Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Characteristics of plasma exosomes in drug-resistant tuberculosis patients.

BACKGROUND: Increasing prevalence of drug-resistant tuberculosis (DR-TB) poses a major challenge to the early detection and effective control of tuberculosis (TB). Exosomes carrying proteins and nucleic acid mediate intercellular communication between host and pathogen including Mycobacterium tuberculosis. However, molecular events of exosomes indicating the status and development of DR-TB remain unknown. This study determined the proteomics of exosome in DR-TB and explored the potential pathogenesis of DR-TB. METHODS: Plasma samples were collected from 17 DR-TB patients and 33 non-drug-resistant tuberculosis (NDR-TB) patients using grouped case-control study design. After exosomes of plasma were isolated and confirmed by compositional and morphological measurement for exosomal characteristics, a label-free quantitative proteomics of exosomes was performed and differential protein components were determined via bioinformatics analysis. RESULTS: Compared with the NDR-TB group, we identified 16 up-regulated proteins and 10 down-regulated proteins in the DR-TB group. The down-regulated proteins were mainly apolipoproteins and mainly enriched in cholesterol metabolism-related pathways. Apolipoproteins family including APOA1, APOB, APOC1 were key proteins in protein-protein interaction network. CONCLUSION: Differentially expressed proteins in the exosomes may indicate the status of DR-TB from NDR-TB. Apolipoproteins family including APOA1, APOB, APOC1 may be involved in the pathogenesis of DR-TB by regulating cholesterol metabolism via exosomes.

Pediococcus pentosaceus PR-1 modulates high-fat-died-induced alterations in gut microbiota, inflammation, and lipid metabolism in zebrafish.

Introduction: Obesity is a health issue worldwide. This study aimed to evaluate the beneficial effects of Pediococcus pentococcus PR-1 on the modulating of gut microbiota, inflammation and lipid metabolism in high-fat-diet (HFD)-fed zebrafish. Methods: Adult zebrafish were fed a commercial (C), high fat (H, 25% fat), probiotic (P, 106 CFU/g), or high fat with probiotic (HP) diets twice daily for 5 weeks. Gut microbiota were analysed using 16S rRNA gene sequencing. Gene expressions of intestinal cytokine, intestinal TJ protein, and liver lipid metabolism were analysed by quantitative real-time polymerase chain reaction. Biochemical and histological analysis were also performed. Results and discussion: P. pentosaceus PR-1 reduced body weight and BMI, indicating its anti-obesity effect. The 16S rRNA sequencing results showed HFD induced a distinct gut microbiota structure from C group, which was restored by probiotic. P. pentosaceus PR-1 improved gut health by decreasing the abundance of Ralstonia and Aeromonas which were increased induced by HFD. Moreover, probiotic restored abundance of Fusobacteria, Cetobacterium and Plesiomonas, which were decreased in HFD-fed zebrafish. The results of quantitative real-time polymerase chain reaction showed probiotic suppressed HFD-induced inflammation by decreasing the expressions of IL-1b and IL-6. Levels of hepatic TNF-α, IL-1ß, and IL-6 were reduced by probiotic in HFD-fed zebrafish. Probiotic also ameliorated gut barrier function by increasing the expressions of occludin, Claudin-1, and ZO-1. Probiotic exerted anti-adipogenic activity through regulating the expressions of SREBP1, FAS and LEPTIN. Levels of hepatic triglyceride, total cholesterol, low density lipoprotein were also reduced by probiotic. Histological analysis showed probiotic alleviated liver steatosis and injury induced by HFD. P. pentosaceus PR-1 might be useful as a dietary health supplement, especially for reducing obesity.

Efficacy of Nimodipine Combined with Latanoprost in Treating Open-Angle Glaucoma and Its Influence on Ocular Hemodynamics and Visual Field Defects.

Background: Open-angle glaucoma is a common ophthalmic disease, which has a great impact on the vision of middle-aged and elderly people. Medication plays an important role in the treatment of glaucoma, so finding effective drug treatment is of great significance to improve the quality of life of glaucoma patients. Objective: To explore the curative effect of nimodipine combined with latanoprost in the treatment of open-angle glaucoma and its effect on ocular hemodynamics and visual field defects. Methods: This study retrospectively analyzed the clinical data of 87 patients with open-angle glaucoma who came to the Shanxi Province Fenyang Hospital and The First Affiliated Hospital of Shanxi Datong University for treatment from January 2019 to January 2021. According to different treatment plans, the patients were divided into two groups: an observation group (n = 46) treated with nimodipine combined with latanoprost, and a control group (n = 41) treated by latanoprost monotherapy. Treatment efficacy, hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters, adverse reactions and quality of life were recorded and compared between two groups of patients. Results: The overall therapeutic effect of the observation group was significantly better than that in the control group. After treatment, ocular hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters and life quality of both groups were obviously improved compared to those before treatment, with more significant improvements in the observation group. In addition, there was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Nimodipine combined with latanoprost eye drops is effective in the treatment of primary open-angle glaucoma, which could effectively improve the ocular hemodynamics and visual field defects of patients with fewer adverse reactions and higher safety. Therefore, it can be further promoted and used in clinical practice.

Adjunctive interleukin-2 for the treatment of drug-susceptible tuberculosis: a randomized control trial in China.

PURPOSE: Evaluation of the efficacy and safety of IL-2 in the treatment of drug-susceptible tuberculosis. METHODS: First, the cases of diagnosed drug-susceptible tuberculosis were randomized into two groups-the control group that received the background regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, and the experimental group that received the background regimen plus IL-2. The efficacy and safety evaluations were performed throughout the therapy process as well as 12 months after the treatment completion. RESULTS: A total of 1151 patients underwent the randomization, among which 539 (96.2%) of the 560 in the experimental group achieved the sputum culture conversion to negative, compared to the 551 (93.2%) of the 591 in the control group, after 2 months of treatment, with significant difference observed between the groups (P = 0.025). Cavity closure after 2 months in the IL-2 (experimental) group was 60/211 (28.4%) compared to 46/248 (18.5%) in the control group, with a significant difference between the groups (P = 0.001). After treatment completion, the proportion of favorable outcomes was 559/560 (99.8%) in the experimental group and 587/591 (99.3%) in the control group, with no significant difference between the groups. Twelve months after treatment completion, relapse occurred in 15/560 (2.6%) in the IL-2 group and 19/591 (3.2%) in the control group, with no significant difference. CONCLUSION: IL-2 may enhance culture conversion and the cavity closure rate in the early treatment phase, although the enhancement may not be significant after treatment completion.

Graph Simplification-Aided ADMM for Decentralized Composite Optimization.

In this article, we consider the problem of decentralized composite optimization over a connected and symmetric graph, in which each node holds its own agent-specific private convex functions, and communications are only allowed between nodes with direct links. A variety of algorithms has been proposed to solve such a problem in an alternating direction method of multiplier (ADMM) framework. Many of these algorithms, however, need to include some extra proximal term in the augmented Lagrangian function such that the resulting algorithm can be implemented in a decentralized manner. The use of the extra proximal term slows down the convergence speed because it forces the current solution to stay close to the solution obtained in the previous iteration. To address this issue, in this article, we first introduce the notion of simplest bipartite graph, which is defined as a bipartite graph that has a minimum number of edges to keep the graph connected. A simple two-step message passing-based procedure is proposed to find a simplest bipartite graph associated with the original graph. We show that the simplest bipartite graph has some interesting properties. By utilizing these properties, an ADMM without involving extra proximal terms can be developed to perform decentralized composite optimization over the simplest bipartite graph. The simulation results show that our proposed method achieves a much faster convergence speed than the existing state-of-the-art decentralized algorithms.

Low serum calcium and phosphorus and their clinical performance in detecting COVID-19 patients.

BACKGROUND: This study aimed to evaluate the clinical performance of low serum calcium and phosphorus in discriminative diagnosis of the severity of patients with coronavirus disease 2019 (COVID-19). We conducted a single-center hospital-based study and consecutively recruited 122 suspected and 104 confirmed patients with COVID-19 during January 24 to April 25, 2020. Clinical risk factors of COVID-19 were identified. The discriminative power of low calcium and phosphorus regarding the disease severity was evaluated. Low calcium and low phosphorus are more prevalent in severe or critical COVID-19 patients than moderate COVID-19 patients (odds ratio [OR], 15.07; 95% confidence interval [CI], 1.59-143.18 for calcium; OR, 6.90; 95% CI, 2.43-19.64 for phosphorus). The specificity in detecting the severe or critical patients among COVID-19 patients reached 98.5% (95% CI, 92.0%-99.7%) and 84.8% (95% CI, 74.3%-91.6%) by low calcium and low phosphorus, respectively, albeit with suboptimal sensitivity. Calcium and phosphorus combined with lymphocyte count could obtain the best discriminative performance for the severe COVID-19 patients (area under the curve [AUC] = 0.80), and combined with oxygenation index was promising (AUC = 0.71). Similar discriminative performances of low calcium and low phosphorus were found between suspected and confirmed COVID-19 patient. Low calcium and low phosphorus could indicate the severity of COVID-19 patients, and may be utilized as promising clinical biomarkers for discriminative diagnosis.

COVID-19 with pleural effusion as the initial symptom: a case study analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified strain of coronavirus in the human body and was reported in Wuhan at the end of 2019. So far, the epidemic is continuing and very serious, with the number of infections and deaths increasing. Despite active investigations around the world to better understand the dynamics of transmission and the scope of clinical disease, COVID-19 continues to spread rapidly from person to person. The common signs and symptoms of SARS-CoV-2 infection include fever, fatigue, dry cough, and dyspnea; in severe cases, patients may have acute respiratory distress syndrome, septic shock, metabolic acidosis difficult to treat and coagulation disorder. However, some patients who test positive for SARS-CoV-2 in their respiratory tract may not have such clinical signs and symptoms. This report presents a case study analysis of a patient admitted in the Fourth Taiyuan People's Hospital, who had suffered traumatic injuries from a car accident and survived COVID-19, with pleural effusion as the initial symptom. We report a case of 2019-NCOV with pleural effusion as the first symptom. Describe in detail the differential diagnosis, diagnosis, clinical management, and cure of this case. In order to combat the novel CoronaviruscoVID-19 in the process to provide lessons and help.

Cathode Local Curvature Affects Lithium Peroxide Growth in Li-O2 Batteries.

The growth of lithium peroxide (Li2O2) in cathodes determines the performance of lithium-oxygen batteries (LOBs). The factor affecting the Li2O2 growth position is of great importance. Here, three hollow carbon spheres with diameters of 200 nm, 500 nm, and 2 µm, corresponding to different curvatures of 10, 4, and 1, respectively, are prepared as LOB cathodes. It is found that the larger the curvature, the more difficult it is for Li2O2 to grow inside the hollow sphere. Increasing the discharge current density can promote the growth of Li2O2 onto a highly curved concave substrate. Therefore, to maximize the battery performance, the applied current density and the local curvature of the porous cathode need to match to optimize the pore space utilization and meanwhile to enhance the interface charge transfer between Li2O2 and electrode. The revealed relationship among the local curvature of the porous electrode, Li2O2 deposition position, and battery performance is valuable to the topography design of the LOB cathode.

Zinc anode with artificial solid electrolyte interface for dendrite-free Ni-Zn secondary battery.

Rechargeable nickel-zinc battery is regarded as a prospective choice for next-generation energy storage device due to its good safety, environmental friendliness and high energy density. However, zinc anode inevitably suffers from uncontrollable growth of zinc dendrites and the dissolution of zinc metal in high-concentration alkaline electrolytes, resulting in poor cycle stability and severely hampering the widespread applications of nickel-zinc batteries. Herein, a unique zinc anode with artificial solid electrolyte interface (ASEI) is facilely constructed via the rolling-tearing of tin and zinc foils and subsequent surface-based chemical reaction in a lead salt solution. The as-prepared ASEI composed of lead film has an efficient protective effect on preventing the dissolution of zinc anode. Meanwhile, the lead element and residual tin can not only enhance hydrogen evolution over-potential of zinc anode but affect the zinc growth mechanism. As a consequence, an excellent cyclic performances upto 100 cycles (capacity retention: 90%) with high reversible capacities are achieved for the zinc anode with AESI.

Structure Determination of Er Doped Ti-Al-Nb Alloy by Neutron Diffraction Analysis.

Neutron diffraction experiments with both conventional powder diffraction setup and under in-situ compressive loading were conducted to investigate the structural origins of large strength and toughness enhancements in Ti-16Al-27Nb alloy after Er addition. The primary phase is determined to be the ordered B2 structure form, in agreement with the previous electron microscopy study. Lattice strains of {210} and {100} planes were measured as a function of applied stress, and elastic anisotropy was found for both, and strong plastic nonlinearity was discovered for (210) reflection. The grain refinement during plastic deformation was proposed by both the 2D diffraction intensity distribution and SEM observations, while stress-induced martensitic phase transition was not observed in this study. It is believed that the activation of different slip systems and grain refinement might be the structural origin of the novel mechanical properties of this alloy.

Self-Adaptive Electrode with SWCNT Bundles as Elastic Substrate for High-Rate and Long-Cycle-Life Lithium/Sodium Ion Batteries.

Massive volume change of active materials in lithium/sodium ion batteries (LIB/SIB) causes severe structural collapse of electrodes and fast capacity decay of batteries. Here, a coaxial composite of single-wall carbon nanotube bundle (SWCNTB/SnO2 ) nanoparticles (NPs)/N-doped carbon shell (SWCNTB@SnO2 @C) is constructed, where SWCNTBs with exceptional elasticity are explored as a self-adaptive substrate to supply a highly resilient conductive network. Within the confinement of hard carbon shells, SWCNTB can produce radially elastic deformation to accommodate the volume change of SnO2 during Li+ /Na+ insertion/extraction. This overcomes the problem of strain fracturing of the outer carbon shell, as well as maintains close electrical contact between SnO2 and the conductive network. The LIB/SIB with the self-adaptive SWCNTB@SnO2 @C electrode presents a series of superior battery performances, for example, a high specific capacity of 608 mAh g-1 at 10 A g-1 and 600 cycles in LIB without capacity decay.

Zigzag carbon as efficient and stable oxygen reduction electrocatalyst for proton exchange membrane fuel cells.

Non-precious-metal or metal-free catalysts with stability are desirable but challenging for proton exchange membrane fuel cells. Here we partially unzip a multiwall carbon nanotube to synthesize zigzag-edged graphene nanoribbons with a carbon nanotube backbone for electrocatalysis of oxygen reduction in proton exchange membrane fuel cells. Zigzag carbon exhibits a peak areal power density of 0.161 W cm-2 and a peak mass power density of 520 W g-1, superior to most non-precious-metal electrocatalysts. Notably, the stability of zigzag carbon is improved in comparison with a representative iron-nitrogen-carbon catalyst in a fuel cell with hydrogen/oxygen gases at 0.5 V. Density functional theory calculation coupled with experimentation reveal that a zigzag carbon atom is the most active site for oxygen reduction among several types of carbon defects on graphene nanoribbons in acid electrolyte. This work demonstrates that zigzag carbon is a promising electrocatalyst for low-cost and durable proton exchange membrane fuel cells.

Colouration mechanism of underglaze copper-red decoration porcelain (AD 13th-14th century), China.

Underglaze copper-red decoration, i.e. the copper colourant used to paint diversified patterns on the surface of a body and then covered by transparent glaze and fired at high temperature in a reductive firing environment, is famous all over the world. However, the red colouration mechanism generated by underglaze copper remains unclear. In particular, the fact that the edges of the red patterns are orange has been ignored in previous research. Here, non-destructive analysis has been carried out on a precious fragment of early underglaze red porcelain using synchrotron radiation X-ray fluorescence, X-ray absorption near-edge spectroscopy (XANES) and reflection spectrometry techniques. The results suggest that the copper content in the red region is higher than that in the orange region, and other colour generation elements do not have obvious content difference, indicating that the colour generation effect of the underglaze red product is related to the copper content. XANES analysis shows that the valence states of copper in the red and orange regions are similar and metal copper contributes to their hues. The results of reflection spectrometry demonstrate that tiny orange hues could be attributed to the Mie scatting effect. Therefore, light-scattering effects should be considered when researching the colouration mechanism of underglaze red.

Oasis land-use change and its environmental impact in Jinta Oasis, arid northwestern China.

Land use change resulted in land degradation is a focus of research on global environmental changes and plays a significant role in the stability and economic development of oases in arid regions of China. Jinta Oasis, a typical oasis of temperate arid zone in northwestern China, was investigated to assess land-use change dynamics during 1988-2003 with the aid of satellite remote sensing and GIS, and to explore the interaction between these changes and oasis environment. Six land-use types were identified, namely: cropland, forestland, grassland, water, urban or built-up land, and barren land. The results indicate that cropland, urban/built-up land, and barren land increase greatly by 30.03, 13.35, and 15.52 km(2), respectively; but grassland and forestland areas decrease rapidly by 58.06, and 1.76 km(2), respectively. These results also show that obvious widespread changes in land-use occur within the whole oasis over the study period and result in severe problems of environmental degradation (i.e. land desertification, decline of groundwater, and vegetation degeneracy).