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Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P 0.001) and viscosity (median 64% versus 58%; P 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.

This retrospective study was designed to compare the treatment response of patients with differentiated thyroid cancer (DTC) prepared for radioiodine ablation (RIA) with thyroid hormone withdrawal (THW) or recombinant human thyrotropin (rhTSH) stimulation. Patients with DTC were followed-up retrospectively between 2013 and 2018 in Kaohsiung Chang Gung Memorial Hospital, Taiwan. We compared the excellent response ratios between THW (49.9%) and rhTSH (50.1%) stimulation. Patients were then divided into subgroups, on the basis of age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage, for analysis. In all, 647 patients were followed-up after RIA. The ratios of THW or rhTSH use in the different subgroups were not statistically significant. In all the patients, the excellent response rate with THW and rhTSH was 80% and 76.5%, respectively, which was not statistically significant. The subgroup analysis, including age, sex, extrathyroidal extension, lymph node metastasis, and tumor-node-metastasis stage (low and high risk), showed similar results. Furthermore, the logistic regression analysis revealed no statistically significant differences among the subgroups. The multivariate analysis showed extrathyroidal extension, lymph node metastasis, and high I

Spinal cord injury (SCI) is a global problem that brings a heavy burden to both patients and society. Recent investigations indicated degenerative disease is taking an increasing part in SCI with the growth of the aging population. However, little insight has been gained about the effect of cervical degenerative disease on the spinal cord during dynamic activities. In this work, a dynamic fluid-structure interaction model was developed and validated to investigate the effect of anterior and posterior encroachment caused by degenerative disease on the spinal cord during normal extension and flexion. Maximum von-Mises stress and maximum principal strain were observed at the end of extension and flexion. The abnormal stress distribution caused by degenerative factors was concentrated in the descending tracts of the spinal cord. Our finding indicates that the excessive motion of the cervical spine could potentially exacerbate spinal cord injury and enlarge injury areas. Stress and strain remained low compared to extension during moderate flexion. This suggests that patients with cervical degenerative disease should avoid frequent or excessive flexion and extension which could result in motor function impairment, whereas moderate flexion is safe. Besides, encroachment caused by degenerative factors that are not significant in static imaging could also cause cord compression during normal activities.

Elucidating the structural variations of lignin during the pretreatment is very important for lignin valorization. Herein, poplar wood was pretreated with an integrated process, which was composed of AlCl

Carboxylic acids are an abundant and structurally diverse class of commercially available materials, which are commonly used as stable reagents in organic synthesis. The Suzuki–Miyaura coupling reaction directly using carboxylic acid as a substrate has been rarely reported. Here, we report an efficient coupling reaction of carboxylic acids with arylboronic acids in toluene in the presence of IPrCl-Cl, Pd(OAc)2, PPh3, and K3PO4·7H2O at 90 °C to give the corresponding aryl ketones.

The efficacy of treatment with hydrogen and Ag-Cu co-deposition on TiO2 photocatalysts has been investigated computationally and experimentally. The hydrogenated Ag-Cu with co-loaded TiO2 (H:(Ag-Cu/TiO2)) achieved a photoactivity about 110 times that of pristine TiO2, which corresponds to a rate of 1.16 mmol h−1 g−1 for hydrogen generation. Soft X-ray spectra and quantum-chemical calculations indicate that the notable promotion of photoactivity on H:(Ag-Cu/TiO2) is ascribable to the synergy between new electronic states and a lattice distortion. The soft X-ray absorption spectra (XAS) indicated that the TiO6 octahedral symmetry and the Ti 3d- orbital orientation are significantly affected by the Ag-Cu decoration and the hydrogenation treatment. The mechanisms involved in this photocatalysis were studied with soft XAS in situ, which showed that the photoexcited electrons transfer from the bimetallic Ag-Cu to the TiO2 conduction band as the photoresponse of this composite photocatalyst. The strategy of coupling hydrogenation with bimetallic Ag-Cu onto TiO2-based photocatalysis provides a facile and promising solution to other environmental and energy applications.

Objectives. Menstrual hygiene management is one of the main barriers to girls’ education attainment in low-and middle-income countries. Poor access to sanitary products and lack of menstrual knowledge affect students’ performance at school compared to the opposite sex. Limited evidence is available to provide solutions for schoolgirls. This study examines the effectiveness of menstrual health education programs on well-being and behavioral change among adolescent girls in rural Uganda. Methods. A cluster randomized controlled trial was conducted across 3 schools, including 66 girls aged 13-17 years, in a rural village in Mukono District, Uganda. Schools were randomly allocated to 2 groups: i) health education program intervention and ii) control group (no intervention). Results. After 5 weeks of the Health Education Program, the schoolgirls in experiment groups showed significantly less fear of sharing the menstruation-related concern with parents and pupils [Mean Difference (MD)=0.87, P=0.029) (MD=2.02, P=0.000), and the sense of shameful feelings during menstruation (MD=1.65, P= 0.004); conversely, the fear to go to school during menstruation did not differ between experiment and control groups (MD=-0.04, P=0.94). However, the changes in feeling comfortable having a period at school were significantly different between the experiment and control groups (P=0.001). Conclusions. The study demonstrated promising results of a low-cost intervention for enhancing girls’ menstrual health education in a low-income context. Puberty education and reusable pad sewing provision were strongly associated with improving schoolgirls’ psychosocial wellbeing related to menstrual management.

Technology trend analysis uses data relevant to historical performance and extrapolates it to estimate and assess the future potential of technology. Such analysis is used to analyze emerging technologies or predict the growing markets that influence the resulting social or economic development to assist in effective decision-making. Traditional trend analysis methods are time-consuming and require considerable labor. Moreover, the implemented processes may largely rely on the specific knowledge of the domain experts. With the advancement in the areas of science and technology, emerging cross-domain trends have received growing attention for its considerable influence on society and the economy. Consequently, emerging cross-domain predictions that combine or complement various technologies or integrate with diverse disciplines may be more critical than other tools and applications in the same domain. This study uses a design science research methodology, a text mining technique, and social network analysis (SNA) to analyze the development trends concerning the presentation of the product or service information on a company's website. This study applies regulatory technology (RegTech) as a case to analyze and justify the emerging cross-disciplinary trend. Furthermore, an experimental study is conducted using the Google search engine to verify and validate the proposed research mechanism at the end of this study. The study results reveal that, compared with Google Trends and Google Correlate, the research mechanism proposed in this study is more illustrative, feasible, and promising because it reduces noise and avoids the additional time and effort required to perform a further in-depth exploration to obtain the information.

This study aims to establish and validate a poroelastic L4-L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72–0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

Green fractionation and a comprehensive overview of lignin molecular structures during the DES (deep eutectic solvent) pretreatment are very important for lignin valorization and the whole biorefinery process. Herein, intractable woody biomass (poplar wood) was pretreated with five types of carboxylic-acid-based DESs (acetamide served as an HBA (hydrogen bond acceptor), propanedioic acid, tartaric acid, malic acid, glutaric acid, and succinic acid served as HBDs (hydrogen bond donors)) under the optimized pretreatment conditions. Results showed that the optimal delignification ratio was achieved for tartaric-acid-based DES at 140 °C for 20 min under microwave-assisted heating. Two-dimensional HSQC NMR data demonstrated that the isolated poplar DES lignin consisted mainly of β-β, β-O-4 (normal and acylated forms), β-5, and esterified p-hydroxybenzoates (PBs) in different contents. Especially, the contents of β-O-4 in the isolated DES lignin fractions varied based on the pretreatment temperature and different chemical compositions of the DES. The antioxidant activity (2,2-diphenyl-1-picrylhydrazyl, DPPH analysis), microstructure (scanning electron microscope, SEM), and molecular weights (gel permeation chromatography, GPC) of the DES lignin fractions demonstrated that the DES delignification promoted the rapid assembly of lignin nanoparticles (LNPs) and could yield homogeneous lignin (1.23 < PDI < 1.58) with controlled nanometer size (30–170 nm) and good antioxidant activity. This study will improve the knowledge of structural changes of lignin during the different carboxylic-acid-based DES pretreatments and maximize the lignin valorization.

Porous carbons with well-developed pores, tunable microstructures and stable chemistry play a significant role in energy storage and environmental pollution control. Biomass is a carbon precursor that is abundant, low cost, sustainable and carbon neutral, and is promising for the large-scale production of porous carbons. Among the various types of biomass, algae usually contain abundant cellulose and heteroatoms, which are suitable precursors for heteroatom-doped carbons. Recent advances in synthesis methods for algae-based porous carbons are reviewed and their pore formation mechanisms discussed. Their potential applications in adsorption, catalysis and energy storage are highlighted, and strategies for improving their performance are proposed. Future research trends and challenges for algae-based carbons are discussed, especially as they relate to their low-cost production and performance improvement.

Juniperus (Cupressaceae, Pinales) plants are widely distributed in the Qinghai-Tibet Plateau of China. The leaves and twigs of at least 8 Juniperus species (J. pingii, J. pingii var. wilsonii, J. squamata, J. recurva var. coxii, J. saltuaria, J. indica, J. tibetica and J. convallium var. microsperma) have been used as the Tibetan medicine Xuba. At present, it is difficult to distinguish among the original species of Xuba based only on their similar morphological characteristics. However, in our previous studies, 4 Xuba samples from different Juniperus species exhibited significant differences in both anticomplementary activity in vitro and anti-inflammatory effects on acute lung injury in vivo. To identify the effective original species of Xuba reliably, in this study, we developed a sequencing-based DNA molecular technology to distinguish 14 populations of 8 Juniperus species collected from Tibet region, using trnS-G, trnD – T, and petN-psbM genomic regions to build phylogenetic trees. In addition, their anticomplementary activities were evaluated. The results showed that combined sequence of these 3 genomic regions could identify 8 Juniperus species clearly and clustered individuals of one species but from different locations, whichever phylogenetic tree was constructed. Moreover, the anticomplementary activities of the 8 species were clustered into 2 groups. Among them, J. saltuaria and J. recurva var. coxii, which formed an independent branch apart from the other 6 species in phylogenetic trees, were the most potent (CH50: 0.029 – 0.032 mg/mL). Consequently, DNA identification of Juniperus using the combined sequence could provide beneficial guidance for further efficacy evaluation and quality control of Xuba.

Background/purpose: Few studies exist investigating the effectiveness of radioiodine (RAI) therapy for hyperthyroidism patients in Asia. We herein investigated the real-world efficacy of single-dose RAI therapy in Taiwanese patients with Graves’ disease (GD). Methods: This is a retrospective study of 243 patients with GD recorded between 1989 and 2016 in a tertiary referral hospital. Eu- or hypothyroid after RAI therapy were defined as the successful group. Kaplan–Meier curve and cox-regression model were used for analysis of prognostic factors. Results: Of the 243 patients, 187 were females, with mean age of 46.9 ± 13.6 years. Most patients (63.8%) did not choose RAI as the first-line therapy. The median dose was 7 mCi, with a mean follow-up period of 107.1 ± 82.8 months. The overall success rate was 70.9%. Univariate analysis revealed calculated- or fixed-dose (P = 0.015), goiter size (P

Objective: Amino acyl modification of lysine residues is an essential mechanism of nutrient sensing that regulates various biological functions including reproduction. At present, the lack of pan-specific antibodies for a recently identified lysine valylation hinders the characterization and detection of this modification. The objective of this study is to raise pan-specific antibodies that may facilitate the identification of novel expression patterns of lysine valylation. Methods: Chicken ovalbumin was valylated as an immunogen to raise polyclonal antibodies (PcAbs) in rabbits. The population of the pan-specific antibodies recognizing valylated lysine was purified using the chemically synthesized valylated peptides consisting of random amino acids. The specificity of the antibodies was evaluated using ELISA, dot blots, Western blots, and immunohistochemistry (IHC) staining in human epididymis as well. Results: A preliminary and simple strategy to make an anti-valylated lysine PcAb was developed. The recognition of the antibodies to valyllysine was evaluated as pan specific. This was useful for the detection of the newly identified valyl modification using ELISA, dot blots, and Western blots. The antibodies were also successfully utilized in IHC assays, which revealed novel valyllysine modification patterns in epididymis tissues of human. Conclusions: A new antibody tool was provided for the study of lysine valylation. The novel expression patterns of valyllysine in the epididymis suggest that this modification may be involved in sperm maturation.

Chiral organic-inorganic perovskites (COIPs) have recently attracted increasing interest due to their unique inherent chirality and potential applications in next-generation optoelectronic and spintronic devices. However, COIP ferroelectrics are very sparse. In this work, for the first time, we present the nickel-nitrite ABX3 COIP ferroelectrics, [(R and S)-N-fluoromethyl-3-quinuclidinol]Ni(NO2)3 ([(R and S)-FMQ]Ni(NO2)3), where the X-site is the rarely seen NO2- bridging ligand. [(R and S)-FMQ]Ni(NO2)3 display mirror-relationship in the crystal structure and vibrational circular dichroism signal. It is emphasized that [(R and S)-FMQ]Ni(NO2)3 show splendid ferroelectricity with both an extremely high phase-transition point of 405 K and a spontaneous polarization of 12 μC/cm2. To our knowledge, [(R and S)-FMQ]Ni(NO2)3 are the first examples of nickel-nitrite based COIP ferroelectrics. This finding expands the COIP family and throws light on exploration of high-performance COIP ferroelectrics.

Cervical cancer is ranked top ten in the ranking of female cancer and the metastasis of cervical cancer is one of the main causes of decreasing five-year-survival rates. Neuroendocrine cervical cancer belongs to rare type of cervical cancer and is one of the more malignant cancer type, compared to squamous cell carcinoma and adenocarcinoma. In the previous work, we have carried out proteomics-based 2D-DIGE and MALDI-TOF-MS to analyze the differentially modulated proteins in neuroendocrine cells (HM-1) and other types of cervical cancer cells (Caski, ME-180, HeLa). In which, galectin-1 (LGALS1) was selected as the candidate protein due to high expression of LGALS1 in HM-1 cells. In this study, use small interfering RNA (siRNA) to knockdown LGALS1 expression in HM-1and HM-2 which isolated from human tissue. The migration ability and proliferation ability of neuroendocrine cervical cancer cells are effectively inhibited. Also, the de-regulation of cell cycle progression was observed during LGALS1 silencing. As a result, LGALS1 affects the migration and proliferation ability in neuroendocrine cervical cancer. The protein is potential to be a candidate to detect and treatment of neuroendocrine cervical cancer.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity (VH) associated with abnormal serotonin/5-hydroxytryptamine (5-HT) metabolism and neurotrophin-dependent mucosal neurite outgrowth. The underlying mechanisms of VH remain poorly understood. We investigated the role of 5-HT

The Pareto Principle, also known as the 80/20 rule is currently an important and popular management rule applied to marketing and customer relationship management (CRM). The rule indicates that the vital few causes inputs or efforts bringing the most results, outputs, or rewards. Analyzing circulation data to understand the usage status of library collections can help libraries comprehend their patrons’ behaviour. However, little research has been done to analyse circulation data of public libraries to reveal patrons’ usage behaviours. This paper aimed to analyse the circulation data generated by a municipality public library in Taiwan to gauge if the Pareto Principle manifested in this context. Subsequently, using bibliomining analysis, this research further identified vital patrons and their characteristics, as well as book-borrowed distributions to help analyse patrons' book borrowing behaviour to improve the efficiency of library management and library marketing as well as CRM. The circulation data of the public library follows the Pareto Principle, approximating to the 80/20 rule. Findings showed that when the accumulative percentage of patron is 24.7 percent, the accumulative percentage of borrowed books is 75.3 percent. The vital few patrons borrow the majority of the collections. This paper is the first study to reveal that the Pareto Principle could be found in circulation data of a public library in Taiwan. It could help libraries identify vital patrons and major collections, and improve the efficiency of their management and marketing activities in future. For other types of libraries, it would be interesting for us to explore the existence of the Pareto Principle further.

Geospatial big data analytics are changing the way that businesses operate, and have enabled various intelligent services in smart cities. User mobility plays an important role in many context-aware applications, such as location-based advertisement, traffic planning, and urban resource management. This paper proposes CityTracker, a hidden Markov model (HMM)-based framework to predict the temporal-spatial individual trajectory and analyze the representative citywide crowd mobility. After the locations are segmented into points of interests and modeled as states, HMM can find the most likely state sequence in a maximum-likelihood sense, and thus perform trajectory prediction with different orders. In addition, CityTracker can integrate the individual trajectories, achieving representative crowd mobility visualization in the target area. The proposed mechanism is evaluated on a database provided by HyXen, which contains temporal-geospatial records from thousands of smartphones in Taipei. Experimental results confirm the effectiveness of CityTracker, which achieves prediction distance errors of approximately 1.28 km and outperforms traditional probabilistic and regression-based methods. The results also show the most representative crowd mobility behaviors in the map, which is essential for citywide applications.

Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood–brain barrier. Our previous works show that bile duct ligation (BDL) impairs expression and function of brain BCRP in rats. Since zidovudine (AZT) is BCRP substrate, we investigated whether impaired expression and function of BCRP increased brain distribution and toxicity of AZT in BDL-D7 rats. After administration of AZT (10 mg/kg, i.v.), BDL markedly increased brain AZT concentrations, compared with sham-operated (SO) rats. The ratio of AZT brain-to-plasma area under concentration curve (AUC) in BDL rats was increased to 1.6-folds of SO rats. After treatment with AZT (100 mg/kg every day, i.v.) for 7 days, BDL significantly impaired cognitive functions compared with SO rats, evidenced by the significantly decreased percentage of alternation in Y-maze test and prolonged escaped latency in two-way passive avoidance trial. Furthermore, AZT treatment caused significant decrease in copies of mitochondrial DNA and mitochondrial membrane potential in hippocampus of BDL rats. Moreover, AZT treatment caused a significant decrease of cortex microtubule-associated protein 2 and hippocampus synaptophysin levels in BDL rats. AZT-induced CNS adverse alterations in BDL rats were not observed in SO rats treated with AZT. In conclusion, BDL decreases the function and expression of brain BCRP in rats, leading to increased brain distribution of AZT, which in turn enhances AZT CNS toxicity, leading to mitochondrial dysfunction, neuronal damage, and ultimately cognitive dysfunction.

Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Drug–drug interactions (DDIs) of metformin occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model characterizing interplay of OCTs and MATEs in the intestine, liver, and kidney to predict metformin DDIs with cimetidine, pyrimethamine, trimethoprim, ondansetron, rabeprazole, and verapamil. Simulations showed that co-administration of perpetrators increased plasma exposures to metformin, which were consistent with clinic observations. Sensitivity analysis demonstrated that contributions of the tested factors to metformin DDI with cimetidine are gastrointestinal transit rate &gt, inhibition of renal OCT2 ≈ inhibition of renal MATEs &gt, inhibition of intestinal OCT3 &gt, intestinal pH &gt, inhibition of hepatic OCT1. Individual contributions of transporters to metformin disposition are renal OCT2 ≈ renal MATEs &gt, intestinal OCT3 &gt, hepatic OCT1 &gt, intestinal PMAT. In conclusion, DDIs of metformin with perpetrators are attributed to integrated effects of inhibitions of these transporters.

Although the majority of nasopharyngeal carcinoma (NPC) patients demonstrate favorable outcomes after radiotherapy and/or chemotherapy, about 8-10% of patients will develop recurrent disease, and genomic alterations (GAs) associated with the recurrence are unclear.This study investigated the GAs in the paired primary tumors and recurrent tumors of 7 NPC patients with relapse, as well as the primary tumors of 15 NPC patients without relapse by deep targeted next-generation sequencing on 440 cancer-related genes.The discovery of GAs associated with recurrence or survival in NPC may serve as potential prognostic gene signatures of high-risk patients. Targeted therapies are available in some of the clinically relevant GAs and may be considered in future clinical trials. Given the limitation of the sample size, validation by a larger cohort is warranted.

Uptake transporter organic anion transporting polypeptides (OATPs), efflux transporters (P-gp, BCRP and MRP2) and cytochrome P450 enzymes (CYP450s) are widely expressed in the liver, intestine or kidney. They coordinately work to control drug disposition, termed as &ldquo, interplay of transporters and enzymes&rdquo, Cyclosporine A (CsA) is an inhibitor of OATPs, P-gp, MRP2, BCRP and CYP3As. Drug&ndash, drug interaction (DDI) of CsA with victim drugs occurs via disordering interplay of transporters and enzymes. We aimed to establish a whole-body physiologically-based pharmacokinetic (PBPK) model which predicts disposition of CsA and nine victim drugs including atorvastatin, cerivastatin, pravastatin, rosuvastatin, fluvastatin, simvastatin, lovastatin, repaglinide and bosentan, as well as drug&ndash, drug interactions (DDIs) of CsA with nine victim drugs to investigate the integrated effect of enzymes and transporters in liver, intestinal and kidney on drug disposition. Predictions were compared with observations. Most of the predictions were within 0.5&ndash, 2.0 folds of observations. Atorvastatin was represented to investigate individual contributions of transporters and CYP3As to atorvastatin disposition and their integrated effect. The contributions to atorvastatin disposition were hepatic OATPs &gt, &gt, hepatic CYP3A &gt, intestinal CYP3As &asymp, efflux transporters (P-gp/BCRP/MRP2). The results got the conclusion that the developed PBPK model characterizing the interplay of enzymes and transporters was successfully applied to predict the pharmacokinetics of 10 OATP substrates and DDIs of CsA with 9 victim drugs.

A novel putative single-stranded RNA virus was discovered from the transcriptome of a bean bug, Riptortus pedestris, infected with the entomopathogenic fungus Beaveria bassiana JEF-007. The complete genome sequence was 9,915 nucleotides long and encoded a 2,916-amino-acid polyprotein. This virus belonged to Iflaviridae based on phylogenetic analysis and was named RiPV-2.