bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Cr Doping on the Voltage Fade of Li-Rich Mn-Rich Li1.11Ni0.33Mn0.56O2 and Li1.2Ni0.2Mn0.6O2 Positive Electrode Materials
Authors: Phattharasupakun Nutthaphon , Geng Chenxi , Johnson Michel B. , Väli Ronald , Sawangphruk Montree , Dahn J. R.
Published: December 2020

Voltage fade during charge-discharge cycling in Layered Li-rich Mn-rich positive electrode materials needs to be overcome for the development of high-energy low cost Li-ion batteries. Several cation dopants have been introduced into the bulk lattice to mitigate voltage decay by limiting transition metal (TM) migration, inhibiting phase transformation, or reducing the extent of oxygen release. Here, a series of electrochemically active Cr substituted (2.5, 5.0, and 10 mol%) Co-free Li1.11Ni0.33Mn0.56O2 and Li1.2Ni0.2Mn0.6O2 compositions were synthesized via dry particle fusion followed by heat treatment with Li2CO3. Cr doping improves specific capacity and capacity retention via multiple electron transfer of Cr3+/Cr6+ as well as mitigates voltage fading to a certain extent. The impact of Cr on voltage decay was studied by careful measurements of dQ/dV vs V on Cr-doped and undoped samples before and after cycle testing.
Communication—Prediction of Thermal Issues for Larger Format 4680 Cylindrical Cells and Their Mitigation with Enhanced Current Collection
Authors: Tranter T. G. , Timms R. , Shearing P. R. , Brett D. J. L.
Published: December 2020

The paper numerically explores the electrochemical and thermal behaviour of a larger format 4680 cylindrical cell recently proposed by Tesla and explains the need to go “tabless.” An idealized spiral geometry is used for 2D simulations with the traditional tab-based current collection method and a new continuous current collection method compared. The new design is found to mitigate the ohmic losses experienced around the “jelly-roll” current collectors which are significant for the traditional tabbed case, thus leading to higher efficiency and capacity and reduced heat production.
Stabilized Phase Transition Process of Layered NaxCoO2 via Ca-Substitution
Authors: Hasegawa Hirona , Ishado Yuji , Okada Shigeto , Mizuhata Minoru , Maki Hideshi , Matsui Masaki
Published: December 2020

We investigated the suppressed capacity fading of a Ca-substituted P3-type NaxCoO2 during the charge/discharge process. The Ca-substituted NaxCoO2 shows similar phase transition behavior to the Ca free one, with an expanded P′3 phase region. The capacity fading of the NaxCoO2 is highly correlated with the phase transition at 4.0 V of P′3–O3′ phase transition and at 2.7 V of O′3–P′3 phase transition. The amount of Co3O4 observed in the cycled electrodes corresponds to the capacity loss during the cycling test. Thus, the migration of the Co3+/4+ ions during the phase transition process causes the capacity fading. The decomposition of the electrolyte solution also accelerates the migration of the Co3+/4+ ions. Though the Ca-substitution does not prevent the phase transition, the Ca-substituted NaxCoO2 shows improved capacity retention.
Microfluidic Device for In Situ Observation of Bottom-Up Copper Electrodeposition in a TSV-Like Structure
Authors: Akita Takanori , Otsuka Yuki , Hayase Masanori
Published: December 2020

Using a microfluidic device with a replica TSV (Through Silicon Via) structure, in situ observation of the copper via filling was made. Although the bottom-up TSV filling is possible by electroplating with a combination of several additives, the mechanism of bottom-up filling is not yet clear. Observation of the filling behavior is important, and cross sectioning of the TSVs is widely used. But the sectioning process takes some time, and continuous observation of the progress of deposition is difficult. In this study, a replica TSV structure was constructed in a microchannel, and real-time observation using the microfluidic device took place. As an example, extreme bottom-up filling obtained with addition of the leveler was monitored, and the effect of the immersion time before the plating, and progress of electrodeposition toward the via opening, were demonstrated. The observed deposition behavior was discussed in terms of the diffusion-adsorption model, and moderate agreement of the initial locations of deposition between the experiments and a simple 1-d numerical model estimate was obtained.
Editors’ Choice—Vibrational Properties of Oxygen-Hydrogen Centers in H+- and D+-Implanted Ga2O3
Authors: Portoff Amanda , Venzie Andrew , Qin Ying , Stavola Michael , Fowler W. Beall , Pearton Stephen J.
Published: December 2020

The ion implantation of H+ and D+ into Ga2O3 produces several O–H and O–D centers that have been investigated by vibrational spectroscopy. These defects include the dominant VGa(1)-2H and VGa(1)-2D centers studied previously along with additional defects that can be converted into this structure by thermal annealing. The polarization dependence of the spectra has also been analyzed to determine the directions of the transition moments of the defects and to provide information about defect structure. Our experimental results show that the implantation of H+ (or D+) into Ga2O3 produces two classes of defects with different polarization properties. Theory finds that these O–H (or O–D) centers are based on two shifted configurations of a Ga(1) vacancy that trap H (or D) atom(s). The interaction of VGa(1)-nD centers with other defects in the implanted samples has also been investigated to help explain the number of O–D lines seen and their reactions upon annealing. Hydrogenated divacancy VGa(1)-VO centers have been considered as an example.
Explosion in the complexity of membrane protein recycling
Authors: McDonald Fiona J.
Published: December 2020

For decades, recycling of membrane proteins has been represented in figures by arrows between the “endosome” and the plasma membrane, but recently there has been an explosion in the understanding of the mechanisms and protein complexes required to facilitate protein recycling. Here, some key discoveries will be introduced, including assigning function to a number of recently recognized protein complexes and linking their function to protein recycling. Furthermore, the importance of lipid interactions and links to diseases and epithelial polarity will be summarized.
Hepatocyte-specific expression of human carboxylesterase 2 attenuates nonalcoholic steatohepatitis in mice
Authors: Xu Yanyong , Pan Xiaoli , Hu Shuwei , Zhu Yingdong , Cassim Bawa Fathima , Li Yuanyuan , Yin Liya , Zhang Yanqiao
Published: December 2020

Human CES2 attenuates high-fat/cholesterol/fructose diet-induced steatohepatitis and reverses steatohepatitis in db/db mice. Mechanistically, human CES2 induces lipolysis, fatty acid and glucose oxidation, and inhibits hepatic glucose production, inflammation, lipid oxidation, and apoptosis. Our data suggest that human CES2 may be targeted for treatment of non-alcoholic steatohepatitis (NASH).
Profibrotic epithelial TGF-β1 signaling involves NOX4-mitochondria cross talk and redox-mediated activation of the tyrosine kinase FYN
Authors: Veith Carmen , Hristova Milena , Danyal Karamatullah , Habibovic Aida , Dustin Christopher M. , McDonough John E. , Vanaudenaerde Bart M. , Kreuter Michael , Schneider Marc A. , Kahn Nicolas , van Schooten Frederik J. , Boots Agnes W. , van der Vliet Albert
Published: December 2020

Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed redox balance and increased production of reactive oxygen species (ROS), which is believed to contribute to epithelial injury and fibrotic lung scarring. The main pulmonary sources of ROS include mitochondria and NADPH oxidases (NOXs), of which the NOX4 isoform has been implicated in IPF. Non-receptor SRC tyrosine kinases (SFK) are important for cellular homeostasis and are often dysregulated in lung diseases. SFK activation by the profibrotic transforming growth factor-β (TGF-β) is thought to contribute to pulmonary fibrosis, but the relevant SFK isoform and its relationship to NOX4 and/or mitochondrial ROS in the context of profibrotic TGF-β signaling is not known. Here, we demonstrate that TGF-β1 can rapidly activate the SRC kinase FYN in human bronchial epithelial cells, which subsequently induces mitochondrial ROS (mtROS) production, genetic damage shown by the DNA damage marker γH2AX, and increased expression of profibrotic genes. Moreover, TGF-β1–induced activation of FYN involves initial activation of NOX4 and direct cysteine oxidation of FYN, and both FYN and mtROS contribute to TGF-β–induced induction of NOX4. NOX4 expression in lung tissues of IPF patients is positively correlated with disease severity, although FYN expression is down-regulated in IPF and does not correlate with disease severity. Collectively, our findings highlight a critical role for FYN in TGF-β1–induced mtROS production, DNA damage response, and induction of profibrotic genes in bronchial epithelial cells, and suggest that altered expression and activation of NOX4 and FYN may contribute to the pathogenesis of pulmonary fibrosis.
Visual responses in the dorsolateral frontal cortex of marmoset monkeys
Authors: Feizpour Azadeh , Majka Piotr , Chaplin Tristan A. , Rowley Declan , Yu Hsin-Hao , Zavitz Elizabeth , Price Nicholas S. C. , Rosa Marcello G. P. , Hagan Maureen A.
Published: December 2020

Behavior and cognition in humans and other primates rely on networks of brain areas guided by the frontal cortex. The marmoset offers exciting new opportunities to study links between brain physiology and behavior, but the functions of frontal cortex areas are still being identified in this species. Here, we provide the first evidence of visual receptive fields in the marmoset dorsolateral frontal cortex, an important step toward future studies of visual cognitive behavior.
Minimally Invasive Ways of Determining Circadian Rhythms in Humans
Authors: Crnko Sandra , Schutte Hilde , Doevendans Pieter A. , Sluijter Joost P. G. , van Laake Linda W.
Published: December 2020

Circadian rhythm exerts a critical role in mammalian health and disease. A malfunctioning circadian clock can be a consequence, as well as the cause of several pathophysiologies. Clinical therapies and research may also be influenced by the clock. Since the most suitable manner of revealing this rhythm in humans is not yet established, we discuss existing methods and seek to determine the most feasible ones.
Interplay of the Circadian Clock and Endothelin System
Authors: Douma Lauren G. , Barral Dominique , Gumz Michelle L.
Published: December 2020

The peptide hormone endothelin-1 and its receptors are linked to several disease states. Pharmacological inhibition of this pathway has proven beneficial in pulmonary hypertension, yet its potential in other disease states remains to be realized. This review considers an often understudied aspect of endothelin biology, circadian rhythm regulation and how understanding the intersection between endothelin signaling and the circadian clock may be leveraged to realize the potential of endothelin-based therapeutics.
Approximate Analytic Solutions of Two-Dimensional Nonlinear Klein–Gordon Equation by Using the Reduced Differential Transform Method
Authors: Belayeh Wayinhareg Gashaw , Mussa Yesuf Obsie , Gizaw Ademe Kebede
Published: December 2020

In this paper, the reduced differential transform method (RDTM) is successfully implemented for solving two-dimensional nonlinear Klein–Gordon equations (NLKGEs) with quadratic and cubic nonlinearities subject to appropriate initial conditions. The proposed technique has the advantage of producing an analytical approximation in a convergent power series form with a reduced number of calculable terms. Two test examples from mathematical physics are discussed to illustrate the validity and efficiency of the method. In addition, numerical solutions of the test examples are presented graphically to show the reliability and accuracy of the method. Also, the results indicate that the introduced method is promising for solving other type systems of NLPDEs.
A Short-Turn Dispatching Strategy to Improve the Reliability of Bus Operation
Authors: Liu Runkun , Yu Haiyang , Wang Pengfei , Yan Hai
Published: December 2020

Bus dwelling time at stops is affected by the number of boarding and alighting passengers. Due to the uncertainty of traffic state, dwelling time will become unstable, resulting in unreliable bus operations. A short-turn strategy shares passenger demand in certain segments of the full-length vehicles; therefore, this strategy can reduce the dwell time of the full-length vehicles and have potential to improve reliability of bus operations. Firstly, this paper builds a bus operation state model considering short-turn vehicles. Secondly, the process of bus operation is analyzed to investigate the impact of passenger demand on reliability. Then, we propose a short-turn dispatching strategy, which can accurately determine the operation area and departure time. Finally, a numerical simulation is used to evaluate different strategies. As the result, the analysis reveals the following: (1) the bus operational reliability of full-length vehicles under high passenger demand could be improved by a well-designed short-turn strategy; (2) it is beneficial to improve the reliability of bus operation when short-turn vehicles departure at the change point; and (3) an undesigned short-turn dispatching strategy has a negative effect on full-length vehicles operational reliability. This study can help design a short-turn strategy and make valuable contributions to the bus management system.
Subglottic Stenosis in Children: Preliminary Experience from a Tertiary Care Hospital
Authors: Ahmad Latoo Manzoor , Jallu Aleena Shafi
Published: December 2020

Introduction. This retrospective study describes our experience in the evaluation and management of infants with subglottic stenosis. Materials and Methods. The study included 10 patients aged between 1 wk and 18 months with 6 cases having congenital subglottic stenosis and 4 cases having acquired subglottic stenosis. Results. 6 patients had grade I, 3 patients had grade II, and 1 patient had grade III subglottic stenosis. Tracheostomy was required in 4 patients at the time of presentation. 7 patients were treated successfully with Bougie dilation followed by topical application of mitomycin, whereas 1 patient who failed to serial dilation needed open reconstructive procedure. Laser excision of the anterior subglottic web was performed in one patient. Another patient with underlying cerebral palsy could not be operated upon and was managed with tracheostomy. Conclusion. Subglottic stenosis may be effectively man-aged with endoscopic surgical techniques, although the number of such sittings required varies with the type and severity of stenosis. Open surgical procedures need to be individualised as per the needs of the patient only after all the other endoscopic possibilities have been exhausted.
A 14-Year Retrospective Analysis of Endogenous Endophthalmitis in a Tertiary Referral Center of Southern Thailand
Authors: Bhurayanontachai Patama , Klongthanakit Phingphan
Published: December 2020

Purpose. To investigate patient characteristics, clinical features, common causative organisms, and visual acuity outcomes in endogenous endophthalmitis. Methods. This was a retrospective chart analysis of patients with endogenous endophthalmitis between January 2006 and December 2019. Collected data included basic patient characteristics, presenting symptoms, causative organisms, treatments, and 3-month and 1-year visual outcomes. Results. Twenty-nine eyes of 27 patients were included in the study. The mean age of the patients was 45.4 ± 19.9 years, and 63% were female. Visual acuity at presentation ranged from counting fingers to no light perception. Systemic comorbidities presented in 66.7% of the patients, the majority of which were related to diabetes mellitus (48.1%). The most common primary infection was a urinary tract infection. Positive blood cultures were identified in 48.1% of patients, and positive cultures from vitreous and aqueous samples were identified in 59.3% and 31.6% of eyes, respectively. Among all the specimens, Gram-positive bacteria were identified in 55.5%, Gram-negative bacteria in 22.2%, fungi in 14.8%, and mixed organisms in 7.4%. Among ocular specimens, 61.1% contained Gram-positive organisms, 16.7% contained Gram-negative organisms, and 22.2% contained fungi. Streptococcus spp. was the most common causative organism. From 29 eyes, 18 (62.1%) underwent vitrectomy, and 12 (42.9%) underwent either evisceration or enucleation. Positive vitreous culture was significantly associated with unfavorable final visual outcome. Final visual acuity ranged from 20/125 to no light perception. Although visual improvement at 3 months was significantly better in younger patients, this had no impact on final visual outcome at 1 year. Conclusion. Eyes with positive vitreous cultures had significantly poorer visual outcomes. Despite full treatment coverage, visual prognosis was extremely poor and the rates of blindness and evisceration/enucleation were still high.
An Accurate Sparse Recovery Algorithm for Range-Angle Localization of Targets via Double-Pulse FDA-MIMO Radar
Authors: Liu Qi , Wang Xianpeng , Wan Liangtian , Huang Mengxing , Sun Lu
Published: December 2020

In this paper, a sparse recovery algorithm based on a double-pulse FDA-MIMO radar is proposed to jointly extract the angle and range estimates of targets. Firstly, the angle estimates of targets are calculated by transmitting a pulse with a zero frequency increment and employing the improved

l

1

-SVD method. Subsequently, the range estimates of targets are achieved by utilizing a pulse with a nonzero frequency increment. Specifically, after obtaining the angle estimates of targets, we perform dimensionality reduction processing on the overcomplete dictionary to achieve the automatically paired range and angle in range estimation. Grid partition will bring a heavy computational burden. Therefore, we adopt an iterative grid refinement method to alleviate the above limitation on parameter estimation and propose a new iteration criterion to improve the error between real parameters and their estimates to get a trade-off between the high-precision grid and the atomic correlation. Finally, the proposed algorithm is evaluated by providing the results of the Cramér-Rao lower bound (CRLB) and numerical root mean square error (RMSE).
Probe into the Target and Mechanism of Jianpi Xiaoke Prescription for Treating Type 2 Diabetes Mellitus through miRNA Expression Profiling
Authors: Guo Qiuyue , Xu Yunsheng , Li Jie , Luo Dan , Li Jun , Xu Cankun , Huang Yanqin
Published: December 2020

Object. To probe into the target and molecular mechanism of Jianpi Xiaoke (JPXK) prescription in the treatment of type 2 diabetes through high‐throughput microRNA (miRNA) sequencing. Methods. Ten of the 31 SPF male Wistar rats were randomly taken as the control group; the remaining rats were fed a high‐sugar and high‐fat diet, combined with Streptozotocin (STZ, 35 mg/kg) that induced a type 2 diabetes model. The model rats were randomly divided into model groups (n = 11) and the JPXK group (n = 10). After 8 weeks of JPXK intervention, we detected the function of islet cells through HE staining and ELISA. High‐pass sequencing technology was adopted to identify the differential expression of miRNA to explore the target of JPXK treatment, assess the relevant target genes, conduct functional analysis, and lastly verify the sequencing data by qRT‐PCR. Results. After treatment, FPG, FINS, and HOMA‐IR levels of the treatment group improved significantly compared with those of the control group (P < 0.05). Among the miRNAs differentially expressed between the model group and the control group, there were 7 reversals after JPXK treatment, including miR‐1‐3p, miR‐135a‐5p, miR‐181d‐5p, miR‐206‐3p, miR‐215, miR‐3473, and miR‐547‐3p (log2FC ≥ 1 or ≤ −1, P < 0.05). Besides, the 1810 target genes associated with these 7 miRNAs were assessed by multiMiR. According to the results of the GO and KEGG analyses, they were associated with biological processes (e.g., glucose transport and fat cell formation), and it covered multiple signaling pathways, capable of regulating islet cell function (e.g., MAPK, PI3K‐Akt, Ras, AMPK, and HIF‐1 signaling pathways). The PCR verification results were consistent with the sequencing results. Conclusion. This discovery interpreted the potential therapeutic targets and signaling pathways of JPXK prescription against T2DM based on miRNA expression profiling. In conclusion, our research provided novel research insights into traditional Chinese medicine (TCM) treatment of diabetes.
The Inhibition Effects of Shenmai Injection on Acetylcholine‐Induced Catecholamine Synthesis and Secretion by Modulating Nicotinic Acetylcholine Receptor Ion Channels in Cultured Bovine Adrenal Medullary Cells
Authors: Zhang Xiting , Li Lin , Wang Yi , Mao Haoping , Chai Lijuan , Miao Lin , Wang Shuang , Gao Xiumei , Zhang Han
Published: December 2020

Shenmai injection (SMI) has been widely used for the treatment of cardiovascular diseases in China. Cardiovascular disorders are often related to excessive catecholamine (CA) secretion. Here, we report the effects of SMI on CA secretion and synthesis in cultured bovine adrenal medullary cells. We found that SMI significantly reduced CA secretion induced by 300 μM acetylcholine (ACh). Cotreatment with SMI (10 μL/mL) and either of the ACh receptor α‐subunit inhibitors, HEX (α3) or DhβE (α4β2), did not produce any further inhibition, indicating that SMI may play a role through α3 and α4β2 channels. Furthermore, SMI reduced tyrosine hydroxylase (TH) activity induced by ACh by inhibiting the phosphorylation of TH at Ser19 and Ser40. TH is phosphorylated at Ser19 by Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II) and at Ser40 by protein kinase A (PKA). KN‐93 and H89, the antagonists of CaM kinase II and PKA, respectively, inhibited the ACh‐induced phosphorylation at Ser19 and Ser40, and the addition of SMI did not augment the inhibitory effect. Taken together, our results show that SMI likely inhibits CA secretion by blocking TH activity at its Ser19 and Ser40 sites.
A Retrospective Clinical Audit of Bracket Failure among Patients Undergoing Orthodontic Therapy
Authors: Kafle Dashrath , Mishra Rajeev Kumar , Hasan Md Riasat , Saito Takashi
Published: December 2020

Objective. Bonding failure is a problem in orthodontic therapy and has been associated with orthodontic emergencies and delayed treatment time. The aim of this study is to determine the bracket failure rate among patients undergoing orthodontic therapy. Materials and Methods. From the archives of posttreatment records, 200 total cases were selected, out of which 122 cases had detailed treatment records. Cases with incomplete records, large restorations, or enamel aberrations were excluded from the study. Descriptive statistics were applied to obtain sample characteristics, and a chi-square test was applied to compare the bracket failure between different categories. Result. Out of the 122 samples enrolled in the study, female and male patients comprised 71% and 29%, respectively. Class I malocclusions were the most common problem (56%), followed by Class II (41%) and Class III (3%). The bracket failure rate was 3.43%, and 32% of the patients had an incidence of bracket failure. There was no significant difference in bracket failure among genders (p=0.344), malocclusion types (p=0.191), or operators (p=0.188). The maxillary left quadrant was the most common site of bracket failure, followed by the mandibular right quadrant. Conclusion. Bracket failure is relatively uncommon. It is not affected by the gender or age of the patient or by malocclusion type. The maxillary left and mandibular right quadrants are the most common sites of bracket failure.
An Accurate Predictor-Corrector-Type Nonstandard Finite Difference Scheme for an SEIR Epidemic Model
Authors: Farooqi Asma , Ahmad Riaz , Farooqi Rashada , Alharbi Sayer O. , Baleanu Dumitru , Rafiq Muhammad , Khan Ilyas , Ahmad M. O.
Published: December 2020

The present work deals with the construction, development, and analysis of a viable normalized predictor-corrector-type nonstandard finite difference scheme for the SEIR model concerning the transmission dynamics of measles. The proposed numerical scheme double refines the solution and gives realistic results even for large step sizes, thus making it economical when integrating over long time periods. Moreover, it is dynamically consistent with a continuous system and unconditionally convergent and preserves the positive behavior of the state variables involved in the system. Simulations are performed to guarantee the results, and its effectiveness is compared with well-known numerical methods such as Runge–Kutta (RK) and Euler method of a predictor-corrector type.
Astragaloside IV Enhances Melanogenesis via the AhR‐Dependent AKT/GSK‐3β/β‐Catenin Pathway in Normal Human Epidermal Melanocytes
Authors: Liu Baoyi , Xie Yongyi , Wu Zhouwei
Published: December 2020

Astragalus membranaceus root has been widely used for repigmentation treatment in vitiligo, but its mechanism is poorly understood. We sought to investigate the effect of astragaloside IV (AS‐IV), a main active extract of the Astragalus membranaceus root, on melanin synthesis in normal human epidermal melanocytes (NHEMs) and to elucidate its underlying mechanisms. Melanin content, tyrosinase activity, qPCR, western blot, and immunofluorescence were employed. Specific inhibitors and small interfering RNA were used to investigate the possible pathway. AS‐IV stimulated melanin synthesis and upregulated the expression of melanogenesis‐related genes in a concentration‐dependent manner in NHEMs. AS‐IV could activate the aryl hydrocarbon receptor (AhR), and AS‐IV‐induced melanogenesis was inhibited in si‐AhR‐transfected NHEMs. In addition, we showed that AS‐IV enhanced the phosphorylation of AKT and GSK‐3β and nuclear translocation of β‐catenin. AS‐IV‐induced MITF expression upregulation and melanin synthesis were decreased in the presence of β‐catenin inhibitor FH353. Furthermore, AhR antagonist CH223191 inhibited the activation of AKT/GSK‐3β/β‐catenin signaling, whereas the expression of CYP1A1 (marker of AhR activation) was not affected by the AKT inhibitor in AS‐IV‐exposed NHEMs. Our findings show that AS‐IV induces melanogenesis through AhR‐dependent AKT/GSK‐3β/β‐catenin pathway activation and could be beneficial in the therapy for depigmented skin disorders.
Residues Analysis and Dissipation Dynamics of Broflanilide in Rice and Its Related Environmental Samples
Authors: Xie Guai , Zhou Wenwen , Jin Mingxia , Yu Ailin , Rao Lei , Jia Horan , Luo Juan , He Yichang , Li Baotong
Published: December 2020

Herein, we present a method for the quantitative analysis of broflanilide residues in water, soil, and rice samples from a paddy field in Jiangxi Province, China. The quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was optimized for the extraction and purification of broflanilide residues. Residual broflanilide concentrations in different matrices were then determined by high-performance liquid chromatography (HPLC). The calibration curve of broflanilide showed good linearity in all matrices for concentrations between 0.005 and 1 mg·L−1, with a correlation coefficient greater than 0.99. The matrix effect varied from −69% to −54%, indicating matrix suppression. The average recoveries ranged between 85.82% and 97.46%, with relative standard deviations of 3.29%–8.15%. The limits of detection ranged from 0.16 to 1.67 μg·kg−1, and the limits of quantification were in the range of 0.54 to 5.48 μg·kg−1. Dissipation dynamic tests indicated broflanilide half-lives of 0.46–2.46, 2.09–5.34, and 1.31–3.32 days in soil, water, and rice straw, respectively. Broflanilide was dissipated more rapidly in water than in soil and rice straw. More than 90% of broflanilide residues dissipated within 14 days. The final residues of broflanilide in rice were all below LOQ at harvest.
Tartaric Acid-Modified Holarrhena antidysenterica and Citrullus colocynthis Biowaste for Efficient Eradication of Crystal Violet Dye from Water
Authors: Basharat Sumaira , Rehman Rabia , Mahmud Tariq , Basharat Sara , Mitu Liviu
Published: December 2020

Two novel adsorbents Holarrhena antidysenterica (HA) and Citrullus colocynthis (CC) were collected from native Pakistan and treated with tartaric acid. The adsorbents were characterized by Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy, and their adsorptive behavior was studied against model cationic dye crystal violet (CV). Role of biosorbent dose, time of contact, temperature studies, agitation rates, and solution pH was investigated. Optimum conditions obtained for the removal of CV dye for H. antidysenterica-tartaric acid modified (HA-TA) were as follows: 0.8 g adsorbent dose, 35 minutes contact time, 5.0 pH, 40°C temperature, and 150 rpm agitation rates as compared to H. antidysenterica that gave 1.4 g adsorbent dose, 40 minutes time of contact, 6.0 pH, 50°C temperature, and 150 rpm agitation speed. C. colocynthis-tartaric acid modified (CC-TA) removed CV dye at 0.6 g adsorbent dose, 30 minutes contact interval, 4.0 pH, 40°C temperature, and 125 rpm agitation speed in contrast to C. colocynthis which gave 0.8 g adsorbent dose, 40 minutes time of contact, 6.0 pH, 50°C temperature, and 125 rpm agitation speed, respectively. Isothermal studies for both raw and modified biosorbents were compliant with the Langmuir model indicating monolayer, chemisorption. The maximum Langmuir capacities were up to 128.20 mg/g, 136.98 mg/g, 144.92 mg/g, and 166.66 mg/g for HA, CC, HA-TA, and CC-TA. Pseudo-second-order kinetic model well fitted the dye removal data. The rate-determining steps involved both surface and intraparticle diffusion mechanisms. Adsorption of dye molecules on active surfaces was governed by electrostatic attractions and chelating abilities. Thermodynamics research revealed the spontaneous and exothermic nature of the reaction. The adsorbents serve promising candidates for the effective removal of hazardous dyes from aqueous solutions.
Synthesis of Ternary Fe3O4/ZnO/Chitosan Magnetic Nanoparticles via an Ultrasound-Assisted Coprecipitation Process for Antibacterial Applications
Authors: Thanh Vu Minh , Huong Nguyen Thi , Nam Dao The , Dung Nguyen Dinh Tien , Le Van Thu  , Nguyen-Le Minh-Tri
Published: December 2020

In this study, Fe3O4/ZnO/chitosan magnetic nanoparticles were synthesized by an ultrasound-assisted coprecipitation method. The magnetic nanoparticles were characterized by XRD, FT-IR, FESEM, and VSM techniques. The effects of ultrasonication time and content of chitosan on crystal size and lattice parameters of the nanoparticles were also studied via XRD spectra. FESEM measurements revealed that the coating consists of Fe3O4/ZnO nanoparticles of 15-20 nm in diameter homogeneously dispersed on the surface of chitosan substance. The VSM measurements at room temperature showed that the Fe3O4/ZnO/chitosan nanoparticles had superparamagnetic properties. These results indicated that ultrasonication time and chitosan content had a significant effect on the characteristics of nanoparticles. The antibacterial activities of the Fe3O4/ZnO/chitosan were tested against both gram-positive Saccharomyces cerevisiae and Bacillus subtilis and gram-negative E. coli bacteria using a disk diffusion method.
Modeled Reductions in Late-stage Cancer with a Multi-Cancer Early Detection Test
Authors: Hubbell Earl , Clarke Christina A. , Aravanis Alexander M. , Berg Christine D.
Published: December 2020

Background:

Cancer is the second leading cause of death globally, with many cases detected at a late stage when prognosis is poor. New technologies enabling multi-cancer early detection (MCED) may make “universal cancer screening” possible. We extend single-cancer models to understand the potential public health effects of adding a MCED test to usual care.

Methods:

We obtained data on stage-specific incidence and survival of all invasive cancers diagnosed in persons aged 50–79 between 2006 and 2015 from the US Surveillance, Epidemiology, and End Results (SEER) program, and combined this with published performance of a MCED test in a state transition model (interception model) to predict diagnostic yield, stage shift, and potential mortality reductions. We model long-term (incident) performance, accounting for constraints on detection due to repeated screening.

Results:

The MCED test could intercept 485 cancers per year per 100,000 persons, reducing late-stage (III+IV) incidence by 78% in those intercepted. Accounting for lead time, this could reduce 5-year cancer mortality by 39% in those intercepted, resulting in an absolute reduction of 104 deaths per 100,000, or 26% of all cancer-related deaths. Findings are robust across tumor growth scenarios.

Conclusions:

Evaluating the impact of a MCED test that affects multiple cancer types simultaneously requires modeling across all cancer incidence. Assuming MCED test metrics hold in a clinical setting, the aggregate potential to improve public health is significant.

Impact:

Modeling performance of a MCED test in a representative population suggests that it could substantially reduce overall cancer mortality if added to usual care.
Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma
Authors: Zhang Qianfei , Ma Chi , Duan Yi , Heinrich Bernd , Rosato Umberto , Diggs Laurence P. , Ma Lichun , Roy Soumen , Fu Qiong , Brown Zachary J. , Wabitsch Simon , Thovarai Vishal , Fu Jianyang , Feng Dechun , Ruf Benjamin , Cui Linda L. , Subramanyam Varun , Frank Karen M. , Wang Sophie , Kleiner David E. , Ritz Thomas , Rupp Christian , Gao Bin , Longerich Thomas , Kroemer Alexander , Wang Xin Wei , Ruchirawat Mathuros , Korangy Firouzeh , Schnabl Bernd , Trinchieri Giorgio , Greten Tim F.
Published: December 2020

Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity in the liver is largely unknown. Here we studied how the gut microbiome affects antitumor immunity in cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development in mice, caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease in gut barrier function observed in mice with PSC and colitis allowed gut-derived bacteria and lipopolysaccharide to appear in the liver and induced CXCL1 expression in hepatocytes through a TLR4-dependent mechanism and an accumulation of CXCR2+ PMN-MDSCs. In contrast, neomycin treatment blocked CXCL1 expression and PMN-MDSC accumulation and inhibited tumor growth even in the absence of liver disease or colitis. Our study demonstrates that the gut microbiome controls hepatocytes to form an immunosuppressive environment by increasing PMN-MDSCs to promote liver cancer.

Significance:

MDSCs have been shown to be induced by tumors and suppress antitumor immunity. Here we show that the gut microbiome can control accumulation of MDSCs in the liver in the context of a benign liver disease or colitis.

See related commentary by Chagani and Kwong, p. 1014.

This article is highlighted in the In This Issue feature, p. 995
MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression
Authors: Knight John R.P. , Alexandrou Constantinos , Skalka George L. , Vlahov Nikola , Pennel Kathryn , Officer Leah , Teodosio Ana , Kanellos Georgios , Gay David M. , May-Wilson Sebastian , Smith Ewan M. , Najumudeen Arafath K. , Gilroy Kathryn , Ridgway Rachel A. , Flanagan Dustin J. , Smith Rachael C.L. , McDonald Laura , MacKay Craig , Cheasty Anne , McArthur Kerri , Stanway Emma , Leach Joshua D. , Jackstadt Rene , Waldron Joseph A. , Campbell Andrew D. , Vlachogiannis Georgios , Valeri Nicola , Haigis Kevin M. , Sonenberg Nahum , Proud Christopher G. , Jones Neil P. , Swarbrick Martin E. , McKinnon Heather J. , Faller William J. , Le Quesne John , Edwards Joanne , Willis Anne E. , Bushell Martin , Sansom Owen J.
Published: December 2020

KRAS-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent in KRAS-mutant colorectal cancer. Using Kras-mutant mouse models and mouse- and patient-derived organoids, we demonstrate that KRAS with G12D mutation fundamentally rewires translation to increase both bulk and mRNA-specific translation initiation. This occurs via the MNK/eIF4E pathway culminating in sustained expression of c-MYC. By genetic and small-molecule targeting of this pathway, we acutely sensitize KRASG12D models to rapamycin via suppression of c-MYC. We show that 45% of colorectal cancers have high signaling through mTORC1 and the MNKs, with this signature correlating with a 3.5-year shorter cancer-specific survival in a subset of patients. This work provides a c-MYC–dependent cotargeting strategy with remarkable potency in multiple Kras-mutant mouse models and metastatic human organoids and identifies a patient population that may benefit from its clinical application.

Significance:

KRAS mutation and elevated c-MYC are widespread in many tumors but remain predominantly untargetable. We find that mutant KRAS modulates translation, culminating in increased expression of c-MYC. We describe an effective strategy targeting mTORC1 and MNK in KRAS-mutant mouse and human models, pathways that are also commonly co-upregulated in colorectal cancer.

This article is highlighted in the In This Issue feature, p. 995
ЛІКУВАННЯ ХВОРИХ З COVID-19 НА СУЧАСНОМУ ЕТАПІ
Authors: Andreychyn M. A. , Nychyk N. A. , Zavidniuk N. H. , Iosyk Ia. I. , Ischuk I. S.
Published: December 2020

На підставі огляду наукової літератури висвітлено сучасні підходи до лікування хворих на COVID-19. Наведено показання до госпіталізації хворих і дані про ефективність препаратів з різним механізмом дії, враховуючи міжнародний досвід. Відзначено, що широка апробація ремдезивіру, гідроксихлорохіну, лопінавіру-ритонавіру, інтерферонів не дала переконливих результатів. Надія з’явилася щодо використання плазми реконвалесцентів і моноклональних антитіл до вірусу, які, однак, потребують ретельної багатоцентрової апробації. Водночас, певних успіхів досягнуто в патогенетичній терапії. Чітко обґрунтовано показання, строки призначення і оптимальні дози кортикостероїдів, інгібіторів інтерлейкінів (тоцилізумаб), антикоагулянтів, переважно низькомолекулярних похідних гепарину, під контролем рівня D-димеру та інших показників гемостазу. Антибіотики рекомендовано призначати при приєднанні бактерійної ко-інфекції, що спостерігається нечасто. Стаття адресована головно для лікарів, які працюють з хворими на COVID-19.
CHANGES IN CARBOHYDRATE METABOLISM AND ADIPOCYTOKINES UNDER THE INFLUENCE OF TREATMENT OF PATIENTS WITH ALCOHOLIC CIRRHOSIS OF THE LIVER IN COMBINATION WITH OBESITY USING ADAMETHIONINUM AND ARGININE GLUTAMATE
Authors: Matkovska N. R.
Published: December 2020

Introduction. Alcohol-related liver cirrhosis is one of the leading causes of hospitalization and disability in patients with gastrointestinal disease.

The aim of the study – to learn the effectiveness of treatment of patients with alcoholic liver cirrhosis (ALC) combined with obesity depending on the stage of decompensation using ademethionine and arginine glutamate.

Research Methods. 215 patients, diagnosed with ALC, took part in the study, including 66 women and 149 men. 109 people had ALC with obesity and 106 people had ALC without obesity. Patients were divided into subgroups depending on the stage of decompensation according to Child-Pugh. Depending on the treatment protocol (b protocol – basic therapy, h protocol – basic therapy in combination with ademethionine and arginine glutamate), all patients were divided into subgroups.

Results and Discussion. In this study, the values of carbohydrate metabolism, adiponectin and leptin were used to evaluate the effectiveness of a three-month treatment regimen with ademethionine and arginine glutamate in patients with ALC in combination with obesity. Obese patients with ALC have a more severe course of the disease, accompanied by more pronounced clinical manifestations, impaired carbohydrate metabolism and imbalance of leptin and adiponectin levels. The inclusion of ademethionine and arginine glutamate in the treatment regimen for 3 months allowed to improve the general condition of patients, their clinical and laboratory parameters and reduce the rate of disease progression, which is reflected in improved carbohydrate metabolism, leptin and adiponectin and reduced indicators of the severity scale according to Child-Pugh and the 3-month MELD mortality score.

Conclusions. Inclusion of ademethionine and arginine glutamate in the complex treatment of patients with ALC in combination with obesity helps to reduce insulin resistance, improve leptin and adiponectin. In patients with ALC in combination with obesity, the inclusion in the complex treatment of ademethionine and arginine glutamate helps to improve the course of the disease according to the indicators of the severity scale using the Child-Pugh and MELD scales.
Uma reflexão sobre as controvérsias teóricas e terminológicas dos falsos amigos português/espanhol
Authors: Costa Zaine Guedes da
Published: December 2020

No presente trabalho tratamos de observar as controvérsias teóricas e de- nominações que envolvem o problema de confusão terminológica entre palavras que apresentam formas parecidas ou iguais, mas com sentidos diferentes, a saber, os falsos amigos português/espanhol. Nesse sentido, averiguamos que não existe unanimidade em relação à alcunha e à teoria que elas abarcam. Refletimos também que é preciso ir mais além da obviedade já constatada pela Linguística Histórica que palavras de línguas diferentes não podem ser configuradas como equivalentes ou correspondentes em sua estrutura. Dessa forma, finalizamos sugerindo, como alternativa plausível, uma abordagem interdisciplinar com o aporte da Psicologia Cognitiva, ou ainda o viés diacrônico, na tentativa de elucidar, pelo menos em parte, quais fatores teriam corroborado para a formação dos homônimos, parônimos e de palavras de mesmo étimo que desenvolveram através do tempo acepções particulares de sentido.
Produtivismo acadêmico
Authors: Teixeira Talita da Silveira Campos , Marqueze Elaine Cristina , Moreno Claudia Roberta de Castro
Published: December 2020

OBJETIVOS: Avaliar a associação entre a percepção da pressão por publicações com a satisfação e o estresse no trabalho. MÉTODOS: Estudo transversal com 64 orientadores de pós-graduação de uma universidade pública da cidade de São Paulo. A coleta de dados ocorreu por meio de um questionário on-line que incluiu: dados sociodemográficos, laborais e de saúde; Escala de Satisfação no Trabalho do Occupational Stress Indicator e modelo Desequilíbrio Esforço-Recompensa (DER). Para avaliar a percepção da pressão por publicação foi criada uma escala numérica na qual o orientador deveria atribuir uma nota de 0 a 10 para o quanto se sentia pressionado a publicar seus trabalhos (sendo 0 nenhuma pressão e 10 muita pressão). Posteriormente, foi utilizado o modelo linear generalizado para testar os fatores associados à alta percepção de pressão para publicação, ajustado pelo tempo de trabalho, função de gestão acadêmica e bolsa produtividade. RESULTADOS: Maiores proporções da percepção de elevada pressão para publicação foram encontradas entre orientadores que já haviam trabalhado em instituição de ensino superior, que realizavam parte do trabalho em casa e que apresentavam estresse laboral. Associou-se essa percepção a um maior esforço e comprometimento excessivo no trabalho, bem como a um maior desequilíbrio entre o esforço empregado e a recompensa recebida no trabalho. CONCLUSÕES: Os achados desta pesquisa sugerem que a organização do trabalho e a saúde mental dos trabalhadores estejam inter-relacionados: quanto maior a percepção de pressão por publicação maior o estresse. No entanto, esse resultado parece não se refletir na satisfação (ou insatisfação) do trabalho. O prolongamento aparentemente deliberado das horas de trabalho oculta a precarização e intensificação do trabalho a que os professores têm sido submetidos nos últimos anos pelas políticas públicas que mercantilizam a educação no Brasil.
Genetic Association Between Hypoplastic Left Heart Syndrome and Cardiomyopathies
Authors: Theis Jeanne L. , Hu Jessie J. , Sundsbak Rhianna S. , Evans Jared M. , Bamlet William R. , Qureshi M. Yasir , O’Leary Patrick W. , Olson Timothy M.
Published: December 2020

Background:

Hypoplastic left heart syndrome (HLHS) with risk of poor outcome has been linked to
MYH6
variants, implicating overlap in genetic etiologies of structural and myopathic heart disease.

Methods:

Whole genome sequencing was performed in 197 probands with HLHS, 43 family members, and 813 controls. Data were filtered for rare, segregating variants in 3 index families comprised of an HLHS proband and relative(s) with cardiomyopathy. Whole genome sequencing data from cases and controls were compared for rare variant burden across 56 cardiomyopathy genes utilizing a weighted burden test approach, accounting for multiple testing using a Bonferroni correction.

Results:

A pathogenic
MYBPC3
nonsense variant was identified in the first proband who underwent cardiac transplantation for diastolic heart failure, her father with left ventricular noncompaction, and 2 fourth-degree relatives with hypertrophic cardiomyopathy. A likely pathogenic
RYR2
missense variant was identified in the second proband, a second-degree relative with aortic dilation, and a fourth-degree relative with dilated cardiomyopathy. A pathogenic
RYR2
exon 3 in-frame deletion was identified in the third proband diagnosed with catecholaminergic polymorphic ventricular tachycardia and his father with left ventricular noncompaction and catecholaminergic polymorphic ventricular tachycardia. To further investigate HLHS-cardiomyopathy gene associations in cases versus controls, rare variant burden testing of 56 genes revealed enrichment in
MYH6
(
P
=0.000068). Rare, predicted-damaging
MYH6
variants were identified in 10% of probands in our cohort—4 with familial congenital heart disease, 4 with compound heterozygosity (3 with systolic ventricular dysfunction), and 4 with
MYH6
–
FLNC
synergistic heterozygosity.

Conclusions:

Whole genome sequencing in multiplex families, proband-parent trios, and case-control cohorts revealed defects in cardiomyopathy-associated genes in patients with HLHS, which may portend impaired functional reserve of the single-ventricle circulation.