Background Brain metastases are the most common intracranial tumours. Variation exists in the use of stereotactic radiosurgery for patients with 10 or more brain metastases. Concerns include an ...increasing number of brain metastases being associated with poor survival, the lack of prospective, randomised data and an increased risk of toxicity. Methods We performed a systematic review and meta-analysis to assess overall survival of patients with ten or more brain metastases treated with stereotactic radiosurgery as primary therapy. The search strings were applied to MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Log hazard ratios and standard errors were estimated from each included study. A random-effects meta-analysis using the DerSimonian and Laird method was applied using the derived log hazard ratios and standard errors on studies which included a control group. Results 15 studies were included for systematic review. 12 studies were used for pooled analysis for overall survival at set time points, with a predicted 12 month survival of 20-40%. The random-effects meta-analysis in five studies of overall survival comparing ten or greater metastases against control showed statistically worse overall survival in the 10 + metastases group (1.10, 95% confidence interval 1.03-1.18, p-value = < 0.01, I.sup.2 = 6%). A funnel plot showed no evidence of bias. There was insufficient information for a meta-analysis of toxicity. Discussion Overall survival outcomes of patients with ten or more brain metastases treated with SRS is acceptable and should not be a deterrent for its use. There is a lack of prospective data and insufficient real-world data to draw conclusions on toxicity. PROSPERO ID CRD42021246115 Keywords: Stereotactic radiosurgery, Radiotherapy, Multiple metastases
Visible-light photoredox catalysis is a powerful and attractive strategy for organic molecule activation and new reaction design owing to its environmental-friendly characteristics and unique ...catalytic mechanisms, and has found wide applications in organic synthesis. This catalytic strategy enables controllable generation of diverse nitrogen-centered radicals (NCRs) under mild conditions, providing access to construction of diverse nitrogen-containing compounds. In this review, we critically illustrate the recent advances in the field of visible-light photoredox-catalyzed cyclization of nitrogen-centered radicals, based on the different radical precursors and activation modes. Wherever possible, particular emphasis is also put on working models and synthetic applications.
Photoredox catalysis has emerged as a powerful tool for efficient generation of various nitrogen-centered radicals, and thus enables synthesis of a wide range of nitrogen heterocycles through radical cyclization reactions. In this review, we critically illustrate the recent advances in this field. Display omitted
Anti-angiogenic therapy represents a promising strategy for non-small-cell lung cancer (NSCLC) but its application in lung squamous cell carcinoma (SQC) is limited due to the high-risk adverse ...effects. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) mediate in tumor progression by participating in the regulation of VEGF in NSCLC, which might guide the development of new antiangiogenic strategies.
Differential lncRNA expression in SQC was analyzed in AE-meta and TCGA datasets, and further confirmed in lung cancer tissues and adjacent normal tissues with RT-qPCR and in-situ hybridization. Statistical analysis was performed to evaluate the clinical correlation between LINC00173.v1 expression and survival characteristics. A tube formation assay, chick embryo chorioallantoic membrane assay and animal experiments were conducted to detect the effect of LINC00173.v1 on the proliferation and migration of vascular endothelial cells and tumorigenesis of SQC in vivo. Bioinformatics analysis, RNA immunoprecipitation and luciferase reporter assays were performed to elucidate the downstream target of LINC00173.v1. The therapeutic efficacy of antisense oligonucleotide (ASO) against LINC00173.v1 was further investigated in vivo. Chromatin immunoprecipitation and high throughput data processing and visualization were performed to identify the cause of LINC00173.v1 overexpression in SQC.
LINC00173.v1 was specifically upregulated in SQC tissues, which predicted poorer overall and progression-free survival in SQC patients. Overexpression of LINC00173.v1 promoted, while silencing LINC00173.v1 inhibited the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells in vitro and in vivo. Our results further revealed that LINC00173.v1 promoted the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC cells by upregulating VEGFA expression by sponging miR-511-5p. Importantly, inhibition of LINC00173.v1 via the ASO strategy reduced the tumor growth of SQC cells, and enhanced the therapeutic sensitivity of SQC cells to cisplatin in vivo. Moreover, our results showed that squamous cell carcinoma-specific factor ΔNp63α contributed to LINC00173.v1 overexpression in SQC.
Our findings clarify the underlying mechanism by which LINC00173.v1 promotes the proliferation and migration of vascular endothelial cells and the tumorigenesis of SQC, demonstrating that LINC00173.v1-targeted drug in combination with cisplatin may serve as a rational regimen against SQC.
Polysaccharides are the main effective components of
's stem that perform biological activities and have positive impacts on immune enhancement. In this study, the polysaccharide CSP-III of
's stem ...was isolated using a DEAE-52 cellulose column through Sephadex G-100 gel column chromatography. Upon analysis, the monosaccharide composition of CSP-III included Mannose (Man), Glucuronic acid (GlcA), Galacturonic acid (GalA), Rhamnose (Rha), Glucose (Glc), Galactose (Gal), and Arabinose (Ara), at a molar ratio of 0.01:0.11:0.03:0.57:0.02:0.32:1. The molecular weight of CSP-III was 4018234 Da. Meanwhile, the capacity of CSP-III, at various concentrations, to stimulate the proliferation of mouse spleen lymphocytes in vitro was compared, and the influence of CSP-III on cell proliferation was examined using RAW264.7 mouse mononuclear macrophages as a model. The influence of CSP-III on the expression of important phosphorylating proteins in the MAPK signaling pathway was initially analyzed by Western blotting. In RAW264.7 cells, CSP-III promoted the phosphorylation of JNK proteins, which thus activated the MAPK signaling cascade and exerted immunomodulatory effects. Moreover, according to in vivo studies using cyclophosphamide (CTX)-induced immunosuppression mouse models, CSP-III improved the CTX-induced histopathological damage, promoted T and B lymphocyte proliferation, upregulated CD4+ and CD8+ T-lymphocyte counts in the spleen, increased the serum levels of IgG and IgM, and activated three essential proteins of the MAPK signaling pathway. As revealed by analysis of intestinal flora, CSP-III improved the immune function by maintaining the homeostasis of the bacterial flora by boosting the relative abundances of some beneficial bacterial groups, such as Bacteroidetes, Desmodium, and Actinomyces, and reducing the relative abundance of Aspergillus phylum. Through in vitro and in vivo experiments, our present study demonstrates that polysaccharides from the stem of
possess strong immunoregulatory effects. Findings in this work provide theoretical support for the potential application of
in the field of health food.
The development of a highly efficient, selective and atom-economical method for the construction of allylic amines are a challenge in green synthetic chemistry. In a recent work published in Nature ...Catalysis, Lei, Qi, and co-workers reported that the combination of a photoredox catalyst and cobaloxime catalyst enables site-selective allylic amination of various olefins with secondary alkyl amines, affording the valuable tertiary aliphatic allylamines, without the need for external oxidants.
The chemistry of axially chiral compounds has emerged as a subject of increasing interest due to their widespread presence in natural products, bioactive molecules, advanced materials, and chiral ...ligands/catalysts. On the other hand, catalytic asymmetric radical-based transformations provide a complementary platform for the construction of enantiomerically enriched molecules that are in growing demand in the chemical and pharmaceutical industries. In recent years, considerable research efforts have been devoted to the development of catalytic asymmetric radical reactions for the construction of axially chiral compounds based on the unique reactivity modes of diverse radicals. In this review, we critically illustrate these recent achievements according to different radical precursors and catalytic activation modes. Wherever possible, special emphasis is also placed on the discussion of mechanistic features underlying these works and substrate scopes. This review should be of great interest to the experts in this area but also serve as a helpful starting point for new researchers in this field.
Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the ...maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and M-bands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs. (Circ J 2013; 77: 1307–1314)
Polycrystalline cubic boron nitride (PCBN) was prepared under high-temperature and ultra high-pressure. The influence of sintering temperature on composition, micro-structure, relative density, ...porosity, micro-hardness and flexural strength of the PCBN was investigated by means of X-ray diffraction (XRD), field scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The results show that the phase components of PCBN have no significant difference, which are composed of BN, TiN, TiB2, W, AlN, W2B and Al3Ti when the sintering temperature at 1500 °C–1600 °C. The cBN crystals connect with each other by the reaction product.
With the increase of sintering temperature, the porosity of PCBN decreased from 1.05% to 0.53%, and the relative density increased from 94.5% to 99%. When the sintering temperature increasing to 1600 °C, the PCBN exhibit optimal comprehensive mechanical properties with a micro-hardness of 34.64GPa and a flexural strength of 1005.23 MPa.
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•There are some rod-like crystals and fibrous crystals extend from the cBN boundary.•The fracture of PCBN is the result of the interaction of crystal fracture and transgranular fracture.•When the sintering temperature increasing to 1600°C, the microhardness is 34.64 GPa and the flexural strength is 1005.23 MPa.
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