Search

AbstractContext Pileostegia tomentella Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.Objective To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.Materials and methods HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.Results HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.Discussion and conclusion TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC.

Abstract Multi-resonance thermally activated delayed fluorophores have been actively studied for high-resolution photonic applications due to their exceptional color purity. However, these compounds encounter challenges associated with the inefficient spin-flip process, compromising device performance. Herein, we report two pure-blue emitters based on an organoboron multi-resonance core, incorporating a conformationally flexible donor, 10-phenyl-5H-phenophosphazinine 10-oxide (or sulfide). This design concept selectively modifies the orbital type of high-lying excited states to a charge transfer configuration while simultaneously providing the necessary conformational freedom to enhance the density of excited states without sacrificing color purity. We show that the different embedded phosphorus motifs (phosphine oxide/sulfide) of the donor can finely tune the electronic structure and conformational freedom, resulting in an accelerated spin-flip process through intense spin-vibronic coupling, achieving over a 20-fold increase in the reverse intersystem crossing rate compared to the parent multi-resonance emitter. Utilizing these emitters, we achieve high-performance pure-blue organic light-emitting diodes, showcasing a top-tier external quantum efficiency of 37.6% with reduced efficiency roll-offs. This proposed strategy not only challenges the conventional notion that flexible electron-donors are undesirable for constructing narrowband emitters but also offer a pathway for designing efficient narrow-spectrum blue organic light-emitting diodes.

BackgroundTraumatic brain injury (TBI) increases the risk of developing Alzheimer’s disease (AD), and a growing number of studies support a potential link between the two disorders. Therefore, the objective of this study is to systematically map the knowledge structure surrounding this topic over the past and to summarize the current state of research and hot frontiers in the field.MethodsData were retrieved from the Web of Science Core Collection (WOSCC) starting from the beginning until December 31, 2023, focusing on articles and reviews in English. Bibliometric tools including Bibliometrix R, VOSviewer, and Microsoft Excel were utilized for data analysis. The analysis included citations, authors, institutions, countries, journals, author keywords, and references.ResultsA total of 1,515 publications were identified, comprising 872 articles (57.56%) and 643 reviews (42.44%). The annual number of publications increased steadily, especially after 2013, with an R2 value of 0.978 indicating a strong upward trend. The USA was the leading country in terms of publications (734 articles), followed by China (162 articles) and the United Kingdom (77 articles). Meanwhile Boston University was the most productive institution. Collaborative networks show strong collaborative author links between the USA and the United Kingdom, as well as China. The analysis also showed that the Journal of Alzheimer’s Disease was the most productive journal, while the article authored by McKee achieved the highest local citations value. The top three author keywords, in terms of occurrences, were “Alzheimer’s disease,” “traumatic brain injury,” and “neurodegeneration.” Thematic mapping showed a consolidation of research themes over time, decreasing from 11 main themes to 8. Emerging themes such as “obesity” and “diffusion tensor imaging” indicate new directions in the field.ConclusionThe research on AD after TBI has attracted a great deal of interest from scientists. Notably, the USA is at the forefront of research in this field. There is a need for further collaborative research between countries. Overall, this study provides a comprehensive overview of developments in TBI and AD research, highlighting key contributors, emerging topics, and potential areas for future investigation.

In order to distinguish terrestrial material sources in the Okinawa Trough (OT), this study analyzed four surface sediment samples from the northern, middle, and southern parts of the OT using detrital zircon U-Pb age analysis. The detrital zircon age distributions in the northern Okinawa Trough (N-OT) predominantly fall into 1,000−2,300 Ma and 100−600 Ma age groups. In contrast, in the middle Okinawa Trough (M-OT) and southern Okinawa Trough (S-OT), the detrital zircon age groups of 100−600 Ma and 600–1,000 Ma increase significantly, while the age groups of 1,000−2,300 Ma and >2,300 Ma decrease. Detrital zircons from the N-OT primarily originate from the Yellow River and mixed with the Old Yellow River, while those from the M-OT come mainly from the Yellow River, Yangtze Rivers, and East China Sea. And Zhuoshui River maybe a potential source for the M-OT. The detrital zircons from the S-OT are mainly influenced by the Yangtze River, with some effects from the Lanyang River. This study utilizes detrital zircon U-Pb age analysis to gain a better understanding of the terrestrial material sources in various regions of the OT. Most of the zircon grain are coarse, with grain sizes of 40–150 μm long and 30–100 μm wide in the N-OT, smaller in the M-OT and S-OT in this study, which are probably not modern deposits, but the products in the low sea level period of last glaciation mixed with modern sediments. The transport and sedimentation processes reflect the comprehensive influence of sea level change, Kuroshio Current, river input, East Asian monsoon and other factors from last glaciation to present.

Carbon fibre dispersion exerts a critical influence on the characteristics of carbon fibre-reinforced cement mortars (CFRCMs). This study accordingly investigated the dispersion of chopped carbon fibres (CCFs) in mortar using physical experiments with a transparent simulated mortar system comprising colloidal silica and silica sand as replacements for cement and aggregate, respectively, and evaluated the microstructures and conductive performances of corresponding CFRCM specimens. In the simulated solutions, bundled CCFs in order were more prone to disperse into single fibres than clustered ones in disorder due to no physical fixation, colloidal silica prevented the formation of CCF clusters during stirring, and the shear force of moving sand dispersed but also broke CCFs. In the CFRCMs, sand aggregates reaggregated dispersed CCFs while larger sand particles increased CCF dispersion and improved specimen conductivity. Thus, decreasing the amount of CCFs clusters before dispersion, and a short stirring time in a single direction should be provided to prepare CFRCMs with well-dispersed CCFs. Meanwhile, a more dispersible aggregate and less formation of void should be also essential.

ObjectiveThis study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population.MethodsA stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA’s Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression.ResultsA comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations.ConclusionThis investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.

Abstract Background Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. Methods By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9–mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. Results Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the 3’UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. Conclusions Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Diabetic kidney disease (DKD) is a disease of abnormal renal structure and function due to long-term hyperglycemia. Podocyte injury is a major cause of renal inflammation, glomerular filtration barrier injury and renal fibrosis. Ubiquitin proteasome system is involved in intracellular protein clearance. Recent studies have confirmed that it plays an important role in podocyte injury of DKD. High glucose-related injury factors cause an abnormal function of podocyte proteasome, an altered expression level of ubiquitin ligase and an enhancement of deubiquitinating enzyme activity. As a result, an accumulation of injurious protein or an abnormal degradation of protective protein in podocyte may accentuate podocyte injury. This review focused upon the mechanisms of podocyte injury and ubiquitin proteasome involvement in DKD.

Abstract Introduction The mitochondrial alanyl‐tRNA synthetase 2 (AARS2) as one of aminoacyl‐tRNA synthases (ARSs) performs amino acid transportation and involves protein synthesis. However, its role in cancer remains largely unexplored. Methods In this study, more than 10,000 samples were enrolled to explore genomic alterations, biological function, prognosis, and clinical treatment based on AARS2 across pan‐cancer. The molecular characterization of AARS2 was confirmed in hepatocellular carcinoma (HCC) using proteomics analysis, quantitative real‐time PCR, western blotting, immunohistochemical staining, and cell experiments. Results For genomic landscape, the AARS2 was dramatically upregulated in multiple cancers, which might be mainly caused by copy number alteration rather than mutation and methylation. The abnormal expression of AARS2 was prominently associated with activity of cancer pathways and performed oncogenic roles in most cancers. Systematic experiments in vitro substantiated the elevated expression of AARS2, and the deficiency of it inhibited cell proliferation and cell migration in HCC. Meanwhile, our findings suggested that AARS2 could serve as a novel promising and stable biomarker for assessing prognosis and immunotherapy. Moreover, a variety of therapeutic drugs and targeted pathways were proposed for cancer treatment, which might enhance clinical efficacy. Conclusion The AARS2 could serve as a new oncogenic gene that promotes cell proliferation and migration in HCC. The comprehensive investigations increased the understanding of AARS2 across human cancers and generated beginning insights of AARS2 in genomic landscape, molecular biological function, prognosis, and clinical treatment.

Stable soft tissue integration around the implant abutment attenuates pathogen penetration, protects underlying bone tissue, prevents peri-implantitis and is essential in maintaining long-term implant stability. The desire for “metal free” and “aesthetic restoration” has favored zirconia over titanium abutments, especially for implant restorations in the anterior region and for patients with thin gingival biotype. Soft tissue attachment to the zirconia abutment surface remains a challenge. A comprehensive review of advances in zirconia surface treatment (micro-design) and structural design (macro-design) affecting soft tissue attachment is presented and strategies and research directions are discussed. Soft tissue models for abutment research are described. Guidelines for development of zirconia abutment surfaces that promote soft tissue integration and evidence-based references to inform clinical choice of abutment structure and postoperative maintenance are presented.