bluuebunny/crossref_metadata_2025 huggingface dataset:
Urupocidin C: a new marine guanidine alkaloid which selectively kills prostate cancer cells via mitochondria targeting
Authors: Dyshlovoy Sergey A. , Kudryashova Ekaterina K. , Kaune Moritz , Makarieva Tatyana N. , Shubina Larisa K. , Busenbender Tobias , Denisenko Vladimir A. , Popov Roman S. , Hauschild Jessica , Fedorov Sergey N. , Bokemeyer Carsten , Graefen Markus , Stonik Valentin A. , von Amsberg Gunhild
Published: June 2020

New bicyclic guanidine alkaloid, urupocidin C (Ur-C) along with the previously known urupocidin A (Ur-A) were isolated from the rare deep-sea marine sponge Monanchora pulchra, harvested in Northwestern Pacific waters. The unique structure of Ur-C was elucidated using 1D and 2D NMR spectroscopy as well as mass spectra. We discovered a promising selectivity of both alkaloids for human prostate cancer (PCa) cells, including highly drug-resistant lines, compared to non-malignant cells. In cancer cells, marine derived compounds were able to induce G1- and S-cell cycle arrest as well as caspase-mediated cell death. For the first time we have identified mitochondrial targeting as a central mechanism of anticancer action for these and similar molecules. Thus, treatment with the isolated alkaloids resulted in mitochondrial membrane permeabilization consequently leading to the release of cytotoxic mitochondrial proteins to cellular cytoplasm, ROS upregulation, consequent activation of caspase-9 and -3, followed by PARP cleavage, DNA fragmentation, and apoptosis. Moreover, synergistic effects were observed when Ur-A and Ur-C were combined with clinically approved PARP inhibitor olaparib. Finally, these alkaloids exhibited additive effects in combination with docetaxel and androgen receptor inhibitor enzalutamide, both applied in PCa therapy. In conclusion, urupocidin-like compounds are promising lead molecules for the development of new drugs for the treatment of advanced PCa.
Femtosecond time-evolution of mid-infrared spectral line shapes of Dirac fermions in topological insulators
Authors: Yeh Tien-Tien , Tu Chien-Ming , Lin Wen-Hao , Cheng Cheng-Maw , Tzeng Wen-Yen , Chang Chen-Yu , Shirai Hideto , Fuji Takao , Sankar Raman , Chou Fang-Cheng , Gospodinov Marin M. , Kobayashi Takayoshi , Luo Chih-Wei
Published: June 2020

Mid-infrared (MIR) light sources have much potential in the study of Dirac-fermions (DFs) in graphene and topological insulators (TIs) because they have a low photon energy. However, the topological surface state transitions (SSTs) in Dirac cones are veiled by the free carrier absorption (FCA) with same spectral line shape that is always seen in static MIR spectra. Therefore, it is difficult to distinguish the SST from the FCA, especially in TIs. Here, we disclose the abnormal MIR spectrum feature of transient reflectivity changes (ΔR/R) for the non-equilibrium states in TIs, and further distinguish FCA and spin-momentum locked SST using time-resolved and linearly polarized ultra-broadband MIR spectroscopy with no environmental perturbation. Although both effects produce similar features in the reflection spectra, they produce completely different variations in the ΔR/R to show their intrinsic ultrafast dynamics.
A novel de novo heterozygous DYRK1A mutation causes complete loss of DYRK1A function and developmental delay
Authors: Lee Kyu-Sun , Choi Miri , Kwon Dae-Woo , Kim Doyoun , Choi Jong-Moon , Kim Ae-Kyeong , Ham Youngwook , Han Sang-Bae , Cho Sungchan , Cheon Chong Kun
Published: June 2020

Dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) is essential for human development, and DYRK1A haploinsufficiency is associated with a recognizable developmental syndrome and variable clinical features. Here, we present a patient with DYRK1A haploinsufficiency syndrome, including facial dysmorphism, delayed motor development, cardiovascular system defects, and brain atrophy. Exome sequencing identified a novel de novo heterozygous mutation of the human DYRK1A gene (c.1185dup), which generated a translational termination codon and resulted in a C-terminally truncated protein (DYRK1A-E396ter). To study the molecular effect of this truncation, we generated mammalian cell and Drosophila models that recapitulated the DYRK1A protein truncation. Analysis of the structure and deformation energy of the mutant protein predicted a reduction in protein stability. Experimentally, the mutant protein was efficiently degraded by the ubiquitin-dependent proteasome pathway and was barely detectable in mammalian cells. More importantly, the mutant kinase was intrinsically inactive and had little negative impact on the wild-type protein. Similarly, the mutant protein had a minimal effect on Drosophila phenotypes, confirming its loss-of-function in vivo. Together, our results suggest that the novel heterozygous mutation of DYRK1A resulted in loss-of-function of the kinase activity of DYRK1A and may contribute to the developmental delay observed in the patient.
Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway
Authors: Li Yaping , Huang Baohua , Yang Hua , Kan Shuang , Yao Yanling , Liu Xin , Pu Shiming , He Guozhang , Khan Taj-Malook , Qi Guangying , Zhou Zuping , Shu Wei , Chen Ming
Published: June 2020

The function of Latexin (LXN) in inflammation has attracted attention. However, no data are available regarding its role in colitis. We report that LXN is a suppressor of colitis. LXN deficiency leads to the severity of colitis in DSS-induced mice, and LXN is required for the therapeutic effect of retinoic acid on colitis. Using a proteomics approach, we demonstrate that LXN interacts and forms a functional complex with HECTD1 (an E3 ubiquitin ligase) and ribosomal protein subunit3 (Rps3). IκBα is one of the substrates of HECTD1. Ectopic expression of LXN leads to IκBα accumulation in intestinal epithelial cells, however, LXN knockdown enhances the interaction of HECTD1 and Rps3, contributing to the ubiquitination degradation of IκBα, and subsequently enhances inflammatory response. Thus, our findings provided a novel mechanism underlying LXN modulates colitis via HECTD1/Rps3/NF-κB pathway and significant implications for the development of novel strategies for the treatment of colitis by targeting LXN.
Point-of-care detection, characterization, and removal of chocolate bloom using a handheld Raman spectrometer
Authors: Heuler Joshua , He Siyu , Ambardar Sharad , Voronine Dmitri V.
Published: June 2020

Chocolate bloom is an off-white coating on the surface of chocolate products due to the altered distribution of the ingredients. Bloom reduces the shelf-life of chocolate and affects its visual and tactile quality, all of which are serious concerns for chocolate manufacturers and consumers. The automated, rapid, and noninvasive point-of-care detection of chocolate bloom has been an essential but challenging problem. The ability to detect and characterize chocolate bloom using portable laser spectroscopy could be used to develop in-situ quality control sensors. In this work, a handheld Raman spectrometer was used to detect chocolate bloom. Raman spectra acquired from bloomed HERSHEY’S milk chocolate, Hawaiian Host milk chocolate covered macadamia nuts, and Babayevsky Russian dark chocolate were used to characterize the type of bloom. The 1064 nm laser beam of the handheld Raman instrument was used to partially remove the fat bloom of the dark chocolate and to induce sugar bloom on the milk chocolate. The handheld Raman approach has a high potential for industrial and consumer applications for the on-site chemical analysis of chocolate bloom and as an alternative laser-based chocolate decoration.
Identification of core genes in the progression of endometrial cancer and cancer cell-derived exosomes by an integrative analysis
Authors: Shi Shuang , Tan Qiang , Feng Fuqiang , Huang Heping , Liang Jingjie , Cao Dingren , Wang Zhengguang
Published: June 2020

Endometrial cancer is one of the most prevalent tumors of the female reproductive system causing serious health effects to women worldwide. Although numerous studies, including analysis of gene expression profile and cellular microenvironment have been reported in this field, pathogenesis of this disease remains unclear. In this study, we performed a system bioinformatics analysis of endometrial cancer using the Gene Expression Omnibus (GEO) datasets (GSE17025, GSE63678, and GSE115810) to identify the core genes. In addition, exosomes derived from endometrial cancer cells were also isolated and identified. First, we analyzed the differentially expressed genes (DEGs) between endometrial cancer tissues and normal tissues in clinic samples. We found that HAND2-AS1, PEG3, OGN, SFRP4, and OSR2 were co-expressed across all 3 datasets. Pathways analysis showed that several pathways associated with endometrial cancer, including “p53 signaling pathway”, “Glutathione metabolism”, “Cell cycle”, and etc. Next, we selected DEGs with highly significant fold change and co-expressed across the 3 datasets and validated them in the TCGA database using Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we performed a survival analysis and identified four genes (TOP2A, ASPM, EFEMP1, and FOXL2) that play key roles in endometrial cancer. We found up-regulation of TOP2A and ASPM in endometrial cancer tissues or cells, while EFEMP1 and FOXL2 were down-regulated. Furthermore, we isolated exosomes from the culturing supernatants of endometrial cancer cells (Ishikawa and HEC-1-A) and found that miR-133a, which regulates expression of FOXL2, were present in exosomes and that they could be delivered to normal endometrial cells. The common DEGs, pathways, and exosomal miRNAs identified in this study might play an important role in progression as well as diagnosis of endometrial cancer. In conclusion, our results provide insights into the pathogenesis and risk assessment of endometrial cancer. Even so, further studies are required to elucidate on the precise mechanism of action of these genes in endometrial cancer.
Coexistence of valley polarization and Chern insulating states in MoS2 monolayers with n-p codoping
Authors: Wei Xinyuan , Zhang Jiayong , Zhao Bao , Yang Zhongqin
Published: June 2020

The electronic and topological properties of MoS2 monolayers with n-p codoping effect are investigated by using first-principles calculations. Two types of the doped Nb atoms play the roles of the p-type and n-type dopants, respectively. The n-p codoping is found inducing a large valley polarization, associated with the strong magnetization induced by the Nb dopants. Interestingly, the system simultaneously owns a perfect Chern insulating band gap opened exactly at the Fermi level. The nontrivial band gap comes from the lifting of the degeneracy of the dxz and dyz orbitals of Nb2 atoms after the spin-orbit coupling is considered. Our work inspires exciting prospects to tune the novel properties of materials with n-p codoping effects.
Spatio-temporal dynamics of arbuscular mycorrhizal fungi and soil organic carbon in coastal saline soil of China
Authors: Zhang Huan-Shi , Zhou Ming-Xi , Zai Xue-Ming , Zhao Fu-Geng , Qin Pei
Published: June 2020

A comprehensive understanding of the relationship between arbuscular mycorrhizal (AM) fungi and coastal saline soil organic carbon (SOC) is crucial for analysis of the function of coastal wetlands in soil carbon sequestration. In a field experiment, the temporal and spatial dynamics of AM fungi, glomalin-related soil protein (GRSP) – which is described as a N-linked glycoprotein and the putative gene product of AM fungi, SOC, and soil aggregates were investigated in halophyte Kosteletzkya virginica rhizosphere soil of coastal saline areas of North Jiangsu, China. Soil samples were collected from a depth of up to 30 cm in two plantation regions from August 2012 to May 2013. Results showed K. virginica formed a strong symbiotic relationship to AM fungi. AM colonization and spore density were the highest in the 10–20 cm soil layer of Jinhai farm in August 2012, because of the presence of numerous fibrous roots in this soil layer. The total GRSP and SOC were the highest in the 0–10 cm soil layer in May 2013 and November 2012, respectively. Correlation coefficient analysis revealed that AM colonization and spore density were positively correlated with total GRSP. Meanwhile, total GRSP was significantly positively correlated with large macroaggregates (>3 mm), SOC, total P, Olsen P, and soil microbial biomass carbon (SMBC), but negatively correlated with microaggregates (<0.25 mm), soil EC, total N, and pH. SOC was positively correlated with spore density, large macroaggregates, small macroaggregates (2–0.25 mm), alkaline N, and SMBC and negatively correlated with microaggregates, EC, pH, and total K. Although it may be a statistical artifact, we found an interesting phenomenon that there was no significant correlation between soil aggregates and AM colonization or spore density. Hence, total GRSP is a vital source of saline soil C pool and an important biological indicator for evaluating coastal saline SOC pool and soil fertility, while AM colonization or spore density may not be.
Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system
Authors: Matsumoto Akira , Kuwata Hirohito , Kimura Shinichiro , Matsumoto Hiroko , Ochi Kozue , Moro-oka Yuki , Watanabe Akiko , Yamada Hironori , Ishii Hitoshi , Miyazawa Taiki , Chen Siyuan , Baba Toshiaki , Yoshida Hiroshi , Nakamura Taichi , Inoue Hiroshi , Ogawa Yoshihiro , Tanaka Miyako , Miyahara Yuji , Suganami Takayoshi
Published: June 2020

Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the glucose fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to the use of electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology that can cope with glucose fluctuations and potentially address the electronics-derived issues. The gel was combined with hemodialysis hollow fibers and scaled suitable for rats, serving as a subcutaneously implantable, insulin-diffusion-active site in a manner dependent on the subcutaneous glucose. Continuous glucose monitoring tests revealed that our device not only normalizes average glucose level of rats, but also markedly ameliorates the fluctuations over timescale of a day without inducing hypoglycemia. With inherent stability, diffusion-dependent scalability, and week-long & acute glucose-responsiveness, our technology may offer a low-cost alternative to current electronics-based approaches.
Teichoic acids anchor distinct cell wall lamellae in an apically growing bacterium
Authors: Ultee Eveline , van der Aart Lizah T. , Zhang Le , van Dissel Dino , Diebolder Christoph A. , van Wezel Gilles P. , Claessen Dennis , Briegel Ariane
Published: June 2020

The bacterial cell wall is a multicomponent structure that provides structural support and protection. In monoderm species, the cell wall is made up predominantly of peptidoglycan, teichoic acids and capsular glycans. Filamentous monoderm Actinobacteria incorporate new cell-wall material at their tips. Here we use cryo-electron tomography to reveal the architecture of the actinobacterial cell wall of Streptomyces coelicolor. Our data shows a density difference between the apex and subapical regions. Removal of teichoic acids results in a patchy cell wall and distinct lamellae. Knock-down of tagO expression using CRISPR-dCas9 interference leads to growth retardation, presumably because build-in of teichoic acids had become rate-limiting. Absence of extracellular glycans produced by MatAB and CslA proteins results in a thinner wall lacking lamellae and patches. We propose that the Streptomyces cell wall is composed of layers of peptidoglycan and extracellular polymers that are structurally supported by teichoic acids.
A responsive photonic crystal film sensor for the ultrasensitive detection of uranyl ions
Authors: Chen Qianshan , Wang Changping , Wang Shihong , Zhou Jun , Wu Zhaoyang
Published: June 2020

A PC film sensor for ultrasensitive and label-free detection of uranyl ions by complexing the ions with lone-pair electrons on both the oxygen and nitrogen atoms in the amidoxime, leading to a decrease in diffraction peak intensity of the film.
A new method to amplify colorimetric signals of paper-based nanobiosensors for simple and sensitive pancreatic cancer biomarker detection
Authors: Prasad K. Sudhakara , Abugalyon Yousef , Li Chunqiang , Xu Feng , Li XiuJun
Published: June 2020

Catalytic properties of gold nanoparticles in colour dye degradation are utilized to amplify colorimetric detection signals of a low-cost paper-based immunosensor for instrument-free detection of pancreatic cancer biomarker PEAK1.
An unexpected discovery of 1,4-benzoquinone as a lipophilic mediator for toxicity detection in water
Authors: Yu Dengbin , Li Jiantao , Kang Zhichao , Liu Ling , He Jingting , Fang Youxing , Yu Hongwen , Dong Shaojun
Published: June 2020

Since most toxicological risk assessments are based on individual single-species tests, there is uncertainty in extrapolating these results to ecosystem assessments.
A near-infrared upconversion luminescence total internal reflection platform for quantitative image analysis
Authors: Xia Wanying , Ling Bo , Wang Lun , Gao Feng , Chen Hongqi
Published: June 2020

A near-infrared upconversion luminescence total internal reflection platform was developed for quantitative image analysis of ClO−.
Disassembly of polymeric nanoparticles with enzyme-triggered polymer unzipping: polyelectrolyte complexes vs. amphiphilic nanoassemblies
Authors: Kumar Vikash , Munkhbat Oyuntuya , Secinti Hatice , Thayumanavan S.
Published: June 2020

Enzyme-induced chain unzipping is shown to cause nanoparticle disassembly. The self-assembly and triggered disassembly are evaluated in two different formats.
Vacancy dynamics on CO-covered Pt(111) electrodes
Authors: Wei Jie , Chen Yan-Xia , Magnussen Olaf M.
Published: June 2020

Diffusing vacancy are observed in the topmost layer of Pt electrodes, induced by interaction of highly mobile CO adsorbates with Pt surface atoms.
Correction: X-ray CT observation and characterization of water transformation in heavy objects
Authors: Takeya Satoshi , Muraoka Michihiro , Muromachi Sanehiro , Hyodo Kazuyuki , Yoneyama Akio
Published: June 2020

Correction for ‘X-ray CT observation and characterization of water transformation in heavy objects’ by Satoshi Takeya et al., Phys. Chem. Chem. Phys., 2020, 22, 3446–3454, DOI: 10.1039/c9cp05983k.
Spruce milled wood lignin: linear, branched or cross-linked?
Authors: Balakshin Mikhail , Capanema Ewellyn Augsten , Zhu Xuhai , Sulaeva Irina , Potthast Antje , Rosenau Thomas , Rojas Orlando J.
Published: June 2020

Plausible up-to-date structural model of spruce MWL in agreement with the current structural and molecular weight data.
Removal of Hg interferences for common Pb correction when dating apatite and titanite by LA-ICP-MS/MS
Authors: Gilbert Sarah E. , Glorie Stijn
Published: June 2020

Improved 204Pb common Pb correction by LA-ICP-MS/MS for apatite and titanite U-Pb dating.
Near-infrared fluorescent protein and bioluminescence-based probes for high-resolution in vivo optical imaging
Authors: Tiwari Dhermendra K. , Tiwari Manisha , Jin Takashi
Published: June 2020

This review presents the recent progress on NIR fluorescent protein and bioluminescence-based probes with high-resolution in vivo imaging techniques.
A La3+-doped TiO2 nanoparticle decorated functionalized-MWCNT catalyst: novel electrochemical non-enzymatic sensing of paraoxon-ethyl
Authors: Nehru Raja , Chen Shen-Ming
Published: June 2020

The development of novel chemical sensors for pesticide detection has found particular application in the area of environmental monitoring.
Effect of a mixed precursor over monolith MnOx/La–Al2O3 catalyst for toluene oxidation
Authors: Zhou Xiaoying , Shang Yingnan , Wei Wei , Lin Tao , Wang Jiecai , Lai Xiaoxiao , Wang Jianli , Chen Yaoqiang
Published: June 2020

The MNMA catalyst prepared with a mixed precursor of Mn(NO3)2 and Mn(Ac)2·4H2O possesses more α-MnO2 species and good dispersion and is more active for toluene oxidation.
Thieno[3,2-c]pyran: an ESIPT based fluorescence “turn-on” molecular chemosensor with AIE properties for the selective recognition of Zn2+ ion
Authors: Singhal Divya , Althagafi Ismail , Kumar Ashish , Yadav Saroj , Prasad Ashok K. , Pratap Ramendra
Published: June 2020

Thieno[3,2-c]pyran was synthesized as a fluorescent turn-on chemosensor for the selective recognition of Zn2+ ions with a low detection limit (0.67 μM), and it also exhibited AIE properties.
Fabrication of injectable hydrogelsviabio-orthogonal chemistry for tissue engineering
Authors: Liu Yuanshan , Liu Min , Zhang Yajie , Cao Yi , Pei Renjun
Published: June 2020

Injectable hydrogelsviabio-orthogonal chemistry.
Copper-catalyzed 1,3-aminothiocyanation of arylcyclopropanes
Authors: Wang Xiaomin , Wang Lihong , Yang Shengbiao , Zhang Linli , Li Yan , Zhang Qian
Published: June 2020

The first example of copper-catalyzed 1,3-aminothiocyanation of arylcyclopropanes with N-fluorobenzenesulfonimide (NFSI) and trimethylsilyl isothiocyanate (TMSNCS) has been developed.
Recent advances of stable Blatter radicals: synthesis, properties and applications
Authors: Ji Yu , Long Lanxin , Zheng Yonghao
Published: June 2020

Radicals, organic molecules with unpaired electrons, are applied across different scientific disciplines such as electronics, energy storage and biochemistry.
A metal-free visible-light-promoted phosphorylation/cyclization reaction in water towards 3-phosphorylated benzothiophenes
Authors: Yuan Xiao-Ya , Zeng Fan-Lin , Zhu Hu-Lin , Liu Yan , Lv Qi-Yan , Chen Xiao-Lan , Peng Lifen , Yu Bing
Published: June 2020

A metal-free visible-light-induced phosphorylation/cyclization reaction was developed in water at room temperature for the synthesis of 3-phosphorylated benzothiophenes.
Accessing alkyl boronic esters via visible light-mediated decarboxylative addition reactions of redox-active esters
Authors: Shu Xianli , Xu Ruting , Ma Qiang , Liao Saihu
Published: June 2020

A visible light-mediated decarboxylative addition reaction for the synthesis of boronic esters based on abundant alkyl carboxylic acid feedstock has been developed.
Transforming waste cigarette filters into 3D carbon scaffolds for form-stable and energy conversion phase change materials
Authors: Umair Malik Muhammad , Zhang Yuang , Zhang Shufen , Jin Xin , Tang Bingtao
Published: June 2020

Synthesis of porous scaffolds via carbonization of GO doped cigarette filters for phase-change materials.
Towards high-throughput optimization of microbial lipid production: from strain development to process monitoring
Authors: Awad Dania , Younes Samer , Glemser Matthias , M. Wagner Franz , Schenk Gerhard , Mehlmer Norbert , Brueck Thomas
Published: June 2020

We describe, for the first time, the use of fast neutron irradiation for the rapid metabolic optimization of an oleaginous yeast. The approach established in this study provides a progressive path towards automatable strain development efforts.
Correction: Reversible densification in nano-Li2MnO3 cation disordered rock-salt Li-ion battery cathodes
Authors: Diaz-Lopez Maria , Chater Philip A. , Joly Yves , Proux Olivier , Hazemann Jean-Louis , Bordet Pierre , Pralong Valerie
Published: June 2020

Correction for ‘Reversible densification in nano-Li2MnO3 cation disordered rock-salt Li-ion battery cathodes’ by Maria Diaz-Lopez et al., J. Mater. Chem. A, 2020, 8, 10998–11010, DOI: 10.1039/d0ta03372c.
The autocrine role of FGF21 in cultured adipocytes
Authors: Justesen Sarah , Haugegaard Kirsten V. , Hansen Jacob B. , Hansen Harald S. , Andersen Birgitte
Published: June 2020

Exposure to cold alters glucose and lipid metabolism of white and brown adipose tissue via activation of β-adrenergic receptor (ADRB). Fibroblast growth factor 21 (FGF21) has been shown to be locally released from adipose tissue upon activation of ADRBs and FGF21 increases glucose uptake in adipocytes. Therefore, FGF21 may play an autocrine role in inducing glucose uptake after β-adrenergic stimulation. To determine the putative autocrine role of FGF21, we stimulated three different types of adipocytes in vitro with Isoprenaline (Iso), an ADRB agonist, in the presence or absence of the FGF receptor (FGFR) inhibitor PD 173074. The three cell lines represent white (3T3-L1), beige (ME3) and brown (WT-1) adipocyte phenotypes, respectively. All three cells systems expressed β-klotho (KLB) and FGFR1 after differentiation and treatment with recombinant FGF21 increased glucose uptake in 3T3-L1 and WT-1 adipocytes, while no significant effect was observed in ME3. Oppositely, all three cell lines responded to Iso treatment and an increase in glucose uptake and lipolysis were observed. Interestingly, in response to the Iso treatment only the WT-1 adipocytes showed an increase in FGF21 in the medium. This was consistent with the observation that PD 173074 decreased Iso-induced glucose uptake in the WT-1 adipocytes. This suggests that FGF21 plays an autocrine role and increases glucose uptake after β-adrenergic stimulation of cultured brown WT-1 adipocytes.
Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders
Authors: Lin Guangyao , Liu Qiaofeng , Dai Antao , Cai Xiaoqing , Zhou Qingtong , Wang Xi , Chen Yan , Ye Chenyu , Li Jie , Yang Dehua , Wang Ming-Wei
Published: June 2020

Glucagon is a peptide hormone secreted by islet α cells. It plays crucial roles in glucose homeostasis and metabolism by activating its cognate glucagon receptor (GCGR). A naturally occurring deleterious mutation V368M in the human GCGR leads to reduced ligand binding and down-regulation of glucagon signaling. To examine the association between this mutation and metabolic disorders, a knock-in mouse model bearing homozygous V369M substitution (equivalent to human V368M) in GCGR was made using CRISPR-Cas9 technology. These GcgrV369M+/+ mice displayed lower fasting blood glucose levels with improved glucose tolerance compared with wild-type controls. They also exhibited hyperglucagonemia, pancreas enlargement and α cell hyperplasia with a lean phenotype. Additionally, V369M mutation resulted in a reduction in adiposity with normal body weight and food intake. Our findings suggest a key role of V369M/V368M mutation in GCGR-mediated glucose homeostasis and pancreatic functions, thereby pointing to a possible interplay between GCGR defect and metabolic disorders.
The predictive value of serum lipids for eye metastases in male nasopharyngeal carcinoma patients
Authors: Xie Zhen , Shao Yi
Published: June 2020

Background: Nasopharyngeal carcinoma (NPC) is a tumor that is commonly found in southern China. NPC has several risk factors, such as infection with the Epstein–Barr virus. However, we know little about the risk factors for eye metastasis (EM) in male patients with NPC. Serum lipids are well recognized as risk factors for cardiovascular disease, and recent studies show that they also have a relationship with the development of NPC.

Purpose: We designed the present study to determine whether they were relevant with the development of EM in male NPC patients by detecting the levels of several serum lipids.

Methods: A total of 1140 male patients with NPC were enrolled in this retrospective study and we divided them into two groups: the metastasis (EM) group and non-eye metastasis (NEM) group. A variety of serum lipids between the two groups were tested and compared.

Results: There were statistical differences in the levels of serum TG and TC between these two groups. Binary logistic regression showed that TG and TC were independent risk factors for EM in male NPC patients with P=0.004 and P<0.001, respectively. The area under the curve of TG and TC were 0.764 and 0.681, respectively, using cutoff values of 0.975 and 3.425 mmol/l, respectively. We found that TG had higher sensitivity and specificity values with 87.5% and 62.7%, respectively, than TC which were 50.0% and 87.2%.

Conclusion: TG and TC are potential risk factors for eye metastases in male NPC patients.
MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-κB pathway in neonatal sepsis
Authors: Chen Xueli , Chen Ying , Dai Li , Wang Na
Published: June 2020

Neonatal septicemia is a serious infectious disease in the neonatal period. MicroRNAs (miRNAs) have been reported to participate in the inflammatory responses in neonatal sepsis. The aim of the present study was to explore the effects and molecular mechanism of miR-96-5p on regulating the inflammatory responses in neonatal sepsis. MiR-96-5p was low expressed while nicotinamide phosphoribosyltransferase (NAMPT) was high expressed in the serum of neonatal septicemia patients. The expression of miR-96-5p was decreased in LPS-induced inflammatory responses. Besides, miR-95-5p relieved LPS-induced inflammatory responses in RAW264.7 cells. NAMPT was demonstrated as a potential target of miR-96-5p, and knockdown of NAMPT reduced inflammatory in RAW264.7 cells stimulated with LPS. Moreover, overexpression of NAMPT reversed the effects of miR-96-5p on LPS-induced inflammatory responses. In addition, miR-96-5p inhibited nuclear factor (NF)-κB signaling pathway in RAW264.7 cells stimulated with LPS. MiR-96-5p alleviated inflammatory responses via targeting NAMPT and inhibiting NF-κB pathway in neonatal sepsis.
A ferredoxin-dependent dihydropyrimidine dehydrogenase in Clostridium chromiireducens
Authors: Wang Feifei , Wei Yifeng , Lu Qiang , Ang Ee Lui , Zhao Huimin , Zhang Yan
Published: June 2020

Dihydropyrimidine dehydrogenase (PydA) catalyzes the first step of the reductive pyrimidine degradation (Pyd) pathway in bacteria and eukaryotes, enabling pyrimidines to be utilized as substrates for growth. PydA homologs studied to date catalyze the reduction of uracil to dihydrouracil, coupled to the oxidation of NAD(P)H. Uracil reduction occurs at a flavin mononucleotide (FMN) site, and NAD(P)H oxidation occurs at a flavin adenine dinucleotide (FAD) site, with two ferredoxin domains thought to mediate inter-site electron transfer. Here, we report the biochemical characterization of a Clostridial PydA homolog (PydAc) from a Pyd gene cluster in the strict anaerobic bacterium Clostridium chromiireducens. PydAc lacks the FAD domain, and instead is able to catalyze uracil reduction using reduced methyl viologen or reduced ferredoxin as the electron source. Homologs of PydAc are present in Pyd gene clusters in many strict anaerobic bacteria, which use reduced ferredoxin as an intermediate in their energy metabolism.
Real‐time non‐intrusive RF biochemical sensor
Authors: Pandit Nidhi , Jaiswal Rahul K. , Pathak Nagendra P.
Published: June 2020

In this Letter, a non‐destructive microwave resonant sensor based on the modified complementary split‐ring resonator has been proposed and analysed with respect to its sensitivity for detecting the aqueous biochemicals. This technique is based on the perturbation theory and only requires to measure resonant frequency and hence, achieving a substantial reduction in the computation time and cost. The proposed sensor is designed to achieve high sensitivity performance with a measured quality factor of the sensor in the bare state, Q B = 631.5, at the centre frequency of f o = 6.31 GHz. The proposed sensor has a maximum sensitivity of S = 6.23 MHz with respect to a unit change in the dielectric constant value. A numerical model is developed for the dielectric constant of the biochemicals as a function of the resonant frequency. The proposed sensor, therefore, provides high sensitivity, simple structure layout and real‐time response with cost effectiveness. The proposed structure can be a potential candidate for the non‐intrusive sensing of aqueous biochemicals.
Integrating layered recurrent ANN with robust control strategy for diverse operating conditions of AGC of the power system
Authors: Sharma Gulshan , Panwar Akhilesh , Arya Yogendra , Kumawat Manoj
Published: June 2020

This study presents the structural, operational and control aspects of doubly fed induction generator (DFIG) based wind integrated power systems. The automatic generation control (AGC) of a meshed power system including DFIG‐based wind turbines has been framed and investigations under various system perturbation are presented. The two‐area system consisting of non‐reheat thermal turbines with DFIG and interconnected through parallel AC/DC tie‐lines is considered for the study. The system non‐idealities such as governor lag and generation rate constraints are taken into consideration. An AGC strategy using a layered recurrent artificial neural network (ANN) is proposed in this work. The gains of the proposed AGC are obtained by effectively training the ANN using a set of reliable data obtained from a widespread range of operating system conditions using robust control strategy. The study also incorporates the design of AGC for the power system using the fuzzy logic concept and other AGC actions such as integral (I), proportional–integral (PI) and proportional–integral–derivative (PID) calculated via the means of particle swarm optimization (PSO). The results obtained with the proposed ANN created AGC are linked and demonstrated their superiority over fuzzy logic PI and traditional PSO‐based I/PI/PID AGC strategies under numerous system operating conditions.
Real‐time detection of vulnerable power system areas to geomagnetic disturbance
Authors: Rezaei‐Zare Mina , Ariannik Mohamadreza , Rezaei‐Zare Afshin
Published: June 2020

This study proposes an approach for the fast and accurate identification of the vulnerable areas of the power system to geomagnetic disturbance (GMD). The proposed method can be used for real‐time situational awareness and preparedness in power system control rooms and proactive mitigation of the GMD threats. In addition, it can be employed as an off‐line GMD vulnerability assessment tool for power system planning analysis. In this study, a generalised mathematical basis is presented to find the maximum geomagnetically induced current (GIC) flow in the multi‐zone earth structure based on the orthogonal GIC components. Furthermore, a real‐time frequency estimation method is developed based on wavelet transform to estimate the frequency of the geomagnetic waveform for the maximum GIC calculation. The proposed approach is applied to the Ontario 500 and 230 kV transmission systems to identify the vulnerable equipment. The results are also compared with the angle sweep results. The numerical results reveal that not only the proposed method is more accurate but also significantly faster than the angle sweep method. Such prominent features introduce the proposed approach as a preferable method for real‐time applications and optimisation of power system operation during GMDs.
7L‐SCBI topology with minimal semiconductor device count
Authors: Prathap Reddy Bhimireddy , Siddique Marif Daula , Iqbal Atif , Mekhilef Saad , Rahman Syed , Maroti Pandav Kiran
Published: June 2020

In this work, a seven‐level switched capacitor boost inverter (7L‐SCBI) is proposed with minimal resource count. The proposed inverter requires only eight switches and two capacitors to generate a seven‐level voltage. The proposed 7L‐SCBI is capable of generating a multilevel voltage as well as boost the input DC‐link voltage up to 1.5 times with a reduced blocking voltage of switches and capacitors. The comparison in terms of efficiency and device count with other switched capacitor topologies is presented in detail. The performance validation of the proposed 7L‐SCBI is done with the help of a laboratory prototype.
V363 Cassiopeiae: a new lithium-rich Galactic Cepheid
Authors: Catanzaro G. , Ripepi V. , Clementini G. , Cusano F. , De Somma G. , Leccia S. , Marconi M. , Molinaro R. , Moretti M. I. , Musella I. , Testa V.
Published: June 2020

Context. Classical Cepheids (DCEPs) are important astrophysical objects not only as standard candles in the determination of the cosmic distance ladder, but also as a testbed for the stellar evolution theory. This is based on the strict connection between their pulsation (period(s) and amplitudes) and stellar parameters (luminosity, mass, effective temperature, and metallicity).

Aims. We examine the nature of the Galactic DCEP V363 Cas and other DCEPs that show cosmic abundances of lithium in their atmospheres.

Methods. We collected three epochs of high-resolution spectroscopy for V363 Cas with HARPS-N at the TNG. We measured accurate stellar parameters: the effective temperatures, gravities, microturbulences, radial velocities, and metal abundances.

Results. We detected a lithium abundance of A(Li) = 2.86 ± 0.10 dex, along with iron, carbon, and oxygen abundances of [Fe/H] = −0.30 ± 0.12 dex, [C/H] = −0.06 ± 0.15 dex, and [O/H] = 0.00 ± 0.12 dex. V363 Cas is the fifth of the Milky Way DCEPs to exhibit a Li-rich feature. An analysis of historical time-series spanning a 100-year interval shows that the period of V363 Cas is increasing, with a sharp acceleration after HJD = 2 453 000 days. This is a clear indication of a first crossing of the instability strip.

Conclusions. Our results favour the scenario in which the five Galactic Li-rich DCEPs are on their first crossing of the instability strip and have had slowly rotating progenitors during their main-sequence phase.
Primär- und Sekundärprävention des Multiplen Myeloms
Authors: Cordas dos Santos David , Erickson Nicole , Gerland Lars , Jundt Franziska , Theurich Sebastian
Published: June 2020

Lifestyle factors such as diet, physical activity and exposure to noxious agents are modifiable factors that have a significant impact on the state of health and life expectancy of humans. The following article is intended to provide an overview of current knowledge on the influence of these lifestyle factors on the development and progression of multiple myeloma and is dedicated to the question of the extent to which prevention strategies can be usefully applied.
Rezidivtherapie des Multiplen Myeloms – Individualisierte Konzepte aus dem Arsenal vielfältiger Optionen
Authors: Weyermann Charlotte , Straka Christian , Einsele Hermann
Published: June 2020

The prognosis of patients with multiple myeloma has improved significantly over the past 20 years. However, the patient population in the relapse situation is very heterogeneous due to increasing age and the previous course of the disease and therapy. In particular, the approval of new targeted substances offers numerous treatment options that can be adapted to the individual situation.

In relapsed multiple myeloma, disease- and patient-specific factors must be considered for an individually adapted therapy. Suitable patients can also receive an autologous stem cell transplant (ASCT) or, in the case of early relapse after ASCT, an allogenic stem cell transplant, if possible as part clinical studies. Proteasome or immunomodulator-based triple combinations are the standard in recurrence. In frail patients, a combination of two can also be used. The new substances also offer very good therapeutic options for high-risk cytogenetics or renal insufficiency. The monoclonal antibodies Daratumumab and Elotuzumab are well tolerated except for infusion reactions and are highly effective in various combinations, even in high-risk cytogenetics.
Die Bedeutung des extrathorakalen Luftraumes für die
Kieferorthopädie
Authors: Hourfar Jan , Kinzinger Gero , Lisson Jörg A.
Published: June 2020

Der „Extrathorakale Luftraum“ findet im klinischen Alltag des
Kieferorthopäden sowohl bei der Fallplanung als auch bei der
Therapie kaum Beachtung. Ziel dieses Beitrages ist es deshalb, Anatomie,
Historie, unterschiedliche Definitionen, bildgebende Verfahren sowie
Simulationstechniken des extrathorakalen Luftraumes darzustellen. Ohne
kritische Aspekte zu vernachlässigen, werden therapeutische
Maßnahmen mit möglichen Auswirkungen auf den extrathorakalen
Luftraum, ausgewählte Studienergebnisse sowie
interdisziplinäre Implikationen aufgezeigt, auch um die Relevanz des
Themas für den Kliniker hervorzuheben.
Akademisierung des Hebammenberufs (Teil 2): Risiken – und wie
sie in den Studiengängen bestmöglich vermieden werden können
Authors: Graf Joachim , Simoes Elisabeth , Plappert Claudia F. , Abele Harald
Published: June 2020

Die jetzt auch in Deutschland einsetzende Vollakademisierung der bisher
fachschulisch verorteten Hebammenausbildung stellt sowohl die Länder als
auch die Hochschulen vor große Herausforderungen. Ziel dieses Artikels
ist vor diesem Hintergrund, mögliche Risiken, die sich aus der
Vollakademisierung und der Neufassung des Hebammengesetzes ergeben, zu
identifizieren und mögliche Lösungsstrategien aufzuzeigen, um
der Implementierung von Studiengängen Vorschub zu leisten.
Autopneumonektomie. Ein vergessenes Krankheitsbild
Authors: Gerhardy H. J. , Weber R. , Lux P. , Klein R. M. , Winter J.
Published: June 2020

Anamnese Die 80-jährige Patientin stellte sich mit einer Arteria-carotis-Stenose links vor. Im Alter von 7 Jahren hatte sie unter Hämoptysen gelitten.

Untersuchungen und Diagnose Das EKG zeigte einen AV-Block II. Grades Typ Mobitz. Im Röntgenbild und Computertomogramm des Thorax imponierten eine Verlagerung des Mediastinums und des Herzens nach links, eine komplette Schrumpfung der linken Lunge sowie eine Überblähung der rechten Lunge. Die Lungenfunktionsanalyse ergab eine mäßige Restriktion. Es wurde die Diagnose Autopneumonektomie gestellt.

Therapie und Verlauf Eine Schrittmacherimplantation über die linke V. cephalica und eine Endarteriektomie der Arteria carotis links wurden komplikationslos durchgeführt.

Folgerung Resultiert nach Autopneumonektomie eine Obstruktion der Atemwege aufgrund der Mediastinalverschiebung, ist eine operative Revision erforderlich. Eine Antibiotikatherapie ist bei Atemwegsinfektionen indiziert. Punktionen der V. subclavia sind kontraindiziert, da eine Fehlpunktion zu einem kompletten Pneumothorax führen kann.
Differential Effects of Components in Artemisia annua Extract on the Induction of Drug-Metabolizing Enzyme Expression Mediated by Nuclear Receptors
Authors: Zhang Xueli , Meng Ran , Wang Haina , Xing Jie
Published: June 2020

Artemisia annua tea is a popular dosage form used to treat and prevent malaria in some developing countries. However, repeated drinking leads to an obviously decreased efficacy, which may be related to the induction of metabolizing enzymes by artemisinin. In the present study, the ability of different components in A. annua to activate the pregnane X receptor and constitutive androstane receptor was evaluated by the dual luciferase reporter gene system. The changes in mRNA and protein expression of CYP3A4 and CYP2B6 were determined by quantitative real-time PCR and Western blotting. Results showed that in the pregnane X receptor-mediated CYP3A4 reporter gene system, chrysosplenetin and arteannuin B exhibited a weak induction effect on pregnane X receptor wt, while arteannuin A had a strong induction effect on pregnane X receptor wt and pregnane X receptor 370 and a weak induction effect on pregnane X receptor 163. In the pregnane X receptor-mediated CYP2B6
reporter gene system, arteannuin A had a moderate induction effect on pregnane X receptor wt and pregnane X receptor 379, and a weak induction effect on pregnane X receptor 403, while arteannuin B had a weak induction effect on pregnane X receptor wt and pregnane X receptor 379. Arteannuin A had a strong induction effect on constitutive androstane receptor 3 in constitutive androstane receptor-mediated CYP3A4/2B6 reporter gene systems, while arteannuin B showed a weak induction effect on constitutive androstane receptor 3 in the constitutive androstane receptor-mediated CYP2B6 reporter gene system. The mRNA and protein expressions of CYP3A4 and CYP2B6 were increased when the pregnane X receptor or constitutive androstane receptor was activated. Various components present in A. annua differentially affect the activities of pregnane X receptor isoforms and the constitutive androstane receptor, which indicates the possibility of a drug-drug interaction. This partly
explains the decline in efficacy after repeated drinking of A. annua tea.
C–H Functionalization Strategies in the Naphthalene Series: Site Selections and Functional Diversity
Authors: Prim Damien , Large Benjamin
Published: June 2020

Naphthalene is certainly not a common arene. In contrast to benzene, the bicyclic feature of naphthalene offers multiple differentiable positions and thus a broad diversity of substitution patterns. Naphthalene is a central building block for the construction of elaborated polycyclic architectures with applications in broad domains such as life and materials sciences. As a result, C–H functionalization strategies specially designed for naphthalene substrates have become essential to install valuable substituents on one or both rings towards polysubstituted naphthalenes. This short review provides a focus on uncommon substitution patterns; however, classical ortho C–H activation is not covered.

1 Introduction

2 C–H Functionalization Using a Directing Group Located at Position 1

2.1 Functionalization on the Ring Bearing the DG: 1,3-Substitution Pattern

2.2 Functionalization on the Ring Bearing the DG: 1,4-Substitution Pattern

2.3 Functionalization on the Neighboring Ring: 1,6-, 1,7- and 1,8-Substitution Patterns

3 C–H Functionalization Using a Directing Group Located at Position 2

3.1 Functionalization on the Ring Bearing the DG: 2,4- and 2,1-Substitution Patterns

3.2 Miscellaneous Substitution Patterns

4 Bis C–H Functionalization

4.1 Symmetrical Bisfunctionalization: 1,2,8-Substitution Pattern

4.2 Symmetrical Bisfunctionalization: 2,3,1-Substitution Pattern

4.2 Unsymmetrical Bisfunctionalization: 2,3,1-Substitution Pattern

4.3 Symmetrical Bisfunctionalization: 2,4,8-Substitution Pattern

5 Conclusion and Outlook
The gridded retarding ion drift sensor for the petitSat cubeSat mission
Authors: Davidson R. L. , Oborn B. , Robertson E. F. , Noel S. , Earle G. D. , Green J. , Kramer J.
Published: June 2020

The Gridded Retarding Ion Drift Sensor (GRIDS) is a small sensor that will fly on the 6 U petitSat CubeSat. It is designed to measure the three-dimensional plasma drift velocity vector in the Earth’s ionosphere. The GRIDS also supplies information about the ion temperature, ion density, and the ratio of light to heavy ions present in the ionospheric plasma. It utilizes well-proven techniques that have been successfully validated by similar instruments on larger satellite missions while meeting CubeSat-compatible requirements for low mass, size, and power consumption. GRIDS performs the functions of a Retarding Potential Analyzer (RPA) and an Ion Drift Meter (IDM) by combining the features of both types of instruments in a single package. The sensor alternates RPA and IDM measurements to produce the full set of measurement parameters listed above. On the petitSat mission, GRIDS will help identify and characterize a phenomenon known as plasma blobs (or enhancements).