Construction of Isoquinolone Scaffolds on DNA via Rhodium(III)-Catalyzed C-H Activation.

Isoquinolone is one of the most common heterocyclic core structures in countless natural products and many bioactive compounds. Here, a highly efficient approach to synthesize isoquinolone scaffolds on DNA via rhodium(III)-catalyzed C-H activation has been described. This chemistry transformation is robust and has shown good compatibility with DNA, which is suitable for DNA-encoded library synthesis.

Global trends and hotspots in the field of mitochondrial dynamics and hepatocellular carcinoma: A bibliometric analysis from 2007 to 2023.

Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was "mitochondria". Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.

Residual cells and nutrient availability guide wound healing in bacterial biofilms.

Biofilms are multicellular heterogeneous bacterial communities characterized by social-like division of labor, and remarkable robustness with respect to external stresses. Increasingly often an analogy between biofilms and arguably more complex eukaryotic tissues is being drawn. One illustrative example of where this analogy can be practically useful is the process of wound healing. While it has been extensively studied in eukaryotic tissues, the mechanism of wound healing in biofilms is virtually unexplored. Combining experiments in Bacillus subtilis bacteria, a model organism for biofilm formation, and a lattice-based theoretical model of biofilm growth, we studied how biofilms recover after macroscopic damage. We suggest that nutrient gradients and the abundance of proliferating cells are key factors augmenting wound closure. Accordingly, in the model, cell quiescence, nutrient fluxes, and biomass represented by cells and self-secreted extracellular matrix are necessary to qualitatively recapitulate the experimental results for damage repair. One of the surprising experimental findings is that residual cells, persisting in a damaged area after removal of a part of the biofilm, prominently affect the healing process. Taken together, our results outline the important roles of nutrient gradients and residual cells on biomass regrowth on macroscopic scales of the whole biofilm. The proposed combined experiment-simulation framework opens the way to further investigate the possible relation between wound healing, cell signaling and cell phenotype alternation in the local microenvironment of the wound.

What are risk factors for subsequent fracture after vertebral augmentation in patients with thoracolumbar osteoporotic vertebral fractures.

BACKGROUND: Due to its unique mechanical characteristics, the incidence of subsequent fracture after vertebral augmentation is higher in thoracolumbar segment, but the causes have not been fully elucidated. This study aimed to comprehensively explore the potential risk factors for subsequent fracture in this region. METHODS: Patients with osteoporotic vertebral fracture in thoracolumbar segment who received vertebral augmentation from January 2019 to December 2020 were retrospectively reviewed. Patients were divided into refracture group and non-refracture group according to the occurrence of refracture. The clinical information, imaging findings (cement distribution, spine sagittal parameters, degree of paraspinal muscle degeneration) and surgery related indicators of the included patients were collected and compared. RESULTS: A total of 109 patients were included, 13 patients in refracture group and 96 patients in non-refracture group. Univariate analysis revealed a significantly higher incidence of previous fracture, intravertebral cleft (IVC) and cement leakage, greater fatty infiltration of psoas (FIPS), fatty infiltration of erector spinae plus multifidus (FIES + MF), correction of body angle (BA), BA restoration rate and vertebral height restoration rate in refracture group. Further binary logistic regression analysis demonstrated previous fracture, IVC, FIPS and BA restoration rate were independent risk factors for subsequent fracture. According to ROC curve analysis, the prediction accuracy of BA restoration rate was the highest (area under the curve was 0.794), and the threshold value was 0.350. CONCLUSIONS: Subsequent fracture might cause by the interplay of multiple risk factors. The previous fracture, IVC, FIPS and BA restoration rate were identified as independent risk factors. When the BA restoration rate exceeded 0.350, refractures were more likely to occur.

DNA Methylation Heterogeneity Induced by Collaborations Between Enhancers.

During mammalian embryo development, reprogramming of DNA methylation plays important roles in the erasure of parental epigenetic memory and the establishment of naive pluripotent cells. Multiple enzymes that regulate the processes of methylation and demethylation work together to shape the pattern of genome-scale DNA methylation and guide the process of cell differentiation. Recent availability of methylome information from single-cell whole genome bisulfite sequencing (scBS-seq) provides an opportunity to study DNA methylation dynamics in the whole genome in individual cells, which reveal the heterogeneous methylation distributions of enhancers in embryo stem cells. In this study, we developed a computational model of enhancer methylation inheritance to study the dynamics of genome-scale DNA methylation reprogramming during exit from pluripotency. The model enables us to track genome-scale DNA methylation reprogramming at single-cell level during the embryo development process and reproduce the DNA methylation heterogeneity reported by scBS-seq. Model simulations show that DNA methylation heterogeneity is an intrinsic property driven by cell division along the development process, and the collaboration between neighboring enhancers is required for heterogeneous methylation. Our study suggests that the mechanism of genome-scale oscillation might not be necessary for the DNA methylation heterogeneity during exit from pluripotency.

Stochastic Telomere Shortening and the Route to Limitless Replicative Potential.

In human tissues, the replicative potential of stem cells is limited by the shortening of telomere, limitless replicative potential is a hallmark of cancer. Telomere length changes stochastically during cell division mainly due to the competition between the end replication problem and telomerase, short telomere can lead to replicative senescence and cell apoptosis. Here, we investigate how stochastic changes of telomere length in individual cells may affect the population dynamics of clonal growth. We established a computational model that couples telomerase-regulated stochastic telomere length changes with the replicative potential of clones. Model simulations reveal qualitative dependence of clone proliferation potential with activities of telomerase; mutations in cells to alter the activities of telomerase and its inhibitors can induce abnormal tissue growth and lead to limitless replicative potential.

Preparation and characterization of dialdehyde ß-cyclodextrin with broad-spectrum antibacterial activity.

Consumers demand more alternatives of riskless antibacterial agents to prevent microbial contamination in food industry. Oxidized carbohydrate may be a potential option as new antibacterial agent. However, the relatively weak antibacterial property of oxidized carbohydrate is not satisfactory. In this paper, dialdehyde ß-cyclodextrins with different oxidation degree were prepared by periodate oxidation and their antibacterial properties were systematically studied. The results showed that multi-aldehyde groups were successfully introduced into ß-cyclodextrin molecules by periodate oxidation. The aqueous solubility and stability of dialdehyde ß-cyclodextrins were improved as expected. It is interesting that dialdehyde ß-cyclodextrins possessed outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations against E. coli, S. aureus and B. subtilis reached 0.63, 1.25 and 0.63 mg/mL, respectively. Moreover, dialdehyde ß-cyclodextrins effectively inhibited bacterial growth on the surface of apples. The results demonstrated that oxidized oligosaccharide with multi-aldehyde groups and good dispersibility in aqueous solution possessed satisfactory antibacterial activity, which can be used as new antibacterial agent in food industry.