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Abstract Chronic stress can provoke depressive-like behaviors through activation of inflammation and apoptosis, leading to a reduction of neurons. Antidepressant therapy may contribute to inhibiting inflammation responses and have neuroprotective effects. Baicalin (BA) has an antidepressant effect in the chronic unpredictable mild stress (CUMS) animal model and exerts anti-inflammation, anti-apoptosis, as well as neuroprotective effects in many central nervous system (CNS)-related diseases. But the effects of BA on neuroprotection, apoptosis, and neuroinflammation and the potential mechanisms in depression are unclear. Here, we focused on examining the therapeutic effects of BA in CUMS-induced depression rats and investigating the molecular mechanisms. Results showed that administration of BA improved depressive-like behaviors and significantly increased the levels of doublecortin (DCX), Neuron-specific enolase (NSE), and Brain-derived neurotrophic factor (BDNF) in hippocampus. Furthermore, administration of BA increased the cell survival by reducing the level of malondialdehyde (MDA) and increasing the level of superoxide dismutase (SOD). Finally, administration of BA significantly decreased CUMS-induced apoptosis and inflammatory cytokines (caspase-1 and IL-1β) in hippocampus. These responses were mediated by Glycogen synthase kinase-3 (GSK3) β/Nuclear factor-κB (NF-κB)/Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) signal pathway. Taken together, these results indicate that BA could promote neuronal maturation and rescue neurons from apoptosis via inhibiting activation of GSK3β/NF-κB/NLRP3 signal pathway that is known to be associated with inflammation, thus exerting neuroprotective effects and preventing CUMS-induced depressive-like behaviors. Highlights • CUMS procedure was used to establish a rat depression model. • Administration of BA improved the depressive-like behaviors. • Administration of BA protected hippocampal neurons. • Administration of BA decreased apoptosis and protected cells from oxidative stress. • BA ameliorated CUMS-induced neuroinflammation via inhibiting activation of GSK3β/NF-κB/NLRP3 signaling. [ABSTRACT FROM AUTHOR]

Electric power systems maintain system security by keeping instantaneous reserves that can substitute for a credible loss of generation. Instantaneous reserves are fast responding generators that maintain electric power system frequency immediately following a sudden mismatch between generation and load, and these are an indispensable system security tool. These are typically offered by partially or unloaded generators which are already synchronised to the AC network. The reserve requirement constrains generator operation, and reduces system flexibility and efficiency. These are important issues in a renewables-based power system. A compressed air energy storage and hydraulic actuation system is proposed to provide instantaneous reserves without constraining existing generators. By rapidly accelerating and synchronising a generator to the AC grid through a pressurised hydraulic drive, the cost of running unloaded or under-loaded spinning generators can be eliminated. This paper presents a novel hydraulic actuation system which is capable of achieving simultaneous frequency and phase matching between the power system and a 100 kW generator within 1 s. The hydraulic drive system, instrumentation, and the nonlinear controller design are described. In simulations, successful synchronisation is achieved under a wide range of system uncertainties. [ABSTRACT FROM AUTHOR]

Background Cockayne syndrome (MIM #133540, Cockayne syndrome B; 216400, Cockayne syndrome A) is a rare autosomal recessive inherited disease in which the characteristic symptoms are premature aging, cachectic dwarfism, lack of subcutaneous fat, neurological alterations, light sensitivity, and failure to thrive. The mutated gene responsible for this syndrome has been identified as usually either CSA ( CKN1 , ERCC8 ) or CSB ( ERCC6 ). In this study, we describe the case of a 7-year-old Chinese boy with characteristic symptoms of Cockayne syndrome A and the conduction of mutation screening of the CSA gene. Methods The patient was diagnosed with Cockayne syndrome in the pediatrics clinic for growth failure and developmental delay. We collected peripheral blood samples of the patient and his parents and then extracted the genomic DNA. DNA samples from control subjects and the patient were subjected to polymerase chain reaction amplification. All exons and the flanking intron-exon boundaries of CSA were amplified; then, the polymerase chain reaction products were directly sequenced for mutation screening. Results Two novel heterozygous CSA mutations, c.551-2A>C and c.394_398delTTACA, were identified in the patient. The c.551-2A>C mutation originates from his father and changed the splice acceptor site AG to CG, thus possibly causing alternative splicing. The c.394_398delTTACA from his mother caused a frameshift after the amino acid at position 132, thus introducing a premature stop codon in the gene sequence. Conclusions These mutations extend the mutation spectrum of Cockayne syndrome in the context of Chinese race and provide possibilities of prenatal diagnosis for future offsprings in this family. [ABSTRACT FROM AUTHOR]

In the practical application of Bacillus licheniformis γ-glutamyltranspeptidase ( Bl GGT), we describe a straightforward enzymatic synthesis of γ-L-glutamyl- S -allyl-L-cysteine (GSAC), a naturally occurring organosulfur compound found in garlic, based on a transpeptidation reaction involving glutamine as the γ-glutamyl donor and S -allyl-L-cysteine as the acceptor. With the help of thin layer chromatography technique and computer-assisted image analysis, we performed the quantitative determination of GSAC. The optimum conditions for a biocatalyzed synthesis of GSAC were 200 mM glutamine, 200 mM S -allyl-L-cysteine, 50 mM Tris–HCl buffer (pH 9.0), and Bl GGT at a final concentration of 1.0 U/mL. After a 15-h incubation of the reaction mixture at 60 °C, the GSAC yield for the free and immobilized enzymes was 19.3% and 18.3%, respectively. The enzymatic synthesis of GSAC was repeated under optimal conditions at 1-mmol preparative level. The reaction products together with the commercially available GSAC were further subjected to an ESI-MS/MS analysis. A significant signal with m / z of 291.1 and the protonated fragments at m / z of 73.0, 130.1, 145.0, and 162.1 were observed in the positive ESI-MS/MS spectrum, which is consistent with those of the standard compound. These results confirm the successful synthesis of GSAC from glutamine and S -allyl-L-cysteine by Bl GGT. [ABSTRACT FROM AUTHOR]

Bi-manual therapy (BT), mirror therapy (MT), and robot-assisted rehabilitation have been conducted in hand training in a wide range of stages in stroke patients; however, the mechanisms of action during training remain unclear. In the present study, participants performed hand tasks under different intervention conditions to study bilateral sensorimotor cortical communication, and EEG was recorded. A multifactorial design of the experiment was used with the factors of manipulating objects (O), robot-assisted bimanual training (RT), and MT. The sum of spectral coherence was applied to analyze the C3 and C4 signals to measure the level of bilateral corticocortical communication. We included stroke patients with onset <6 months (n = 6), between 6 months and 1 year (n = 14), and onset >1 year (n = 20), and their Brunnstrom recovery stage ranged from 2 to 4. The results showed that stroke duration might influence the effects of hand rehabilitation in bilateral cortical corticocortical communication with significant main effects under different conditions in the alpha and beta bands. Therefore, stroke duration may influence the effects of hand rehabilitation on interhemispheric coherence. [ABSTRACT FROM AUTHOR]

As handheld electronic products move toward smaller and thinner form factor, the demand of high reliability under stringent field usage also increasing. Drop test, based on the JEDEC JESD22-B111A, accompanied with temperature cycling (TC) test, based on JEDEC JESD22-A104F, are two of the most critical board-level reliability tests for handheld makers. In terms of solder joint reliability (SJR), total 7 candidates of LF35-liked lead-free solder alloys are investigated for its drop performance, and TC reliability evaluation. Among 7 solders, leg 4 and 5 exhibit both decent drop and TC behavior, which are likely owing to the silver (Ag) precipitation hardening and bismuth (Bi) solid solution hardening effect respectively. In addition, the shearing mechanical characterization of 7 solder alloys are being studied. Shear strength of leg 4 and 5 shows higher strength value than others. In terms of failure analysis under drop test, three main fracture modes are observed, including via cracking at PCB side, solder/intermetallic compound (IMC) cracking at package side, and Cu trace broken at package side. Furthermore, in terms of failure modes of TC test, solder/IMC cracking at package side are the main fracture modes. In summary, this study provides an overall reliability performance mapping for 7 solders, and list out a table comprising of shear strength, void% analysis, TC reliability, and drop reliability performance for each LF35 solders which lays out potential future solder alloy to meet higher handheld phone drop reliability margin. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel metallo-polymers containing light-emitting poly(fluorene/ethynylene/(terpyridyl)zinc(II)) backbones and electron-transporting 1,3,4-oxadiazole (OXD) pendants (attached to the C-9 position of fluorene by long alkyl spacers) were synthesized by self-assembled reactions. The integrated ratios of 1H NMR spectra reveal a facile result to distinguish the well-defined main-chain metallo-polymeric structures which were constructed by different monomer ligand systems (i.e. single, double, and triple monomer ligands with various pendants). Furthermore, UV–vis and photoluminescence (PL) spectral titration experiments were carried out to verify the metallo-polymeric structures by varying the molar ratios of zinc(II) ions to monomers. As a result, the enhancement of thermal stability (T d) and quantum yields were introduced by the metallo-polymerization, and their physical properties were mainly affected by the nature of the pendants. The photophysical properties of these metallo-polymers exhibited blue PL emissions (around 418nm) with quantum yields of 34–53% (in DMF). In contrast to metallo-polymers containing alkyl pendants, the quantum yields were greatly enhanced by introducing 1,3,4-OXD pendants but reduced by carbazole (CAZ) pendants. Moreover, electroluminescent (EL) devices with these light-emitting metallo-polymers as emitters showed green EL emissions (around 550nm) with turn-on voltages of 6.0–6.5V, maximum efficiencies of 1.05–1.35cdA−1 (at 100mA/cm−2), and maximum luminances of 2313–3550cd/m2 (around 15V), respectively. [Copyright &y& Elsevier]

Qianlabeo striatus gen. et sp. nov. is described from a stream tributary to the Beipan Jiang of the upper Zhu Jiang (Pearl River) drainage in Matou, Anshun County, Guizhou Province, China. This monotypic genus is mainly characterized by its oromadibular morphology, namely an upper lip only present in and fully adnate to the side of the upper jaw, not covered by the pendulous rostral fold; the median portion of the upper jaw lacking an upper lip but bearing a thin, flexible and cornified cutting edge that is fully covered by the pendulous rostral fold; a postlabial groove prolonged, extended anteromedially close to the anteromost point of the midline of the lower lip but not to meet with its counterpart. The type species of this genus, Q. striatus has a longitudinal dark stripe along the side of the body. [ABSTRACT FROM AUTHOR]

Developing ruthenium‐based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect‐rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm−2) and long‐term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron‐rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O‐terminal and B‐terminal edge establishes electronic back‐donation, effectively suppressing the over‐oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface. [ABSTRACT FROM AUTHOR]

Developing ruthenium‐based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect‐rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm−2) and long‐term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron‐rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O‐terminal and B‐terminal edge establishes electronic back‐donation, effectively suppressing the over‐oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface. [ABSTRACT FROM AUTHOR]

Water electrolysis, a pivotal process for the production of green hydrogen, is a crucial step toward realizing the hydrogen economy. To advance its industrialization, it is essential to develop a highly efficient and economical catalyst along with a low-resistance electrolyzers. In pursuit of this goal, we synthesize a cost-effective iron-doped nickel phosphide electrocatalyst through a hydrothermal synthesis followed by post-phosphorization process. This catalyst exhibits exceptional performance, with an overpotential at 10 mA cm-2 (η 10) of 216 mV for oxygen evolution reaction, the rate-determining step for water electrolysis. It overperforms the that of pristine nickel phosphide (NiPx, η 10 = 284 mV). Operando X-ray absorption spectroscopy reveals the robust nature of the iron-doped nickel phosphide catalyst during water electrolysis, in stark contrast to the pristine nickel phosphide, which undergoes oxidation, thereby impacting overall catalytic activity. When integrated into a membrane-electrode assembly (MEA) system, our iron-doped nickel phosphide displays voltages of 1.51 V at 10 mA cm-2 (EE = 81.5%) and 1.66 V at 100 mA cm-2 (EE = 76.4%) without iR-correction. Moreover, it achieves a current density of 345 mA cm-2 at an applied voltage of 2 V without iR-correction, meeting industrial criteria. These findings underscore the superior catalytic activity of the robust phosphide phase for water electrolysis. [ABSTRACT FROM AUTHOR]

Though previous studies have documented various clinical outcomes after cervical arthroplasty for degenerative cervical disc disease, none of them reported the impact of cervical arthroplasty on severe cervical disc degeneration (CDD). This retrospective cohort study included severe 40 CDD (C3-C7) patients who underwent single-level cervical arthroplasty using ProDisc-C between January 2017 and December 2019. After surgical intervention, the range of motion (ROM) was determined, whereas clinical outcomes were measured in terms of the Visual Analogue Scale (VAS) and Neck Disability Index (NDI) to evaluate neck pain and disability, respectively. Compared to the mean preoperative ROM (6.57 ± 4.85°), the cervical dynamic ROM was increased 3 months after cervical arthroplasty, and the increment was maintained for at least 1 year. The increased ROM is attributed to the extension and not flexion components. The mean preoperative ROM of 6.57 ± 4.85° significantly increased to 11.67 ± 4.98° (P = 0.0005), 10.05 ± 5.18° (P = 0.0426) and 10.46 ± 4.73° (P = 0.0247) after 3 months, 6 months and 1 year, respectively. The extension ROM also revealed a similar trend. VAS for neck and arm decreased from 7.4 and 6.6 to 1.4 and 1.2, respectively. Consistently, the preoperative mean Neck Disability Index (NDI) score of 27.6 decreased to 14.6. We recorded a case of device subsidence, but without extrusion. Cervical arthroplasty can improve clinical outcomes and restore ROM in severe CDD patients. [ABSTRACT FROM AUTHOR]

Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA‐seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis. [ABSTRACT FROM AUTHOR]

γ-Glutamyl transpeptidases (γ-GTs) are members of N-terminal nucleophile hydrolase superfamily. They are synthetized as single-chain precursors, which are then cleaved to form mature enzymes. Basic aspects of autocatalytic processing of these pro-enzymes are still unknown. Here we describe the X-ray structure of the precursor mimic of Bacillus licheniformis γ-GT ( Bl GT), obtained by mutating catalytically important threonine to alanine (T399A- Bl GT), and report results of autoprocessing of mutants of His401, Thr415, Thr417, Glu419 and Arg571. Data suggest that Thr417 is in a competent position to activate the catalytic threonine (Thr399) for nucleophilic attack of the scissile peptide bond and that Thr415 plays a major role in assisting the process. On the basis of these new structural results, a possible mechanism of autoprocessing is proposed. This mechanism, which guesses the existence of a six-membered transition state involving one carbonyl and two hydroxyl groups, is in agreement with all the available experimental data collected on γ-GTs from different species and with our new Ala-scanning mutagenesis data. [ABSTRACT FROM AUTHOR]

γ-Glutamyl transpeptidases (γ-GTs, EC 2.3.2.2) are a class of ubiquitous enzymes which initiate the cleavage of extracellular glutathione (γ-Glu-Cys-Gly, GSH) into its constituent glutamate, cysteine, and glycine and catalyze the transfer of its γ-glutamyl group to water (hydrolysis), amino acids or small peptides (transpeptidation). These proteins utilize a conserved Thr residue to process their chains into a large and a small subunit that then form the catalytically competent enzyme. Multiple sequence alignments have shown that some bacterial γ-GTs, including that from Bacillus licheniformis ( Bl GT), possess an extra sequence at the C-terminal tail of the large subunit, whose role is unknown. Here, autoprocessing, structure, catalytic activity and stability against both temperature and the chemical denaturant guanidinium hydrochloride of six Bl GT extra-sequence deletion mutants have been characterized by SDS-PAGE, circular dichroism, intrinsic fluorescence and homology modeling. Data suggest that the extra sequence has a crucial role in enzyme activation and structural stability. Our results assist in the development of a structure-based interpretation of the autoprocessing reaction of γ-GTs and are helpful to unveil the molecular bases of their structural stability. [ABSTRACT FROM AUTHOR]

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (−25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels. • Zein/gamma-polyglutamic acid/low-molecular-weight chitosan/fucoidan NPEncapsulated Quercetin (Qu-ZrLCF NP) • Qu-ZrLCF NP coated with fucoidan exhibited sustained antioxidant activity with uncoated NP. • Qu-ZrLCF NP demonstrated effective delivery to HUVEC and EA.hy926 endothelial cells and endothelial cells of zebrafish larvae. • Utilizing rat models successfully show in vivo targeting of Qu-ZrLCF NP into inflamed endothelial cells. [ABSTRACT FROM AUTHOR]

Recent studies have shown the evocation of lateral spread response (LSR) due to the compression of the facial nerve in hemifacial spasm (HFS). Intraoperative monitoring (IOM) of LSR could help locate neurovascular conflicts and confirm adequate micro-vascular decompression (MVD) while treatment of hemifacial spasm (HFS). However, studies on early LSR loss before decompression in HFS surgery are sparse, indicating the need to understand various perceptions on it. Therefore, we retrospectively analyzed 50 adult HFS patients who underwent MVD during the period of September 2018–June 2021. We employed IOM combining traditional LSR (tLSR) and dual LSR (dLSR). One patient was excluded owing to the lack of LSR induction throughout the surgery, while 49 were divided into groups A (n = 14) and B (n = 35), designated as with or without early LSR loss groups, respectively, and offending vessels were analyzed. The mean age of group A patients was significantly younger (47.8 ± 8.6) than that of group B (53.9 ± 10.6) (p = 0.0393). The significant predominating offending vessel in group A was the anterior inferior cerebellar artery (AICA, 78.57%). However, group B included those with AICA (28.57%), posterior inferior cerebellar artery (PICA, 22.86%), vertebral artery (VA) involved (25.71%), and combined AICA and PICA (22.86%). Group B exhibited poorer clinical outcomes with more complications. Conclusively, early LSR loss might occur in the younger population, possibly due to the AICA offending vessel. The compression severity of offending vessels may determine the occurrence of early LSR loss. [ABSTRACT FROM AUTHOR]

Abstract: The oligomeric states of Bacillus licheniformis and Escherichia coli γ-glutamyltranspeptidases (BlGGT and EcGGT) in solution have been investigated by analytical ultracentrifugation. The results showed that BlGGT has a sedimentation coefficient of 5.12S, which can be transformed into an experimental molecular mass of approximately 62,680Da. The monomeric conformation is conserved in EcGGT. SDS-PAGE analysis and cross-linking studies further proved that the autocatalytically processed BlGGT and EcGGT form a heterodimeric association. Unfolding analyses using circular dichroism and tryptophan emission fluorescence revealed that these two proteins had a different sensitivity towards temperature- and guanidine hydrochloride (GdnHCl)-induced denaturation. BlGGT and EcGGT had a T m value of 59.5 and 49.2°C, respectively, and thermal unfolding of both proteins was found to be highly irreversible. Chemical unfolding of BlGGT was independent to the pH value ranging from 5 to 10, whereas the pH environment was found to significantly influence the GdnHCl-induced denaturation of EcGGT. Both enzymes did not reactivate from the completely unfolded states, accessible at 6M GdnHCl. BlGGT was active in the presence of 4M NaCl, whereas the activity of EcGGT was significantly decreased at the high-salt condition. Taken together, these findings suggest that the biophysical properties of the homologous GGTs from two mesophilic sources are quite different. [Copyright &y& Elsevier]

Abstract: In this paper the transverse vibration characteristics of piezoceramic rectangular plates, with completely free and completely clamped boundary conditions, are investigated by theoretical analysis, experimental measurement, and numerical calculation. Using Ritz''s method together with the equivalent material constants carries out the theoretical evaluations for resonant frequencies. Two optical techniques, amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI) and laser Doppler vibrometer (LDV), based on the displacement measurement are employed to determine the transverse vibration modes. In addition, the impedance analyzer is also used to measure the electrical impedance variation. From the experimental results, it is found that the transverse vibration modes cannot be obtained by impedance analysis for the completely free piezoceramic plate; however, certain modes can be unexpectedly measured for the completely clamped piezoceramic plate owing to the imperfect boundary simulation in experiments. Numerical calculations using the finite element method (FEM) are performed and good agreement is obtained when comparing the theoretical analysis and experimental measurements. According to the theoretical analysis, frequency parameter versus equivalent Poisson''s ratios ranging from 0.25 to 0.6 with different aspect ratios and material types are also presented for the first three transverse modes. [Copyright &y& Elsevier]

What is known and objectives: Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life‐threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC0‐24h/MIC ≥400. Methods: Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non‐linear mixed‐effects modelling programme. Goodness‐of‐fit (GOF) plots, non‐parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. Results: Fifty‐three patients with 106 samples were included. A one‐compartment model with first‐order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70）0.75 × e0.0467; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC0‐24h/MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC0‐24h/MIC ≥400 increased. What is new and conclusion: A one‐compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased. [ABSTRACT FROM AUTHOR]

Several γ-glutamyl compounds are known to have favorable features for a variety of biotechnological and pharmaceutical applications. However, so far only a limited number of γ-glutamyl compounds have been synthesized through γ-glutamyltranspeptidase (GGT). With the help of thin layer chromatography and computer-assisted image analysis techniques, we performed an enzymatic method involving Bacillus licheniformis GGT (BlGGT) for the synthesis of γ-glutamyl-L-leucine (γ-Glu- Leu). The optimum conditions for a biocatalytic synthesis of γ- Glu-Leu were determined to be 200 mM glutamine, 200 mM leucine, 50 mM Tris-HCl buffer (pH 9.0), and BlGGT at a working concentration of 2.0 U/mL. Upon a 5-h incubation of the reaction mixture at 50°C, the product yield could reach approximately 52%. The preparative synthesis of γ-Glu-Leu by BlGGT was done under optimal conditions at millimol scale level. The reaction products were subjected to mass spectrometry/nuclear magnetic resonance analyses to ensure the successful synthesis of γ-Glu-Leu. Taken together, the present study demonstrates the high potentiality of BlGGT-catalyzed reaction in the synthesis of γ-glutamyl compounds. [ABSTRACT FROM AUTHOR]

Objective Target-controlled infusion (TCI) of propofol is an effective way of delivering propofol during endoscopy. However, the ideal effect-site concentration ( Ce) of propofol has not yet been defined in an Asian population. This study aimed to determine the ideal Ce of propofol in painless gastrointestinal endoscopy in a Taiwanese population. Methods A total of 121 consecutive patients undergoing diagnostic endoscopy were recruited for this study. The endoscopic procedure was carried out within 1 h. TCI of propofol was utilized during the procedure. All patients received the same regimen to induce conscious sedation, including a bolus of midazolam (0.04 mg/kg) and fentanyl (0.5 μg/kg). The Ce of propofol was calculated using the Schneider model. Patients were randomly assigned to either the low Ce group (1.5-2.5 μg/mL) or high Ce group (3.0-4.0 μg/m L). Their cardiovascular and respiratory events were monitored during the procedure and the patients' post-procedure satisfaction was evaluated. Results The mean requirement for propofol was 232.02 mg in the low Ce group and 329.56 mg in the high Ce group, respectively ( P < 0.0001). No unexpected event was observed in either group. However, more episodes of hypotension were observed in the high Ce group ( P = 0.026). The post-procedure satisfaction rate between the two groups was comparable. Conclusion A low Ce of propofol TCI (1.5-2.5 μg/m L) achieved adequate anesthesia, reduced the risk of hypotension, and attained a high satisfaction rate in a Taiwanese population undergoing diagnostic painless endoscopy. [ABSTRACT FROM AUTHOR]

Heavy metals, including arsenic and lead, may lead to cellular oxidative damage that is linked to hypertension. Manganese superoxide dismutase (MnSOD) is a scavenger of reactive oxygen species, and 8-oxoguanine DNA glycosylase (OGG1) is the major glycosylase that repairs DNA lesions. Interestingly, whether there is an elevated risk of hypertension with arsenic or lead exposure in individuals with genetic variations in MnSOD or OGG1 has not yet been investigated. Questionnaires were administered to 240 Taiwanese rural residents. Blood pressure and biochemical indicators were assessed in each subject. Urinary levels of arsenic and lead were measured with atomic absorption spectrometry; and MnSOD and OGG1 genotypes were identified via polymerase chain reaction. There was a dose-response relationship between urinary arsenic levels and risk of hypertension ( P = 0.021, test for trend). However, there was no association between urinary lead levels and hypertension risk. Individuals with high urinary arsenic levels and the MnSOD Val- Ala/Ala- Ala genotypes had a greater risk of hypertension than those with low urinary arsenic levels and the MnSOD Val- Val genotype (odds ratio [OR] = 4.2, 95% confidence interval [CI] = 1.7-10.3). Subjects with a high urinary arsenic level and the OGG1 Cys- Cys genotype also had a greater risk of hypertension than those with a low urinary arsenic level and the OGG1 Ser- Ser/Ser- Cys genotypes (OR = 3.4, 95% CI = 1.1-10.7). Thus, both MnSOD and OGG1 genotypes may be prone to an increased risk of hypertension associated with arsenic exposure. [ABSTRACT FROM AUTHOR]

A highly conserved 458PLSSMXP464 sequence in the small subunit (S-subunit) of an industrially important Bacillus licheniformis γ-glutamyltranspeptidase (BlGGT) was identified by sequence alignment. Molecular structures of the precursor mimic and the mature form of BlGGT clearly reveal that this peptide sequence is in close spatial proximity to the self-processing and catalytic sites of the enzyme. To probe the role of this conserved sequence, ten mutant enzymes of BlGGT were created through a series of deletion and alanine-scanning mutagenesis. SDS-PAGE and densitometric analyses showed that the intrinsic ability of BlGGT to undergo autocatalytic processing was detrimentally affected by the deletion-associated mutations. However, loss of self-activating capacity was not obviously observed in most of the Ala-replacement mutants. The Ala-replacement mutants had a specific activity comparable to or greater than that of the wild-type enzyme; conversely, all deletion mutants completely lost their enzymatic activity. As compared with BlGGT, S460A and S461S showed greatly enhanced kcat/Km values by 2.73- and 2.67-fold, respectively. The intrinsic tryptophan fluorescence and circular dichroism spectral profiles of Ala-replacement and deletion mutants were typically similar to those of BlGGT. However, heat and guanidine hydrochloride-induced unfolding transitions of the deletion-associated mutant proteins were severely reduced as compared with the wild-type enzyme. The predictive mutant models suggest that the microenvironments required for both self-activation and catalytic reaction of BlGGT can be altered upon mutations. [ABSTRACT FROM AUTHOR]