A Facile Synthetic Method for Anhydride from Carboxylic Acid with the Promotion of Triphenylphosphine Oxide and Oxaloyl Chloride

A highly efficient synthesis reaction of carboxylic anhydrides catalyzed by triphenylphosphine oxide is described for the quick synthesis of a range of symmetric carboxylic anhydrides and cyclic anhydrides under mild and neutral conditions with a high yield. The system adopts the strong reactive intermediate Ph3PCl2 as the catalyst of carboxylic acid salt; driven by catalytic reaction, the synthesis takes a relatively short time to complete

Enzalutamide-Induced Signatures Revealed by Epigenetic Plasticity Using Single-Cell Multi-Omics Sequencing in Prostate Cancer

Prostate cancer is morphologically and molecularly heterogeneous, which poses obstacles for early diagnosis and treatment. Advancements in understanding the heterogeneity of prostate cancer will help navigate through these challenges and ultimately benefit patients. In this study, we integrated single-cell sequencing for transposase-accessible chromatin and whole transcriptome in prostate cancer cell lines, aiming to decode the epigenetic plasticity upon enzalutamide (ENZ) treatment. By comparing the cell populations representing early-treatment response or resistance to the initial tumor cells, we identified seven signature gene sets; they present consistent trends of chromatin closing co-occurred with down-regulated genes during early response and chromatin opening with up-regulated genes upon maintaining drug resistance. In the molecular signatures, we found gene

IL-8 Produced Via Bidirectional Communication Between Prostate Cancer and M2 Macrophages as a Potential Diagnostic and Prognostic Biomarker

PURPOSE: Owing to the mortality associated with metastatic prostate cancer and the shortcomings of the current parameters in predicting the disease prognosis, we require the identification of viable biomarkers, which would help in the diagnosis and prognosis of the disease. We aimed to determine whether the interleukin-8 level in the tumor microenvironment could serve as a potential clinical diagnostic marker and prognostic factor for prostate cancer. METHODS: The migration assay of prostate cancer cells was performed in an in vitro co-culture model. Cell lines PC3 and DU145 were divided into two groups and co-cultured with M0 and M2 macrophages, respectively. We used reverse transcription-quantitative polymerase chain reaction to detect M2 macrophage marker expression levels. Immunohistochemistry analyses of tissue microarrays were performed to analyze the correlation between the increased expression of interleukin-8 and the prognosis of prostate cancer. A retrospective analysis based on 142 residual serum specimens was performed to analyze the level of interleukin-8. RESULTS: We observed that M2 macrophages promoted the migration of prostate cancer cells and significantly increased the concentrations of interleukin-8 in the co-culture supernatants. We observed increased expression of CD163 and interleukin-8 in prostate cancer tissues. Furthermore, the levels of interleukin-8 in the serum of prostate cancer patients were higher than those in healthy controls. Untreated patients had higher levels of interleukin-8, which could be a predictor of a higher metastasis rate. CONCLUSION: These results suggest that interleukin-8 produced via bidirectional communication between prostate cancer cells and M2 macrophages is a putative biomarker for prostate cancer diagnosis and treatment

Investigating Cellular Heterogeneity at the Single-Cell Level by the Flexible and Mobile Extrachromosomal Circular DNA

Extrachromosomal circular DNA (eccDNA) is a special class of DNA derived from linear chromosomes. It coexists independently with linear chromosomes in the nucleus. eccDNA has been identified in multiple organisms, including Homo sapiens, and has been shown to play important roles relevant to tumor progression and drug resistance. To date, computational tools developed for eccDNA detection are only applicable to bulk tissue. Investigating eccDNA at the single-cell level using a computational approach will elucidate the heterogeneous and cell-type-specific landscape of eccDNA within cellular context. Here, we performed the first eccDNA analysis at the single-cell level using data generated by single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) in adult and pediatric glioblastoma (GBM) samples. Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system with a poor prognosis. Our analysis provides an overview of cellular origins, genomic distribution, as well as the differential regulations between linear and circular genome under disease- and cell-type-specific conditions across the open chromatin regions in GBM. We focused on some eccDNA elements that are potential mobile enhancers acting in a trans-regulation manner. In summary, this pilot study revealed novel eccDNA features in the cellular context of brain tumor, supporting the strong need for eccDNA investigation at the single-cell level

The efficacy of dapagliflozin for type 1 diabetes: a meta-analysis of randomized controlled studies

Introduction: The efficacy of dapagliflozin for type 1 diabetes remains controversial. We conduct a systematic review and meta-analysis to explore the treatment efficacy of dapagliflozin versus placebo in patients with type 1 diabetes. Methods: We have searched PubMed, EMbase, Web of science, EBSCO and Cochrane library databases through May 2019 for randomized controlled trials (RCTs) assessing the effect of dapagliflozin versus placebo for type 1 diabetes. This meta-analysis is performed using the random-effect model. Results: Six RCTs are included in the meta-analysis. Overall, compared with control group for type 1 diabetes, dapagliflozin treatment shows favorable impact on glycated hemoglobin HbA1c ( standard mean difference SMD=-3.93; 95% confidence interval CI =-4.44 to -3.48; P<0.00001), HbA1c reduction of 650.5% (risk ratio RR=1.98; 95% CI=1.65 to 2.39; P<0.00001), and fasting plasma glucose FPG (SMD=-0.93; 95% CI=-1.77 to -0.10; P=0.03). There is no statistical difference of hypoglycemia (RR=1.09; 95% CI=0.66 to 1.79; P=0.75) or adverse events (RR=1.07; 95% CI=0.96 to 1.20; P=0.20) between two groups, but the incidence of ketone-related events is higher than those in control group (RR=0.28; 95% CI=3.96 to 11.52; P=0.01). Conclusions: Dapagliflozin treatment benefits to reduce HbA1c and FPG for type 1 diabetes

The cadmium–mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots

Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA–QDs) were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA) that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles

Treatment of avulsion fracture of posterior cruciate ligament tibial insertion by minimally invasive approach in posterior medial knee

ObjectiveThe study aims to explore the feasibility and clinical effect of posterior minimally invasive treatment of cruciate ligament tibial avulsion fracture.MethodsPosterior knee minimally invasive approach was used to treat avulsion fracture of posterior cruciate ligament (PCL) tibia in 15 males and 11 females. The length of the incision, intraoperative blood loss, operation time, postoperative hospital stay, residual relaxation, and fracture healing time were analyzed to evaluate the curative effect, learning curve, and advantages of the new technology. Neurovascular complications were recorded. During the postoperative follow-up, the International Knee Joint Documentation Committee (IKDC), Lysholm knee joint score, and knee joint range of motion were recorded to evaluate the function.ResultsAll 26 patients were followed up for 18–24 months, with an average of 24.42 ± 5.00 months. The incision length was 3–6 cm, with an average of 4.04 ± 0.82 cm. The intraoperative blood loss was about 45–60 ml, with an average of 48.85 ± 5.88 ml. The operation time was 39–64 min, with an average of 52.46 ± 7.64 min. The postoperative hospital stay was 2–5 days, with an average of 2.73 ± 0.87 days. All incisions healed grade I without neurovascular injury. All fractures healed well with an average healing time of 9.46 ± 1.33 weeks (range, 8–12 weeks). The Lysholm score of the affected knee was 89–98 (mean, 94.12 ± 2.49) at 12-month follow-up. The IKDC score was 87–95 with an average of 91.85 ± 2.19, and the knee range of motion was 129–148° with an average of 137.08 ± 5.59°. The residual relaxation was 1–3 mm, with an average of 1.46 ± 0.65 mm.ConclusionThis minimally invasive method provides sufficient exposure for internal fixation of PCL tibial avulsion fractures without the surgical complications associated with traditional open surgical methods. The process is safe, less invasive, and does not require a long learning curve