Advanced Buffering Acidic Aqueous Electrolytes for Ultra-Long Life Aqueous Zinc-Ion Batteries.

Mild aqueous Zn batteries have attracted increasing attention for energy storage due to the advantages of high safety and low cost; however, the rechargeability of Zn anodes is one major issue for practical applications. In this work, an effective approach is proposed to improve the reversibility and stability of Zn anodes using advanced acidic electrolytes. A trace amount of acetic acid (HAc) is employed as a buffering agent to provide a stable pH environment in aqueous Zn electrolytes, and thus suppress passivation from precipitation reactions on Zn electrodes. Meanwhile, tetramethylene sulfone (TMS) is introduced as the critical component to stabilize the Zn anodes in the acidic electrolyte. TMS greatly strengthens the hydrogen-bonding network with reduced H2 O activity and extends the electrochemical window of acidic electrolytes. With the optimal 3 m Zn(OTF)2 in (H2 O-HAc)/TMS acidic electrolyte (pH 1.6), the Zn electrode exhibits a coulombic efficiency of >99.8% and smooth Zn deposition. The Zn-V2 O5 full cell demonstrates ultra-stable cycling over 20 000 cycles with a low decay rate of 0.0009% for each cycle at a negative/postive capacity ratio of 6.5. This work provides an insightful perspective to stabilize Zn electrodes by regulating the pH environment and limiting the H2 O activity simultaneously for long-life Zn anodes.

Insulin in high concentration recede cigarette smoke extract induced cellular senescence of airway epithelial cell through autophagy pathway.

Recent clinical researches demonstrated "obesity paradox" in chronic obstructive pulmonary disease (COPD) patients. However, why obesity is beneficial to COPD development remains unclear. Obesity is distinguished by hyperinsulinemia, and cellular senescence of airway epithelial cells (AEC) is involved in COPD progression. In this study, we aim to investigate the roles of insulin in high concentration in AEC cellular senescence. Human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (HSAEpiC) were used for experiments and treated with insulin in indicated time period and concentration with or without 1% cigarette smoke extract (CSE) exposure, and autophagy activator (rapamycin) or inhibitor (chloroquine) after exposed to 1% CSE. The expression of senescence protein (p21), cell cycle related protein (cyclinE), and autophagy protein (LC3B, Beclin-1 and p62) were determined by western blot. Cellular senescence was detected by Senescence-ß-Galactosidase staining. Autophagy level was detected by GFP-LC3B fluorescent light. Results showed that insulin receded cellular senescence in different time and concentration, as indicated by decreased expression of p21, increased expression of cyclinE and down-regulated ratio of SA-ß-Gal stained cells in BEAS-2B and HSAEpiC under physiological or CSE exposure condition. 5 µg/ml insulin treated for 48 h up-regulated the ratio of LC3B II/I, Beclin-1 and number of spot dots of GFP-LC3B, and down-regulated the level of p62 in AEC cells after 1% CSE exposure, while 1% CSE showed an opposite effect. Activating autophagy receded cellular senescence, and vice versa. Meanwhile, the effect of 5 µg/ml insulin on receding cellular senescence could be alleviated by autophagy inhibitor chloroquine or reinforced by autophagy activator rapamycin. In conclusion, insulin in high concentration could reduce the CSE induced cellular senescence of human airway epithelial cells through autophagy pathway.

Metabolomics profiling of cleidocranial dysplasia.

OBJECTIVES: Cleidocranial dysplasia (CCD) is a rare autosomal-dominantly inherited skeletal dysplasia that is predominantly associated with heterozygous mutations of RUNX2. However, no information is available regarding metabolic changes associated with CCD at present. MATERIALS AND METHODS: We analyzed members of a CCD family and checked for mutations in the RUNX2 coding sequence using the nucleotide BLAST program. The 3D protein structure of mutant RUNX2 was predicted by I-TASSER. Finally, we analyzed metabolites extracted from plasma using LC-MS/MS. RESULTS: We identified a novel mutation (c.1061insT) that generates a premature termination in the RUNX2 coding region, which, based on protein structure prediction models, likely alters the protein's function. Interestingly, metabolomics profiling indicated that 30 metabolites belonging to 13 metabolic pathways were significantly changed in the CCD patients compared to normal controls. CONCLUSIONS: The results highlight interesting correlations between a RUNX2 mutation, metabolic changes, and the clinical features in a family with CCD. The results also contribute to our understanding of the pathogenetic processes underlying this rare disorder. CLINICAL RELEVANCE: This study provides the first metabolomics profiling in CCD patients, expands our insights into the pathogenesis of the disorder, may help in diagnostics and its refinements, and may lead to novel therapeutic approaches to CCD.

Unraveling the Interphasial Chemistry for Highly Reversible Aqueous Zn Ion Batteries.

A robust solid electrolyte interface (SEI) is crucial to widen the electrochemical stability window of the electrolyte and enable sustainably stable electrode reactions in aqueous Zn ion batteries. Different from the SEI in nonaqueous electrolytes, it is of great importance to form a functional and stable SEI due to parasitic reactions with water in aqueous Zn ion batteries. However, the concrete SEI formation in aqueous electrolytes has been elusive so far. Here, we regulate and unravel the decomposition mechanisms of organic Zn salts at the Zn anode-electrolyte interface in the widely studied zinc triflate-based aqueous electrolytes. By introducing a buffering adsorption layer with an optimal concentration of acetate anions, the uncontrollable decomposition of organic zinc triflate salt is greatly inhibited on Zn anodes, resulting in a stable interface. The average Coulombic efficiency of the Zn anode thus can reach as high as 99.95% and stable cycling for 4200 h. With the cooperation of buffering adsorption layers, the tetraethyl ammonium trifluoromethanesulfonate additive as the decomposition promoter could further regulate the decomposition of triflate anions for the formation of robust SEI layers for Zn anodes in electrolytes with a dilute salt concentration. Zn-polyaniline (PANI) full cells demonstrate stable cycling with controlled N/P ratios in such electrolytes. This work proposes an insightful perspective on rational regulation of the decomposition pathway of electrolyte components by forming a stable electrode-electrolyte interface for improved electrochemical performance of aqueous Zn ion batteries.

Constructing Three-Dimensional Topological Zn Deposition for Long-Life Aqueous Zn-Ion Batteries.

Uniform and compact Zn deposition-dissolution is essential to achieve high Coulombic efficiency and long lifespan for Zn anodes. More attention has been commonly focused on the suppression of macroscopic Zn dendrites in the previous reports. The rational control of the microstructure of Zn deposition to prevent the intrinsic volume expansion and pulverization of Zn metal so as to stabilize Zn anodes is less discussed. Herein, we construct a three-dimensional topological Zn deposition at the nanoscale through an in situ electrochemical process in the optimal hybrid aqueous electrolyte. The topological electrode structure can efficiently accommodate microscopic strain and volume variation and thus largely preserve the macroscopic integrity and electrical contact of Zn anodes, leading to enhanced reversibility and stability. With the unique topological structure of Zn deposition, the Coulombic efficiency of Zn anodes could reach >99.9% with excellent cycling over 1182 h at 2 mA cm-2 and 2 mA h cm-2 (Zn utilization: 11.4%). The evolution of "dead" Zn during repeated cycling is first investigated using a homemade semiquantitative analysis method to determine the critical "short slab" for aqueous Zn batteries under the practical application. This work provides an insightful method to regulate the microscopic morphology of Zn deposition for high-performance Zn batteries.

Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study.

Objective: Although previous epidemiological studies have reported substantial links between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and celiac disease (CeD), the causal relationship between the two remains unknown. The purpose of the current study was to evaluate the bidirectional causation between IBD and CeD using Mendelian randomization (MR). Method: We obtained genome-wide association study (GWAS) summary data of IBD (CD and UC) and CeD of thoroughly European ancestry from the IEU GWAS database. We screened eligible instrumental variables (IVs) according to the three assumptions of MR. MR was performed using MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods. The MR-Egger intercept and MR-PRESSO method investigated the horizontal pleiotropy effect. A leave-one-out analysis was performed to prevent bias caused by a single SNP. Results: The study assessed a bidirectional causal effect between CD and CeD; CD increased the risk of CeD (IVW odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.19-1.35, p = 3.75E-13) and vice-a-versa (IVW OR = 1.09, 95% CI = 1.05-1.13, p = 1.39E-05). Additionally, CeD was influenced by IBD (IVW OR = 1.24, 95% CI = 1.16-1.34, p = 9.42E-10) and UC (IVW OR = 0.90, 95% CI = 0.83-0.98, p = 0.017). However, we observed no evidence of a causal relationship between CeD and IBD (IVW OR = 1.00, 95% CI = 0.97-1.04, p = 0.900) or UC (IVW OR = 0.96, 95% CI = 0.92-1.02, p = 0.172). Conclusion: The present study revealed that IBD and CeD have a bidirectional causal relationship. However, it is slightly different from the results of previous observational studies, recommending that future studies focus on the mechanisms of interaction between CD and CeD.

Endobronchial Valve Treatment of Tuberculous Cavities in Patients with Multidrug-Resistant Pulmonary Tuberculosis: A Randomized Clinical Study.

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

5-Lipoxygenase as an emerging target against age-related brain disorders.

Neuroinflammation is a common feature of age-related brain disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and cerebral ischemia. 5-lipoxygenase (5-LOX), a proinflammatory enzyme, modulates inflammation by generating leukotrienes. Abnormal activation of 5-LOX and excessive production of leukotrienes have been detected in the development of age-related brain pathology. In this review, we provide an update on the current understanding of 5-LOX activation and several groups of functionally related inhibitors. In addition, the modulatory roles of 5-LOX in the pathogenesis and progression of the age-related brain disorders have been comprehensively highlighted and discussed. Inhibition of 5-LOX activation may represent a promising therapeutic strategy for AD, PD and cerebral ischemia.

Small airway remodeling in diabetic and smoking chronic obstructive pulmonary disease patients.

Diabetes mellitus can reinforce the small airway dysfunction of chronic obstructive pulmonary disease (COPD) patients. The epithelial-mesenchymal transition (EMT) that is associated with small airway remodeling is activated in the airway epithelial cells (AECs) of both COPD patients and diabetic patients. Transforming growth factor ß (TGF-ß) can induce EMT via the TGF-ß/Smad pathway. We found that the small airway dysfunction and airflow limitations were worse in COPD patients with a history of smoking or diabetes than in simple COPD patients, and were even worse in COPD patients with both histories. Pulmonary ventilation tests in rats confirmed these findings. EMT and the TGF-ß/Smad pathway were activated in the AECs of rats with COPD or diabetes, and the combination of COPD and diabetes amplified those effects, as indicated by downregulation of Zo1 and upregulation of vimentin, TGF-ß and Smad4 in immunohistochemical experiments. Twenty-four-hour treatment with 25 mM glucose and/or 1% cigarette smoke extract upregulated vimentin, TGF-ß, Smad2/3/4 and p-Smad2/3, but downregulated Zo1 in AECs. Suppressing the TGF-ß/Smad pathway prevented EMT activation and small airway remodeling following cigarette smoke exposure and hyperglycemia. Thus, cigarette smoke and high glucose exposure induces EMT via the TGF-ß/Smad pathway in AECs.

ß2-microglobulin as a biomarker of pulmonary fibrosis development in COPD patients.

Expression of ß2-microglobulin (ß2M) is involved in fibrosis progression in kidney, liver, and heart. In this case-controlled retrospective study, we investigated the role of ß2M in the development of pulmonary fibrosis in patients with chronic obstructive pulmonary disease (COPD). Analysis of 450 COPD patients revealed that patients with decreased pulmonary diffusing capacity (DLCO) had increased ß2M serum levels. Compared to patients with lower ß2M serum levels, patients with increased ß2M levels exhibited increased alveolar wall/septal thickening and lung tissue ß2M expression. In addition, patients with increased ß2M levels had increased lung expression of TGF-ß1, Smad4, and a-SMA. Animal experiments showed that increased ß2M expression resulted in epithelial-mesenchymal transition (EMT), alveolar wall/septal thickening, and pulmonary fibrosis in a rat COPD model. Together, these results indicate that ß2M serum levels may serve as a new indicator for assessment of pulmonary diffusion function and pulmonary fibrosis severity in clinical practice and may provide a potential target for treatment of pulmonary fibrosis in the future.

Novel drug delivery system based on hollow mesoporous magnetic nanoparticles for head and neck cancers--targeted therapy in vitro and in vivo.

Magnetic targeting delivery of anti-cancer drug with controlled drug release function has been recognized as a promising strategy for pursuit of the increased chemotherapeutic efficacy and reduced adverse effects. Superparamagnetic nano-carrier is proved to be an efficient manner for superficial tumor therapy like head and neck cancers. The anti-tumor effect of chemotherapy drug can be enhanced by combining with external magnet. Herein, we reported the fabrication and functionalization of biocompatible and superparamagnetic hollow mesoporous nanoparticles with magnetic targeting. The nanoparticles drug delivery system was constructed by surface-engineering polyacrylic acid (PAA) onto the superparamagnetic nanoparticles which can load bleomycin (BLM) both in the mesoporous structure and via bonding with PAA. The drug was targeted and retained to the focal area under the magnetic field with the nano-carriers, and released sustainably. Detailed investigations demonstrated that PAA-functionalized magnetite nanoparticles loading BLM could stimulate tumor cells to apoptosis locally. The drug loaded and delivery system endowed the anticancer drug with targeting capability in vitro and suppressed the growth of tumor in vivo. The present targeted drug delivery system is a rather simple method without sophisticated chemistry or materials engineering and is promising in contributing to the progress of nanotherapeutics toward efficient head and neck cancer treatment.

Body mass index of patients with chronic obstructive pulmonary disease is associated with pulmonary function and exacerbations: a retrospective real world research.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is prevalent in China. The role of body mass index (BMI) in COPD progression and prognosis is unclear. We analyzed the association between BMI and pulmonary function, inflammation levels and exacerbation in Chinese COPD patients. METHODS: Our retrospective real world research included 744 patients with COPD diagnosed by spirometry and hospitalized from January 1st, 2014 to December 31st, 2016. The indicators were gathered from hospital records database and frequency of exacerbation in the three years were followed up. All 744 patients were divided into four groups by BMI grades. We analyzed the association between BMI and pulmonary function, inflammation levels and exacerbation by Spearman bivariate correlations, Kruskal-Wallis test, Mann-Whitney U test and logistic regression. RESULTS: The singly proportion (median of BMI) of these patients in underweight, normal weight, overweight and obesity was 7.80% (17.54), 45.97% (22.12), 27.96% (27.00) and 18.28% (31.25) respectively. With increasing of BMI grades, the values of forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced expiratory flow (FEF25/50/75) and diffusing capacity of carbon monoxide (DLCO) were correspondingly increasing; the percentage of neutrophils and C-reactive protein (CRP) presented significant declining trend while the trend of the percentage of eosinophils was negative; the dose of systemic corticosteroid and length of stay present decreasing tendency; the frequency of exacerbation and hospitalization were decreasing. These were similar results in gender, smoking status COPD subgroups. CONCLUSIONS: In our study, BMI was moderately correlated with pulmonary function positively and exacerbations negatively. To some extent, BMI might be a useful indicator to predict the prognosis of COPD patients and for long-term management.

Fabrication of metal-free two dimensional/two dimensional homojunction photocatalyst using various carbon nitride nanosheets as building blocks.

Semiconductor photocatalysis currently suffered three main problems, low solar energy utilization, high photo-generated charge recombination rate and the heavy metal ions release by the photo-corrosion. Herein, we developed a visible-light-driven homojunction photocatalyst with the metal-free two-dimensional (2D) graphitic carbon nitride nanosheets (CNNS). By employing liquid exfoliation and chemical blowing approaches, we obtained two kinds of CNNS materials (le-CNNS and cb-CNNS) with different band structures, and subsequently fabricated the homojunction photocatalyst. This 2D/2D nanocomposited homojunction photocatalyst exhibited enhanced photocatalytic performance compared to these individual 2D nanosheets materials. Moreover, its well universality and reusability were also demonstrated by photo-degradation of various organic pollutants and five successive runs. By studying the optical properties and the electrochemical behavior, the band alignment of this homojunction was illustrated and the possible mechanism was proposed, where the transmitted electrons on the conduction band (CB) of le-CNNS would transport to the CB of cb-CNNS, and the holes on the valence band (VB) of cb-CNNS transferred to the VB of le-CNNS, therefore promoting the photo-induced carrier separation. Additionally, the photoluminescence, electrochemical impendence and photocurrent measurements further demonstrated that the recombination of photo-excited electron-hole pairs had been efficiently suppressed in the homojunction and were respectively collected on different CNNS components.

Response of endothelial cells to decellularized extracellular matrix deposited by bone marrow mesenchymal stem cells.

OBJECTIVE: Evaluate the behavior and function of human umbilical vein endothelial cells (HUVECs) on decellularized extracellular matrix (ECM) deposited by bone marrow mesenchymal stem cells (BMSCs). METHODS: Prepared through chemical approach, decellularized ECM was characterized by use of immunofluorescence staining. The morphology, attachment, proliferation and migration of HUVECs cultured on six-well tissue culture plastic (TCP) and decellularized ECM were investigated. RESULTS: Decellularized ECM was successfully prepared without three-dimensional architecture disruption. This biological scaffold is similar to nature vascular ECM, preserved various matrix proteins such as type I collagen, type III collagen and fibronection. HUVECs on decellularized ECM showed well attachment and regular arrangement. Decellularized ECM could also significantly enhance the migration and proliferation potential of HUVECs in contrast to TCP. CONCLUSION: Deposited by BMSCs, ECM can affect the behavior of endothelial cell and could be used as a promising material in tissue engineering.