Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

GDF15 is a dynamic biomarker of the integrated stress response in the central nervous system.

AIM: Characterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the integrated stress response (ISR) within the central nervous system (CNS). METHODS: We determined GDF15 levels utilizing in vitro and in vivo neuronal systems wherein the ISR was activated. Primarily, we used the murine model of vanishing white matter disease (VWMD), a neurological disease driven by persistent ISR in the CNS, to establish a link between levels of GDF15 in the cerebrospinal fluid (CSF) and ISR gene expression signature in the CNS. GDF15 was also determined in the CSF of VWM patients. RESULTS: GDF15 expression was increased concomitant to ISR activation in stress-induced primary astrocytes as well as in retinal ganglion cells following optic nerve crush, while treatment with 2Bact, a specific eIF2B activator, suppressed both the ISR and GDF15. In the VWMD model, CSF GDF15 levels corresponded with the magnitude of the ISR and were reduced by 2BAct. In VWM patients, mean CSF GDF15 was elevated >20-fold as compared to healthy controls, whereas plasma GDF15 was undifferentiated. CONCLUSIONS: These data suggest that CSF GDF15 is a dynamic marker of ISR activation in the CNS and may serve as a pharmacodynamic biomarker for ISR-modulating therapies.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

3D mouse pose from single-view video and a new dataset.

We present a method to infer the 3D pose of mice, including the limbs and feet, from monocular videos. Many human clinical conditions and their corresponding animal models result in abnormal motion, and accurately measuring 3D motion at scale offers insights into health. The 3D poses improve classification of health-related attributes over 2D representations. The inferred poses are accurate enough to estimate stride length even when the feet are mostly occluded. This method could be applied as part of a continuous monitoring system to non-invasively measure animal health, as demonstrated by its use in successfully classifying animals based on age and genotype. We introduce the Mouse Pose Analysis Dataset, the first large scale video dataset of lab mice in their home cage with ground truth keypoint and behavior labels. The dataset also contains high resolution mouse CT scans, which we use to build the shape models for 3D pose reconstruction.

An immune-based tool platform for in vivo cell clearance.

Immunological targeting of pathological cells has been successful in oncology and is expanding to other pathobiological contexts. Here, we present a flexible platform that allows labeling cells of interest with the surface-expressed model antigen ovalbumin (OVA), which can be eliminated via either antigen-specific T cells or newly developed OVA antibodies. We demonstrate that hepatocytes can be effectively targeted by either modality. In contrast, pro-fibrotic fibroblasts associated with pulmonary fibrosis are only eliminated by T cells in initial experiments, which reduced collagen deposition in a fibrosis model. This new experimental platform will facilitate development of immune-based approaches to clear potential pathological cell types in vivo.

Do environmental, social, and governance scores improve green innovation? Empirical evidence from Chinese-listed companies.

Environmental, social, and governance (ESG) has become a buzzword in investment circles as ecological damage and climate warming occur. ESG assessment is one of the important institutions of the green financial system, which plays a significant part in boosting corporate green development. We use the number of green patent applications and green patent citations to measure corporate green innovation and analyze the micro-green effects of the ESG score system using the panel fixed effects models, which means that we explore the impact of the ESG scores on corporate green innovation performance, the specific mechanism of this effect, and the asymmetry of this impact under different moderation effects by using Chinese listed A-shares in Shanghai and Shenzhen from 2010-2019 as our research sample. We find that ESG positively affects corporate green innovation; the higher the ESG evaluation, the more it improves firms' green innovation performance. The promotion effect is reflected quantitatively and qualitatively and remains valid after several robustness tests. In addition, the contribution of ESG to corporate green innovation is achieved through two main paths improving corporate investment efficiency and government-enterprise relations. Corporate black attributes inhibit the contribution of ESG to green innovation, while green attributes strengthen the contribution of ESG to green innovation performance. Our study demonstrates the importance of corporate participation in environmental, social, and governance practices for corporate green innovation, which is beneficial for achieving win-win environmental, social, and economic results. Furthermore, our research completes the research on the effects of corporate green performance and green finance. It can provide empirical references for promoting corporate green development and improving the ESG evaluation system.

Renewable energy, industrial upgradation, and import-export quality: green finance and CO2 emission reduction nexus.

There has been a steady decline in carbon dioxide emissions in the world's 19 most industrialized nations even as GDP has increased. These nations' efforts to reduce emissions of carbon dioxide, therefore, to reduction of CO2 and development of renewable energy are the objective of this research. With the years 1995-2019 as a point of reference, we have selected gross domestic product, GDP, RE, industrial upgrading, and import and export as our independent variables. A panel nonlinear autoregressive distributed lag (NARDL) method is utilized to investigate the links between carbon dioxide emission and these independent variables. For the purpose of determining the direction of causation, the panel heterogeneous causality test is used. RE and standards of export and import were shown to be contributing variables in the decrease of carbon dioxide emissions. The environmental Kuznets curve hypothesis was validated by the estimated findings. Increased carbon dioxide emissions are countered by the positive impulses of technological progress, such as R&D development spending and standards of import and export index. Industrial upgrading and emissions of carbon dioxide, gross domestic product and RE, and industrial upgrading and emissions of carbon dioxide, all have a bidirectional causal link. In particular, a one-way causality between gross domestic product and emissions of carbon dioxide, standards of imports and exports, and industrial upgrading, and industrial upgrading and standards of imports and exports is demonstrated. Following the results, policy suggestions are put out.

Triple-threat quantitative multiplexed plasma proteomics analysis on immune complex disease MRL-lpr mice.

Systemic lupus erythematosus is a common autoimmune inflammatory disease which is associated with increases in autoantibodies and immune complexes that deposit in the kidney. The MRL-lpr mouse is a common mouse model used for the study of lupus and immune complex glomerulonephritis but very little is known about the plasma proteome changes in this model. We performed in-depth quantitative proteome profiling on MRL-lpr and control (strain MpJ) mice to investigate the changes in the proteome, immunoglobulins and their glycoproteome as well as protein and immune complexes. Methodologies used included immunohistochemistry, immunoglobulin isotyping, multiplexed proteome profiling, immunoglobulin immunoprecipitation with glycoproteome profiling, and size exclusion chromatography (SEC) profiling to enable a comprehensive proteome profiling of proteins and protein complexes. We also used a novel native multiplexed plasma proteome profiling (NativeMP3) method that relies on native enrichment of plasma proteins enabling ultra-deep single shot profiling where we identified 922 plasma proteins at 1% false discovery rate (FDR) in a single shot mass spectrometry run. We observed many large plasma protein differences between the MRL-lpr and control strain including differences in the immunoglobulins, immunoglobulins against specific antigens, chemokines, and proteases as well as changes in protein complexes such as the immunoproteasome.

Diverse partial reprogramming strategies restore youthful gene expression and transiently suppress cell identity.

Partial pluripotent reprogramming can reverse features of aging in mammalian cells, but the impact on somatic identity and the necessity of individual reprogramming factors remain unknown. Here, we used single-cell genomics to map the identity trajectory induced by partial reprogramming in multiple murine cell types and dissected the influence of each factor by screening all Yamanaka Factor subsets with pooled single-cell screens. We found that partial reprogramming restored youthful expression in adipogenic and mesenchymal stem cells but also temporarily suppressed somatic identity programs. Our pooled screens revealed that many subsets of the Yamanaka Factors both restore youthful expression and suppress somatic identity, but these effects were not tightly entangled. We also found that a multipotent reprogramming strategy inspired by amphibian regeneration restored youthful expression in myogenic cells. Our results suggest that various sets of reprogramming factors can restore youthful expression with varying degrees of somatic identity suppression. A record of this paper's Transparent Peer Review process is included in the supplemental information.

CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging.

Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals.

Energy policy and financial performance in China: mediation effect of financial inclusion.

The issues of cleaner production and socioeconomic advancements have taken a central stage due to the dynamism of the correlation between energy use and ecology. Given this background, the research delves into how to construct a framework to unravel diverse understandings of energy policy vis-a-vis green economy by examining the mediating role of financial inclusion. The analysis applied a non-radial DEA and longitudinal dataset model for the scenarios of thirty regions in China, relying on their longitudinal dataset from 2010-2017. The findings indicate that the Chinese regions' total green economic performance indicator (EPI) has advanced by 9.88% between 2010 and 2017. In addition, the econometric analyses prove that regional renewable energy policies and pollution abatement programs explicitly influence the improvement of the environmental performance index. Again, the results show that the probability figures of the individual specific limit equation and the dual limit values crossed the 1% significance analysis level simultaneously, indicating a dual limit impact. 0.74 to 1 is the range that marks the green EPI for Jiangsu, Shandong, Guangdong, Hainan, Zhejiang, Shanghai and Fujian. Ultimately, the analysis serves as a policy inference tool for policy formulators and regulators on encouraging green economic performance in China.

Gonadotropin-releasing hormone agonist versus expectant management for treating multiple leiomyomas after myomectomy: the study protocol for a multicentre, prospective, randomised controlled clinical trial.

INTRODUCTION: Leiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy. METHODS AND ANALYSIS: We are conducting a phase IV randomised controlled trial in women aged 18-45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17012992.

Synthesis, DNA binding, antibacterial and anticancer properties of two novel water-soluble copper(II) complexes containing gluconate.

In this paper, two new Cu(II) complexes, [Cu(Gluc)(HPB)(H2O)]Gluc (CuG1) and [Cu(Gluc)(HPBC)(H2O)]Gluc (CuG2) (where HPB = 2-(2'-pyridyl)benzimidazole, HPBC = 5-chloro-2-(2'-pyridyl)benzimidazole, Gluc = d-Gluconic acid), with good water solubility were synthesized and characterized. These complexes exhibited a five-coordinated tetragonal pyramidal geometry. The DNA binding and cleavage properties of the complexes were investigated using multi-spectroscopy, viscosity measurement, molecular docking and gel electrophoresis analysis methods. The results showed that the complexes could interact with DNA by insertion and groove binding, and cleave CT-DNA through a singlet oxygen-dependent pathway in the presence of ascorbic acid. The studies on antibacterial and anticancer activities in vitro demonstrated that both complexes had good inhibitory activity against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes) and one Gram-negative bacterium (Escherichia coli) and good cytotoxic activity toward the tested cancer cells (A549, HeLa and SGC-7901). CuG2 showed higher antimicrobial and cytotoxic activities than CuG1, which was consistent with their binding strength and cleavage ability to DNA, indicating that their antimicrobial and cytotoxic activities may be related to the DNA interaction. Moreover, the cell-based mechanism studies have indicated that CuG1 and CuG2 could arrest the cell cycle at G2/M phase, elevate the levels of intracellular reactive oxygen species (ROS) and decrease the mitochondrial membrane potential (MMP). The results showed that the complexes could induce apoptosis through DNA-damaged and ROS-mediated mitochondrial dysfunction pathways. Finally, the in vivo antitumor study revealed that CuG2 inhibited tumor growth by 50.44%, which is better than that of cisplatin (40.94%).

Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis: study protocol for a multicenter, prospective, randomized controlled trial.

BACKGROUND: The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate. METHOD/DESIGN: Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery. DISCUSSION: The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014340. Registered on 6 January 2018.

The Presence of High Levels of Circulating Trimethylamine N-Oxide Exacerbates Central and Peripheral Inflammation and Inflammatory Hyperalgesia in Rats Following Carrageenan Injection.

Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has recently been shown to promote inflammation in peripheral tissues and the central nervous system (CNS), contributing to the pathogenesis of various human diseases. Here, we examined whether the presence of high levels of circulating TMAO would influence central and peripheral inflammation and inflammatory hyperalgesia in a carrageenan (CG)-induced rat model of inflammation. Rats were treated with vehicle or TMAO in drinking water. After 2 weeks of treatment, rats received intraplantar injection of saline or CG into the hind paw. Acute nociception was unaltered in TMAO-treated rats that had elevated plasma TMAO. Following CG injection, TMAO-treated rats were significantly more sensitive to thermal and mechanical stimulation of the inflamed paw and displayed greater paw edema. Molecular studies revealed that CG injection induced increases in recruitment of neutrophils/macrophages in the paw and activation of microglia in the spinal cord, along with increased activation of nuclear factor (NF)-kB and production of proinflammatory mediators in both vehicle-treated rats and TMAO-treated rats. However, the increases in the above parameters were more pronounced in TMAO-treated rats. Moreover, TMAO treatment decreased protein levels of anti-inflammatory mediator regulator of G protein signaling (RGS)-10 in both saline-injected rats and CG-injected rats. These findings suggest that the presence of high levels of circulating TMAO downregulates anti-inflammatory mediator RGS10 in both peripheral tissues and the CNS, which may increase the susceptibility to inflammatory challenge-induced NF-kB activity, leading to greater increase in production of inflammatory mediators and consequent exacerbation of peripheral inflammation and inflammatory hyperalgesia.

Efficacy of antifungal drugs in the treatment of vulvovaginal candidiasis: a Bayesian network meta-analysis.

PURPOSE: Antifungal drugs are used frequently in the treatment of vulvovaginal candidiasis (VVC), but have shown controversial results. In this study, we aimed to evaluate the effectiveness of different antifungal drugs in the treatment of VVC and to provide an evidence-based reference for clinical use. METHODS: The published studies on the effectiveness of antifungal drugs in the treatment of VVC (up to April 2018) were retrieved from PubMed, Embase, the Cochrane Library, and Clini-calTrials.gov. We sifted through the literature according to Patients, Interventions, Comparisons and Outcomes principle, extracted data on the basic characteristics of the study, and evaluated the quality of included studies. We used R software for statistical analysis. RESULTS: In total, 41 randomized controlled trials were included in this meta-analysis. The relative risk of VVC associated with ten drugs, including placebo, fluconazole, clotrimazole, miconazole, itraconazole, ketoconazole, econazole, butoconazole, terbinafine, and terconazole, was analyzed. The following drugs appeared to show more efficacy than placebo in the treated patients: fluconazole (OR =6.45, 95% CrI 4.42-9.41), clotrimazole (OR =2.99, 95% CrI 1.61-5.55), miconazole (OR =5.96, 95% CrI 3.17-11.2), itraconazole (OR =2.29, 95% CrI 1.21-4.33), ketoconazole (OR =2.40, 95% CrI 1.55-3.71), butoconazole (OR =1.18, 95% CrI 1.06-1.31), and terconazole (OR =5.60, 95% CrI 2.78-11.3). The value of surface under the cumulative ranking curve of each drug was as follows: placebo (0.5%), fluconazole (91.5%), clotrimazole (61.8%), miconazole (33.8%), itraconazole (50.5%), ketoconazole (42.8%), econazole (46.8%), butoconazole (82.2%), terbinafine (20.9%), and terconazole (65.0%). CONCLUSION: Antifungal drugs are effective in the treatment of VVC. Fluconazole appeared to be the best drug for the treatment of VVC according to our analysis.

Synthesis, characterization, DNA/HSA interactions and in vitro cytotoxic activities of two novel water-soluble copper(II) complexes with 1,3,5-triazine derivative ligand and amino acids.

Two water-soluble copper(II) complexes of 6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine (pzta) and amino acids, [Cu(pzta)(L-ArgH)(H2O)](ClO4)2 (1) and [Cu(pzta)(L-Met)(H2O)]ClO4·3H2O (2) (L-ArgH: protonated L-Argininate; L-Met: L-Methioninate), were synthesized and characterized. The determined X-ray crystallographic structures of 1 and 2 exhibited distorted square-pyramidal coordination geometries. Their binding properties toward calf thymus DNA (CT-DNA) and human serum protein (HSA) were measured by spectroscopic (UV-Vis, fluorescence, circular dichroism (CD)), calorimetric (isothermal titration calorimetry (ITC)) and molecular docking technology. DNA binding experiments showed that the complexes bound to DNA through a groove binding mode, the positive ΔH and ΔS values indicated that the hydrophobic interaction was the main force in the binding between the complexes and DNA. Besides, the complexes caused the fluorescence quenching of HSA through a static quenching procedure, changed the secondary structure and microenvironment of the Trp-214 residue, and preferably bound to subdomain IIA of HSA driven by hydrophobic and hydrogen-bond interactions. These results were further verified by the molecular docking technology. Furthermore, the in vitro cytotoxicities of the complexes against three human carcinoma cell lines (A549, PC-3 and HeLa) were evaluated, which confirmed that the complexation improved the anticancer activity of the pzta ligand significantly.

CM-101: Type I Collagen-targeted MR Imaging Probe for Detection of Liver Fibrosis.

Purpose To evaluate the biodistribution, metabolism, and pharmacokinetics of a new type I collagen-targeted magnetic resonance (MR) probe, CM-101, and to assess its ability to help quantify liver fibrosis in animal models. Materials and Methods Biodistribution, pharmacokinetics, and stability of CM-101 in rats were measured with mass spectrometry. Bile duct-ligated (BDL) and sham-treated rats were imaged 19 days after the procedure by using a 1.5-T clinical MR imaging unit. Mice were treated with carbon tetrachloride (CCl4) or with vehicle two times a week for 10 weeks and were imaged with a 7.0-T preclinical MR imaging unit at baseline and 1 week after the last CCl4 treatment. Animals were imaged before and after injection of 10 µmol/kg CM-101. Change in contrast-to-noise ratio (ΔCNR) between liver and muscle tissue after CM-101 injection was used to quantify liver fibrosis. Liver tissue was analyzed for Sirius Red staining and hydroxyproline content. The institutional subcommittee for research animal care approved all in vivo procedures. Results CM-101 demonstrated rapid blood clearance (half-life = 6.8 minutes ± 2.4) and predominately renal elimination in rats. Biodistribution showed low tissue gadolinium levels at 24 hours (<3.9% injected dose [ID]/g ± 0.6) and 10-fold lower levels at 14 days (<0.33% ID/g ± 12) after CM-101 injection with negligible accumulation in bone (0.07% ID/g ± 0.02 and 0.010% ID/g ± 0.004 at 1 and 14 days, respectively). ΔCNR was significantly (P < .001) higher in BDL rats (13.6 ± 3.2) than in sham-treated rats (5.7 ± 4.2) and in the CCl4-treated mice (18.3 ± 6.5) compared with baseline values (5.2 ± 1.0). Conclusion CM-101 demonstrated fast blood clearance and whole-body elimination, negligible accumulation of gadolinium in bone or tissue, and robust detection of fibrosis in rat BDL and mouse CCl4 models of liver fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

Sensitive amperometric detection of riboflavin with a whole-cell electrochemical sensor.

A novel whole-cell electrochemical sensor was developed and applied for sensitive amperometric detection of riboflavin. In this work, a whole-cell based riboflavin redox cycling system was characterized, in which electroactive bacteria Shewanella oneidensis MR-1 was employed as the biocatalyst to regenerate the reduced riboflavin after the electrode oxidation. This redox cycling system efficiently enhanced the electrochemical response of riboflavin and enabled a stable current output at poised electrode potential. Thus, a sensitive amperometric biosensing system for riboflavin detection was developed by integrating this whole-cell redox cycling system with the conventional riboflavin electrochemical sensor. Remarkably, this riboflavin biosensor exhibited high sensitivity (LOD = 0.85 ± 0.09 nM, S/N = 3), excellent selectivity and stability. Additionally, reliable analysis of real samples (food and pharmaceutical samples) by this biosensor was achieved. This work provided sensitive and practical tool for riboflavin detection, and demonstrated that the integration of electroactive bacteria and using its outwards electron transfer for redox cycling would be a powerful and promising strategy to improve the performance of electrochemical sensing system.

Use of Microcomputed Tomography to Measure the Relaxin-induced Expansion of Intrapubic Ligaments in Mice.

Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that µCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points. Female CD1 mice were used to compare µCT imaging with the current standard. Both protocols revealed significant differences in intrapubic ligament length, with the µCT data having greater power when corrected for baseline imaging. From these data, we concluded that using µCT to measure the intrapubic ligament in mice primed with estrogen and dosed with relaxin is a viable refinement and will allow the use of fewer animals in longitudinal studies and provide more robust data, because animals can serve as their own controls.