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A biopolymer derived from Jatropha oil-based poly(ethyl carbamate) (PUA) has been used as gel polymer electrolyte (GPE) in optoelectronic devices and photoelectrochemical cells (PEC) as photodiode devices. The quasi-solid-state photodiode device was characterized through photo current–voltage analysis, photogenerated charge carrier dynamic analysis, electrochemical impedance spectroscopy (EIS) analysis, and voltammetry analysis. Sample A2 biopolymer electrolyte (95 wt.% PUA, 5 wt.% LiI, 5 wt.% I2) revealed the highest ionic conductivity (2.34 ± 0.01) × 10−4 S cm−1 and power conversion efficiency (5.09 ± 0.23) %, along with the highest short-circuit current density (17.80 ± 0.41) mA cm−2, open-circuit voltage (0.52 ± 0.01) V, and fill factor (0.55 ± 0.04). respectively. Moreover, sample A2 biopolymer electrolyte featuring a triiodide ion diffusivity of 1.82 × 10−8 cm2 s−1 demonstrated electrochemical stability up to 2.1 V and remained functional for a duration of 2000 cycles. The charge dynamic mechanism in the PEC proved that sample A2 biopolymer electrolyte recorded lowest values of Rs, Rpt, Rct, and Rd of (18.60 ± 0.01) Ω, (1.20 ± 0.01) Ω, (10.0 ± 0.01) Ω, and (11.50 ± 0.01) Ω, respectively. [ABSTRACT FROM AUTHOR]

To improve the isolation ability of the existing equipment for low-frequency line spectrum, this paper presents an electromagnetic double-layer vibration isolation system (ED-VIS) for the first time. The negative and positive stiffness values of the ED-VIS are provided by the electromagnet and the linear spring, respectively. To better analyze the vibration isolation system designed in this paper, the dynamic model of the ED-VIS is established, and the effects of damping ratio, excitation force amplitude, and mass ratio on the force transmissibility feature of the isolator are analyzed. Then, the ED-VIS test bench is built, and the low-frequency vibration isolation capability of the ED-VIS is measured by a frequency sweep test. According to the sweep test results, a method to improve the low-frequency vibration isolation capability of the isolator is proposed. Finally, the reliability of the system in isolating low-frequency vibration is verified. The results show that compared with the equivalent linear vibration isolation system, ED-VIS is more sensitive to low-frequency vibration and has a lower initial vibration isolation frequency. Therefore, this paper designs the ED-VIS has better low-frequency vibration isolation performance. [ABSTRACT FROM AUTHOR]

Objectives: This propensity score–matched population-based cohort study compared stroke risk between patients with type 2 diabetes mellitus with and without preexisting sarcopenia. Research Design and Methods: We used data from Taiwan's National Health Insurance Research Database for the period from January 2008 to December 2019. We recruited patients with type 2 diabetes mellitus and categorized them into two groups at a ratio of 1:1 on the basis of diagnosed sarcopenia. The matching variables were age, sex, income level, urbanization level, diabetes severity (adapted Diabetes Complications Severity Index [aDCSI Scores]), Charlson Comorbidity Index (CCI), other comorbidities associated with stroke, smoking status, medication use, and types of antidiabetic medications. The matching process yielded a final cohort of 104,120 patients (52,060 and 52,060 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for inclusion in subsequent analyses. Results: In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of stroke for the sarcopenia diabetes group compared with the control group was 1.13 (1.{vn10}, 1.16; P < 0.001), after controlling for age, sex, CCI, and aDCSI scores. The incidence rates of stroke for the sarcopenia and nonsarcopenia groups were 295.98 and 260.68 per 10,000 person-years, respectively. The significant IRR (95% CI) of stroke was 1.14 (1.09, 1.17) for the sarcopenia diabetes group compared with the nonsarcopenic diabetes group. Conclusion: Preexisting sarcopenia increased the risk of stroke in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Jatropha oil-based polyurethane acylate gel polymer electrolyte was mixed with different concentrations of tetrabutylammonium iodide salt (TBAI). The temperature dependences of ionic conductivity, dielectric modulus and relaxation time were studied in the range of 298 to 393 K. The highest ionic conductivity of (1.88 ± 0.020) × 10–4 Scm−1 at 298 K was achieved when the gel contained 30 wt% of TBAI and 2.06 wt% of I2. Furthermore, the study found that conductivity-temperature dependence followed the Vogel-Tammann Fulcher equation. From that, it could be clearly observed that 30 wt% TBAI indicated the lowest activation energy of 6.947 kJ mol−1. By using the fitting method on the Nyquist plot, the number density, mobility and diffusion coefficient of the charge carrier were determined. The charge properties were analysed using the dielectric permittivity, modulus and dissipation factor. Apart from this, the stoke drag and capacitance were determined. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the bioequivalence of China-manufactured biosimilar, HLX02, to reference China (CN)- and European Union (EU)-sourced trastuzumab.Methods: This was a two-part Phase 1 study conducted in healthy Chinese males. Part 1 evaluated the safety of different doses of HLX02 (2, 4, 6 or 8 mg/kg; intravenous infusion over 90 min, n = 3 per group). Part 2, a randomized, double-blind study, investigated the pharmacokinetics (PK), safety and immunogenicity of study drugs (HLX02 [n = 37], CN-trastuzumab [n = 35] or EU-trastuzumab [n = 37] at the dose suggested by Part 1 results). The primary PK endpoint was the area under the serum concentration-time curve from time 0 to infinity (AUCinf). Equivalence was concluded if the 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) fell in the equivalence criteria of 0.80-1.25.Results: In Part 1, all doses of HLX02 were well tolerated and 6 mg/kg was suggested for Part 2. The GLSMRs and 90% CIs for AUCinf were: 0.950 (0.891-1.013), 0.914 (0.858-0.973) and 0.962 (0.902-1.025) for HLX02 versus CN-trastuzumab, HLX02 versus EU-trastuzumab and CN-trastuzumab versus EU-trastuzumab, respectively. Secondary endpoints comparisons also fell in the equivalence criteria. Treatment-emergent adverse events were reported in 75.7, 86.5 and 70.3% of the subjects in HLX02, CN-trastuzumab, and EU-trastuzumab groups, respectively. No serious adverse events or deaths occurred. No treatment-related anti-drug antibodies were detected.Conclusion: This study demonstrated comparable safety profiles and PK bioequivalence among HLX02, CN-trastuzumab and EU-trastuzumab in healthy Chinese male subjects.Clinical Trial Registration: ClinicalTrials.gov, NCT02581748, registered at October 19, 2015. [ABSTRACT FROM AUTHOR]

Upregulation of the kynurenine pathway (KP) of tryptophan metabolism is commonly observed in neurodegenerative disease. When activated, L-kynurenine (KYN) increases in the periphery and central nervous system where it is further metabolised to other neuroactive metabolites including 3-hydroxykynurenine (3-HK), kynurenic acid (KYNA) and quinolinic acid (QUIN). Particularly biologically relevant metabolites are 3-HK and QUIN, formed downstream of the enzyme kynurenine 3-monooxygenase (KMO) which plays a pivotal role in maintaining KP homeostasis. Indeed, excessive production of 3-HK and QUIN has been described in neurodegenerative disease including Alzheimer's disease and Huntington's disease. In this study, we characterise KMO activity in human primary neurons and identified new mechanisms by which KMO activation mediates neurotoxicity. We show that while transient activation of the KP promotes synthesis of the essential co-enzyme nicotinamide adenine dinucleotide (NAD+), allowing cells to meet short-term increased energy demands, chronic KMO activation induces production of reactive oxygen species (ROS), mitochondrial damage and decreases spare-respiratory capacity (SRC). We further found that these events generate a vicious-cycle, as mitochondrial dysfunction further shunts the KP towards the KMO branch of the KP to presumably enhance QUIN production. These mechanisms may be especially relevant in neurodegenerative disease as neurons are highly sensitive to oxidative stress and mitochondrial impairment. [ABSTRACT FROM AUTHOR]

β-Methylamino- l-alanine (BMAA) is implicated in neurodegeneration and neurotoxicity, particularly in ALS-Parkinson Dementia Complex. Neurotoxic properties of BMAA have been partly elucidated, while its transcellular spreading capacity has not been examined. Using reconstructed neuronal networks in microfluidic chips, separating neuronal cells into two subcompartments-(1) the proximal, containing first-order neuronal soma and dendrites, and (2) a distal compartment, containing either only axons originating from first-order neurons or second-order striatal neurons-creates a cortico-striatal network. Using this system, we investigated the toxicity and spreading of BMAA in murine primary neurons. We used a newly developed antibody to detect BMAA in cells. After treatment with 10 μM BMAA, the cyanotoxin was incorporated in first-degree neurons. We also observed a rapid trans-neuronal spread of BMAA to unexposed second-degree neurons in 48 h, followed by axonal degeneration, with limited somatic death. This in vitro study demonstrates BMAA axonal toxicity at sublethal concentrations and, for the first time, the transcellular spreading abilities of BMAA. This neuronal dying forward spread that could possibly be associated with progression of some neurodegenerative diseases especially amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

The NMDA-receptor antagonist ketamine has proven efficient in reducing symptoms of suicidality, although the mechanisms explaining this effect have not been detailed in psychiatric patients. Recent evidence points towards a low-grade inflammation in brains of suicide victims. Inflammation leads to production of quinolinic acid (QUIN) and kynurenic acid (KYNA), an agonist and antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, respectively. We here measured QUIN and KYNA in the cerebrospinal fluid (CSF) of 64 medication-free suicide attempters and 36 controls, using gas chromatography mass spectrometry and high-performance liquid chromatography. We assessed the patients clinically using the Suicide Intent Scale and the Montgomery-Asberg Depression Rating Scale (MADRS). We found that QUIN, but not KYNA, was significantly elevated in the CSF of suicide attempters (P<0.001). As predicted, the increase in QUIN was associated with higher levels of CSF interleukin-6. Moreover, QUIN levels correlated with the total scores on Suicide Intent Scale. There was a significant decrease of QUIN in patients who came for follow-up lumbar punctures within 6 months after the suicide attempt. In summary, we here present clinical evidence of increased QUIN in the CSF of suicide attempters. An increased QUIN/KYNA quotient speaks in favor of an overall NMDA-receptor stimulation. The correlation between QUIN and the Suicide Intent Scale indicates that changes in glutamatergic neurotransmission could be specifically linked to suicidality. Our findings have important implications for the detection and specific treatment of suicidal patients, and might explain the observed remedial effects of ketamine. [ABSTRACT FROM AUTHOR]

Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers. [ABSTRACT FROM AUTHOR]