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Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to15 kg: 200 mg; bodyweight ≥15 kg to30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.Sanofi and Regeneron Pharmaceuticals.

An ideal carbon-based supercapacitor electrode requires abundant micropores that are favorable for charge accumulation, and suitable mesopores that are beneficial for fast electrolyte ions transport. Herein, 3D porous carbon microspheres (carbon nanotube-ketjen black/activated carbon, CNT-KB/AC), where the CNT-KB microspheres (CKMS) as the framework providing mesopores and the activated carbon as the core providing micropores, have been constructed by spray drying and KOH activation. The obtained carbon composites exhibit a homogeneous spherical structure and high specific surface area (up to 1751 m2 g−1). The CNT-KB/AC electrode with an areal density of 3 mg cm−2 can achieve a high areal capacitance of 506.9 mF cm−2 at the current density of 0.2 A g−1 in 6 M KOH solution, which is much larger than that of the CNT/AC electrode (232.6 mF cm−2) and CNT-AB/AC electrode (179.5 mF cm−2). Besides, when the areal density is increased up to 9 mg cm−2, the areal capacitance of CNT-KB/AC is increased up to 998.9 mF cm−2 at 0.2 A g−1 and 724.9 mF cm−2 at 20 A g−1. Furthermore, it exhibits excellent long-term cycling stability (achieving capacitance retention of 94% after 10,000 cycles). These results indicate that the CNT-KB/AC composites are promising electrode materials for high-areal-density supercapacitors.

A fast, simple and environmentally friendly method for the digestion of solid samples of Gentiana rigescens Franch. ex Hemsl. (G. rigescens) based on deep eutectic solvent (DES) was established, and inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to quantify Ni, Zn, Co, Cr and Cu in DES digestion solution. Under optimized conditions, limits of detection (LOD) and limits of quantification (LOQ) ranged from 0.4 to 2.5 and 1.2-8.2 μg g

EPR spectroscopy was used to monitor formation of free radicals in human hair upon UV irradiation. While the EPR spectra of brown hair were dominated by melanin signal, those of white hair were keratin-derived. The decay of UV induced keratin radicals was enhanced at increased ambient humidity. We argue that at higher humidity the swollen hair provides a more liquid-like environment, and higher molecular mobility in this environment leads to faster radical reactions. This interpretation is consistent with the increased UV-triggered protein damage in hair at high humidity as demonstrated by the protein loss, MALDI-TOF and FT-IR data.

In this work, switchable hydrophilicity solvent-based ultrasound-assisted liquid phase microextraction (SHS-UA-LPME) was combined with micro-volume UV-vis spectrophotometry for the determination of trace nickel in the medicinal plant Gentiana rigescens Franch. ex Hemsl. (G. rigescens) samples for the first time. Micro-volume spectrophotometry has the characteristics of microanalysis, economy and low operation cost, which is feasible to be combined with miniaturized enrichment method. Dipropylamine (DPA) as a switchable solvent completed the extraction during the phase conversion process. It was changed from hydrophobic to hydrophilic under the action of HCl, and then completed phase transition under the action of NaOH. The parameters influencing the extraction efficiency were investigated. Under the optimal conditions, the enhancement factor (EF), the limit of detection (LOD), the limit of quantitation (LOQ) and relative standard deviation (RSD, n = 7) were 28, 0.02 µg/L, 0.067 µg/L and 1.4%, respectively. The established method was applied to the determination of G. rigescens samples collected from the local field with satisfactory results.

Novel heavy atom free 5,5-dioxoyphenothiazine-based “D–A–D” emitters with aggregation-induced emission (AIE), room-temperature phosphorescence (RTP), white light emission and dual-mode mechanochromic luminescence (MCL) characteristics have been designed and synthesized. Impressively, DCzCs and DCzCs-Et showed persistent RTP (pRTP) in the crystalline state with lifetimes of 528 ms and 137 ms in air, respectively. DCzCs-Ac exhibited white light emission with a CIE coordinate of (0.25, 0.26), due to the dual emission of fluorescence and phosphorescence. Detailed studies have shown that through simply functional group modification on the acceptor skeleton to modulate the molecular structure and intermolecular interactions, we fine-tuned the optical properties of the luminogens and realized white light emission. The dense crystal packing was proved to be closely related to the phosphorescence of the system and the special dual-mode MCL behavior was attributed to the conversion of crystalline-amorphous state under external force.

Two novel aggregation-induced emission (AIE) based fluorescent probes, TPANI-DNs and PCZNI-DNs, have been designed and synthesized for “turn-on” detection of H2S. Chromophore napthalimide fused triphenylamine (or phenylcarbazole) unit as fluorophore in combination with 2,4-dinitrobenzenesulfonyl as recognition moiety constructed probes. The design strategy of the twisted D-π-A structure can efficiently transform the aggregation-caused quenching (ACQ) system into the AIE system by strengthening the restriction of intramolecular motion and preventing the intermolecular π-π stacking. The consequences showed that both TPANI-DNs and PCZNI-DNs displayed large stokes shift (135 nm and 120 nm, respectively), high selective and sensitive detection. The response mechanisms and fluorescent properties were further investigated through the time-dependent density functional theory (TDDFT). Importantly, since the strong AIE properties, a H2S test board has been prepared and used to detect H2S onsite easily and sensitively, displaying potential practical applications.

Surface coating is an efficient strategy to enhance the interfacial stability of the electrode. Graphene quantum dots (GQDs) have advantages of excellent dispersion in water, outstanding electron and ion conductivities and high specific surface area. In this work, GQDs were coated directly on the surface of LiCoO2 particles (GQDs-LiCoO2) through liquid phase method. Compared to bare LiCoO2, the cycling performance, rate capacity and thermo-stability of the GQDs-LiCoO2 have been significantly improved in the voltage range of 3.04.5 V. GQDs-LiCoO2 showed a much higher capacity retention than that of bare LiCoO2 (82.8 % vs 46.1 %) after 100 cycles at 0.5 C. The excellent improvement of the GQDs-LiCoO2 was mainly attributed to the formation of a uniform, stable, dense and well-conductive protective layer on the surface of LiCoO2 particles by the surface coating of GQDs. The detailed analysis of the cycled electrodes reveals that the GQDs coating stabilizes the crystal structure of LiCoO2 and suppresses undesirable interfacial side reactions between the cathode and electrolyte, leading to the improvement of battery performance.

The pH-dependent structures of the 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) self-assembled monolayers (SAMs) on the silver surface were studied by surface enhanced Raman scattering (SERS) spectroscopy. The resulting SERS spectra show that the adsorption fashion of AMT monolayers formed at pH 1 could exhibit the strongest interaction with the silver surface among the investigated pH values at 1, 7, and 13. Electrochemical impedance spectroscopy (EIS) illuminates that the anticorrosive effect of AMT monolayers formed under pH 1 is the best. The inhibition efficiencies of AMT SAMs formed under pH 1, 7 and 13 are 72.2, 39.1 and 4.97%, respectively, according to experimental results of their Tafel plots.

Anticorrosive behaviors of 2-mercaptobenzothiazole (MBT) self-assembled monolayers (SAMs) on silver and zinc electrodes were comparatively studied by means of electrochemical impedance spectroscopy (EIS). The promising inhibition effect of the MBT for silver and zinc from corrosion had been confirmed. The adsorption geometries of MBT monolayers on zinc and silver electrodes were observed by surface enhanced Raman scattering (SERS) technique. The SERS spectra implied that monolayers of MBT could be self-assembled on Ag surface through S 10 and N 3 atoms and the molecular plane should be tilted with respect to the surface. On Zn surface, MBT molecules formed monolayers via both S atoms and the other moieties of the molecule away from the surface. From the in situ electrochemical SERS results it can be found that MBT monolayers on both Ag and Zn surfaces experienced the changes of adsorption fashions as the potential shifting to more negative direction.

Kinetic interactions of β-lactam antibiotics such as penicillin-G and cefotaxime with normal, penicillin-susceptible PBP2x from Streptococcus pneumoniae and a penicillin-resistant PBP2x (PBP2xR) from a resistant clinical isolate (CS109) of the bacterium have been extensively characterized using electrospray mass spectrometry coupled with a fast reaction (quench flow) technique. Kinetic evidence for a two-step acylation of PBP2x by penicillin-G has been demonstrated, and the dissociation constant, K d of 0.9 mm, and the acylation rate constant, k 2 of 180 s−1, have been determined for the first time. The millimolar range K d implies that the β-lactam fits to the active site pocket of the penicillin-sensitive PBP rather poorly, whereas the extremely fast k 2 value indicates that this step contributes most of the binding affinity of the β-lactam. The values of K d (4 mm) and k 2 (0.56 s−1) were also determined for PBP2xR. The combined value ofk 2/K d, known as overall binding efficiency, for PBP2xR (137m −1 s−1) was over 1000-fold slower than that for PBP2x (200,000 m −1s−1), indicating that a major part is played by the acylation steps in penicillin resistance. Most of the decreased binding efficiency of PBP2xR comes from the decreased (∼300-fold)k 2. Kinetic studies of cefotaxime acylation of the two PBP2x proteins confirmed all of the above findings. Deacylation rate constants (k 3) for the third step of the interactions were determined to be 8 × 10−6s−1 for penicilloyl-PBP2x and 5.7 × 10−4 s−1 for penicilloyl-PBP2xR, corresponding to over 70-fold increase of the deacylation rate for the resistant PBP2xR. Similarly, over 80-fold enhancement of the deacylation rate was found for cefotaxime-PBP2xRcomplex (k 3 = 3 × 10−4s−1) as compared with that of cefotaxime-PBP2x complex (3.5 × 10−6 s−1). This is the first time that such a significant increase ofk 3 values was found for a β-lactam-resistant penicillin-binding protein. These data indicate that the deacylation step also plays a role, which is much more important than previously thought, in PBP2xR resistance to β-lactams.

The oxidation of ascorbic acid leads to the formation of several compounds which are capable of reacting with protein amino groups via a Maillard reaction. Radioactivity from [1- 14 C]ascorbic acid was linearly incorporated into lens crystallins over a 10 day period in the presence of NaCNBH 3 . This rate of incorporation was 6–7-fold more rapid than that obtained with [[ 14 C]glucose under the same conditions. SDS-PAGE showed a linear incorporation into all the cyrstallin subunits. [1- 14 ]Ascorbic acid-label led α-crystallin was separated into into its component A and B subunits, and each was digested with chymotrypsin. HPLC peptide analysis showed a differential labelling of the various lysine residues. Analysis of the peptides by mass spectrometry allowed the identification of the sites and the extent of modification. These values ranged from 6% for Lys-78 to 36% for Lys-11 in the A subunit and from 5% for Lys-82 to an average of 38% for the peptide containing Lys-166, Lys-174 and Lys-175 in the B subunit. Amino acid analysis demonstrated a single modification reaction producing N ϵ -(carboxymethyl)lysine. This agreed with the mass increase of 58 observed for each modified peptide.

s / Biol Blood Marrow Transplant 19 (2013) S178eS193 S186 may be warranted to discern if DM pts may benefit from different methods of mobilization or if long term transplant outcomes are impacted.

In addition to reducing the analysis time, the direct examination of proteolytic digests by fast atom bombardment mass spectrometry (FABMS) greatly extends the information that is available from peptide mapping experiments. Mass spectral data are particularly useful for identifying post-translationally modified peptides. For example, the molecular weight of a disulfide-containing peptide may be used to locate the disulfide bond in the protein from which the peptide was derived. This paper describes a new procedure, which is useful for identifying disulfide-bonded peptides. Peptides are treated with performic acid to modify certain residues and thereby cause a characteristic change in the peptide molecular weight. This change in molecular weight is determined by FABMS and used to help identify peptides. Results for a series of small peptides demonstrate that Cys, Met, and Trp are the only residues that undergo a change in molecular weight under the conditions used here. Furthermore, these changes in molecular weight are diagnostic for each of the residues. Cysteinyl-containing peptides are of particular interest, because their identification is essential for locating disulfide bonds. The molecular weight of a peptide increases by 48 mu for each cysteinyl residue present. This approach is used to identify peptides that contain both cysteinyl and cystinyl residues in the peptic digest of bovine insulin. The method is extended to the analysis of a tryptic digest of cyanogen bromide-treated ribonuclease A. A computer-assisted analysis procedure is used to demonstrate the specifity with which peptide molecular weight is related to specific segments of the protein. These results demonstrate that the shift in peptide molecular weight, after the digest is treated with performic acid, leads to unique assignment of the six cysteinyl-containing peptides found in the digest.