with constant resistance and large deformation is proposed. This study aims to investigate the dynamic constitutive models and microstructure of HSHT steel under extreme loading conditions. A series of dynamic tension tests were conducted using a Split Hopkinson Tensile Bar (SHTB) system with a high-speed camera. The results revealed that the HSHT steel exhibited a positive strain rate effect. As the strain rate increased from 1000 s−1 to 5000 s−1, the yield strength and ultimate strength of the HSHT steel increased gradually. However, no obvious changes in the uniform elongation. Specifically, the yield strength, tension strength, and uniform elongation of strain rate at 5000 s−1 were 1100 MPa, 1170 MPa, and 30%, respectively. According to the results of the SHTB tests, a modified Johnson-Cook model was proposed. Additionally, we investigated the microstructure of HSHT steel at a high strain rate through microscopic characterization techniques. A large number of fine and deep dimples were observed near the fracture of HSHT steel under dynamic loading. Moreover, the HSHT steel demonstrates a significant presence of nano-twins, which effectively impedes crack propagation both within the grain interior and along grain boundaries. The above findings reveal the relationship between mechanical behavior and microstructure in HSHT steel within dynamic loading conditions, providing valuable insights for the design of HSHT steel in underground engineering.

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression. Methods Via the analysis of whole-exome sequencing results of tumor samples from 90 ovarian cancer patients, we compared the mutational landscape of ovarian cancer patients with that of TCGA patients to identify similarities and differences. The sequencing data were subjected to bioinformatics analysis to explore tumor driver genes and their functional roles. Furthermore, we conducted basic medical experiments to validate the results obtained from the bioinformatics analysis. Results Whole-exome sequencing revealed the mutational profile of HGSOC, including BRCA1, BRCA2 and TP53 mutations. AP3S1 emerged as the most weighted tumor driver gene. Further analysis of AP3S1 mutations and expression demonstrated their associations with patient survival and the tumor immune response. AP3S1 knockdown experiments in ovarian cancer cells demonstrated its regulatory role in tumor cell migration and invasion through the TGF-β/SMAD pathway. Conclusion This comprehensive analysis of somatic mutations in HGSOC provides insight into potential therapeutic targets and molecular pathways for targeted interventions. AP3S1 was identified as being a key player in tumor immunity and prognosis, thus providing new perspectives for personalized treatment strategies. The findings of this study contribute to the understanding of HGSOC pathogenesis and provide a foundation for improved outcomes in patients with this aggressive disease.

The emergence of natural products has provided extremely valuable references for the treatment of various diseases. Cucurbitacin B, a tetracyclic triterpenoid compound isolated from cucurbitaceae and other plants, is the most abundant member of the cucurbitin family and exhibits a wide range of biological activities, including anti-inflammatory, anti-cancer, and even agricultural applications. Due to its high toxicity and narrow therapeutic window, structural modification and dosage form development are necessary to address these issues with cucurbitacin B. This paper reviews recent research progress in the pharmacological action, structural modification, and application of cucurbitacin B. This review aims to enhance understanding of advancements in this field and provide constructive suggestions for further research on cucurbitacin B.

Summary: Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients’ survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. Methods: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. Findings: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. Interpretation: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. Funding: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

The study investigated Chinese secondary school teachers' views on ethicality of teachers' practices in classroom assessment. Participants included 1,871 teachers from 205 secondary schools in 23 provinces, 4 municipalities, and 4 autonomous regions in China. A survey study with 14 authentic assessment scenarios revealed that there is no evident consensus on ethicality of teachers' practices in classroom assessment among the participant teachers, and discrepancies exist between teachers' views and the views of assessment professionals in the literature. Chinese secondary school teachers reported low agreement with the literature in assessment confidentiality, communication about grading, grading practice, and test administration. Gender and subject taught are significantly associated with teachers' ethical perceptions. The findings suggest that ethical issues in classroom assessment are complicated, and they are often interwoven with other factors including cultural background, educational policy, and institutional guidelines in assessments. The study findings are informative for the development of secondary school teacher education program, teachers' professional learning, and educational policy making.