bluuebunny/crossref_metadata_2025_split huggingface dataset:
MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5
Authors: Cheung Alvin Ho-Kwan , Wong Kit-Yee , Liu Xiaoli , Ji Fenfen , Hui Chris Ho-Lam , Zhang Yihan , Kwan Johnny Sheung-Him , Chen Bonan , Dong Yujuan , Lung Raymond Wai-Ming , Yu Jun , Lo Kwok Wai , Wong Chi Chun , Kang Wei , To Ka-Fai 
Published: July 2023

AbstractMLK4, a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, has been implicated in cancer progression. However, its role in lung adenocarcinoma has not been characterized. Here, we showed that MLK4 was overexpressed in a significant subset of lung adenocarcinoma, associated with a worse prognosis, and exerted an oncogenic function in vitro and in vivo. Bioinformatics analyses of clinical datasets identified phosphoenolpyruvate carboxykinase 1 (PCK1) as a novel target of MLK4. We validated that MLK4 regulated PCK1 expression at transcriptional level, by phosphorylating the transcription factor CREB, which in turn mediated PCK1 expression. We further demonstrated that PCK1 is an oncogenic factor in lung adenocarcinoma. Given the importance of PCK1 in the regulation of cellular metabolism, we next deciphered the metabolic effects of MLK4. Metabolic and mass spectrometry analyses showed that MLK4 knockdown led to significant reduction of glycolysis and decreased levels of glycolytic pathway metabolites including phosphoenolpyruvate and lactate. Finally, the promoter analysis of MLK4 unravelled a binding site of transcription factor KLF5, which in turn, positively regulated MLK4 expression in lung adenocarcinoma. In summary, we have revealed a KLF5-MLK4-PCK1 signalling pathway involved in lung tumorigenesis and established an unusual link between MAP3K signalling and cancer metabolism.
Genome-wide screening in pluripotent cells identifies Mtf1 as a suppressor of mutant huntingtin toxicity
Authors: Ferlazzo Giorgia Maria , Gambetta Anna Maria , Amato Sonia , Cannizzaro Noemi , Angiolillo Silvia , Arboit Mattia , Diamante Linda , Carbognin Elena , Romani Patrizia , La Torre Federico , Galimberti Elena , Pflug Florian , Luoni Mirko , Giannelli Serena , Pepe Giuseppe , Capocci Luca , Di Pardo Alba , Vanzani Paola , Zennaro Lucio , Broccoli Vania , Leeb Martin , Moro Enrico , Maglione Vittorio , Martello Graziano 
Published: July 2023

AbstractHuntington’s disease (HD) is a neurodegenerative disorder caused by CAG-repeat expansions in the huntingtin (HTT) gene. The resulting mutant HTT (mHTT) protein induces toxicity and cell death via multiple mechanisms and no effective therapy is available. Here, we employ a genome-wide screening in pluripotent mouse embryonic stem cells (ESCs) to identify suppressors of mHTT toxicity. Among the identified suppressors, linked to HD-associated processes, we focus on Metal response element binding transcription factor 1 (Mtf1). Forced expression of Mtf1 counteracts cell death and oxidative stress caused by mHTT in mouse ESCs and in human neuronal precursor cells. In zebrafish, Mtf1 reduces malformations and apoptosis induced by mHTT. In R6/2 mice, Mtf1 ablates motor defects and reduces mHTT aggregates and oxidative stress. Our screening strategy enables a quick in vitro identification of promising suppressor genes and their validation in vivo, and it can be applied to other monogenic diseases.
Cavity-enhanced single-shot readout of a quantum dot spin within 3 nanoseconds
Authors: Antoniadis Nadia O. , Hogg Mark R. , Stehl Willy F. , Javadi Alisa , Tomm Natasha , Schott Rüdiger , Valentin Sascha R. , Wieck Andreas D. , Ludwig Arne , Warburton Richard J. 
Published: July 2023

AbstractRapid, high-fidelity single-shot readout of quantum states is a ubiquitous requirement in quantum information technologies. For emitters with a spin-preserving optical transition, spin readout can be achieved by driving the transition with a laser and detecting the emitted photons. The speed and fidelity of this approach is typically limited by low photon collection rates and measurement back-action. Here we use an open microcavity to enhance the optical readout signal from a semiconductor quantum dot spin state, largely overcoming these limitations. We achieve single-shot readout of an electron spin in only 3 nanoseconds with a fidelity of (95.2 ± 0.7)%, and observe quantum jumps using repeated single-shot measurements. Owing to the speed of our readout, errors resulting from measurement-induced back-action have minimal impact. Our work reduces the spin readout-time well below both the achievable spin relaxation and dephasing times in semiconductor quantum dots, opening up new possibilities for their use in quantum technologies.
UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma
Authors: Kostyrko Kaja , Román Marta , Lee Alex G. , Simpson David R. , Dinh Phuong T. , Leung Stanley G. , Marini Kieren D. , Kelly Marcus R. , Broyde Joshua , Califano Andrea , Jackson Peter K. , Sweet-Cordero E. Alejandro 
Published: July 2023

AbstractKRAS is a frequent driver in lung cancer. To identify KRAS-specific vulnerabilities in lung cancer, we performed RNAi screens in primary spheroids derived from a Kras mutant mouse lung cancer model and discovered an epigenetic regulator Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). In human lung cancer models UHRF1 knock-out selectively impaired growth and induced apoptosis only in KRAS mutant cells. Genome-wide methylation and gene expression analysis of UHRF1-depleted KRAS mutant cells revealed global DNA hypomethylation leading to upregulation of tumor suppressor genes (TSGs). A focused CRISPR/Cas9 screen validated several of these TSGs as mediators of UHRF1-driven tumorigenesis. In vivo, UHRF1 knock-out inhibited tumor growth of KRAS-driven mouse lung cancer models. Finally, in lung cancer patients high UHRF1 expression is anti-correlated with TSG expression and predicts worse outcomes for patients with KRAS mutant tumors. These results nominate UHRF1 as a KRAS-specific vulnerability and potential target for therapeutic intervention.
Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan
Authors: Wang Peng , Liu Jiang , Zhu Xiaomei , Kenry  , Yan Zhengqing , Yan Jiahui , Jiang Jitong , Fu Manlin , Ge Jingyan , Zhu Qing , Zheng Yuguo 
Published: July 2023

AbstractCyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvβ3overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.
Improved oxidation resistance of Cr-Si coated Zircaloy with an in-situ formed Zr2Si diffusion barrier
Authors: Zeng Song , Li Jun-Feng , Chen Chen , Meng Yan , Zhu Chao-Wen , Han Xiao-Chun , Bao Yi-Wang , Zhang Hai-Bin 
Published: July 2023

AbstractIn the present study, the dense Cr and Cr0.92Si0.08 coatings have been deposited on Zircaloy-4 substrates by the magnetron sputtering technique. The high-temperature oxidation resistance of coatings is evaluated in 1200 °C steam for 1–4 h. The Cr0.92Si0.08 coating shows better oxidation resistance than the Cr coating. The in-situ formed Zr2Si diffusion barrier inhibits the mutual diffusion of Cr and Zr. And the formation of a Cr2O3/SiO2 double-layer scale effectively improves the oxidation resistance of a single Cr2O3 layer. The formation of the in-situ diffusion barrier, Cr2O3/SiO2 scales and oxidation protection mechanisms of the Cr0.92Si0.08 coating have been discussed in detail.
Diversity under a magnifier lens: the case of Typhlotanaidae (Crustacea: Tanaidacea) in the N Atlantic
Authors: Gellert Marta , Błażewicz Magdalena , Mamos Tomasz , Bird Graham J. 
Published: July 2023

AbstractResearch focusing on ‘stout-bodied’ typhlotanaids collected from several sites around Iceland and adjacent N Atlantic region has resulted in the description of 15 species new to science, as well as the creation of eight new genera.Typhlotanais eximiusHansen, 1913 is redescribed and transferred to a new genus, whileTyphlotanais crassusandPeraeospinosus adipatusare transferred to the genusLarsenotanais. The morphological and the molecular data were combined to consolidate and confirm the validity of the results obtained from both approaches. The polyphyletic nature of the Typhlotanaidae and its serious of its taxonomic diversity are emphasized, although molecular analysis reveals that the ‘stout-bodied’ Typhlotanaidae form monophyletic clade. Depth and temperature are identified as the main environmental parameters determining the distribution of this group of Typhlotanaidae. Several species are clearly associated with the shelf and upper bathyal of Iceland. The Greenland-Iceland-Faroe Ridge is shown to be a distinct zoogeographical barrier for typhlotanaids inhabiting the deeper slope and abyssal regions around Iceland.
Methods for assessing change in brain plasticity at night and psychological resilience during daytime between repeated long-duration space missions
Authors: Otsuka Kuniaki , Cornelissen Germaine , Kubo Yutaka , Shibata Koichi , Mizuno Koh , Aiba Tatsuya , Furukawa Satoshi , Ohshima Hiroshi , Mukai Chiaki 
Published: July 2023

AbstractThis study was designed to examine the feasibility of analyzing heart rate variability (HRV) data from repeat-flier astronauts at matching days on two separate missions to assess any effect of repeated missions on brain plasticity and psychological resilience, as conjectured by Demertzi. As an example, on the second mission of a healthy astronaut studied about 20 days after launch, sleep duration lengthened, sleep quality improved, and spectral power (ms2) co-varying with activity of the salience network (SN) increased at night. HF-component (0.15–0.50 Hz) increased by 61.55%, and HF-band (0.30–0.40 Hz) by 92.60%. Spectral power of HRV indices during daytime, which correlate negatively with psychological resilience, decreased, HF-component by 22.18% and HF-band by 37.26%. LF-component and LF-band, reflecting activity of the default mode network, did not change significantly. During the second mission, 24-h acrophases of HRV endpoints did not change but the 12-h acrophase of TF-HRV did (P < 0.0001), perhaps consolidating the circadian system to help adapt to space by taking advantage of brain plasticity at night and psychological resilience during daytime. While this N-of-1 study prevents drawing definitive conclusions, the methodology used herein to monitor markers of brain plasticity could pave the way for further studies that could add to the present results.
A novel method of determining the active drag profile in swimming via data manipulation of multiple tension force collection methods
Authors: Haskins A. , McCabe C. , Kennedy R. , McWade R. , Lennon A. B. , Chandar D. 
Published: July 2023

AbstractA novel method aimed at evaluating the active drag profile during front-crawl swimming is proposed. Fourteen full trials were conducted with each trial using a stationary load cell set-up and a commercial resistance trainer to record the tension force in a rope, caused by an athlete swimming. Seven different stroke cycles in each experiment were identified for resampling time dependent data into position dependent data. Active drag was then calculated by subtracting resistance trainer force data away from the stationary load cell force data. Mean active drag values across the stroke cycle were calculated for comparison with existing methods, with mean active drag values calculated between 76 and 140 N depending on the trial. Comparing results with established active drag methods, such as the Velocity Perturbation Method (VPM), shows agreement in the magnitude of the mean active drag forces. Repeatability was investigated using one athlete, repeating the load cell set-up experiment, indicating results collected could range by 88 N depending on stroke cycle position. Variation in results is likely due to inconsistencies in swimmer technique and power output, although further investigation is required. The method outlined is proposed as a representation of the active drag profile over a full stroke cycle.
Soliton solutions of fractional extended nonlinear Schrödinger equation arising in plasma physics and nonlinear optical fiber
Authors: Ahmad Jamshad , Akram Sonia , Noor Kanza , Nadeem Muhammad , Bucur Amelia , Alsayaad Yahya 
Published: July 2023

AbstractIn this research, we study traveling wave solutions to the fractional extended nonlinear SchrÖdinger equation (NLSE), and the effects of the third-order dispersion parameter. This equation is used to simulate the propagation of femtosecond, plasma physic and in nonlinear optical fiber. To accomplish this goal, we use the extended simple equation approach and the improved F-expansion method to secure a variety of distinct solutions in the form of dark, singular, periodic, rational, and exponential waves. Also, the stability of the outcomes is effectively examined. Several graphs have been sketched under appropriate parametric values to reinforce some reported findings. Computational work along with a graphical demonstration confirms the exactness of the proposed methods. The issue has not previously been investigated by taking into account the impact of the third order dispersion parameter. The main objective of this study is to obtain the different kinds of traveling wave solutions of fractional extended NLSE which are absent in the literature which justify the novelty of this study. We believe that these novel solutions hold a prominent place in the fields of nonlinear sciences and optical engineering because these solutions will enables a through understanding of the development and dynamic nature of such models. The obtained results indicate the reliability, efficiency, and capability of the implemented technique to determine wide-spectral stable traveling wave solutions to nonlinear equations emerging in various branches of scientific, technological, and engineering domains.
Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells
Authors: Jeong Gyeong Han , Lee Hanui , Woo So-Yeun , Lee Hong-Ki , Chung Byung Yeoup , Bai Hyoung-Woo 
Published: July 2023

AbstractRadiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages.
A new point cloud processing method unveiled hidden coastal boulders from deep vegetation
Authors: Nakata Koki , Yanagisawa Hideaki , Goto Kazuhisa 
Published: July 2023

AbstractHuge coastal boulders are useful to reconstruct the size of past extreme waves such as those associated with tsunamis and storms using inverse-type or forward-type boulder transport models. These models fundamentally require the precise shape of boulders. Traditionally, they have often been assumed to be rectangular or ellipsoidal with three axes measured in the field. However, if the boulder’s shape is complex, this method is unable to represent the actual shape accurately. Therefore, it prevents estimation of the tsunami or storm size reasonably using models. For this reason, boulders have recently been surveyed using 3D scanning techniques such as LiDAR. However, coastal boulders now on land in tropical and subtropical areas such as Japan and Tonga are often covered by deep vegetation, which makes 3D surveys difficult. This report presents new methods to ascertain boulder shapes when they are obscured by vegetation. First, using UAV-type and mobile-type LiDAR, we scanned well-known tsunami boulders in southwestern Japan that had been covered with deep vegetation. Then, we developed a new method to extract only boulders and filter out vegetation from a point cloud. Thereby, we created 3D models of the boulders. We improved the boulder transport model further to assume the 3D boulder model accurately. In addition to coastal boulders, this filtering method is expected to be useful for unveiling any object, such as an archaeological structure, that is hidden in deep vegetation.
Optimal lipid-lowering therapy in patients who were functionally deferred percutaneous coronary intervention
Authors: Abe Takuro , Shimazaki Kensuke , Moriyama Tetsu , Murohashi Akira , Iwanami Yuji , Sasaki Akihito , Saito Katsumi , Jujo Kentaro 
Published: July 2023

AbstractDeferral of percutaneous coronary intervention (PCI) for functionally insignificant stenosis, defined as fractional flow reserve (FFR) > 0.80, is associated with favorable long-term prognoses. The lower-the-better strategy for low-density lipoprotein cholesterol (LDL-C) management is an established non-angioplasty therapy to improve the clinical outcomes of patients undergoing PCI. We examined the optimal LDL-C management in cases of intermediate coronary stenosis with deferred PCI on the basis of FFR values. This observational study included 273 consecutive patients with a single target vessel and deferred PCI with an FFR > 0.80. Patients with an FFR of 0.81–0.85 (n = 93) and those with FFR > 0.85 (n = 180) were classified into the lower (< 100 mg/dL) and higher (≥ 100 mg/dL) LDL-C groups. The endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including death, non-fatal myocardial infarction, ischemic stroke, heart failure hospitalization, and unplanned revascularization. Patients with an FFR of 0.81–0.85 had a significantly higher MACCE rate than those with an FFR > 0.85 (log-rank, p = 0.003). In patients with an FFR of 0.81–0.85, the lower LDL-C group showed a significantly lower MACCE rate than the higher LDL-C group (log-rank, p = 0.006). However, the event rate did not differ significantly between the two groups in patients with FFR > 0.85 (log-rank, p = 0.84). Uncontrolled LDL-C levels were associated with higher MACCE rates in cases with deferred PCI due to an FFR of 0.81–0.85. This high-risk population for adverse cardiovascular events should receive strict LDL-C-lowering therapy.
Regulatory mechanisms of glucose absorption in the mouse proximal small intestine during fasting and feeding
Authors: Nakamura Chisato , Ishizuka Noriko , Yokoyama Kanako , Yazaki Yuyu , Tatsumi Fumiya , Ikumi Naotaka , Hempstock Wendy , Ikari Akira , Yoshino Yuta , Hayashi Hisayoshi 
Published: July 2023

AbstractFasting is known to alter the function of various organs and the mechanisms of glucose metabolism, which affect health outcomes and slow aging. However, it remains unclear how fasting and feeding affects glucose absorption function in the small intestine. We studied the effects of the fasting and feeding on glucose-induced short-circuit current (Isc) in vitro using an Ussing chamber technique. Glucose-induced Isc by SGLT1 was observed in the ileum, but little or no Isc was observed in the jejunum in ad libitum-fed mice. However, in mice fasted for 24–48 h, in addition to the ileum, robust glucose-induced Isc was observed over time in the jejunum. The expression of SGLT1 in the brush border membranes was significantly decreased in the jejunum under fed conditions compared to 48 h fasting, as analyzed by western blotting. Additionally, when mice were fed a 60% high glucose diet for 3 days, the increase in glucose-induced Isc was observed only in the ileum, and totally suppressed in the jejunum. An increase in Na+ permeability between epithelial cells was concomitantly observed in the jejunum of fasted mice. Transepithelial glucose flux was assessed using a non-metabolizable glucose analog, 14C-methyl α-d-glucopyranoside glucose (MGP). Regardless of whether fed or fasted, no glucose diffusion mechanism was observed. Fasting increased the SGLT1-mediated MGP flux in the jejunum. In conclusion, segment-dependent up- and down-regulation mechanisms during fasting and feeding are important for efficient glucose absorption once the fast is broken. Additionally, these mechanisms may play a crucial role in the small intestine's ability to autoregulate glucose absorption, preventing acute hyperglycemia when large amounts of glucose are ingested.
Improving adsorption performance of l-ascorbic acid from aqueous solution using magnetic rice husk as an adsorbent: experimental and RSM modeling
Authors: Aslani Azam , Masoumi Hadiseh , Ghanadzadeh Gilani Hossein , Ghaemi Ahad 
Published: July 2023

AbstractIn this research, rice husk (RH) was utilized to prepare a magnetic adsorbent for adsorption of ascorbic acid (AA). The magnetic agent is iron(III) chloride (FeCl3). The impact of acid concentration in the range of 400–800 ppm, adsorbent dosage in the range of 0.5–1 g, and contact time in the range of 10–130 min were studied. The Langmuir model had the highest R2 of 0.9982, 0.9996, and 0.9985 at the temperature of 15, 25, and 35 °C, respectively, and the qmax values in these temperatures have been calculated at 19.157, 31.34, and 38.75 mg/g, respectively. The pseudo-second-order kinetic model had the best agreement with the experimental results. In this kinetic model, the values of q have been measured at 36.496, 45.248, and 49.019 mg/g at the acid concentration of 418, 600, and 718 ppm, respectively. The values of ΔHo and ΔSo were measured 31.972 kJ/mol and 120.253 kJ/mol K, respectively, which proves the endothermic and irregularity nature of the adsorption of AA. Besides, the optimum conditions of the design-expert software have been obtained 486.929 ppm of acid concentration, 0.875 g of the adsorbent dosage, and 105.397 min of the contact time, and the adsorption efficiency in these conditions was determined at 92.94%. The surface area of the RH and modified RH was determined of 98.17 and 120.23 m2/g, respectively, which confirms the high surface area of these two adsorbents.