bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing an efficient salinomycin biosynthetic pathway in three heterologous Streptomyces hosts by constructing a 106‐kb multioperon artificial gene cluster
Authors: Jiang Chanjuan , Zhou Haibo , Sun Hongluan , He Ruoting , Song Chaoyi , Cui Tianqi , Luan Ji , Fu Jun , Zhang Youming , Jiao Nianzhi , Wang Hailong 
Published: August 2021

AbstractSalinomycin is a promising anticancer drug for chemotherapy. A highly productive biosynthetic gene cluster will facilitate the creation of analogs with improved therapeutic activity and reduced side effects. In this study, we engineered an artificial 106‐kb salinomycin gene cluster and achieved efficient heterologous expression in three hosts: Streptomyces coelicolor CH999, S. lividans K4‐114, and S. albus J1074. The six‐operon artificial gene cluster consists of 25 genes from the native gene cluster organized into five operons and five fatty acid β‐oxidation genes into one operon. All operons are driven by strong constitutive promoters. For K4‐114 and J1074 harboring the artificial gene cluster, salinomycin production in shake flask cultures was 14.3 mg L−1 and 19.3 mg L−1, respectively. The production was 1.3‐fold and 1.7‐fold higher, respectively, than that of the native producer S. albus DSM41398. K4‐114 and J1074 harboring the native gene cluster produced an undetectable amount of salinomycin and 0.5 mg L−1, respectively. CH999 harboring the artificial gene cluster produced 10.3 mg L−1 of salinomycin, which was 92% of the production by DSM41398. The efficient heterologous expression system based on the 106‐kb multioperon artificial gene cluster established in this study will facilitate structural diversification of salinomycin, which is valuable for drug development and structure–activity studies.
Organic–inorganic hybrid gate dielectric using bifunctional polyhedral oligomeric silsesquioxane for low‐voltage organic thin‐film transistors
Authors: Yu Byungseok , Ha Young‐Geun 
Published: August 2021

AbstractHerein, we report the facile fabrication of rationally designed, high‐performance organic–inorganic hybrid dielectric films constructed by combining a one‐step solution processing and ultraviolet (UV) irradiation under ambient conditions. For the exceptional dielectric properties and facile fabrication process, we use bifunctional polyhedral oligomeric silsesquioxane (POSS) with UV cross‐linking and hydrophobic properties to prepare precursor solutions for the hybrid dielectric films. The bifunctional POSS enables the fabrication of a dense network of hybrid films with UV curing at under ambient conditions. The prepared hybrid gate dielectrics exhibit high capacitance (~300 nF/cm2), exceptional surface smoothness (root‐mean‐square roughness <0.4 nm), and excellent leakage current properties (10−6 A/cm2 at 2 MV/cm). In addition, the hydrophobic function of bifunctional POSS enables the low surface energy of fabricated hybrid gate dielectrics without further treatment. Pentacene‐based organic thin‐film transistors, fabricated with a hybrid dielectric, function well at low voltage with excellent thin‐film transistor performances.
Alitretinoin in the treatment of cutaneous T‐cell lymphoma
Authors: Kaemmerer Till , Stadler Pia‐Charlotte , Helene Frommherz Leonie , Guertler Anne , Einar French Lars , Reinholz Markus 
Published: August 2021

AbstractIntroductionIn this survey, we analyzed data from patients suffering from the most common cutaneous T‐cell lymphomas (CTCLs) subtypes mycosis fungoides (MF) and Sézary syndrome (SS), treated with the retinoid alitretinoin during a 7‐year period at our outpatient department between 2015 and 2020.Materials and MethodsWe analyzed patient medical records including TNMB stage, side effects under therapy with alitretinoin, time to next treatment (TTNT), and previous photo documentation.ResultsA total of 35 patients with MF (n = 28) and SS (n = 7) were included in the study, of whom 69% were male and 31% were female. The mean age of onset was 56 ± 15 years in MF and 65.4 ± 10.8 years in SS with 51.4% having early stage (IA–IIA) and 48.6% having advanced stage (IIB–IVA) CTCL.Of these patients 37.2% responded to alitretinoin, 28.6% had a stable course, and 34.3% experienced progression. Alitretinoin was administered as a monotherapy (25.7%) or combined with five concomitant therapies (74.2%), most frequently with ECP (31.4%) and PUVA (11.4%). 63% did not report any side effects, most often hypertriglyceridemia (20%) was described.ConclusionConsidering that nearly two thirds of the CTCL patients treated with alitretinoin showed a response or stable disease, together with a low number of side effects and low cost compared to bexarotene, alitretinoin may be a potential alternative in the treatment of less advanced CTCLs. This survey represents the largest number of recorded therapies with the retinoid alitretinoin in CTCLs in a European patient collective.
Point‐of‐care Doppler ultrasound in the management of hyponatremia: Another string to nephrologists' Bow
Authors: Samant Samira , Koratala Abhilash 
Published: August 2021

AbstractObjective assessment of fluid status is vital for the appropriate management of patients with hyponatremia. Conventional physical examination suffers from several limitations in this regard, and point‐of‐care Doppler ultrasonography can be used as an adjunct to clinical and laboratory data in evaluating these patients.
Structure‐Designed Preparation of Pod‐Like CuCo2S4/rGO as Advanced Anode Material Targeting Superior Sodium Storage
Authors: Li Qun , Jiao Qingze , Zhou Wei , Gu Tingting , Li Zuze , Zhao Yun , Li Hansheng , Shi Daxin , Feng Caihong 
Published: August 2021

AbstractIt is urgent to design and assemble anode materials with long cycling life and high capacity for sodium‐ion batteries (SIBs). Thereby, pod‐like CuCo2S4/rGO, with a unique core‐shell structure, was successfully fabricated through a solvothermal method, a green reduction process, and a following liquid‐nitrogen treatment. CuCo2S4 spheres were embedded into rGO nanosheet scrolls, forming a unique pod‐like structure due to the shrinkage of rGO during the liquid‐nitrogen treatment. The pod‐like CuCo2S4/rGO material exhibits a superior electrochemical performance compared to bare CuCo2S4, including a high capacity (557.5 mAh g−1 at 0.1 A g−1) and good rate capability (372 mAh g−1 at 2 A g−1). In addition, a long cycling life with a high capacity of 341 mAh g−1 over 5000 cycles at 2 A g−1 is achieved. The improved electrochemical performance can be ascribed to the unique pod‐like core‐shell structure, which cannot only provide efficient pathways to facilitate electron/ion transportation, but also relieve the strain caused by volume change to maintain the structural stability. This work offers a simple strategy to prepare rGO‐wrapped CuCo2S4 nanocomposites with stable pod‐like structure, proving their potential application as anode materials for SIBs.
Photo‐Induced Ruthenium‐Catalyzed C−H Benzylations and Allylations at Room Temperature
Authors: Struwe Julia , Korvorapun Korkit , Zangarelli Agnese , Ackermann Lutz 
Published: August 2021

AbstractThe ruthenium‐catalyzed synthesis of diarylmethane compounds was realized under exceedingly mild photoredox conditions without the use of exogenous photocatalysts. The versatility and robustness of the ruthenium‐catalyzed C−H benzylation was reflected by an ample scope, including multifold C−H functionalizations, as well as transformable pyrazoles, imidates and sensitive nucleosides. Mechanistic studies were indicative of a photoactive cyclometalated ruthenium complex, which also enabled versatile C−H allylations.
Metastasis suppressor 1 interacts with α‐actinin 4 to affect its localization and regulate formation of membrane ruffling
Authors: Liang Lijun , Liang Xiaoping , Jiang Peng , Zhou Lu , Zhong Luanluan , Wang Mei , Lin Shuyun , Guo Zhen , Yu Juan , Yang Changcheng , Chen Yu , Zhuo Chengjie , Chen Ping , Wang Ying 
Published: August 2021

AbstractMembrane ruffling plays an important role in the directed cell migration and escape of tumor cells from the monolayer. Metastasis suppressor 1 (MTSS1), also known as missing in metastasis, has been implicated in cell morphology, motility, metastasis, and development. Here, the dynamic interaction proteins associated with MTSS1 and involved in membrane ruffling were determined by cross‐linking and mass spectrometry analysis. We identified α‐actinin 4 (ACTN4) as an interacting protein and confirmed a direct interaction between MTSS1 and ACTN4. Moreover, co‐expression of MTSS1 in fibroblasts recruited cytoplasmic ACTN4 to the cell periphery, at which point ruffling became thick and rigid. In MCF‐7 cells, MTSS1 knockdown did not show an obvious effect on the cell shape or the distribution of endogenous ACTN4; however, ACTN4 overexpression transformed cell morphology from an epidermal‐ to a fibroblast‐like shape, and further MTSS1 depletion significantly increased the ratio of fibroblast cells exhibiting prominent ruffling. Furthermore, biochemical data suggested that MTSS1 cross‐linking with ACTN4 induced the formation of actin fiber bundles into more organized structures in vitro. These data indicated that MTSS1 might recruit cytoplasmic ACTN4 to the cell periphery and regulate cytoskeleton dynamics to restrict its performance in membrane ruffling.
Namib beetle optimization algorithm: A new meta‐heuristic method for feature selection and dimension reduction
Authors: Chahardoli Meysam , Eraghi Nafiseh Osati , Nazari Sara 
Published: August 2021

SummaryToday, large amounts of data are generated in various applications such as smart cities and social networks, and their processing requires a lot of time. One of the methods of processing data types and reducing computational time on data is the use of dimension reduction methods. Reducing dimensions is a problem with the optimization approach and meta‐heuristic methods can be used to solve it. Namib beetles are an example of intelligent insects and creatures in nature that use an interesting strategy to survive and collect water in the desert. In this article, the behavior of Namib beetles has been used to collect water in the desert to model the Namib beetle optimization (NBO) algorithm. In the second phase of a binary version, this algorithm is used to select features and reduce dimensions. Experiments on CEC functions show that the proposed method has fewer errors than the DE, BBO, SHO, WOA, GOA, and HHO algorithms. In large dimensions such as 200, 500, and 1000 dimensions, the NBO algorithm of meta‐heuristic algorithms such as HHO and WOA has a better rank in the optimal calculation of benchmark functions. Experiments show that the proposed algorithm has a greater ability to reduce dimensions and feature selection than similar meta‐heuristic algorithms. In 87.5% of the experiments, the proposed method reduces the data space more than other compared methods.
An extra virgin olive oil‐enriched chocolate spread positively modulates insulin‐resistance markers compared with a palm oil‐enriched one in healthy young adults: A double‐blind, cross‐over, randomised controlled trial
Authors: Tuccinardi Dario , Di Mauro Antonio , Lattanzi Greta , Rossini Giovanni , Monte Lavinia , Beato Ivan , Spiezia Chiara , Bravo Maria , Watanabe Mikiko , Soare Andreea , Kyanvash Shadi , Armirotti Andrea , Bertozzi Sine Mandrup , Gastaldelli Amalia , Pedone Claudio , Khazrai Yeganeh Manon , Pozzilli Paolo , Manfrini Silvia 
Published: August 2021

AbstractAimsTo investigate if extra virgin olive oil (EVOO) or palm oil enriched chocolate spreads consumption leads to different results in terms of plasma ceramides concentration, glucose and lipid metabolism, inflammatory markers and appetite regulation in young healthy subjects.MethodsIn a 2‐week, double‐blind, cross‐over, randomised controlled trial, 20 healthy, normal‐weight subjects with a mean age of 24.2 years (SD: 1.2), consumed chocolate spread snacks (73% of energy [%E] from fat, 20% from carbohydrates and 7% from proteins), providing 570 Kcal/day added to an isocaloric diet. The chocolate spreads were identical, except for the type of fat: EVOO oil, rich in monounsaturated fatty acids (MUFAs), or palm oil, rich in Saturated Fatty Acids (SFAs).ResultsEVOO‐enriched chocolate spread consumption led to better circulating sphingolipids and glucose profile, with reduced plasma ceramide C16:0, ceramide C16:0/ceramide C22:0‐ceramide C24:0 ratio and sphingomyelin C18:0 (P = 0.030, P= 0.032 and P = 0.042, respectively) compared to the palm oil‐enriched chocolate spread diet. HOMA‐IR and plasma insulin were lower, while the Quicki and the McAuley Index were higher after the EVOO diet compared to the palm oil diet (P = 0.046, P = 0.045, P = 0.018 and P = 0.039 respectively). Subjects maintained a stable weight throughout the study. No major significant changes in total cholesterol, triglycerides, HDL, inflammatory markers, and appetite‐regulating hormones/visual analogue scale were observed between the groups.ConclusionsPartially replacing SFAs with MUFAs in a chocolate‐based snack as part of a short‐term isocaloric diet in healthy individuals may limit SFAs detrimental effects on insulin sensitivity and decrease circulating harmful sphingolipids in young adults.
Reexamining forest disturbance thresholds for managing cumulative hydrological impacts
Authors: Wei Xiaohua , Hou Yiping , Zhang Mingfang , Li Qiang , Giles‐Hansen Krysta , Liu Wenfei 
Published: August 2021

AbstractForest disturbance thresholds, defined as those at or above which significant hydrological impacts are caused, are important guides to support forest and watershed management decisions for protecting hydrological functions and minimizing negative environmental impacts. Our literature review suggests that despite their significance, the research on this topic is surprisingly limited (<20 publications), where the paired watershed experiments (PWEs) primarily designed for detecting hydrological responses to forest cover change at the small watersheds were used to derive the thresholds. However, the widely used thresholds (e.g., 20%) based on the PWEs were identified from visual interpretation rather than determined from hydrological response curves, suffering from methodological shortcomings, and thus, may lack reliability. To advance this topic, we provided a robust technique (the modified double mass curve, MDMC) for quantitatively determining forest disturbance thresholds on annual mean flow as it allows the development of a hydrological response curve between cumulative hydrological effects and forest disturbance over time at the watershed scale. We applied this robust technique in eight large watersheds in British Columbia, Canada, and found that the forest disturbance thresholds ranged from 12 to 25%. We highly recommend that the widely used forest disturbance thresholds must be reexamined, and more studies are needed with rigorous methods and in consideration of other hydrological variables in forested watersheds.
Comparison of the return period for landslide‐triggering rainfall events in Japan based on standardization of the rainfall period
Authors: Tsunetaka Haruka 
Published: August 2021

AbstractThe intensity of rainfall events with potential to cause landslides has varying temporal characteristics. In this study, the time at which the 72‐h accumulated rainfall reached its maximum was used to standardize the period of rainfall measurement. The proposed standardization of the rainfall period was used in conjunction with the return level of rainfall intensity, obtained from intensity–duration–frequency curves, to investigate rainfall intensity anomalies associated with 10 hazardous rainfall events that triggered numerous landslides at the regional scale in Japan. These landslides included shallow landslides in volcanic and non‐volcanic areas, as well as deep‐seated landslides. The rainfall events that triggered the shallow landslides were divided into two types: downpours that repeatedly reached close to the 100‐year return level within approximately 3–4 h, and accumulated rainfall that reached close to 200–400 mm over longer time intervals but within 72 h. Lithological differences seemed unrelated to the differences between the two types of shallow‐landslide‐triggering rainfall; however, precipitation >1000 mm was necessary to trigger deep‐seated landslides. Although the characteristics of the hyetographs differed markedly among the landslide‐triggering rainfall events, all the landslides could have been triggered when the mean rainfall intensity reached the 100‐year rainfall level during the standardized period. Thus, the landslide trigger can be evaluated indirectly based on the increase in the return level of the mean rainfall intensity, which could provide a means for estimating the time of landslide occurrence.
Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile
Authors: Vedeld Hege Marie , Grimsrud Marit M. , Andresen Kim , Pharo Heidi D. , von Seth Erik , Karlsen Tom H. , Honne Hilde , Paulsen Vemund , Färkkilä Martti A. , Bergquist Annika , Jeanmougin Marine , Aabakken Lars , Boberg Kirsten M. , Folseraas Trine , Lind Guro E. 
Published: August 2021

Abstract

Background and Aims
Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC.

Approach and Results
Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC‐associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77–0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA ≤ 12 months following bile collection increased the accuracy for cancer detection, with a combined sensitivity of 100% (28/28) and a specificity of 90% (20/203). The specificity increased to 93% when only including patients with PSC with longtime follow‐up (> 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA‐PSC ≤ 12 patients, all positive for the biomarkers, included both early‐stage and late‐stage CCA, different tumor growth patterns, anatomical locations, and carbohydrate antigen 19‐9 levels.

Conclusions
Using highly sensitive ddPCR to analyze robust epigenetic biomarkers, CCA in PSC was accurately detected in bile, irrespective of clinical and molecular features, up to 12 months before CCA diagnosis. The findings suggest a potential for these biomarkers to complement current detection and screening methods for CCA in patients with PSC.
A conventional immune regulator mitochondrial antiviral signaling protein blocks hepatic steatosis by maintaining mitochondrial homeostasis
Authors: Fu Jiajun , Hu Fengjiao , Ma Tengfei , Zhao Wen‐Jie , Tian Han , Zhang Yan , Hu Manli , Zhou Junjie , Zhang Yanfang , Jian Chongshu , Ji Yan‐Xiao , Zhang Xiao‐Jing , Jiang Jingwei , She Zhi‐Gang , Cheng Xu , Zhang Peng , Bai Lan , Yang Juan , Li Hongliang 
Published: August 2021

Background and Aims
Although the prevalence of NAFLD has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease because of uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown.

Approach and Results
Based on expression analysis, we identified a marked down‐regulation of MAVS in hepatocytes during NAFLD progression. By using MAVS global knockout and hepatocyte‐specific MAVS knockout mice, we found that MAVS is protective against diet‐induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis, which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N‐terminal stretch of voltage‐dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis.

Conclusions
In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent an avenue for treating NAFLD.
Finite element analysis on the hydrothermal pattern of radiative natural convective nanofluid flow inside a square enclosure having nonuniform heated walls
Authors: Acharya Nilankush 
Published: August 2021

AbstractThe present article enlightens us on the hydrothermal pattern of a steady incompressible laminar natural convective nanofluid flow inside a heated square chamber. The square enclosure is filled with water‐based spherical‐shaped ferrous (Fe3O4) nanoparticles. Magnetic effect and thermal radiation are presumed within the flow. The left‐sided vertical wall and one bottom wall of the chamber are nonuniformly and uniformly heated, while the remaining right‐sided vertical wall is isothermally cooled at a constant temperature and the upper wall is insulated. A detailed analysis is conducted to exhibit that how nonuniform and uniform heated walls influence flow within the square chamber. The leading dimensional equations are made into a dimensionless form using apposite similarity variables and the Galerkin finite element technique is executed to solve those equations. The grid independence test and a parallel comparison with existing literature are presented to verify the validity of the outcomes. The streamlines, isotherms, temperature, velocities, and average Nusselt number are depicted through several graphs for several parametric values of Rayleigh number, Hartmann number, thermal radiation, and nanoparticle volume fraction. The outcomes showed that increasing nanoparticle concentration and Rayleigh number lead to improve the Nusselt number, while heat transport is reduced for Hartmann number and radiation parameter. The uniformly heated walls convey better heat transport as compared to nonuniformly heated walls.