Metal-Organic Frameworks as Bacteria Mimicking Delivery Systems for Tuberculosis

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb), with an estimated 1.5 million deaths and 10 million infections each year. Although TB can be effectively treated with antibiotics, because of the complications and length of treatment, many people fail to complete the treatment which exacerbates the emergence of drug-resistant M. tb strains. The goal of this work is to develop biomimetic particles as host-directed therapy to target the infected macrophages. Two types of metal-organic frameworks (MOFs), MIL-100(Fe) and MIL-88A(Fe) were developed for bacteriamimicking particles. As a proof-of-concept, Mannose was selected as a ligand to target macrophages because many pathogens express mannose on the surface. MOFs were successfully modified with mannose via EDC/NHS coupling method. No difference was observed in cell uptake between MIL-100(Fe) and mannose-MIL-100(Fe). Mannose- MIL-88A(Fe) showed a significant increase in macrophage uptake compared to its unmodified counterpart. MIL-88A(Fe) is rod-shaped and has a size similar to M. tb making it a natural platform for mycobacteria mimicking. MIL-88A(Fe) was coated with two-layer hybrid lipids and mycolic acid (MA), the most abundant lipid in mycobacteria cell wall, was also incorporated. The coating was confirmed by transmission electron microscopy with energy dispersive x-ray analysis (TEM-EDX). Lipids coated MIL- 88A(Fe) with MA directly extracted from Mycobacterium. Avium exhibited the highest cell uptake compared to lipids coated MIL-88A(Fe) with commercial MA or without MA. As MIL-100(Fe) is readily taken by macrophages, unlike MIL-88A(Fe) for bacteria mimicking, MIL-100 (Fe) nanoparticles were designed to have immunomodulatory property by functionalized with the immunomodulatory ligand curdlan. Curdlan coated MIL-100(Fe) was prepared by nanoprecipitation method. The difference in surface charge, intracellular stability, and thermal property confirms the coat of curdlan on MIL- 100(Fe). Overall, MOFs are promising candidates for the development of biomimetic particles as HDT to target infected cells. M.tb-mimetic MIL-88A(Fe) particles and immunomodulator MIL-100(Fe) may potentially enhance host cell response to an M.tb infection by encapsulated HDT drugs or the carriers themselves

Metal-Organic Framework-Based Sensor for Bacterial Trehalose in Beef Products

Objective The objective is to detect trehalose from pathogenic bacteria using an electrochemical sensor based on alkali earth metal-organic frameworks (AE-MOFS)

Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR) after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1) was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z), 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04) were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73) up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery – A Meta-Analysis

ABSTRACT Introduction: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. Methods: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. Results: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. Conclusion: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients

Key technologies and understandings on the construction of Smart Fields

Key issues for smart fields have been discussed in this paper, including the main features, trends, solutions, construction elements and technical differences in China and abroad. Smart fields include three elements: real-time monitoring, modeling, decision-making and implementation. Their main features are real time, integration and continuity. The essence of smart fields is the optimization based on the model system, including 4 levels: single-well optimization, production optimization, reservoir optimization and optimization of the overall assets. And the overall system optimization is the ultimate objective. For smart fields, the smart is a method of constructing smart fields and efficient development is its purpose. Data is the basis and key of smart fields. The essence of smart field decision-making is based on the model. Smart fields can not go without the support of high-tech industry. The difference of smart fields technologies between home and abroad mainly lies in the oil and gas exploration and development mode and management concepts, technical means and research team, the timeliness of decision making, the responsibilities of different professionals and development objects. Key words: smart field, modeling, decision-making and implementation, real-time monitorin

3-D geological modeling for tight sand gas reservoir of braided river facies

Considering the poor applicability of conventional geological modeling to tight sand gas reservoir in braided river facies, a modeling method of “multi-stage constraints, hierarchical facies control and multi-step modeling” was put forward taking Sulige gas field in Ordos Basin as the study object. The method obtains the GR field by seismic inversion constrained by logging data, and GR model is built under the control of the prior geological knowledge; the relation regression is realized between the GR model and the sandstone probability, sandstone probability model is built, and rock facies model is obtained by multi-point geostatistics theory; sedimentary microfacies model controlled by rock facies and braided-river-system is made; and eventually an effective sand body model is built by integrating sedimentary microfacies, effective sand body scale and reservoir properties distribution. The research method discussed in this paper has put geological constraints into the model as far as possible, enhanced the inter-well sand body predictability and improved the precision rate, thus it can provide a more reliable geological basis for gas reservoir development. Key words: Sulige gas field, tight sand gas, geological modeling, rock facies model, sedimentary microfacies model, multi-stage constraint, hierarchical facie

Establishment and Its Biological Characteristics of Patient-derived Lung Cancer Xenograft Modelse

Background and objective With the ongoing need to improve therapy for lung cancer, there has been an increasing interest in the development of reliable preclinical models to test novel therapeutics. The aim of this study is to establish a patient-derived lung cancer xenograft model in mice and to observe the biological characteristics of xenografts. Methods Surgically resectected tumor specimens from patients with lung cancer were implanted in the subcutaneous layer of the NOD/SCID mice. Cancer specimens of percutaneous lung biopsy by CT fluoroscopy were implanted into the subrenal capsule of nude mouse. The subcutaneous carcinoma was surgically removed when it grew to approximately 1.0 cm in diameter, and then re-transplanted into new nude mice. The growth process of transplanted tumor was observed. Expression of CEA, cytokeratin, and Ki67 were detected by immunohistochemistry. Mutations in the exons 18-21 of EGFR and exons 12,59 of K-ras of primary and xenograft tumors were examined. The cell cycle of xenograft tumor cells was analyzed by flow cytometry. Results Eleven cases were conducted for NOD/SCID mice and nude mice modelling. The patient-derived lung cancer xenografts have been established successfully, and the tumor could be passed to new nude mice, including No 2 model (adenocasinoma), No. 3 model (small cell lung cancer), and No. 5 model (squamous cell cancer). High homogeneity was found between xenograft tumors and human lung cancer in histopathology, immunohistochemical phenotype, and EGFR, K-ras mutation status . The S-phase fraction of xenograft cell cycle was prolonged, which indicated that the xenografts remains highly proliferated. Conclusion The xenotransplantation models established for patient-derived lung cancer in immune deficient mice. The success rate is 27%. This model system displayed the biological characteristics of human lung cancer, suggesting that it may provide a stable, reliable, and useful animal model in human lung cancer research