Electrocatalytic nitrate reduction (NRR) represents one promising alternative to the Haber–Bosch process for NH3 production due to the lower reaction energy barrier compared to N2 reduction and the ...potential recycling of nitrogen source from nitrate wastewater. The metal oxides with oxygen vacancy (Ov) display high NH3 selectivities in NRR (NO2−/N2 as side products), but the complexity in Ov enrichment and the inferior hydrogen adsorption on oxides make NRR an inefficient process. Herein, one superior dual-site NRR electrocatalyst that is composed of Ov-enriched MnO2 nanosheets (MnO2-Ov) and Pd nanoparticles (deposited on MnO2) is constructed over the three-dimensional porous nickel foam (Pd–MnO2-Ov/Ni foam). In a continuous-flow reaction cell, this electrode delivers a NO3−-N conversion rate of 642 mg N m−2electrode h−1 and a NH3 selectivity of 87.64% at −0.85 V vs. Ag/AgCl when feeding 22.5 mg L−1 of NO3−–N (0.875 mL min−1), outperforming the Pd/Ni foam (369 mg N m−2electrode h−1, 85.02%) and MnO2-Ov/Ni foam (118 mg N m−2electrode h−1, 32.25%). Increasing the feeding NO3−–N concentration and flow rate to 180.0 mg L−1 and 2.81 mL min−1 can further lift the conversion rate to 1933 and 1171 mg N m−2electrode h−1, respectively. The combination of experimental characterizations and theoretical calculations reveal that the MnO2-Ov adsorbs, immobilizes, and activates the NO3− and N-intermediates, while the Pd supplies the Ov sites with sufficient adsorbed hydrogen (H*) for both the NRR and Ov refreshment. Our work presents a good example of utilizing dual-site catalysis in the highly selective conversion of NO3− to NH3 that is important for nitrate pollution abatement, nitrogen resource recycling, as well as sustainable NH3 production.
E7050 is a potent inhibitor of c-Met receptor tyrosine kinase and has potential for cancer therapy. However, the underlying molecular mechanism involved in the anti-cancer property of E7050 has not ...been fully elucidated. The main objective of this study was to investigate the anti-tumor activity of E7050 in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells in vitro and in vivo, and to define its mechanisms. Our results revealed that E7050 reduced cell viability of MES-SA/Dx5 cells, which was associated with the induction of apoptosis and S phase cell cycle arrest. Additionally, E7050 treatment significantly upregulated the expression of Bax, cleaved PARP, cleaved caspase-3, p21, p53 and cyclin D1, while it downregulated the expression of survivin and cyclin A. On the other hand, the mechanistic study demonstrated that E7050 inhibited the phosphorylation of c-Met, Src, Akt and p38 in HGF-stimulated MES-SA/Dx5 cells. Further in vivo experiments showed that treatment of athymic nude mice carrying MES-SA/Dx5 xenograft tumors with E7050 remarkably suppressed tumor growth. E7050 treatment also decreased the expression of Ki-67 and p-Met, and increased the expression of cleaved caspase-3 in MES-SA/Dx5 tumor sections. Therefore, E7050 is a promising drug that can be developed for the treatment of multidrug-resistant uterine sarcoma.
The expression of both high-mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) is upregulated in degenerated discs. HMGB1 is known to function as a coupling factor ...between hypoxia and inflammation in arthritis, and this inflammatory response is modulated by microRNAs (miRNAs), with miR-107 expression downregulated during hypoxia. In this study, we investigated the regulation of the miR-107/HMGB1/RAGE pathway in degenerated nucleus pulposus cells (NPCs) after hyperbaric oxygen (HBO) treatment.
NPCs were separated from human degenerated intervertebral disc tissues. The control cells were maintained in 5% CO
/95% air, and the hyperoxic cells were exposed to 100% O
at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The cellular protein and mRNA levels of HMGB1, RAGE, and inducible nitric oxide synthase (iNOS) were assessed, and the phosphorylation of MAPK (p38MAPK, ERK, and JNK) was evaluated. Additionally, cytosolic and nuclear fractions of the IκBα and NF-κB p65 proteins were analyzed, and secreted HMGB1 and metalloprotease (MMP) levels in the conditioned media were quantified.
Using microarray analyses, 96 miRNAs were identified as upregulated and 66 downregulated following HBO treatment. Based on these results, miR-107 was selected for further investigation. Bioinformatics analyses indicated that the 3' untranslated region of the HMGB1 mRNA contained the "seed-matched-sequence" for hsa-miR-107, which was validated via dual-luciferase reporter assays. MiR-107 was markedly induced by HBO, and simultaneous suppression of HMGB1 was observed in NPCs. Knockdown of miR-107 resulted in upregulation of HMGB1 expression in HBO-treated cells, and HBO treatment downregulated the mRNA and protein levels of HMGB1, RAGE, and iNOS and the secretion of HMGB1. In addition, HBO treatment upregulated the protein levels of cytosolic IκBα and decreased the nuclear translocation of NF-κB in NPCs. Moreover, HBO treatment downregulated the phosphorylation of p38MAPK, ERK, and JNK and significantly decreased the secretion of MMP-3, MMP-9, and MMP-13.
HBO inhibits pathways related to HMGB1/RAGE signaling via upregulation of miR-107 expression in degenerated human NPCs.
Background
The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression ...grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.
Materials and Methods
This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.
Results
The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.
Conclusion
AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.
Implications for Practice
The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.
The aim of this large cohort study was to define the clinical significance of the AJCC/CAP tumor regression grading system for locally advanced rectal cancer, which could potentially be used to select the patients who would benefit from more intensive adjuvant chemotherapy as well as to protect patients from excessive treatment.
E7050 is an inhibitor of VEGFR2 with anti-tumor activity; however, its therapeutic mechanism remains incompletely understood. In the present study, we aim to evaluate the anti-angiogenic activity of ...E7050 in vitro and in vivo and define the underlying molecular mechanism. It was observed that treatment with E7050 markedly inhibited proliferation, migration, and capillary-like tube formation in cultured human umbilical vein endothelial cells (HUVECs). E7050 exposure in the chick embryo chorioallantoic membrane (CAM) also reduced the amount of neovessel formation in chick embryos. To understand the molecular basis, E7050 was found to suppress the phosphorylation of VEGFR2 and its downstream signaling pathway components, including PLCγ1, FAK, Src, Akt, JNK, and p38 MAPK in VEGF-stimulated HUVECs. Moreover, E7050 suppressed the phosphorylation of VEGFR2, FAK, Src, Akt, JNK, and p38 MAPK in HUVECs exposed to MES-SA/Dx5 cells-derived conditioned medium (CM). The multidrug-resistant human uterine sarcoma xenograft study revealed that E7050 significantly attenuated the growth of MES-SA/Dx5 tumor xenografts, which was associated with inhibition of tumor angiogenesis. E7050 treatment also decreased the expression of CD31 and p-VEGFR2 in MES-SA/Dx5 tumor tissue sections in comparison with the vehicle control. Collectively, E7050 may serve as a potential agent for the treatment of cancer and angiogenesis-related disorders.
A 3D pillar-layer framework (1) with uncoordinated carboxyl groups exhibits exceptional stability. It can effectively and selectively adsorb Cu(2+) ions and has been applied as a chromatographic ...column for separating Cu(2+)/Co(2+) ions.
Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. ...Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named “ion induction and deduction” was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple “net-hubs” and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.
Summary
An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive ...significance in anemia patients. With further research, a treatment algorithm can be developed to potentially identify patients at high risk of preoperative mortality.
Introduction
Red blood cell distribution width (RDW) is an independent predictor of various disease states in elderly individuals, but its association with the prognosis of elderly hip fracture patients is controversial. This study aimed to evaluate the prognostic value of RDW in such patients, construct a prediction model containing RDW using random survival forest (RSF) and Cox regression analysis, and compare RDW in patients with and without anemia.
Methods
We retrospectively analyzed the data of elderly patients who underwent hip fracture surgery, selected the best variables using RSF, stratified the independent variables by Cox regression analysis, constructed a 1-year mortality prediction model of elderly hip fracture with RDW, and conducted internal validation and external validation.
Results
Two thousand one hundred six patients were included in this study. The RSF algorithm selects 12 important influencing factors, and Cox regression analysis showed that eight variables including preoperative RDW (pre-RDW) were independent risk factors for death within 1-year after hip fracture surgery in elderly patients. Stratified analysis showed that pre-RDW was still independently associated with 1-year mortality in the non-anemia group and not in the anemia group. The nomogram prediction model had high differentiation and fit, and the prediction model constructed by the total cohort of patients was also used for validation of patients in the anemia patients and obtained good clinical benefits.
Conclusion
An independent correlation between pre-RDW and 1-year mortality after surgery in elderly hip fracture can be used to predict mortality in elderly hip fracture patients and has predictive significance in anemia patients.
Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due ...to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.
Boron derivatives are playing an increasingly important role on drug discovery campaigns. Here, we reviewed the use and pharmacological properties of boronic acids as therapeutic agents for various diseases. Display omitted
Utilizing porous polyacrylonitrile (PAN) fibers as the precursors, porous carbon fibers were obtained by cross-linking of precursor fibers with hydrazine hydrate and subsequent heat treatment. A ...nitrogen content of more than 14 wt % was achieved in the carbon fibers. The porous carbon fiber that was prepared at low concentration of hydrazine hydrate (5 wt %) showed an optimal BET surface area of 277.4 m2/g with micro-/meso-/macropores. The CO2 adsorbed amount of this porous carbon fiber was 101 mg/g at 25 °C under atmospheric pressure, which was 2.1 times that of the fiber without cross-linking with hydrazine hydrate. In the simulated flue gas environment (10% CO2/90% N2), the adsorption capacity of the above-mentioned porous fiber was 32 mg/g at 25 °C, which was 1.4 times that of the fiber without cross-linking. These CO2 adsorption results demonstrated that the nitrogen functionalities and porous structure of the porous carbon fiber played an equivalent important role in the adsorption of CO2. The porous carbon fiber also owned an excellent CO2 reusability, and 96% of the adsorption capacity was maintained after 20 cycles of CO2 adsorption and desorption. The porous carbon fibers enriched with nitrogen could thus be a potential material for CO2 capture.
PDF
