Tumor suppressor genes are reactivated by miR-26A1 via enhancer reprogramming in NSCLC.

Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.

Continuous-Flow Microreactor Accelerates Molecular Collisions for Lignin Depolymerization to Phenolic Monomers and Oligomers.

Effective depolymerization of lignin is the most important step for its comprehensive utilization. So far, most of the studies on depolymerization of lignin focused on batch processing, whereas only a few studies relied on the microreactor. In this study, we developed a continuous-flow microreactor for depolymerization of lignin into monomeric and oligomeric compounds. The yields of monomers and oligomers can be adjusted by varying the temperature, pressure, residence time, NaOH dosage, and solvent. Under optimized conditions, the lignin conversion rate was 77.73 wt %, and the monomer yield was 13.26 wt %, with 77.81% being phenolic compounds. In addition, comparative characterizations on the raw lignin and products demonstrated that the oil products were mainly composed of phenolic tetramers and trimers, and the effective cleavage of the ß-O-4 linkage of S-type lignin was responsible for the high yield of 2,6-dimethoxyphenol. It indicated that raw lignin could be effectively depolymerized continuously using the continuous-flow microreactor, and it will be a new strategy for comprehensive utilization of lignin to produce fine-chemical intermediates.

Risk factors associated with pain in patients with venous malformations of the extremities.

Pain is a common symptom and the major complaint in patients with venous malformations of the extremities, which may lead to joint dysfunction and even walking disabilities. Therefore, this study aimed to investigate determined independent risk factors for pain in these patients. We retrospectively collected data for 168 patients with venous malformations of the extremities from January 16, 2013 to August 13, 2015. They were categorized into painful and painless groups according to the symptom and pain scores. Associations between pain and candidate factors were determined using univariate and multivariate analyses. A total of 125 (74.4%) patients with an average pain score of 4.4 were included in the painful group. In univariate analysis, age, lesion size, tissue involvement, and phleboliths were associated with pain. In the multivariate analysis, only type-II tissue involvement (adjusted odds ratio 4.57; p = 0.001) and phleboliths (adjusted odds ratio 2.44; p = 0.039) were identified as the independent risk factors. In conclusion, this study revealed that prevalence of pain in patients with venous malformations of the extremities was high. Patients who presented with type-II tissue involvement and phleboliths are more likely to suffer from pain.

Intralesional Lidocaine Anesthesia: A Novel Facilitated Anesthesia Technique for Ethanol Sclerotherapy of Venous Malformation.

OBJECTIVE: The aim of this study was to describe a novel anesthesia, intralesional lidocaine anesthesia (ILA), for ethanol sclerotherapy of venous malformation and evaluate the efficacy and safety. METHODS: A prospective study of 100 patients with venous malformations undergoing 100 sclerotherapy procedures with intralesional lidocaine anesthesia (ILA) was conducted. Pain was evaluated by numeric rating scale (NRS) immediately following the procedure. The grade of pain was classified by the NRS as no pain (0), mild (1-3), moderate (4-6), and severe (7-10). Local and systemic complications caused by lidocaine were recorded. RESULTS: The median injected volume of absolute ethanol and 0.25% lidocaine was 5.9 mL and 17.0 mL, respectively. In ILA group, 13 patients had no pain during the procedure, 42 patients had mild pain, 38 patients had moderate pain, and 7 patients had severe pain. The mean NRS scores of the whole ILA group were 3.2 (0-8). No local or systemic complications attributed to lidocaine were reported. CONCLUSION: In a limited series, intralesional lidocaine anethesia seems to be efficient and safe for use in pain management for ethanol sclerotherapy of venous malformation. This anesthesia technique may be a promising first approach for the ethanol sclerotherapy of venous malformations, as it is easy to handle and has minimal sequelae.

Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman's disease: A case report.

Multicentric Castleman disease (MCD) is a heterogeneous, life-threatening disease. A subgroup of HIV-negative and HHV-8-negative MCD is defined as idiopathic MCD (iMCD) with a poor prognosis. Here we report an unusual case of a 47-year-old male patient with iMCD who experienced multiple treatment regimens such as chemotherapy, immunomodulatory therapy, and targeted therapy, all of which were considered ineffective. Subsequently, he was started on bortezomib in combination with dexamethasone for six cycles and he was in complete remission. The patient has survived nearly 13 years to date - the longest survival of any iMCD patient treated with bortezomib in combination with dexamethasone. Bortezomib combined with dexamethasone may be an effective salvage strategy for severe and refractory iMCD.

High-entropy PtCuSnWNb nanoalloys as efficient and stable catalysts for ethanol oxidation electrocatalysis.

Ternary nanoalloys used as electrochemical ethanol oxidation catalysts for direct ethanol fuel cells are confronted with poor stability issues under harsh acidic operating conditions. To address this issue, a carbon-supported quinary PtCuSnWNb high-entropy nanoalloy (denoted as PtCuSnWNb/C) was synthesized by using a polyol reduction method. Due to the unique high-entropy mixing states and strong catalyst-support interactions, PtCuSnWNb/C shows robust structural and compositional stability.

Sulfur doped FeNC catalysts derived from Dual-Ligand zeolitic imidazolate framework for the oxygen reduction reaction.

Iron-nitrogen-carbon (FeNC) catalysts derived from zeolitic-imidazolate frameworks (ZIFs) are worldwide accepted to be the most promising candidates for the oxygen reduction reaction (ORR), but the insufficient stability, the low FeNx exposure and poor density restrict their ORR activity. Here, we demonstrate a strategy to synthesize FeNx sites embedded in a micro/mesoporous N, S co-doped graphitic carbon (FeNC/MUS) by tuning the ligand linkers via the addition of 2-undecylimidazole as a co-ligand in ZIF precursors, and optimizing the electronic structure of Fe center by an in-situ addition of thiourea molecules as sulfur (S) source. 2-undecylimidazole offered an open porous structure to incorporate more FeNx, while the S-doping increased the density of FeNx. Besides, 2-undeclyimidazole cooperatively with S-doping caused favorable changes into the catalyst structure, particularly improved the exposure and density of FeNx sites and doubled the Brunauer-Emmetter-Teller surface area to 1132 m2 g-1 contrasted to the pristine FeNC/M (544 m2 g-1). FeNC/MUS displayed an accelerated ORR activity with a higher half-wave potential of 0.86 V (vs. reversible hydrogen electrode (RHE)) than that of Pt/C (0.84 V) in addition of a longer durability with a 11 % of activity decay after 30000 s in alkaline media. This work offers a new insight to design optimal ZIFs precursor and a facile electron withdrawing S-doping strategy for efficient electrocatalysis.