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Unlike angiogenesis in normal tissues, tumor angiogenesis is typically dysregulated, during which the HIF1/VEGFA signaling pathway plays a pivotal role. Solid tumors generate immature vessels, which promote tumor progression and treatment resistance. NSD1 can di-methylate histone 3 lysine 36 and regulate transcription factors binding to the promoters of various genes. However, the role of NSD1 in tumorigenesis remains elusive. Here, we evaluated the relationship between NSD1 signaling and HIF1 signaling. It was found that NSD1 transcriptionally regulates HIF1α expression by recruiting STAT3 molecule into the HIF1α promoter. In vivo xenograft experiments further confirmed that HIF1α and STAT3 maintenance is essential for NSD1-mediated tumor progression and angiogenesis. Therefore, the NSD1/STAT3/HIF1α signaling pathway may be a novel and effective treatment target for ESCA. [ABSTRACT FROM AUTHOR]

Introduction: Ground glass opacity featured lung adenocarcinomas (GGO-LUAD) display more indolent biological behavior than solid nodule featured lung adenocarcinomas (SN-LUAD) and have an excellent prognosis. However, the cellular immune characteristics of GGO-LUAD remain poorly understood. Methods: Immunohistochemistry technique was performed to stain related immune markers (CD8, CD103, CD20, CD138, CD4, FOXP3, CD68, CD163, PD-1 and PD-L1) and TGF-β from 15 patients with pure GGO-LUAD and 15 patients with SN-LUAD tissue sections (Paired cohort), and then, the related markers with significant differences were verified on 10 patients (Verified cohort) with both pure GGO-LUAD and SN-LUAD. For localization analysis of CD68 + tumor-associated macrophages (TAMs) and FOXP3 + Terg cells in tumor areas, pure GGO-LUAD and SN-LUAD were also stained for simultaneous detection of pan-CK, CD68 and FOXP3 by multiplex immunofluorescence. Results: In the Paired cohort, compared with SN-LUAD, only the infiltration of TAMs and Treg cells was significantly lower in GGO-LUAD. The infiltration of the remaining immune cells including CD8 + T cells, CD4 + T cells, CD103 + T cells, CD20 + B cells and CD138 + Plasma cells in GGO-LUAD, although relatively low, was not significantly different. Meanwhile, the expression of TGF-β was significantly higher in SN-LUAD. And the above results have also been confirmed in the Verified cohort. Moreover, there was no significantly difference in PD-L1 expression in GGO-LUAD compared to SN-LUAD both in the Paired cohort and Verified cohort. Conclusions: GGO-LUAD demonstrates an overall less active immune landscape as compared with SN-LUAD. TAMs and TGF-β may play an important role in the progression of GGO-LUAD. More importantly, PD-L1 expression in GGO-LUAD is comparable to that in SN-LUAD, indicating that there may be other reasons for the insensitivity of GGO-LUAD to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) dissection along left recurrent laryngeal nerve (RLN) is challenging in esophagectomy for esophageal cancer, and double-lumen endotracheal tube (DLT) impedes the exposure of this area. The aim of this study was to determine whether bronchial blockers (BB) could be a better choice for this procedure. Methods: The clinical characteristics of patients who received McKeown esophagectomy with radical lymph node dissection in Wuhan Tongji Hospital between August 2017 and July 2019 were retrospectively analyzed. The 1:1 propensity score match analysis was performed to compare the short-term effectiveness, the numbers of lymph nodes dissected, and the patterns of recurrence and survival between the two groups. Results: A total of 294 patients (192 and 102 in the DLT and BB group, respectively) were enrolled in the study. After matching, 204 patients (102 pairs) who underwent one-lung ventilation with DLT or BB displayed no significant variance in baseline characteristics. The BB group had higher number of LNs resected along left RLN (1.8 ± 2.3 vs. 2.5 ± 2.5, P = 0.001). For patients with metastatic left RLN LN, the BB group had longer medium survival time (15 vs. 32 months, P = 0.045), and tended to have longer medium recurrence-free survival time (6 vs. 15 months, P = 0.079), and lower rate of upper mediastinal and cervical LN recurrence (30.00% vs. 66.67%, P = 0.198). The postoperative complications were similar in both groups. Conclusions: Compared with DLT, using BB in esophagectomy may allow more radical lymphadenectomy along left RLN. [ABSTRACT FROM AUTHOR]

In this study, regenerated cellulose-based macrogels with abundant carboxyl groups and interconnected microporous structures were synthesized from cellulose fibers (CFs)/cellulose nanofibers (CNFs) and utilized as stable, efficient, and recyclable platforms for enzyme immobilization. CNFs with different carboxyl contents were prepared by a TEMPO (2, 2, 6, 6 -tetramethylpiperidine-1-oxyl radical)-medium oxidation system. The cellulose-based macrogels were prepared by dissolving CFs and CNFs in a NaOH/urea aqueous solution and a followed extrusion process. The carboxyl groups within the macrogels were then activated by an N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC·HCl)/Nhydroxysuccinimide (NHS) system, which provides these macrogels with efficient binding sites for enzyme immobilization. The three-dimensional network structures of the macrogels facilitate the enzymes to infiltrate into the core of the macrogels and be fixed on the abundant pore walls. The immobilized enzymes maintain activity at a higher pH than free enzymes. Moreover, the immobilized enzymes have higher temperature tolerance, and their optimal reaction temperature is about 10 °C higher than that of free enzymes. The immobilized enzymes retain 24% of the initial activity after repeated use for 7 times. The microporous regenerated cellulose-based macrogels show potential in the fields of enzyme immobilization and biocatalysis. [ABSTRACT FROM AUTHOR]

Both long non-coding RNA (lncRNA) RMRP and heat shock protein (HSP) 70 have been known to play crucial roles in inflammation. The present study investigated the roles of lncRNA RMRP and HSP70 protein 4 (HSPA4) in lipopolysaccharide (LPS)-induced sepsis. The C57BL/6 mice were treated with LPS, following which the cardiomyocytes were isolated for in vitro experiments. Further, a cardiac muscle cell line, HL-1 was transfected with plasmids expressing RMRP and HSPA4, si-NC, si-HSPA4, miR-1-5p mimic, and controls in vitro. Cell apoptosis, mitochondrial membrane potential (MMP), and levels of intracellular reactive oxygen species (ROS), mRNAs, and proteins were detected in the transfected mice tissues and cells. The LPS treatment significantly reduced the expression levels of RMRP, MMP, and mitochondrial cytochrome C. Moreover, it enhanced the cardiomyocyte apoptosis, intracellular ROS levels, cytoplasm cytochrome C levels, and the expression of caspase-3 and caspase-9 and nuclear factor κB (NF-κB) p65 subunit. The predicted RMRP-miR-1-5p-HSPA4 network was validated by co-transfection experiments in vitro in HL-1 cells. The transfection of miR-1-5p-treated cells with pcDNA-RMRP enhanced the levels of the protein HSPA4; however, no change at the mRNA level was observed. Moreover, miR-1-5p mimic attenuated the protective effect of pcDNA-HSPA4 against LPS-induced mitochondrial damage and apoptosis. In addition, we observed that silencing of HSPA4 increased the expression of nuclear p65; however, this effect could be reversed by co-transfection with pcDNA-RMRP. The lncRNA RMRP axis acts as a sponge for miR-1-5p. RMRP inhibits LPS-induced apoptosis of cardiomyocytes and mitochondrial damage by suppressing the post-transcriptional regulatory function of miR-1-5p on HSPA4. We believe that RMRP exhibits therapeutic potential for LPS-induced myocardial dysfunction both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Increasing degradation of amoxicillin in water by low-cost advanced functional activated carbon-based materials derived from bagasse is an effective and economic way to remove the antibiotic residue pollutant and for high-valued utilization and transformation of plant wastes. In this work, bagasse was pyrolyzed and Zn2+ was activated for designing a high-efficiency bagasse-based activated carbon, which was characterized by FTIR, XRD, XPS, SEM, EDS, and ζ potential analyses. These analyses illustrated the mechanism of amoxicillin degradation, and microscale zero-valent zinc in bagasse-based activated carbon has a key role in amoxicillin degradation. Amoxicillin was broken down by reductive degraded radicals, which were produced by microscale zero-valent zinc corrosion in water. After the amoxicillin degradation, the byproduct of zinc hydroxide being adsorbed onto the used bagasse-based activated carbon can provide possibility of sustainable regeneration. Mass spectra analysis illustrated the main degradation products of amoxicillin. The kinetic experiments were adopted to observe the process of amoxicillin degradation, followed by the pseudo-first-order kinetic model. The isotherm experiments demonstrated that the maximum amoxicillin degradation capacity of bagasse-based activated carbon was about 46 mg g−1. The bagasse wastes were used as carbon source to design potential advanced activated carbon materials for increasing degradation of amoxicillin in water. [ABSTRACT FROM AUTHOR]

The utilization of bagasse as a raw material to prepare activated carbon adsorbents is an effective way to solve the water pollution problem, while achieving the goal of treating waste simultaneously. An effective activated carbon-based adsorbent was prepared from sugar cane bagasse with a one-step method of pyrolysis and ZnCl2 activation for efficient Cr(VI) removal from water. Morphology, physicochemical properties and structure of the adsorbent samples were studied by Scanning Electron Microscope, Energy Dispersive Spectroscopy, X-ray Diffraction, N2 adsorption and desorption, Fourier Transform infrared spectroscopy and X-ray Photoelectron Spectroscopy. The batch and fixed bed adsorption experiments were adopted to confirm the one-step preparation of pyrolysis and ZnCl2 during the activation process and to investigate the adsorption mechanism of Cr(VI). The maximum adsorption capacity was 80.880 mg g−1, while the adsorption behavior fitted better with Freundlich equation and pseudo-second-order kinetics. These results confirmed that chemical adsorption is the strongest adsorption interaction during the adsorbing process of Cr(VI), and the adsorbents could effectively capture Cr(VI) to form monodentate and bidentate complexes. [ABSTRACT FROM AUTHOR]

Purpose: UGT1A1*28/*6 as predictors of severe irinotecan-related diarrhea (SIRD) were duplicated by many studies. However, some patients of lower risk genotype ( UGT1A1*1/*1) still suffered SIRD and the extremely low frequency of UGT1A1*6/*6 limited its clinical usage. Previous studies proved that the transforming growth factor (TGFB) family may have some effect on MTX-induced mucositis. However, the associations between TGFB gene variants and SIRD have never been reported so far. Our aim was to improve the predictive value of UGT1A1 gene variants on SIRD. Methods: Six SNPs ( TGFB1 rs1800469; TGFBR1 rs10733710, rs334354 and rs6478974; TGFBR2 rs3087465; UGT1A1*6) and UGT1A1*28 were selected for genotyping in 160 metastatic colorectal cancer patients treated with irinotecan in a prospective multicenter trial (NCT01282658). Results: UGT1A1*6, UGT1A1*28, rs1800469 and rs3087465 were all associated with SIRD ( p = 0.026, 0.014, 0.047 and 0.045 respectively). A novel genetic score model (with a cut off value of 1.5) based on them was created to predict SIRD (OR = 11.718; 95 % CI 2.489-55.157, p = 0.002). In patients of gene score > 1.5, the risk of SIRD was much higher (23.5 vs. 2.8 %, p = 2.24E−04) and continued in the first 6 cycles of chemotherapy, while in patients with gene score ≤1.5, the risk was much lower and none of them suffered SIRD after the first cycle of chemotherapy ( p = 0.0003). Conclusions: The novel genetic score model improved the predictive value of UGT1A1 on SIRD. If validated, it will provide valuable information for clinical use of irinotecan. [ABSTRACT FROM AUTHOR]

The αvβ6 integrin is a cell surface adhesion molecule that plays critical roles in the injury and inflammation processes. We hypothesized that polymorphisms in αvβ6 integrin genes (ITGAV and ITGB6) might be associated with the risk of radiation pneumonitis (RP) in lung cancer patients treated with thoracic radiation. We genotyped three potentially functional αvβ6 integrin single-nucleotide polymorphisms (rs1839123 and rs4129787 in ITGAV, and rs4665162 in ITGB6) and found that the genotypes of rs4665162 single-nucleotide polymorphisms were predictors of RP development (for grade ≥2 RP, HR = 1.505, 95 % CI 1.069-2.119, P = 0.019; for grade ≥3 RP, HR = 3.006, 95 % CI 1.431-6.313, P = 0.004). Our results showed that AG/GG genotypes of ITGB6 rs4665162 gene were associated with a higher risk of RP in patients with lung cancer receiving radiotherapy and thus may serve as a reliable predictor of RP. Further studies will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutation status is the best predictor of patient response to treatments with tyrosine kinase inhibitors in primary lung adenocarcinoma and is typically analyzed by DNA-based techniques, such as direct DNA sequencing and allele-specific PCR. Recently, however, two mutation-specific antibodies against delE746-A750 in exon 19 and L858R in exon 21 have opened the door for a more convenient and more efficient strategy to determine EGFR mutation status. To evaluate the clinical application of a new mutation-specific mouse monoclonal antibody for EGFR (L858R), we performed immunohistochemistry (IHC) studies with tumor samples from primary lung adenocarcinoma in retrospective and validation settings. A total of 215 cases of primary lung adenocarcinoma were examined and compared using a combination of DNA-based techniques (direct DNA sequencing and/or allele-specific PCR) and protein-based IHC. IHC staining was assessed on a 0 to 3+ score scale, and a cutoff value of 2+ was used as positive by IHC. In the retrospective setting, statistical analyses of the data showed that the sensitivity of IHC was 90.9 % and the specificity was 96.8 %. Findings from the validation study demonstrated that the sensitivity and specificity of IHC were 88.2 % and 100 %, respectively. IHC with the novel mutation-specific antibody could be used as a screening method to assess the EGFR L858R mutation status in primary lung adenocarcinoma. [ABSTRACT FROM AUTHOR]