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p53, the major tumor suppressor, is frequently mutated in many cancers, and up to 84% of human melanomas harbor wild-type p53, which is considered to be an ideal target for melanoma therapy. Here, we evaluated the antitumor activity of a carbazole derivative, 9-ethyl-9H-carbazole-3-carbaldehyde (ECCA), on melanoma cells. ECCA had a selectively strong inhibitory activity against the growth of BRAF-mutated and BRAF-wild-type melanoma cells but had little effect on normal human primary melanocytes. ECCA inhibited melanoma cell growth by increasing cell apoptosis, which was associated with the upregulation of caspase activities and was significantly abrogated by the addition of a caspase inhibitor. In vivo assays confirmed that ECCA suppressed melanoma growth by enhancing cell apoptosis and reducing cell proliferation, and importantly ECCA did not have any evident toxic effects on normal tissues. RNA-Seq analysis identified several pathways related to cell apoptosis that were affected by ECCA, notably, activation of the p53 signaling pathway. Biochemical assays demonstrated that ECCA enhanced the phosphorylation of p53 at Ser15 in melanoma cells harboring wild-type p53, and importantly, the knockdown or deletion of p53 in those cells counteracted the ECCA-induced apoptosis, as well as senescence. Further investigations revealed that ECCA enhanced the phosphorylation of p38-MAPK and c-Jun N-terminal kinase (JNK), and treatment with either a p38-MAPK or a JNK inhibitor rescued the cell growth inhibition elicited by ECCA, which depended on the expression of the p53 gene. Finally, the combination of ECCA with a BRAF inhibitor significantly enhanced the growth inhibition of melanoma cells. In summary, our study demonstrates that the carbazole derivative, ECCA, induces melanoma cell apoptosis and senescence through the activation of p53 to significantly and selectively suppress the growth of melanoma cells without affecting normal human melanocytes, suggesting its potential to develop a new drug for melanoma therapy.

Exploring the morphology-property relationship is an important role in addressing the mechanism of hydrogen production. In this work, WO3 photocatalysts with different morphology were prepared via a solvothermal method. Our first prepared porous WO3 with the exposed (100) crystal plane, the WO3 porous nano disk demonstrates a better photocatalytic activity, which is higher than the WO3 nanorod, WO3 nanoflower and WO3 nano block. Further characterizations indicate the WO3 porous nano disk exhibits high absorption capacity and active lattice structure. Meanwhile, with the introduction of non-noble metal Ni as the co-catalyst, the photocatalytic H2 evolution was enhanced. This work reveals the importance of regulating surface atomic configuration and catalytic active sites, opens a new avenue for the development of solar-driven water splitting.

Aim: The aim of this study was to establish a population pharmacokinetic (PPK) model for rivaroxaban in Chinese elderly patients with NVAF to evaluate precision dosing regimens and analyze hemorrhagic risk after rivaroxaban treatment. Method: A population pharmacokinetic model was developed using the nonlinear mixed-effects model (NONMEM). The plasma concentration of rivaroxaban was detected by UPLC-MS/MS method and the gene polymorphisms were detected by Sanger dideoxy DNA sequencing method. A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates for the target range of therapeutic drug monitoring concentrations (Cmax,ss, Cmin,ss). Exposure of rivaroxaban was simulated and assessed in hemorrhagic risk evaluation. Results: Model-building dataset including 360 plasma concentrations from 180 Chinese elderly patients (median age 81year). A one-compartment population PK model with estimated glomerular filtration rate (eGFR), total bilirubin (TBIL) and ABCB1 rs1045642 as major covariates for apparent clearance were developed. The average probability of target attainment (PTA) of optimal dosing regimens with different covariates levels for targeted Cmax,ss and Cmin,ss were 29.35%-31.30% and 64.91%-65.80%, respectively. 10 mg of rivaroxaban in Chinese elderly patients with normal renal and liver function was appropriate. AUC24,ss was statistically significant associated with the increased risk of the bleeding events (OR 1.0006; 95%CL 1.0003-1.001; p

Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by circulating autoantibodies against one of eight aminoacyl-tRNA synthetases (aaRSs). Although these autoantibodies are believed to play critical roles in ASSD pathogenesis, the nature of their roles remains unclear. Here we describe ASSD pathogenesis and discuss ASSD-linked aaRSs - from the WHEP domain that may impart immunogenicity to the role of tRNA in eliciting the innate immune response and the secretion of aaRSs from cells. Through these explorations, we propose that ASSD pathogenesis involves the tissue-specific secretion of aaRSs and that extracellular tRNAs or tRNA fragments and their ability to engage Toll-like receptor signaling may be important disease factors.

Recent studies show that user’s visual attention during virtual reality museum navigation can be effectively estimated with deep learning models. However, these models rely on large-scale datasets that usually are of high structure complexity and context specific, which is challenging for nonspecialist researchers and designers. Therefore, we present the deep learning model, ALRF, to generalise on real-time user visual attention prediction in virtual reality context. The model combines two parallel deep learning streams to process the compact dataset of temporal–spatial salient features of user’s eye movements and virtual object coordinates. The prediction accuracy outperformed the state-of-the-art deep learning models by reaching record high 91.03%. Importantly, with quick parametric tuning, the model showed flexible applicability across different environments of the virtual reality museum and outdoor scenes. Implications for how the proposed model may be implemented as a generalising tool for adaptive virtual reality application design and evaluation are discussed.

Patients with Alzheimer's disease (AD) related dementia and mild cognitive impairment experience difficulties with spatial navigation (SN). However, SN has rarely been investigated in individuals with subjective cognitive decline (SCD), a preclinical stage with elevated progression rate to symptomatic AD. In this study, 30 SCD subjects and 30 controls underwent cognitive scale (CS) evaluation, a 2D computerized SN test, and resting-state functional magnetic resonance imaging scanning. Two SN brain networks (ego-network and allo-network), each with 10 selected spherical regions, were defined. We calculated the average network functional connectivity (FC) and region-to-region FC within the two networks and evaluated correlations with SN performance. Compared with the controls, the SCD group performed worse in the SN test and showed decreased FC between the right retrosplenial and right prefrontal cortices in the ego-network, and between the right retrosplenial cortex and right hippocampus in the allo-network. The logistic regression model based on SN and FC measures revealed a high area under the curve of .880 in differentiating SCD individuals from controls. These results suggest that SN network disconnection contributes to spatial deficits in SCD, and SN and FC measures could benefit the preclinical detection of subjects with incipient AD dementia.

Purpose: Early phase clinical studies are ongoing to evaluate the role of immune checkpoint inhibitors in adenoid cystic carcinoma (ACC) despite a paucity of information on the immune microenvironment. This study aims to better characterize the immune microenvironment of ACC tumours and evaluate survival outcomes based on tumour infiltrating lymphocyte (TIL) and programmed death-ligand 1 (PD-L1) expression. Methods: Patient characteristics, treatment and outcome data were collected for 24 ACC patients. The CD8+(cluster of differentiation 8) TIL and PD-L1 expression were quantified by immunohistochemistry. Marker expression and survival outcomes were evaluated by Kaplan-Meier analysis. Results: All cases were negative for PD-L1 expression; four cases had focal high, eight cases had focal moderate and 12 cases had low TIL expression. Based on TIL expression, there was no difference in disease-free or overall survival. Conclusion: Adenoid cystic carcinoma tumours were found to be associated with a poor immunogenic microenvironment, with absent PD-L1 expression and low CD8+ TILs. There was no association between TIL expression and survival. These data suggest that PD-L1 and TIL expression are unlikely to be useful as predictive biomarkers for response to immunotherapy.

Devising new versatile catalytic systems for the efficient removal of chlorinated environmental pollutants from water has enormous implications for the environment and human health. By combining the advantages of both electrochemistry and nanotechnology, here we report a conceptually new, general approach of electrochemical-driven nanoparticulate catalysis for highly efficient dehalogenation of organic chlorides. By implementing this strategy, a continuous-flow removal of 4-chlorophenol was rapidly achieved with 100% of dechlorination efficiency within 120 min, and importantly, the dechlorination product phenol could further undergo hydrogenation reaction to completely transform into the mixture of cyclohexanone and cyclohexanol, significantly better than any reported catalytic methods. The essence of activation mechanism was attributed to the electric field-driven nanoparticles for activating the electrogenerated H2 to make numerous reactive species (e.g., atomic hydrogen) and for promoting direct electron transfer on the particles surface, thereby efficiently enabling their fast reactions with the adjacent pollutants. By conducting cyclic voltammetry and atomic-hydrogen quenching investigations, we first showed the direct and indirect reduction of chlorinated environmental pollutants in the voltammogram and provided a new evidence for the presence of these two mechanisms in the dehalogenation process. This work provides the first insight into electrochemical-driven nanoparticulate catalysis for dehalogenation of chlorinated environmental pollutants, showing a promising application for the remediation of these contaminants in water.

Sustainable energy storage system requires high-performance rechargeable batteries with earth-abundant elements and cost-effective electrodes. Prussian blue (PB) and its analogs (PBAs) are a large family of materials with open frameworks. Benefiting from nanoarchitectonics, the PBAs are receiving great attention as cathodic materials for various rechargeable batteries. In this review, we present a general summary and evaluation on the recent advances of PBAs for the rechargeable batteries applications. The general synthetic methods and the chemical properties of PBAs have also been discussed. This review aims to provide a brief outlook on the current and future research strategies of PBAs in the electrochemical energy storage.

Objectives Acute kidney injury (AKI) is a common complication after lung transplantation (LTx) which is closely related to the poor prognosis of patients. We aimed to explore potential risk factors and outcomes associated with early post-operative AKI after LTx. Methods A retrospective study was conducted in 136 patients who underwent LTx at our institution from 2017 to 2019. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Univariate and multivariate analyses were conducted to identify risk factors related to AKI. The primary outcome was the incidence of AKI after LTx. Secondary outcomes were associations between AKI and short-term clinical outcomes and mortality. Results Of the 136 patients analyzed, 110 developed AKI (80.9%). AKI was associated with higher baseline eGFR (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00–1.03)) and median tacrolimus (TAC) concentration (OR 1.15 (95% CI: 1.02–1.30)). Patients with AKI suffered longer mechanical ventilation days (p = .015) and ICU stay days (p = .011). AKI stage 2–3 patients had higher risk of 1-year mortality (HR 16.98 (95% CI: 2.25–128.45)) compared with no-AKI and stage 1 patients. Conclusions Our results suggested early post-operative AKI may be associated with higher baseline eGFR and TAC concentrations. AKI stage 1 may have no influence on survival rate, whereas AKI stage 2–3 may be associated with increased mortality at 1-year.

In this work, ZIF-67 derivative Co3S4 with diamond dodecahedron structure was firstly synthesized via a series of reactions, and ZnIn2S4@Co3S4 heterostructures with adjustable band gaps were successfully obtained through a simple hydrothermal method. Consequently, ZnIn2S4@Co3S4 heterostructures have significantly enhanced visible light absorption and improved photocatalytic efficiency, among which the ZC-5 composite exhibits the highest photocatalytic hydrogen production rate up to 4261 μmol g−1 h−1 under simulated sunlight, to be approximately 4.8 times higher than that of pure ZnIn2S4. The enhanced photocatalytic activity can be attributed to faster electron transfer and more efficient electron–hole pairs separation derived from the heterostructures which form at the interface between Co3S4 and ZnIn2S4. Thus, this study provides a good strategy for photocatalytic hydrogen production without precious metals using heterostructures.

Polymorphic nucleation behavior of carbamazepine (CBZ) was investigated in terms of supersaturation in several solvents: nitromethane, acetonitrile, acetone, ethanol, 2-propanol and toluene. The solubility was measured and the effects of interaction between the solvent and CBZ on solubility and polymorphic nucleation were discussed. It was found that the polymorphic forms of CBZ largely depended on the solvent type and supersaturation ratio. The carbonyl group in acetone blocked the NH⋯O interaction between the dimer in form II by mimicking the same interaction with CBZ, then favored the nucleation of form III. The aromatic–aromatic interaction between CBZ and the solvent like toluene decreased the solute–solute interaction and favored the formation of form II. The nucleation domains of CBZ polymorphs (forms II and III) were separated as a function of supersaturation ratio range in each solvent, and the effects of solvents and supersaturation ratios on the induction time and transformation process were also explored. The interfacial energies of forms II and III in different solvents were calculated, and it was found that, at all investigated supersaturation ratios, the interfacial energy of form II in all solvents except acetone was always lower than that of form III, indicating that nucleation kinetics preferably favored the formation of form II. However, at lower supersaturation ratios, thermodynamics was critical and form III was obtained.

Oxidative stress and endoplasmic reticulum (ER) stress are the key contributing factors for cataract progression. In our previous studies, we demonstrated that the nuclear factor erythroid 2-like-2 (Nrf-2)/heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis protects lens epithelial cells (LECs) against oxidants and ER stress. In the present study, transgenic FVB/N mice overexpressing the negative dominant mutant HO-1 G143H (TgHO-1 G143H) were generated to evaluate the crosstalk among HO-1, oxidative stress and ER stress in maintaining lens transparency. Slit-lamp examination revealed that nuclear cataracts occurred at 4 months in the TgHO-1 G143H mice, which was 5 months earlier than that of the control mice. The lenses of the transgenic mice showed an accumulation of malondialdehyde and protein carbonyl with a decrease in glutathione and protein sulfhydryl levels. Elevated concentrations of ER stress biomarkers (Bip, PERK, ATF6, IRE1, CHOP, caspase-12 and caspase-3) in the lenses of the TgHO-1 G143H mice were identified by western blotting. Furthermore, we confirmed that overexpressed HO-1 G143H in LECs resulted in oxidative insult and apoptosis in vitro. All of these data suggested that HO-1 enzymatic activity loss induces early-onset nuclear cataracts by activating oxidative stress and ER stress.

Strontium titanate (SrTiO3) is considered to be a promising photocatalyst. However, the rapid recombination of photo-generated charge carriers limits the practical applications of SrTiO3-based photocatalysts. In this work, we prepared hydrogenated SrTiO3 using NaBH4 as a reducing reagent. The optimized photocatalyst shows a H2-evolution rate up to 409.5 μmol g-1 h-1 with a CuS co-catalyst, which is 152, 14 and 1.8 times higher than those of pure SrTiO3, hydrogenated SrTiO3, and CuS/SrTiO3, respectively. The enhanced photocatalytic H2-evolution activity can be attributed to the synergistic effect of the CuS co-catalyst and the appropriate oxygen vacancies produced by hydrogenation, which are beneficial for lowering the separation of photo-generated charge carriers. The present finding could shed light on the design of efficient SrTiO3-based photocatalysts.

Augmented reality museums allow visitors to jointly view and interact with exhibits. However, real-time exhibit browsing does not accommodate latecomers to museums and offers limited support to temporally separated visitors. To stimulate asynchronous exhibit browsing, we developed a distance-driven user interface that divided the augmented reality exhibit-egocentric space into four distance ranges, each having a set of social networking features and different privileges for exhibit viewing and interaction. The user interface enables asynchronous exhibit browsing for visitors participating at different times. We conducted empirical studies to evaluate how the user interface affected visitors’ collaborative exhibit browsing in terms of perceived usability and learning gains. The results show that the perceived usability of the user interface is consistently high across all distance ranges. The user interface stimulates collaborative exhibit browsing with significant improvements in learning efficiency and learning attention durations, although learning satisfaction showed no difference across the participants. Implications for how the distance-driven user interface can be generalized for other interactive applications are discussed.

Photocatalytic hydrogen production using renewable energy sources is promising as a new method of energy supply. Research on photocatalytic materials has received increasing attention. In this work, efficient photocatalytic hydrogen production was achieved by using ZnIn2S4@CoS2 heterostructures as photocatalysts. The heterostructures were prepared by a simple hydrothermal method using ZIF-67 derived Co3O4 as a precursor. ZIF-67 derived Co3O4 inherits the dodecahedral structure of ZIF-67. ZnIn2S4 nanosheets uniformly grew on the surface of CoS2, which is prepared from Co3O4. The heterostructures achieved a high hydrogen production rate, about 3.2 times higher than that of pristine ZnIn2S4 under simulated sunlight. The enhanced photocatalytic activity can be attributed to the faster electron transfer and more efficient electron–hole pair separation, which are formed in the heterostructure at the interface between CoS2 and ZnIn2S4. This study provides a strategy for noble metal-free photocatalytic hydrogen production using heterostructures.

Objectives: Noninvasive high-frequency oscillatory ventilation (nHFOV) is a novel respiratory support mode for premature infants. This retrospective study aimed to compare the effect of nHFOV and bi-level nasal continuous positive airway pressure (BiPAP) in premature infants with neonatal respiratory failure (NRF) as initial noninvasive ventilation (NIV) support mode. Methods: We retrospectively analyzed medical records of preterm infants admitted to the tertiary neonatal intensive care units (NICUs) of Fujian Maternal and Child Health Hospital from January 2019 to December 2020. Preterm infants with the gestational age of 25-34 weeks, diagnosed with NRF, used nHFOV or BiPAP as the initial respiratory support mode were analyzed. The rates of invasive mechanical ventilation (IMV) within the first seven days after birth and adverse outcomes were compared between the two groups. Results: Two hundred fifty-five preterm infants were analyzed (128 in nHFOV group,127 in BiPAP group). There was no significant difference in baseline characteristics between the two groups. Compared with the BiPAP group, the nHFOV group had significantly lower need for IMV within the first seven days after birth (18/128 vs. 33/127, p = 0.01) and PCO2 at 12 and 24 hours post-treatment (46.34±5.24mmHg vs. 51.18±4.83mmHg, P

Soil salinization, a common land degradation mode, restricts the ecological environment and is a global issue due to climate change. Accurately, quickly and effectively monitoring soil salinity is critical for governmental institutions that develop hazard prevention and mitigation strategies. Remote sensing (RS) technology provides a viable alternative to traditional field work due to its large area coverage, abundant spectral information and nearly constant observations. Key issues in RS-based soil salinity monitoring include the lack of both data-mining techniques for obtaining spectral band information and comprehensive considerations of synergies among different spectra. The main objective of this study was to provide in-depth explorations of data mining and integration algorithms from different satellites to multidimensionally evaluate soil salinity models. The Ebinur Lake Wetland Reserve (Xinjiang Province, China) was selected as a case study. First, ground-measured visible and near infrared (VIS-NIR) spectral data were combined with the RS band to simulate Landsat 8 (L8) and Sentinel 2 (S2) and 3 (S3) data. Second, one-dimensional RS bands and 15 soil salinity and vegetation indices were selected, and 15 spectral data transformations (reciprocal, differential, absorbance, etc.) were obtained. Two- and three-dimensional spectral indices were constructed, and the response relationships between different spectral indices and soil electrical conductivity (EC) were comprehensively explored. Finally, an integrated multidimensional algorithm was used to estimate soil salinity in high-performance models for the three satellites. The results showed that all data-mining-based model combinations performed well for all satellites (R

It remains a huge challenge to integrate the sensitivity, stability, reproducibility, and anti-fouling ability of electrochemical biosensors for practical applications. Herein, we propose a self-assembled electrode combining hexanethiol (HT), poly-adenine (poly-A), and cholesteryl-modified DNA to meet this challenge. HT can tightly pack at the electrode interface to form a hydrophobic self-assembled monolayer (SAM), effectively improving the stability and signal-to-noise ratio (SNR) of electrochemical detection. Cholesteryl-modified DNA was immobilized at the electrode through the hydrophobic interaction with HT to avoid the competition between the SAM and the DNA probe on the gold site. Thus, the assembly efficiency and uniformity of the DNA probe as well as the detection reproducibility were increased remarkedly. Poly-A was added on the HT assembled electrode to occupy the unreacted sites of gold to further enhance the anti-fouling ability. The combination of HT and poly-A allows the electrode to ensure favorable anti-fouling ability without sacrificing the detection performance. On this basis, we proposed a dual-signal amplification electrochemical biosensor for the detection of exosomal microRNAs, which showed excellent sensitivity with a detection limit down to 1.46 aM. Importantly, this method has been successfully applied to detect exosomal microRNA-21 in cells and human serum samples, proving its potential utility in cancer diagnosis.

Tacrolimus and voriconazole are usually used simultaneously in lung transplantations. Voriconazole can increase tacrolimus concentrations by inhibiting the cytochrome P450 (CYP) enzyme, which poses a great challenge for dose adjustment. The aim of this study is to clarify the correlation between voriconazole exposure and tacrolimus trough concentrations (C

On-demand video has become a seamless part of the fabric of information consumption. Initially inspired by the popularity of video guides for practical skills such as cooking and DIY, instructional videos were developed for equipment used in the first-year chemical engineering undergraduate teaching laboratory at Imperial College London. During 2016/2017, the effect of the videos on the students’ learning was measured using video viewership metrics, a survey, focus groups with students and Graduate Teaching Assistants (GTAs) and rounded off through interviews with the module teaching team. Student reactions were overall positive, with >90% of students stating they found the videos useful. The outcome of our study indicated that because of access to the videos before, during, and after lab sessions, students were more confident in their own ability, spent more time engaging with theory, applied practical lab skills in a more targeted way, and produced better outputs. Rather than being just a video version of the experiment handout, the video influenced the behavior of both learners and teachers, freeing up time to engage in deeper exploration of topics. The results of the study suggest that the use of video-led instruction in undergraduate laboratory teaching improves student experience, saves GTA time, and decidedly shifts the teaching focus from demonstration to exploration.

The structural characterization of sublayer surfaces of MIL-101 is reported by low-dose spherical aberration-corrected high-resolution transmission electron microscopy (HRTEM). The state-of-the-art microscopy directly images atomic/molecular configurations in thin crystals from charge density projections, and uncovers the structures of sublayer surfaces and their evolution to stable surfaces regulated by inorganic Cr3 (μ3 -O) trimers. This study provides compelling evidence of metal-organic frameworks (MOFs) crystal growth via the assembly of sublayer surfaces and has important implications in understanding the crystal growth and surface-related properties of MOFs.

Partial or complete deficiency in the dihydropyrimidine dehydrogenase (DPD) has been observed in 3%–5% and 0.1% of the general population, respectively. It causes severe toxicity in the context of ...

What is known and objective The influence of venovenous extracorporeal membrane oxygenation (VV-ECMO) on the population pharmacokinetics (PPK) of vancomycin in recipients after lung transplantation (LTx) is unknown. We investigated whether VV-ECMO influences vancomycin PPK and determined optimal recommended dosage for patients after LTx. Methods We tested vancomycin serum concentration and calculated PPK parameters using NONMEM. To check for any potential influence of ECMO on vancomycin PK, we compared ECMO patients with a non-ECMO patient control group, and patients before and after ECMO weaning as self-control to analysed changes in vancomycin PK. Monte Carlo dosing simulation was conducted to explore vancomycin dosing regimens. Results Nineteen ECMO and 6 non-ECMO lung transplant recipients were enrolled. Vancomycin serum concentrations did not significantly differ between patients with and without ECMO support. Comparison of separate vancomycin population pharmacokinetic models showed that ECMO patients had smaller peripheral compartment volume of distribution (V2 ) [Estimate (relative standard error, RSE, %) 19.7 (12) vs. 22 (17) L, P = .003] than non-ECMO patients. For treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections with MIC ≤ 0.5 µg/mL, venous infusion of 400 mg vancomycin every 8 hours was recommended. For MRSA infection with MIC ≤ 1 µg/mL, the proposed dosage was 600 mg every 8 hours. What is new and conclusion Venovenous extracorporeal membrane oxygenation slightly alters vancomycin PK but does not significantly impact vancomycin serum concentration in patients after LTx. Dose adjustment is not necessary for VV-ECMO support. Specific vancomycin dosing regimens with lower nephrotoxicity may benefit LTx recipients with VV-ECMO.

Purpose. To evaluate visual acuity (VA) and refractive status in patients with cataract and irregular astigmatism with a regular central component after phacoemulsification with implantation of a toric intraocular lens (IOL). Methods. Patients with cataract associated with irregular astigmatism with a regular central component were enrolled. All patients underwent phacoemulsification and toric IOL implantation. Postoperative visual acuity, residual astigmatism, toric IOL rotation, higher-order aberration, and objective and subjective visual quality were measured 3 months after surgery. Results. Twenty-three eyes were included in the study. The logMAR corrected and uncorrected distance visual acuity values were decreased at 3 months postoperatively (p < 0.005). The preoperative average corneal astigmatism and postoperative residual astigmatism were 1.15–6.97 D (1.99 ± 1.26 D) and 0–2.75 D (0.65 ± 0.57 D), respectively. The average IOL rotation was 3.17 ± 2.01°. Some objective indicators of visual quality, including the modulation transfer function (p < 0.05), Strehl ratio (p < 0.005), 100% VA (p < 0.005), 20% VA (p < 0.005), and 9% VA (p < 0.005), were significantly higher than the corresponding preoperative values. The objective scatter index (p < 0.005) was significantly lower than that before surgery. The postoperative VF-14 scale score was 83.99 ± 14.58. Conclusion. Toric IOL implantation has a good corrective effect on certain specific types of corneal irregular astigmatism with cataract. This effect can be attributed to its ability to correct the regular component of irregular astigmatism. The indications for toric IOL implantation could be expanded to some extent, thereby bringing benefit to more patients.

The objective of the presented module is to train students with no background in process development and scaleup of chromatographic processes to a high level of competency within 40 contact hours. The key pedagogical approach is “progression” where students’ capabilities are gradually built up with appropriate scaffolding provided at each stage of their learning. The module is broken up into three steps, with each step covering a different aspect of chromatography. Knowledge gained in one step is the foundation for work in the next. In the first step, students investigate several chromatographic column packing materials and perform a solvent selection process. Design of experiment (DOE) to systematically vary process parameters for method development is introduced in the second step. In the last step, students use a preparative-LC system to perform a larger-scale separation. Students explore different scale-up scenarios, including volume fraction collection and column overloading. Pedagogic outcomes of the module were determined through surveys, interviews, and personal interaction during the study. Results clearly indicate that students engaged well with the module while meeting overall learning objectives. The module is equally suitable for third- or fourth-year university students or industry practitioners unfamiliar with chromatography as part of continuing professional development.

What is known and objective Teicoplanin is widely used for the treatment of infections caused by drug-resistant Gram-positive bacteria. Since there is a good correlation between trough levels and clinical outcome, therapeutic drug monitoring (TDM) is recommended to achieve better clinical curative effects. However, TDM of teicoplanin is not routine in China. So, a programme was initiated in 2017, including both HPLC method establishment and interlaboratory quality assessment, for the measurement of teicoplanin. Methods A main centre and a quality control centre were set up in the study. An HPLC-based method of teicoplanin determination in plasma was developed by the main centre. Analysis was performed using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phase was NaH2 PO4 (0.01 mol/L) and acetonitrile (75:25 v/v; pH 3.3), with a flow rate of 1.0 mL/min and a detection wavelength of 215 nm. Piperacillin sodium was selected as an internal standard (IS). Twenty-six additional TDM centres were then recruited to adopt this method. Then, all the centres were asked to take part in a quality control assessment evaluated by the quality control centre. Results For all TDM centres, linearity of teicoplanin concentration ranges was between 3.125 and 100 µg/mL. Intraday and interday accuracies ranged from 87.1% to 118.4%. Intraday and interday precision ranged from 0.3% to 13.8%. Therapeutic drug monitoring centres all passed inter-room quality assessment. All samples tested met the acceptance criteria. Then, 542 samples were collected. Patients with sub-optimal (≤10 mg/L) plasma teicoplanin concentrations constituted 42% of the total study population. What is new and conclusions For the first time, a simple, rapid and accurate HPLC method for determining teicoplanin levels was successfully applied to therapeutic drug monitoring in clinical practice for twenty-seven TDM centres in China. The results demonstrated excellent interlaboratory agreement for teicoplanin testing and provide support for clinical laboratory quality management and results inter-accreditation.

Strontium titanate (SrTiO3) is a promising photocatalyst because of its high chemical stability and excellent photocatalytic activity. However, the requirement of near-ultraviolet (UV) irradiation for effective photocatalysis limits its practical application. In this work, we prepared a novel Ni(OH)2-modified SrTiO3 composite using a simple precipitation method and confirmed that the Ni(OH)2 nanoparticles were successfully deposited on the SrTiO3 surface rather than incorporated into the lattice. The optimal Ni(OH)2 loading amount for high H2 evolution was found to be 20%, giving an activation rate of up to 1.46 mmol h−1 g−1, which is ca. 15 times higher than that of the pure SrTiO3. This significant enhancement of activity could be ascribed to the lower recombination of electrons and holes in the presence of Ni(OH)2, which was confirmed by photo-luminescence spectroscopy (PL) and photo-current response property. The present finding could shed light on the design of efficient perovskite-type oxide based photocatalysts.

The Ebinur Lake watershed is an important ecological barrier for environmental changes in the Junggar Basin in Xinjiang Uygur Autonomous Region (XUAR). Due to the tremendous changes in the underlying surface environment of the watershed in the past few decades, the watershed has become a typical region of ecological degradation. Drought affects the surface dynamics and characterizes the regional dry and wet environments, while the dynamic variation in lakes and vegetation are indicators of dynamic changes in land surfaces. Thus, a quantitative assessment of the response of lakes and vegetation to drought conditions at multiple temporal scales is critical for assessing the potential impacts of regional climate change on terrestrial ecosystems and ecological restoration. The standardized precipitation evapotranspiration index (SPEI), the spectral water index (NDWI) and the normalized difference vegetation index (NDVI) were used to analyse the evolution of drought, the variation in lake surface area and the sustainable variation in vegetation. Furthermore, we quantitatively evaluated the response patterns of vegetation to droughts of multiple temporal scales (1-, 3-, 6-, 12-, 24-month). The conclusions showed that (1) overall, the area of Ebinur Lake experienced drastic fluctuations, and the lake area has decreased significantly since 2003, with a dynamic area of 817.63 km2 in 2003 and 384.60 km2 in 2015, and the lake area had shrank severely. (2) The interannual variation of wet and dry changed alternately during the observation period, and persistent drought events occurred from 2006 to 2010 across the Ebinur Lake watershed. (3) The vegetation area of cultivated land expanded continuously across the watershed, and the grassland degraded severely. (4) The changes in lake surface area are significantly correlated with the inflow water volume (correlation coefficient = 0.64, P

The structure–property relationship plays a crucial role in further exploring the mechanism of hydrogen production by photocatalytic water splitting. Here, we utilize a simple hydrothermal method to synthesize three Co3O4 catalysts with different exposed crystal facets to elucidate their catalytic mechanism at the atomic level. Co3O4 microflowers, nanotruncated octahedra and nanorods have mainly exposed {112}, {011} and {001} crystal planes, respectively, and the concentration and distribution of Co2+ and Co3+ active sites on the surface are different. Further results indicate that the {112} and {011} planes with abundant Co3+ sites exhibit catalytic activity superior to that of the {001} plane. Surface atomic configuration and EPR studies manifest that the presence of octahedral coordinated Co3+ sites optimizes the photocatalytic hydrogen evolution activity. This work reveals the importance of regulating surface atomic configuration and catalytic active sites, and opens a new avenue for the development of solar-driven water splitting.

Layered ZnWO4 is a promising photocatalyst; however, its poor light absorption properties limit its practical applications. In this work, Mo-doped ZnWO4 (ZnW1−xMoxO4) was prepared by a hydrothermal method. X-ray diffraction data for ZnW1−xMoxO4 revealed that the materials retained the layered structure after Mo doping. The synthesized layered ZnW1−xMoxO4 had absorption edges at around 390 nm when x = 0.4. In the presence of Mo, ZnW1−xMoxO4 produced H2 from an aqueous solution containing Na2SO3 and Na2S as reversible electron donors which was ca. 2.2 times higher than that of ZnWO4 (607.1 μmol g−1 h−1vs. 271.2 μmol g−1 h−1). This high activity could be attributed to the formation of a trap level after Mo doping, which was confirmed by X-ray photoelectron spectroscopy. In addition, by combining ZnW1−xMoxO4 with CdS to form an n–n heterojunction, an approximately 9.8 times higher activity than that of ZnWO4 was observed (2658.1 μmol g−1 h−1vs. 271.2 μmol g−1 h−1). This work provides a method for the modification of wide band gap semiconductors, which sheds new light on the future design of high activity photocatalysts.

Root penetration ability is critical for plant growth and development. When roots encounter soil impedance, hormones are activated that affect cells and tissues, leading to changes in root morphology and configuration that often increase root penetration ability. Factors, such as root system architecture, root anatomic traits, rhizosphere exudation and root-induced phytohormones, influencing root penetration ability and how they affect plant performance under soil impedance were summarized. Root penetration ability affects plant capturing water and nutrients, and thus determines plant performance and productivity in adverse environments. Great efforts have been made in searching for the underlying mechanisms of root penetration ability, and tools have been developed for phenotyping variability in root penetration ability. Therefore, with the continued development of agroecosystems based on the advocated low input costs and controlled tillage, crops or genotypes of a crop species with stronger root penetration ability may have the potential for developing new varieties with enhanced adaptation and grain yield under mechanical impedance in soil.

The analysis of microRNAs (miRNAs) in exosomes offers significant information for a rapid and non-invasive diagnosis of cancer. However, the clinical utility of miRNAs as biomarkers is often hampered by their low abundance in exosomes. Herein, we develop a dual-signal amplification biosensor for the sensitive detection of exosomal miRNA-21 (miR-21). In the presence of a cognate target, it hybridizes with a biotin-modified capture probe (Cp) to form a DNA-RNA heteroduplex that serves as a substrate for duplex-specific nuclease (DSN). With the assistance of DSN, the Cps are enzymatically hydrolyzed and numerous DNA catalysts are released, leading to the first signal amplification. After magnetic isolation, the DNA catalyst remaining in the supernatant triggers a strand displacement reaction based on the nicking-assisted reactant recycling strategy, without depleting the reactants, to implement the second signal amplification. Using this dual-signal amplification concept, our biosensor achieves a limit of detection of miR-21 of 0.34 fM, with a linear range of 0.5-100 fM. The receiver operating characteristic curve generated during clinical sample analysis indicates that the exosomal miR-21 outperforms serum carcinoembryonic antigen in discriminating between patients with gastric cancer (GC) and patients with precancerous (PC) lesions (area under the curve: 0.89 versus 0.74, n = 40). Moreover, the proposed biosensor exhibits an 83.9% accuracy in classifying patients with GC or PC lesions and healthy donors using a confusion matrix. Furthermore, patients with GC with or without metastases are discriminated using the proposed biosensor. Our technology may expand the applications of DNA-based biosensor-enabled cancer diagnostic tools.

Polyolefins such as polyethylene (PE) and polypropylene (PP) are abundant components of plastic waste. Chemical recycling of PE and PP via pyrolysis followed by chemical vapor deposition typically results in the growth of multi-walled carbon nanotubes (CNTs). Here, a tandem catalytic system for the growth of few-walled CNTs is reported. The successful synthesis of few-walled CNTs in the system relies on the catalytic processing of pyrolysis gas from plastics into intermediate gas mixtures containing mainly paraffins and hydrogen (700 °C, catalyst: 40 wt% Co, 10 wt% Mo and 50 wt% MgO). Under appropriate conditions (1000 °C, catalyst: Co 3 wt%, Mo 2 wt% and MgO 95 wt%, synthesis time: 20 min), the obtained intermediate gas mixture was selectively converted into few-walled CNTs with > 95% CNTs having small outer diameters of 1-7 nm, containing CNTs with as little as three walls and having distinct radial breathing mode in Raman spectra at wave lengths 100-400 cm-1. The proposed synthesis process opens new opportunities for production of high value few-walled CNTs from plastic waste. Economic Development Board (EDB) Nanyang Technological University The authors would like to acknowledge the Nanyang Environment and Water Research Institute, Nanyang Technological University (Singapore) and Economic Development Board (Singapore) for financial support of this research.

IntroductionThe active-fluidics system is a new irrigation system of phacoemulsification that automatically detects and maintains stable intraocular pressure at the set value. This trial is designed to compare the efficacy, visual outcomes, safety and patients’ subjective perceptions of cataract surgery with the active-fluidics system and gravity-fluidics system.Methods and analysisThis trial will recruit 110 patients with age-related cataract at the Chinese People’s Liberation Army (PLA) General Hospital (Beijing, China) and they will be randomly assigned to the active-fluidics group and gravity-fluidics group in a ratio of 1:1 to have phacoemulsification. Patients will be followed up at 1 day, 1 week, 1 month and 3 months postoperatively. The primary outcomes are the cumulative dissipated energy and best corrected visual acuity. Secondary outcomes include: estimated fluid usage, U/S time, total aspiration time, intraocular pressure, corneal endothelium parameters, retinal thickness, macular superficial vessel density, pain scores, scores of the Cataract surgery Patient-Reported Outcome Measures Questionnaire and the complication rates. The data will be independently analysed by the statistical team, who will be masked for the allocation information as participants are.Ethics and disseminationThis study was approved by the Ethics Committee of Chinese PLA General Hospital (approval no. S2021-068-01). Informed consent will be obtained from each participant. All the results will be published in peer-reviewed journals and used for scholarly communication or technical guidance. Protocol version 1.0.Trial registration numberChinese Clinical Trial Registry (ChiCTR2100044409).

Oxyfluorides possess considerable attention for their multiple excellent properties, but the conventional high-temperature solid-state syntheses have seen bottlenecks in the synthesis of new compounds. Herein, we report a novel layered oxyfluoride ZnMoO

Nanoscale zerovalent iron (nZVI) represents a promising reduction technology for water remediation, but its broad application is largely hampered by the tendency of nZVI to aggregate and the low electron transferability due to the interfacial charge resistance. Herein, by combining the advantages of polypyrrole (PPY) and nZVI, we prepared a composite material (i.e., PPY supported palladium‑iron bimetallic nanoparticles (Pd/Fe@PPY)) and applied it for the simultaneous removal of 4-chlorophenol (4-CP) and Cr(VI). Our results showed that this material had superior catalytic performances with a complete removal of 4-CP (50 mg·L

The drug release efficiency of microneedle is usually slower than that of oral delivery or hypodermic injection, which severely restricts its widespread use. Herein, a FeThe mechanical property and characterization of FeFe

We previously reported that cyclophilin A (CyPA) production is upregulated in preeclampsia (PE). Moreover, CyPA is known to induce PE-like features in pregnant mice and impair trophoblast invasiveness. In this study, we further illustrated the role of CyPA in PE. RNA-seq analysis, RT-qPCR, immunohistochemical (IHC) staining, and western blotting of mouse placentae revealed that CyPA increased the levels of extracellular matrix (ECM) proteins, such as collagen I and fibronectin, and activated the TGF-β/Smad3 signaling pathway. Additionally, CyPA inhibited the expression of genes involved in epithelial-mesenchymal transition (EMT) (e.g., E-cadherin, N-cadherin, and vimentin) in mouse placentae. We then constructed stable overexpressing and knock-down CyPA cell models (using HTR8/SVneo cells) to clarify the molecular mechanism. We found that CyPA regulated the levels of ECM-related proteins and the EMT process through the TGF-β/Smad3 pathway. We also identified SERPINH1 as a putative CyPA-binding protein, using liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. SERPINH1 was found to be upregulated in the placentae of PE. Silencing SERPINH1 expression reversed the upregulation of ECM proteins and inhibition of the EMT process induced by the overexpression of CyPA. These findings revealed the functions of CyPA in the impaired invasiveness of trophoblasts in PE and indicated that CyPA and SERPINH1 may represent promising targets for the treatment of PE.

Preeclampsia (PE) is a pregnancy-associated complication accompanied by gestational hypertension and proteinuria, affecting 2-8% of pregnancies globally. The placental trophoblast cell invasion of decidua and myometrium during early gestation is crucial for healthy placentation. Thus, trophoblast dysfunction might contribute to PE onset. Therefore, further investigations are needed to elucidate the underlying mechanism of trophoblast cell functions. In the present study, we identified a novel pseudogene named C-Type Lectin Domain Family 4 Member G Pseudogene 1 (CLEC4GP1), which was aberrantly expressed in PE placental tissues. In vitro analyses showed that CLEC4GP1 overexpression significantly increased the cell viability and invasiveness and decreased the apoptosis rate of HTR-8/SVneo and JEG-3 cells, while CLEC4GP1 knockdown exerted opposite effects, suggesting the beneficial role of CLEC4GP1 in trophoblast cells. Next, co-expression analysis found that CLEC4GP1 was negatively correlated with Interleukin 15 (IL-15). The expression of IL-15 dramatically increased in PE placental tissues. In HTR-8/SVneo and JEG-3 cells, IL-15 exhibited detrimental effects, opposite to CLEC4GP1, and they were negatively correlated. In addition, CLEC4GP1 attenuates the mRNA stability of IL-16 by inhibiting the binding between human antigen R (HuR) protein and IL-15 RNA. Finally, the obverse effects of CLEC4GP1 and IL-15 were investigated, and results showed that IL-15 reverted CLEC4GP1 induced cellular functions. In brief, these data suggest that CLEC4GP1/IL-15 axis might modulate the occurrence and progression of PE via influencing the trophoblast cell viability, apoptosis, and invasive capability. This study provided cognizance of targeting the CLEC4GP1/IL-15 axis as a novel therapeutic approach to mitigate PE progression.

Tantalum-based layered perovskites have always been an interesting topic in photocatalysis, but limited information has been reported in terms of their layer factor. In this work, we have synthesized Dion–Jacobson layered perovskites (A′[An−1TanO3n+1]) of LaTaO4, KLaTa2O7, and KCa2Ta3O10 with n = 1, 2, and 3, respectively. With the modification of 1 wt% Pt co-catalysts, the photocatalytic analysis showed that the performance order of these layered perovskites with different layers is KLaTa2O7 (n = 2) > KCa2Ta3O10 (n = 3) ≫ LaTaO4 (n = 1) with both methanol and NaI as the sacrificial agents. This suggested the importance of interlayer K+ for high photocatalytic performance. We further analyzed the layered perovskites in detail by BET, photoelectrochemical analysis, Mott–Schottky, and VB-XPS test. The combined results indicated that the positions of the conduction band are the dominant factors for the photocatalytic performance of tantalum-based Dion–Jacobson layered perovskites with n = 2 and 3. This work sheds new light on the field of layered perovskites as efficient photocatalysts.

Nanoscale zerovalent iron (nZVI) reduction offers a wide range of applications in source-zone remediation, but the reactivity of nZVI is largely hampered due to its low electron-transfer ability and tendency to aggregate. Based on the dual function of conductive polymers (CPs) as support and electron transfer carrier, we combined CPs with nZVI and prepared a series of Pd/Fe bimetallic materials that successfully address the challenges of nZVI reduction. These Pd/Fe@CPs particles showed strong catalytic ability for the simultaneous removal of 4-chlorophenol (4-CP) and Cr(VI). The removal rate of 4-CP was significantly enhanced by 1.5 - 6.2 times after supporting Pd/Fe nanoparticles (NPs) with CPs. The enhanced reactivity of supported Pd/Fe NPs was attributed to their highly stabilized and dispersed state and the promoted electron transfer due to the synergistic effect between CPs and nZVI bimetallic particles. The various catalytic activity over Pd/Fe@CPs was attributed to the distinctive properties of CPs and their different interfacial electron transfer ability. Importantly, this study provides insights into distinguishing both mechanisms of direct electron transfer and atomic-hydrogen-mediated indirect electron transfer, and their quantitative relationship to the dehalogenation performance over Pd/Fe@CPs materials. This work provides better understanding of the remediation process and mechanisms of nZVI reduction.