High-Efficiency and Emission-Tunable Inorganic Blue Perovskite Light-Emitting Diodes Based on Vacuum Deposition.

The fabrication of perovskite light-emitting diodes (PeLEDs) with vacuum deposition shows great potential and commercial value in realizing large-area display panel manufacturing. However, the electroluminescence (EL) performance of vacuum-deposited PeLEDs still lags behind the counterparts fabricated by solution process, especially in the field of blue PeLEDs. Here, the fabrication of high-quality CsPbBr3- x Clx film through tri-source co-evaporation is reported to achieve high photoluminescence quantum yield (PLQY). Compared with the conventional traditional dual-source co-evaporation, the tri-source co-evaporation method allows for freely adjustable elemental ratios, enabling the introduction of the lattice-matched Cs4 Pb(Br/Cl)6 phase with the quantum-limited effect into the inorganic CsPb(Br/Cl)3 emitter. By adjusting the phase distribution, the surface defects of the emitter can be effectively reduced, leading to better blue emission and film quality. Further, the effects of Cs/Pb ratio and Br/Cl ratio on the PLQY and carrier recombination dynamics of perovskite films are investigated. By optimizing the deposition rate of each precursor source, spectrally stable blue PeLEDs are achieved with tunable emission ranging from 468 to 488 nm. Particularly, the PeLEDs with an EL peak at 488 nm show an external quantum efficiency (EQE) of 4.56%, which is the highest EQE value for mixed-halide PeLEDs fabricated by vacuum deposition.

RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma.

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

Construction of 3,4-Dihydroquinolone Derivatives through Pd-Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with α-Alkylidene Succinimides.

The construction of 3,4-dihydroquinolone derivatives has attracted a considerable amount of attention due to their extensive applications in medicinal chemistry. In this study, we present the Pd-catalyzed [4+2] cycloaddition of vinyl benzoxazinanones with α-alkylidene succinimides for the efficient synthesis of 3,4-dihydroquinolones. This approach presents numerous advantages, including the ready availability of starting materials, mild reaction conditions without the use of additional bases, and a wide range of substrates. In particular, all of the desired products can be easily afforded in high yields (≤99%) and excellent diastereoselectivities (>20:1). The practicality and reliability of this strategy were demonstrated by the successful scale-up synthesis and subsequent straightforward synthetic transformations.

3DVizSNP: a tool for rapidly visualizing missense mutations identified in high throughput experiments in iCn3D.

BACKGROUND: High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation. RESULTS: We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations. CONCLUSIONS: This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP .

Disrupted dynamic functional connectivity of hippocampal subregions mediated the slowed information processing speed in late-life depression.

BACKGROUND: Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear. METHODS: One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed. RESULTS: Cognitive impairment (global cognition, verbal memory, language, visual-spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS. CONCLUSIONS: Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.

Lower Dorsal Lateral Prefrontal Cortex Functional Connectivity in Late-Life Depression With Suicidal Ideation.

OBJECTIVE: The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. RESULTS: Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. CONCLUSION: The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

Regulation of the pigment production by changing Cell morphology and gene expression of Monascus ruber in high-sugar synergistic high-salt stress fermentation.

AIMS: Extreme environment of microbial fermentation is the focus of research, which provides new thinking for the production and application of Monascus pigments (MPs). In this work, the high-sugar synergistic high-salt stress fermentation (HSSF) of MPs was investigated. METHODS AND RESULTS: The Monascus fungus grew well under HSSF conditions with 35 g L-1 NaCl and 150 g L-1 glucose, and the extracellular yellow pigment and intracellular orange pigment yield in HSSF was 98% and 43% higher than that in conventional fermentation, respectively. Moreover, the mycelial morphology was maintained in a better status with more branches and complete surface structure, indicating good biocatalytic activity for pigment synthesis. Four extracellular yellow pigments (Y1, Y2, Y3, and Y4) were transformed into each other, and ratio of the relative content of intracellular orange pigments to yellow pigments (O/Y) significantly (P < 0.05) changed. Moreover, the ratio of unsaturated fatty acids to saturated fatty acids (unsaturated/saturated) was significantly (P < 0.05) increased, indicating that the metabolism and secretion of intracellular and extracellular pigment might be regulated in HSSF. The pigment biosynthesis genes mppB, mppC, mppD, MpPKS5, and MpFasB2 were up-regulated, whereas the genes mppR1, mppR2, and mppE were down-regulated, suggesting that the gene expression to regulate pigment biosynthesis might be a dynamic change process in HSSF. CONCLUSIONS: The HSSF system of MPs is successfully performed to improve the pigment yields. Mycelial morphology is varied to enhanced pigment secretion, and gene expression is dynamically regulated to promote pigment accumulation in HSSF.

Analytical enantioseparation of N-alkyl drugs by reversed-phase liquid chromatography with carboxymethyl-ß-cyclodextrin as mobile phase additive.

Carboxymethyl-ß-cyclodextrins (CM-ß-CDs) with five kinds of degrees of substitution were synthesized and characterized. Analytical enantioseparation of six basic drugs containing N-alkyl groups, including pheniramine, chlorpheniramine, labetalol, propranolol, venlafaxine, and trans-paroxol, was achieved by reversed-phase high-performance liquid chromatography (RP-HPLC) using the synthesized CM-ß-CD as chiral mobile phase additives. Key influence factors were optimized, including organic modifier, pH value, CM-ß-CD with different degrees of substitution, and concentration of CM-ß-CD. The mobile phase was composed of methanol and 10 mmol L-1 of phosphate buffer pH 4.0 containing 10 mmol L-1 of CM-ß-CD. Peak resolution for six racemic drugs was gradually increased with an increasing degree of substitution of the synthesized CM-ß-CD. The stoichiometric ratio and binding constants for the inclusion complex formed by CM-ß-CD and enantiomer were determined, which showed that the stoichiometric ratio for each inclusion complex was 1:1.

High-performance liquid chromatography micro-fraction bioactive evaluation combined with countercurrent chromatographic separation of antioxidants from Citrus peel and their tyrosinase inhibition activities.

In the present study, high-performance liquid chromatography micro-fraction bioactive evaluation and high speed countercurrent chromatography were performed on screening, identification and isolation of antioxidants from Citrus peel. Three compounds were screened as antioxidants and tyrosinase inhibitors using 2,2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation scavenging assay and tyrosinase activity test, then they were identified as eriocitrin, narirutin and hesperidin. Moreover, the solvent system ethyl acetate-n-butanol-water (6:4:10, v/v/v) was used for separation of ethyl acetate extract of Citrus peel by high speed countercurrent chromatography. In total, 0.45 mg of eriocitrin with 87.10% purity, 2.04 mg of narirutin with 95.19% purity and 1.35 mg of hesperidin with 95.19% purity were obtained from 20 mg of ethyl acetate extract of Citrus peel in a single run and then each component was subjected to 2,2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation scavenging assay and tyrosinase inhibition assay. Eriocitrin showed great antioxidant activity (the half-maximum concentration: 3.65 µM) and tyrosinase inhibition activity (the half-maximum concentration: 115.67 µM), while narirutin and hesperidin exhibited moderate activity. Tyrosinase inhibition activity for eriocitrin in vitro was reported for the first time. Furthermore, molecular docking between eriocitrin and mushroom tyrosinase was also studied.

High-resolution monophenolase/diphenolase/radical scavenging profiling for rapid screening of natural whitening candidates from Rosa rugosa cv. 'Plena'.

Antioxidants and tyrosinase inhibitory components were successfully screened and separated from Rosa rugosa cv. 'Plena' by high-performance liquid chromatography microfractionation bioactive screening combined with several separation and purification methods. Ethyl acetate extract of Rosa rugosa cv. 'Plena' showed high antioxidant activity and tyrosinase inhibitory activity. High-speed countercurrent chromatography, silica gel column chromatography, and semi-preparative high-performance liquid chromatography were used for the preparative separation of four bioactive components from ethyl acetate extract. Two tyrosinase-inhibiting active substances, flavogallonic acid, and N1 -N5 -N10 -tri-4-p-coumaroylspermidine, were isolated from Rosa rugosa cv. 'Plena', and they showed great monophenolase inhibition activity (half-maximal inhibitory concentration: 664.60 and 23.77 µg/ml, respectively) and excellent diphenolase inhibition activity (half-maximal inhibitory concentration: 23 614.61 and 16.80 µg/ml, respectively). Meanwhile, gallic acid, flavogallonic acid, and ellagic acid were shown to have excellent 1,1-diphenyl-2-picryl-hydrazyl antioxidant activity (half maximal inhibitory concentration: 6.66, 20.17, and 13.45 µg/ml), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant activity (half maximal inhibitory concentration: 3.53, 3.83, and 2.78 µg/ml). Molecular docking revealed that flavogallonic acid and N1 -N5 -N10 -tri-4-p-coumaroylspermidine had a strong binding affinity (-9.3 and -10 kcal/mol, respectively) to tyrosinase through hydrogen bonding and hydrophobic interactions.

The pathogenesis and regulatory role of HIF-1 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease that involves the overgrowth and inflammation of synovial tissue, leading to the degeneration and impairment of joints. In recent years, numerous studies have shown a close relationship between the hypoxic microenvironment in joints and the occurrence and progression of RA. The main cause of the pathological changes in RA is widely believed to be the abnormal expression of hypoxia-inducible factor-1 (HIF-1) in joints. This paper describes and illustrates the structure and primary functions of HIF-1 and explains the main regulatory methods of HIF-1, including the PHDs/HIF-1 α/pVHL pathway, factor-inhibiting HIF (FIH), regulation of inflammatory cytokines, and the NF-κB pathway. Furthermore, this paper discusses the mechanism of HIF-1 and its impact on inflammation, angiogenesis, and cartilage destruction in greater detail. We summarize previous research findings on the mechanism of HIF-1 and propose new potential treatments for RA based on the pathogenesis of HIF-1 in RA.

Deciphering gp120 sequence variation and structural dynamics in HIV neutralization phenotype by molecular dynamics simulations and graph machine learning.

Human immunodeficiency virus (HIV) exploits the sequence variation and structural dynamics of the envelope glycoprotein gp120 to evade the immune attack of neutralization antibodies, contributing to various HIV neutralization phenotypes. Although the HIV neutralization phenotype has been experimentally characterized, the roles of rapid sequence variability and significant structural dynamics of gp120 are not well understood. Here, 45 prefusion gp120 from different HIV strains belong to three tiers of sensitive, moderate, and resistant neutralization phenotype are structurally modeled by homology modeling and then investigated by molecular dynamics (MD) simulations and graph machine learning (ML). Our results show that the structural deviations, population distribution, and conformational flexibility of gp120 are related to the HIV neutralization phenotype. Per-residue dynamics indicate the local regions especially in the second structural elements with high-flexibility, may be responsible for the HIV neutralization phenotype. Moreover, a graph ML model with the attention mechanism was trained to explore inherent representation related to the classification of the HIV neutralization phenotype, further distinguishing the strong related gp120 sequence variation together with structural dynamics in the HIV neutralization phenotype. Our study not only deciphers gp120 sequence variation and structural dynamics in the HIV neutralization phenotype but also explores complex relationships between the sequence, structure, and dynamics of protein by combining MD simulations and ML.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Asymmetric [4 + 2] Annulation of Cyclobutenones and Pyrazolone 4,5-Diones: Access to Novel δ-Lactone-Fused Spiropyrazolones.

Although numerous chiral pyrazolones with a six-membered spirocyclic center at the C4 position have been developed, the asymmetric construction of six-membered oxa-spiropyrazolones is still a challenging task in organic synthesis. Herein, we describe the [4 + 2] annulation of cyclobutanones and pyrazoline-4,5-diones for the efficient synthesis of δ-lactone-fused spiropyrazolone derivatives with generally high yields and good enantioselectivities under mild conditions. The successful scale-up synthesis and further transformation of the final product highlight the practicality and reliability of this reaction.

Fine and hyperfine interactions of PbF studied by laser-induced fluorescence spectroscopy.

The fine and hyperfine interactions in PbF have been studied using the laser-induced fluorescence (LIF) spectroscopy method. Cold PbF molecular beam was produced by laser-ablating a Pb rod under jet-cooled conditions, followed by the reaction with SF6. The LIF excitation spectrum of the (0, 0) band in the B2Σ+-X2Π1/2 system of the 208PbF, 207PbF, and 206PbF isotopologues has been recorded with rotational, fine structure, and hyperfine-structure resolution. Transitions in the LIF spectrum were assigned and combined with the previous X2Π3/2-X2Π1/2 emission spectrum in the near-infrared region [Ziebarth et al., J. Mol. Spectrosc. 191, 108-116 (1998)] and the X2Π1/2 state pure rotational spectrum of PbF [Mawhorter et al., Phys. Rev. A 84, 022508 (2011)] in a global fit to derive the rotational, spin-orbit, spin-rotation, and hyperfine interaction parameters of the ground (X2Π1/2) and the excited (B2Σ+) electronic states. Molecular constants determined in the present work are compared with previously reported values. Particularly, the significance of the hyperfine parameters, A⊥ and A‖, of 207Pb is discussed.

Enantioseparation of N-methyl duloxetine, duloxetine, and fluoxetine by countercurrent chromatography using anionic ß-cyclodextrin as chiral selector.

Two anionic ß-cyclodextrins as chiral selectors were successfully applied in the enantioseparation of N-methyl duloxetine, duloxetine, and fluoxetine by countercurrent chromatography. Sulfobutyl ether-ß-cyclodextrin and carboxymethyl-ß-cyclodextrin showed opposite enantioselectivity for both duloxetine and N-methyl duloxetine enantiomers. Two biphasic solvent systems, n-hexane: 0.1 mol/L phosphate buffer pH 7.6 with 50 mmol/L of sulfobutyl ether-ß-cyclodextrin (1:1, v/v) and n-hexane: 0.1 mol/L phosphate buffer pH 7.2 with 50 mmol/L of carboxymethyl-ß-cyclodextrin (1:1, v/v), were selected for N-methyl duloxetine. Enantioseparation of duloxetine was achieved by recycling countercurrent chromatography using a solvent system composed of n-butyl acetate: 0.1 mol/L phosphate buffer pH 7.2 with 20 mmol/L of sulfobutyl ether-ß-cyclodextrin or carboxymethyl-ß-cyclodextrin (1:1, v/v). A solvent system composed of n-hexane: n-butyl acetate: 0.1 mol/L phosphate buffer pH 7.6 containing 20 mmol/L of sulfobutyl ether-ß-cyclodextrin (6:4:10, v/v) was selected for enantioseparation of fluoxetine.

Enantioseparation of five racemic N-alkyl drugs by reverse phase HPLC using sulfobutylether-ß-cyclodextrin as a chiral mobile phase additive.

Analytical enantioseparations of five N-alkyl drugs, fluoxetine hydrochloride, labetalol, venlafaxine hydrochloride, trans-paroxol, and atropine sulfate, were investigated by reverse phase high-performance liquid chromatography with sulfobutylether-ß-cyclodextrin as chiral mobile phase additive. Effects of various factors such as composition of mobile phase, concentration of cyclodextrins, and column temperature on retention and enantioselectivity were studied. Apparent formation constant between methanol, acetonitrile, and sulfobutylether-ß-cyclodextrin were determined to be 2.90 × 10-3 and 1.00 × 10-4 L mmol-1 under 25°C using UV-spectrophotometry. Van't Hoff plots were used to investigate thermodynamic parameters for enantiomers-stationary phase interaction and formation of inclusion complex. Two retention models were employed individually for evaluation of inclusion complexation between five racemates and sulfobutylether-ß-cyclodextrin. The second model with complex adsorption was more accord with the retention behavior of fluoxetine hydrochloride, labetalol, and venlafaxine hydrochloride enantiomers, while the first model was more consistent with the retention behaviors of trans-paroxol and atropine sulfate. In the selected mobile phase, stoichiometric ratio for both of inclusion complex was found to be 1:1.

The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: a prospective randomized controlled study.

BACKGROUND: Ciprofol is a recently developed, short-acting γ-aminobutyric acid receptor agonist sedative that is more potent than propofol, but there have been few clinical studies of this agent to date. Here, we sought to examine the safety and efficacy of ciprofol use for the induction of general anesthesia in individuals undergoing gynecological surgery. METHODS: Women between the ages of 18 and 60 years (ASA physical status 1 or 2) who were scheduled to undergo elective gynecological surgery under general anesthesia were randomly assigned to two equally sized groups in which anesthesia induction was performed using either ciprofol or propofol. General anesthesia induction success rates were the primary outcome for this study, while secondary outcomes included changes in BIS during the 10 min following the first administration of the study drug, the duration of successful induction, and adverse event incidence. RESULTS: A total of 120 women were included in the study. A 100% rate of successful induction was achieved in both the ciprofol and propofol groups, with no significant differences between these groups with respect to the duration of successful induction (34.8 ± 15.5 s vs 35.4 ± 9.5 s, P = 0.832), the time to the disappearance of the eyelash reflex (33.7 ± 10.6 s vs 34.0 ± 6.5 s, P = 0.860), or tracheal intubation (58.2 ± 31.1 s vs 53.9 ± 25.4 s, P = 0.448). Adverse event rates, including intubation responses, were significantly lower in the ciprofol group as compared to the propofol group(20% vs 48.33%, P = 0.0019). Ciprofol was associated with reduced injection pain relative to propofol (16.7% vs 58.3%, P < 0.001). CONCLUSIONS: Ciprofol exhibits comparable efficacy to that of propofol when used for the induction of general anesthesia in individuals undergoing gynecological surgery and is associated with fewer adverse events.

The prevalence and clinical features of chronic obstructive pulmonary disease patients with traits of asthma in Taiwan.

BACKGROUND/PURPOSE: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations has not been well studied although such identification is important in clinical practice. Thus, we aimed to investigate the prevalence and features of COPD coexistent with asthma traits diagnosed based on the 2015 GINA/GOLD strategies, and explore the gap between guidelines and routine practice in the diagnosis and pharmacological management of such condition in a COPD cohort. METHODS: COPD subjects were enrolled retrospectively throughout Taiwan. A patient record form was completed for each participant and the data were analyzed. RESULTS: Of 340 participants, the prevalence of COPD coexistent with traits of asthma was 39.4% and 30.3% based on guidelines and physician's judgment, respectively. Coexistent patients were characterized by blood eosinophilia, higher total immunoglobulin E (IgE) levels, preserved lung function, and the presence of gastro-esophageal reflux disease and atopic disease while total IgE level > 100 kU/L and the presence of atopic disease were predictors for coexistent patients. Gaps existed in the diagnosis (a weak agreement with kappa = 0.53) and treatment (non-adherence to the preferred therapy in 18.4% of physician-judged coexistent patients) in COPD patients with asthma traits. The exacerbation history was similar between coexistent and non-coexistent patients. CONCLUSION: We found that measuring circulatory eosinophil and total IgE levels may raise clinicians' awareness of the presence of traits of asthma in the management of COPD.

Efficient Protein-Protein Couplings Mediated by Small Molecules under Mild Conditions.

Protein-protein coupling reactions under physiological conditions that do not impact the three-dimensional structures of the proteins are in high demand. Owing to the combination of phenylsulfonyl and aldehyde groups in 5-fluoro-4-(phenylsulfonyl)picolinaldehyde (FPPA), the fluorine substituent shows high reactivity toward free thiols. In FPPA, the fluorine is more reactive than phenylsulfonyl for free thiols. Thus the first quantitative nucleophilic substitution can be followed by selective substitution of phenylsulfonyl by an additional thiol or cyclization of aldehyde with a 1,2-aminothiol molecule. The FPPA mediated protein-protein coupling proceeds efficiently under mild conditions, resulting in stable protein conjugates. This coupling method has negligible 3D structural perturbations on the target proteins, and it produces overall intact, nearly traceless, and native structural folds of proteins. It is highly suitable for reconstruction of proteins that are difficult to make and segmental isotopic labeling of multidomain proteins.