bluuebunny/crossref_metadata_2025_split huggingface dataset:
KLK10 promotes the progression of KRAS mutant colorectal cancer via PAR1‐PDK1‐AKT signaling pathway
Authors: Wu Kun , Wu Boyu , Yan Kangpeng , Ding Qunhua , Miao Zhiguo 
Published: December 2023

AbstractKirsten rat sarcoma virus (KRAS) gene mutation is common in colorectal cancer (CRC) and is often predictive of treatment failure and poor prognosis. To understand the mechanism, we compared the transcriptome of CRC patients with wild‐type and mutant KRAS and found that KRAS mutation is associated with the overexpression of a secreted serine protease, kallikrein‐related peptidase 10 (KLK10). Moreover, using in vitro and in vivo models, we found that KLK10 overexpression favors the rapid growth and liver metastasis of KRAS mutant CRC and can also impair the efficacy of KRAS inhibitors, leading to drug resistance and poor survival. Further functional assays revealed that the oncogenic role of KLK10 is mediated by protease‐activated receptor 1 (PAR1). KLK10 cleaves and activates PAR1, which further activates 3‐phosphoinositide‐dependent kinase 1 (PDK1)‐AKT oncogenic pathway. Notably, suppressing PAR1‐PDK1‐AKT cascade via KLK10 knockdown can effectively inhibit CRC progression and improve the sensitivity to KRAS inhibitor, providing a promising therapeutic strategy. Taken together, our study showed that KLK10 promotes the progression of KRAS mutant CRC via activating PAR1‐PDK1‐AKT signaling pathway. These findings expanded our knowledge of CRC development, especially in the setting of KRAS mutation, and also provided novel targets for clinical intervention.
Comment on “Asymmetric Bistricyclic Aromatic Enes”
Authors: Agranat Israel 
Published: December 2023

AbstractThis Correspondence argues against the use of the adjectives “symmetrical” and “asymmetric” in the recent publication entitled “Fluorenylidene‐Cyclopentadithiophene Based Asymmetric Bistricyclic Aromatic Ene Compounds: Synthesis and Substituents Effects”, by Beibei Xiao, Yongrui Yang, Shengnan Chen, Ye Zou, Xing Chen, Kanglei Liu, Nan Wang, Yali Qiao, and Xiaodong Yin (Chem. Eur. J., 2023, 29, e202301055).[1]
Fe and Cu Intercalations Enhance SERS of MoO3 through Different Mechanistic Pathways
Authors: Wang Hengan , An Guangyu , Xu Song , Xu Qun 
Published: December 2023

AbstractSurface Enhanced Raman spectroscopy (SERS) is a molecular‐specific analytical technique with various applications. Although electromagnetic (EM) and chemical (CM) mechanisms have been proposed to be the main origins of SERS, exploring highly sensitive SERS substrates with well‐defined mechanistic pathways remains challenging. Since surface and electronic structures of substrates were crucial for SERS activity, zero‐valent transition metals (Fe and Cu) were intercalated into MoO3 to modulate its surface and electronic structures, leading to unexceptional high enhancement factors (1.0×108 and 1.1×1010 for Fe‐MoO3 and Cu‐MoO3, respectively) with decent reproducibility and stability. Interestingly, different mechanistic pathways (CM and EM) were proposed for Fe‐MoO3 and Cu‐MoO3 according to mechanistic investigations. The different mechanisms of Fe‐MoO3 and Cu‐MoO3 were rationalized by the electronic structures of the intercalated Fe(0) and Cu(0), which modulates the surface and electronic structures of Fe‐MoO3 and Cu‐MoO3 to differentiate their SERS mechanisms.
trans‐Cyclooctenes as Scavengers of Bromine Involved in Catalytic Bromination
Authors: Murata Ryuichi , Shitamichi Kenta , Hiramatsu Masatsugu , Matsubara Seijiro , Uraguchi Daisuke , Asano Keisuke 
Published: December 2023

AbstractScavengers that capture reactive chemical substances are used to prevent the decomposition of materials. However, in the field of catalysis, the development of scavengers that inhibit background pathways has attracted little attention, although the concept will open up an otherwise inaccessible reaction space. In catalytic bromination, fast non‐catalyzed background reactions disturb the catalytic control of the selectivity, even when using N‐bromoamide reagents, which have a milder reactivity than bromine (Br2). Here, we developed a trans‐cyclooctene (TCO) bearing a 2‐pyridylethyl group to efficiently retard background reactions by capturing Br2 in bromocyclization using N‐bromosuccinimide. The use of less than a stoichiometric amount of the TCO was sufficient to inhibit non‐catalyzed reactions, and mechanistic studies using the TCO revealed that in situ‐generated Br2 provides non‐catalyzed reaction pathways based on a chain mechanism. The TCO is useful as an additive for improving enantioselectivity and regioselectivity in catalytic reactions. Cooperative systems using the TCO with selective catalysts offer an alternative strategy for optimizing catalyst‐controlled selectivity during bromination. Moreover, it also served as an indicator of Br2 involved in catalytic reaction pathways; thus, the TCO was useful as a probe for mechanistic investigations into the involvement of Br2 in bromination reactions of interest.
Effect of pyrolysis temperature and hydrothermal activation on structure, physicochemical, thermal and dye adsorption characteristics of the biocarbons
Authors: Charmas Barbara , Wawrzaszek Barbara , Jedynak Katarzyna 
Published: December 2023

AbstractIn this study, the possibility of using sawdust from mixed woods to obtain biocarbons in the pyrolysis and steam activation using microwave radiation as an energy source was investigated. Biocarbons were characterized based on the results of N2 adsorption, thermogravimetric analysis (TGA), Fourier spectroscopy (ATR‐FTIR), and Raman spectroscopy. Surface characterization was performed by Boehm titration and pHpzc determination. The adsorption capacity of methylene blue (MB) and methyl orange (MO) was studied. It was proved that the pyrolysis temperature and hydrothermal activation increased the biocarbons structural, surface and adsorption parameters of the obtained biocarbons. The amorphous materials of small specific surface area with a significant share of micropores were obtained. The steam activation resulted in significant development of the porous structure (to SBET=729.2 m2/g and Vp=0.36 cm3/g). The presence of functional groups, mainly phenolic ones, and pHpzc values indicating a potential for adsorption applications regarding MO and MB were found. The highest sorption capacity concerning MB (qe=122.8 mg/g) and MO (qe=99.1 mg/g) was observed for the steam‐activated biocarbon BC‐800MW. Using microwave energy hydrothermal activation proved very efficient, resulting in significant surface area and porosity development with a small loss of carbon matter.
Development of a Thermodynamically Favorable Multi‐enzyme Cascade Reaction for Efficient Sustainable Production of ω‐Amino Fatty Acids and α,ω‐Diamines
Authors: Li Ju‐Mou , Shi Kun , Li Ai‐Tao , Zhang Zhi‐Jun , Yu Hui‐Lei , Xu Jian‐He 
Published: December 2023

AbstractAliphatic ω‐amino fatty acids (ω‐AFAs) and α,ω‐diamines (α,ω‐DMs) are essential monomers for the production of nylons. Development of a sustainable biosynthesis route for ω‐AFAs and α,ω‐DMs is crucial in addressing the challenges posed by climate change. Herein, we constructed an unprecedented thermodynamically favorable multi‐enzyme cascade (TherFavMEC) for the efficient sustainable biosynthesis of ω‐AFAs and α,ω‐DMs from cheap α,ω‐dicarboxylic acids (α,ω‐DAs). This TherFavMEC was developed by incorporating bioretrosynthesis analysis tools, reaction Gibbs free energy calculations, thermodynamic equilibrium shift strategies and cofactor (NADPH&ATP) regeneration systems. The molar yield of 6‐aminohexanoic acid (6‐ACA) from adipic acid (AA) was 92.3 %, while the molar yield from 6‐ACA to 1,6‐hexanediamine (1,6‐HMD) was 96.1 %, which were significantly higher than those of previously reported routes. Furthermore, the biosynthesis of ω‐AFAs and α,ω‐DMs from 20.0 mM α,ω‐DAs (C6‐C9) was also performed, giving 11.2 mM 1,6‐HMD (56.0 % yield), 14.8 mM 1,7‐heptanediamine (74.0 % yield), 17.4 mM 1,8‐octanediamine (87.0 % yield), and 19.7 mM 1,9‐nonanediamine (98.5 % yield), respectively. The titers of 1,9‐nonanediamine, 1,8‐octanediamine, 1,7‐heptanediamine and 1,6‐HMD were improved by 328‐fold, 1740‐fold, 87‐fold and 3.8‐fold compared to previous work. Therefore, this work holds great potential for the bioproduction of ω‐AFAs and α,ω‐DMs.
A quick demagnetization approach for low torque ripple in three‐phase switched reluctance motor drive system for electric vehicle applications
Authors: Damarla Indira , Mahendran Venmathi , Ganji Ramudu , A Sangari 
Published: December 2023

SummaryElectric vehicles (EVs) have gained a forward approach for achieving the low carbon economy and green transportation. Switched reluctance (SR) motor‐based propulsion mechanisms have been popularly used for EVs due to the wide speed range capability. The conventional phase current regulation technique does not give the satisfactory reduction of torque ripple in SR motor drive, particularly for automotive applications. To overcome the issue, a frontend boost converter (FEBC) is proposed to realize the quick excitation and demagnetization. Initially, the problems associated with the conventional asymmetric half bridge converter are investigated at various levels of phase current. The various operating modes of proposed drive system with FEBC are explained in detail. The proposed FEBC has the significant benefit of being able to provide variable boosting voltages based on the dynamic behavior of the SR motor. The phase voltages are increased during the fast magnetization and demagnetization modes due to the inclusion of FEBC, and hence, quick magnetization and demagnetization have been achieved. The proposed FEBC drive system has been simulated through the Matlab Simulink toolbox. The experimental results are also carried out in order to validate the simulation results.
Single‐cell and spatial transcriptomics reveal POSTN+ cancer‐associated fibroblasts correlated with immune suppression and tumour progression in non‐small cell lung cancer
Authors: Chen Chao , Guo Qiang , Liu Yang , Hou Qinghua , Liao Mengying , Guo Yanying , Zang Yupeng , Wang Fei , Liu Huanyu , Luan Xinyu , Liang Yanling , Guan Zhuojue , Li Yanling , Liu Haozhen , Dong Xuan , Zhang Xiuqing , Liu Jixian , Xu Qumiao 
Published: December 2023

AbstractBackgroundCancer‐associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, the influence of CAF subpopulations on the progression of lung cancer is still unclear, which impedes the translational advances in targeting CAFs.MethodsWe performed single‐cell RNA sequencing (scRNA‐seq) on tumour, paired tumour‐adjacent, and normal samples from 16 non‐small cell lung cancer (NSCLC) patients. CAF subpopulations were analyzed after integration with published NSCLC scRNA‐seq data. SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) was applied in tumour and tumour‐adjacent samples from seven NSCLC patients to map the architecture of major cell populations in tumour microenvironment (TME). Immunohistochemistry (IHC) and multiplexed IHC (mIHC) were used to validate marker gene expression and the association of CAFs with immune infiltration in TME.ResultsA subcluster of myofibroblastic CAFs, POSTN+ CAFs, were significantly enriched in advanced tumours and presented gene expression signatures related to extracellular matrix remodeling, tumour invasion pathways and immune suppression. Stereo‐seq and mIHC demonstrated that POSTN+ CAFs were in close localization with SPP1+ macrophages and were associated with the exhausted phenotype and lower infiltration of T cells. POSTN expression or the abundance of POSTN+ CAFs were associated with poor prognosis of NSCLC.ConclusionsOur study identified a myofibroblastic CAF subpopulation, POSTN+ CAFs, which might associate with SPP1+ macrophages to promote the formation of desmoplastic architecture and participate in immune suppression. Furthermore, we showed that POSTN+ CAFs associated with cancer progression and poor clinical outcomes and may provide new insights on the treatment of NSCLC.
Flow field analysis and particle erosion of tunnel‐slope systems under coupling between runoff and fast (slow) seepage
Authors: Zhang Shuai , Song Danqing , Zhang Ruiliang , Zhang Kai , Zhao Qi , Sharma Suraksha 
Published: December 2023

AbstractThe presence of particles on the surface of a tunnel slope renders it susceptible to erosion by water flow, which is a major cause of soil and water loss. In this study, a nonlinear mathematical model and a mechanical equilibrium model are developed to investigate the distribution of flow fields and particle motion characteristics of tunnel slopes, respectively. The mathematical model of flow fields comprises three parts: a runoff region, a highly permeable soil layer, and a weakly permeable soil layer. The Navier‒Stokes equation controls fluid motion in the runoff region, while the Brinkman‐extended Darcy equation governs fast and slow seepage in the highly and weakly permeable soil layers, respectively. Analytical solutions are derived for the velocity profile and shear stress expression of the model flow field under the boundary condition of continuous transition of velocity and stress at the fluid‒solid interface. The shear stress distribution shows that the shear stress at the tunnel‐slope surface is the largest, followed by the shear stress of the soil interface, indicating that particles in these two locations are most vulnerable to erosion. A mechanical equilibrium model of sliding and rolling of single particles is established at the fluid‒solid interface, and the safety factor of particle motion (sliding and rolling) is derived. Sensitivity analysis shows that by increasing the runoff depth, slope angle, and soil permeability, the erosion of soil particles will be aggravated on the tunnel‐slope surface, but by increasing the particle diameter, particle‐specific gravity, and particle stacking angle, the erosion resistance ability of the tunnel‐slope surface particles will be enhanced. This study can serve as a reference for the analysis of surface soil and water loss in tunnel‐slope systems.
Female little brown bats require both building and natural roosts in a mountainous environment with short summers
Authors: Micalizzi E. W. , Forshner S. A. , Low E. B. , Johnston B. , Skarsgard S. A. , Barclay R. M. R. 
Published: December 2023

AbstractThe little brown bat (Myotis lucifugus) is an endangered species that occurs throughout most of North America. The recovery strategy for little brown bats in Canada identifies a need to understand habitat use and protect important bat habitat across the species' Canadian range; however, bat roosting habitat requirements have not been well studied in mountainous environments within the northern part of the species' range. Our objective was to understand the use of building and natural roosts by female little brown bats in the Canadian Rocky Mountains. Over two summers, we captured little brown bats in Banff, Yoho, and Kootenay National Parks, in Alberta and British Columbia, Canada, and tracked 49 females to their day roosts. Buildings were the only roost type used by radio‐tagged bats of all reproductive stages, the dominant roost type used throughout the reproductive period, and the only structures in which we located maternity colonies. Buildings also appeared to shape the distribution of foraging female and reproductive female bats such that few were captured at long distances from towns and building clusters. Compared with bats in more southern and in non‐mountainous areas, bats in our study area had delayed juvenile weaning and volancy, began hibernation early, and had low reproductive rates. We suggest that buildings are a key habitat for female little brown bats to persist at their current levels in our study area, by providing thermal conditions that promote overwinter survival; additional reproductive delays caused by torpor use in cool natural roosts would likely reduce juvenile and adult female overwinter survival below the levels required to sustain populations. Nevertheless, building colonies were unusually small, and bats had relatively low fidelity to particular building roosts, suggesting that building roosts may not consistently meet bats' needs. Some nonreproductive and pregnant females also frequently used natural roosts, particularly after colder nights; these roosts may be important in facilitating torpor and energy conservation for these bats. Because bats are long‐lived with low reproductive output and low juvenile survival, addressing the needs of both reproductive and nonreproductive individuals is important for population persistence.
N‐terminal pro‐B‐type natriuretic peptide concentrations, testing and associations with worsening heart failure events
Authors: Ferrannini Giulia , Benson Lina , Lautsch Dominik , Dahlström Ulf , Lund Lars H. , Savarese Gianluigi , Carrero Juan Jesus 
Published: December 2023

AbstractAimsIn patients with heart failure (HF), we aimed to assess (i) the time trends in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) testing; (ii) patient characteristics associated with NT‐proBNP testing; (iii) distribution of NT‐proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT‐proBNP levels over time.Methods and resultsNT‐proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT‐proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT‐proBNP testing and (ii) changes in NT‐proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT‐proBNP testing increased over time, up to 55% in 2018, and was almost two‐fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT‐proBNP was 3070 ng/L (Q1–Q3: 1220–7395), approximately three‐fold higher in WHFE vs. NWHFE. Compared with stable low NT‐proBNP levels, increased (OR 4.27, 95% CI 2.47–7.37) and stable high levels (OR 2.48, 95% CI 1.58–3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population.ConclusionsNT‐proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT‐proBNP testing in clinical practice.
Vinylene Carbonate as Latent Formylmethyl Surrogate: The Expediency of Ruthenium(II) Catalysis in Accessing Arylacetaldehydes, Arylacetates and Acetals
Authors: Thalakottukara Dolly David , Gandhi Thirumanavelan 
Published: December 2023

AbstractArylacetaldehydes and its corresponding esters are fundamental structural motifs widespread in natural products and pharmaceuticals. Herein, we developed a ruthenium(II)‐catalyzed direct formylmethylation and sequential dehydrogenative esterification of phthalazinones by adopting vinylene carbonate as a C2 synthon (formylmethyl equivalent). The reaction is compatible with a repertoire of substrates bearing both electron‐donating and electron‐withdrawing substituents. Strikingly, the products obtained are governed by the additive used. A number of control experiments are conducted to elucidate the reaction mechanism. Furthermore, an important highlight is confirmation of possible intermediates by mass spectrometry.
Learn how to interpret and use intracranial EEG findings
Authors: Frauscher B. , Mansilla D. , Abdallah C. , Astner‐Rohracher A. , Beniczky S. , Brazdil M. , Gnatkovsky V. , Jacobs J. , Kalamangalam G. , Perucca P. , Ryvlin P. , Schuele S. , Tao J. , Wang Y. , Zijlmans M. , McGonigal A. 
Published: December 2023

AbstractEpilepsy surgery is the therapy of choice for many patients with drug‐resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure‐onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective “1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings” of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.