Expert consensus on resection of chest wall tumors and chest wall reconstruction

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T$_{3-4}$N$_{0-1}$M$_{0}$. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years

Regulation of RhoA/ROCK1 signaling pathway by miR 26b in sepsis induced acute lung injury

Purpose: To investigate the role of miR-26b in the regulation of RhoA/ ROCK1 signaling pathway in acute lung injury (ALI) caused by sepsis. Methods: Thirty male rats were randomized into sham group (SG), cecal ligation and puncture (CLP) group (CG) and miR-26b mimic group (MG). Hematoxylin and eosin (H & E) staining assay was performed to determine the pathological characteristics of rat lung tissues in each group, while enzyme-linked immunosorbent assay (ELISA) was conducted to determine TNF-α and IL-1β levels. The miR-26b expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), while RhoA and Rock1 protein levels were assessed using western blotting. Results: The CG had significant lung injury in comparison with the SG. There were significant elevation in TNF-α and IL-1β levels (p < 0.05). RhoA and ROCK1 levels in lung tissue were noticeably elevated in CG (p < 0.05). After treatment, lung injury in MG was reduced in contrast to CG. The MG showed statistically significant decrease (p < 0.05) in the levels of TNF-α and IL-1β, while the lung tissue mRNA expression and the RhoA and ROCK1 expression levels were significantly reduced in MG (p < 0.05). Conclusion: The MiR-26b mimics plays an important role in the treatment of ALI induced by sepsis in rats by regulating RhoA/ROCK1 signaling pathway. Thus, the findings of this study provide a theoretical basis for clinical studies on the use of miR-26b in the therapy of sepsis

A Nested Semiparametric Method for Case-control study with missingness

We propose a nested semiparametric model to analyze a case-control study where genuine case status is missing for some individuals. The concept of a noncase is introduced to allow for the imputation of the missing genuine cases. The odds ratio parameter of the genuine cases compared to controls is of interest. The imputation procedure predicts the probability of being a genuine case compared to a noncase semiparametrically in a dimension reduction fashion. This procedure is flexible, and vastly generalizes the existing methods. We establish the root-n asymptotic normality of the odds ratio parameter estimator. Our method yields stable odds ratio parameter estimation owing to the application of an efficient semiparametric sufficient dimension reduction estimator. We conduct finite sample numerical simulations to illustrate the performance of our approach, and apply it to a dilated cardiomyopathy study

Ionic liquid-assisted synthesis of Yb3+-Tm3+ codoped Y7O6F9 petal shaped microcrystals with enhanced upconversion emission

Petal-like Yb3+-Tm3+ codoped Y7O6F9 microparticles were achieved via ionic liquid-assisted (IL) hydrothermal process. The emission efficiency of Y7O6F9:Yb3+/Tm3+ powders is much stronger than that of Y2O3:Yb3+/Tm3+ sample. Under excitation at 980 nm with an unfocused laser beam under weak pump density of ∼0.1 W/cm2 (pump power 10 mW), the UC emission of the sample can been seen clearly. Four emission bands at 477, 540, 647 and 692 nm are observed and correspond to the 1G4 state to 3H6 state, 1D2 state to 3H5 state, 1G4 sate to 3F4 state, and 3F3 state to 3H6 state transition of Tm3+ ions. The enhanced UC emission is related to high crystallinity and lower effective phonon energy of oxyfluorides. The ionic liquid (IL) of [BMIM][BF4] is used both as the reaction medium and the source of F−

Iohexol Degradation by Biogenic Palladium Nanoparticles Hosted in Anaerobic Granular Sludge

To improve the degradation ability of anaerobic granular sludge (AGS) toward the iodinated contrast media (ICM) iohexol, biogenic nanoscale palladium (Pd) was formed in AGS via microbial reduction. The Pd hosted in AGS (Pd-AGS) was used for iohexol degradation. The effects of the electron donor, reaction medium, iodide ion fouling, and polymer embedding of the Pd-AGS on the reactivity were investigated. Our results showed the Pd-AGS increased the degradation rate of iohexol, with a conversion rate constant increased by 86.3-fold compared to the AGS control. Various organic compounds were investigated as electron donors to initiate the catalytic activity of Pd-AGS and the promotion achieved with the tested electron donors was in the following order: formate > lactate > ethanol > glucose > acetate. The Pd-AGS had high reactivity in deionized water at mild pH, and almost no reactivity under acidic (pH = 1.2) and alkaline (pH > 11) conditions. The presence of iodide ions in the medium inhibited the catalytic activity of Pd-AGS toward iohexol because of catalyst fouling. Embedding the Pd-AGS in alginate, chitosan, or polyvinyl alcohol (PVA) could prevent Pd loss but it also retarded the iohexol degradation rate. The Pd-AGS, as a combination of Pd catalyst and AGS, provides a novel strategy for iohexol degradation in polluted water and wastewater

Design, Synthesis and Biological Evaluation of Biphenylamide Derivatives as Hsp90 C-terminal Inhibitors

Modulation of Hsp90 C-terminal function represents a promising therapeutic approach for the treatment of cancer and neurodegenerative diseases. Current drug discovery efforts toward Hsp90 C-terminal inhibition focus on novobiocin, an antibiotic that was transformed into an Hsp90 inhibitor. Based on structural information obtained during the development of novobiocin derivatives and molecular docking studies, scaffolds containing a biphenyl moiety in lieu of the coumarin ring present in novobiocin were identified as new Hsp90 C-terminal inhibitors. Structure-activity relationship studies produced new derivatives that inhibit the proliferation of breast cancer cell lines at nanomolar concentrations, which corresponded directly with Hsp90 inhibition

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages

Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1- and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM- and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies

Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors

Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued

NHX antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development

AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the ER-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were co-localized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+-leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes