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Omalizumab is widely used in clinical practice; however, knowledge gaps in the dosage of omalizumab for children aged 2–6 years with moderate‐to‐severe persistent allergic asthma have been identified. The aim of this study was to explore dosing regimens for moderately‐to‐severely allergic pediatric patients aged 2–6 years. The physiologically‐based pharmacokinetic (PBPK) model of omalizumab was developed and verified in adult patients, extrapolated to pediatric patients, and simulated for omalizumab by adding two observation chambers (free IgE and total IgE). The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (Cmax) were between 0.5 and 2.0, and the average folding error and the absolute average folding error values for all concentration‐time data points were 1.09 and 1.48, respectively. The PBPK model combined with pharmacokinetic/pharmacodynamic analysis of omalizumab demonstrated that both the model‐derived dose and the original dose could control the average free IgE of 2–6‐year‐old children with moderate‐to‐severe allergic asthma below 25 ng/mL, and some of the model‐derived doses were lower. This conclusion provides a basis for the selection of dosage in clinical practice reference. [ABSTRACT FROM AUTHOR]

Considerable signal crosstalk exists in the regulatory network of senescence and stress response. Numerous senescence‐associated genes are also involved in plant stress tolerance. However, the underlying mechanisms and application potential of these genes in stress‐tolerant crop breeding remain poorly explored. We found that overexpression of SENESCENCE‐SUPPRESSED PROTEIN PHOSPHATASE (SSPP), a negative regulator of leaf senescence, significantly improved plant salt tolerance by increasing reactive oxygen species (ROS) scavenging in both Arabidopsis and soybean. However, overexpression of SSPP severely suppressed normal plant growth, limiting its direct use in agriculture. We previously revealed that the N‐terminal 1–14 residues of ACS7 (termed 'N7') negatively regulated its protein stability through the ubiquitin/proteasome pathway, and the N7‐mediated protein degradation was suppressed by environmental and senescence signals. To avoid the adverse effects of SSPP, the N7 element was fused to the N‐terminus of SSPP. We demonstrated that N7‐SSPP fusion gene effectively rescued SSPP‐induced growth suppression but maintained enhanced salt tolerance in Arabidopsis and soybean. Particularly, N7‐SSPP enhanced tolerance to long‐term salt stress and increased seed yield in soybean. These results suggest that N7‐SSPP overcomes the disadvantages of SSPP on plant growth inhibition and effectively improves salt tolerance through enhanced ROS scavenging, providing an effective strategy of using posttranslational regulatory element for salt‐tolerant crop breeding. Numerous senescence‐associated genes are also involved in stress tolerance, but the underlying mechanisms and application potentials are poorly investigated. We found that SSPP, a negative regulator of leaf senescence, enhances plant salt tolerance through ROS scavenging. Fusing N7, a regulatory element in the N‐degron pathway, to SSPP rescued SSPP‐induced growth suppression but did not affect salt tolerance in Arabidopsis and soybean. Notably, N7‐SSPP enhanced long‐term salt tolerance and increased yield in soybean. This study supported that manipulation of key senescence‐associated genes can effectively modulate plant stress responses and provided an effective strategy of using regulatory elements in the N‐degron pathway for salt‐tolerant crop breeding. [ABSTRACT FROM AUTHOR]

Mussel‐inspired polydopamine (PDA) coating has been proved to be a universal surface modification strategy with remarkable versatility and active post‐modification ability. However, the traditional preparation of PDA coating shows low polymerization efficiency and alkaline environment dependency. Herein, a robust method to accelerate the in situ generation of PDA coating based on a photosensitizer entrapped substrate is reported. It is demonstrated that the chlorin e6 (Ce6)‐incorporated substrates induce sustained reactive oxygen species (ROS) production via laser irradiation at 660 nm, which dramatically promotes the preparation of PDA coating even in acidic conditions. The thickness of the PDA coating reaches over 4 nm with only 10 min irradiation (pH 6). Patterned PDA coatings can also be achieved by using a photomask. The functionality of this interfacial ROS‐induced PDA coating including photothermal ability and secondary modification ability is also verified. The obtained PDA coating realizes the reduction of Ag+ to Ag NPs, which shows excellent antibacterial ability. This interfacial ROS generation strategy offers a facile and efficient way to construct the PDA coating and expands the potential applications in the biomedical field. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment‐related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36‐fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration–time curve was predicted to increase 1.25‐fold, 1.95‐fold, and 2.82‐fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12‐hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between necrotic collections on endoscopic ultrasound (EUS) and outcomes of the endoscopic transmural step‐up approach in necrotizing pancreatitis (NP). Methods: Adult NP patients who had undergone endoscopic transmural step‐up approach, endoscopic transmural drainage or endoscopic transmural necrosectomy, were retrospectively enrolled, and divided into groups 1, 2 and 3 based on the amount of solid necrotic debris (quantified as a percentage of the total collection size of <30%, 30%‐50%, and >50%). Results: A total of 134 patients were included, of whom 52, 59 and 23 patients were categorized into groups 1, 2 and 3. Patients with more solid necrotic debris required more necrosectomy sessions (group 3 vs group 2 vs group 1: 2.0 vs 1.0 vs 1.0, P < 0.001), were more likely to experience stent occlusion (group 3 vs group 2 vs group 1: 34.8% vs 16.9% vs 9.6%, P = 0.011), and had a longer hospitalization (group 3 vs group 2 vs group 1: 40.0 d vs 28.0 d vs 25.5 d, P = 0.015). High procalcitonin level (adjusted odds ratio [aOR] 6.14, 95% confidence interval [CI] 1.40–26.94, P = 0.016) and any organ failure (aOR 11.51, 95% CI 2.42‐54.78, P = 0.002) were independently associated with clinical failure of endoscopic transmural step‐up approach. Conclusions: More solid necrotic debris on EUS is related to more necrosectomy sessions, higher incidence of stent occlusion and longer hospitalization. A nomogram combining procalcitonin and any organ failure performs well in predicting clinical failure of endoscopic transmural step‐up approach. [ABSTRACT FROM AUTHOR]

Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients. [ABSTRACT FROM AUTHOR]

Aim: To assess the methodological and reporting quality of paediatric clinical practice guidelines (CPGs) in National Guideline Clearinghouse (NGC) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and Reporting Items for Practice Guidelines in Healthcare (RIGHT) standard.Methods: We identified all published CPGs through the NGC, and search records were screened in duplicate for inclusion. Two researchers evaluated the methodological and reporting quality of paediatric CPGs using the AGREE II instrument and RIGHT standard. STATA version 12.0 and SPSS version 22.0 software were used to analyse the related data.Results: A total of 50 paediatric CPGs were included. The scores for all six domains by AGREE II instrument were presented as follows: scope and purpose (85.6 ± 9.59), stakeholder involvement (69.15 ± 19.32), rigour of development (73.19 ± 17.18), clarity of presentation (78.51 ± 14.36), applicability (54.61 ± 22.63) and editorial independence (68.42 ± 13.06). In the seven domains of the RIGHT standard, the reporting rate of the recommendation domain was the lowest (52.86%).The highest reporting rate was the other information domain, which was 68%.There was a high correlation between reporting the completeness of CPGs using the AGREE II instrument and RIGHT standard (r = 0.77, P < 0.001).Conclusions: The paediatric CPGs from NGC have good quality. There was a high correlation in the completeness of reporting for paediatric CPGs using the AGREE II instrument and RIGHT standard. It could be concluded that the CPGs of good methodological quality have good reporting quality. Maybe the researcher should effectively combine the AGREE II instrument and RIGHT standard in the development process of CPGs. [ABSTRACT FROM AUTHOR]

Metal halide perovskite (MHP) nanocrystals (NCs) have attained ever‐increasing attention in the field of artificial photosynthesis, due to their desirable strong light‐harvesting capacity and long lifetime of photogenerated carriers. However, the well‐known inherent instability and inferior activity of MHP NCs limit their application foreground in photocatalysis. Herein, a series of 2D MHP nanosheets have been synthesized based on a facile approach at room temperature. These 2D materials are used as photocatalysts for the photocatalysis of CO2 reduction without any organic sacrificial agents, which display significantly improved stability compared to traditional MHP NCs in water‐contained reaction system. More importantly, benefitting from the large proportion of low‐coordinated metal atoms and short carrier diffusion distance, these MHP nanosheets exhibit a remarkably increased performance for photocatalytic CO2 reduction. The judicious modulation of halide component endows the MHP nanosheets with a highest electron consumption rate of 87.8 μmol g−1 h−1 among the reported pure MHP catalysts for photocatalytic CO2 conversion, which is over seven times higher than that of traditional MHP NCs. [ABSTRACT FROM AUTHOR]

The well‐known toxicity of lead‐halide‐perovskite (LHP) nanocrystals limits their commercial applications in photocatalysis. Herein, an in situ controlled growth strategy is reported for lead‐free perovskite nanocrystals (Cs3Bi2I9) on the surface of ultrathin Bi2WO6 nanosheets through co‐sharing Bi atoms, to generate a direct Z‐scheme heterojunction of Cs3Bi2I9/Bi2WO6. Co‐sharing of the Bi atom can enable intimate contact and strong electron coupling between Cs3Bi2I9 and Bi2WO6, which can effectively promote the interfacial charge transfer between Cs3Bi2I9 and Bi2WO6 complying with a Z‐scheme pathway. The resulting efficient charge transfer and well‐preserved redox ability of Cs3Bi2I9/Bi2WO6 heterojunction endow it with a significant improvement of photocatalytic activity for the conversion of CO2‐to‐CO integrated with water oxidation, exhibiting a fourfold increase compared with pure Cs3Bi2I9 nanocrystals. This study paves a new avenue for the construction of efficient Z‐scheme heterojunction based on lead‐free halide perovskite, which should stimulate further passion on the development of high performance of lead‐free halide perovskite materials for photocatalytic application. [ABSTRACT FROM AUTHOR]

Capping ligands are indispensable for the preparation of metal‐halide‐perovskite (MHP) nanocrystals (NCs) with good stability; however, the long alkyl‐chain capping ligands in conventional MHP NCs will be unfavorable for CO2 adsorption and hinder the efficient carrier separation on the surface of MHP NCs, leading to inferior catalytic activity in artificial photosynthesis. Herein, CsPbBr3 nanocrystals with short‐chain glycine as ligand are constructed through a facile ligand‐exchange strategy. Owing to the reduced hindrance of glycine and the presence of the amine group in glycine, the photogenerated carrier separation and CO2 uptake capacity are noticeably improved without compromising the stability of the MHP NCs. The CsPbBr3 nanocrystals with glycine ligands exhibit a significantly increased yield of 27.7 μmol g−1 h−1 for photocatalytic CO2‐to‐CO conversion without any organic sacrificial reagents, which is over five times higher than that of control CsPbBr3 NCs with conventional long alkyl‐chain capping ligands. [ABSTRACT FROM AUTHOR]

Neither Cadmium (Cd) nor lead (Pb) is necessary for crop growth, and they both cause severe soil pollution in many countries. A cross‐stress experiment was designed to investigate the feasibility of diagnosing the type and the level of Cd–Pb cross‐stress by observing rice canopy hyperspectral images. Two‐way analysis of variance and random forest algorithm were employed to select the sensitive indices for Cd–Pb cross‐stress diagnosing. Following the exploration of bandwidth expansion from 1 to 20 nm, the final sensitive indices were proposed. We proposed two indices for distinguishing the two heavy metals named: the cadmium stress vegetation index (CSVI) and the lead stress vegetation index (LSVI). The diagnostic accuracies of CSVI distinguishing the four different Cd‐stressed levels (0, 2, 5, 8 mg L−1) reached 0.85, 0.92, 0.96, and 0.92, respectively, while the precision for four Pb‐stressed levels (0, 50, 100, 500 mg L−1) based on the LSVI were 0.92, 0.94, 0.96, and 0.96, respectively. The two indices are CSVI = [(R772 + R773 + R774 + ... + R789) ‐ (R754 + R755 + R756 + ... + R771)]/18, LSVI = [(R711 + R712 + R713 + ... + R718) – (R703 + R704 + R705 + ... + R710)]/8, located in near‐infrared ranges with 18 and 8 nm bandwidth, respectively. Therefore, it was feasible to diagnose the type and the level of Cd–Pb cross‐stress by examining the hyperspectral dataset of the rice canopy. Finally, the experiment compared the diagnostic ability of the proposed indices with the typical spectral indices for the physiological characterization of rice. The results showed that the proposed indices had state‐of‐the‐art distinguishing accuracies. [ABSTRACT FROM AUTHOR]

Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively. [ABSTRACT FROM AUTHOR]

Summary: Amino acid transport via phloem is one of the major source‐to‐sink nitrogen translocation pathways in most plant species. Amino acid permeases (AAPs) play essential roles in amino acid transport between plant cells and subsequent phloem or seed loading. In this study, a soybean AAP gene, annotated as GmAAP6a, was cloned and demonstrated to be significantly induced by nitrogen starvation. Histochemical staining of GmAAP6a:GmAAP6a‐GUS transgenic soybean revealed that GmAAP6a is predominantly expressed in phloem and xylem parenchyma cells. Growth and transport studies using toxic amino acid analogs or single amino acids as a sole nitrogen source suggest that GmAAP6a can selectively absorb and transport neutral and acidic amino acids. Overexpression of GmAAP6a in Arabidopsis and soybean resulted in elevated tolerance to nitrogen limitation. Furthermore, the source‐to‐sink transfer of amino acids in the transgenic soybean was markedly improved under low nitrogen conditions. At the vegetative stage, GmAAP6a‐overexpressing soybean showed significantly increased nitrogen export from source cotyledons and simultaneously enhanced nitrogen import into sink primary leaves. At the reproductive stage, nitrogen import into seeds was greatly enhanced under both sufficient and limited nitrogen conditions. Collectively, our results imply that overexpression of GmAAP6a enhances nitrogen stress tolerance and source‐to‐sink transport and improves seed quality in soybean. Co‐expression of GmAAP6a with genes specialized in source nitrogen recycling and seed loading may represent an interesting application potential in breeding. [ABSTRACT FROM AUTHOR]

A new strategy has been established for the synthesis of polysubstituted morpholin‐2‐ones through Stevens rearrangements of tertiary amines via in situ activation with epoxides. A range of α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines reacted with epoxides in the presence of zinc halide catalysts to afford structurally diverse allyl‐, allenyl‐, and benzyl‐substituted morpholin‐2‐ones, respectively, in moderate‐to‐good yields with high regioselectivity. The process involves [2,3]‐ and [1,2]‐Stevens rearrangements of quaternary ammonium ylide intermediates and constitutes a very convenient method to prepare polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds. Moreover, replacing epoxides with aziridines permitted the synthesis of polysubstituted piperazin‐2‐ones. New Stevens rearrangement: Zinc‐halide‐catalyzed ring‐opening of epoxides with α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines followed by [2,3]‐ and [1,2]‐Stevens rearrangements of the resulting quaternary ammonium ylide intermediates has been established as a convenient method to access polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds (see scheme). [ABSTRACT FROM AUTHOR]

The adsorption of the energetic molecule methyl nitrate ( CH3ONO2) on α- Al2O3(0001) and γ- Al2O3(110) surfaces was investigated using first-principles calculations based on density functional theory and the generalized gradient approximation. We found that CH3ONO2 approaches the two surfaces by either the oxygen connected with carbon atom or an oxygen atom of the nitro group; however, the former interaction is more stable. If CH3ONO2 approaches the surface through the oxygen atom of the nitro group, the adsorption is non-dissociative; while it is nearly dissociative if CH3ONO2 adsorbs on the surface via the oxygen connected with carbon atom and a surface tri-coordinated Al atom. Moreover, the dissociation trend on the γ- Al2O3(110) surface is more pronounced. In addition, the adsorption of CH3ONO2 on the γ- Al2O3(110) surface is more favorable. Finally, although strong interactions exist between CH3ONO2 and the surfaces, the structures of the alumina films are not affected by the adsorption of CH3ONO2. [ABSTRACT FROM AUTHOR]

Th article reports on the perioperative medications during endoscopic submucosal dissection (ESD) for gastric lesions. Topics discussed include the indications and contraindications of gastric ESD, complications of ESD, and diagnosis of perforation. Also being discussed are the aim and types of perioperative medications.

A by-product-catalyzed redox-neutral process has been established through tandem sulfenylation/deiodination/aromatization of cyclic alkenyl iodides with sulfonyl hydrazides. In the absence of external catalysts and additives a range of 4-iodo-1,2-dihydronaphthalenes reacted with sulfonyl hydrazides to give structurally diverse 2-naphthyl thioethers in good yields. Mechanistic studies showed that at an early stage sulfonyl hydrazides decomposed completely to thiosulfonates and disulfides and at a late stage the resulting thiosulfonates underwent tandem sulfenylation/deiodination/aromatization with 4-iodo-1,2-dihydronaphthalenes involving a [1,5]-sigmatropic hydrogen shift. Importantly, iodine was generated as a by-product from 4-iodo-1,2-dihydronaphthalenes upon heating and served as a catalyst for the decomposition of sulfonyl hydrazides and subsequent formation of 2-naphthyl thioethers. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether 3‐dimensional (3D) speckle‐tracking echocardiography could provide a new way to assess myocardial viability in patients with myocardial infarction (MI). Methods: Forty‐five patients with MI underwent routine echocardiography, 2‐dimensional (2D) speckle‐tracking echocardiography, and 3D speckle‐tracking echocardiography. Radionuclide myocardial perfusion/metabolic imaging was used as a reference standard to define viable and nonviable myocardia. Results: Among 720 myocardial segments in 45 patients, 368 showed abnormal motion on routine echocardiography; 204 of 368 were categorized as viable on single‐photon emission computed tomography/positron emission tomography (SPECT/PET), whereas 164 were defined as nonviable; 300 normal segments on SPECT/PET among 352 segments without abnormal motion on routine echocardiography were categorized as a control group. The radial, longitudinal, 3D, and area strain on 3D speckle‐tracking echocardiography had significant differences between control and nonviable groups (P <.001), whereas none of the parameters had significant differences between control and viable groups. There were no significant differences in circumferential, radial, and longitudinal peak systolic strain from 2D speckle‐tracking echocardiography between viable and nonviable groups. Although there was no significant difference in circumferential strain between the groups, radial and longitudinal strain from 3D speckle‐tracking echocardiography decreased significantly in the nonviable group. Moreover, 3D and area strain values were lower in the nonviable segments than the viable segments. By receiver operating characteristic analysis, radial strain from 3D speckle‐tracking echocardiography with a cutoff of 11.1% had sensitivity of 95.1% and specificity of 53.4% for viable segments; longitudinal strain with a cutoff of 14.3% had sensitivity of 65.2% and specificity of 65.7%; 3D strain with a cutoff of 17.4% had sensitivity of 70.6% and specificity of 77.2%; and area strain with a cutoff of 23.2% had sensitivity of 91.5% and specificity of 82.8%. Conclusions: Three‐dimensional speckle‐tracking echocardiography might have potential for detection of myocardial viability in patients with cardiac dysfunction due to MI. [ABSTRACT FROM AUTHOR]