bluuebunny/crossref_metadata_2025_split huggingface dataset:
Well‐posedness and Mittag–Leffler stability for a nonlinear fractional telegraph problem
Authors: Othmani Sakina , Tatar Nasser‐Eddine 
Published: May 2023

AbstractThe ordinary diffusion models in continuous media are derived from basic principles: Conservation of energy and momentum. The classical telegraph equation is one of the earliest and most commonly used equation to describe the transmission of electromagnetic waves. In fractal and disordered media, to capture the complex diffusion feature, we consider rather fractional models. Indeed, the mean square displacement in anomalous media is no longer proportional to the time but rather proportional to a power of time whose exponent may be between zero and one or between one and two. This is the case for the present fractional telegraph equation in the presence of non‐negligible voltage wave. Here, the well‐posedness and stability of a telegraph problem with two time‐fractional derivatives is discussed. In addition to being a noninteger problem, the equation in the model is subject to a nonlinear source as well as a nonlinear lower order fractional derivative term. First, the well‐posedness in an appropriate underlying space is established by the use of resolvent operators. Then, it is proved that, despite the presence of these nonlinearities, solutions are Mittag–Leffler stable. This confirms (and extends) the fact that the lower order term plays the role of a damper in the fractional case. To this end, we combine the energy method with some properties of the Caputo fractional derivative.
Development of delivery strategies for CRISPR‐Cas9 genome editing
Authors: Liu Qi , Yang Jianhui , Xing Yumeng , Zhao Yu , Liu Yang 
Published: May 2023

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐related protein 9 (Cas9) genome editing system has attracted much attention due to its powerful genome editing capacity. However, CRISPR‐Cas9 components are easily degraded by acids, enzymes, and other substances in the body fluids after entering the organism, thus efficiently delivering the CRISPR‐Cas9 system into targeted organs or cells has been a central theme for promoting the application of CRISPR‐Cas9 technology. Although several physical methods and viral vectors have been developed for CRISPR‐Cas9 delivery, their clinical application still suffers from disadvantages, such as the risks of mutagenesis, cell damage, and poor specificity. As an alternative, non‐viral nanocarriers hold great promise for circumventing these challenges. Furthermore, with aim to realize more efficient and precise genome editing and reduce the undesirable side effects, stimuli‐responsive nanocarriers are designed for the spatiotemporal CRISPR‐Cas9 delivery in responsive to various stimuli. In this review, we will summarize the recent progress in delivery strategies for CRISPR‐Cas9 genome editing. The mechanisms and advantages of these strategies were reviewed, providing a comprehensive review of the rational design of materials and techniques for efficient and precise genome editing. At last, the potential challenges of current CRISPR‐Cas9 delivery are discussed.
Visualizing timeline‐anchored comments enhanced social presence and information searching in video‐based learning
Authors: Chen Yue , Gao Qin 
Published: May 2023

AbstractNumerous learners watch knowledgeable videos with comments or annotations anchored to the video timeline. These comments are learners’ discussions with abundant informational and social content along with video timelines, but the content is usually fragmented and scattered. To extract, organize, and highlight useful information from the discussion, we adopted text mining approaches and designed an interactive visualization tool in the lecture interface for learners, including the following components along with the video timeline: (1) the relevance of comments to the lecture, (2) the comment topics throughout the lecture, and (3) the difficulty level perceived by learners. We conducted a lab experiment with 24 students to examine the effects of the visualization tool on the learning process and outcomes. We found that learners perceived a significantly higher social presence and performed better in open‐book quizzes, searching tasks, and summarizing lectures using the visualization tool. This suggests that the visualization of timeline‐anchored commenting potentially facilitates learners’ participation in discussions and contributions to the learning community.
Amenyunnaosides A–C, Three New Neolignans Isolated from Amentotaxus yunnanensis and Their Anti‐inflammatory Activities
Authors: Trung Thanh Nguyen , Thi Thuy La , Thi Xuyen Do , Quynh Mai Le , Van Hai Do , Sinh Khang Nguyen , Thi Trang Do , Huu Tai Bui , Van Kiem Phan 
Published: May 2023

AbstractPhytochemical study on the leaves of Amentotaxus yunnanensis led to the isolation of seventeen phenolic compounds including sixteen neolignans and lignans, and one flavone glycoside. Three among the isolates were previously unreported neolignans and named as amenyunnaosides A–C, respectively. Their structures were elucidated by extensive analyses of HR‐ESI‐MS, 1D and 2D NMR, and ECD spectra. The isolated neolignans potentially inhibited NO production in LPS‐activated RAW264.7 cells with their IC50 values ranging from 11.05 to 44.07 μM, compared to that of the positive control compound, dexamethasone, IC50 value of 16.93 μM. Additionally, amenyunnaoside A dose‐dependently reduced production of IL‐6 and COX‐2 but did not effect to that of TNF‐α at concentrations of 0.8, 4, and 20 μM.
Inhibition of TGF‐β type I receptor by SB505124 down‐regulates osteoblast differentiation and mineralization of human mesenchymal stem cells
Authors: Almuraikhi Nihal 
Published: May 2023

AbstractNumerous signaling pathways are well‐known in osteoblastic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), including transforming growth factor‐beta (TGF‐β) signaling pathway, which sends signals through specific type I and II serine/threonine kinase receptors. However, the key role of TGF‐β signaling during bone formation and remodeling is yet to be studied. A TGF‐β type I receptor inhibitor, SB505124, discovered through a screening of a small molecule library for their effect of osteoblast differentiation of hBMSCs. Alkaline phosphatase quantification and staining were tested as indicators of osteoblastic differentiation and Alizarin red staining was tested as an indicator of in vitro mineralization. Changes in gene expressions were assessed using qRT‐PCR. SB505124 showed significant inhibition of the osteoblast differentiation of hBMSCs, as confirmed by reduced alkaline phosphatase, in vitro mineralization, and downregulation of osteoblast‐associated gene expression. To further understand the molecular mechanisms involved in the inhibition of the TGF‐β type I receptor, we assessed the effects on signature genes of several signaling pathways identified in the osteoblast differentiation of hBMSCs. SB505124 downregulated gene expression of many genes linked to osteoblast‐related signaling pathways including TGF‐β, insulin, focal adhesion, Notch, Vitamin D, interleukin (IL)‐6, osteoblast signaling, and cytokines and inflammatory. We report TGF‐β type I receptor inhibitor (SB505124) is a potent inhibitor of osteoblastic differentiation of hBMSCs that could be a valuable innovative therapeutic tool to cure bone disorders with increased bone formation, besides its potential use to treat patients with cancer and fibrosis.
Autophagy‐related gene PXN as a prognostic marker: Promotion of ovarian cancer progression by suppressing the p110β/Vps34/Beclin1 pathway
Authors: Wu Qiaoling , Cui Zhaolei , Jiang Shan , Xia Hongmei , Liu Li , You Yiqing , Sun Yang 
Published: May 2023

AbstractAmong gynecological malignancies, ovarian cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy‐related genes that determine patient prognosis using limma differential expression and Kaplan–Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK‐8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of autophagy proteins and the PI3K/Akt/mTOR and p110β/Vps34/Beclin1 pathway proteins in ovarian cancer cells was detected using western blot; autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy‐related genes were found to be overexpressed in ovarian ‐cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p < .05). PXN activates and regulates signaling pathways related to cellular autophagy, ubiquitination, lysosomes, PI3K‐Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3Ⅰ, inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110β) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian cancer and is associated with poor patient prognosis. It may promote ovarian cancer cell proliferation, migration, and invasion by inhibiting cellular autophagy via suppression of the p110β/Vps34/Beclin1 pathway.
Dispersion Function of a Protein, DP‐1, Identified inCollimonas sp. D‐25, for the Synthesis of Gold Nanoparticles
Authors: Tang Donglin , Kato Yugo , Zhang Dingkun , Negishi Lumi , Kurumizaka Hitoshi , Hirata Takafumi , Nakakido Makoto , Tsumoto Kouhei , Shuji Fujisawa , Tsuguyuki Saito , Okumura Taiga , Nagata Koji , Suzuki Michio 
Published: May 2023

AbstractCollimonas sp. (D‐25), found in the soil of Akita Prefecture, is a gram‐negative bacterium with the ability to synthesize gold nanoparticles (AuNPs). During the synthesis of AuNPs, one specific protein (DP‐1) was found to have disappeared in the sonicated solution of the bacterium. Recombinant DP‐1 (rDP‐1) fromEscherichia coliBL21 (DE3) was used to study the effect of DP‐1 on the synthesis of AuNPs. AuNPs synthesized with rDP‐1 result in small, stabilized nanoparticles. AuNPs synthesized by DP‐1 retained the stability of both the dispersion and nano‐size particles under high salt concentrations. Isothermal titration calorimetry was employed to investigate the bonding ratio of rDP‐1 to AuNPs. Several thousand rDP‐1 proteins are attached to the surface of an AuNP to form a protein corona containing multiple layers. These results suggest that DP‐1 obtained from D‐25 has a size and stability control function during AuNP synthesis.
Peptide Amphiphilic Supramolecular Nanogels: Competent Host for Notably Efficient Lipase‐Catalyzed Hydrolysis of Water‐Insoluble Substrates
Authors: Pal Sudeshna , Khan Aftab Hossain , Chowdhury Monalisa , Das Prasanta Kumar 
Published: May 2023

AbstractThe present work depicts the development of stable nanogels in an aqueous medium that were exploited for efficient surface‐active lipase‐catalyzed hydrolysis of water‐insoluble substrates. Surfactant‐coated gel nanoparticles (neutral NG1, anionic NG2, and cationic NG3) were prepared from peptide amphiphilic hydrogelator (G1, G2, and G3, respectively) at different hydrophilic and lipophilic balance (HLB). Chromobacterium viscosum (CV) lipase activity towards hydrolysis of water‐insoluble substrates (p‐nitrophyenyl‐n‐alkanoates (C4–C10)) in the presence of nanogels got remarkably improved by ~1.7–8.0 fold in comparison to that in aqueous buffer and other self‐aggregates. An increase in hydrophobicity of the substrate led to a notable improvement in lipase activity in the hydrophilic domain (HLB>8.0) of nanogels. The micro‐heterogeneous interface of small‐sized (10–65 nm) nanogel was found to be an appropriate scaffold for immobilizing surface‐active lipase to exhibit superior catalytic efficiency. Concurrently, the flexible conformation of lipase immobilized in nanogels was reflected in its secondary structure having the highest α‐helix content from the circular dichroism spectra.
Narcolepsy following COVID‐19: A case report and review of potential mechanisms
Authors: Roya Yazdani , Farzaneh Barzkar , Mostafa Almasi‐Dooghaee , Mahsa Shojaie , Babak Zamani 
Published: May 2023

Key Clinical MessageThe immune activation in COVID‐19 may trigger narcolepsy in vulnerable patients. We suggest clinicians carefully evaluate patients with post‐COVID fatigue and hypersomnia for primary sleep disorders, specifically narcolepsy.AbstractThe patient is a 33‐year‐old Iranian woman without a significant past medical history with the full range of narcolepsy symptoms that started within 2 weeks after her recovery from COVID‐19. Sleep studies revealed increased sleep latency and three sleep‐onset rapid eye movement events, compatible with a narcolepsy‐cataplexy diagnosis.
A case of vagal cephalgia as a manifestation of a lung neoplasm—A case report and review of literature
Authors: Sanker Vivek , Devaragudi Sanjana , Shariff Sanobar , Deva Sheryl , Mathew Robert , Gupta Umang 
Published: May 2023

Key Clinical MessageLung cancer can present with unilateral atypical facial pain, a rare symptom due to vagus nerve involvement or paraneoplastic syndrome. This manifestation is usually missed, delaying the diagnosis and prognosis. We discuss a case of a 45‐year‐old male who presented with right‐sided hemifacial pain and with normal neurological investigations.
Racial animosity and Black financial advisor underrepresentation
Authors: DiBartolomeo Jeffrey A. , Kothakota Michael G. , Parks‐Stamm Elizabeth J. , Tharp Derek T. 
Published: May 2023

AbstractThis study provides compelling evidence for Black underrepresenation in the financial advisor industry. Using a dataset of all U.S. securities‐licensed individuals (N = 642,543), we first estimate the racial and ethnic composition of the industry using an algorithm that accounts for name, gender, and location. Second, we use a dataset enhanced by a commercial vendor to restrict the analysis to only those identified as working as financial advisors (n = 237,435). Using Google search volume for a racial epithet as a proxy for area racism, we find that greater racism in a market is associated with greater Black advisor underrepresentation. Overall, we estimate at the individual level that 10.1% of financial advisors are Black (relative to 13.4% of the U.S. population). Furthermore, our results suggest market‐level racial animosity toward Blacks is negatively associated with Black advisor representation. We estimate a difference of 0.9 percentage points when comparing markets with the highest and lowest levels of animosity. For the average market with an estimated 11.4% Black advisor representation, an increase of 0.9 percentage points would represent a 7.9% increase in Black advisor representation.
Hydration Rearrangement in the 4‐Aminobenzonitrile−(H2O)2 Cluster Induced by Photoionization: The Effect of Solvent‐Solvent Interactions
Authors: Matsuno Risako , Dopfer Otto , Fujii Masaaki , Miyazaki Mitsuhiko 
Published: May 2023

AbstractThe interplay between solute‐solvent and solvent‐solvent interactions plays an essential role in solvation dynamics that has important effects on the mechanism and dynamics of chemical reactions in solution. In this study, the rearrangement of the hydration shell induced by photoionization of a solute molecule is probed in a state‐ and isomer‐specific manner by resonant multiphoton ionization detected IR spectroscopy of the prototypical 4‐aminobenzonitrile−(H2O)2 cluster produced in a molecular beam. IR spectra reveal that the water molecules form a cyclic solvent network around the CN group in the initial neutral state (S0). Different from the singly‐hydrated cluster, in which either the CN or the NH2 group is hydrated, hydration of the NH2 group is not observed in the dihydrated cluster. IR spectra obtained after ionizing the solute molecule into the cation ground state (D0) exhibit features ascribed to both NH‐bound and CN‐bound isomers, indicating that water molecules migrate from the CN to the NH site upon ionization with a yield depending on the ionization excess energy. Analysis of the IR spectra as a function of the excess energy shows that migration produces two different NH2 solvated structures, namely (i) the most stable structure in which both N−H bonds are singly hydrated and (ii) the second most stable isomer in which one of the N−H bonds is hydrated by a H‐bonded (H2O)2 dimer. The product branching ratio of the two isomers depends on the excess energy. The role of the water‐water interaction in the hydration rearrangement is discussed based on the potential energy landscape. Solvation dynamics plays an important role in reaction mechanisms in the condensed phase, where not only solute‐solvent solvation but also solvent‐solvent interactions have a significant influence on the dynamics. Thus, the investigation of solvation dynamics at the molecular level substantially contributes to our understanding of the reaction mechanism. In this study, the dihydrated cluster of 4ABN was utilized as a model for the first solvation layer to elucidate solvent motions induced by ionization of the solute and the role of W−W interactions for the solvent relaxation.
Enzymatic Synthesis of l‐Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade**
Authors: Mohr Michael K. F. , Saleem‐Batcha Raspudin , Cornelissen Nicolas V. , Andexer Jennifer N. 
Published: May 2023

AbstractChemical modification of small molecules is a key step for the development of pharmaceuticals. S‐adenosyl‐l‐methionine (SAM) analogues are used by methyltransferases (MTs) to transfer alkyl, allyl and benzyl moieties chemo‐, stereo‐ and regioselectively onto nucleophilic substrates, enabling an enzymatic way for specific derivatisation of a wide range of molecules. l‐Methionine analogues are required for the synthesis of SAM analogues. Most of these are not commercially available. In nature, O‐acetyl‐l‐homoserine sulfhydrolases (OAHS) catalyse the synthesis of l‐methionine from O‐acetyl‐l‐homoserine or l‐homocysteine, and methyl mercaptan. Here, we investigated the substrate scope of ScOAHS from Saccharomyces cerevisiae for the production of l‐methionine analogues from l‐homocysteine and organic thiols. The promiscuous enzyme was used to synthesise nine different l‐methionine analogues with modifications on the thioether residue up to a conversion of 75 %. ScOAHS was combined with an established MT dependent three‐enzyme alkylation cascade, allowing transfer of in total seven moieties onto two MT substrates. For ethylation, conversion was nearly doubled with the new four‐enzyme cascade, indicating a beneficial effect of the in situ production of l‐methionine analogues with ScOAHS.
Deoxygenative Radical Boration of Inert Amides via a Combination of Relay and Cooperative Catalysis
Authors: Jiang Feng , Li Jing'an , Wang Xiaoming 
Published: May 2023

AbstractInvited for the cover of this issue is the group of Prof. Xiaoming Wang at the Shanghai Institute of Organic Chemistry and Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences. The image depicts a combination of relay and cooperative catalysis with a triple iridium–photoredox–organocatalysis system to achieve an unprecedented reductive boration of amides. Read the full text of the article at 10.1002/chem.202301199.
A Bacterial Cytochrome P450 Enzyme Catalyzes Multistep Oxidation Reactions in Pyrroindomycin Biosynthesis
Authors: Wang Jiabao , Xu Yu , Chen Dandan , Tao Jiang , Wang Hongbo , Liu Wen 
Published: May 2023

Comprehensive SummaryCytochrome P450 enzymes (P450s) belong to a large family of oxidative hemeproteins and catalyze highly diverse oxygenation reactions that are involved in the biosynthesis of various natural products. Here, we report a multifunctional cytochrome P450 enzyme, PyrE2, which catalyzes the regioselective, successive 6‐electron oxidation of an inert methyl group to produce a carboxyl product through formation of the hydroxyl and aldehyde intermediates in pyrroindomycin biosynthesis. The time‐course biotransformation was characterized by the presence of the hydroxyl and aldehyde intermediates, the lag of the formation of the carboxyl product, and the subsequent loss of both intermediates, indicating that each 2‐electron oxidation exhibits the distributive mechanism that requires substrate binding and product releasing. Bioinformatics analysis shows that the homologs of pyrE2 are common in the gene clusters of the spirotetronates varying in the oxidative state of the corresponding exocyclic carbon, indicating the generality and diversity of P450‐catalyzed oxygenation in related biosynthetic pathways.
Query cost estimation in graph databases via emphasizing query dependencies by using a neural reasoning network
Authors: He Zhenzhen , Yu Jiong , Gu Tiquan , Li Zhe , Du Xusheng , Li Ping 
Published: May 2023

SummaryWith the increasing complexity of graph queries, query cost estimation has become a key challenge in graph databases. Accurate estimation results are critical for database administrators or database management systems to perform query processing or optimization tasks. An efficient and accurate estimation model can improve the estimation quality and make the produced results credible. Although learning‐based methods have been applied in query cost estimation, most of them are directed at relational queries and cannot be directly used for graph queries. Furthermore, most estimation approaches focus on the correlations between predicates or columns. The dependencies between query schema and query filter conditions and the correlation between query schema are ignored. In this study, we construct a novel deep learning model composed of reasoning and retrieval processes that can accurately capture the potential logical relationships in graph queries. This solves the above problems to some extent. In addition, we propose a query estimation framework that divides the estimation task into query workload generation, training data collection, feature extraction and encoding, and estimation model construction. The results of the experiment on real‐world datasets show that our estimation model can improve the estimation quality and outperforms other compared deep learning models in terms of estimation accuracy.