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Methyl 2-{[1-(5-fluoropentyl)-1H-indazole-3-carbonyl]amino}-3,3-dimethylbutanoate (5F-ADB), which is classified as an illicit drug in China and most European countries, is susceptible to abuse. The abuse of 5F-ADB must avoid entering the water environment. However, the aquatic toxic effects of 5F-ADB remain unclear. In this study, Daphnia magna (D. magna) was used to investigate the potential toxicity of 5F-ADB at concentrations of 0, 0.01, 1, and 100 μg/L. The results showed that 5F-ADB caused significant developmental, reproductive, and neurodevelopmental toxicity in D. magna. Compared with the control group, exposure to 5F-ADB significantly reduced daphnia body length, weight, heartbeat, total number of offspring, while increased daphnia respiratory rate, and swimming behavior. Superoxide dismutase (SOD) activity increased significantly, while catalase (CAT) activity decreased, indicating that the exposed daphnia suffered obvious oxidative damage. 5F-ADB also triggered the inhibition of the serotonergic and noradrenergic systems, which ultimately stimulated the swimming behavior of D. magna. This study demonstrates that 5F-ADB has a significant toxic effect on the vital activity of D. magna upon entering aquatic environments, and that synthetic cannabinoid analogs such as 5F-ADB may pose potential ecological risks to organisms in aquatic ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Ltd.)

Pollutants often exhibit different environmental behaviors at varying redox potentials, and the fate and microbial response of 6-OH-BDE-47 and 6-MeO-BDE-47 under these conditions remain unclear. Herein, 14 C-labeled 6-OH-BDE-47 and 6-MeO-BDE-47 were used to investigate their fate in water-sediment systems at different redox potentials. For 6-OH-BDE-47, aerobic microorganisms and nitrate electron acceptors promoted nonextractable residues (NERs) formation and anaerobic microorganisms facilitated their release and was highest formed in the O 2 -containing group. For 6-MeO-BDE-47, aerobic microorganisms, electron acceptors, and anaerobic microorganisms promoted NER formation, and was highest formed in the nitrate group. Microorganisms markedly promoted 6-OH/MeO-BDE-47 transformation. For 6-OH-BDE-47, the degradation followed the order nitrate group (29.6 %) > O 2 -containing group (6.5 %) > sulfate group (1.45 %) > anaerobic group (0 %), while for 6-MeO-BDE-47, the order was O 2 -containing group (8.8 %) > nitrate group = sulfate group = anaerobic group (0 %). The complexity of the 6-OH-BDE-47 and 6-MeO-BDE-47 microbial community network was consistent with the results of redox potentials, where microbial networks connectivity linking were more complex under O 2 -containing and nitrate conditions. Overall, our study comprehensively revealed the fate of 6-OH-BDE-47 and 6-MeO-BDE-47 under different redox conditions, showing that electron acceptors can alter microbial community structure and regulating interactions. It provided guidelines for selecting electron acceptors in the remediation of 6-OH-BDE-47 and 6-MeO-BDE-47., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations., Results: Protein kinase C isoform ζ (PKCζ), which is highly expressed in breast cancer cells, accumulates in the nuclei of human mammary epithelial cells overexpressing human rhomboid family-1 (RHBDF1), an endoplasmic reticulum membrane protein. Nuclear translocation of PKCζ results in the failure of the formation of the cytosolic apicobasal polarity complex Par, of which PKCζ is an essential component. Additionally, enhanced nuclear translocation of PKCζ is accompanied by an inhibition of the expression of cell tight junction and adherens junction proteins and an increase of cell mobility. Mechanistically, RHBDF1 is able to interact with importin β1 and PKCζ and promote PKCζ phosphorylation. Consistently, treatment of RHBDF1-overexpressing cells with an inhibitor of PKCζ phosphorylation leads to restoration of apicobasal polarity and cell-cell junctions, as well as suppressed cell mobility., Conclusions: RHBDF1-facilitated nuclear translocation of PKCζ is critically responsible for the dismantlement of epithelial cell apicobasal polarity, and thus may serve as a target in the development of therapeutic approaches against early stages of breast cancer., Competing Interests: Declarations. Ethics approval and consent to participate: Breast tissue samples were collected from the full information database of breast cancer patients in the Breast Cancer Pathology and Research Laboratory of Cancer Hospital of Tianjin Medical University (Tianjin, China), including para-cancerous tissue and breast cancer tissue diagnosed as invasive breast cancer by two senior pathologists of six patients. The research procedure of this work is in line with the ethical standards of Tianjin Medical Oncology Institute and Hospital Ethics Committee. This study was approved by the Evaluation Committee of Cancer Hospital of Tianjin Medical University and all breast cancer patients were fully informed and signed the informed consent form. Conflict of interest: The authors declare no conflict of interest. Consent to participate and consent to publish: All authors consent to the publication of the data., (© 2024. The Author(s).)

High ammonia pollution is a common problem in water bodies. However, research on the mechanisms underlying the toxic effects on organisms at different nutritional levels is still insufficient. Herein, based on the environmental concentration, the toxic effects of high ammonia pollution on Daphnia magna were investigated. Overall, the feeding and filtration rates of D. magna were significantly decreased by ammonia. Growth inhibition of D. magna by ammonia was confirmed by the decreased body length. After ammonia exposure, the metabolic status of D. magna changed, the correlation network weakened, and the correlations between metabolites were disrupted. Changes occurred in metabolites primarily involved in oxidative stress, fatty acid oxidation, tricarboxylic acid cycle, and protein digestion, absorption, and synthesis, which were validated through alterations in multiple biomarkers. In addition, mitochondrial function was evaluated and was found to inhibit mitochondrial activity, which was accompanied by a decreased marker of mitochondrial activity contents and ATPase activity. Thus, the results suggested that energy metabolism and oxidative stress were involved in ammonia-induced growth toxicity. This study provides new insights into the impact of ammonia on aquatic ecological health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Basal cell carcinoma (BCC) is the most common skin cancer, lacking reliable biomarkers or therapeutic targets for effective treatment. Genome-wide association studies (GWAS) can aid in identifying drug targets, repurposing existing drugs, predicting clinical trial side effects, and reclassifying patients in clinical utility. Hence, the present study investigates the association between plasma proteins and skin cancer to identify effective biomarkers and therapeutic targets for BCC., Methods: Proteome-wide mendelian randomization was performed using inverse-variance-weight and Wald Ratio methods, leveraging 1 Mb cis protein quantitative trait loci (cis-pQTLs) in the UK Biobank Pharma Proteomics Project (UKB-PPP) and the deCODE Health Study, to determine the causal relationship between plasma proteins and skin cancer and its subtypes in the FinnGen R10 study and the SAIGE database of Lee lab. Significant association with skin cancer and its subtypes was defined as a false discovery rate (FDR) < 0.05. pQTL to GWAS colocalization analysis was executed using a Bayesian model to evaluate five exclusive hypotheses. Strong colocalization evidence was defined as a posterior probability for shared causal variants (PP.H4) of ≥0.85. Mendelian randomization-Phenome-wide association studies (MR-PheWAS) were used to evaluate potential biomarkers and therapeutic targets for skin cancer and its subtypes within a phenome-wide human disease category., Results: PTGES2, RNASET2, SF3B4, STX8, ENO2, and HS3ST3B1 (besides RNASET2, five other plasma proteins were previously unknown in expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL)) were significantly associated with BCC after FDR correction in the UKB-PPP and deCODE studies. Reverse MR showed no association between BCC and these proteins. PTGES2 and RNASET2 exhibited strong evidence of colocalization with BCC based on a posterior probability PP.H4 >0.92. Furthermore, MR-PheWAS analysis showed that BCC was the most significant phenotype associated with PTGES2 and RNASET2 among 2,408 phenotypes in the FinnGen R10 study. Therefore, PTGES2 and RNASET2 are highlighted as effective biomarkers and therapeutic targets for BCC within the phenome-wide human disease category., Conclusion: The study identifies PTGES2 and RNASET2 plasma proteins as novel, reliable biomarkers and therapeutic targets for BCC, suggesting more effective clinical application strategies for patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Zhu, Sun, Ding, Wang and Zhang.)

Pharmaceuticals and biologically active natural products usually contain multiple stereocenters. The development of catalytic asymmetric reactions for the direct construction of complex motifs containing three nonadjacent stereocenters is a particularly important and formidable challenge. In this paper, we report an unprecedented method for the direct asymmetric construction of complex chiral amines with 1,3,5- or 1,3,4-stereocenters from readily available achiral and racemic starting materials. The reaction was made possible by the development of highly efficient chiral ammonium catalysts that serve three distinct functions: promoting efficient kinetic resolution by chiral recognition of racemic electrophiles, promoting asymmetric C-C bond forming reactions by recognizing enantiotropic faces of achiral nucleophiles, and mediating a highly stereoselective protonation of carbanions. Using these trifunctional catalysts, the reaction of imines and tulipane derivatives proceeded in a highly regio-, chemo-, and stereoselective manner to produce synthetically useful yields of complex chiral amines. We believe that trifunctional catalysis can be applied in a variety of asymmetric transformations for the streamlined asymmetric synthesis of complex chiral molecules with multiple stereocenters.

This study introduces a new wearable fiber-optic sensor glove. The glove utilizes a flexible material, polydimethylsiloxane (PDMS), and a silicone tube to encapsulate fiber Bragg gratings (FBGs). It is employed to enable the self-perception of hand posture, gesture recognition, and the prediction of grasping objects. The investigation employs the Support Vector Machine (SVM) approach for predicting grasping objects. The proposed fiber-optic sensor glove can concurrently monitor the motion of 14 hand joints comprising 5 metacarpophalangeal joints (MCP), 5 proximal interphalangeal joints (PIP), and 4 distal interphalangeal joints (DIP). To expand the measurement range of the sensors, a sinusoidal layout incorporates the FBG array into the glove. The experimental results indicate that the wearable sensing glove can track finger flexion within a range of 0° to 100°, with a modest minimum measurement error (Error) of 0.176° and a minimum standard deviation (SD) of 0.685°. Notably, the glove accurately detects hand gestures in real-time and even forecasts grasping actions. The fiber-optic smart glove technology proposed herein holds promising potential for industrial applications, including object grasping, 3D displays via virtual reality, and human-computer interaction.

Context: It remains controversial whether the choice of the daily eating window early or later in time-restricted eating (TRE) intervention (early or later TRE) has different effects on weight loss and metabolic health., Objective: A network meta-analysis was performed to evaluate the efficacy between early and later TRE in adults with obesity or overweight., Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published until October 16, 2022. We conducted a network meta-analysis to evaluate the efficacy of early and later TRE on body weight and metabolic parameters, including glycemic metabolism, blood pressure, and lipid profiles., Results: Twelve RCTs with 730 obese or overweight adults were included in this meta-analysis. Early TRE and later TRE both elicited moderate reductions in body weight and insulin resistance (IR) (homeostasis model assessment of IR) when compared to non-TRE. Interestingly, early TRE showed more effectiveness than later TRE in improving IR (early vs later TRE: -0.44; 95% CI, -0.86 to -0.02; P < .05), whereas no statistically significant difference was detected in weight loss (early vs later TRE: -0.31 kg; 95% CI, -1.15 to 0.53 kg; P >.05). In addition, early TRE rather than later TRE showed significant benefits in glycemic metabolism and blood pressure when compared to non-TRE. No significant differences between early and later TRE were observed for fasting blood glucose, blood pressure, and lipid profiles., Conclusion: This meta-analysis suggests that people may choose early TRE for more effective weight management and metabolic benefits. Nevertheless, further large-scale RCTs are warranted to verify our findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with device detected atrial high-rate episodes (AHRE) have an increased risk of MACE. The R 2 CHA 2 DS 2 -VASc, CHADS 2 , R 2 CHADS 2 and CHA 2 DS 2 -VASc score have been investigated for predicting major adverse cardiovascular events (MACE) in different groups of patients. We aimed to evaluate the R 2 CHA 2 DS 2 -VASc score in combination with AHRE ≥ 6 min for predicting MACE in patients with dual-chamber PPM but no prior atrial fibrillation (AF). We retrospectively enrolled 376 consecutive patients undergoing dual-chamber PPM implantation and no prior AF. The primary endpoint was subsequent MACE. For all patients in the cohort, CHADS 2 , R 2 CHADS 2 , CHA 2 DS 2 -VASc, R 2 CHA 2 DS 2 -VASc scores and AHRE ≥ or < 6 min were determined. AHRE was recorded as a heart rate > 175 bpm (Medtronic) or > 200 bpm (Biotronik) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine the independent predictors of MACE. ROC-AUC analysis was performed for CHADS 2 , R 2 CHADS 2 , CHA 2 DS 2 -VASc, and R 2 CHA 2 DS 2 -VASc scores and then adding AHRE ≥ 6 min to the four scores. The median age was 77 years, and 107 patients (28.5%) developed AHRE ≥ 6 min. After a median follow-up of 32 months, 46 (12.2%) MACE occurred. Multivariate Cox regression analysis showed that R 2 CHA 2 DS 2 -VASc score (HR, 1.485; 95% CI, 1.212-1.818; p < 0.001) and AHRE ≥ 6 min (HR, 2.125; 95% CI, 1.162-3.887; p = 0.014) were independent predictors for MACE. The optimal R 2 CHA 2 DS 2 -VASc score cutoff value was 4.5 (set at ≥ 5), with the highest Youden index (AUC, 0.770; 95% CI, 0.709-0.831; p < 0.001). ROC-AUC analysis of the four risk scores separately combined with AHRE ≥ 6 min all showed better discriminatory power than the four scores alone (All Z-statistic p < 0.05). In patients with PPM who develop AHRE ≥ 6 min, it is crucial to perform risk assessment with either four scores to further stratify risk for MACE., (© 2023. The Author(s).)

Three new constituents: 1,5 R -dihydroxy-3,8 S -dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3 S ,4 R ,16 S ,17 R )-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3- O - β -D-glucopyranoside (2), and new natural product ( S )-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea . Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7 , 9 and 14 showed antioxidant activities with IC 50 values of 68.9, 50.8 and 48.2 μM, respectively.

Background: T cell exhaustion (TEX) heterogeneity leads to unfavorable immunotherapeutic responses in patients with cancer. Classification of TEX molecular phenotypes is pivotal to overcoming TEX and improving immunotherapies in the clinical setting. Cuproptosis is a novel form of programmed cell death associated with tumor progression. However, the relation between cuproptosis-related genes (CuRGs) and the different TEX phenotypes has not been investigated in lung adenocarcinoma (LUAD). Methods: Unsupervised hierarchical clustering and principal component analysis (PCA) algorithm were performed to determine CuRGs-related molecular subtypes and scores for patients with LUAD. The tumor immune microenvironment (TIME) landscape in these molecular subtypes and scores was estimated using ESTIMATE and ssGSEA algorithms. Furthermore, TEX characteristics and phenotypes were evaluated in distinct molecular subtypes and scores through GSVA and Spearman correlation analysis. Finally, TIDE scores, immunophenoscore, pRRophetic, GSE78220, and IMvigor210 datasets were employed to appraise the distinguishing capacity of CuRGscore in immunotherapy and pharmacotherapy effectiveness. Results: We identified three CuRGclusters, three geneClusters, and CuRGscore based on 1012 LUAD transcriptional profiles from five datasets. Compared with other molecular subtypes, CuRGcluster B, geneCluster C, and low-CuRGscore group with good prognosis presented fewer TEX characteristics, including immunosuppressive cells infiltration and TEX-associated gene signatures, signal pathways, checkpoint genes, transcription and inflammatory factors. These molecular subtypes were also responsive in distinguishing TEX phenotype in the terminal, GZMK+, and OXPHOS- TEX subtypes, but not the TCF7+ TEX subtype. Notably, copper importer and exporter, SLC31A1 and ATP7B, were remarkably associated with four TEX phenotypes and nine checkpoint genes such as PDCD1 , CTLA4 , HAVCR2 , TIGIT , LAG3 , IDO1 , SIGLEC7 , CD274 , PDCD1LG2 , indicating that cuproptosis was involved in the development of TEX and immunosuppressive environment in patients with LUAD. Moreover, CuRGscore was significantly related to the TIDE score, immunophenoscore, and terminal TEX score (Spearman R = 0.62, p < 0.001) to effectively predict immunotherapy and drug sensitivity in both training and external validation cohorts. Conclusion: Our study demonstrated the extensive effect of cuproptosis on TEX. CuRGs-related molecular subtypes and scores could illuminate the heterogeneity of TEX phenotype as reliable tools in predicting prognosis and directing more effective immunotherapeutic and chemotherapeutic strategies for patients with LUAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Deng, Wang, Rahat, Sun and Zhang.)

Monocyte chemotactic protein-1 (MCP-1) is known to be able to facilitate vascular endothelial growth factor (VEGF) gene expression, hence promoting vascular hyperpermeability and neovascularization. We show here that a microRNA molecule, miR-374b-5p can target the 3'-untranslated region of the VEGF mRNA, thus preventing VEGF production. Additionally, MCP-1 promotes the acetylation of transcription factor stat3 at Lys685, which facilitates the formation of an ac-stat3-DNA methyltransferase-histone methyltransferase complex (ac-stat3/DNMT1/EZH2) that binds to the promoter of the miR-374b-5p gene. This results in diminished miR-374b-5p expression and enhanced VEGF production. Moreover, treatment of appropriate animal models either with a miR-374b-5p mimicry or with inhibitors of either stat3 acetylation, DNMT1, or EZH2, leads to marked inhibition of MCP-1-promoted neovascularization and tumor growth. These findings indicate that MCP-1 facilitated inhibition of miR-374b-5p gene expression leads to the removal of a block of VEGF mRNA translation by miR-374b-5p. This mechanism could be of importance in the modulation of inflammatory conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Extracellular vesicles (EVs) were reported to participate in various cellular processes based on the biomolecules, particularly microRNAs. Numerous commercial EVs isolation reagents are available. However, whether these reagents are suitable for separating EVs from the culture medium supernatant supernatant of model cell lines, such as HepG2, and whether the isolated products are suitable for High-throughput sequencing remains unclear. Methods: We examined three commonly used EVs isolation kits: the ExoQuick-TC exosome precipitation solution (EQ), Total Exosome Isolation from cell culture medium (EI), and exoEasy Maxi Kit (EM), to isolate EVs from HepG2 cell culture medium supernatants. EVs were identified based on marker proteins, particle size measurements, and electron microscopy analysis. The total amounts of microRNA and microRNA High-throughput sequencing data quality from EVs isolated by each kit were compared. Results: The total amount of EVs' microRNA isolated from the EI and EM groups were higher than that obtained from the EQ group (EQ/EI: p = 0.036, EI/EM: p = 0.024). High-throughput sequencing data quality evaluation showed that the EI group possessed higher quality than those in the EM group. Conclusion: For the cell culture medium from HepG2, EVs' microRNA isolated by EI reagents might be more suitable for High-throughput sequencing applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiong, Fan, Chen, Huang, Quan, Yi, Xiao, Huang and Hu.)

Deep learning is an artificial intelligence technique in which models express geometric transformations over multiple levels. This method has shown great promise in various fields, including drug development. The availability of public structure databases prompted the researchers to use generative artificial intelligence models to narrow down their search of the chemical space, a novel approach to chemogenomics and de novo drug development. In this study, we developed a strategy that combined an accelerated LSTM&#95;Chem (long short-term memory for de novo compounds generation), dense fully convolutional neural network (DFCNN), and docking to generate a large number of de novo small molecular chemical compounds for given targets. To demonstrate its efficacy and applicability, six important targets that account for various human disorders were used as test examples. Moreover, using the M protease as a proof-of-concept example, we find that iteratively training with previously selected candidates can significantly increase the chance of obtaining novel compounds with higher and higher predicted binding affinities. In addition, we also check the potential benefit of obtaining reliable final de novo compounds with the help of MD simulation and metadynamics simulation. The generation of de novo compounds and the discovery of binders against various targets proposed here would be a practical and effective approach. Assessing the efficacy of these top de novo compounds with biochemical studies is promising to promote related drug development., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

To evaluate the efficacy and safety of sodium oligomannate in the treatment of Alzheimer's disease. Patients with mild-to-moderate AD were randomly divided into three groups, the scores of ADAS-Cog, ADL, CIBIC-plus, NPI and CSDD were evaluated at the 0th, 12th, 24th, 36th and 48th weeks of medication. Comparing the mean scores of each scale in each cycle of each group. Using SPSS21.0 software for measurement data using t test, Chi-square test was used for counting data. A total of 72 patients with AD were included. The difference of CIBIC-plus score at week 12(P=0.007) and 24(P=0.005), ADAS-Cog scores (P=0.01) at week 24 in GV-971 group was statistically significant compared with that in the control group. The CIBIC-plus score at week 24(P=0.01) and week 48 (P=0.04), CSDD scores at week 48(P=0.02) of GV-971 group was statistically significant compared with that of donepezil group. There were 2 cases of adverse reaction of increased stool frequency in GV-971 (5.67%), and 2 cases of adverse reaction of nausea in donepezil group (8.33%), the difference was statistically significant. GV-971 is as effective as donepezil in the treatment of Alzheimer's disease, and may even be better. It has good safety.

The magnetic manipulation of droplets is one of the emerging magnetofluidic technologies that integrate multiple disciplines, such as electromagnetics, fluid mechanics and so on. The directly driven droplets are mainly composed of ferrofluid or liquid metal. This kind of magnetically induced droplet manipulation provides a remote, wireless and programmable approach beneficial for research and engineering applications, such as drug synthesis, biochemistry, sample preparation in life sciences, biomedicine, tissue engineering, etc. Based on the significant growth in the study of magneto droplet handling achieved over the past decades, further and more profound explorations in this field gained impetus, raising concentrations on the construction of a comprehensive working mechanism and the commercialization of this technology. Current challenges faced are not limited to the design and fabrication of the magnetic field, the material, the acquisition of precise and stable droplet performance, other constraints in processing speed and so on. The rotational devices or systems could give rise to additional issues on bulky appearance, high cost, low reliability, etc. Various magnetically introduced droplet behaviors, such as deformation, displacement, rotation, levitation, splitting and fusion, are mainly introduced in this work, involving the basic theory, functions and working principles.

Assembling genomes from single-cell sequencing data is essential for single-cell studies. However, single-cell assemblies are challenging due to (i) the highly non-uniform read coverage and (ii) the elevated levels of sequencing errors and chimeric reads. Although several assemblers for single-cell data have been proposed in recent years, most of them fail to construct correct long contigs. In this study, we present a new framework called EPGA-SC for de novo assembly of single-cell sequencing reads. The EPGA assembler has designed strategies to solve the problems caused by sequencing errors, sequencing biases, and repetitive regions. However, the extremely unbalanced and richer error types prevent EPGA to achieve high performance in single-cell sequencing data. In this study, we designed EPGA-SC based on EPGA. The main innovations of EPGA-SC are as follows: (i) classifying reads to reduce the proportion of false reads; (ii) using multiple sets of high precision paired-end reads generated from the high precision assemblies produced by other assembler such as SPAdes to overcome the impact of sequencing biases and repetitive regions; and (iii) developing novel algorithms for removing chimeric errors and extending contigs. We test EPGA-SC with seven datasets. The experimental results show that EPGA-SC can generate better assemblies than most current tools in most time in term of MAX contig, N50, NG50, NA50, and NGA50.

The complete mitochondrial (mt) genome of Micromus paganus (Linnaeus, 1767) (Neuroptera: Hemerobiidae: Microminae) was assembled and the phylogenetic analysis of Chrysopoidea was conducted. The mt genome was 16,607 bp long including 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a control region (CR). Twelve PCGs started with typical ATN, but COI initiated with TCG. The control region was 1335 bp long and the base composition was 89.66% of A + T. Phylogenetic analysis revealed that M. paganus was the sister group to Micromus sp. + M. angulatus . Hemerobiinae and Microminae were recovered monophyletic with high support values. However, the monophyly of Drepanepteryginae was not recovered, which needed more samplings from this subfamily in the further study. The closer relationship between Microminae and Drepanepteryginae was supported. Hemerobiidae was demonstrated monophyletic and being the sister group to Chrysopidae., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The computed tomography angiography (CTA) Spot Sign is an effective means of predicting hematoma expansion (HE) in the context of spontaneous intracerebral hemorrhage (ICH). We investigated whether continuous CTA source images could differentiate the Spot Sign and blood vessels in the hematoma, and whether it would improve Spot Sign accuracy as an HE predictor. We screened for the presence of CTA Spot Sign in individuals affected by spontaneous ICH within 24 h of symptom development. Based on our findings, we determined the sensitivity, specificity, and positive/negative predictive values of this sign as a predictor of HE both on its own and following the exclusion of blood vessels. In addition, a receiver-operating characteristic approach was used to assess the accuracy of Spot Sign with and without elimination of vascular interference. A total of 265 patients were included in this study. The Spot Sign was observed in 100 patients, including in 29 patients wherein it was confirmed to be blood vessels as determined based upon continuous CTA source images. With respect to predicting HE, Spot Sign sensitivity, specificity, positive predictive values, and negative predictive values were 57%, 71%, 48% and 78%, respectively. Following the exclusion of blood vessels, these values were 57%, 87%, 68% and 81%, respectively. Spot Sign area under the curve after excluding blood vessels was 0.718, which was higher than that of the Spot Sign (0.638). After continuous CTA, source images are used to exclude blood vessels in the hematoma, the Spot Sign is thus more accurate in predicting HE.

Background: Chewable areca products are popular in Asian countries, including India, Pakistan, Malaysia, and China. The major alkaloids present in areca products are guvacine, arecaidine, guvacoline, and arecoline which cause carcinogenicity and addiction., Objective: The objective of this study was the quantitative analysis of the alkaloid content of areca chewable products from different countries and regions using HPLC-UV, as well as the benefit of their safety evaluation products., Method: An HPLC-UV method was established for qualitative and quantitative analyses of 65 batches of areca chewable products from different countries and regions. Additionally, similarity evaluation of chromatographic fingerprints was applied for data analysis., Results: These results reveal a significant variation in the levels of areca alkaloids among tested products, specifically guvacoline (0.060-1.216 mg/g), arecoline (0.376-3.592 mg/g), guvacine (0.028-1.184 mg/g), and arecaidine (0.184-1.291 mg/g). There were significant differences in the alkaloid content of areca chewable products from different producing areas., Conclusions: The method will be useful in the safety evaluation of different areca chewable products., Highlights: The established HPLC-UV method can be adopted for safety evaluation of areca chewable products from different countries and regions due to its general applicability., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Catalytic asymmetric reactions in which water is a substrate are rare. Enantioselective transition-metal-catalyzed insertion of carbenes into the O-H bond of water can be used to incorporate water into the stereogenic center, but the reported chiral catalysts give good results only when α-aryl-α-diazoesters are used as the carbene precursors. Herein we report the first highly enantioselective O-H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors, with catalysis by a combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides. Participation of the phosphoric acids or phosphoramides in the carbene transfer reaction markedly suppressed competing side reactions, such as β-H migration, carbene dimerization, and olefin isomerization, and thus ensured good yields of the desired products. Fine-tuning of the ester moiety facilitated enantiocontrol of the proton transfer reactions of the enol intermediates and resulted in excellent enantioselectivity. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters, which readily undergo various transformations and can thus be used for the synthesis of bioactive compounds. Mechanistic studies revealed that the phosphoric acids and phosphoramides promoted highly enantioselective [1,2]- and [1,3]-proton transfer reactions of the enol intermediates. Maximization of molecular orbital overlap in the transition states of the proton transfer reactions was the original driving force to involve the proton shuttle catalysts in this process.

A highly efficient asymmetric Michael addition of thiols to exocyclic enones was achieved by using chiral spiro phosphoramide catalysts. The precisely chiral control in the protonation of the enol intermediate ensured high enantioselectivity. The reaction features high activity (yields up to 99%, turnover numbers up to 8400) and high enantioselectivity (up to 97% ee) with a broad substrate scope, and it has the potential for wide application in the synthesis of chiral sulfides.

In this study, ultraviolet (UV) irradiation, ozonation (O 3 ) and their combination (UV/O 3 ) were used to decompose clofibric acid (CA). The results show that UV system exhibited a very high CA removal rate (0.20 min -1 ) but the lowest mineralization (14.8%) accompanied by the formation of more toxic products. Ozonation achieved a much lower removal rate (0.05 min -1 ) but a higher mineralization efficiency (22.7%) in comparison with UV photolysis. The introduction of UV irradiation into O 3 system significantly enhanced the removal rate (0.21 min -1 ) and the mineralization efficiency (68.2%) of CA. The acute toxicity of the reaction solution to Daphnia magna in the UV/O 3 process increased during the first 20 min and then decreased, which illustrates that UV/O 3 is an effective and safe method for the removal of CA. The intermediate products were identified by LC-MS analysis and the degradation pathways for all the three processes were proposed. The direct photolysis and hydrous electron reduction contributed to the CA elimination in UV alone process. In O 3 alone system, the removal of CA occurred via direct ozone oxidation and indirect free radical oxidation. The free radical, ozone, hydrous electron and direct photolysis were involved in the degradation of CA in the UV/O 3 process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this research, the corrosion behavior of printed circuit boards with an immersion silver layer (PCB-ImAg) exposed to Bacillus cereus bacteria in Luria-Bertani broth was investigated. The growth test demonstrated that B. cereus had a high copper tolerance. Analysis of surface and cross-sectional view of the samples after immersion test indicated that metabolites produced by B. cereus accelerated the microporous corrosion of PCB-ImAg, and the biofilm that adhered to the surface led to oxygen concentration corrosion. Electrochemical impedance spectroscopy tests confirmed that the microbiologically influenced corrosion of PCB-ImAg was related to the biofilm formation and metabolism.

Neuroptera (lacewings) is one of the ancient holometabolous insect groups, but some extant species stand as important natural enemies for biological control. As the capital city of China, Beijing has a rich fauna of Neuroptera, previously with 47 species recorded and sorted in 32 genera of seven families. In this study, DNA barcoding based on sequences of COI gene fragments is used to discriminate lacewing species from Beijing. 217 DNA barcode sequences belonging to 49 species were successfully obtained. The COI barcode data worked well for identification of almost all lacewing species herein examined except Pseudomalladaprasinus (Burmeister), in which cryptic species may exist. Twenty species of Neuroptera are newly recorded from Beijing. Besides, Nothochrysinae is first recorded from Beijing. Chrysopidiaciliata (Wesmael) and Drepanepteryxalgida (Erichson) are first recorded from China.

The role played by mould in the electrochemical migration (ECM) behaviour of an immersion silver finished printed circuit board (PCB-ImAg) under a direct current (DC) bias was investigated. An interesting phenomenon is found whereby mould, especially Aspergillus niger, can preferentially grow well on PCB-ImAg under electrical bias and then bridge integrated circuits and form a migration path. The cooperation of the mould and DC bias aggravates the ECM process occurring on PCB-ImAg. When the bias voltage is below 15V, ECM almost does not occur for Ag coating. Mechanisms that explain the ECM processes of PCB-ImAg in the presence of mould and DC bias are proposed., (Copyright © 2017. Published by Elsevier B.V.)

The influence of Bacillus subtilis (BS) on tin-coated copper in an aqueous environment was investigated by exposing the sample to a culture medium inoculated with BS. Scanning electron microscopy, electrochemical measurements and chemical analyses were performed to study the corrosion mechanism. The experimental results show that BS can adhere and gather on the surface of the sample, resulting in oxygen consumption at the place where the bacteria are densely attached. Increases in the R ct values after the initial immersion showed that corrosion was inhibited, while decreases in the R ct values after the later immersion showed that corrosion was accelerated. Our results suggest that differences in oxygen concentration due to activity of BS are the main reason for corrosion of tin-coated copper., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The electrochemical corrosion behavior of a silver-plated circuit board (PCB-ImAg) in a polluted marine atmosphere environment (Qingdao in China) is studied through a simulated experiment. The morphologies of PCB-ImAg show some micropores on the surface that act as the corrosion-active points in the tests. Cl - mainly induces microporous corrosion, whereas SO₂ causes general corrosion. Notably, the silver color changes significantly under SO₂ influence. EIS results show that the initial charge transfer resistance in the test containing SO₂ and Cl - is 9.847 × 10³, while it is 3.701 × 10⁴ in the test containing Cl - only, which demonstrates that corrosion accelerates in a mixed atmosphere. Polarization curves further show that corrosion potential is lower in mixed solutions (between -0.397 V SCE and -0.214 V SCE) than it in the solution containing Cl - only (-0.168 V SCE), indicating that corrosion tendency increases with increased HSO₃ - concentration., Competing Interests: The authors declare no conflict of interest.

We report the first intramolecular enantioselective cyclopropanation of indoles, which was accomplished in good to high yield (up to 94%) with excellent enantioselectivity (up to >99.9% ee) by using copper or iron complexes of chiral spiro bisoxazolines as catalysts. This reaction is a straightforward, efficient method for constructing polycyclic compounds with an all-carbon quaternary stereogenic center at the 3-position of the indole skeleton, a core structure shared by numerous natural products and bioactive compounds.

We report a protocol for the highly efficient iridium-catalyzed asymmetric hydrogenation of racemic α-substituted lactones via dynamic kinetic resolution. Using Ir-SpiroPAP ( R )- 1d as a catalyst, a wide range of chiral diols were prepared in a high yield (80-95%) with a high enantioselectivity (up to 95% ee) under mild reaction conditions. This protocol was used for enantioselective syntheses of (-)-preclamol and a chiral 2,5-disubstituted tetrahydropyran.

The electrochemical migration (ECM) behavior of copper-clad laminate (PCB-Cu) and electroless nickel/immersion gold printed circuit boards (PCB-ENIG) under thin electrolyte layers of different thicknesses containing 0.1 M Na₂SO₄ was studied. Results showed that, under the bias voltage of 12 V, the reverse migration of ions occurred. For PCB-Cu, both copper dendrites and sulfate precipitates were found on the surface of FR-4 (board material) between two plates. Moreover, the Cu dendrite was produced between the two plates and migrated toward cathode. Compared to PCB-Cu, PCB-ENIG exhibited a higher tendency of ECM failure and suffered from seriously short circuit failure under high relative humidity (RH) environment. SKP results demonstrated that surface potentials of the anode plates were greater than those of the cathode plates, and those potentials of the two plates exhibited a descending trend as the RH increased. At the end of the paper, an electrochemical migration corrosion failure model of PCB was proposed.

Intracellular tension is the most important characteristic of neuron polarization as well as the growth and regeneration of axons, which can be generated by motor proteins and conducted along the cytoskeleton. To better understand this process, we created Förster resonance energy transfer (FRET)-based tension probes that can be incorporated into microfilaments to provide a real-time measurement of forces in neuron cytoskeletons. We found that our probe could be used to assess the structural tension of neuron polarity. Nerve growth factor (NGF) upregulated structural forces, whereas the glial-scar inhibitors chondroitin sulfate proteoglycan (CSPG) and aggrecan weakened such forces. Notably, the tension across axons was distributed uniformly and remarkably stronger than that in the cell body in NGF-stimulated neurons. The mechanosensors talin/vinculin could antagonize the effect of glial-scar inhibitors via structural forces. However, E-cadherin was closely associated with glial-scar inhibitor-induced downregulation of structural forces. Talin/vinculin was involved in the negative regulation of E-cadherin transcription through the nuclear factor-kappa B pathway. Collectively, this study clarified the mechanism underlying intracellular tension in the growth and regeneration of axons which, conversely, can be regulated by talin and E-cadherin.

Fusarium graminearum is the major causal agent of Fusarium head blight (FHB) of wheat and barley and is considered to be one of the most devastating plant diseases worldwide. Chitin is a critical component of the fungal cell wall and is polymerized from UDP-N-acetyl-alpha-D-glucosamine by chitin synthase. We characterized FgCHS8, a new class of the chitin synthase gene in F. graminearum. Disruption of FgCHS8 resulted in reduced accumulation of chitin, decreased chitin synthase activity, and had no effect on conidia growth when compared with the wild-type isolate. ΔFgCHS8 had a growth rate comparable to that of the wild-type isolate in vitro. However, ΔFgCHS8 had reduced growth when grown on agar supplemented with either 0.025% SDS or 0.9 mM salicylic acid. ΔFgCHS8 produced significantly less deoxynivalenol and exhibited reduced pathogenicity in wheat spikes. Re-introduction of a functional FgCHS8 gene into the ΔFgCHS8 mutant strain restored the wild-type phenotypes. Fluorescence microscopy revealed that FgCHS8 protein was initially expressed in the septa zone, and then gradually distributed over the entire cellular membrane, indicating that FgCHS8 was required for cell wall development. Our results demonstrated that FgCHS8 is important for cell wall sensitivity to environmental stress factors and deoxynivalenol production in F. graminearum., (Copyright © 2016 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

An iridium complex with a newly prepared chiral spiro amino-phosphine ligand efficiently catalyzed the hydrogenation of both β-aryl-β-methyl-nitroalkenes and β-alkyl-β-methyl-nitroalkenes to the corresponding saturated nitroalkanes, which represents the first report of a chiral catalyst that exhibits high enantioselectivity for the challenging hydrogenation of β,β-dialkyl-nitroalkenes.

Background: In this prospective case series, we aimed to characterise the temporal evolution of functional and structural measures in the afferent visual pathway of patients with acute optic neuritis (ON)., Methods: Fifty patients with ON were followed over 12 months. Testing with spectral-domain optical coherence tomography, Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (LogMAR) visual acuity and Humphrey perimetry central 30-2 threshold (SITA strategy) was performed at baseline, 3, 6 and 12 months after symptom onset. The main outcome measure was mean peripapillary retinal nerve fibre layer (RNFL) thickness in ON eyes. Secondary outcomes included mean ganglion cell layer (GCL) thickness, LogMAR visual acuity, and Humphrey perimetry measured visual field mean deviation (VFMD). Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test., Results: Over 12 months, RNFL and GCL values progressively declined in ON eyes, and intereye differences were significantly different across all time points. When functional recovery was defined as a VFMD better than -5.00 dB in ON eyes, the mean recovery time for the entire cohort was 3 months (survival was 48%, SE=0.09, 95% CI 0.30 to 0.64). There were significant differences in cumulative recovery when comparisons were made between genders: 3 months after symptom onset there was a higher percentage cumulative recovery for female (75%) versus male (25%) patients., Conclusions: Structural and functional measures evolve over time in patients with ON. There may be sex-specific differences in recovery after an acute ON event., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The increase of protein-protein interaction (PPI) data of different species makes it possible to identify common subnetworks (conserved protein complexes) across species via local alignment of their PPI networks, which benefits us to study biological evolution. Local alignment algorithms compare PPI network of different species at both protein sequence and network structure levels. For computational and biological reasons, it is hard to find common subnetworks with strict similar topology from two input PPI networks. Consequently some methods introduce less strict criteria for topological similarity. However those methods fail to consider the differences of the two input networks and adopt equally lenient criteria on them. In this work, a new dividing-and-matching-based method, namely UEDAMAlign is proposed to detect conserved protein complexes. This method firstly uses known protein complexes or computational methods to divide one of the two input PPI networks into subnetworks and then maps the proteins in these subnetworks to the other PPI network to get their homologous proteins. After that, UEDAMAlign conducts unequally lenient criteria on the two input networks to find common connected components from the proteins in the subnetworks and their homologous proteins in the other network. We carry out network alignments between S. cerevisiae and D. melanogaster, H. sapiens and D. melanogaster, respectively. Comparisons are made between other six existing methods and UEDAMAlign. The experimental results show that UEDAMAlign outperforms other existing methods in recovering conserved protein complexes that both match well with known protein complexes and have similar functions.

In this work, crude polysaccharide extracts were obtained from mycelia of the edible fungus Ganoderma capense (Lloyd) Teng. After removal of proteins by the Sevage method, fractionation and purification by anion-exchange and gel-permeation chromatography, a polysaccharide (GCPB-3) was isolated. The relative molecular weight of GCPB-3 was 124kDa determined by high performance gel permeation chromatography (HPGPC). The homogeneous polysaccharide was composed of d-xylose and l-arabinose in the ratio of 1:1, and showed a specific optical rotation of [α]D(25)=+145°(c 1.0, H2O). Its structural features were determined by monosaccharide analysis, partial acid hydrolysis, methylation analysis, periodic acid oxidation, gas chromatography-mass spectrometry (GC-MS), Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy ((1)H, (13)C, HMQC and HMBC). The results characterized GCPB-3 as a heteropolysaccharide with backbone consisting of β-l-Arap and β-d-Xylp, linked with 1→4 sugar bonds. Interestingly, GCPB-3 showed some DPPH•- and hydroxy-radical scavenging activities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

High mobility group protein box1 (HMGB1) and its receptor-receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor, but the role of HMGB1-RAGE axis in hepatocellular carcinoma (HCC) especially its effects on metastasis and recurrence remains obscure. Here, we report the role of HMGB1-RAGE axis in the biological behaviors of HCC cell lines and the underlying molecular mechanism. We show that the expressions of HMGB1, RAGE, and extracellular HMGB1 increase consistently according to cell metastasis potentials, while the concentration of soluble form of RAGE (sRAGE) is inversely related to metastasis potential of HCC cells. Furthermore, our data show that rhHMGB1 promotes cellular proliferation, migration, and invasion, and increases the level of nuclear factor kappa B (NF-κB), while administrations of HMGB1-siRNA, RAGE-siRNA, anti-HMGB1 neutralizing antibody, anti-RAGE neutralizing antibody, and sRAGE inhibit cellular proliferation, migration, and invasion. Moreover, we also demonstrate that the expression of NF-кB is inhibited by knockdown of HMGB1 or RAGE. Collectively, these data demonstrate that HMGB1 activates RAGE signaling pathways and induces NF-кB activation to promote cellular proliferation, invasion, and metastasis, in HCC cell lines. Taken together, HMGB1-RAGE axis may become a potential target in HCC therapy.

The crude polysaccharides were extracted from fruits of Psidium guajava Linn. by hot water. After removal of proteins, isolation and purification by DEAE-52 Cellulose chromatography and Sephadex G-75 gel filtration, a polysaccharide (GP70-2) was obtained and structurally characterized. GP70-2 has a relative molecular weight of 74 kDa and was composed of D-galactose and L-arabinose in the ratio of 1:1, with a specific optical rotation of [a]D(25) = +101°. Structural characterization of this novel polysaccharide was carried out using infrared spectroscopy, methylation analyses, and NMR studies ((1)H, (13)C, (1)H-(1)H-COSY, HMQC, and HMBC). Based on the above data, the following structure was assigned to the repeated core unit of GP70-2: [Formula: see text]. This polysaccharide showed a concentration dependent DPPH· radical scavenging activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Rationale: Human genetics studies in African Americans have shown a strong correlation between polymorphisms in the ApoL1 gene and chronic kidney disease (CKD). To gain further insight into the etiology of ApoL1-associated kidney diseases, the determination of circulating levels of both wild type as well as ApoL1 variants could be of significant use. To date, antibodies that discriminate between all three ApoL1 variant forms (wild type, G1 and G2) are not available. We aimed to develop a rapid method for detecting and quantifying ApoL1 variants and total levels in plasma., Methods: Ultra-performance liquid chromatography (UPLC) and tandem mass spectrometry (MS/MS) in multiple-reaction monitoring acquisition mode was used to quantify ApoL1., Results: We demonstrated that it is feasible to detect and quantify ApoL1 variants (wild type, G1 and G2), and total ApoL1 concentrations in plasma. ApoL1 genotypes determined by LC/MS agreed perfectly with the traditional method DNA sequencing for 74 human subjects. The method exhibited at least three orders of linearity with a lower limit of quantification of 10 nM. Moreover, the method can readily be multiplexed for the quantification of a panel of protein markers in a single sample., Conclusions: The method reported herein obviates the need to perform DNA genotyping of ApoL1 variants, which is of significant value in cases where stored samples are unsuitable for DNA analysis. More importantly, the method could potentially be of use in the early identification of individuals at risk of developing CKD, and for the stratification of patients for treatment with future ApoL1-modifying therapies., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Hepatitis B virus infection remains 1 of the major health threats worldwide. Currently, lamivudine plus adefovir combination therapy or entecavir monotherapy is usually used for the treatment of patients with lamivudine-resistant chronic hepatitis B (CHB). However, there are few systematic comparisons between the efficacy of lamivudine plus adefovir and the efficacy of entecavir in the treatment of these patients., Objective: The goal of this systematic study and meta-analysis was to assess the efficacy of lamivudine plus adefovir compared with entecavir for the treatment of patients with lamivudine-resistant CHB., Methods: A comprehensive literature search of PUBMED, Web of Science, WANFANG database, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Review, were screened to obtain citations from January 1990 to January 2012 in this study. Data analysis was done by using the Review Manager Software 5.1., Results: Eight studies were suitable for analysis. A total of 696 patients with lamivudine-resistant CHB were studied and grouped according to treatment: 341 patients in the entecavir group and 355 patients in the lamivudine plus adefovir group. The results found that the rates of undetectable hepatitis B virus DNA levels, alanine aminotransferase normalization, hepatitis B e antigen loss, and hepatitis B e antigen seroconversion were not significantly different between the lamivudine plus adefovir group and the entecavir group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups. However, virologic breakthrough for the patients with lamivudine resistance was higher in the entecavir group than in the lamivudine plus adefovir group., Conclusions: For these CHB patients with lamivudine resistance, lamivudine plus adefovir was a better treatment option than entecavir alone., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)

Liver cells release the high mobility group box-1 (HMGB1) protein when exposed to lipopolysaccharides (LPSs). However, the timing and levels of protein released remain unclear. The present study aimed to characterize the secretion of the late pro-inflammatory cytokine HMGB1 by liver L02 and HepG2 cells. The human mononuclear macrophage cell line U937 was used as a control. Various concentrations of LPS were added to human U937, L02 and HepG2 cells for different durations, and the cells were analyzed at different time-points following this addition. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure cellular HMGB1 mRNA levels, western blotting was performed to detect HMGB1 in cellular supernatants and the translocation of HMGB1 from the nucleus to the cytosol was examined using immunofluorescence staining. L02 and HepG2 cells exhibited higher HMGB1 mRNA levels compared with the control U937 cells 20 and 24 h following continuous exposure to LPS. U937 cells exhibited higher HMGB1 mRNA levels compared with the corresponding L02 and HepG2 cells 16 h following LPS exposure. The phase of HMGB1 protein detected in the cellular supernatants of L02 and HepG2 cells (16 h) was later than that of U937 cells (8 h). For the three cell lines, HMGB1 levels demonstrated a time dependency; however, the protein level was the highest in U937 cells. In the three cell lines, translocation of HMGB1 from the nucleus to the cytosol occurred; however, the phases of HMGB1 translocation in L02 and HepG2 cells occurred later than in U937 cells. LPS-induced secretion of the late pro‑inflammatory cytokine HMGB1 by liver cells is characterized by a late phase of release and smaller quantity, and the process of HMGB1 secretion appears to be associated with HMGB1 translocation.

Objective: The primary objective of this study was to explore the potential influence of gender on recovery from optic neuritis (ON) by determining whether differences in retinal nerve fiber layer (RNFL) thickness can be detected between men and women 6 months after an ON event., Methods: In this prospective cohort study, 39 men and 105 women with acute ON underwent repeat visual and optical coherence tomography (OCT) testing. The main outcome measures were change in RNFL measurements for male and female patients 6 months after ON., Results: Men were older (mean age = 39 years) than women (35 years) (p = 0.05) in this study, and more men (62%) than women (41%) had a diagnosis of relapsing-remitting multiple sclerosis (MS) (p = 0.02). Because age and MS subtype were 2 significant covariates, both variables were controlled for in multiple regression analyses. Other covariates controlled for in the multivariate regression included disease duration (years), use of disease-modifying therapy (yes/no), and use of high-dose corticosteroids for acute ON (yes/no). After 6 months, mean RNFL values were lower in men (74 μm) than women (91 μm) (p < 0.001). Men showed more apparent change in RNFL thickness in their ON eyes from baseline to 6 months after ON than women (p = 0.003)., Conclusions: There may be differences in recovery between men and women after ON, which can be difficult to detect with conventional visual testing. Our findings raise interesting questions about the potential influence of gender in MS, which may be explored in future studies.

Macrophages play an important role in tumor inflammatory microenvironment, lipoxin (LX), the 'stop signal' for inflammation, has been extensively studied preclinically for its anti-inflammatory or inflammatory pro-resolving effect. Here, we showed that LXA(4) could promote the apoptosis and inhibit the proliferation, migration and angiogenesis of HepG2 hepatocarcinoma cells stimulated by lipopolysaccharide (LPS) or activated macrophage-conditioned media (ACM). Moreover, BML-111, the analog of LXA(4), effectively inhibited the proliferation, invasion and angiogenesis of tumor in H22 hepatocarcinoma cell bearing mice. These results showed that LXA(4) could be a possible candidate for liver cancer therapy, and blocking the activation of macrophages would be an effective drug target., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT) are used to lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG). We report long-term follow-up data comparing SLT to ALT., Design: Follow-up of prospective randomized clinical trial., Participants: Patients with glaucoma from the practices of three ophthalmologists at the University of Ottawa., Methods: We randomized 176 eyes of 152 patients with uncontrolled IOP on maximal tolerated medical therapy (MTMT, with or without previous ALT) to undergo either SLT or ALT. Data were available for 142 eyes at 3 years, 134 eyes at 4 years, and 120 eyes at 5 years. The primary outcome was change in IOP from pretreatment baseline., Results: Comparison of baseline parameters was similar in the two groups. Lowering of IOP were similar at 3 years (SLT -6.7 ± 7.1 vs ALT -6.1 ± 5.1); at 4 years (SLT 7.0 ± 7.7 vs ALT -6.3 ± 5.0); and at 5 years (SLT -7.4 ± 7.3 vs ALT -6.7 ± 6.6). There was no statistically significant change in IOP in either of the two groups. Medication changes were equivalent in each group. A number of interventions were required in both groups, cumulatively, over the 5-year follow-up period (49 SLT and 33 ALT). Survival analysis indicated that the time to 50% failure in each group was approximately 2 years., Conclusions: The IOP-lowering effect of SLT and ALT was similar over 5 years in this group of patients with open-angle glaucoma on MTMT., (Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)