The Mangrove-Derived Diterpenoid Diaporthe B Inhibits the Stemness and Increases the Efficacy of Docetaxel in Prostate Cancer PC-3 Cells

The absolute configuration of diaporthe B, a pimarane diterpene isolated from the mangrove derived endophytic fungus Eutypella sp #3E, was determined by a single-crystal x-ray diffraction study. The present study aimed to investigate the effects of diaporthe B on docetaxel-resistant prostate cancer PC-3 cells. Results of our studies showed that docetaxel-resistant PC-3 cells had higher sphere-forming efficiency and an increase in adherence to collagen-coated culture plates. The protein levels of cancer stem cell (CSC)-related markers CD44, CD133, and ALDH1A1 were higher in the docetaxel-resistant PC-3 cells than in the parental cells. Treatment with diaporthe B dose-dependently inhibited the growth and induced apoptosis in the resistant cells. Moreover, diaporthe B treatment decreased the sphere-forming efficiency and the adherence to collagen-coated plates in docetaxel-resistant PC-3 cells. Diaporthe B also decreased the protein levels of CSC-related markers CD44, CD133, and ALDH1A1 in the resistant cells. In addition, a combination of diaporthe B and docetaxel had a more potent effect on growth inhibition and apoptosis in the resistant cells than either agent alone. Our studies suggest that diaporthe B inhibits the stemness of prostate cancer cells and may have therapeutic potential for enhancing the efficacy of docetaxel in docetaxel-resistant prostate cancer cells.

Influence of the Different Combination of Diameters of Two Tool Heads on Forming Quality in Double Sided Incremental Forming

The existing double sided incremental forming (DSIF) mostly uses two tools with the same diameter as the upper/lower tools, which is not conducive to improve the forming quality and forming efficiency. In this paper, the influence of the different combination of the upper and lower tool head diameters on the thickness distribution and the contour dimension accuracy of the formed part is studied by using ANSYS / LS-DYNA software and by taking the model with bidirectional convex features as the research object. It is found that the reasonable combination of different diameters of the upper/lower tools based on the characteristics of the parts to be formed can improve the forming quality and forming efficiency.

Differences in Pore-forming Efficiency among Organic Macerals and Its Restriction against Reservoir Quality: A Case Study Based on the Marine Shale Reservoir in the Longmaxi Formation, Southern Sichuan Basin, China

Organic matter pores are of important significance in the shale formation system rich of organic matters. Although a lot of studies have discussed controlling factors of organic matter pores in the past, it still lacks a quantitative analysis on contributions of organic macerals to organic matter pores. In this study, a case study based on the overmature marine facies shale reservoir in the first submember of the Longmaxi Formation of Silurian in the Weiyuan area was carried out. Besides, qualitative and quantitative identifications of organic macerals and their pore development capacity were provided using the scanning electron microscopy (SEM). The results showed that (1) pore-forming efficiency is one controlling factor over pore development of organic matter. Sapropelinite shows the highest pore-forming efficiency (avg. 38.5%) and while the vitrinite, inertinite, and exinite have the lower pore-forming efficiency. (2) The content of sapropelinite is the highest (avg. 82.4%), and the content of sapropelinite is higher in the Long111 and Long113 layers. (3) The content of sapropelinite has a strong positive correlation with the organic surface porosity. (4) Organic surface porosity, organic porosity, and total porosity present basically consistent variations along the vertical direction of single well. Organic surface porosity restricts the organic porosity which is the dominant type in total porosity. Hence, pore-forming efficiency of organic macerals restricts performances of the reservoir.

Improvement of Mechanical Properties and Forming Efficiency during Hot Gas Forming of CFRP Curved Surface Components

Carbon fiber reinforced plastics (CFRP) are widely used in aerospace and new energy vehicles due to their high specific strength and flexible design ability. At present, the traditional forming process of CFRP curved surface components has problems of low mechanical properties and long processing time. In this paper, a new method of hot gas forming was proposed to obtain CFRP components. By applying high temperature and high-pressure gas on one side of CFRP, the material was forced to deform and solidify at the same time. A special device for hot gas forming was designed and developed. The curing behavior and mechanical properties of original CFRP plates were studied. The main defects and the corresponding control methods of hot gas forming parts were analyzed by forming spherical parts, and the feasibility of the hot gas forming process was verified. Taking the battery cover plate of a new energy vehicle as the research object, the influence of forming temperature, gas pressure, pressurization rate and other process parameters on the mechanical properties of complex CFRP components were analyzed. The mechanism of both strength and efficiency improvement was analyzed. The results showed that with the increasing of gas pressure, the tensile strength and forming efficiency of the CFRP curved components were improved obviously. Under reasonable forming parameters, the tensile strength of the obtained parts was increased by 37%, and the forming efficiency was increased by 58%. The fiber bundles were distributed more evenly and compactly under the hot gas forming. This showed that the use of hot gas forming had good potential in the preparation of high-performance CFRP parts, which was helpful to improve the processing efficiency and forming quality of CFRP curved parts in the aerospace and new energy automotive fields.

Identification of novel COX-2 / CYP19A1 axis involved in the mesothelioma pathogenesis opens new therapeutic opportunities

Background Based on previous studies highlighting that the induction of cyclooxygenase-2 (COX-2) and high prostaglandin E2 (PGE2) levels contribute to the pathogenesis of malignant pleural mesothelioma (MPM), and that aromatase (CYP19A1), an enzyme that plays a key role in estrogen biosynthesis, along with estradiol (E2) were expressed in MPM, this study aimed to investigate the possible interplay between COX-2 and CYP19A1 in the pathogenesis of mesothelioma, as well as the underlying mechanism. Methods The interaction between COX-2 and CYP19A1 was first investigated on different MPM lines upon PGE2, and COX-2 inhibitor (rofecoxib) treatment by western blot, RT-PCR. The key regulatory pathways involved in the COX-2 and CYP19A1 axis were further studied in MPM cells, after rofecoxib and exemestane (CYP19A1 inhibitor) treatment in monotherapy and in combination, by cell cycle distribution, western blot, and combination index analysis. To explore the role of COX-2/CYP19A1 axis in 3D preclinical models of MPM cells, we analyzed the effect of combination of COX-2 and CYP19A1 inhibitors in mesosphere formation. Immunohistochemical analysis of MPM mesosphere and specimens was utilized to evaluate the involvement of COX-2 on the CYP19A1 activity and the relationship between E2 and COX-2. Results PGE2 or rofecoxib treatment caused in MPM cells an increased or decreased, respectively, CYP19A1 expression at mRNA and protein levels. The effect of rofecoxib and exemestane combination in MPM cell proliferation was synergistic. Activation of caspase-3 and cleavage of PARP confirmed an apoptotic death for MPM cell lines. Increased expression levels of p53, p21, and p27, downregulation of cyclin D1 and inhibition of Akt activation (pAKT) were also found. The antagonistic effect of rofecoxib and exemestane combination found only in one cell line, was reverted by pretreatment with MK2206, a pAKT inhibitor, indicating pAKT as an actionable mediator in the COX-2-CYP19A1 axis. Reduction of size and sphere-forming efficiency in MPM spheres after treatment with both inhibitor and a decrease in COX-2 and E2 staining was found. Moreover, immunohistochemical analysis of 46 MPM samples showed a significant positive correlation between COX-2 and E2. Conclusions Collectively, the results highlighted a novel COX-2/CYP19A1 axis in the pathogenesis of MPM that can be pharmacologically targeted, consequently opening up new therapeutic options.

The Efficiency of a Head’s of a Forensic Organization Activity: Assessment Criteria, Conditions for Achieving and Correlation with the Goals of Forensic Activity

The article addresses the issues of the efficiency of forensic activity and its impact on the successful performance of forensic conduct. The author offers a systematic analysis of the processes of forming efficiency indicators for forensic activity and assessment criteria for a Head’s of a forensic organization activity. The paper also describes qualitative and quantitative indicators of the efficiency of a forensic organization when assessing the efficacy of a head’s performance, including by the efficiency indicators approved by the Ministry of Justice of the Russian Federation for forensic institutions of the system of the Ministry of Justice of the Russian Federation. The author analyzes the probabilities of the negative efficiency of a head’s activity and its impact on expert conduct. The article determines the trends of the further research of the issues of improving the efficacy of forensic organizations’ activities by forming new criteria for assessing a forensic organization head’s performance influencing the quality of forensic conduct.

A New Method for Automatic Detection of Defects in Selective Laser Melting Based on Machine Vision

Selective laser melting (SLM) is a forming technology in the field of metal additive manufacturing. In order to improve the quality of formed parts, it is necessary to monitor the selective laser melting forming process. At present, most of the research on the monitoring of the selective laser melting forming process focuses on the monitoring of the melting pool, but the quality of forming parts cannot be controlled in real-time. As an indispensable link in the SLM forming process, the quality of powder spreading directly affects the quality of the formed parts. Therefore, this paper proposes a detection method for SLM powder spreading defects, mainly using industrial cameras to collect SLM powder spreading surfaces, designing corresponding image processing algorithms to extract three common powder spreading defects, and establishing appropriate classifiers to distinguish different types of powder spreading defects. It is determined that the multilayer perceptron (MLP) is the most accurate classifier. This detection method has high recognition rate and fast detection speed, which cannot only meet the SLM forming efficiency, but also improve the quality of the formed parts through feedback control.

A Domino Approach for the Synthesis of 4-Carboxamide Oxazolines from Azirines

A regio- and the diastereoselective ring-expansion reaction of N-acyl aziridine has been described for the synthesis of 4-carboxamide oxazolines using InCl3. A domino Ugi-Joullié/ring expansion reaction of arylphenylazirines, isocyanides, and carboxylic acids led to the target product through N-acylaziridine intermediate in the presence of indium catalyst. The oxazolines were synthesized in moderate to excellent yields with high atom-economy and high bond-forming efficiency under mild reaction conditions.

Epithelial Regeneration Ability of Crohn’s Disease Assessed Using Patient-Derived Intestinal Organoids

Little is known about the ability for epithelial regeneration and wound healing in patients with inflammatory bowel diseases. We evaluated the epithelial proliferation and wound healing ability of patients with Crohn’s disease (CD) using patient-derived intestinal organoids. Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < 0.001). Long-term cultured organoids (≥6 passages) derived from controls and CD patients showed an indistinguishable microscopic appearance and culturing behavior. Under TNFα-enriched conditions (30 ng/mL), the organoid reconstitution rate and cell viability of CD patient-derived organoids were significantly lower than those of the control organoids (p < 0.05 for each). The number of EdU+ cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < 0.05). In a wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < 0.001). The wound healing ability of CD patient-derived organoids is reduced in TNFα-enriched conditions, due to reduced cell proliferation. Epithelial regeneration ability may be impaired in patients with CD.

Epithelial Regeneration Ability of Crohn's Disease Assessed Using Patient-Derived Intestinal Organoids

Background: Little is known about the ability of epithelial regeneration and wound healing in patients with inflammatory bowel disease, since the ethical issue of clinical trials and the inherent limitations of tumor-derived epithelial cell lines and animal models. We evaluated the epithelial proliferation and wound healing ability of the patients with Crohn’s disease (CD) using the patient-derived intestinal organoids. Methods: Human intestinal organoids were constructed in a three-dimensional intestinal crypt culture of enteroscopic biopsy samples from controls and CD patients. The epithelial regeneration ability of intestinal organoids was assessed using organoid reconstitution, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), and wound healing assays. Tumor necrosis factor-alpha (TNFa) is a major pro-inflammatory effector during the CD pathogenesis. Under the TNFa-enriched conditions, the epithelial regeneration ability of CD patient-derived organoids was compared with that of control organoids.Results: The organoid-forming efficiency of ileal crypts derived from CD patients was reduced compared with those from control subjects (p < .001). Long-term cultured organoids (≥ 6 passages) derived from controls and CD patients showed inseparable morphologic and cultural features. Under the TNFa-enriched conditions, organoid reconstitution assay and MTT assay revealed that the organoid reconstitution and viability of CD patient-derived organoids were significantly lower than those of control organoids (p <.05 for each). The number of EdU+ proliferative cells was significantly lower in TNFα-treated organoids derived from CD patients than in TNFα-treated control organoids (p < .05). In the wound healing assay, the unhealed area in TNFα-treated CD patient-derived organoids was significantly larger than that of TNFα-treated control organoids (p < .001). Conclusions: Under TNFα-enriched conditions, the wound healing ability of CD patient-derived organoids is reduced due to the reduced cell proliferation compared with that of control organoids. The epithelial regeneration ability may be impaired in patients with CD.