Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype.

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.

Aqueous Solution Enhanced Room Temperature Phosphorescence through Coordination-Induced Structural Rigidity.

Achieving aqueous solution enhanced room temperature phosphorescence (RTP) is critical for the applications of RTP materials in solution phase, but which faces a great challenge. Herein, for the first time, a strategy of coordination-induced structural rigidity is proposed to achieve enhanced quantum efficiency of aluminum/scandium-doped phosphorescent microcubes (Al/Sc-PMCs) in aqueous solution. The Al/Sc-PMCs in a dry state exhibit a nearly invisible blue RTP. However, they emit a strong RTP emission in aqueous solution with a RTP intensity increase of up to 22.16-times, which is opposite to common solution-quenched RTP. The RTP enhancement mechanism is attributed to the abundant metal sites (Al3+ and Sc3+ ions) on the Al/Sc-PMCs surface that can tightly combine with water molecules through the strong coordination. Subsequently, these coordinated water molecules as the bridging agent can bind with surface groups by hydrogen bonding interaction, thereby rigidifying chemical groups and inhibiting their motions, resulting in the transition from the nonradiative decay to the radiative decay, which greatly enhances the RTP efficiency of the Al/Sc-PMCs. This work not only develops a coordination rigidity strategy to enhance RTP intensity in aqueous solution, but also constructs a phosphorescent probe to achieve reliable and accurate determination of analyte in complex biological matrices.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions.

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.

Enhanced Polysulfide Trapping and Conversion by Amorphous-Crystalline Heterostructured MnO2 Interlayers for Li-S Batteries.

The practical application of lithium-sulfur batteries (LSBs) is still hindered by several technical issues, including severe polysulfide shuttling and sluggish redox kinetics, which reduces the sulfur utilization and further results in low energy density. Herein, amorphous-crystalline heterostructured MnO2 (ACM) prepared through a simple calcination process was employed as the functional interlayer to play a double role as effective trapper and multifunctional electrocatalyst for LSBs. ACM not only combines the strong sulfur chemisorption of the amorphous MnO2 (AM) and fast Li+ transportation of the crystalline MnO2(CM) but also accelerates the interface charge transfer at the amorphous/crystalline interfaces. The LSBs with such unique interlayer exhibited an excellent rate performance of 1155.5 mAh·g-1 at 0.2 C and 692.9 mAh·g-1 at 3 C and a low decay rate of 0.071% per cycle over 500 cycles at 0.5 C. Even for a high sulfur loading of 5 mg·cm-2 at 0.1 C, a high capacity retention of 92.3% could also be achieved after 100 cycles. The concept of amorphous-crystalline heterostructures prepared by crystallization regulation might also be used for other electronic devices and catalyst designs.

Inorganic salt recrystallization strategy for achieving ultralong room temperature phosphorescence through structural confinement and aluminized reconstruction.

Achieving highly efficient and stable room temperature phosphorescence (RTP) with ultralong lifetime is critical for the multi-purpose applications of phosphorescent materials. In this work, we propose an inorganic salt heating recrystallization strategy to simultaneously improve the lifetime, quantum efficiency, and stability of phosphorescent scandium/leucine microspheres (Sc/Leu-MSs). Inorganic salt-treated Sc/Leu-MSs are obtained by simply heating and drying inorganic salt solution containing Sc/Leu-MSs, which can achieve a maximum lifetime increase of 4.42-times from 208.37 ms (Sc/Leu-MSs) to 920.08 ms (Al2(SO4)3-treated Sc/Leu-MSs), accompanied by a RTP intensity increase up to 24.08-times. The enhancement mechanism of RTP efficiency is attributed to the stabilization of triplet excitons caused by inorganic salt coating that suppresses molecular motion and isolates oxygen on the one hand, and the efficient intersystem crossing promoted by aluminized reconstruction-caused duplex heavy atom effects on the other hand. This study provides new design principle and a facile strategy to construct RTP materials with ultralong lifetime, high phosphorescent quantum efficiency, and high stability for promising applications such as anti-counterfeiting and light emitting diodes.

[Research Progress on the Application of Intervention Mapping in Tertiary Prevention of Cancer].

Intervention mapping (IM) is a framework for formulating theory-and evidence-based health education projects with participatory approaches from ecological perspectives.The intervention program designed via IM plays a role in reducing the exposure of cancer risk factors,increasing cancer prevention behaviors,and promoting early cancer screening and rehabilitation of cancer patients.This study summarizes the characteristics,implementation steps,and application status of IM in tertiary prevention of cancer,aiming to provide reference for the application of IM in the health education projects for cancer in China.

Carbon dots with hydrogen bond-controlled aggregation behavior.

Here, hydrophilic carbon dots (H-CDs) are prepared by a facile room temperature method. The strength of hydrogen bonds can be controlled by introducing proton and aprotic solvents, respectively, so as to realize the tunable aggregation state of H-CDs. Because of the ultrasensitive response to dimethyl sulfoxide (DMSO), H-CDs can serve as optical probes for detecting DMSO in a linear range of 0.005% to 0.75% and with a detection limit of 0.001%.

Built-In Electric Field on the Mott-Schottky Heterointerface-Enabled Fast Kinetics Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries (LSBs) have been considered one of the most potential candidates to substitute traditional Li-ion batteries (LIBs), owing to their high theoretical energy density and low cost. Nevertheless, the shuttle effect and the sluggish redox kinetics of lithium polysulfides (LiPSs) have long been obstacles to realizing stable LSBs with high reversible capacity. In this study, we proposed a metal-semiconductor (Mo and MoO2) heterostructure with the hollow microsphere morphology as an effective Mott-Schottky electrocatalyst to boost sulfur electrochemistry. The hollow structure can physically inhibit the shuttling of LiPSs and accommodate the volume fluctuation during cycling. More importantly, the built-in electric field at the heterointerfacial sites can effectively accelerate the reduction of LiPSs and oxidation of Li2S, thereby reaching a high sulfur utilization. With the assistance of the Mo/MoO2 catalyst, the cell exhibited prominent rate capability and stable long-term cycling performance, showing a high capacity of 630 mA h·g-1 at 4 C and a low decay of 0.073% at 1 C after 500 cycles. Even with high areal sulfur loading of 10.0 mg·cm-2, high capacity and good cycle stability were achieved at 0.2 C under lean electrolyte conditions (E/S ratio of 6 µL·mg-1).

Reversible polymerization of carbon dots based on dynamic covalent imine bond.

Carbon dots (CDs), as new type of carbon-based nanoparticles, are considered to be an aggregate with irreversible polymerization. Achieving the reversible tunability of CDs luminescence based on their reversible polymerization is a challenging subject. Herein, we, for the first time, design and construct the blue-emitting CDs with reversible polymerization by a room-temperature Schiff base reaction between tannic acid and ethylenediamine. The formation of CDs is proven to be due to the crosslinking polymerization of precursors caused by imine bond. As a dynamic covalent bond, imine bond endows CDs with controllable structural transformation properties, and the prepared CDs can be depolymerized and polymerized reversibly by pH-controlled imine bond cleavage and re-formation. These properties of reversible fluorescence photoswitching make the CDs have a good application prospect in reversible information encryption.

Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases worldwide. At present, there are no effective pharmacological therapies for NAFLD except lifestyle intervention-mediated weight loss. Atractylenolide III (ATL III), the major bioactive component found in Atractylode smacrocephala Koidz, has been shown to exert anti-oxidant, anti-tumor, anti-allergic response, anti-bacterial effects and cognitive protection. Here we investigate the therapeutic potential and underlying mechanisms of ATL III for the treatment of NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated with ATL III. Lipid accumulation was analyzed by Oil Red O staining in liver tissues and free fatty acids (FFAs)-treated hepatocytes. AMP-activated protein (AMPK) and sirtuin 1(SIRT1) signaling pathways were inhibited by Compound C and EX527 in vitro, respectively. Small-interfering RNA (siRNA) was used to knockdown adiponectin receptor 1 (AdipoR1) expression in HepG2 cells. Results: ATL III treatment ameliorated liver injury and hepatic lipid accumulation in the HFD-induced NAFLD mouse model as demonstrated by that ATL III administration significantly reduced serum levels of alanine aminotransferase, glutamic oxaloacetic transaminase, triglycerides, total cholesterol and low-density lipoprotein. Furthermore, treatment with ATL III alleviated hepatic oxidative stress, inflammation and fibrosis in the HFD feeding model. To study the underlying mechanisms, we performed Computer Aided Design assay and found that open-formed AdipoR1 and adiponectin receptor 2 were the potential receptors targeted by ATL III. Interestingly, HFD feeding or FFAs treatment only reduced hepatic AdipoR1 expression, while such reduction was abolished by ATL III administration. In addition, in vitro treatment with ATL III activated the AdipoR1 downstream AMPK /SIRT1 signaling pathway and reduced lipid deposition in HepG2 cells, which was diminished by silencing AdipoR1. Finally, inhibition of AMPK or SIRT1, the AdipoR1 downstream signaling, abolished the protective effects of ATL III on lipid deposition and oxidative stress in FFAs-treated HepG2 cells. Conclusion: Our findings suggest that ATL III is a therapeutic drug for the treatment of NAFLD and such protective effect is mediated by activating hepatic AdipoR1-mediated AMPK/SIRT1 signaling pathway.

[Improvement on compactibility of the alcoholic extract of Zingiberis Rhizoma by co-spray drying with HPMC].

Aiming to solve the poor compactibility of the alcoholic extract of Zingiberis Rhizoma(ZR), this study explored the feasibility of its physical modification using co-spray drying with a small amount of hydroxypropyl methyl cellulose(HPMC). Based on the univariate analysis, the influence of two independent variables(the HPMC content in the product and the solid content of spray material) on the powder properties and tablet properties of the dried product was investigated by the central composite design. With the tensile strength and disintegration time of the tablets as the evaluation indexes, the optimal prescription was determined as follows: the HPMC content was 15% and the solid content of spray material was 25.6%. The accuracy of the regression model established for predicting tensile strength and disintegration time of tablets was verified, and the results revealed that the measured values were close to the predicted ones with deviations of 0.47% and-8.2%, indicating good prediction and reproducibility of the model. The tensile strength(4.24 MPa) of tablets prepared with the optimal prescription was 3.59 times that(1.18 MPa, far lower than the baseline of 2 MPa for qualified tablets) with the spray-dried powder of the ZR. On the other hand, due to the addition of HPMC, the disintegration time of tablets increased from 7.3 min to 24.6 min. On the whole, this study provided a new strategy to solve the common problem of poor compactibility of raw Chinese medicinal materials, which facilitated the successful preparation of Chinese medicinal tablets with high drug loads.

Corrigendum to "Immunomodulatory Effects of Combination Therapy with Bushen Formula plus Entecavir for Chronic Hepatitis B Patients".

[This corrects the article DOI: 10.1155/2019/8983903.].

Carbon dots induced in-situ formation of porous europium micro-networks with enhanced photocatalysis.

Excellent photocatalysts are highly desirable for clean energy and pollutant treatment. Carbon dots (CDs)-based composite photocatalysts have been widely studied and utilized in catalytic fields. However, the preparation of the photocatalysts with high catalytic activity still faces a great challenge. Herein, white-light-driven CDs-based porous europium micro-networks (CDs@P-Eu-MNs) composite photocatalysts are prepared by a facile in-situ growth strategy. CDs can affect the morphology and produce a large number of porous structures of CDs@P-Eu-MNs. Importantly, the introduction of CDs not only increases the light absorption, but also promotes the separation of photogenerated charge carriers, and thus improve photocatalytic performance of CDs@P-Eu-MNs composites. CDs@P-Eu-MNs show the highest photocurrent density, which can be used for the highly-efficient photodegradation of rhodamine 6G dyes with almost 95% degradation rate under low power white light (20 W) without any radical generating agents such as H2O2. Therefore, this new and efficient CDs@P-Eu-MNs photocatalyst will have a great application prospect in water pollution treatment.

Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano-groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin-based intracellular force, while the space constraint (micro-groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Chemical characters and protective effect of Baqi Lingmao formula on experimental liver injury.

OBJECTIVE: To investigate the chemical characters of water-extract of Baqi Lingmao formula (BQLM formula) and its effects on anti-liver injury in model mice and live cells. METHODS: BQLM formula was composed of ten herbal medicines. We determined the contents of alkaloids, saponins, phenolic acids and flavonoid in BQLM formula by UV spectrophotometry. The active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC chromatography. The anti-hepatic injury effects of BQLM formula were investigated with concanavalin A (ConA)-induced hepatitis model of mice, human liver LO2 and HepG2.2.15 cells. RESULTS: BQLM formula (2 and 10 g/kg, orally) significantly improved the damages of liver tissues and functions caused by ConA in mice, reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ, tumor necrosis factor-α and interleukin-6. BQLM formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum, and recovered the superoxide dismutase and catalase activities of liver to normal levels in ConA-induced hepatic-injury mice. The serum of BQLM formula group stimulated the human liver LO2 cell proliferation in vitro. Further, BQLM formula obviously promoted the proliferation of normal hepatocytes (LO2 cells) and inhibited the hepatocytes death induced by ConA. It also significantly inhibited the proliferation of HepG2.2.15 cells and decreased the secretion of HBsAg and HBeAg in vitro. CONCLUSIONS: BQLM formula has anti-inflammation and anti-hepatitis virus Beffects, and is capable of improving liver injury in vivo and in vitro.

Dual-Emitting Carbonized Polymer Dots Synthesized at Room Temperature for Ratiometric Fluorescence Sensing of Vitamin B12.

Ratiometric fluorescence (FL) probes are highly desirable for highly sensitive and reliable assays. Dual-emitting carbonized polymer dots (CPDs) have great application prospects in building ratiometric FL sensors. However, dual-emitting CPDs are usually synthesized at high temperatures and high pressures, which not only increases the cost but also complicates the structure of CPDs. Here, we developed a facile strategy for the fabrication of dual-emitting CPDs at room temperature using tetrachlorobenzoquinone and ethylenediamine. The formation of CPDs was induced by Schiff base condensation reaction, enabling the following cross-linking polymerization process. The dual-emitting CPDs demonstrate good photostability and antioxidant capacity. Importantly, the typical dual-emission bands of the as-prepared CPDs are found to have a blue emission band at 445 nm with a maximum excitation of 350 nm and a yellow emission band at 575 nm with a maximum excitation of 440 nm. Based on the dual-emitting property of CPDs, a ratiometric FL nanoprobe is obtained for sensitive determination of vitamin B12 (VB12), as the inner filtering and static quenching effects between VB12 and CPDs allow effective quenching of the blue FL of CPDs, while the yellow FL is maintained. The established assay shows linear detection ranges of 0.25-100 µM with a low limit of detection of 0.14 µM. These findings provide new guidance for the facile preparation of CPDs with excellent dual-emitting optical properties, indicating good prospects in biosensing.

[Research Progress of Adaptive Intervention].

Adaptive intervention(AI)is a methodology which dynamically evaluates adaptive variables at decision points and timely adjusts and develops tailored strategies to meet individual needs.The study reviewed the origin and development and elaborated the core elements(including intervention outcomes,intervention options,decision points,tailoring variables,and decision rules)and the classification of AI.Based on the literature,the key points of the design and implementation of AI were prospected,which can provide evidence for the research and development of health behavior intervention.

Correlation between Occupational Stress and Coronary Heart Disease in Northwestern China: A Case Study of Xinjiang.

OBJECTIVE: To study the correlation between occupational stress and coronary heart disease in western China. METHOD: A case-control design was used. From June 2016 to May 2017, 310 patients with coronary heart disease (CHD) confirmed by coronary angiography (CAG) at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University were recruited by cluster sampling, along with 536 healthy controls. The questionnaire was developed based on a Job Content Questionnaire (JCQ). An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. RESULTS: (1) In the Han population, there were statistically significant differences in the composition of smoking, diets, sleep duration, sleep quality, and physical activity between two groups (all P < 0.05). In the Uygur population, statistically significant differences in the composition of smoking, drinking, diets, sleep quality, and physical activity were found between two groups (all P < 0.05). (2) Differences in sleep duration and physical activity between the Han and Uygur case groups were statistically significant (P < 0.05). (3) Differences in Gensini scores between the Han and Uygur case groups were statistically significant (P < 0.05). Differences in coronary artery lesions between the Han and Uygur case groups were statistically significant (P < 0.05). (4) In the Uygur population, the difference between the occupational stress level and CHD were statistically significant (P < 0.05). (5) The differences between the number of different pathological changes and the level of occupational stress in the Han and Uygur case groups were not statistically significant (P > 0.05). In the Han and Uygur case groups, the difference between the occupational stress level and Gensini high-level group were statistically significant (P < 0.05). (6) After adjustment for age and sex, significant increased risk effects for Han patients with CHD were found to be associated with sleep quality (OR = 1.88; 95% CI: 1.047-1.782; P < 0.05). Uygur patients with CHD was significantly associated with smoking (OR = 3.094; 95% CI: 1.025-1.103; P < 0.05) and occupation stress (OR = 1.523; 95% CI: 1.757-3.062; P < 0.05). CONCLUSION: Occupational stress is correlated with CHD for the Uygur population.

Synthesis and biological evaluation of fluorinated 3,4-dihydroquinolin-2(1H)-ones and 2-oxindoles for anti-hepatic fibrosis.

(Z)-4-(Iodomethylene)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinolin-2(1H)-ones and fluorinated 3,3-disubstituted 2-oxindoles are synthesized and evaluated for anti-hepatic fibrosis. CCK-8 assay indicates that most of the compounds have no obvious cytotoxicity on the human hepatic stellate cells (HSC) cell line. Collagen I and fibrosin expression levels are tested by ELISA, and the results show that several compounds can inhibit the expression of collagen I and fibrosin. Additionally, results from real time-PCR reveal that only one compound can inhibit the expression level of α-SMA, suggesting that this compound can inhibit the activation of the HSC cell line. These studies demonstrate that this compound may be a potential novel drug candidate for anti-hepatic fibrosis (approximately 5-6 lines).