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The Taihu Lake region has undergone intensive land-use conversions from natural wetlands (NW) to conventional rice-wheat rotation fields (RW) and further to greenhouse vegetable fields (GH). Nevertheless, the effects of these conversions on soil microbes, particularly in wetland ecosystem, are not well explicit. To explore the impact of land-use intensification on soil microbial communities, monthly soil samples were obtained from replicate plots representing three land-use types (NW, RW, and GH) in subtropical wetlands and then subjected to amplicon sequencing. Land-use intensification had direct effects on bacterial and fungal community composition, with a more pronounced impact on bacteria than on fungi. These changes in bacterial communities were closely correlated with variations in soil environmental variables, such as NO 3 - -N, pH, and electrical conductivity. Land-use intensification led to a decrease in bacterial deterministic processes, with an opposing trend observed in the fungal community. In addition, arable lands (RW and GH), which are affected by anthropogenic activities, exhibited more complex networks. Potential metabolic functional groups in GH had higher absolute abundance. Seasonal variations significantly influenced microbial diversity, composition, and potential metabolic functional groups within each land-use type, particularly in summer, although the magnitude of this impact was much smaller than the impact of land-use intensification. Our findings emphasize the importance of comprehending the ecological consequences of land-use intensification in wetlands for sustainable resource management and biodiversity conservation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Potassium ion signaling mediates microbial communication in electroactive biofilms within microbial fuel cells (MFCs), but its role in nitrogen removal remains unclear. This study investigated the impact of inhibiting potassium signaling on nitrogen removal in MFCs using tetraethylammonium chloride (TEA) as an inhibitor. Results demonstrated that 5 mM and 10 mM TEA reduced the maximum power generation of MFCs from 77.95 mW/cm 2 to 57.18 mW/cm 2 and 48.23 mW/cm 2 , respectively. Correspondingly, total nitrogen (TN) removal efficiency was decreased from 46.57 ± 1.01% to 35.93 ± 0.63% and 38.97 ± 0.74%, respectively. This decline was attributed to inhibited potassium ion signaling, which compromised the electrochemical performance of the MFC and hindered the nitrogen removal process. The relative abundance of exoelectrogen Geobactor decreased from 15.37% to 5.17% and 8.05%, while the relative abundance of cathodic nitrifying bacteria Nitrosomonas decreased from 17.87% to 4.92% and 3.63% under 5 mM and 10 mM TEA. These findings underscore the crucial role of potassium ion signaling in enhancing the bioelectrochemical nitrogen removal process in MFCs., 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. Published by Elsevier Inc.)

Breast cancer is a major public health concern worldwide, being the most commonly diagnosed cancer among women and a leading cause of cancer-related deaths. Recent studies have highlighted the significance of non-histone methylation in breast cancer, which modulates the activity, interaction, localization, and stability of target proteins. This regulation affects critical processes such as oncogenesis, tumor growth, proliferation, invasion, migration, and immune responses. This review delves into the enzymes responsible for non-histone methylation, such as protein arginine methyltransferases (PRMTs), lysine methyltransferases (KMTs), and demethylases, and explores their roles in breast cancer. By elucidating the molecular mechanisms and functional consequences of non-histone methylation, this review aims to provide insights into novel therapeutic strategies targeting these pathways. The therapeutic potential of targeting non-histone methylation to overcome drug resistance and enhance treatment efficacy in breast cancer is also discussed, highlighting promising avenues for future research and clinical applications., 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. Published by Elsevier Ltd.)

The preservation of the native conformation and functionality of membrane proteins has posed considerable challenges. While detergents and liposome reconstitution have been traditional approaches, nanodiscs (NDs) offer a promising solution by embedding membrane proteins in phospholipids encircled by an amphipathic helical protein MSP belt. Nevertheless, a drawback of commonly used NDs is their limited homogeneity and stability. In this study, we present a novel approach to construct covalent annular nanodiscs (cNDs) by leveraging microbial transglutaminase (MTGase) to catalyze isopeptide bond formation between the side chains of terminal amino acids, specifically Lysine (K) and Glutamine (Q). This methodology significantly enhances the homogeneity and stability of NDs. Characterization of cNDs and the assembly of membrane proteins within them validate the successful reconstitution of membrane proteins with improved homogeneity and stability. Our findings suggest that cNDs represent a more suitable tool for investigating interactions between membrane proteins and lipids, as well as for analyzing membrane protein structures., (Copyright © 2024. Published by Elsevier Inc.)

Study Objective: HRAD± was developed to quickly assess pediatric perioperative affect and cooperation. HRAD± represents: Happy, Relaxed, Anxious, Distressed, with a yes/no answer to cooperativity. The primary aim of this study was to investigate the clinical utility of HRAD± as an affect and cooperation assessment tool for inhalational mask induction. Secondary aims examined inter-rater reliability (IRR) of HRAD± and predictive validity of induction HRAD± with emergence delirium., Design: This was a prospective observational investigation., Setting: We conducted this investigation at Lucile Packard Children's Hospital Stanford, an academic, quaternary care children's hospital in Northern California., Patients: A total of 197 patients were included in this investigation. Children 1-14 years of age, who underwent daytime procedures with inhalational induction of anesthesia and American Society of Anesthesiologists physical status I-III were eligible., Interventions: During mask induction, two trained research assistants (RAs) independently scored the patient's affect and cooperation. After extubation, the same investigators observed the patient's emergence., Measurements: RAs scored each mask induction using the following scales: HRAD±, modified Yale Preoperative Anxiety Scale (mYPAS), Observation Scale of Behavioral Distress (OSBD), and Induction Compliance Checklist (ICC). Correlations were calculated to HRAD±. IRR of HRAD± between the RAs as well as predictive validity of HRAD± to Pediatric Anesthesia Emergence Delirium (PAED), Watcha and Cravero scales were calculated., Main Results: HRAD± scores strongly correlated with mYPAS (r = 0.840, p < 0.0001) with moderate correlation to OSBD (r = 0.685, p < 0.0001) and ICC (-0.663, p < 0.0001). IRR was moderate for the affect and cooperation portion of the HRAD± scale, respectively (κ = 0.595 [p < 0.0001], κ = 0.478 [p < 0.0001]). A weak correlation was observed with PAED (r = 0.134 [p = 0.0597]) vs HRAD±. No correlations were observed between Watcha (r = 0.013 [p = 0.8559]) and Cravero and HRAD± scales (r = 0.002 [p = 0.9767])., Conclusions: HRAD± is a clinically useful and simple scale for evaluating pediatric affect and cooperation during inhalational mask induction. Results demonstrate correlation with commonly utilized research assessment scales., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN., Methods: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis., Results: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016)., Conclusion: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear., Objectives: This study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs., Methods: A total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group., Results: Herein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of β-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver., Conclusions: Using fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that the time of day (ToD) of ICI administration could impact the outcomes of patients with cancer. The consistency of ToD effects on ICI efficacy awaits initial evaluation., Materials and Methods: This meta-analysis integrates progression-free survival (PFS) and overall survival (OS) data from studies with a defined 'cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] of an earlier progression or death according to 'early' or 'late' ToD of ICIs were collected from each report and pooled., Results: Thirteen studies involved 1663 patients (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) with non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial cancer (5%), or esophageal carcinoma (4%). Most patients received anti-programmed cell death protein 1 or anti-programmed death-ligand 1 (98%), and a small proportion also received anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) (18%). ToD cut-offs were 13:00 or 14:00 (i.e. ICI median infusion time), for six studies, and 16:00 or 16:30 (i.e. reported threshold for weaker vaccination responses) for seven studies. Pooled analyses revealed that the early ToD groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) and PFS (HR 0.51, 95% CI 0.42-0.61; P < 0.00001) compared with the late ToD groups., Conclusions: Patients with selected metastatic cancers seemed to largely benefit from early ToD ICI infusions, which is consistent with circadian mechanisms in immune-cell functions and trafficking. Prospective randomized trials are needed to establish recommendations for optimal circadian timing of ICI-based cancer therapies., Competing Interests: Disclosure JBA reports grants, travel, and honoraria from Sanofi, GSK, and BMS; CC reports grants, travel, and honoraria from AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen, Viatris, Chugai, Pierre Fabre, and Amgen; and BD reports grants, travel, and honoraria from Roche, Pfizer, Astra Zeneca, Chiesi, Amgen, Lilly, Medscape, MSD, Sanofi, and Oxyvie. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lack of highly efficient, inexpensive, and easily available catalysts severely limits the practical applicability of electrochemically sensing assay towards 5-hydroxytryptamine (5-HT). Herein, four kinds of Fe-Co bimetallic Prussian blue analogues (FeCo-PBAs) with different molar ratios of Fe to Co were prepared using a simple coprecipitation method. Interestingly, Fe(III) in K 3 [Fe(CN) 6 ] can be reduced to Fe(II) by adding trisodium citrate dehydrate, which could offer a new clue to synthesize PBAs with Fe(II) core ions. With the optimizational FeCo-PBA synthesized at a 0.5/1 M ratio of Fe to Co as an electrocatalyst, the constructed sensor shows excellent comprehensive performance for the 5-HT assay with a high sensitivity of 0.856 μA μM -1 and an ultralow detection limit of 8.4 nM. Under the optimum conditions, linearity was obtained in the ranges of 0.1-10.0 μM and 10.0-200.0 μM and preferable recoveries ranged from 97.8% to 103.0% with relative standard deviation (RSD) < 4.0%. The integrated properties of FeCo-PBA can be comparable to previously reported electrocatalysts for the 5-HT assay including noble metal-based and expensive carbon (graphene and carbon nanotubes)-based electrocatalysts. The proposed sensor also exhibits outstanding selectivity, reproducibility, and practicality for real sample analyses. This work is the first report on the PBA-based sensor for the 5-HT assay, verifying the practicability of this high-performance sensor for the 5-HT assay., 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 B.V. All rights reserved.)

Pain is one of the most severe complications affecting the quality of life of cancer patients. Although substantial progress has been made in the diagnosis and treatment of cancer, the neurobiological mechanism of cancer pain is still unclear. In the present study, we identified the critical role of CXC chemokine 2 (CXCL2), released by Schwann cells after being activated by cancer cells, in maintaining cancer-induced macrophage infiltration and the resulting mechanical hypersensitivity and persistent spontaneous nociception. In vitro, Schwann cells cocultured with breast cancer cells exhibited a significant increase in CXCL2 expression; in addition, conditioned medium from Schwann cells activated by breast cancer cells had a similar effect to recombinant CXCL2 in terms of inducing macrophage migration. Targeting CXCL2 signaling by both CXC chemokine receptor 2 (CXCR2) antagonist pharmacological blockade and anti-CXCL2 mAb immunological blockade robustly prevented conditioned medium-induced macrophage migration. In vivo, both application of recombinant CXCL2 and perineural breast cancer cell implantation resulted in mechanical hypersensitivity and persistent spontaneous nociception in mice, along with increased macrophage infiltration into the sciatic nerves. Similar to the in vitro results, inhibition of CXCL2/CXCR2 signaling or conditional knockdown of CXCL2 in sciatic nerve Schwann cells effectively attenuated breast cancer cell-induced mechanical hypersensitivity, persistent spontaneous nociception, and macrophage recruitment in the sciatic nerve. Mechanistically, we found that redox effector factor-1 (Ref-1) secreted by breast cancer cells activated hypoxia inducible factor-1α (HIF-1α) expression and inhibited reactive oxygen species (ROS) production in Schwann cells, ultimately inducing CXCL2 expression in Schwann cells. In brief, the present study expands new insights into cancer pain mechanisms from promising animal models to provide new strategies for the control of cancer pain., 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 © 2023 Elsevier Inc. All rights reserved.)

Knee cartilage defects caused by osteoarthritis are major musculoskeletal disorders, leading to joint necrosis or even disability if not intervened at early stage. Deep learning has demonstrated its effectiveness in computer-aided diagnosis, but it is time-consuming to prepare a large set of well-annotated data by experienced radiologists for model training. In this paper, we propose a semi-supervised framework to effectively use unlabeled data for better evaluation of knee cartilage defect grading. Our framework is developed based on the widely-used mean-teacher classification model, by designing a novel dual-consistency strategy to boost the consistency between the teacher and student models. The main contributions are three-fold: (1) We define an attention loss function to make the network focus on the cartilage regions, which can both achieve accurate attention masks and boost classification performance simultaneously; (2) Besides enforcing the consistency of classification results, we further design a novel attention consistency mechanism to ensure the focusing of the student and teacher networks on the same defect regions; (3) We introduce an aggregation approach to ensemble the slice-level classification outcomes for deriving the final subject-level diagnosis. Experimental results show that our proposed method can significantly improve both classification and localization performances of knee cartilage defects. Our code is available on https://github.com/King-HAW/DC-MT., 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 B.V. All rights reserved.)

Zingiber officinale and Panax ginseng, as well-known traditional Chinese medicines, have been used together to clinically treat ulcerative colitis with synergistic effects for thousands of years. However, their compatibility mechanism remains unclear. In this study, the shift of gut microbiome and fecal metabolic profiles were monitored by 16S rRNA sequencing technology and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis, respectively, which aimed to reveal the synergistic mechanism of Zingiber officinale and Panax ginseng on the amelioration of ulcerative colitis. The results showed that the relative abundance of beneficial bacteria (such as Muribaculaceae&#95;norank, Lachnospiraceae NK4A136 group and Akkermansia) was significantly increased and the abundance of pathogenic bacteria (such as Bacteroides, Parabacteroides and Desulfovibrio) was markedly decreased after the intervention of Zingiber officinale-Panax ginseng herb pair. And a total of 16 differential metabolites related to ulcerative colitis were identified by the metabolomics analysis, which were majorly associated with the metabolic pathways, including arachidonic acid metabolism, tryptophan metabolism, and steroid biosynthesis. Based on these findings, it was suggested that the regulation of the gut microbiota-metabolite axis might be a potential target for the synergistic mechanism of Zingiber officinale-Panax ginseng herb pair in the treatment of ulcerative colitis. Furthermore, the integrated analysis of microbiome and metabolomics used in this study could also serve as a useful template for exploring the mechanism of other drugs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Polyethylene microplastics (PE-MPs) and glyphosate (GLY) occur widely and have toxic characteristics, resulting in increased research interest. In this study, common carp were used to assess the individual and combined toxicity of PE-MPs (0, 1.5, or 4.5 mg/L) and GLY (0, 5, or 15 mg/L) on the brain-gut axis. After 60 days of exposure, the developmental toxicity, blood-brain barrier (BBB), locomotor behavior, intestinal barrier (physical barrier, chemical barrier, microbial barrier), and intestinal content metabolism of common carp were evaluated. Results showed that 15 mg/L of GLY exposure significantly reduced the mRNA expression of tight-junction genes (occludin, claudin-2, and ZO-1) in the brain, and acetylcholinesterase (AChE) activity was clearly inhibited by high concentrations of GLY. However, different concentrations of PE-MPs had no significant effect on the activity of AChE. Furthermore, the free-swimming behavior of common carp was distinctly inhibited by treatment with a combination of 15 mg/L GLY and 4.5 mg/L PE-MPs. Histological studies indicated that PE-MPs alone and in combination with GLY could disrupt the physical and chemical intestinal barriers of common carp. Additionally, the abundance and diversity of gut microbiota in common carp were significantly changed when exposed to a combination of PE-MPs and GLY. Metabolomics further revealed that PE-MPs combined with GLY triggered metabolic changes and that differential metabolites were related to amino acid and lipid metabolism. These findings illustrate that exposure to PE-MPs or GLY alone is toxic to fish and results in physiological changes to the brain-gut axis. This work offers a robust analysis to understand the mechanisms underlying GLY and MP-induced aquatic toxicity., 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 © 2021 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic altered the workplace for medical education. As restrictions ease, the opportunities provided by virtual rotations remain. Radiation oncology rotations based on virtual participation with patients (consultations, follow-ups, and brachytherapy), contouring and reviewing external beam plans, didactics, and unstructured office hours have been well received at multiple institutions. Virtual rotations decrease barriers to access including lack of a radiation oncology department at one's home institute and the high cost of travel and housing. Furthermore, rotations can be adapted to preclinical students and those with prior radiation oncology rotation experience. However, the virtual format creates and exacerbates several challenges including technical difficulties with electronic medical record or treatment planning software, lack of the spontaneous interactions common to in-person rotations, and unexpected delays in the clinic. We recommend early scheduled time with information technology services to troubleshoot any potential issues, scheduled office hours with faculty and videoconferencing with nonphysician team members to mitigate omission of in-person introductions, and provision of complete contact information for all staff scheduled to meet with students to facilitate communication when unexpected clinic issues arise. Although we are all excited for quarantine restrictions to safely be lifted, we support the continued development of virtual away rotations as a flexible, more affordable option to increase exposure to the field., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are related to many biological processes and regarded as biomarkers of disease. Rapid, sensitive, and specific methods for miRNA assay are very important for early disease diagnostic and therapy. In the present work, an ultrasensitive electrochemical biosensing platform has been developed for miRNA-21 assay by combining CRISPR-Cas13a system and catalytic hairpin assembly (CHA). In the presence of miRNA-21, it would hybridize with the spacer region of Cas13a/crRNA duplex to activate the cleavage activity of CRISPR-Cas13a system, leading to the release of initiator of CHA to generate amplified electrochemical signals. Base on the CRISPR-Cas13a-mediated cascade signal amplification strategy, the developed electrochemical biosensing platform exhibited high sensitivity with a low detection limit of 2.6 fM (S/N = 3), indicating that the platform has great potential for application in early clinical diagnostic., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Objective: To automatically identify and locate various types and states of the ureteral orifice (UO) in real endoscopy scenarios, we developed and verified a real-time computer-aided UO detection and tracking system using an improved real-time deep convolutional neural network and a robust tracking algorithm., Methods: The single-shot multibox detector (SSD) was refined to perform the detection task. We trained both the SSD and Refined-SSD using 447 resectoscopy images with UO and tested them on 818 ureteroscopy images. We also evaluated the detection performance on endoscopy video frames, which comprised 892 resectoscopy frames and 1366 ureteroscopy frames. UOs could not be identified with certainty because sometimes they appeared on the screen in a closed state of peristaltic contraction. To mitigate this problem and mimic the inspection behavior of urologists, we integrated the SSD and Refined-SSD with five different tracking algorithms., Results: When tested on 818 ureteroscopy images, our proposed UO detection network, Refined-SSD, achieved an accuracy of 0.902. In the video sequence analysis, our detection model yielded test sensitivities of 0.840 and 0.922 on resectoscopy and ureteroscopy video frames, respectively. In addition, by testing Refined-SSD on 1366 ureteroscopy video frames, the sensitivity achieved a value of 0.922, and a lowest false positive per image of 0.049 was obtained. For UO tracking performance, our proposed UO detection and tracking system (Refined-SSD integrated with CSRT) performed the best overall. At an overlap threshold of 0.5, the success rate of our proposed UO detection and tracking system was greater than 0.95 on 17 resectoscopy video clips and achieved nearly 0.95 on 40 ureteroscopy video clips., Conclusions: We developed a deep learning system that could be used for detecting and tracking UOs in endoscopy scenarios in real time. This system can simultaneously maintain high accuracy. This approach has great potential to serve as an excellent learning and feedback system for trainees and new urologists in clinical settings., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: Prostate-specific G-protein coupled receptor (PSGR) in prostate cancer (Pca) are associated with poor overall survival. However, the effect of exosomal PSGR on PCa metastasis remains unknown., Main Methods: The effect of exosome derived from PSGR-overexpressed PC3 cells (PC3 PSGR+ exosomes) on migration, invasion, epithelial-mesenchymal transition (EMT) and stemness of low invasive cells (LNCaP and RWPE-1) was assessed. Transcriptome sequencing was performed to identify differentially expressed (DE) mRNAs in low invasive cells incubated by PC3 PSGR+ exosomes or negative control (NC) exosomes., Key Findings: The PSGR was stably overexpressed in PC3 cells. The PC3 PSGR+ exosomes were internalized in LNCaP and RWPE-1cells, and significantly promoted cells migration and invasion. The expression of E-cadherin was decreased, and Vimentin, Snail, SOX2 and OCT4a was increased in low invasive cells after PC3 PSGR+ exosome incubation. Additionally, a total of 993 and 1170 DE mRNAs were respectively identified in LNCaP and RWPE-1 cells after PC3 PSGR+ exosome incubation, and 5 upregulated mRNAs and 11 down regulated mRNAs were shared. The DE mRNAs were predominantly implicated in "activation of Rho GTPase activity" and "response to zinc ion" in LNCaP cells, and "extracellular matrix organization" and "patterning of blood vessels" in RWPE-1 cells. The KEGG analysis showed the DE mRNAs were enriched in pathways associated with EMT such as "Adherens junction", "Cell adhesion molecules (CAMs)" and "Focal adhesion"., Significance: Exosomal PSGR promoted migration, invasion, stemness and epithelial-mesenchymal transitions, and reshaped the mRNAs profiling of LNCaP and RWPE-1 cells., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of an educational intervention for type 2 diabetes mellitus (T2DM) in primary care in rural China, on fasting blood glucose (FBG) level and diabetes knowledge., Methods: Patients with T2DM (n = 1,589) in 18 township health centres in three counties in Jiangsu Province were randomly divided into an intervention group receiving educational intervention and follow-up visits, and a control group with standard care. Questionnaires and medical records, including FBG level and diabetes knowledge score, were compared, at baseline and follow-up. Propensity score matching and Difference-in-Difference analysis were used., Results: The FBG level decreased significantly in the intervention group compared to the control group, DID=-0.53 mmol/l, (CI95 % -0.90 to -0.16). The diabetes knowledge score increased significantly in the intervention group compared to the control group, DID = 0.91, (CI95 % 0.64-1.18). The FBG level and diabetes knowledge score improved significantly in the intervention group in all counties., Conclusions: The educational intervention and increased collaboration between hospitals and primary care improved the FBG level and diabetes knowledge score in the intervention group compared to the control group after one year., Practice Implications: Educational intervention and increased collaboration between hospitals and primary care may improve diabetes care in rural China., Competing Interests: Declaration of Competing Interest The authors (SC, DQ, KB, BB) declare they have no conflicting interests., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this study a systematic comparison in morphology, long-term degradation, regeneration and reuse were conducted between palladized and sulfidized nanoscale zero-valent iron (Pd-Fe and S-Fe). Pd-Fe and S-Fe were prepared, after the synthesis of precursor Fe 0 nanoparticles (spherical, ~35 nm radius) for carbon tetrachloride (CTC) treatment. With HAADF-TEM-EDS characterization, dispersive Pd islets were found on the Fe core of Pd-Fe. However, the Fe core was covered by the FeS x shell of S-Fe (FeS/FeS 2 = 0.47). With an excessive Pd dose (10 mol%), the Pd-Fe were dramatically deformed to dendritic structures which significantly decreased reactivity. For CTC degradation, Pd-Fe (0.3 atomic% Pd) increased the degradation rate by 20-fold (k sa = 0.580 Lm -2 min -1 ) while S-Fe presented a greater life time. The major intermediate chloroform (CF) was further degraded and less than 5% CF was observed after 24 h using Pd-Fe or S-Fe while above 50% CF remained using Fe. During aging, the Fe core was converted to FeOOH and Fe 3 O 4 /γ-Fe 2 O 3 . The restoration of Fe 0 was achieved using NaBH 4 , which regenerated Fe and Pd-Fe. However, the formed FeS x shell on S-Fe was disappeared. The results suggest that S-Fe extends longevity of Fe, but the loss of FeS x after aging makes S-Fe eventually perform like Fe in terms of CTC degradation., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Although the bioactive compounds in goji have been thoroughly identified and quantified, little information is available on the bitter compounds in the berries, and no systematic works on the substances responsible for their bitterness have been performed. Herein, the substances contributing to the bitterness of berries were isolated and purified from bitter-tasting goji by the combined use of column chromatography and high-pressure liquid chromatography (HPLC). The bitterness of the isolated compounds was evaluated using a biosensor with immobilized rat taste-bud tissues. The structures were elucidated via comprehensive mass spectrometry (MS) and nuclear magnetic resonance (NMR) analyses. Seven spermine or spermidine alkaloids were identified, including four new compounds (lyciamarspermidines A and B and lyciamarspermines A and B). The intensities of the bitterness levels of the isolated compounds differed with the number of glucose substituents. These isolated compounds all contribute to the bitterness of goji. The results of this study provide opportunities for the further investigation of the bitterness of goji., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anaplasma species are obligate intracellular pathogens that threaten the health of both humans and animals worldwide. This study aimed to determine the prevalence of Anaplasma species in stray dogs in Anhui Province, China. Blood samples from 201 apparently healthy stray dogs were collected from August 2017 to January 2018, and Anaplasma spp. infection in these dogs was evaluated by nested PCR and phylogenetic analysis. The overall infection rate of Anaplasma spp. in stray dogs was 38.3% (77/201). The prevalences of single infection of A. platys, A. phagocytophilum and A. ovis were 15.4%, 11.9%, and 8.5%, respectively. Co-infection rate of A. platys and A. phagocytophilum was 1.5% and that of A. platys and A. ovis was 0.5%. Co-infection by these three pathogens was found in one sample (0.5%). This is the first report of Anaplasma spp. infections in stray dogs from Anhui, China., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Most psoriasis-related genes or loci identified by GWAS represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR. Gene-based analysis was performed on the annotation results. A total of 250 and 35 genes in the Exome&#95;Fine and Exome&#95;Asian array cohorts, respectively, exceeded the threshold (P < 4.43 × 10 -6 ). Merged gene-based analysis was then conducted on the same set of SNPs from seven genes common to both arrays, and the chi-square test was used to confirm all gene-based results. Ultimately, four susceptibility genes were identified: BBS7 (P combine  = 1.38 × 10 -29 ), GSTCD (P combine  = 8.35 × 10 -47 ), LIPK (P combine  = 1.02 × 10 -19 ), and PPP4R3B (P combine  = 1.79 × 10 -33 ). This study identified four susceptibility genes for psoriasis via a gene-based method using rare variants, contributing to our understanding of the pathogenesis of psoriasis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing evidence has suggested that paracrine mechanisms might be involved in the underlying mechanism of mesenchymal stem cells (MSCs) transplantation, and exosomes are an important component of this paracrine role. However, MSCs are usually exposed to normoxia (21% O 2 ) in vitro but experience large differences in oxygen concentration in the body under hypoxia. Indeed, hypoxic precondition of MSCs can enhance their paracrine effects. The main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (Hypo-Exos) exhibit greater effects on bone fracture healing than those under normoxia (Exos). Using in vivo bone fracture model and in vitro experiments including cell proliferation assay, cell migration assay and so on, we confirmed that Hypo-Exos administration promoted angiogenesis, proliferation and migration to a greater extent when compared to Exos. Furthermore, utilizing a series in vitro and in vivo gain and loss of function experiments, we confirmed a functional role for exosomal miR-126 in the process of bone fracture healing. Meanwhile, we found that knockdown of hypoxia inducible factor 1 (HIF-1α) resulted in a significant decrease of miR-126 in MSCs and exosomes, thereby abolishing the effects of Hypo-Exos. In conclusion, our results demonstrated a mechanism by which Hypo-Exos promote bone fracture healing through exosomal miR-126. Moreover, hypoxia preconditioning mediated enhanced production of exosomal miR-126 through the activation of HIF-1α. Hypoxia preconditioning represents an effective and promising method for the optimization of the therapeutic actions of MSC-derived exosomes for bone fracture healing. STATEMENT OF SIGNIFICANCE: Studies have confirmed that transplantation of exosomes exhibit similar therapeutic effects and functional properties to directly-transplanted stem cells but have less significant adverse effects. However, during in vitro culture conditions, MSCs are usually exposed to normoxia (21% O 2 ) which is very different to the oxygen concentrations found in the body under natural physiological conditions. Our results demonstrated a mechanism by which Hypo-Exos promote bone fracture healing through exosomal miR-126 and the SPRED1/Ras/Erk signaling pathway. Moreover, hypoxia preconditioning mediated enhanced production of exosomal miR-126 through the activation of HIF-1α. Hypoxia preconditioning represents an effective and promising method for the optimization of the therapeutic actions of MSC-derived exosomes for bone fracture healing., (Copyright © 2019. Published by Elsevier Ltd.)

Aims: Severe acute pancreatitis (SAP) is an acute disease of the digestive system accompanied by pancreatic necrosis. We have found that bone marrow-derived mesenchymal stem cells (BMSCs) can attenuate SAP, but the underlying mechanism remains unclear. The present study was conducted to explore the possible mechanisms by which BMSCs alleviate SAP., Main Methods: BMSCs and BMSCs engineered to overexpress microRNA (miR)-9 (miR-9-BMSCs) were transplanted into rat models of SAP via the tail vein. Pancreatic acinar cells (PACs) were isolated from rat pancreatic tissues and induced by tumor necrosis factor-α (TNF-α) in vitro., Key Findings: miR-9-BMSCs significantly reduced the systemic inflammatory response, impeded the necroptosis signaling pathway and promoted regeneration of damaged pancreas in vivo. miR-9-BMSCs secreted miR-9, which targeted the gene encoding receptor interacting protein kinase 1 in PACs induced by TNF-α, to inhibit necroptosis and ameliorate SAP., Significance: miR-9-BMSCs can reduce SAP-induced injury to pancreatic tissues and PACs by regulating miR-9 to suppress necroptosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Taking advantage of the mesoporous structure of bismuth sulfide nanostars (Bi 2 S 3 NSs), a chemotherapeutic drug of doxorubicin (DOX) and a photosensitizer of chlorin e6 (Ce6) were concurrently loaded in the PEGylated Bi 2 S 3 NSs to formulate a multifunctional nanocomplex (BPDC NSs) for tumor theranostics. BPDC NSs have excellent photothermal conversion efficiency and a capacity of yielding reactive oxygen species (ROS) upon laser irradiation, and can realize on-demand drug release by either pH-activation or thermal induction. Accumulation of the nanodrug could be monitored in real-time by infrared thermal imaging, fluorescence imaging and computed tomography (CT). More importantly, the combination effects of photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy were demonstrated to dramatically suppress solid tumors without recurrence in vivo. Featuring low systemic toxicity and high biocompatibility, this nanoplatform could be a promising derivative of Bi 2 S 3 NSs for imaging-guided theranostics of cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1)., Methods: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated., Results: Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP., Conclusions: BMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and anti-oxidant effects, reduce apoptosis and promote angiogenesis., (Copyright © 2018 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

An innovative electrochemical sensor was fabricated for the sensitive and selective determination of tinidazole (TNZ), based on a carbon paste electrode (CPE) modified with multi-walled carbon nanotubes (MWCNTs) and boron-embedded molecularly imprinted composite membranes (B-MICMs). Density functional theory (DFT) calculations were carried out to investigate the utility of template-monomer interactions to screen appropriate monomers for the rational design of B-MICMs. The distinct synergic effect of MWCNTs and B-MICMs was evidenced by the positive shift of the reduction peak potential of TNZ at B-MICMs/MWCNTs modified CPE (B-MICMs/MWCNTs/CPE) by about 200 mV, and the 12-fold amplification of the peak current, compared with a bare carbon paste electrode (CPE). Moreover, the coordinate interactions between trisubstituted boron atoms embedded in B-MICMs matrix and nitrogen atoms of TNZ endow the sensor with advanced affinity and specific directionality. Thereafter, a highly sensitive electrochemical analytical method for TNZ was established by different pulse voltammetry (DPV) at B-MICMs/MWCNTs/CPE with a lower detection limit (1.25 × 10 -12  mol L -1 ) (S/N = 3). The practical application of the sensor was demonstrated by determining TNZ in pharmaceutical and biological samples with good precision (RSD 1.36% to 3.85%) and acceptable recoveries (82.40%-104.0%)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo, oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to describe the prevalence and associated factors of spectacles need and ownership among multiethnic school students in rural China., Study Design: School-based cross-sectional study., Methods: This school-based eye study was conducted in Yunnan province located in Southwestern China. Questionnaires were filled out by children with the help of their parents concerning demographic characteristics, spectacles usage, and myopia-related lifestyle exposures. Spectacles need was defined as participants who had an uncorrected visual acuity (VA) of less than 6/12 but could be corrected to more than 6/12 in the better-seeing eye, with myopia of less than -0.5 diopters (D), hyperopia of more than +2.0 D, or astigmatism of more than 0.75 D in both eyes. Definition of spectacles ownership was based on spectacles wearing at school on the examination day., Results: Among the 7681 students aged 5-16 years participating in this study, 7166 (93.3% of the study participants) successfully completed VA tests and questionnaires. The rate of spectacles need among children with an uncorrected VA of 6/12 or worse in either eye was 68.3% (623/912). Among the students who needed spectacles, only 18.9% owned them. Multivariate analyses revealed that spectacles ownership was significantly associated with increasing age (odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.08-1.55), more time on reading and writing (OR = 1.66; 95% CI: 1.15-2.40), having myopic friend(s) (OR: 1.90; 95% CI: 1.01-3.56), self-awareness of myopia (OR: 6.67; 95% CI: 2.48-17.92), and poorer uncorrected VA (OR: 4.57; 95% CI: 2.78-7.52)., Conclusions: We observed a lower rate of spectacles ownership among rural children compared with those of similar ages in urban China. These findings may have important public health implications for China and other countries regarding vision-related health resources allocation., (Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Nanoscale zerovalent iron (nZVI) shows great promise in valuable metal recovery from wastewater due to its high removal capacity. However, nZVI-based processes mainly focus on the sequestration step, ignoring the desorption step, which is crucial for recovery. In this study, a novel method for simultaneous Mo(VI) recovery and hazardous metal ions immobilization by nZVI was developed and the reaction mechanism was further investigated. Results shown that removal capacity of nZVI was significantly influenced by surface charge and the number of active adsorption sites. X-ray photoelectron spectroscopy analysis demonstrated that Mo(VI) reduction occurred in the inner Fe(0) core. K-edge X-ray Absorption Near Edge Structure analysis further confirmed that 5.4% and 18.0% of Mo(VI) are reduced to Mo(IV) at pH 6 and 9, respectively, suggesting that high pH favors for Mo(VI) reduction and H + is responsible for the hollow-out structure at pH 6. Through adjusting the pH of wastewater from 3 to 12, over 80% of adsorbed Mo(VI) could be recovered while other metal ions remained immobilized and limited influence with common ions/anions. Overall, the proposed mechanism was significant to the research of metal reduction and competition for proton of nZVI, and the developed method had great prospects in valuable anions recovery., (Copyright © 2017. Published by Elsevier B.V.)

Tailored designs/fabrications of hierarchical porous advanced electrode materials are of great importance for developing high-performance electrochemical sensors. Herein, we demonstrate a simple and low-cost in situ chemical approach for the facile synthesis of MnO 2 -embedded hierarchical porous carbon microspheres (MnO 2 /CM). By the characterizations of scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray powder diffraction and energy dispersive spectroscopy, we evidenced that the synthesized product were flower-like carbon microspheres (CM) assembled by the bent flakes with thickness of about several nanometers and MnO 2 nanorods were highly dispersed and successfully decorated on the CM layers, resulting in a rough surface and three-dimensional microstructure. The greatest benefit from the combined porous CM with MnO 2 nanorods is that the MnO 2 /CM modified electrode has the synergetic catalysis effect on the electro-oxidation of caffeic acid, leading to the remarkable increase in the electron transfer rate and significant decrease in the over-potential for the caffeic acid oxidation in contrast to the bare electrode and CM modified electrode. This implies that the prepared MnO 2 /CM can be employed as an enhanced electrocatalyst for the sensitive detection of caffeic acid. Under the optimum conditions, the anodic peak current of caffeic acid is linear with its concentration in the range of 0.01-15.00 μmol L -1 , and a detection limit of 2.7 nmol L -1 is achieved based on S/N = 3. The developed sensor shows good selectivity, sensitivity, reproducibility, and also excellent recovery in the detections of real samples, revealing the promising practicality of the sensor for the caffeic acid detection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3'-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3'-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Xiang-Fu-Si-Wu Decoction (XFSWD) has been used to treat gynecology diseases in clinical practice for hundreds of years in China, especially for primary dysmenorrheal of QiZhi Type. In previous researches, both essential oils (XEO) and non-volatile components (NXEO) extracted from XFSWD showed significant pharmacological activities, but the influence of XEO on NXEO was unclear. The purpose of this paper was to develop a validated analytical method for simultaneous determination of ten components including Vanillic acid, Ferulic acid, Caffeic acid, Gallic acid, Paeoniflorin, Albiflorin, Tetrahydropalmatine, Protopine, Berberine and Tetrahydrocolumbamine, and to compare the pharmacokinetic parameters of these components to illustrate the influences of XEO on NXEO in normal rats. After being extracted by methanol (1:3, v/v), the plasma samples were analyzed with Clarithromycin (IS 1 ) and Chloramphenicol (IS 2 ) as mixed internal standard (IS). Then the analytes were separated on a ACQUITY UPLC BEH C 18 (100×2.1mm, 1.7μm) column with gradient mobile phase (containing 0.1% formic acid aqueous solution and acetonitrile) at a flow rate of 0.4mL/min. All analytes and mixed IS were performed on an electrospray ionization source (ESI) using multiple-reaction monitoring (MRM) with positive and negative ionization mode. The calibration curves of all the analytes showed good linearity (r >0.99), and the lower limits of quantification (LLOQ) were 0.66-46.88ng/mL. The intra- and inter-day precisions ranged 1.24-12.45% and 2.49-13.24% for all the analytes. The mean extraction recoveries of the analytes were in the range of 73.10-93.71% and the average matrix effects were within 82.39-93.18%. The validated method has been fully applied to compare the pharmacokinetic parameters of ten components in rat plasma after oral administration of NXEO, NXEO+β-cyclodextrin (β-CD), NXEO+XEO, and NXEO+β-XEO (the inclusion of XEO by β-CD). It was found that the area under the concentration curves (AUC 0-t ) of ten constituents in group NXEO+β-CD increased compared with group NXEO especially Paeoniflorin, Tetrahydropalmatine and Tetrahydrocolumbamine (p <0.05). The maximum concentration (C max ) and AUC 0-t of ten compounds in group NXEO+XEO and NXEO+β-XEO had varying degree of increasing in comparison with group NXEO. The growth of group NXEO+β-XEO ran higher than group NXEO+XEO. As can be seen from above-mentioned results, β-CD could remarkably increase the absorption of Paeoniflorin, Tetrahydropalmatine and Tetrahydrocolumbamine. Both of XEO and β-XEO could improve the absorption and bioavailability of all the ten non-volatile compositions. The promotion effect of β-XEO was stronger than XEO due to the double functions of XEO and β-CD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Abelmoschus manihot (Linn.) Medicus has been clinically used to treat chronic kidney disease, oral ulcers, burns, and dysmenorrhea in China for many centuries. The major pharmacologically-active components of A. manihot are flavonoids. In this study, a rapid and highly sensitive UPLC-MS/MS analysis method was established and successfully applied to the simultaneous determination of five major flavonoids (rutin, hyperoside, isoquercitrin, quercetin, and myricetin) in different parts of A. manihot harvested at ten growth periods. Under the optimized chromatographic conditions, good separation for five target components was obtained on an Acquity UPLC BEH C18 column within 18min. The total contents of the five investigated flavonoids in A. manihot roots, stems, leaves and flowers ranged from 2.86 to 123.7μg/g, 46.39 to 141.0μg/g, 929.4 to 3096μg/g, and 10,150 to 19,390μg/g, respectively, indicating that the total flavonoids in the four parts could be mainly arranged in a decreasing order as flower>leaf>stem>root. The peak of total flavonoids in flowers and leaves appeared at G8 and G9, respectively. These results will be helpful for the determination of the suitable harvest time of A. manihot and the improvement of the utility value of the disused parts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In vitro fertilized (IVF) embryos show both cell cycle and developmental arrest. We previously showed oxidative damage activates the ATM → Chk1 → Cdc25B/Cdc25C cascade to mediate G2/M cell cycle arrest for repair of hydrogen peroxide (H2O2)-induced oxidative damage in sperm. However, the mechanisms underlying the developmental delay of zygotes are unknown. To develop a model of oxidative-damaged zygotes, we treated mouse zygotes with different concentrations of H2O2 (0, 0.01, 0.02, 0.03, 0.04, 0.05 mM), and evaluated in vitro zygote development, BrdU incorporation to detect the duration of S phase. We also examined reactive oxygen species level and used immunofluorescence to detect activation of γH2AX, Cdc2, and Cdc25. Oxidatively damaged zygotes showed a delay in G2/M phase and produced a higher level of ROS. At the same time, γH2AX was detected in oxidatively damaged zygotes as well as phospho-Cdc25B (Ser323), phospho-Cdc25C (Ser216), and phospho-Cdc2 (Tyr15). Our study indicates that oxidative stress-induced DNA damage of mouse zygotes triggers the cell cycle checkpoint, which results in G2/M cell cycle arrest, and that phospho-Cdc25B (Ser323), phospho-Cdc25C (Ser216), and phospho-Cdc2 (Tyr15) participate in activating the G2/M checkpoint.

Aims: The ubiquitin-activating enzyme E1 (UBA1, E1), the apex of the ubiquitin proteasome pathway, plays a critical role in protein degradation and in pathological processes. Whether UBA1 participates the development of vascular restenosis remains unknown. This study aims to determine the role of UBA1 in the development of balloon injury induced neointimal formation., Methods and Results: Immunostaining and western blots were used to examine the expression of the ubiquitinated protein in the injured carotid after angioplasty. Higher levels of ubiquitinated protein were observed in the neointima. Local delivery of potent chemical UBA1 inhibitor PYR-41 (100 μM) and UBA1 shRNA lentivirus both resulted in a substantial decrease in intimal hyperplasia at 2 weeks and 4 weeks after balloon injury. UBA1 inhibition also reduced Ki-67 positive cell percentage and inflammatory response in the carotid artery wall. We further determined that in vitro UBA1 inhibition was able to ameliorate TNF-α-induced nuclear factor-kappa B (NF-κB) activation by reducing IκB degradation in vascular smooth muscle cells (VSMCs). UBA1 inhibition also led to the accumulation of short-lived proteins such as p53, p21 and c-jun, which may account for the UBA1 inhibition-induced cell cycle delay. Thus, VSMCs proliferation was blocked., Conclusions: UBA1 inhibition effectively suppresses neointimal thickening through its anti-proliferative and anti-inflammatory effects. Our results provide further evidence that the ubiquitin-proteasome system is a potential new target for the prevention of vascular restenosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The international comparisons that provided useful epidemiologic information of hypertension in the elderly people is still sparse; we aim to provide the latest international estimates on the burden of hypertension. These sampling methods of the selection of surveys mainly used multistage population registry; this cross-national study of 63,014 adults aged ≥50 years was from in four high-income countries, four upper-middle-income countries (UMICs), and three low-middle-income countries (LMICs). Overall, the age-standardized prevalence of hypertension among the adult population aged ≥50 years was 53.2% (51.9% of men and 54.3% of women). The high-income countries and UMICs had more or less twice the prevalence of hypertension compare with LMICs. The rates of awareness, treatment, and control of hypertension were 55.6%, 44.1%, and 17.1%, respectively, and awareness and control of hypertension were lowest in UMICs and treatment of hypertension was lowest in LMICs. Among this multiple national study population, hypertension was very common among elderly population. Even more worrisome is that the rates of awareness, treatment, and control of hypertension were relatively low in UMICs and IMICs. These results indicate that improving the ability to control and prevention of hypertension in resource-limited settings is needed., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

A sensitive and rapid method for determination of loganin, morroniside, catalpol and acteoside in rat plasma after oral administration of Rehmannia glutinosa Libosch and Cornus officinalis Sieb drug pair based on ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS). Chromatographic separation was achieved using an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the mobile phase A and B. Loganin, morroniside, catalpol, acteoside and the internal standard (chloramphenicol) were detected by selected reaction monitoring in the negative ion mode with the mass transition of m/z 451.0→179.0 (morroniside), m/z 435.0→227.0 (loganin), m/z 407.1→199.1 (catalpol), m/z 623.2→161.0 (acteoside) and m/z 320.8→151.9 (chloramphenicol), respectively. All calibration curves showed good linearity (r>0.991). The precision was evaluated by intra-day and inter-day assays and the RSD% were all within 9.58%. The recovery ranged from 67.62 to 80.14%. The method was successfully applied to pharmacokinetic study of the analytes in normal and doxorubicin-induced chronic kidney disease rat plasma., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We report herein the effects of Ultrasonic Nano-crystal Surface Modification (UNSM), a severe surface plastic deformation process, on the microstructure, mechanical (hardness, wear), wettability and biocompatibility properties of NiTi shape memory alloy. Complete surface amorphization of NiTi was achieved by this process, which was confirmed by X-ray diffraction and high-resolution transmission electron microscopy. The wear resistance of the samples after UNSM processing was significantly improved compared with the non-processed samples due to increased surface hardness of the alloy by this process. In addition, cell culture study demonstrated that the biocompatibility of the samples after UNSM processing has not been compromised compared to the non-processed sample. The combination of high wear resistance and good biocompatibility makes UNSM an appealing process for treating alloy-based biomedical devices., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

To extract expert clinic information from the Deep Web, there are two challenges to face. The first one is to make a judgment on forms. A novel method based on a domain model, which is a tree structure constructed by the attributes of query interfaces is proposed. With this model, query interfaces can be classified to a domain and filled in with domain keywords. Another challenge is to extract information from response Web pages indexed by query interfaces. To filter the noisy information on a Web page, a block importance model is proposed, both content and spatial features are taken into account in this model. The experimental results indicate that the domain model yields a precision 4.89% higher than that of the rule-based method, whereas the block importance model yields an F1 measure 10.5% higher than that of the XPath method., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A sensitive ultrafast liquid chromatography coupled with triple quadrupole mass spectrometric (UFLC-MS/MS) method for the quantification of anhydrosafflor yellow B (AHSYB), a major active water-soluble pigment from Carthamus tinctorius, in rat plasma has been developed and validated. Sample preparation was achieved by protein precipitation of plasma with four volumes of methanol. Rutin was used as the internal standard (IS). The analytes were separated using a C18 column with an 8min gradient elution, followed by mass spectrometric detection using negative electrospray ionization (ESI(-)) in multiple reaction monitoring (MRM) mode. The method was linear in the concentration range of 25-10,000ng/mL for AHSYB. Intra-day and inter-day precision variation was less than 6.5%. The relative error of accuracy was within ±9.4%. The mean recovery of AHSYB was higher than 70.9%. The established method was successfully applied to the pharmacokinetic study after intravenous (2.5mg/kg) and oral (30mg/kg) dosing of AHSYB in normal rats. And the pharmacokinetic properties of AHSYB in rats with acute blood stasis and the differences between normal and acute blood stasis syndrome rats were also investigated. The results showed that the compound was poorly absorbed (∼0.3%) and the AUC0-t, AUC0-∞ and F were all significantly lower (P<0.05) in acute blood stasis syndrome rats, suggesting that disease condition may alter the body metabolism by enhancing metabolite enzyme activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Morroniside, the most abundant iridoid glycoside in the valuable traditional Chinese medicine Fructus Corni, exhibits various pharmacological activities and biological effects. Intestinal flora plays an important role in the metabolism of drug compounds, which might lead to the variation of ethnopharmacological profile of the medicine. However, little is known of the interactions of the morroniside with human intestinal bacteria. In this study, different pure bacteria were isolated from human feces and their capability to convert morroniside were investigated. The metabolites of morroniside were analyzed by ultra high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique using Metabolynx™ software. Parent compound and three metabolites were detected and tentatively identified based on the characteristics of their protonated ions. The parent is proposed to be metabolized by three main metabolic pathways including deglycosylation, dehydroxylation and methylation. Morroniside was firstly metabolized to its aglycone (M1), and then was further converted to dehydroxylated aglycone (M2) and methylated aglycone (M3). This is the first report of the metabolism of morroniside by human intestinal bacteria. These metabolites might influence the biological activities of morroniside in vivo, which could affect the clinical effects of medicines. Thus, the study on the metabolism of morroniside by human intestinal bacteria is very helpful to unravel how traditional medicines work., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The coordinated polarization of neighboring cells within the plane of the tissue, known as planar cell polarity (PCP), is a recurring theme in biology. It is required for numerous developmental processes for the form and function of many tissues and organs across species. The genetic pathway regulating PCP was first discovered in Drosophila, and an analogous but distinct pathway is emerging in vertebrates. It consists of membrane protein complexes known as core PCP proteins that are conserved across species. Here we report that the over-expression of the murine Ankrd6 (mAnkrd6) gene that shares homology with Drosophila core PCP gene diego causes a typical PCP phenotype in Drosophila, and mAnkrd6 can rescue the loss of function of diego in Drosophila. In mice, mAnkrd6 protein is asymmetrically localized in cells of the inner ear sensory organs, characteristic of components of conserved core PCP complexes. The loss of mAnkrd6 causes PCP defects in the inner ear sensory organs. Moreover, canonical Wnt signaling is significantly increased in mouse embryonic fibroblasts from mAnkrd6 knockout mice in comparison to wild type controls. Together, these results indicated that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and act to suppress canonical Wnt signaling., (Copyright © 2014 Elsevier Inc. All rights reserved.)