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Bacterial keratitis (BK) is one of the most threatening ocular diseases, leading to stromal injury, corneal perforation, or even blindness. Avoiding side effect is necessary for efficient BK treatment. Herein, we develop GDY-Ag@AgCl heterojunction catalysts to achieve BK treatment via mild phototherapy strategy. Mild photothermal therapy (PTT) can greatly enhance the generation of ROS produced by photocatalytic therapy (PCT), which can decrease the dosage of photosensitizer, as well as solve the issue of uncontrolled local overheating and the accumulation of PTT agents, minimizing side effects and avoiding secondary injuries. The results demonstrate that lower dosage of PTT/PCT agents, and milder and controlled thermal effect of GDY-Ag@AgCl exhibits excellent inactivation performance against ampicillin-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, this phototherapy strategy not only achieves more effective treatment of BK induced by MRSA with no side effects but also shows a superior ability to alleviate inflammation. This strategy offers a safe and promising theragnostic approach for treating ocular drug-resistant bacterial infections. [Display omitted] • Mild PTT-enhanced PCT exhibits excellent anti-bacterial performance. • The Milder and controlled thermal effect of GDY-Ag@AgCl avoids secondary injuries. • Mild phototherapy strategy has a superior ability to alleviate inflammation. • A safe and promising treatment for ocular bacterial infections has been developed. [ABSTRACT FROM AUTHOR]

Objectives: Polymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.Methods: An open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.Results: One female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.Conclusions: This study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B. [ABSTRACT FROM AUTHOR]

The COVID-19 epidemic has had an unexpected impact on global carbon emissions. In this context, carbon emission prediction is very important for policy formulation and implementation. It is worth pondering how the grey model deals with the prediction of unexpected events. Considering the spatial dependence of carbon emissions, this paper improves the multivariate grey model, gives new information a higher reference weight, and constructs a metabolic multivariate grey model -MMGM(1,m | λ) which takes new information as the priority. An optimization algorithm is constructed with the minimum error as the goal to determine the value of the weight adjustment parameter λ. Then we simulate and predict the carbon emissions of three regions: China's Yangtze River Delta (Shanghai, Jiangsu, Zhejiang, and Anhui), the North American Free Trade Area (Canada, Mexico, and the US), and West Europe (the UK and France). These three cases have different regions, different numbers of behavioural variables, different degrees of influence by COVID-19, and different trends, which are comparative. The results show that the new model has a good fitting effect, and it is still applicable in dealing with unexpected events. The new model can reflect regional carbon emission changes more systematically and accurately. Finally, according to cases and discussions, we get some management enlightenment to promote regional environmental collaborative governance. [ABSTRACT FROM AUTHOR]

Abstract Aim Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune inhibitory receptor which is expressed within most types of hematopoietic cells and negatively regulates immune responses. Recently, we found LAIR-1 expression to be present within tumors of nonhematopoietic lineages. However, the roles of LAIR-1 in hepatocellular carcinoma (HCC) have yet to be examined. The purpose of this study was to investigate the expression of LAIR-1 in HCC tissue and assess its clinical significance at this site. Materials and methods Expression levels of LAIR-1 within HCC samples collected from 90 patients and compared with that of slides of normal liver tissue collected from 9 non-HCC patients were measured by immunohistochemistry using tissue microarrays. A semiquantitative score was assigned, as was based on staining intensity and percent of positive cells and a Spearman Rank correlation test was used to assess any potential significant correlations between LAIR-1 expression and clinicopathological factors. Overall survival analysis was performed using the Kaplan-Meier and Log Rank statistical test. Results LAIR-1 expression was detected in cancer tissue and adjacent tumor tissue, but not in normal liver tissue. The percent of LAIR-1-positive expression in cancer tissue of HCC samples was 97.78% (88/90) while that in adjacent tumor tissue was 96.67% (87/90). Significantly greater expression levels of LAIR-1 were obtained from cancer tissue (Mean ± SD = 5.722 ± 2.145) than that in adjacent tumor tissue (4.141 ± 1.486). In addition, LAIR-1 expression was found to be significantly correlated with pathological grade of HCC, T stage, and age. Expression levels of LAIR-1 were related with worse overall survival rates of HCC patients, especially in HCC patients with hepatic cirrhosis. Conclusion Results of this study show that LAIR-1 is expressed in HCC tissues and that high levels of LAIR-1 expression are associated with the poor cancer differentiation. In addition, overexpression of LAIR-1 was significantly associated with worse overall survival in the patients with HCC. These data suggest that LAIR-1 may be an independent predictor for clinical outcomes in patients with HCC. [ABSTRACT FROM AUTHOR]

Highlights • Low-frequency stimulation of the prefrontal cortex induces a long-term depression at synapses of the nucleus accumbens in naïve rats. • The long-term depression requires the activation of N -methyl-d-aspartate receptor and type 2/3 but not type 5 metabotropic glutamate receptor. • Withdrawal from chronic morphine abolishes the long-term depression via downregulating the expression of metabotropic glutamate type 2/3. Abstract Drugs of abuse modify synaptic long-term potentiation and long-term depression (LTD) in the nucleus accumbens, and the impairment of synaptic plasticity in this brain region may be a universal feature of drug addiction. It is unknown whether metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity induced by drugs such as morphine. The neurochemical, electrophysiological, and Western blotting experiments reported here reveal a novel form of LTD in synapses of the shell region of the nucleus accumbens induced in vivo by low-frequency stimulation of the medial prefrontal cortex. This plasticity required the activation of N -methyl- d -aspartate receptors and mGluR2/3 but not mGluR5. The expression of mGluR2/3 was downregulated during withdrawal from repeated morphine exposure (10 days after the last injection), resulting in impaired low-frequency stimulation-induced LTD. These results indicate that withdrawal-induced mGluR2/3 downregulation alters neural plasticity after morphine exposure, which may be a mechanism contributing to drug addiction. [ABSTRACT FROM AUTHOR]

Background Endothelial migration is a critical physiological process during vascular angiogenesis, growth and development, as well as in various disease conditions, such as cancer and cardiovascular diseases. Neutrophil migration, known as the important characteristic of immune responses, is also recognized as a contributor to the diseases involving endothelial migration. Herein, the mutually dependent relationship between neutrophil recruitment and endothelial migration was studied on a microfluidic platform for the first time. Methods An in vivo -like microenvironment is created inside microfluidic devices by embedding a gel scaffold into the micro-chambers. This approach, with controllable stable chemical gradients and the ability to quantitate interaction characteristics, overcomes the limitations of the current in vivo and in vitro assays for cell migration studies. Results The number of neutrophils migrating through the endothelial cell layer is heavily influenced by the concentration of vascular endothelial growth factor (VEGF) that induces endothelial cell migration in the gel scaffold, and is not as correlated to the concentration of chemokine solution used for initiating neutrophil migration. More importantly, neutrophil migration diminishes the effects of the drug that inhibits endothelial migration and this process is regulated by the concentration of chemokine molecules instead of VEGF concentration. Conclusions The results presented herein demonstrate the complicated cellular interactions between endothelial cells and neutrophils: endothelial migration delicately regulates neutrophil migration while the presence of neutrophils stabilizes the structures of endothelial migration. General significance This study provides deeper understanding of the dynamic cellular interactions between neutrophils and endothelial cells as well as the pathogenesis of relevant diseases. [ABSTRACT FROM AUTHOR]

To eliminate the effect of humidity on nanopapers from nanocellulose, esters of CNCs (ECNCs) were synthesized via acylation of cellulose nanocrystals (CNCs) with fatty acids and Trifluoroacetic anhydride (TFAA). The structure information of ECNCs was confirmed via FTIR, degree of substitution (DS) determination, and XRD, respectively. With the increase of DS, the ECNCs could be dissolved in dichloromethane, which provided a ready way for fabrication of ECNCs films via casting/evaporation method. The tensile property, transmittance, hydrophobicity, thermal property and oxygen permeability of films were tested with universal tensile tester, UV–vis spectrophotometer, Contact angle tester, Simultaneous thermal analyzer and Oxygen permeability tester, respectively. With the increase of DS, the contact angles of ECNCs increased, and the water uptake decreased. The enhancement of hydrophobicity promised the preservation of tensile parameters for films after water absorbing. The hydrophobicity, high transmittance, and high oxygen barrier property make films have potential application in packaging filed. [ABSTRACT FROM AUTHOR]

Organo-metal halide perovskite solar cells have shown unique charms in the upgrade rate of maximum power conversion efficiency, the diversity of device architecture and facilitated fabrication process. And the clear understanding of the role of each component and the basic working mechanisms in solar cells is important for further improvement in efficiency, especially for mesoscopic perovskite solar cells. Here, a two-dimensional modeling of the TiO 2 nanowire-based organic–inorganic hybrid perovskite solar cells was performed combining the optical and electrical responses to reveal the impact of the properties of TiO 2 nanowire array and absorber layer. Simulation results show a great dependence of device performance on the electron concentration of TiO 2 nanowires, which decided the electron field distribution inside cells, and an optimum thickness of 600 nm is obtained for the TiO 2 nanowires with low electron concentration. The collection of carriers is primarily within perovskite itself, and the ratio through TiO 2 nanowire is less than 5%. These findings can facilitate device optimization and enhance the performance of the perovskite solar cells. [ABSTRACT FROM AUTHOR]

In this work, granular Y 2 O 3 /Y 3 Al 5 O 12 (YAG) heterostructure thin films with 100–200 nm holes on surface were fabricated by depositing metal yttrium on c-plane sapphire and subsequent thermal anneal. Such Y 2 O 3 /YAG thin films are excellent matrix for luminescent materials based on rare earth. Based on this matrix, a Cr 3 + /(Pr 3 + /Yb 3 + ) broadband down-converter was fabricated for improving the photovoltaic conversion efficiency of crystalline silicon solar cell (c-Si SC). Cr 3 + was used to harvest the incident light and sensitize Pr 3 + /Yb 3 + quantum cutting (QC) couple. QC down-conversion to Yb 3 + infrared emission was realized in the region of 230 nm to 500 nm, which approaches the maximum bandwidth of QC down-conversion for c-Si SC. [ABSTRACT FROM AUTHOR]

Abstract: We unexpectedly discover that there are much lower GC3 and GC-content and higher Gibbs free energy on editing exons than other exons in the Drosophila synaptotagmin I transcripts, which was further, confirmed statistically by others 47 experimentally-validated samples. Sequence alignment, Ks and Ka/Ks assays suggest that rapidly ascending purifying selection occur in editing exons which constrains nucleotide divergency. The presence of specific molecular characteristics such as lower GC-content in editing exons imply an unexpected requirement and are likely to direct RNA editing occurrence. Thus, relations between molecular characteristics of DNA, RNA editing and purifying selection might be present. [Copyright &y& Elsevier]

Purpose This study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects. Methods The study was composed of 3 sequential periods. Period 1 was a randomized, double-blind, placebo-controlled, sequential ascending dose (50 to 1800 mg) study. Period 2 included one arm as a randomized, open-label, 3-period, 3 × 3 Latin square single-dose study of 300, 600, and 900 mg MRX-I administration and another arm as a crossover study to evaluate high-fat diet effect. Period 3 was a randomized, double-blind, placebo-controlled multiple-dose study with 600 or 800 mg, q12h regimens over 15 days. Findings MRX-I was rapidly absorbed and reached peak plasma concentration at about 2 hours post dose. The C max was 8.07, 12.24, and 15.25 mg/L and the corresponding AUC 0−∞ 29.21, 48.27, and 59.60 mg/h/L, in 300-, 600-, and 900-mg dosing groups, respectively. High-fat diet increased the exposure of MRX-I. No discernable drug accumulation was observed after 15 days of continuous drug administration. About 2% of MRX-I was excreted via kidneys in unchanged form. No obvious hematologic toxicity by MRX-I was observed during the entire study. Based on Monte Carlo simulation, 600 or 800 mg BID can produce satisfactory efficacy against methicillin-resistant Staphylococcus aureus . Implications MRX-I was well tolerated in healthy Chinese subjects (50–1800 mg). No serious or severe adverse effects were observed. MRX-I 600 or 800 mg BID up to 15 days can be recommended in future clinical trials. Chinese Clinical Trial Registration ( http://www.chinadrugtrials.org.cn ) identifier: CTR20131214. [ABSTRACT FROM AUTHOR]

The dynamical evolution of geostationary transfer orbits (GTOs) is a fundamental issue for the space debris mitigation in this orbit region. In this paper, the long-term dynamical evolution and orbital lifetime of low-inclination GTOs are investigated based on the Semi-analytic Tool for End of Life Analysis software (STELA) with the solar radiation pressure (SRP) and Earth's shadow taken into account. We carry out numerical investigations of long-term orbital evolution of objects with area-to-mass ratio (A/m) between 0.02 m2/kg and 1 m2/kg in the GTO region. Their dynamical orbital lifetime is recorded and presented in the Ω– ω (right ascension of ascending node–argument of perigee) plane to investigate its dependence on the initial conditions and physical parameters, particularly the initial azimuth of the Sun with respect to the apsidal line and the value of A/m. Based on these results, we further analyze the effect of SRP on the long-term dynamical evolution, as well as the solar apsidal resonances. The results are helpful to enrich the knowledge about long-term evolution and orbital lifetimes of GTO objects with relatively high A/m as well as to promote uncatalogued objects observation and identification. • The long-term evolution of low-inclination GTOs with medium area-to-mass ratio is investigated. • The coupling effect of SRP and other perturbations on the orbital lifetime is analyzed. • The dependency of orbital lifetime on the initial conditions is revealed. • The effect of SRP on the solar apsidal resonance is revealed in details. [ABSTRACT FROM AUTHOR]

Eif2s3y (eukaryotic translation initiation factor 2, subunit 3, structural gene Y-linked, Eif2s3y) is an essential gene for spermatogenesis. Early studies have shown that Eif2s3y can promote the proliferation of spermatogonial stem cells (SSCs) and can replace the Y chromosome together with sex-determining region Y (Sry) to transform SSCs into round spermatozoa. We injected lentiviral particles into the seminiferous tubules of mouse testes by sterile surgery surgically to establish overexpressing Eif2s3y testes. And then the mice were intraperitoneally injected with LPS to established the model of testis inflammation. Through RNA sequencing, qRT–PCR analysis, Western blot, co-culture etc., we found that Eif2s3y alleviated LPS-induced damage in mouse testes and maintained spermatogenesis. In testes with Eif2s3y overexpression, the seminiferous tubules were more regularly organized after exposure to LPS compared with the control. Eif2s3y performs its function by negatively regulating Adamts5 (a disintegrin and metalloproteinase containing a thrombospondin-1 motif), an extracellular matrix-degrading enzyme. ADAMTS5 shows a disruptive effect when the testis is exposed to LPS. Overexpression of Eif2s3y inhibited the TLR4/NFκB signaling pathway in the testis in response to LPS. Generally, our research shows that Eif2s3y protects the testis from LPS and maintains spermatogenesis by negatively regulating A damts5. • Overexpression of Eif2s3y alleviates testicular injury induced by LPS. • Eif2s3y is a negative regulator of Adamts5. • Eif2s3y alleviates LPS-induced germ cell damage by negatively regulating Adamts5. • Eif2s3y maintains testicular immune homeostasis through negative regulation of Adamts5. [ABSTRACT FROM AUTHOR]

To quantitatively estimate the association of age at menarche with the risk of childhood- and adult-onset asthma separately. A retrospective cohort study of 24,282 US girls and women was conducted using continuous National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2018, and Cox proportional hazards regression models with censoring ages of 19 and 79 years were employed to separately estimate hazard ratios of childhood- and adult-onset asthma associated with age at menarche. Each one-year increase in age at menarche was significantly associated with a 16% (hazard ratio [HR] = 0.84; 95% confidence interval [CI]: 0.77-0.91) decrease in the risk of childhood-onset asthma. Compared with age at menarche of 12-14 years, we observed a 56% (HR = 1.56; 95% CI: 1.19-2.04) increased risk of childhood-onset asthma for early menarche (age at menarche < 12 years) and a 40% (HR = 0.60; 95% CI: 0.32-1.10) decreased risk for late menarche (age at menarche ≥ 15 years). No significant association was noted between age at menarche and adult-onset asthma. Early menarche may represent a risk factor for childhood-onset asthma, which indicates the need for timely and effective management of individuals with early menarche to prevent asthma. [ABSTRACT FROM AUTHOR]

Graphite-like carbon nitride (g-C 3 N 4) has been regarded as a promising photocatalyst for solar-to-chemical conversion. Nevertheless, the narrow absorption of light extremely limited its photocatalytic performance under near-infrared (NIR) irradiation. Herein, the Cu 7. 2 S 4 with outstanding NIR absorption was successfully introduced to g-C 3 N 4 nanosheets through a simple in-situ growth procedure. As expected, the constructed Cu 7.2 S 4 /g-C 3 N 4 (CSCN) photocatalysts exhibit superior H 2 production activity of 82 μmol g−1 h−1 under NIR light irradiation (λ > 800 nm), which outperforms currently reported g–C 3 N 4 –based NIR-driven H 2 production systems. Especially, the optimal sample CSCN-5 displays a robust activity of 66 μmol g−1 h−1 at λ = 850 nm monochromatic light irradiation. The excellent photocatalytic performance is linked to the extended optical absorption as well as the efficient separation efficiency of photoinduced carriers, which are evidenced by the UV-visible absorption spectroscopy and photoelectrochemical test. This work provides an effective approach for constructing a Cu 7.2 S 4 /g-C 3 N 4 photocatalytic system for the transformation of NIR solar energy into hydrogen. The novel NIR-driven Cu 7. 2 S 4 /g-C 3 N 4 composite photocatalyst was constructed through a convenient in situ growth process. As expected, the outstanding photocatalytic H 2 yield was 82 μmol g−1 h−1 under the irradiation of NIR light (λ > 800 nm), which outperforms currently reported g–C 3 N 4 –based NIR-driven H 2 production systems. More significantly, the sample CSCN-5 shows an optimum activity (66 μmol g−1 h−1) under λ = 850 nm monochromatic light irradiation. This work provides a feasible approach for achieving g–C 3 N 4 –based photocatalyst NIR-induced superior solar-to-chemical conversion. [Display omitted] • Cu 7·2 S 4 modified g-C 3 N 4 is prepared by a facile hydrothermal treatment method. • The Cu 7·2 S 4 /g-C 3 N 4 composites show a superior optical adsorption from visible to NIR. • The Cu 7·2 S 4 /g–C 3 N 4 –5 composite exhibits excellent HER of 82 μmol g−1 h−1 (λ > 800 nm). • The HER of Cu 7·2 S 4 /g–C 3 N 4 –5 shows no obvious change after 4 runs within 20 h. [ABSTRACT FROM AUTHOR]

Organic–inorganic hybrid perovskite solar cells have made great breakthroughs in the past few years, and spurred researchers to develop and experiment a variety of new architectures. One-dimensional nanostructures are naturally introduced in solar cells, because of their excellent charge transport properties and open-pore structure. However, the performances of these solar cells are inferior to their mesoporous counterparts, suggesting that some unique mechanisms maybe held behind devices operation. Here, a three-dimensional optical model combined with a two-dimensional axisymmetric semiconductor model is applied to investigate the influence of the architectural design of scaffolds on the properties of perovskite solar cells based on Al 2 O 3 nanorod arrays. Simulation results show a great dependence of device performance on the density, length and porosity of Al 2 O 3 nanorods, which decided the electron field distribution and carrier recombination loss inside the cells. Strikingly, an optimal length of 450 nm for Al 2 O 3 nanorods is obtained for the perovskite solar cells with efficiency over 20% at porosity of 0.7. The results obtained have some guidance function on the fabrication of high efficiency PSCs based on nanorods. [ABSTRACT FROM AUTHOR]

Purpose Levornidazole, the levo-isomer of ornidazole, is a third-generation nitroimidazole derivative newly developed after metronidazole, tinidazole, and ornidazole. An open-label, parallel-controlled, single-dose study was conducted for the investigation of the pharmacokinetic (PK) profile of levornidazole and its metabolites in healthy elderly Chinese subjects, and for the evaluation of 2 dosing regimens in the elderly. Methods Levornidazole was intravenously administered at 500 mg to healthy elderly (aged 60–80 years) or young subjects (aged 19–45 years). The PK profiles of levornidazole and its metabolites in elderly subjects were evaluated and compared with those in the young group. WinNonlin software was used for simulating the PK profile of levornidazole in the elderly population following the dosing regimens of 500 mg BID and 750 mg once daily for 7 days. Monte Carlo simulation was used for estimating the cumulative fraction of response and probability of target attainment of both dosing regimens against Bacteroides spp. Results The C max , AUC 0–24, and AUC 0–∞ values of levornidazole in the elderly group were 11.98 μg/mL, 131.36 μg·h/mL, and 173.61 μg·h/mL, respectively. The t 1/2 , CL t , and mean residence time from time 0 to infinity were 12.21 hours, 2.91 L/h, and 16.46 hours. The metabolic ratios of metabolites (M) 1, 2, 4, and 6 were <3.0%, and that of M16 was 17.70%. The urinary excretion values of levornidazole, M1, M2, M4, M6, and M16 over 96 hours were 10.21%, 0.92%, ~0%, 2.69%, 0.54%, and 41.98%. The PK properties of levornidazole and the urinary excretion of all metabolites were not statistically different between the 2 groups. The cumulative fraction of response was >90% against B fragilis and other Bacteroides spp, and the probability of target attainment was >90% when the minimum inhibitory concentration was ≤1 μg/mL, in both groups. Implications No dosing regimen adjustment is suggested when levornidazole is used in elderly patients with normal hepatic functioning and mild renal dysfunction. The findings from the PK/PD analysis imply that both regimens may achieve satisfactory clinical and microbiological efficacy against anaerobic infections in elderly patients. Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) identifier: ChiCTR-OPC-16007938. [ABSTRACT FROM AUTHOR]

• Design of virtual impedance-based fault current limiting control (VIFCL). • Integrated solution for the global fault current limiting at both DC and AC sides of the MMC. • Proposing a global fault current limiting control that can reduce the interrupted currents of the DCCB and DC current limiting reactor (CLR). The large current limiting reactor (CLR) and DC circuit breaker (DCCB) are required in the half-bridge modular multilevel converter (HB-MMC) project to isolate the DC fault. To limit the fault current and reduce the CLR, a global virtual impedance-based fault current limiting (VIFCL) control strategy is proposed in this paper. This strategy includes two parts: the first part is a simplified adaptive fault current limiting control for limiting the DC fault current by reducing the arm modulating voltage of the MMC adaptively. The second part is a virtual impedance control for limiting the AC currents and the arm currents of the MMCs by mapping the virtual impedance to the reactive power control. The effectiveness of the proposed VIFCL control strategy is verified in the PSCAD/EMTDC using a four-terminal HVDC grid. The proposed global VIFCL control can limit the interrupted currents of the DCCBs and reduce the CLR. The proposed strategy is beneficial for the MMCs to ride through the DC faults safely without a significant influence on the power recovery of the HVDC system. [ABSTRACT FROM AUTHOR]

While video games are one of the most common online entertainment activities, Internet gaming disorder (IGD) in adolescents is a critical issue that has become a widely raised public concern. This one-year longitudinal study examined the reciprocal associations between shyness, depression, and IGD symptoms in a sample of Chinese adolescents. A fully cross-lagged panel design was used, in which shyness, depression, and IGD symptoms were assessed at two time points with an interval of one year (T1 and T2). A total of 1,047 junior high school students (504 boys; 543 girls; mean age = 12.45 years) participated in the study. Cross-lagged analysis results indicated a significant positive correlation between shyness, depression, and IGD symptoms, as well as a dynamic and bidirectional relationship between them. Specifically, T1 shyness positively predicted T2 depression symptoms (β = 0.167, p < 0.001), T1 depression symptoms positively predicted T2 shyness (β = 0.141, p < 0.01), and T1 IGD symptoms positively predicted T2 depression symptoms (β = 0.073, p < 0.05). In addition to these findings, gender differences were identified in shyness (T1 and T2), IGD symptoms (T1 and T2), and depression symptoms (T2). The results also indicated that shyness and symptoms of depression could significantly positively predict each other over time, and IGD symptoms could significantly predict depression symptoms. However, depression symptoms could not significantly predict IGD symptoms over the one-year study period, and there was no significant two-way prediction between shyness and IGD symptoms. Thus, this study reveals possible reciprocal associations between shyness, depression, and IGD symptoms in Chinese adolescents and provides insights and suggestions for reducing online gaming addiction among adolescents from the perspective of shyness and depression. [ABSTRACT FROM AUTHOR]

Abstract: The effect of small addition of different sintering aids (MoO3 and WO3) on the electrical properties of Ce0.9Nd0.1O2−δ has been investigated. The (Ce0.9Nd0.1)1−x M x O2−δ (x = 0.0; M = Mo, W, x = 0.01; Ce0.9Nd0.1O2−δ : NDC, (Ce0.9Nd0.1)0.99Mo0.01O2−δ : NDCMo; (Ce0.9Nd0.1)0.99W0.01O2−δ : NDCW) solid solutions were prepared and characterized. The X-ray diffraction patterns indicate that all the samples are single phases with a cubic fluorite structure. Moreover, from the field-emission scanning electron microscopy results, it is found (Ce0.9Nd0.1)0.99M0.01O2−δ (M = Mo, W) sintered at 1300 °C for 15 h have better sinterability than Ce0.9Nd0.1O2−δ . The total conductivity by electrochemical impedance spectroscopy are ranked as: NDCW  > NDCMo  > NDC measured at 700 °C, which is attributed to microstructures. It can be concluded that MoO3 and WO3 are both effective and WO3 seems to be more potential as sintering aids on the optimization of electrical properties for ceria-based electrolytes. [Copyright &y& Elsevier]

Abstract: In order to identify competitive ion-conducting materials in ceria-carbonates composite electrolytes, M-NLCO (M = Ce0.8Sm0.2O2-δ (SDC), Ce0.8Gd0.2O2-δ (GDC), Ce0.8Y0.2O2-δ (YDC); NLCO = 0.53Li2CO3–0.47Na2CO3) sintered at different temperatures (600° C, 625° C, 650° C, 675° C and 700° C) have been prepared and characterized. It is found that independent of systems, the 675° C-sintered composites in M-NLCO always present the highest conductivities because of the best NLCO distribution and interfacial microstructures. Moreover, among three composites (sintered at 675° C), the total () and grain boundary () conductivities measured at 600° C are ranked as: SDC-NLCO (, ) ﹥ GDC-NLCO (, ) ﹥ YDC-NLCO (, ), which is attributed to ionic-radius compatibility between the dopant and the host as well as the NLCO distribution and interfacial microstructures. It can be concluded that ionic-radius compatibility between the dopant and the host, NLCO distribution and interfacial microstructures have important effects on improving ionic conductivities for ceria-carbonates composite electrolytes. [Copyright &y& Elsevier]

Abstract: MicroRNAs (miRNAs) are an extensive class of small non-coding RNAs with important roles in the regulation of gene expression. Little study has been performed on identifying miRNAs in Bombyx mori (silkworm). Here, 41 conserved miRNAs were identified by a computational homology search approach and some of them were selected and confirmed experimentally. Some characteristics such as position-specific nucleotide distribution, evolutionary conservation and clustered organization have been described. Through general method of miRNA target identification, we also find that at least 4 miRNAs (miR-33/-190/-276/-7) target fibroin L chain transcripts, suggesting that miRNAs might play an important role in the regulation of silk protein production. In order to validate this, 3′-UTR of fibroin L chain mRNA was cloned and several expression vectors were constructed. Assays of semi-RT-PCR, histochemical and biochemical assays after agroinfiltration indicated that miRNAs can repress reporter gene (GUS) expression with sequence complement. Clearly, agroinfiltration proved a highly efficient method to identify the function of miRNAs inhibiting their targets mRNA in heterologous system. [Copyright &y& Elsevier]

• 9MW1411 is a humanised IgG1 mAb specifically neutralising S. aureus alpha-toxin. • This first-in-human trial characterised the safety, PK and immunogenicity of 9MW1411. • 9MW1411 had good safety and low immunogenicity after a single dose from 200 to 5000 mg. • Cmax, AUC0-t and AUC0-∞ of 9MW1411 demonstrated dose proportionality. • A single dose of 3000 mg 9MW1411 is appropriate for use in subsequent studies. 9MW1411 is a humanised monoclonal antibody against Staphylococcus aureus alpha-toxin. The safety, pharmacokinetics (PK) and immunogenicity of 9MW1411 should be characterised in humans before further clinical development. A single-centre, randomised, double-blind, placebo-controlled phase I clinical study was conducted in humans for the first time. A total of 42 healthy Chinese subjects were randomised to receive a single ascending dose of 9MW1411 (200, 600, 1500, 3000 or 5000 mg) or placebo. Safety, PK parameters and anti-drug antibody (ADA) were analysed. Monte Carlo simulations (MCS) were performed to predict the probability of target attainment (PTA) after single dose IV administration of 1500, 3000 and 5000 mg of 9MW1411. Thirty-four subjects received 9MW1411, completed the study and were included in data analysis. Five cases of drug-related AEs occurred in four subjects. All the adverse events (AEs) were mild or moderate. The C max , AUC 0-t and AUC 0-∞ of 9MW1411 increased with dose after IV administration of 200 to 5000 mg 9MW1411. The mean C max increased from 85.40 ± 5.43 to 2082.11 ± 343.10 µg/mL and AUC 0-∞ from 29,511.68 ± 5550.91 to 729,985.49 ± 124,932.18 h·µg/mL. The elimination half-life (T 1/2) was 19–23 days. 9MW1411 ADA was positive in three subjects. MCS indicated that a single dose of 3000 or 5000 mg 9MW1411 could achieve PTA > 90% for S. aureus. 9MW1411 has shown a good safety profile in healthy Chinese subjects after a single dose up to 5000 mg. A single dose of 3000 mg 9MW1411 is appropriate for use in subsequent studies. [ABSTRACT FROM AUTHOR]

Contezolid (MRX-I) is a novel oxazolidinone with potent in vitro activity against gram-positive pathogens. The aim of this study was to establish the dose-pharmacokinetic (PK) exposure-pharmacodynamic (PD)–response relationship and to quantitatively evaluate the variability of MRX-I after continuous oral administration of 600 mg BID and 800 mg BID for 14 days under fed conditions in patients with skin and skin structure infections. Another goal was to evaluate the 2 dosing regimens against methicillin-resistant Staphylococcus aureus infections based on PK/PD analysis. PK data from healthy volunteers and patients were pooled to develop a population PK model using a nonlinear mixed effect modeling method. Monte Carlo simulations were used to predict probability of target attainment (PTA) and cumulative fraction of response after single oral administration of 600 and 800 mg of MRX-I under fed conditions. The PK profile of oral administration of MRX-I was described by using a 2-compartment model with first-order elimination. Absorption of MRX-I may be affected by food intake. Type of volunteers could affect absorption constant rate and volume of distribution in the peripheral compartment, and weight could affect volume of distribution in the central department. No obvious effect on PK parameters was identified for other factors such as age, sex, creatinine clearance, concomitant medicine, and baseline diseases. Based on Monte Carlo simulation, MRX-I 600 or 800 mg BID up to 14 days on ordinary fed status could produce satisfactory efficacy against methicillin-resistant S aureus , with cumulative fraction of response >90% for f AUC 0–24 /MIC targeted at 2.3. At MIC ≤2.0 μg/mL for MRX-I 600 mg BID, or at MIC ≤4.0 μg/mL for MRX-I 800 mg BID, with continuous administration for 14 days at fed status, both regimens could obtain satisfactory clinical and antibacterial efficacy, with PTA >90%. Hence, the MRX-I regimen of 800 mg BID for 7–14 days can be recommended for confirmative clinical trials in patients with skin and skin structure infections. PK profiles of MRX-I were well captured by using a 2-compartment PK model, and disease status, food intake, and weight were found to significantly affect PK profiles. A dosing regimen of 800 mg BID for 7–14 days with ordinary food intake was recommended for pivotal study based on simulated f AUC 0–24 /MIC and PTA values. Results suggest that dose adjustments are not necessary for patient sex in confirmatory studies. Chinese Clinical Trial Registration identifier: CTR20140056. [ABSTRACT FROM AUTHOR]

Thermoplastic carbon fibre reinforced polyetheretherketone (CF/PEEK) and thermoset CF/epoxy composites have been widely applied in various industries. However, there is still a lack of knowledge concerning the milling performance and residual mechanical behavior of these two types of composites. To address this issue, we conducted a comprehensive investigation of the machinability during milling of both composites, with a focus on cutting force, machining temperature, chip characteristics, and milling-induced damages. To our knowledge, this is the first report documenting the correlation between surface integrity under different cutting conditions and residual tensile behaviour in both composites. The results demonstrate that CF/PEEK exhibits better machining quality than CF/epoxy due to its ductile matrix and strong interface bonding with fibres. Furthermore, down-milling was found to be preferable to up-milling for minimizing top layer surface damage, while petal-shaped chips with good integrity were found to be generated by CF/PEEK during milling. Moreover, CF/PEEK exhibited a significantly higher residual tensile strength (12.05%–63.22%) compared to CF/epoxy. • This study provides the investigation of milling performance in CF/PEEK and CF/epoxy, filling a knowledge gap. • The effects of two milling strategies on damages were systematically investigated to obtain preferable milling strategy. • The findings on residual tensile strength indicated that CF/PEEK has significantly higher resilience compared to CF/epoxy. [ABSTRACT FROM AUTHOR]

• The first population pharmacokinetic model of levornidazole in Chinese subjects was developed. • Pharmacokinetic/pharmacodynamic analysis of four sequential dosing regimens was performed. • Body weight was identified as a significant covariate of levornidazole clearance. • 750 mg q24h was proposed for patients against Bacteroides spp. (minimum inhibitory concentration ≤1 mg/L). Although sequential treatment with levornidazole has been used for anaerobic infection in clinical practice, there is no evidence-based dosing regimen. This study aimed to evaluate the pharmacokinetics (PK) of levornidazole in healthy subjects and patients, and to propose an evidence-based sequential dosing regimen by pharmacokinetic/pharmacodynamic (PK/PD) analysis. A population PK model was built using the data of 116 Chinese subjects, including 88 healthy young subjects, 12 healthy elderly subjects, and 16 patients with intra-abdominal anaerobic infection. PK/PD analysis was performed combining the minimum inhibitory concentration (MIC) values of levornidazole against 375 anaerobic strains. Four sequential dosing regimens (500 mg q12h, 1000 mg loading dose followed by 500 mg q12h, 750 mg q24h, and 1000 mg q24h) were evaluated in terms of cumulative fraction of response (CFR) and probability of target attainment (PTA) by Monte Carlo simulation. The concentration data of levornidazole and its active metabolites were described adequately by two- and one-compartment models, respectively. Body weight was identified as a significant covariate of levornidazole clearance. Simulations showed that satisfactory PTA (>90%) was achieved for the four dosing regimens when MIC ≤1 mg/L. Considering the simulation results, patients' safety and compliance, levornidazole 750 mg intravenous infusion q24h for 2 days followed by 750 mg oral dose q24h for 5 days was optimal for Bacteroides spp. with an identified MIC ≤1 mg/L. [ABSTRACT FROM AUTHOR]

Due to the excellent properties of PEEK and their widely applications in medical industry, it is necessary to conduct a comparative study into the drilling performance and residual tensile behavior of PEEK plates under varying cutting conditions. In this study, the effects of tool geometry, drilling parameters, and slope angles on the thrust force, tool temperature, hole quality are discussed. The residual tensile behavior of the drilled PEEK plates is elucidated in terms of the full-field strain evolution during tensile testing by the Digital Image Correction system. The results showed that drilling parameter and tool geometry affect significantly cutting forces, tool temperature, and resulting hole quality. The relationship between the machinability and the residual tensile property of PEEK is reported for the first time. Full-field strains during tensile testing are sensitive to the level of drilling-induced damages, which have an impact on the residual tensile property of PEEK components. • The relationship between the machinability and the residual tensile property of PEEK is reported for the first time. • The cutting performance of tool geometry on perpendicular and non-perpendicular drilling was systematically investigated. • The crescent drill can reduce cutting forces and tool temperature, improve hole quality and the residual tensile strength. [ABSTRACT FROM AUTHOR]

Bi-doped La 2- x Bi x Cu 0.5 Mn 1.5 O 6 (LBCM- x , x = 0, 0.1 and 0.2) were synthesized as potential cathode materials for intermediate-temperature solid oxide fuel cells. The effects of 6s 2 lone pair electrons on the electrical and electrochemical properties of LBCMs were investigated. The results reveal that Bi 3+ affects the properties of LBCMs in two ways. First, Bi doping can promotes the formation of oxygen vacancies, which is consistent with the results of first-principles calculations. The formation of oxygen vacancies can increase the amount of Mn 3+ /Mn 4+ pairs for the hopping of electrons and accelerate the oxygen transportation. Second, Bi doping can affect the microstructure of LBCMs and make LBCM-0.1 has the smallest grain size. The dual effects of Bi doping result in the highest electrical conductivity (143.91 Scm −1 ) as well as the lowest polarization resistance (0.101 Ωcm 2 ) of LBCM-0.1 at 850 °C and make it a superior cathode candidate for solid oxide fuel cells. [ABSTRACT FROM AUTHOR]

Objective Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration. Methods A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem. Results The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively. Conclusions Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens. [ABSTRACT FROM AUTHOR]

Recently, organo–metal halide perovskites have attracted much attention of the scientific community relating to their successful application in the absorber layer of low-cost solar cells. However, enough is known about the material and device properties, to realize that much remains to be learned. In this study, a two-dimensional modeling of planar heterojunction perovskite solar cells was performed combining the optical and electrical responses to reveal the impact of the carrier diffusion length, the relative permittivity of absorber layer and the valence band offset of absorber/hole transport material (HTM). Simulation results presented a great dependence of power conversion efficiency (PCE) on the carrier diffusion length of perovskite layer. Meanwhile, to achieve high PCE, the frequency depended dielectric constant should not exceeded 40 and the double HTMs design was very effective to match the valence bands between the absorber and HTM. [ABSTRACT FROM AUTHOR]

A series of novel composite electrolytes based on 20 mol% Gd doped CeO 2 with varying amounts of (Li/Na) 2 SO 4 have been synthesized. X-ray diffraction, thermogravimetry and differential scanning calorimetry, scanning electron microscope and transmission electron microscope were applied to characterize the phase components and microstructures of the composite electrolytes. Their ionic conductivities were determined by AC impedance spectroscopy. It has been found that the optimum sintering temperature and sulphate content for the composite electrolyte is 870 °C and 20 wt% (Li/Na) 2 SO 4 , respectively. Above 550 °C, a sharp increase in conductivity occurred, which can be interpreted as superionic phase transitions in the interface phases between GDC and sulphates. Both the high ionic conductivities above the transition temperature, 0.191, 0.298 and 0.372 S cm −1 at 550, 650 and 750 °C respectively, and low activation energy (0.303 eV) highlight composite GDC-20 wt% (Li/Na) 2 SO 4 a promising electrolyte candidate for application in intermediate temperature solid oxide fuel cells. [ABSTRACT FROM AUTHOR]