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Advancements in nanotechnology and molecular biology have promoted the development of a diverse range of models to intervene in various disorders (from diagnosis to treatment and even theranostics). Manganese dioxide nanosheets (MnO NSs), a typical two-dimensional (2D) transition metal oxide of nanomaterial that possesses unique structure and distinct properties have been employed in multiple disciplines in recent decades, especially in the field of biomedicine, including biocatalysis, fluorescence sensing, magnetic resonance imaging and cargo-loading functionality. A brief overview of the different synthetic methodologies for MnO NSs and their state-of-the-art biomedical applications is presented below, as well as the challenges and future perspectives of MnO NSs.

The NF1 gene encodes neurofibromin, which is one of the primary negative regulatory factors of the Ras protein. Neurofibromin stimulates the GTPase activity of Ras to convert it from an active GTP-bound form to its inactive GDP-bound form through its GTPase activating protein-related domain (GRD). Therefore, neurofibromin serves as a shutdown signal for all vertebrate RAS GTPases. NF1 mutations cause a resultant decrease in neurofibromin expression, which has been detected in many human malignancies, including NSCLC, breast cancer and so on. NF1 mutations are associated with the underlying mechanisms of treatment resistance discovered in multiple malignancies. This paper reviews the possible mechanisms of NF1 mutation-induced therapeutic resistance to chemotherapy, endocrine therapy and targeted therapy in malignancies. Then, we further discuss advancements in targeted therapy for NF1 -mutated malignant tumors. In addition, therapies targeting the downstream molecules of NF1 might be potential novel strategies for the treatment of advanced malignancies.

The aim of the present study was to elucidate the role and downstream mechanism of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the process of cervical cancer cell pyroptosis. The effect of inhibiting lncRNA MALAT1 on cervical cancer cells was determined using primary cells isolated from patients and U14 cervical tumor-bearing nude mice. The level of lncRNA MALAT1 expression and cell viability were determined for relationship analysis. Pyroptosis was then investigated in HeLa cells with lncRNA MALAT1 knockdown or overexpression with or without lipopolysaccharide (LPS) treatment. Bioinformatics tools were used to identify downstream factors of lncRNA MALAT1, which were subsequently verified by gain- or loss-of-function analyses in the process of cervical cancer cell pyroptosis. It was observed that the level of lncRNA MALAT1 was markedly higher in cervical carcinoma cells compared with expression in paracarcinoma cells, and knockdown of lncRNA MALAT1 induced cervical cancer cell death through pyroptosis. By contrast, overexpression of lncRNA MALAT1 blocked LPS-induced pyroptosis. These results, combined with bioinformatics statistical tools, demonstrated that the microRNA (miR)-124/sirtuin 1 (SIRT1) axis may affect the progression of cervical cancer at least partly by mediating the effect of lncRNA MALAT1 on the pyroptosis of cervical cancer cells. In conclusion, the lncRNA MALAT1/miR-124/SIRT1 regulatory axis in cervical cancer cells may mediate pyroptosis and may provide potential targets against the progression of cervical cancer.

Objective Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Histone lysine-specific demethylase 1 (LSD1) is a flavin-containing amino oxidase that can repress or activate transcription. The aim of this study is to explore the mechanism of LSD1 aggravating DN-induced renal fibrosis. Methods The STZ-induced DN rat model was established for in vivo study. The rats were divided into four groups: Sham, STZ, STZ + Ad-shNC and Ad-shLSD1. The Hematoxylin–eosin (HE) staining was used to evaluate the renal injury. The Immunofluorescence assay was used to determine the LSD1, Fibronectin and α-SMA expression. The related protein expression was detected by western blot. Results Knockdown of LSD1 alleviated STZ-induced renal injury. Moreover, knockdown of LSD1 decreased the expression of serum biochemical markers, containing urine output (24 h), urinary protein (24 h), serum creatinine, BUN and UACR. Furthermore, we proved that knockdown of LSD1 alleviated renal fibrosis in STZ-induced DN rats. In vitro, knockdown of LSD1 suppressed NRK-49F cells activation and overexpression of LSD1 induced renal fibrosis. In addition, knockdown of LSD1 could deactivate TGF-β1/Smad3 pathway and promote sirtuin 3 (SIRT3) expression in vivo and in vitro. The rescue experiments confirmed that LSD1 induced renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway. Conclusion LSD1 deficiency leads to alleviate STZ-induced renal injury and overexpression of LSD1 induces renal fibrosis via decreasing SIRT3 expression and activating TGF-β1/Smad3 pathway, which provides a reasonable strategy for developing novel drugs targeting LDS1 to block renal fibrosis.

This study aimed to identify key cell cycle–related genes involved in cervical cancer progression using comprehensive bioinformatics analyses and to explore their potential implications in neuromuscular complications associated with cancer pathology or treatment. Gene expression profiles related to cervical cancer (GSE63514, GSE6791, GSE52903, and GSE9750) were retrieved from the GEO database. Differentially Expressed Genes (DEGs) distinguishing tumor tissues from normal tissues were determined through Venn diagram analysis. Functional enrichment was conducted via Gene Ontology (GO) and KEGG pathway analyses. A Protein-Protein Interaction (PPI) network was constructed using the STRING database, and core hub genes were screened through Cytoscape. Validation of selected genes was performed using GEPIA. A total of 117 DEGs were identified, with 89 upregulated and 28 downregulated genes. In this case, five hub genes—CDK1, CCNA2, CDC20, TOP2A, and EXO1—displayed significant overexpression in cervical cancer tissues with p values lower than 0.05. It is noteworthy that CCNA2 was associated with increased tumor stage and worse Disease-Free Survival (DFS), and CDK1 with worse Overall Survival (OS). These genes play crucial roles in the regulatory circuits of the cell cycle, and their altered expression may impact a range of cellular processes beyond cancer, such as the neuromuscular signalling abnormalities seen in some patients with cervical cancer. The specific genes associated with the cell cycle can act as prognostic biomarkers and may also have an influence in mediating neuromuscular complications due to their impact on mitotic control and molecular signaling pathways throughout the body. This latter aspect is helpful for the prognosis of cancer, including cervical cancer, as well as for the multidisciplinary treatment of neuromuscular symptoms that some cervical cancer patients may have.

Early diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.BACKGROUNDEarly diagnosis of renal cell carcinoma is extremely significant for the effective treatment of kidney cancer. The development of AS1411 aptamer modified Mn-MoS2 QDs provides a promising fluorescence/magnetic resonance (MR) dual-modal imaging probe for the precise diagnosis of renal clear cell carcinoma.In this work, Mn-MoS2 QDs were synthesized through a simple \"bottom-up\" one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.METHODSIn this work, Mn-MoS2 QDs were synthesized through a simple \"bottom-up\" one-step hydrothermal method. AS1411 aptamer was modified on the Mn-MoS2 QDs to improve the specificity to renal cell carcinoma. The characteristics of Mn-MoS2 QDs were confirmed by transmission electronic microscopy (TEM), atomic force microscope (AFM), X-ray photoelectron spectrometer (XPS), photoluminescence (PL) emission spectra, etc. Cellular fluorescence labelling was investigated using the Mn-MoS2 QDs and AS1411-Mn-MoS2 QDs. The T1-weighted MR imaging was assessed by the in vitro MR cell imaging and in vivo MR imaging. Finally, the long-term toxicity of Mn-MoS2 QDs was investigated by the hematology and histological analysis.The prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM-1s-1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.RESULTSThe prepared Mn-MoS2 QDs exhibited excellent aqueous property, intense fluorescence, low toxicity, high quantum yield of 41.45% and high T1 relaxivity of 16.95 mM-1s-1. After conjugated with AS1411 aptamer, the AS1411-Mn-MoS2 QDs could specifically fluorescently label the renal carcinoma cells and present a specific MRI signal enhancement in the tumor region of mice bearing renal carcinoma tumors. Furthermore, Mn-MoS2 QDs revealed low toxicity to the mice via hematology and histological analysis.These results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.CONCLUSIONThese results demonstrated the potential of AS1411-Mn-MoS2 QD as a novel nanoprobe for targeted MR imaging and fluorescence labelling of renal cell carcinoma.

Polydatin (PD), a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum, is widely used in inhibiting the inflammatory response and oxidative stress. PD has an anti‐inflammatory effect on colitis mice; however, information regulating the mechanism by which maintains the intestinal epithelium barrier is currently scarce. Here, we assessed the anti‐inflammatory and antioxidant of PD in lipopolysaccharide (LPS)‐induced macrophages in vitro, and explored its effects on inhibiting intestinal inflammation and maintaining the intestinal epithelium barrier in dextran sodium sulfate (DSS)‐induced colitis mice. Results showed that PD reduced the level of proinflammatory cytokines and enzymes, including tumor necrosis factor‐α, interleukin‐4 (IL‐4), IL‐6, cyclooxygenase‐2, and inducible nitric oxide synthase, in LPS‐induced macrophages, and improved the expression level of IL‐10. PD maintained the expression of tight junction proteins in medium (LPS‐induced macrophages medium)‐induced MCEC cells. Additionally, PD inhibited the phosphorylation of nuclear factor‐κB (NF‐κB), p65, extracellular signal‐regulated kinase‐1/2, c‐Jun N‐terminal kinase, and p38 signaling pathways in LPS‐induced macrophages and facilitated the phosphorylation of AKT and the nuclear translocation of Nrf2, improving the expression of HO‐1 and NQO1. Furthermore, PD ameliorated the intestinal inflammatory response and improved the dysfunction of the colon epithelium barrier in DSS‐induced colitis mice. Taken together, our results indicated that PD inhibited inflammation and oxidative stress, maintained the intestinal epithelium barrier, and the protective role of PD was associated with the NF‐κB p65, itogen‐activated protein kinases, and AKT/Nrf2/HO‐1/NQO1 signaling pathway.

The complex anatomy of coronary bifurcation lesions (CBLs) remains a major challenge in percutaneous coronary interventions (PCIs). Currently, the single-stent strategy offers procedural simplicity; however, this strategy carries a higher risk of side-branch occlusion. Conversely, the two-stent technique improves branch coverage but is associated with increased risks of metal carina formation and late stent thrombosis. This article reviews the technical key points and indications of the provisional stent, T-stent, Crush, and Culotte techniques. Moreover, this article focuses on discussing the core challenges of different methods according to anatomical characteristics, post-dilatation stent morphology, and procedural variability of lesions during PCI. Furthermore, corresponding optimization strategies were explored to guide individualized treatment of CBLs using the Visual Risk Prediction of Side-branch Occlusion in Coronary Bifurcation Intervention (V-RESOLVE) score, functional assessments, and intracoronary imaging combined with the DEFINITION criteria.

Cultivar and sowing date selection are major factors in determining the yield potential of any crop and in any region. To explore how climate change affects these choices, this study performed a regional scale analysis using the well-validated APSIM-maize model for the Northeast China Plain (NEC) which is the leading maize (Zea mays L.) producing area in China. Results indicated that high temperature had a significantly negative effect on grain yield, while effective accumulated temperature and solar radiation had significant positive effects on grain yield and kernel number. Cloudy and rainy weather in flowering stage had significant negative effects on kernel number. Delayed sowing led to less cloudy and rainy weather during flowering and reduced the negative effect on kernel number. Higher diurnal thermal range and less precipitation during the grain-filling stage also increased the 1000-kernel weight. Delayed sowing, however, also significantly increased the risk of early senescence and frost (>80%) in middle and high latitude areas. In the middle and high latitude areas of the NEC, the grain yield of a long-season cultivar (LS) under early sowing (I) (6.2–19.9%) was significantly higher than under medium sowing (II) or late sowing (III), and higher than that of an early sown (I) short-season (SS) and medium-season cultivar (MS). In the low latitude area of the NEC, the grain yield of MS under medium sowing date (II) was higher than that under I and III, meanwhile, this was also higher than that of SS and LS. Therefore, under climate warming, LS sown earlier in high and medium latitudes and MS sown medium in low latitude were the appropriate cultivar and sowing date choices, which could mitigate the stress of high temperatures and reduce the risk of early senescence and frost. Cultivar and sowing date selection are effective measures to alleviate negative effects of climate change on maize production in the NEC, and provides valuable advice for breeders on cultivar selection, and the choice of varieties and sowing dates for farmers in actual production.

Ricin (RT) and abrin (AT) are plant toxins extracted from Ricinus communis and Abrus precatorius, respectively, and both have N-glycosidase activity. The detection of these toxins is vital because of their accessibility and bioterrorism potential. While ricin can be effectively detected based on its depurination activity, only a few tests are available for detecting the depurination activity of abrin. Therefore, it is unclear whether they share the same optimal reaction substrate and conditions. Here, we established optimum depurination conditions for ricin and abrin, facilitating the in vitro detection of their depurination activity using high-performance liquid chromatography–tandem mass spectrometry. The parameters optimized were the reaction substrate, bovine serum albumin (BSA), buffer, pH, temperature, time, antibodies, and magnetic beads. Both toxins showed better depurination with single-stranded DNA. However, substrate length, adenine content, BSA concentration, buffer concentration, reaction temperature, and reaction time differed between the two toxins. The optimal conditions for ricin depurination involved a reaction in 1 mM ammonium acetate solution (0.5 μM DNA15A, 20 μg/mL BSA, and 1 mM Zn2+, with pH 4.0) at 55 °C for 1 h. The optimal conditions for abrin depurination involved a reaction in 1 mM ammonium citrate solution (0.2 μM DNA20A, 10 μg/mL BSA, 1 mM Mg2+, and 0.5 mM EDTA, with pH 4.0) at 45 °C for 2 h. After optimization, the limits of detection (LOD) for ricin and abrin were 0.506 ng/mL and 0.168 ng/mL, respectively. The detection time was also significantly reduced.