Sugammadex, a selective antagonist of steroidal non‐depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor ...recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2–17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1 mg∙kg−1 of rocuronium, sugammadex (2, 4, and 8 mg∙kg−1) or a conventional dose of neostigmine (0.03 mg∙kg−1) was administered randomly after confirmation of zero post‐tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2 min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train‐of‐four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three‐compartment PK model was established for sugammadex. The median (interquartile range IQR) time from injection of 8 mg∙kg−1 of sugammadex to recovery of T4/T1greater than or equal to 0.9 at train‐of‐four stimulation was 1.1 (IQR: 0.88–1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium‐induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4/T1 greater than or equal to 0.9 at train‐of‐four stimulation with 8 mg∙kg−1 of sugammadex was less than 3 min and comparable to that in adults.
Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the ...receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
To overcome the lithium storage barriers of current lithium‐ion batteries, it is imperative that conventional low capacity graphite anodes be replaced with other higher capacity anode materials. ...Silicon is a promising alternative anode material due to its huge energy densities; however, its lithium‐concentration‐dependent volumetric changes can induce severely adverse effects that lead to drastic degradations in capacity during cycling. The dealloying of Si–metal alloys is recently suggested as a scalable approach to fabricate high‐performance porous Si anode materials. Herein, a microstructure controlled porous Si is developed by the dealloying in conjunction with wet alkaline chemical etching. The resulting 3D networked structure enables enhancement in lithium storage properties when the Si‐based material is applied not only as a single active material but also in a graphite‐blended electrode.
A microstructure‐controlled 3D porous Si material is fabricated by dual chemical etching of a designed Si‐alloy in which Si and the metal‐alloy are entangled. Benefiting from the enlarged pore volume and reduced Si domain size, the resulting 3D porous Si anode shows improvement in lithium‐storage properties in terms of cyclability and energy density.
To evaluate a fully deep learning mask region-based convolutional neural network (R-CNN) method for automated tooth segmentation using individual annotation of panoramic radiographs.
In total, 846 ...images with tooth annotations from 30 panoramic radiographs were used for training, and 20 panoramic images as the validation and test sets. An oral radiologist manually performed individual tooth annotation on the panoramic radiographs to generate the ground truth of each tooth structure. We used the augmentation technique to reduce overfitting and obtained 1024 training samples from 846 original data points. A fully deep learning method using the mask R-CNN model was implemented through a fine-tuning process to detect and localize the tooth structures. For performance evaluation, the F1 score, mean intersection over union (IoU), and visual analysis were utilized.
The proposed method produced an F1 score of 0.875 (precision: 0.858, recall: 0.893) and a mean IoU of 0.877. A visual evaluation of the segmentation method showed a close resemblance to the ground truth.
The method achieved high performance for automation of tooth segmentation on dental panoramic images. The proposed method might be applied in the first step of diagnosis automation and in forensic identification, which involves similar segmentation tasks.
Autophagy is a stress response protecting cells from unfavorable conditions, such as nutrient starvation. The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates ...both intracellular vesicle trafficking and autophagy induction. Here, we show that AMPK plays a key role in regulating different Vps34 complexes. AMPK inhibits the nonautophagy Vps34 complex by phosphorylating T163/S165 in Vps34 and therefore suppresses overall PI(3)P production and protects cells from starvation. In parallel, AMPK activates the proautophagy Vps34 complex by phosphorylating S91/S94 in Beclin1 to induce autophagy. Atg14L, an autophagy-essential gene present only in the proautophagy Vps34 complex, inhibits Vps34 phosphorylation but increases Beclin1 phosphorylation by AMPK. As such, Atg14L dictates the differential regulation (either inhibition or activation) of different Vps34 complexes in response to glucose starvation. Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK in nutrient stress response and autophagy.
Display omitted
► Different Vps34 complexes are distinctly regulated upon energy stress ► AMPK activates the proautophagy Vps34 complex by phosphorylating Beclin1 ► AMPK inhibits the nonautophagic Vps34 complex by phosphorylating Vps34 ► ATG14L determines whether the Vps34 complex is activated or inhibited by AMPK
Atg14 acts as a molecular switch to modulate the outcome of AMPK phosphorylation of Vps34 complexes during nutrient stress signaling. Atg14 suppresses Vps34 phosphorylation, and thus vesicle trafficking, while stimulating Beclin phosphorylation and autophagy.
Summary
Background and Aims
An immersive virtual reality tour of the operating theater could reduce preoperative anxiety. This study was designed to determine whether a preoperative immersive virtual ...reality tour demonstrates a reduction in emergence delirium through reducing the preoperative anxiety in children undergoing general anesthesia.
Methods
Eighty‐six children were randomly allocated into either the control or virtual reality group. The control group received conventional education regarding the perioperative process. The virtual reality group watched a 4‐minute virtual reality video showing the operating theater and explaining the perioperative process. Incidence and severity of emergence delirium were the main outcomes. Secondary outcomes included preoperative anxiety using modified Yale Preoperative Anxiety Scale and postoperative behavioral disturbance.
Results
Eighty children completed the final analysis (control group = 39, virtual reality group = 41). The incidence (risk ratio 95% CI: 1.1 0.5‐2.8, P = 0.773) and severity of emergence delirium (mean difference 95% CI: −0.2 −2.7 to 2.2, P = 0.791) were similar in the two groups. After the intervention, children in the virtual reality group had a significantly lower modified Yale Preoperative Anxiety score than those in the control group (mean difference 95% CI: 9.2 0.3‐18.2, P = 0.022). No difference was observed regarding postoperative behavioral disturbance between the two groups at postoperative 1 day (mean difference 95% CI: −0.1 −0.3 to 0.1, P = 0.671) and 14 day (mean difference 95% CI: −0.0 −0.1 to 0.0, P = 0.329).
Conclusion
Preoperative immersive virtual reality tour of the operating theater did not reduce the incidence and severity of emergence delirium, although it was effective in alleviating preoperative anxiety in children.
Hot pepper (Capsicum annuum), one of the oldest domesticated crops in the Americas, is the most widely grown spice crop in the world. We report whole-genome sequencing and assembly of the hot pepper ...(Mexican landrace of Capsicum annuum cv. CM334) at 186.6× coverage. We also report resequencing of two cultivated peppers and de novo sequencing of the wild species Capsicum chinense. The genome size of the hot pepper was approximately fourfold larger than that of its close relative tomato, and the genome showed an accumulation of Gypsy and Caulimoviridae family elements. Integrative genomic and transcriptomic analyses suggested that change in gene expression and neofunctionalization of capsaicin synthase have shaped capsaicinoid biosynthesis. We found differential molecular patterns of ripening regulators and ethylene synthesis in hot pepper and tomato. The reference genome will serve as a platform for improving the nutritional and medicinal values of Capsicum species.
Healed defects on photocatalysts surface and their interaction with plasmonic nanoparticles (NPs) have attracted attention in H2 production process. In this study, surface oxygen vacancy (Vo) defects ...are created on ZnO (Vo‐ZnO) NPs by directly pyrolyzing zeolitic imidazolate framework. The surface defects on Vo‐ZnO provide active sites for the diffusion of single Au atoms and as nucleation sites for the formation of Au NPs by the in situ photodeposition process. The electronically healed surface defects by single Au atoms help in the formation of a heterojunction between the ZnO and plasmonic Au NPs. The formed Au/Vo‐Au:ZnO‐4 heterojunction prolongs photoelectron lifetimes and increases donor charge density. Therefore, the optimized photocatalysts of Au/Vo‐Au:ZnO‐4 has 21.28 times higher H2 production rate than the pristine Vo‐ZnO under UV–visible light in 0.35 m Na2SO4 and 0.25 m Na2SO3. However in 0.35 m Na2S and 0.25 m Na2SO3, the H2 production rate is 25.84 mmole h−1 g−1. Furthermore, Au/Vo‐Au:ZnO‐4 shows visible light activity by generating hot carries via induced surface plasmonic effects. It has 48.58 times higher H2 production rate than pristine Vo‐ZnO. Therefore, this study infers new insight for defect healing mediated preparation of Au/Vo‐Au:ZnO heterojunction for efficient photocatalytic H2 production.
Surface defects on ZnO are filled by Au atoms and simultaneously enable the in‐situ growth of plasmonic Au nanoparticles on their surface through the photo‐deposition process. Au atom‐mediated nanocomposite catalysts are beneficial for interfacial charge transfer between plasmonic Au nanoparticles and healed defect Vo‐ZnO for visible‐light‐responsive photocatalytic hydrogen production.
Programmed cell death‐ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single‐chain fragment of variable domain ...(scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof‐of‐concept data for the effect of scFv using PDL1‐expressing cells was lacking. In this study, we conducted two kinds of cell‐based immunoassays, western blotting and enzyme‐linked immunosorbent assay, using anti‐PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell‐based immunoassays to detect PDL1.
In this study, phosphoric acid was used to attach anions to the weak interlayer structure of sericite, one of the clay minerals composed of a tetrahedral structure of silicate, to increase the ...adsorption capacity of cations. Natural sericite beads (NSB) and activated sericite beads with phosphoric acid (PSB) were prepared as beads in order to increase reusability and facilitate the separation of adsorbates and adsorbents. Using this, lead (Pb(II)) removal efficiency from an aqueous solution was comparatively analyzed. The pHpzc was 6.43 in NSB but lowered to 3.96 in PSB, confirming that more acidic functional groups were attached to the PSB surface. According to FT-IR analysis, P=O, P-O-C, P=OOH and P-O-P bonds appeared on the surface of the PSB adsorbent, and the peaks of carboxyl groups and OH-groups were large and broad. The maximum adsorption capacity of Langmuir was 52.08 mg/g for NSB and 163.93 mg/g for PSB. The adsorption process was close to physical adsorption for NSB and chemical adsorption for PSB, and both adsorbents were endothermic reactions in nature in that the higher the temperature, the higher the adsorption efficiency. The adsorption mechanism of Pb(II) to PSB was achieved by ion exchange, electrostatic interaction, hydrogen bonding, and complexation. The adsorption of Pb(II) using PSB was not significantly affected by the adsorption of competing ions and showed a high adsorption efficiency of 94% in reuse up to 6 times. This confirms the favorable feasibility of removing Pb(II) from industrial wastewater using PSB.
PDF
