Search

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.

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.

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).

This work aims to study the constitutive models and microstructures of a novel high-strength and high-ductility (HSHD) steel under cryogenic temperature. A series of cryogenic tensile tests were conducted using a testing machine equipped with a cryogenic chamber. The results showed that the HSHD steel exhibits an obvious temperature-dependence effect. As the temperature decreased, the yield strength and tensile strength gradually increased, while the uniform elongation increased and then decreased. At a cryogenic temperature of −196 °C, the HSHD steel exhibited significantly enhanced mechanical properties. Specifically, the yield strength, tensile strength, and uniform elongation were 1200 MPa, 1620 MPa, and 30 % respectively. Based on the obtained temperature-dependence effect, the classic Ludwigson constitutive model that all parameters were functions related to temperature was developed and its accuracy was verified through numerical analysis. Furthermore, the microstructure of HSHD steel was investigated during the different deformation stages through microstructure characterization techniques. The excellent cryogenic mechanical properties of HSHD steel stem from the synergic effects of high-density dislocations, denser mechanical twins, and Lomer-Cottrell locks as well as their extensive interactions, rarely observed in their siblings deformed at room temperature. Furthermore, the transformation-induced plasticity (TRIP) effect, which is a significant mechanism for plasticity and favors strain hardening, delays the initiation of necking at −196 °C. These findings reveal the relationship between mechanical behavior and deformation mechanisms in HSHD steel within the low-temperature regime, providing valuable insights for the design of HSHD steel in cryogenic applications.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

Introduction: The prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown. Objectives: This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation. Methods: LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P

Dendrobium officinale Kimura & Migo (D. officinale) is a common, high medicinal value food and herbal medicine used in the treatment of yin-deficient diseases. Adulterants obtained with similar inexpensive species of Dendrobium plants are available in the market. However, Dendrobium species with different quality levels or from different regions as well as analogous species have a similar appearance, which makes the discrimination of Dendrobium species difficult. Reliable objective methods for authenticating D. officinale are lacking. Here, samples of Dendrobium officinale Kimura & Migo (D. officinale) from two regions with three quality levels and sample of the analogous species Dendrobium compactum Rolfe ex W. Hackett (D. compactum) were subjected to genome-wide biological response fingerprinting (BioReF) in RAW264.7 ​cells by RNA sequencing. The biological pathways affected by these samples could distinguish D. officinale from D. compactum. The high-quality D. officinale samples from Yunnan exhibited the strongest inhibition of lipopolysaccharide (LPS) induced inflammatory genes and pathways, followed by samples from Myanmar. The medium- and low-quality samples from Yunnan exhibited weaker effects, and D. compactum exerted mild effects. The RNA sequencing results were strengthened by the results from analyses of the expression of the inflammation-related genes Il6, Ccl5, and Cox2 and the production of nitric oxide. Thus, transcriptomic profiling can be used to evaluate the quality of D. officinale and distinguish its origin.

Summary: Ovarian cancer (OC) is a heterogeneous disease with the highest mortality rate and the poorest prognosis among gynecological malignancies. Because of the absence of specific early symptoms, most OC patients are often diagnosed at late stages. Thus, improved biomarkers of OC for use in research and clinical practice are urgently needed. The last decade has seen increasingly rapid advances in sequencing and biotechnological methodologies. Consequently, multiple omics technologies, including genomic/transcriptomic sequencings and proteomic/metabolomic mass spectra, have been widely applied to analyze tissue- and liquid-derived samples from OC patients. The integration of multi-omics data has increased our knowledge of the disease and identified valuable OC biomarkers. In this review, we summarize the recent advances and perspectives in the use of multi-omics technologies in OC research and highlight potential applications of multi-omics for identifying novel biomarkers and improving clinical assessments.

Multifunctional materials have become the development trend of current material preparation. We reported a typical layer-by-layer method for the fabrication of multifunctional Fe3O4@mTiO2@noble metal triplex core-shell composite nanoparticle (NP), which is composed of a magnetic Fe3O4 particle as the core, a mesoporous TiO2 interlayer and a layer of Ag nanoparticles or Au nanorods as the shell. The obtained Fe3O4@mTiO2@noble metal composite NPs have shown excellent surface enhanced Raman scattering (SERS) sensitivity. Raman results present that the limit of detection (LOD) for crystal violet (CV), p-aminothiophnol (p-ATP) and p-mercaptobenzoic acid (p-MBA) of the Fe3O4@mTiO2@noble metal composite NPs substrates are as low as 1.0 × 10−9 M, 1.0 × 10−12 M and 1.0 × 10−9 M, respectively. In addition, the composite NPs also show high reproducibility and stability across the entire area with relative standard deviations (RSD) less than 15.00%. These highly sensitivity with good reproducibility can be attributed to the presence of plentiful “hot spots” produced by magnetic aggregation and target molecules enrichment by mesoporous TiO2 adsorption for practical application. Fe3O4@mTiO2@Ag composite NPs were used for thiram detection and the detection limit can reach to 5.0 × 10−8 M (about 0.012 ppm), which is lower than the maximal residue limit of 7 ppm in fruit prescribed by the U.S. Environmental Protection Agency. These multifunctional composite NPs provide easy separation, enrichment and trace detection of the analyte, exhibiting a great prospect as a potential SERS sensor in complex environments. Keywords: Surface enhanced Raman scattering, Fe3O4@mTiO2@Ag, Fe3O4@mTiO2@Au NR, Thiram, Trace detection

Microplastics are widespread in freshwater environments, their biological effects and combined effects of other pollutants have attracted extensive attention. In this study, we investigated the adsorption properties of heavy metals onto polystyrene (PS) microplastics as well as the bioavailability and toxicity of microplastics and heavy metals by hydroponic wheat seedlings experiment. Results showed that PS microplastics (0.5 µm, 100 mg/L) had no significant effect on wheat seedlings growth, photosynthesis, and reactive oxygen species (ROS) content. However, PS microplastics could adsorb copper and cadmium, with a predominantly chemisorption. The accumulation of copper and cadmium in wheat seedlings reduced in the presence of PS microplastics, which meant the toxic effect by heavy metals might be mitigated. Compared with single heavy metals treatments, the combination of PS microplastics and heavy metals increased chlorophyll content, enhanced photosynthesis and reduced the accumulation of ROS. These findings suggest that PS microplastics (0.5 µm, 100 mg/L) have a mitigating effect on the bioavailability and toxicity of copper and cadmium.

The failure of T cells to eradicate tumour cells in the tumour microenvironment is mainly due to the dysfunction of T cells. Senescent T cells, with defects in proliferation and effector functions, accumulate in ageing, chronic viral infections, and autoimmune disorders where antigen stimulation persists. Increasing evidence suggests that inducing T cell senescence is a key strategy used by malignant tumours to evade immune surveillance. In this review, we summarize the general features, functional regulation, and signalling network of senescent T cells in tumour development and highlight their potential as prognostic biomarkers in multiple cancer treatments, including chemotherapy, radiotherapy, and immunotherapy. Moreover, we discuss possible therapeutic strategies for preventing or rejuvenating senescence in tumour-specific T cells. Understanding these critical issues may provide novel strategies to enhance cancer immunotherapy.

In-situ immobilization is an effective and economically viable strategy for remediation of soil extensively polluted with heavy metals. The long-term sustainability is critical for the remediation practice. In the present study, a ten-year experiment was performed in a Cd-polluted agricultural field to evaluate the long-term stability of lime, silicon fertilizer (SF), fused calcium magnesium phosphate fertilizer (FCMP), bone charcoal, steel slag, and blast furnace slag with one-off application. All amendments had no significant effect on biomass but significantly reduced Cd uptake by Artemisia selengensis at higher dose. Among them, SF and FCMP applied at 1% could reduce Cd uptake by more than 40% to meet the Chinese maximum permissible limit for Cd content in food products (50 μg kg−1). These amendments stimulated high Cd immobilization by increasing the soil pH and decreasing the soil acid-extractable Cd content, which were closely associated with Cd uptake. In addition, the two amendments altered the soil microbial structure and stimulated metabolism pathways, including amino acid, carbohydrate, and lipid metabolism, which are beneficial for soil function and quality. The results proved that SF and FCMP at 1% are stable and ecologically safe amendments, suitable for long-term Cd immobilization, and provide a strategy to mitigate the risk of food product contamination in heavy-metal-polluted soil.

Physiological and biochemical perturbations in the liver of Carassius auratus were investigated in vivo following 40 days of exposure to ytterbium solutions of different concentration. Glutamate-pyruvate transaminase (GPT) activity in goldfish liver was stimulated at 0.05 mg/L Yb3+ and inhibited at higher Yb3+ concentrations. Activity of the antioxidant enzyme superoxide dismutase (SOD) was stimulated at Yb3+ higher than 0.05 mg/L, and catalase (CAT) activity was strongly inhibited after 40 days of exposure. Detoxifying enzymes glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were stimulated at 0.05 mg/L and inhibited at 0.1 mg/L after 40 days of exposure. Among the parameters determined, CAT in goldfish liver was most sensitive to Yb3+, indicating that CAT might be considered a potential tool in the biomonitoring of exposure to Yb3+ in an aquatic ecosystem.