bluuebunny/crossref_metadata_2025_split huggingface dataset:
A refined Uni‐vector prime editing system improves genome editing outcomes in mammalian cells
Authors: Huang Ching‐Hui , Chiu Szu‐Ying , Chou Yu‐Chi , Wu Kou‐Juey 
Published: February 2024

AbstractPrime editing is an advanced technology in CRISPR/Cas research with increasing numbers of improved methodologies. The original multi‐vector method hampers the efficiency and precision of prime editing and also has inherent difficulty in generating homozygous mutations in mammalian cells. To overcome these technical issues, we developed a Uni‐vector prime editing system, wherein the major components for prime editing were constructed in all‐in‐one plasmids, pPE3‐pPuro and pePEmax‐pPuro. The Uni‐vector prime editing plasmids enhance the editing efficiency of prime editing and improved the generation of homozygous mutated mammalian cell lines. The editing efficiency is dependent of the transfection efficiency. Remarkably, the Uni‐vector ePE5max system achieved an impressive editing rate approximately 79% in average, even in cell lines that are traditionally difficult to transfect, such as FaDu cell line. Furthermore, it resulted in a high frequency of homozygous knocked‐in cells, with a rate of 99% in HeLa and 85% in FaDu cells. Together, our Uni‐vector approach simplifies the delivery of editing components and improves the editing efficiency, especially in cells with low transfection efficiency. This approach presents an advancement in the field of prime editing.
Exploring engineering strategies that enhance de novo production of exotic cyclopropane fatty acids in Saccharomyces cerevisiae
Authors: Jiang Wei , Peng Huadong , He Lizhong , Lesma‐Amaro Rodrigo , Haritos Victoria S. 
Published: February 2024

AbstractCycloalkanes have broad applications as specialty fuels, lubricants, and pharmaceuticals but are not currently available from renewable sources, whereas, production of microbial cycloalkanes such as cyclopropane fatty acids (CFA) has bottlenecks. Here, a systematic investigation was undertaken into the biosynthesis of CFA in Saccharomyces cerevisiae heterologously expressing bacterial CFA synthase. The enzyme catalyzes formation of a 3‐membered ring in unsaturated fatty acids. Monounsaturated fatty acids in phospholipids (PL) are the site of CFA synthesis; precursor cis‐Δ9 C16 and C18 fatty acids were enhanced through OLE1 and SAM2 overexpression which enhanced CFA in PL. CFA turnover from PL to storage in triacylglycerols (TAG) was achieved by phospholipase PBL2 overexpression and acyl‐CoA synthase to increase flux to TAG. Consequently, CFA storage as TAG reached 12 mg g−1 DCW, improved 3‐fold over the base strain and >22% of TAG was CFA. Our research improves understanding of cycloalkane biosynthesis in yeast and offers insights into processing of other exotic fatty acids.
SERPINE2 promotes liver cancer metastasis by inhibiting c‐Cbl‐mediated EGFR ubiquitination and degradation
Authors: Zhang Shiyu , Jia Xing , Dai Haojiang , Zhu Xingxin , Song Wenfeng , Bian Suchen , Wu Hao , Chen Shinuo , Tang Yangbo , Chen Junran , Jin Cheng , Zhou Mengqiao , Xie Haiyang , Zheng Shusen , Song Penghong 
Published: February 2024

AbstractBackgroundLiver cancer is a malignancy with high morbidity and mortality rates. Serpin family E member 2 (SERPINE2) has been reported to play a key role in the metastasis of many tumors. In this study, we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.MethodsThe Cancer Genome Atlas database (TCGA), including DNA methylation and transcriptome sequencing data, was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver cancer. Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clinical parameters of patients. DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells. RNA sequencing, cytokine assays, immunoprecipitation (IP) and mass spectrometry (MS) assays, protein stability assays, and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis. Patient‐derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.ResultsBased on the public database screening, SERPINE2 was identified as a tumor promoter regulated by DNA methylation. SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer. SERPINE2 promoted liver cancer metastasis by enhancing cell pseudopodia formation, cell adhesion, cancer‐associated fibroblast activation, extracellular matrix remodeling, and angiogenesis. IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor (EGFR) and its downstream signaling pathways by interacting with EGFR. Mechanistically, SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase, c‐Cbl. Additionally, EGFR was activated in liver cancer cells after sorafenib treatment, and SERPINE2 knockdown‐induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer. Furthermore, we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment.ConclusionsSERPINE2 promoted liver cancer metastasis by preventing EGFR degradation via c‐Cbl‐mediated ubiquitination, suggesting that inhibition of the SERPINE2‐EGFR axis may be a potential target for liver cancer treatment.
Biomarkers of systemic inflammation provide additional prognostic stratification in cancers of unknown primary
Authors: Harvey Svenja , Stares Mark , Scott Julie‐Anne , Thottiyil Tharun Joseph Vattam , Conway Alicia‐Marie , Haigh Rachel , Brown Jackie , Knowles Gillian , Dasgupta Sonali , Shiu Kai‐Keen , Mitchell Claire , Barrie Colin , Cook Natalie , Clive Sally 
Published: February 2024

AbstractBackgroundBiomarkers of systemic inflammation have been shown to predict outcomes in patients with cancer of unknown primary (CUP). We sought to validate these findings in patients with confirmed CUP (cCUP) and explore their role alongside existing clinicopathological prognostic categories.Patients and MethodsCUP oncologist from across the United Kingdom were invited to include patients with cCUP referred to their local CUP multidisciplinary team. Patient demographics, clinical, pathological and outcome data were recorded and analysed.ResultsData were available for 548 patients from four CUP services. 23% (n = 124) of patients met clinicopathological criteria for favourable‐risk cCUP. On multivariate analysis c‐reactive protein (CRP) (p < 0.001) and the Scottish Inflammatory Prognostic Score (SIPS: combining albumin and neutrophil count) (p < 0.001) were independently predictive of survival. CRP and SIPS effectively stratified survival in patients with both favourable‐risk and poor‐risk cCUP based on clinicopathological features.ConclusionsBiomarkers of systemic inflammation are reliable prognostic factors in patients with cCUP, regardless of clinicopathological subgroup. We recommend that CRP or SIPS are incorporated into routine clinical assessments of patients with cCUP as a tool to aid investigation and/or treatment decision‐making across all groups. Established clinicopathological factors can then be used to inform management pathways and specific systemic anticancer therapy selection.
Origanum Grosii Extracts as Novel Eco‐Friendly Corrosion Inhibitors for Mild Steel In HCl Medium
Authors: Elyoussfi Abdellah , Hassouni Hafssa EL , Benhiba Fouad , Outada Halima , Amhamdi Hassan , Zarrouk Abdelkader , Romane Abderrahmane , Dafali Ali 
Published: February 2024

AbstractTwo green inhibitors extracted from an endemic species (Origanum grosii (Og)) using two solvents of different polarity (water and ethanol), OgW (aqueous extract) and OgE (ethanolic extract), were used for the anticorrosion of mild steel (M steel) in a 1 M HCl medium. Anticorrosive performance of OgW and OgE was assessed using standard electrochemical techniques, EIS/PDP measurements, weight loss method and SEM/EDX surface analysis. The results show that OgW achieves a maximum inhibition efficiency of 92 % and that the extract in aqueous medium (more polar) is more efficient than the extract in ethanolic medium (less polar). Both extracts act as mixed inhibitors and their corrosion process is predominantly governed by a charge transfer. Concentration and temperature effect was studied and shown that they are two antagonistic parameters for the evolution of inhibitory effectiveness of both OgW and OgE. The adsorption isotherms of the two inhibitors OgE and OgW obey to the Langmuir adsorption model. Moreover, the examination of SEM images and EDX spectra support a deposit of both extracts on the metal surface by an adsorption phenomenon. Besides, theoretical approach of the molecular structures of the major compounds M‐OgW and M‐OgE and inhibition efficiency was examined via DFT calculations and molecular dynamics simulations and it was consistent with the experimental findings.
Evaluation of the Phenolic Content and the Nutraceutical Potential of Ancestor and Cultivated Artichokes
Authors: Ucar Turker Arzu , Basay Sevinc , Cimen Ayca , Baba Yavuz , Birinci Yildirim Arzu 
Published: February 2024

AbstractWild cardoon (Cynara cardunculus var. sylvestris) is the ancestor of many cultivated forms, including globe artichoke (C. cardunculus var. scolymus). Four organs (receptacles, bracts, leaves and stems) of wild and cultivated artichokes (organic and conventional) were assessed considering their individual phenolic constituents (HPLC‐DAD), total phenol–flavonoid content, and pharmaceutical potentials (antibacterial and antioxidant). All three sources of artichokes had the highest concentration of 1,3‐dicaffeoylquinic acid (cynarin) in their receptacles and cultivated artichoke receptacles had more cynarin than wild one. On the other hand, receptacles of wild cardoon had the highest 1,5‐dicaffeoylquinic acid and caffeic acid than the cultivated ones. Generally, receptacles, stems and leaves of wild cardoon were superior to both cultivated artichokes on antioxidant potential, and total phenol–flavonoid content. The rise in total phenolic content can be attributed to an increase in antioxidant capacity in all artichoke organs. Only the leaves of all different artichokes showed antibacterial activity against Gram–positive bacteria. The investigated wild cardoon was believed to be a true ancestor since a comparison of wild and cultivated varieties revealed similar trends in terms of phenolic profile and biological properties. The nutraceutical industry can profit from this invasive wild cardoon due to their strong antioxidant potential and phenolic content.
Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine
Authors: Kim HaRam , Taslakjian Boghos , Kim Sarah , Tirrell Matthew V. , Guler Mustafa O. 
Published: February 2024

AbstractPeptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self‐assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug‐loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor‐mediated endocytosis and cell‐penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease‐specific targeting for diagnostics and therapeutics in diseases such as cancer.
Assessment of the MANTA closure device in real‐life transfemoral transcatheter aortic valve replacement: A single‐centre observational study
Authors: Boussofara Amine , Godin Matthieu , Canville Alexandre , Baala Brahim , Berland Jacques , Koning René , Landolff Quentin 
Published: February 2024

AbstractBackgroundVascular complications increase morbidity and mortality in transcatheter aortic valve replacement (TAVR). Data involving suture‐based percutaneous vascular closure devices (VCDs) have been extensive. Although promising, data regarding the efficacy and safety of the MANTA VCD (Teleflex) are scarce. We sought to assess the safety and effectiveness of the MANTA device in a real‐life unselected cohort of patients undergoing transfemoral‐TAVR (TF‐TAVR).MethodsThis single‐center retrospective observational study included a cohort of consecutive patients with severe aortic stenosis (AS) treated by our team using TAVR between January 2020 to December 2022. The primary outcome measure was access‐related major and minor vascular complications according to the Valve Academic Research Consortium (VARC‐3) definition criteria.ResultsFrom January 2020 to December 2022, a total of 347 patients underwent TF‐TAVR were treated using the MANTA 18 Fr VCD system for vascular closure. Mean age was 82.4 ± 6.1 years (56–98 years). There were no significant differences in preoperative and procedural characteristics between patients with and without VCD‐related major vascular complications. Access site‐related major and minor vascular complications occurred in 20 of 347 patients (5.7%). Overall, major vascular complications occurred in 5 patients (1.4%) and device failure was seen in 17 patients (4.9%).ConclusionThis French real world evaluation of large‐bore arteriotomy closure in TF‐TAVR indicated that MANTA VCD is a feasible alternative with an acceptable low rate of access‐site‐related complications.
Structure Activity Relationships for Second‐Coordination Sphere Functional Group Dependent CO2 Reduction by Manganese Bipyridyl Electrocatalysts
Authors: Blasczak Vanna , Murphy Alana , Suntrup Lisa , Ngo Ken T. , Reed Blake , Groysman Stanislav , Grills David C. , Rochford Jonathan 
Published: February 2024

AbstractA series of twelve second coordination sphere (SCS) functionalized manganese tricarbonyl bipyridyl complexes are investigated for their electrocatalytic CO2 reduction properties in acetonitrile. A qualitative and quantitative assessment of the SCS functional groups is discussed with respect to the catalysts’ thermodynamic and kinetic efficiencies, and their product selectivities. In probing a broad scope of functional groups, it is clear that only the aprotic ortho‐arylester SCS is capable of promoting the highly desired low‐overpotential proton‐transfer electron‐transfer (PT‐ET) pathway for selective CO production. The ortho‐phenolic analogues cause an increase in overpotential with a product selectivity favoring H2 evolution, consistent with a high‐overpotential pathway via the anionic [Mn−H]− intermediate. Alternative aprotic Lewis base functional groups such as trifluoromethyl, morpholine and acetamide are shown to also be capable of intermediate manganese hydride generation. The tertiary amine substituent, 2‐morpholinophenyl, exhibits a desirable product distribution characteristic of syn‐gas (CO : H2=30 : 48) with an impressive turnover frequency, while the secondary amine group, 2‐acetamidophenyl, induces a notable shift in selectivity with a faradaic yield of 55 % for the formate (HCO2−) product. In addition to their catalytic properties, cyclic voltammetry and infrared spectroelectrochemistry (IR‐SEC) studies are presented to probe pre‐catalyst electronic properties and the two‐electron reduction activation pathway.
Modeling and Interpretation of Responses of Concretes in Four‐Probe Impedance Measurements
Authors: Bandarenka Siarhei N. , Bandarenka Aliaksandr S. 
Published: February 2024

AbstractTypically, a detailed non‐destructive characterization and quality assessment of concretes under “real‐world”, for example, road conditions, are complicated. Impedance spectroscopy is a powerful technique for obtaining insights into concrete property changes during its usage in various environments. However, interpreting and analyzing impedance responses can be challenging due to the lack of explicit physical impedance models of different concretes. In this work, we have elaborated and verified such a model for the so‐called four‐electrode impedance measurements for dry materials and concrete exposed to aqueous K2SO4 solutions, which can cause concrete corrosion. A differential impedance analysis, which does not use any preliminary model assumption, suggested the elements′ presence originating from different types of pores and the contribution of the grain boundary capacitance. Based on this information, the equivalent circuit model was constructed using rules typical in solid‐state ionics and verified by fitting the impedance data to the model; and its parameter changes after adding the K2SO4 solutions were analyzed. The model demonstrated excellent agreement with the measured spectra. Its parameter changes generally agree with the expected behavior of the concrete samples in the corrosive environment. Possible applications of such impedance analysis are briefly discussed.
Study on the anti‐cancer activity of α‐phenethylamine ferrocenecarboxylic acid co‐crystals
Authors: Youyin Liao , Yuexing Ma , Jiahao Chen , Kun Qian , Jie Yang , Rongbin Pan , Yiyong Xu 
Published: February 2024

AbstractFerrocene derivatives show a wide range of pharmacological activities in the medical field, especially in the anti‐tumor field, and can be used as candidate drugs or lead compounds for the treatment of tumors and other diseases. And α‐phenethylamine is an important intermediate for the preparation of fine chemical products. (R)‐(+)‐1‐Phenethylamine ferrocenecarboxylic acid/(S)‐(−)‐1‐phenethylamine ferrocenecarboxylic acid were prepared, named compounds 1 and 2, respectively. Single crystal X‐ray diffraction showed that compounds 1 and 2 crystallized in the orthorhombic system space group P212121, and the crystal structures of compounds 1 and 2 exhibited mirror symmetry. The inhibitory effect of two compounds on SW480, MDA‐MB‐231, and H1299 cells was tested by MTT colorimetry. The IC50 values of the compounds against cancer cells were also calculated. The anti‐cancer effect was more pronounced for compounds in the S‐configuration. Compound 2 made the wild‐type cancer cells undergo apoptosis, thus preventing cancer; it also had the function of helping the cell gene repair defects.
Synthesis of nanostructured titanium carbide (TiC) from bitumen coke by mechanical alloying process
Authors: Xing Tingyong , Gieleciak Rafal , Chen Jinwen 
Published: February 2024

AbstractThis study explored synthesizing titanium carbide (TiC) from bitumen coke using mechanical alloying. Initially, raw bitumen coke (5.9 wt.% sulphur) from delayed coking was desulphurized to produce low sulphur coke with a sulphur content of 0.2 wt.% for comparison purposes. Both high and low sulphur coke samples were mechanically alloyed with titanium (Ti) powder in a planetary ball mill under various conditions (milling time, milling speed, and ball‐to‐material ratios [BMR]). TiC was successfully produced from both high sulphur and low sulphur coke samples. The formation of TiC was confirmed by X‐ray diffraction (XRD) analysis. The effects of the experimental parameters on the production of TiC were evaluated. The experimental results showed that the high sulphur coke and Ti were converted into TiC after 10 h milling, whereas the low sulphur coke and Ti were converted into TiC much faster (after 5 h milling) at the same milling speed and BMR. Under the same milling time and BMR, the high sulphur coke and Ti were converted into TiC at 400 rpm, whereas the low sulphur coke and Ti were converted into TiC at 300 rpm. In addition, the high sulphur coke and Ti were converted into TiC when the BMR was 60:1, and the low sulphur coke and Ti were converted into TiC when the BMR was 40:1 under the same milling time and speed. Overall, preliminary results suggest that the conversion of low sulphur coke samples is easier and requires less energy to produce TiC compared to the high sulphur coke samples.
The effect of COVID‐19 on employment: A bibliometric review of a she‐cession
Authors: Enciso‐Alfaro Saudi‐Yulieth , Marhroub Salma , Martínez‐Córdoba Pedro‐José , García‐Sánchez Isabel‐María 
Published: February 2024

AbstractThe effort to close the gender gaps in employment is one of the priorities worldwide to help address the disparity that exists between men and women in terms of rights and opportunities and to grow the economy in a sustainable way. Several academics and international organizations are interested in understanding its evolution, as well as the reasons and consequences of its existence. In this sense, the crisis alters the labor markets, affecting male and female employment ratios to varying degrees. To determine the foundations and consequences of the COVID‐19 in the labor sphere: we first discuss the most relevant international analysis of employment in pre‐and post‐COVID‐19 times. Second, we synthesize the state of the art of the most relevant literature on gender gap in employment and its drivers, especially those related to the impact of the coronavirus. To achieve this, we revised 731 papers since 1989 until January 2024. The reports of different organizations, as well as scientific studies indicate that the coronavirus has represented a setback for female empowerment. This is evident in higher rates of destroyed employment due to the pandemic impact on more feminized sectors, and women have assumed greater responsibilities at home compared to males. With a sample of 394 articles published between 2020 and January 2024, we employed a bibliometric approach to understand the evolution of scientific research on the subject. Our results provide a theoretical and conceptual framework that facilitates academic progress in understanding gender inequality, as well as practical guidance in identifying gaps.
Recommendations for using artificial intelligence in clinical flow cytometry
Authors: Ng David P. , Simonson Paul D. , Tarnok Attila , Lucas Fabienne , Kern Wolfgang , Rolf Nina , Bogdanoski Goce , Green Cherie , Brinkman Ryan R. , Czechowska Kamila 
Published: February 2024

AbstractFlow cytometry is a key clinical tool in the diagnosis of many hematologic malignancies and traditionally requires close inspection of digital data by hematopathologists with expert domain knowledge. Advances in artificial intelligence (AI) are transferable to flow cytometry and have the potential to improve efficiency and prioritization of cases, reduce errors, and highlight fundamental, previously unrecognized associations with underlying biological processes. As a multidisciplinary group of stakeholders, we review a range of critical considerations for appropriately applying AI to clinical flow cytometry, including use case identification, low and high risk use cases, validation, revalidation, computational considerations, and the present regulatory frameworks surrounding AI in clinical medicine. In particular, we provide practical guidance for the development, implementation, and suggestions for potential regulation of AI‐based methods in the clinical flow cytometry laboratory. We expect these recommendations to be a helpful initial framework of reference, which will also require additional updates as the field matures.
Cover Image, Volume 62, Issue 1
Authors: Zhang Mingyi , Feng Jifan , Li Yue , Qin Peter Z. , Chai Yang 
Published: February 2024

Cover illustration: The cover image is based on the Technical Note Generation of tamoxifen‐inducible Tfap2b‐CreERT2 mice using CRISPR‐Cas9 by Mingyi Zhang et al., https://doi.org/10.1002/dvg.23582image