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Molecular doping, as an effective technique for controlling the electrical property of organic semiconductors (OSCs) by introducing additional charges, has been proven to adjust important device parameters in organic thin-film transistors (OTFTs). Doping highly crystalline OSCs without disrupting structural order is a crucial challenge, as it significantly affects the charge carrier mobility. Here, we demonstrate a molecular doping method without disrupting the molecular ordering to improve the charge carrier mobility of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) based OTFTs via a simple thermal spin-coating method. The key is to introduce micro-nano pores into C8-BTBT thin-film for channel doping, which is achieved by mixing with the unsubstituted BTBT as it can be easily removed from the thin-film through an ordinary annealing process. Micro-nano pores allow the dopant molecules (2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, F4-TCNQ) to access the conductive channel of OTFT, which is beneficial for charge injection. Indeed, we further discover that F4-TCNQ doped porous C8-BTBT thin-films exhibit better charge mobility than those of neat and F4-TCNQ doped C8-BTBT films in OTFTs. This work proposes an effective way to expose OSC conjugated core to the dopant, which not only improves the charge transfer reaction between organic/dopant semiconductor through cofacial stacking, but also reduces the trap density and contact resistance. [ABSTRACT FROM AUTHOR]

Polysorbate-80 (PS-80) is a common surfactant used in biologics formulations. However, the tendency of oxidation to PS-80 when exposed to stainless steel surfaces brings various challenges during manufacturing processes, such as inconsistent shelf-life of PS-80 solutions, which can further impact the biologics and vaccines production. In this work, the root causes of PS-80 oxidation when in contact with stainless steel conditions were thoroughly investigated through the use of various complementary analytical techniques including U/HPLC-CAD, LC-MS, ICP-MS, peroxide assay, and EPR spectroscopy. The analytical tool kit used in this work successfully revealed a PS-80 degradation mechanism from the perspective of PS-80 content, PS-80 profile, iron content, peroxide production, and radical species. The combined datasets reveal that PS-80 oxidative degradation occurs in the presence of histidine and iron in addition to being combined with the hydroperoxides in PS-80 material. The oxidative pathway and potential degradants were identified by LC-MS. The PS-80 profile based on the U/HPLC-CAD assay provided an effective way to identify early-signs of PS-80 degradation. The results from a peroxide assay observed increased hydroperoxide along with PS-80 degradation. EPR spectra confirmed the presence of histidine-related radicals during PS-80 oxidation identifying how histidine is involved in the oxidation. All assays and findings introduced in this work will provide insight into how PS-80 oxidative degradation can be avoided, controlled, or detected. It will also provide valuable evaluations on techniques that can be used to identify PS-80 degradation related events that occur during the manufacturing process. [ABSTRACT FROM AUTHOR]

Abstract Metal-containing monomers are the building blocks for metallopolymers, and play very important role in their functions. As a class of new building block, the incorporation of organically modified polyoxometalates (OMPs) to metallopolymers not only broaden the kind of metal elements in metallopolymers, but also introduce novel functions. Herein, a survey of the progress in the OMPs-based metallopolymers is given. The organic modification methods of OMPs, synthetic strategy of OMPs-based metallopolymers, as well as their applications will be discussed. Graphical abstract Image 1 Highlights • Design and synthesis of POMs-containing monomer were summarized. • Preparation of POMs-containing metallopolymers were summarized. • Supramolecular self-assembly and applications of POMs-containing metallopolymers were summarized. [ABSTRACT FROM AUTHOR]

Abstract Ultrafast affinity extraction was evaluated and used with microcolumns containing human serum albumin (HSA) to measure the global affinity constants and dissociation rate constants for several second- and third-generation sulfonylurea drugs with solution-phase normal HSA or glycated HSA. Glibenclamide, glimepiride and glipizide were used as model drugs for this work. Both single- and two-column systems were considered for the analysis of global affinities for the model drugs. These methods were optimized with respect to the flow rates, column sizes and sample residence times that were employed with each drug for ultrafast affinity extraction. Data acquired with single-column systems were further utilized to estimate the dissociation rate constants for normal HSA and glycated HSA with the given drugs. The binding constants obtained by the single- and two-column systems showed good agreement with each other and with values obtained from the literature. Use of a single-column system indicated that levels of glycation found in controlled or advanced diabetes resulted in a 18–44% decrease in the overall binding strength of the model drugs with HSA. Although the two-column system allowed work with smaller free drug fractions and clinically-relevant drug/protein concentrations, the single-column system required less protein, provided better precision, and was easier to use in binding studies. Highlights • Ultrafast affinity extraction was used to study binding by sulfonylureas with albumin • Both single- and two-column systems were optimized and compared for this work • Normal and glycated human serum albumin were examined in these studies • The global affinity constants obtained showed good agreement with the literature • The dissociation rate constants of these interactions were also measured [ABSTRACT FROM AUTHOR]

A number of tools based on high-performance affinity separations have been developed for studying drug-protein interactions. An example of one recent approach is ultrafast affinity extraction. This method has been employed to examine the free (or non-bound) fractions of drugs and other solutes in simple or complex samples that contain soluble binding agents. These free fractions have also been used to determine the binding constants and rate constants for the interactions of drugs with these soluble agents. This report describes the general principles of ultrafast affinity extraction and the experimental conditions under which it can be used to characterize such interactions. This method will be illustrated by utilizing data that have been obtained when using this approach to measure the binding and dissociation of various drugs with the serum transport proteins human serum albumin and alpha 1 -acid glycoprotein. A number of practical factors will be discussed that should be considered in the design and optimization of this approach for use with single-column or multi-column systems. Techniques will also be described for analyzing the resulting data for the determination of free fractions, rate constants and binding constants. In addition, the extension of this method to complex samples, such as clinical specimens, will be considered. [ABSTRACT FROM AUTHOR]

In the circulatory system, many drugs are reversibly bound to serum proteins such as human serum albumin (HSA) and alpha 1 -acid glycoprotein (AGP), resulting in both free and protein-bound fractions for these drugs. This report examined the use of microcolumns containing immobilized AGP for the measurement of free drug fractions by ultrafast affinity extraction and a two-dimensional affinity system. Several drugs known to bind AGP were used as models to develop and evaluate this approach. Factors considered during the creation of this method included the retention of the drugs on the microcolumns, the injection flow rate, the microcolumn size, and the times at which a second AGP column was placed on-line with the microcolumn. The final system had residence times of only 110–830 ms during sample passage through the AGP microcolumns and allowed free drug fractions to be determined within 10–20 min when using only 3–10 μL of sample per injection. This method was used to measure the free fractions of the model drugs at typical therapeutic levels in serum, giving good agreement with the results obtained by ultrafiltration. This approach was also used to estimate the binding constants for each drug with AGP in serum, even for drugs that had significant interactions with both AGP and HSA in such samples. These results indicated that AGP microcolumns could be used with ultrafast affinity extraction to measure free drug fractions in a label-free manner and to study the binding of drugs with AGP in complex samples such as serum. [ABSTRACT FROM AUTHOR]

Ultrafast affinity extraction and a two-dimensional high performance affinity chromatographic system were used to measure the free fractions for various drugs in serum and at typical therapeutic concentrations. Pooled samples of normal serum or serum from diabetic patients were utilized in this work. Several drug models (i.e., quinidine, diazepam, gliclazide, tolbutamide, and acetohexamide) were examined that represented a relatively wide range of therapeutic concentrations and affinities for human serum albumin (HSA). The two-dimensional system consisted of an HSA microcolumn for the extraction of a free drug fraction, followed by a larger HSA analytical column for the further separation and measurement of this fraction. Factors that were optimized in this method included the flow rates, column sizes, and column switching times that were employed. The final extraction times used for isolating the free drug fractions were 333-665 ms or less. The dissociation rate constants for several of the drugs with soluble HSA were measured during system optimization, giving results that agreed with reference values. In the final system, free drug fractions in the range of 0.7-9.5 % were measured and gave good agreement with values that were determined by ultrafiltration. Association equilibrium constants or global affinities were also estimated by this approach for the drugs with soluble HSA. The results for the two-dimensional system were obtained in 5-10 min or less and required only 1-5 μL of serum per injection. The same approach could be adapted for work with other drugs and proteins in clinical samples or for biomedical research. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The rates at which biological interactions occur can provide important information concerning the mechanism and behavior of these processes in living systems. This review discusses several analytical methods that can be used to examine the kinetics of biological interactions. These techniques include common or traditional methods such as stopped-flow analysis and surface plasmon resonance spectroscopy, as well as alternative methods based on affinity chromatography and capillary electrophoresis. The general principles and theory behind these approaches are examined, and it is shown how each technique can be utilized to provide information on the kinetics of biological interactions. Examples of applications are also given for each method. In addition, a discussion is provided on the relative advantages or potential limitations of each technique regarding its use in kinetic studies. [ABSTRACT FROM AUTHOR]

A hybrid method was examined for increasing the binding capacity and activity of protein-based affinity columns by using a combination of protein cross-linking/modification and covalent immobilization. Various applications of this approach in the study of drug–protein interactions and in use with affinity microcolumns were considered. Human serum albumin (HSA) was utilized as a model protein for this work. Bismaleimidohexane (BMH, a homobifunctional maleimide) was used to modify and/or cross-link HSA through the single free sulfhydryl group that is present on this protein. Up to a 75–113% increase in protein content was obtained when comparing affinity supports that were prepared with BMH versus reference supports that were made by using only covalent immobilization. Several drugs that are known to bind HSA (e.g., warfarin, verapamil and carbamazepine) were further found to have a significant increase in retention on HSA microcolumns that were treated with BMH (i.e., a 70–100% increase in protein-based retention). These BMH-treated HSA microcolumns were used in chiral separations and in ultrafast affinity extraction to measure free drug fractions in drug/protein mixtures, with the latter method giving association equilibrium constants that had good agreement with literature values. In addition, it was found that the reversible binding of HSA with ethacrynic acid, an agent that can combine irreversibly with the free sulfhydryl group on this protein, could be examined by using the BMH-treated HSA microcolumns. The same hybrid immobilization method could be extended to other proteins or alternative applications that may require protein-based affinity columns with enhanced binding capacities and activities. [ABSTRACT FROM AUTHOR]

Ultrafast affinity extraction and a multi-dimensional affinity system were developed for measuring free drug fractions at therapeutic levels. This approach was used to compare the free fractions and global affinity constants of several sulfonylurea drugs in the presence of normal human serum albumin (HSA) or glycated forms of this protein, as are produced during diabetes. Affinity microcolumns containing immobilized HSA were first used to extract the free drug fractions in injected drug/protein mixtures. As the retained drug eluted from the HSA microcolumn, it was passed through a second HSA column for further separation and measurement. Items that were considered during the optimization of this approach included the column sizes and flow rates that were used, and the time at which the second column was placed on-line with the HSA microcolumn. This method required only 1.0 μL of a sample per injection and was able to measure free drug fractions as small as 0.09–2.58% with an absolute precision of ±0.02–0.5%. The results that were obtained indicated that glycation can affect the free fractions of sulfonylurea drugs at typical therapeutic levels and that the size of this effect varies with the level of HSA glycation. Global affinity constants that were estimated from these free drug fractions gave good agreement with those predicted from previous binding studies or determined through a reference method. The same approach could be utilized with other drugs and proteins or modified binding agents of clinical or pharmaceutical interest. [ABSTRACT FROM AUTHOR]

Affinity chromatography has become an important tool for characterizing biomolecular interactions. The use of affinity microcolumns, which contain immobilized binding agents and have volumes in the mid-to-low microliter range, has received particular attention in recent years. Potential advantages of affinity microcolumns include the many analysis and detection formats that can be used with these columns, as well as the need for only small amounts of supports and immobilized binding agents. This review examines how affinity microcolumns have been used to examine biomolecular interactions. Both capillary-based microcolumns and short microcolumns are considered. The use of affinity microcolumns with zonal elution and frontal analysis methods are discussed. The techniques of peak decay analysis, ultrafast affinity extraction, split-peak analysis, and band-broadening studies are also explored. The principles of these methods are examined and various applications are provided to illustrate the use of these methods with affinity microcolumns. It is shown how these techniques can be utilized to provide information on the binding strength and kinetics of an interaction, as well as on the number and types of binding sites. It is further demonstrated how information on competition or displacement effects can be obtained by these methods. [ABSTRACT FROM AUTHOR]

A multi-dimensional chromatographic approach was developed to measure the free fractions of drug enantiomers in samples that also contained a binding protein or serum. This method, which combined ultrafast affinity extraction with a chiral stationary phase, was demonstrated using the drug warfarin and the protein human serum albumin. [ABSTRACT FROM AUTHOR]

Background: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage. [ABSTRACT FROM AUTHOR]

Background: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. Methods: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. Results: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. Conclusion: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage. [ABSTRACT FROM AUTHOR]

Surface plasmon resonance and biolayer interferometry are two common real-time and label-free assays that quantify binding events by providing kinetic parameters. There is increased interest in using these techniques to characterize whole virus-ligand interactions, as the methods allow for more accurate characterization than that of a viral subunit-ligand interaction. This review aims to summarize and evaluate the uses of these technologies specifically in virus–ligand and virus-like particle–ligand binding cases to guide the field towards studies that apply these robust methods for whole virus-based studies. [ABSTRACT FROM AUTHOR]

In terms of molecular structures, benzothieno[3,2-b][1]benzothiophene (BTBT) derivatives qualify as the best-performing organic semiconductors for hole transport, but it exhibits poor luminescence properties. For instance, a classical molecule of 2,7-Dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) only shows photoluminescence quantum yields (PLQYs) of 5.0% in chlorobenzene. Herein, we present three kinds of organic semiconductors based on phenyl-BTBT molecule core, namely, 2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT), 2,7-bis(4-ethylphenyl) benzothieno[3,2-b][1] benzothiophene (DBEP-BTBT), and 2,7-bis(4-methoxyphenyl)benzothieno[3,2-b][1]benzothiophene (DBOP-BTBT). Notably, blue fluorescence with relatively high PLQYs of 27%, 36%, and 48% in chlorobenzene was shown. Due to the surface defects and grain boundaries in the thin films, the PLQYs decrease to 3.4% for DPh-BTBT and 7.4% for DBOP-BTBT , respectively. Nevertheless, the DBEP-BTBT film still exhibits an absolute PLQY as high as 12%, which is a rare and precious characteristic in BTBT derivatives. Meanwhile, the differences in photophysical characteristics, crystal structures, and charge transport properties of the three BTBT derivatives were systematically studied. Similar to DPh-BTBT and DBOP-BTBT , the DBEP-BTBT crystals display typical layered herringbone packing structure with multi- and strong intermolecular interactions, which are conductive to form a two-dimensional charge transport network in layered thin films for high mobility. The mobility of DBEP-BTBT in polycrystalline thin film transistors is up to 3.22 cm2V−1s−1 in ambient air, which is close to DPh-BTBT (3.64 cm2V−1s−1) and much higher than that of DBOP-BTBT (0.5 cm2V−1s−1). Moreover, the calculations show that the intermolecular transfer integrals of HOMOs are almost isotropic for six nearest neighbour contacts in DBEP-BTBT and DPh-BTBT crystals, implying their possibility of isotropic hole transport property in single crystals. The benzothieno [3,2-b][1]benzothiophene (BTBT) derivatives have the potential to simultaneously achieve high charge mobility and luminescence property. [Display omitted] • DPh-BTBT, DBEP-BTBT, and DBOP-BTBT possess fluorescence characteristics. • DBEP-BTBT based OLEDs exhibit a EQE max of 1.76% with CIE coordinates of (0.144, 0141). • DBEP-BTBT based OFETs show hole mobility up to 3.22 cm2V−1s−1 in ambient air. • The transfer integral calculations reveal isotropic charge transfer of DBEP-BTBT crystal. [ABSTRACT FROM AUTHOR]

Aim: Klotho expression significantly declines in alveolar macrophages and airway epithelial cells in chronic obstructive pulmonary disease (COPD) patients, and cigarette smoke extract dramatically inhibits the expression and secretion of α-Klotho. This suggests that the silencing of Klotho is the major factor promoting COPD related inflammatory responses. This study aims to investigate the mechanism of Klotho downregulation and its effect on the inflammatory cytokines secretion and cell apoptosis. Methods: Expression of DNA methyltransferases (DNMTs) and Notch signaling activation were quantified in MH-S and 16HBE cells stimulated with cigarette smoke extract (CSE) solution. Specific inhibitors of DNMTs or Notch pathway were added together with CSE into treated and control cells. Inflammatory cytokines, cell viability and cell death were determined to explore the effect of Klotho on COPD related inflammation. Results: CSE treatment statistically increased the level of DNMTs expression, Klotho promoter methylation, and activated the Notch signaling pathway. Notch signal activation played a critical role in the process of modification of Klotho promoter methylation. The inhibition of DNMTs and Notch pathway rescued Klotho levels and inhibited inflammation and cell apoptosis after CSE treatment. Conclusion: Notch-mediated Klotho hypermethylation inhibited Klotho expression, which promoted inflammatory response and cell apoptosis that were associated with the development of COPD. [ABSTRACT FROM AUTHOR]

Interactions with serum proteins such as alpha 1 -acid glycoprotein (AGP) can have a significant effect on the behavior and pharmacokinetics of drugs. Ultrafast affinity extraction and peak profiling were used with AGP microcolumns to examine these processes for several model drugs (i.e., chlorpromazine, disopyramide, imipramine, lidocaine, propranolol and verapamil). The association equilibrium constants measured for these drugs with soluble AGP by ultrafast affinity extraction were in the general range of 10 4 –10 6 M −1 at pH 7.4 and 37 °C and gave good agreement with literature values. Some of these values were dependent on the relative drug and protein concentrations that were present when using a single-site binding model; these results suggested a more complex mixed-mode interaction was actually present, which was also then used to analyze the data. The apparent dissociation rate constants that were obtained by ultrafast affinity extraction when using a single-site model varied from 0.14 to 7.0 s −1 and were dependent on the relative drug and protein concentrations. Lower apparent dissociation rate constants were obtained by this approach as the relative amount of drug versus protein was decreased, with the results approaching those measured by peak profiling at low drug concentrations. This information should be useful in better understanding how these and other drugs interact with AGP in the circulation. In addition, the chromatographic approaches that were optimized and used in this report to examine these systems can be adapted for the analysis of other solute-protein interactions of biomedical interest. [ABSTRACT FROM AUTHOR]

High-performance affinity chromatography (HPAC) was used in a variety of formats to examine multi-site interactions between glimepiride, a third-generation sulfonylurea drug, and normal or in vitro glycated forms of the transport protein human serum albumin (HSA). Frontal analysis revealed that glimepiride interacts with normal HSA and glycated HSA at a group of high affinity sites (association equilibrium constant, or K a , 9.2–11.8 × 10 5 M −1 at pH 7.4 and 37 °C) and a group of lower affinity regions ( K a , 5.9–16 × 10 3 M −1 ). Zonal elution competition studies were designed and carried out in both normal- and reversed-role formats to investigate the binding by this drug at specific sites. These experiments indicated that glimepiride was interacting at both Sudlow sites I and II. Allosteric effects were also noted with R -warfarin at Sudlow site I and with tamoxifen at the tamoxifen site on HSA. The binding at Sudlow site I had a 2.1- to 2.3-fold increase in affinity in going from normal HSA to the glycated samples of HSA. There was no significant change in the affinity for glimepiride at Sudlow site II in going from normal HSA to a moderately glycated sample of HSA, but a slight decrease in affinity was seen in going to a more highly glycated HSA sample. These results demonstrated how various HPAC-based methods can be used to profile and characterize multi-site binding by a drug such as glimepiride to a protein and its modified forms. The information obtained from this study should be useful in providing a better understanding of how drug–protein binding may be affected by glycation and of how separation and analysis methods based on HPAC can be employed to study systems with complex interactions or that involve modified proteins. [ABSTRACT FROM AUTHOR]

In diabetes, the elevated levels of glucose in the bloodstream can result in the nonenzymatic glycation of proteins such as human serum albumin (HSA). This type of modification has been shown to affect the interactions of some drugs with HSA, including several sulfonylurea drugs that are used to treat type II diabetes. This study used high-performance affinity chromatography (HPAC) to examine the interactions of glipizide (i.e., a second-generation sulfonylurea drug) with normal HSA or HSA that contained various levels of in vitro glycation. Frontal analysis indicated that glipizide was interacting with both normal and glycated HSA through two general groups of sites: a set of relatively strong interactions and a set of weaker interactions with average association equilibrium constants at pH 7.4 and 37 °C in the range of 2.4-6.0 × 10 and 1.7-3.7 × 10 M, respectively. Zonal elution competition studies revealed that glipizide was interacting at both Sudlow sites I and II, which were estimated to have affinities of 3.2-3.9 × 10 and 1.1-1.4 × 10 M. Allosteric effects were also noted to occur for this drug between the tamoxifen site and the binding of R-warfarin at Sudlow site I. Up to an 18 % decrease in the affinity for glipizide was observed at Sudlow site I ongoing from normal HSA to glycated HSA, while up to a 27 % increase was noted at Sudlow site II. This information should be useful in indicating how HPAC can be used to investigate other drugs that have complex interactions with proteins. These results should also be valuable in providing a better understanding of how glycation may affect drug-protein interactions and the serum transport of drugs such as glipizide during diabetes. [ABSTRACT FROM AUTHOR]

Background: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism.Objective: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD.Methods: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed.Results: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3+GARP+ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3+GARP- Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood.Conclusion: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage. [ABSTRACT FROM AUTHOR]

The lung microbiota have been found to be substantially altered in numerous pulmonary disorders, and crosstalk between the host pathophysiology and lung microbiota plays critical roles in the regulation of disease states. The aim of this study was to investigate dynamic changes in the lung microbiota during different stages of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Rats receiving an intraperitoneal administration of lipopolysaccharide (LPS) were sacrificed at 12 and 48 h after injection, and the hematological parameters, serum cytokine levels, and histological characteristics of the lung tissue and lung microbiota were assessed. After LPS injection, along with fluctuations of systemic cytokine levels and the onset and regression of pulmonary edema, the diversity, components, and functionalities of the pulmonary microbiota underwent significant dynamic changes. The volatility of the α-diversity indices narrowed after LPS injection, and the indices significantly decreased 48 h later. The abundance of 18 genera and functionality of adenosine triphosphate–binding cassette (ABC) transporters, pentose phosphate, and bacterial chemotaxis pathways were found to significantly differ between specified time points. Several significant correlations between the components and functionalities of the lung microbiota and indicative symptoms of ALI/ARDS were also observed. Brevibacterium was correlated with cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-6 and with hematological percentage of neutrophils (NEU%); Wnt, Notch, and chronic myeloid leukemia signaling pathways were correlated with IL-1β; mitogen-activated protein kinase (MAPK) signaling pathway–yeast was correlated with IL-10; and the pathways of ascorbate and aldarate metabolism and basal transcription factors were correlated with platelet-related indicators. The correlations between the lung microbiota and indicative symptoms of ALI/ARDS identified in this study support further investigation into the underlying mechanism of host–microbiota interactions during lung injury and repair. [ABSTRACT FROM AUTHOR]

[Display omitted] • Adamantyl end-capped groups have potential to boost blue MR-TADF OLEDs' stability. • Adamantyl stabilize excited states by reducing vibronic relaxation in backbones. • Solution-processed deep-blue OLEDs achieved CIE y < 0.08 with a high LT 95 of 55.7 h. Stable solution-processable emitters, particularly deep-blue emitters, are critical for cost-effective and energy-efficient organic light-emitting diodes (OLEDs). In this study, three new multiple resonance (MR) type deep blue emitters with through dual-introduction of methyl and adamantyl as end-capped groups are designed for highly efficient and stable blue fluorescent OLEDs, contributing to doubled device lifetime. Through end-capped modification, the excited states are stabilized via reducing vibronic couplings. Stable deep blue device based on m-DABNA-AdCz are achieved with high current efficiency (CE) of 6.0 cd/A in solution process fluorescent OLEDs and device lifetime up to 95 % of the initial luminance (LT 95) of 55.7 h at 1000 cd m−2, along with the Commission Internationale de l'Eclairage (CIE) coordinates of (0.133, 0.076). This lifetime is the best yet among solution-processed OLEDs of CIE y < 0.08 according to literature to our best knowledge. This work presents a viable strategy for the development of high-performance solution process deep blue fluorescent OLEDs with high color purity and long device lifetime. [ABSTRACT FROM AUTHOR]

The authors would like to call the reader's attention to the following corrections in this article. In the description given for the process of preparing glycated human serum albumin under "In vitro glycation of HSA", the concentrations of D-glucose that were employed were 15 mM and 30 mM. [ABSTRACT FROM AUTHOR]

The last few decades have witnessed the development of many high-performance separation methods that use biologically related binding agents. The combination of HPLC with these binding agents results in a technique known as high performance affinity chromatography (HPAC). This review will discuss the general principles of HPAC and related techniques, with an emphasis on their use for the analysis of biological compounds and pharmaceutical agents. Various types of binding agents for these methods will be considered, including antibodies, immunoglobulin-binding proteins, aptamers, enzymes, lectins, transport proteins, lipids, and carbohydrates. Formats that will be discussed for these methods range from the direct detection of an analyte to indirect detection based on chromatographic immunoassays, as well as schemes based on analyte extraction or depletion, post-column detection, and multi-column systems. The use of biological agents in HPLC for chiral separations will also be considered, along with the use of HPAC as a tool to screen or study biological interactions. Various examples will be presented to illustrate these approaches and their applications in fields such as biochemistry, clinical chemistry, and pharmaceutical research. [ABSTRACT FROM AUTHOR]

One-site immunometric assays that utilize affinity microcolumns were developed and evaluated for the analysis of protein biomarkers. This approach used labeled antibodies that were monitored through on-line fluorescence or near-infrared (NIR) fluorescence detection. Human serum albumin (HSA) was utilized as a model target protein for this approach. In these assays, a fixed amount of labeled anti-HSA antibodies was mixed with samples or standards containing HSA, followed by the injection of this mixture onto an HSA microcolumn to remove excess antibodies and detect the non-retained labeled antibodies that were bound to HSA from the sample. The affinity microcolumns were 2.1 mm i.d. × 5 mm and contained 8–9 nmol of immobilized HSA. These microcolumns were used from 0.10 to 1.0 mL/min and gave results within 35 s to 2.8 min of sample injection. Limits of detection down to 0.10–0.28 ng/mL (1.5–4.2 pM) or 25–30 pg/mL (0.38–0.45 pM) were achieved when using fluorescein or a NIR fluorescent dye as the label, with an assay precision of ±0.1–4.2%. Several parameters were examined during the optimization of these assays, and general guidelines and procedures were developed for the extension of this approach for use with other types of affinity microcolumns and protein biomarkers. [ABSTRACT FROM AUTHOR]

Abstract: Affinity chromatography is a separation technique that has become increasingly important in work with biological samples and pharmaceutical agents. This method is based on the use of a biologically related agent as a stationary phase to selectively retain analytes or to study biological interactions. This review discusses the basic principles behind affinity chromatography and examines recent developments that have occurred in the use of this method for biomedical and pharmaceutical analysis. Techniques based on traditional affinity supports are discussed, but an emphasis is placed on methods in which affinity columns are used as part of HPLC systems or in combination with other analytical methods. General formats for affinity chromatography that are considered include step elution schemes, weak affinity chromatography, affinity extraction and affinity depletion. Specific separation techniques that are examined include lectin affinity chromatography, boronate affinity chromatography, immunoaffinity chromatography, and immobilized metal ion affinity chromatography. Approaches for the study of biological interactions by affinity chromatography are also presented, such as the measurement of equilibrium constants, rate constants, or competition and displacement effects. In addition, related developments in the use of immobilized enzyme reactors, molecularly imprinted polymers, dye ligands and aptamers are briefly considered. [Copyright &y& Elsevier]