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The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin–NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis. How tumor cells control metastatic niche formation is not fully understood. Here, the authors show in a lung metastatic niche, high-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that leads to activation of β1-integrin-NF-κBsignalling, converting fibroblasts to cancer-associated fibroblasts.

A sensitive electrochemical sensor for the determination of carbendazim (CBZ) was developed with Ni-doping nanoporous carbon-graphene composite (G-Ni/C) as the electrode material. The combination of graphene and Ni-doping nanoporous carbon not only prevented the aggregation of graphene, but also improved electric conductivity and substantially enhanced the electro catalytic activity for CBZ sensing. The electrochemical characterization of G-Ni/C towards CBZ determination was conducted by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) . The sensor based on G-Ni/C/GCE exhibits good electroanalytical activity towards the electro-oxidation of CBZ at the potential of + 0.6 V vs Ag/AgCl. Some key factors including sample pH, scan rates, accumulation potential, and accumulation time were investigated. The method offered a wide linear range of 0.04 to 10.0 µM with a detection limit of 8.9 nM. The obtained sensor was successfully employed for the determination of CBZ in pond water and juice samples with RSD < 5.7% and recoveries in the range 91.3–111%. Graphical Abstract In the present work, Ni-doping nanoporous carbon-graphene composite (G-Ni/C) was prepared by directly pyrolysis of GO/Ni-MOF. The electrochemical sensor based on G-Ni/C /GCE was applied for sensitive determination of carbendazim (CBZ) in pond water, peach, and lemon juices samples.

Stomatology education has experienced substantial transformations over recent decades. Nevertheless, a comprehensive summary encompassing the entirety of this field remains absent in the literature. This study aimed to perform a bibliometric analysis to evaluate the research status, current focus, and emerging trends in this field over the last two decades. We retrieved publications concerning teaching and learning in stomatology education from the Web of Science core collection covering the period from 2003 to 2023. Subsequently, we conducted a bibliometric analysis and visualization using R-Bibliometrix and CiteSpace. In total, 5528 publications focusing on teaching and learning in stomatology education were identified. The annual number of publications in this field has shown a consistent upward trend. The United States and the United Kingdom emerged as the leading contributors to research. Among academic institutions, the University of Iowa produced the highest number of publications. The Journal of Dental Education was identified as the journal with the highest citation. Wanchek T authored the most highly cited articles in the field. Emerging research hotspots were characterized by keywords such as \"deep learning,\" \"machine learning,\" \"online learning,\" \"virtual reality,\" and \"convolutional neural network.\" The thematic map analysis further revealed that \"surgery\" and \"accuracy\" were categorized as emerging themes. The visualization bibliometric analysis of the literature clearly depicts the current hotspots and emerging topics in stomatology education concerning teaching and learning. The findings are intended to serve as a reference to advance the development of stomatology education research globally.

A number of modifications have been developed in order to enhance surface cytocompatibility for prosthetic support of dental implants. Among them, ultraviolet (UV) light and non-thermal plasma (NTP) treatment are promising methods. The objective of this study was to compare the effects of UV light and NTP on machined titanium, zirconia and modified polyetheretherketone (PEEK, BioHPP) surfaces in vitro. Machined samples of titanium, zirconia and BioHPP were treated by UV light and NTP of argon or oxygen for 12 min each. Non-treated disks were set as controls. A mouse fibroblast and a human gingival fibroblast cell line were used for in vitro experiments. After 2, 24 and 48 h of incubation, the attachment, viability and cytotoxicity of cells on surfaces were assessed. Results: Titanium, zirconia and BioHPP surfaces treated by UV light and oxygen plasma were more favorable to the early attachment of soft-tissue cells than non-treated surfaces, and the number of cells on those treated surfaces was significantly increased after 2, 24 and 48 h of incubation (p < 0.05). However, the effects of argon plasma treatment on the cytocompatibility of soft tissue cells varied with the type of cells and the treated material. UV light and oxygen plasma treatments may improve the attachment of fibroblast cells on machined titanium, zirconia and PEEK surfaces, that are materials for prosthetic support of dental implants.

As a widely used anticancer drug for the treatment of chronic myeloid leukemia, ponatinib is known to cause severe cardiovascular toxicities. Cardiomyocytes are the major functional units in the myocardium, and impairment of their viability and function plays a crucial role in cardiotoxic responses. Previous studies have indicated direct toxicity of ponatinib on cardiomyocytes, but the effect of ponatinib on adult human primary cardiomyocytes (hPCMs) remains unknown, largely due to sample scarcity and the technical challenges associated with the adult human cardiomyocyte model. Based upon our previous work establishing hPCMs as a pharmacologically competent model, we tested the direct toxicity of ponatinib on these cells. We reveal suppression of AKT, but not ERK, phosphorylation upon ponatinib treatment. Treatment of hPCMs with AKT inhibitor MK‐2206 phenocopied ponatinib, while restoration of AKT signaling with UCL‐TRO‐1938 or insulin partially rescued hPCMs from cell death, suggesting a potential protective effect.

Codon optimization is a widely employed strategy to enhance protein expression. However, it occasionally leads to unexpected transcriptional repression despite preserving amino acid sequences. This study investigates the mechanistic basis of such transcriptional attenuation by analyzing two gene candidates (0432 and Fluc) in the common expression chassis P. pastoris. Both genes experienced severe mRNA reduction following codon optimization. Evidenced by histone H3 chromatin immunoprecipitation (ChIP) and a DNase I hypersensitivity assay, gene sequences with transcriptional repression displayed elevated nucleosome occupancy and reduced chromatin accessibility. The above change was caused by an ORF sequence change independent of the promoter, since transcriptional attenuation and compromised chromatin accessibility were still observed after replacing the strong promoter PGAP with Ppor1 or Prps8b. Our findings challenge the conventional view of codon optimization as solely translation-centric, revealing its capacity to preemptively modulate transcription through chromatin accessibility. This work underscores the necessity of integrating chromatin-level considerations into synthetic gene design to avoid unintended transcriptional silencing and optimize expression outcomes.

Silage quality remains an important issue in farming, as do limitations in the range of products suitable for animal fodder. We therefore explored the microorganisms that are critical for the fermentation quality of paper mulberry silage. Low (unwilted) and high (wilted) dry matter (DM) paper mulberry were harvested at two cutting times. These were ensiled for 0, 3, 7, 14, and 56 days, respectively. Compared with unwilted silages, wilting significantly decreased (p < 0.05) silage pH value, ammonia‐N concentration, and yeast counts but increased (p < 0.05) lactic acid content. In addition, higher (p < 0.05) crude protein (CP) contents were also observed in wilted silages. Next‐generation sequencing (NGS) analysis revealed that wilting reduced the abundance of Enterobacter, while increasing that of Lactobacillus. Single‐molecule real‐time sequencing (SMRT) revealed that the silage was enriched in the lactic acid bacteria (LAB), Lactobacillus rhamnosus after wilting, which showed a positive correlation with CP and lactic acid content. We conclude that wilting may help preserve paper mulberry silage, facilitating its use as a new fodder resource. Moreover, L. rhamnosus has the potential to be developed as a new inoculant for the modulation in wilted silages, particularly paper mulberry silage. Bacterial community was analyzed by combination of NGS and SMRT sequencing. Wilting enriched the abundance of Lactobacillus rhamnosus. Lactobacillus rhamnosus was the critical species showing the most positively correlation with wilted silage quality, and have the potential to be developed as new silage inoculant.

Ultraviolet (UV) light and non-thermal plasma (NTP) treatment are chairside methods that can efficiently improve the biological aging of implant material surfaces caused by customary storage. However, the behaviors of stem cells on these treated surfaces of the implant are still unclear. This study aimed to investigate the effects of UV light and NTP treated surfaces of titanium, zirconia and modified polyetheretherketone (PEEK, BioHPP) on the attachment and osteogenic potential of human dental pulp stem cells (DPSCs) in vitro. Machined disks were treated using UV light and argon or oxygen NTP for 12 min each. Untreated disks were set as controls. DPSCs were cultured from the wisdom teeth of adults that gave informed consent. After 24 h of incubation, the attachment and viability of cells on surfaces were assessed. Cells were further osteogenically induced, alkaline phosphatase (ALP) activity was detected via a p-Nitrophenyl phosphate assay (day 14 and 21) and mineralization degree was measured using a Calcium Assay kit (day 21). UV light and NTP treated titanium, zirconia and BioHPP surfaces improved the early attachment and viability of DPSCs. ALP activity and mineralization degree of osteoinductive DPSCs were significantly increased on UV light and NTP treated surfaces of titanium, zirconia and also oxygen plasma treated Bio-HPP (p < 0.05). In conclusion, UV light and NTP treatments may improve the attachment of DPSCs on titanium, zirconia and BioHPP surfaces. Osteogenic differentiation of DPSCs can be enhanced on UV light and NTP treated surfaces of titanium and zirconia, as well as on oxygen plasma treated Bio-HPP.

Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO 2 ), which were modified with hyaluronic acid (HA-UCNP@mSiO 2 ) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.

There are few studies on the application of lactic acid bacteria in the reduction of anti-nutrient factors in paper mulberry silage. This study aimed to investigate the effects of different lactic acid bacteria on the fermentation quality and the amount of anti-nutritional factors in paper mulberry silage. Two strains of Lactobacillus plantarum (GX, isolated from paper mulberry silage; GZ, provided by Sichuan Gaofuji Biotechnology Co. Ltd.) were added as silage additives. On days 7, 15, 30 and 60 of the ensiling process, the fermentation quality, and the amount of anti-nutritional factors were measured. Compared with the control group, inoculation with Lactobacillus plantarum could rapidly reduce pH values, leading to lower NH3-N/TN. Besides, it also significantly increased the lactic acid content (p < 0.05). The two strains of L. plantarum significantly reduced the content of hydrolysed tannin, condensed tannin, total tannin, oxalic acid, phytic acid and saponin (p < 0.05). Overall, this study found that the addition of lactic acid bacteria could significantly improve the fermentation quality of paper mulberry and reduce the amount of anti-nutrient factors (p < 0.05).