Mass cytometry-based peripheral blood analysis as a novel tool for early detection of solid tumours: a multicentre study.

OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.

The efficacy of Rhodiola Rosea based on DTI image Segmentation Algorithm for patients with delayed Encephalopathy caused by CO poisoning.

OBJECTIVES: By using DTI image segmentation algorithm investigate the effect of large plants Rhodiola injection on myocardial injury in patients with acute severe CO poisoning (ACOP), and to explore the clinical and CT delayed encephalopathy after ACOP. METHODS: Seventy-two ACOP patients were randomly divided into control and observation group, 36 cases in each group from December 2015 - December 2017. The control group received hyperbaric oxygen, mannitol, dexamethasone, citicoline injection, gangliosides, dracone; observation group were large strain Rhodiola injection treatment group based on the once daily for two weeks of continuous treatment. The head CT, head MRI results were analyzed retrospectively. RESULTS: (1) hsCRP and ET-1 in the observation group were significantly lower than those in the control group, and VEGF was significantly higher than that in the control group (P<0.01). No, NOS, and iNOS were significantly lower than those of the control group (P<0.01); (2) CT images of 16 cases showed bilateral symmetrical fusion lesions with blurred edges, low density, and oval center around the ventricle; (3) MRI showed that the lesion was located in the cerebral cortex, white matter lateral ventricle and/or basal ganglia in 12 cases. CONCLUSION: Rhodiola can reduce myocardial vascular endothelial cell injury, improve cardiac function, and protect the damaged myocardium. Meanwhile, after acute CO poisoning delayed encephalopathy early for CT and MRI examination facilitate analysis and prognosis of the disease.

[Comparative study on specific chromatograms and main active components of wild and cultivated rhizomes of Paris polyphylla var. yunnanensis].

The present study is to compare specific chromatograms and main acitive components between wild and cultivated rhizomes of Paris polyphylla var. yunnanensis by HPLC. HPLC analysis was performed on a Waters XSelect HSS T3 C18 clumn (4.6 mm×250 mm, 5 µm), with a mobile phase consisting of acetonitrile (A)-water (B) at a flow rate of 1 mL•min⁻¹ (0-50 min,30%-50%A;50-80 min,50% A,80-85 min,50%-30%A;85-100 min,30% A). The detection wavelength was 203 nm and the column temperature was controlled at 30 ℃, and the injection volume was 10 µL. HPLC specific chromatograms of wild and cultivated rhizomes of P. polyphylla var. yunnanensis were established and nine steroidal saponins were simultaneously determined by the above method. The mean contents of paris saponin Ⅶ, paris saponin H and total average contents of four pennogenyl saponins in Rhizomes of wild samples were significantly higher than those of cultivated ones. However, this result is opposite from the average content of paris saponin Ⅰ and total average contents of five dioscins in the wild and cultivated samples. Because the significant differences occurred for the specific chromatograms and main active components between the wild and cultivated P. polyphylla var. yunnanensis, much more pharmacological and clinical researches are therefore necessary.

Subsurface A-site vacancy activates lattice oxygen in perovskite ferrites for methane anaerobic oxidation to syngas.

Tuning the oxygen activity in perovskite oxides (ABO3) is promising to surmount the trade-off between activity and selectivity in redox reactions. However, this remains challenging due to the limited understanding in its activation mechanism. Herein, we propose the discovery that generating subsurface A-site cation (Lasub.) vacancy beneath surface Fe-O layer greatly improved the oxygen activity in LaFeO3, rendering enhanced methane conversion that is 2.9-fold higher than stoichiometric LaFeO3 while maintaining high syngas selectivity of 98% in anaerobic oxidation. Experimental and theoretical studies reveal that absence of Lasub.-O interaction lowered the electron density over oxygen and improved the oxygen mobility, which reduced the barrier for C-H bond cleavage and promoted the oxidation of C-atom, substantially boosting methane-to-syngas conversion. This discovery highlights the importance of A-site cations in modulating electronic state of oxygen, which is fundamentally different from the traditional scheme that mainly credits the redox activity to B-site cations and can pave a new avenue for designing prospective redox catalysts.

Study on Restart Safety of Waxy Crude Pipelines Based on Reliability Principle under Constant Flow.

The restart process of waxy crude pipelines is an unsteady thermo-hydraulic coupling process, which mainly includes two modes of the constant flow and constant pressure in industry. However, some parameters involved in the restart process have obvious uncertainties, such as the operating parameters, physical parameters of crude oil, environmental parameters, and pipeline parameters, resulting in the traditional deterministic method that cannot scientifically describe the safety of the pipeline restart process. To do this, this study introduces the reliability-based limit state method and interference principle into the safety evaluation of waxy crude pipelines during the restart process. Considering the random fluctuation characteristics of the mentioned parameters, the restart physical process, the flow and heat transfer mathematical model, and the restart failure limit state function were established. On this basis, the failure probability during the restart process for one waxy crude pipeline under constant flow was determined. This research has realized the quantitative evaluation of restart safety of waxy crude pipelines.

[Scl1 of M41-type group A streptococcus binds low-density lipoprotein].

OBJECTIVE: To study the interaction of streptococcal collagen-like protein 1 (Scl1) of M41-type group A streptococcus (GAS) ATCC12373 with low-density lipoprotein (LDL). METHODS: We cloned, expressed and purified the recombinant proteins rScl1 and its V region rScl1-V, designated as C176 and C176V, derived from Scl1. 41 of M41-type GAS. The binding of rScl1 to LDL was detected with affinity chromatography-binding assay, Western blot analysis and enzyme-linked immunosorbent assay (ELISA), and whole cell binding assays were used to detect the interactions of whole GAS cells with LDL. RESULTS: The results demonstrated that C176 and C176V could specifically bind purified LDL, and M41-type GAS cells expressing native Sell could bind LDL whereas M6-type GAS could not. CONCLUSION: The Sell of M41-type GAS specifically binds LDL.

Aberrant miR-219-5p is correlated with TLR4 and serves as a novel biomarker in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning.

This study aimed to investigate the clinical significance of serum microRNA-219-5p (miR-219-5p) in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat (PQ) poisoning, and its correlation with Toll-like Receptor 4 (TLR4). Luciferase reporter assay was used to investigate in vitro the correlation of miR-219-5p with TLR4. Serum miR-219-5p levels were evaluated by quantitative real-time polymerase chain reaction. Serum levels of TLR4, IL-1ß, and TNF-α were measured by Enzyme-linked immune sorbent assay (ELISA). ROC analysis was performed to assess the diagnostic significance, Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-219-5p in MODS patients. TLR4 was a target gene of miR-219-5p and was increased in MODS patients. Serum miR-219-5p level was decreased and negatively correlated with TLR4 level in MODS patients (r = -0.660, P < 0.001), which had important diagnostic value and negatively correlated with APACHE II score in MODS patients. The miR-219-5p expression was markedly associated with the WBC, ALT, AST, PaCO2, Lac, and APACHE II score. Non-survivals had more patients with low miR-219-5p expression. Patients with low miR-219-5p expression had shorter survival time. MiR-219-5p and APACHE II score were two independently prognostic factors for 28-day survival. MiR-219-5p was negatively correlated with, while TLR4 was positively correlated with the levels of IL-1ß and TNF-α. The serum miR-219-5p level may be a potential biomarker for acute PQ-induced MODS diagnosis and prognosis. Furthermore, miR-219-5p may be associated with the progression of MODS by regulating TLR4-related inflammatory response.

Silence of miR-32-5p promotes endothelial cell viability by targeting KLF2 and serves as a diagnostic biomarker of acute myocardial infarction.

BACKGROUND: MicroRNAs (miRNAs) have been investigated in various cardiovascular diseases. As a fatal disease, acute myocardial infarction (AMI) is a serious global health burden. The purpose of this study was to investigate the role of miR-32-5p in AMI patients and human umbilical vein endothelial cells (HUVECs) to explore novel diagnostic and therapeutic approaches for AMI. METHODS: A target prediction tool miRanda and the luciferase activity assay were used to confirm the interaction of miR-32-5p with Kruppel-like factor 2 (KLF2). Effect of miR-32-5p on HUVECs viability was examined using CCK-8 assay. Serum miR-32-5p expression was measured using quantitative Real-Time PCR, and its correlation with myocardial damage and endothelial injury markers and pro-inflammatory cytokines was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of miR-32-5p in AMI patients. RESULTS: miR-32-5p, as a direct regulator of KLF2, could suppress the cell proliferation of HUVECs. Serum miR-32-5p expression was elevated in AMI patients and positively correlated with the biomarker levels of myocardial damage and endothelial injury and pro-inflammatory cytokines. The area under the ROC curve for miR-32-5p was 0.949, indicating the relatively high diagnostic accuracy of miR-32-5p in AMI patients. CONCLUSION: The data of this study revealed that the increased serum miR-32-5p expression serves as a candidate diagnostic biomarker of AMI, and that miR-32-5p may be involved in the myocardial damage, endothelial injury and inflammatory responses of AMI by targeting KLF2, indicating the potential of miR-32-5p as a diagnostic biomarker and molecular target to improve the treatment of AMI.

Study on the Operation Safety and Reliability of a Waxy Hot Oil Pipeline with Low Throughput Using the Probabilistic Method.

When the hot oil pipeline is running at a low throughput, it easily enters into an unstable condition, which seriously threatens the safety of the hot oil pipeline operation. In this study, the unsteady heat transfer and flow mathematical models for the hot oil pipeline system were established first by comprehensively considering the uncertainty of parameters during pipeline operation, such as the operating parameters (throughput and oil temperature), physical properties of crude oil (freezing point, viscosity, and thixotropic parameters), and environmental parameters (buried deep soil temperature and soil thermal conductivity). Then, the efficient Latin hypercube sampling (LHS) stochastic numerical algorithm was applied and further developed to quantitatively describe the operation safety of hot oil pipelines with low throughput in the form of probability. On the basis of the abovementioned research, the qualitative relationship between pipeline flowrate and friction loss is obtained. Finally, taking an actual crude oil pipeline as an example, the failure probabilities of the pipeline under different operating conditions were analyzed in detail. Combined with the target safety level of pipeline operation, the minimum allowable throughput of pipelines was determined. This study revealed the flow and heat transfer law of hot oil pipelines with low throughput and determined its operation safety and reliability under different operating conditions.

High capacity mercury adsorption on freshly ozone-treated carbon surfaces.

A set of carbon materials was treated by a choice of common oxidizers to investigate the mercury capture capacities at varying temperature conditions. It was found that ozone treatment dramatically increases the mercury capture capacity of carbon surfaces by factors up to 134, but the activity is easily destroyed by exposure to the atmosphere, to water vapor, or by mild heating. Freshly ozone-treated carbon surfaces are shown to oxidize iodide to iodine in solution and this ability fades with aging. FTIR analysis shows broad C-O stretch features from 950 to 1300 cm(-1), which decay upon atmospheric exposure and are similar to the C-O-C asymmetric stretch features of ethylene secondary ozonide. The combined results suggest that the ultra-high mercury capture efficiency is due to a subset of labile C-O functional groups with residual oxidizing power that are likely epoxides or (epoxide-containing) secondary ozonides. The results open the possibility for in situ ozonolysis to create high-performance carbon-based Hg sorbents.

Inhibition of biofilm formation by Cd2+ on Bacillus subtilis 1JN2 depressed its biocontrol efficiency against Ralstonia wilt on tomato.

Bacillus subtilis 1JN2 can serve as an effective biocontrol agent against Ralstonia wilt on tomato, but the efficiency of control depends on the levels of heavy metals in the rhizosphere soil. Here, we investigated how the heavy metal Cd2+ affects the biocontrol efficacy of B.subtilis 1JN2 on Ralstonia wilt. We found that low Cd2+ content of 2 mM or lower had no effects on the biofilm formation of 1JN2, while media containing 3 mM or higher Cd2+ levels inhibited biofilm formation. Interestingly, high concentration of Cd2+ (5 mM) showed inhibition of B.subtilis 1JN2 cell growth. We next tested the effects of Cd2+ on the colonization of 1JN2 by supplementing artificial Cd2+ in the tomato rhizosphere in a greenhouse setting. We found that 3 mM Cd2+ in the tomato rhizosphere inhibited the colonization of B.subtilis 1JN2, Only 103 CFU/mL 1JN2 was detected one week post treated with 107 CFU/mL but 105 CFU/mL could be detected without Cd2+ in the soil. The presence of Cd2+ had no effect on the colonization of Ralstonia solanacearum on tomato, but the biocontrol efficacy against Ralstonia wilt by 1JN2 decreased 54.2% when the soil contained 3 mM Cd2+ compared to the control without Cd2+. Taken together, we found that the failure of biofilm formation of Bacillus subtilis 1JN2 that affected by Cd2+ lead to the decrease of its biocontrol efficacy against Ralstonia wilt on tomato.

Mercury vapor release from broken compact fluorescent lamps and in situ capture by new nanomaterial sorbents.

The projected increase in the use of compact fluorescent lamps (CFLs) motivates the development of methods to manage consumer exposure to mercury and its environmental release at the end of lamp life. This work characterizes the time-resolved release of mercury vapor from broken CFLs and from underlying substrates after removal of glass fragments to simulate cleanup. In new lamps, mercury vapor is released gradually in amounts that reach 1.3 mg or 30% of the total lamp inventory after four days. Similar time profiles but smaller amounts are released from spent lamps or from underlying substrates. Nanoscale formulations of S, Se, Cu, Ni, Zn, Ag, and WS2 are evaluated for capture of Hg vapor under these conditions and compared to conventional microscale formulations. Adsorption capacities range over 7 orders of magnitude, from 0.005 (Zn micropowder) to 188 000 microg/g (unstabilized nano-Se), depending on sorbent chemistry and particle size. Nanosynthesis offers clear advantages for most sorbent chemistries. Unstabilized nano-selenium in two forms (dry powder and impregnated cloth) was successfully used in a proof-of-principle test for the in situ, real-time suppression of Hg vapor escape following CFL fracture.