bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chiral BINOL-phosphate assembled single hexagonal nanotube in aqueous solution for confined rearrangement acceleration
Authors: Li Kang , Qin Wei-Min , Su Wen-Xia , Hu Jia-Min , Cai Yue-Peng 
Published: March 2024

AbstractCreating microenvironments that mimic an enzyme’s active site is a critical aspect of supramolecular confined catalysis. In this study, we employ the commonly used chiral 1,1’-bi-2-naphthol (BINOL) phosphates as subcomponents to construct supramolecular hollow nanotube in an aqueous medium through non-covalent intermolecular recognition and arrangement. The hexagonal nanotubular structure is characterized by various techniques, including X-ray, NMR, ESI-MS, AFM, and TEM, and is confirmed to exist in a homogeneous aqueous solution stably. The nanotube’s length in solution depends on the concentration of chiral BINOL-phosphate as a monomer. Additionally, the assembled nanotube can accelerate the rate of the 3-aza-Cope rearrangement reaction by up to 85-fold due to the interior confinement effect. Based on the detailed kinetic and thermodynamic analyses, we propose that the chain-like substrates are constrained and pre-organized into a reactive chair-like conformation, which stabilizes the transition state of the reaction in the confined nanospace of the nanotube. Notably, due to the restricted conformer with less degrees of freedom, the entropic barrier is significantly reduced compared to the enthalpic barrier, resulting in a more pronounced acceleration effect.
A conserved NR5A1-responsive enhancer regulates SRY in testis-determination
Authors: Houzelstein Denis , Eozenou Caroline , Lagos Carlos F. , Elzaiat Maëva , Bignon-Topalovic Joelle , Gonzalez Inma , Laville Vincent , Schlick Laurène , Wankanit Somboon , Madon Prochi , Kirtane Jyotsna , Athalye Arundhati , Buonocore Federica , Bigou Stéphanie , Conway Gerard S. , Bohl Delphine , Achermann John C. , Bashamboo Anu , McElreavey Ken 
Published: March 2024

AbstractThe Y-linked SRY gene initiates mammalian testis-determination. However, how the expression of SRY is regulated remains elusive. Here, we demonstrate that a conserved steroidogenic factor-1 (SF-1)/NR5A1 binding enhancer is required for appropriate SRY expression to initiate testis-determination in humans. Comparative sequence analysis of SRY 5’ regions in mammals identified an evolutionary conserved SF-1/NR5A1-binding motif within a 250 bp region of open chromatin located 5 kilobases upstream of the SRY transcription start site. Genomic analysis of 46,XY individuals with disrupted testis-determination, including a large multigenerational family, identified unique single-base substitutions of highly conserved residues within the SF-1/NR5A1-binding element. In silico modelling and in vitro assays demonstrate the enhancer properties of the NR5A1 motif. Deletion of this hemizygous element by genome-editing, in a novel in vitro cellular model recapitulating human Sertoli cell formation, resulted in a significant reduction in expression of SRY. Therefore, human NR5A1 acts as a regulatory switch between testis and ovary development by upregulating SRY expression, a role that may predate the eutherian radiation. We show that disruption of an enhancer can phenocopy variants in the coding regions of SRY that cause human testis dysgenesis. Since disease causing variants in enhancers are currently rare, the regulation of gene expression in testis-determination offers a paradigm to define enhancer activity in a key developmental process.
Electroreduction of unactivated alkenes using water as hydrogen source
Authors: Wang Yanwei , Wang Qian , Wu Lei , Jia Kangping , Wang Minyan , Qiu Youai 
Published: March 2024

AbstractHerein, we report an electroreduction of unactivated alkyl alkenes enabled by [Fe]-H, which is provided through the combination of anodic iron salts and the silane generated in situ via cathodic reduction, using H2O as an H-source. The catalytic amounts of Si-additive work as an H-carrier from H2O to generate a highly active silane species in situ under continuous electrochemical conditions. This approach shows a broad substrate scope and good functional group compatibility. In addition to hydrogenation, the use of D2O instead of H2O provides the desired deuterated products in good yields with excellent D-incorporation (up to >99%). Further late-stage hydrogenation of complex molecules and drug derivatives demonstrate potential application in the pharmaceutical industry. Mechanistic studies are performed and provide support for the proposed mechanistic pathway.
Autonomous closed-loop mechanistic investigation of molecular electrochemistry via automation
Authors: Sheng Hongyuan , Sun Jingwen , Rodríguez Oliver , Hoar Benjamin B. , Zhang Weitong , Xiang Danlei , Tang Tianhua , Hazra Avijit , Min Daniel S. , Doyle Abigail G. , Sigman Matthew S. , Costentin Cyrille , Gu Quanquan , Rodríguez-López Joaquín , Liu Chong 
Published: March 2024

AbstractElectrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Recent advances in automated instrumentation and machine-learning algorithms unlock the possibility for accelerated studies of electrochemical fundamentals via high-throughput, online decision-making. Here we report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry. As a proof-of-concept, this platform autonomously identifies and investigates an EC mechanism, an interfacial electron transfer (E step) followed by a solution reaction (C step), for cobalt tetraphenylporphyrin exposed to a library of organohalide electrophiles. The generally applicable workflow accurately discerns the EC mechanism’s presence amid negative controls and outliers, adaptively designs desired experimental conditions, and quantitatively extracts kinetic information of the C step spanning over 7 orders of magnitude, from which mechanistic insights into oxidative addition pathways are gained. This work opens opportunities for autonomous mechanistic discoveries in self-driving electrochemistry laboratories without manual intervention.
The CHK1 inhibitor prexasertib in BRCA wild-type platinum-resistant recurrent high-grade serous ovarian carcinoma: a phase 2 trial
Authors: Giudice Elena , Huang Tzu-Ting , Nair Jayakumar R. , Zurcher Grant , McCoy Ann , Nousome Darryl , Radke Marc R. , Swisher Elizabeth M. , Lipkowitz Stanley , Ibanez Kristen , Donohue Duncan , Malys Tyler , Lee Min-Jung , Redd Bernadette , Levy Elliot , Rastogi Shraddha , Sato Nahoko , Trepel Jane B. , Lee Jung-Min 
Published: March 2024

Abstract
The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS < 6 months]. Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.
Coconut rhinoceros beetle digestive symbiosis with potential plant cell wall degrading microbes
Authors: Han Chiao-Jung , Cheng Chih-Hsin , Yeh Ting-Feng , Pauchet Yannick , Shelomi Matan 
Published: March 2024

AbstractCoconut rhinoceros beetle (CRB, Oryctes rhinoceros) is an invasive palm pest whose larvae eat wood, yet lack the necessary digestive enzymes. This study confirmed endogenous CRB cellulase is inactive, suggesting microbial fermentation. The inner lining of the CRB hindgut has tree-like structures covered with a conspicuous biofilm. To identify possible symbionts, 16 S rRNA amplicon sequencing was used on individuals from across Taiwan. Several taxa of Clostridia, an anaerobic class including many cellulolytic bacteria, were highly abundant in most individuals from all locations. Whole metagenome sequencing further confirmed many lignocellulose degrading enzymes are derived from these taxa. Analyses of eggs, larvae, adults, and soil found these cellulolytic microbes are not transmitted vertically or transstadially. The core microbiomes of the larval CRB are likely acquired and enriched from the environment with each molt, and enable efficient digestion of wood.
Effect of solution ions on the charge and performance of nanofiltration membranes
Authors: Roth Rebecca S. , Birnhack Liat , Avidar Mor , Hjelvik Elizabeth A. , Straub Anthony P. , Epsztein Razi 
Published: March 2024

AbstractConsidering growing efforts to understand and improve the solute-specific selectivity of nanofiltration (NF) membranes, we explored the ion-specific effects that govern the charge and performance of a loose polyamide NF membrane that is commonly used for solute-solute separations. Specifically, we systematically evaluated the zeta potential of the membrane under different conditions of pH, salinity, and ionic composition, and correlated the obtained data with membrane performance tested under similar conditions. Our results identify the pKa of both carboxylic and amine groups bonded to the membrane surface and suggest that the highly polarizable chloride anions in the solution adsorb to the polyamide, increasing its negative charge. We also show that monovalent cations of different “stickiness” can neutralize the negative membrane charge to different extents due to their varying tendency to sorb to the polymer matrix or screen the fixed carboxyl groups on the membrane surface. Notably, our correlation between zeta potential measurements and permeability experiments indicates the substantial contribution of solution ions to Donnan exclusion in NF membranes.
Cell-in-cell phenomena across the tree of life
Authors: Kapsetaki Stefania E. , Cisneros Luis H. , Maley Carlo C. 
Published: March 2024

AbstractCells in obligately multicellular organisms by definition have aligned fitness interests, minimum conflict, and cannot reproduce independently. However, some cells eat other cells within the same body, sometimes called cell cannibalism. Such cell-in-cell events have not been thoroughly discussed in the framework of major transitions to multicellularity. We performed a systematic screening of 508 articles, from which we chose 115 relevant articles in a search for cell-in-cell events across the tree of life, the age of cell-in-cell-related genes, and whether cell-in-cell events are associated with normal multicellular development or cancer. Cell-in-cell events are found across the tree of life, from some unicellular to many multicellular organisms, including non-neoplastic and neoplastic tissue. Additionally, out of the 38 cell-in-cell-related genes found in the literature, 14 genes were over 2.2 billion years old, i.e., older than the common ancestor of some facultatively multicellular taxa. All of this suggests that cell-in-cell events may have originated before the origins of obligate multicellularity. Thus, our results show that cell-in-cell events exist in obligate multicellular organisms, but are not a defining feature of them. The idea of eradicating cell-in-cell events from obligate multicellular organisms as a way of treating cancer, without considering that cell-in-cell events are also part of normal development, should be abandoned.
Identification and validation of a metabolism-related gene signature for predicting the prognosis of paediatric medulloblastoma
Authors: Su Jun , Xie Qin , Xie Longlong 
Published: March 2024

AbstractMedulloblastoma (MB) is a malignant brain tumour that is highly common in children and has a tendency to spread to the brain and spinal cord. MB is thought to be a metabolically driven brain tumour. Understanding tumour cell metabolic patterns and characteristics can provide a promising foundation for understanding MB pathogenesis and developing treatments. Here, by analysing RNA-seq data of MB samples from the Gene Expression Omnibus (GEO) database, 12 differentially expressed metabolic-related genes (DE-MRGs) were chosen for the construction of a predictive risk score model for MB. This model demonstrated outstanding accuracy in predicting the outcomes of MB patients and served as a standalone predictor. An evaluation of functional enrichment revealed that the risk score showed enrichment in pathways related to cancer promotion and the immune response. In addition, a high risk score was an independent poor prognostic factor for MB in patients with different ages, sexes, metastasis stages and subgroups (SHH and Group 4). Consistently, the metabolic enzyme ornithine decarboxylase (ODC1) was upregulated in MB patients with poor survival time. Inhibition of ODC1 in primary and metastatic MB cell lines decreased cell proliferation, migration and invasion but increased immune infiltration. This study could aid in identifying metabolic targets for MB as well as optimizing risk stratification systems and individual treatment plans for MB patients via the use of a metabolism-related gene prognostic risk score signature.
Exploring the surge current degradation of natural ester oil-based nanofluids
Authors: Tsovilis Thomas , Peppas George , Staikos Evangelos , Hadjicostas Alexandros , Datsios Zacharias 
Published: March 2024

AbstractThe surge endurance of natural ester oil-based nanofluids against surge events is investigated experimentally. The focus of this work is the examination, through dielectric spectroscopy measurements, of the alteration of the real and imaginary parts of the complex relative permittivity of iron oxide nanofluids as a result of an accelerated degradation test employing a sequence of repetitive current impulses produced via a 12 kV/6 kA combination wave generator. The target is the exploration of a possible implementation of nanofluids as multipurpose liquids that act, in addition to insulation and coolants, as surge absorption media. Promising experimental results are discussed and compared with those of mineral oil that is widely used as a conventional insulating liquid in power transformers.
Process design for acidic and alcohol based deep eutectic solvent pretreatment and high pressure homogenization of palm bunches for nanocellulose production
Authors: Sonyeam Janejira , Chaipanya Ratanaporn , Suksomboon Sudarat , Khan Mohd Jahir , Amatariyakul Krongkarn , Wibowo Agung , Posoknistakul Pattaraporn , Charnnok Boonya , Liu Chen Guang , Laosiripojana Navadol , Sakdaronnarong Chularat 
Published: March 2024

AbstractThis research aimed to study on nanocellulose production from palm bunch using process design and cost analysis. Choline chloride based deep eutectic solvent pretreatment was selected for high-purity cellulose separation at mild condition, followed by nano-fibrillation using mechanical treatment. Three types of choline chloride-based deep eutectic solvents employing different hydrogen-bond donors (HBDs) namely lactic acid, 1,3-butanediol and oxalic acid were studied. The optimal cellulose extraction condition was choline chloride/lactic acid (ChLa80C) pretreatment of palm empty bunch at 80 °C followed by bleaching yielding 94.96%w/w cellulose content in product. Size reduction using ultrasonication and high-pressure homogenization produced nanocellulose at 67.12%w/w based on cellulose in raw material. Different morphologies of nanocellulose were tunable in the forms of nanocrystals, nano-rods and nanofibers by using dissimilar deep eutectic solvents. This work offered a sustainable and environmentally friendly process as well as provided analysis of DES pretreatment and overview operating cost for nanocellulose production. Application of nanocellulose for the fabrication of highly functional and biodegradable material for nanomedicine, electronic, optical, and micromechanical devices is achievable in the near future.
Identification of molecular subtypes and a prognostic signature based on m6A/m5C/m1A-related genes in lung adenocarcinoma
Authors: Zhang Yu , Jia Qiuye , Li Fangfang , Luo Xuan , Wang Zhiyuan , Wang Xiaofang , Wang Yanghao , Zhang Yinglin , Li Muye , Bian Li 
Published: March 2024

AbstractLung cancer, specifically the histological subtype lung adenocarcinoma (LUAD), has the highest global occurrence and fatality rate. Extensive research has indicated that RNA alterations encompassing m6A, m5C, and m1A contribute actively to tumorigenesis, drug resistance, and immunotherapy responses in LUAD. Nevertheless, the absence of a dependable predictive model based on m6A/m5C/m1A-associated genes hinders accurately predicting the prognosis of patients diagnosed with LUAD. In this study, we collected patient data from The Cancer Genome Atlas (TCGA) and identified genes related to m6A/m5C/m1A modifications using the GeneCards database. The “ConsensusClusterPlus” R package was used to produce molecular subtypes by utilizing genes relevant to m6A/m5C/m1A identified through differential expression and univariate Cox analyses. An independent prognostic factor was identified by constructing a prognostic signature comprising six genes (SNHG12, PABPC1, IGF2BP1, FOXM1, CBFA2T3, and CASC8). Poor overall survival and elevated expression of human leukocyte antigens and immune checkpoints were correlated with higher risk scores. We examined the associations between the sets of genes regulated by m6A/m5C/m1A and the risk model, as well as the immune cell infiltration, using algorithms such as ESTIMATE, CIBERSORT, TIMER, ssGSEA, and exclusion (TIDE). Moreover, we compared tumor stemness indices (TSIs) by considering the molecular subtypes related to m6A/m5C/m1A and risk signatures. Analyses were performed based on the risk signature, including stratification, somatic mutation analysis, nomogram construction, chemotherapeutic response prediction, and small-molecule drug prediction. In summary, we developed a prognostic signature consisting of six genes that have the potential for prognostication in patients with LUAD and the design of personalized treatments that could provide new versions of personalized management for these patients.
Clinical and mutational characteristics of oculocutaneous albinism type 7
Authors: Kruijt C. C. , de Wit G. C. , van Minderhout H. M. , Schalij-Delfos N. E. , van Genderen M. M. 
Published: March 2024

AbstractThe purpose of this paper is to expand on the phenotype of oculocutaneous albinism type 7 (OCA7). We described three patients with OCA7: two from a consanguineous family of Kurdish origin and one patient of Dutch origin. We compared them with all patients described to date in the literature. All newly described patients had severely reduced visual acuity (VA), nystagmus, hypopigmentation of the fundus, severe foveal hypoplasia, and chiasmal misrouting. None had iris translucency. All patients had normal pigmentation of skin and hair. We found one novel mutation in the Dutch patient: c.565G > A; p.(Gly189Ser). We compared our patients to the 15 described in the literature to date. All 18 patients had substantially pigmented skin and hair, very poor VA (0.4–1.3 logMAR), nystagmus, (mild) ocular hypopigmentation, foveal hypoplasia, and misrouting. Although pigmentation levels were mildly affected in OCA7, patients had a severe ocular phenotype with VA at the poorer end of the albinism spectrum, severe foveal hypoplasia, and chiasmal misrouting. OCA7 patients had a phenotype restricted to the eyes, and similar to that of X-linked ocular albinism. We therefore propose to rename the disorder in ocular albinism type 2. Unfolding the role of LRMDA in OCA7, may bring us a step closer in identifying the responsible factors for the co-occurrence of foveal hypoplasia and misrouting.
Effect of gamma rays on the essential oil and biochemical characteristics of the Satureja mutica Fisch & C. A. Mey
Authors: Mahdi Navehsi Fatemeh , Abdossi Vahid , Abbaszadeh Bohloul , Azimi Razieh , Dianat Marjan 
Published: March 2024

AbstractThere are 16 species in the genus Satureja L. (Lamiaceae), of which 10 are native. This research aimed to investigate the effect of gamma rays and storage conditions and duration on the percentage and components of the essential oil and some biochemical characteristics of Satureja mutica Fisch & C.A. Mey at the Research Institute of Forests and Rangelands. Plants were collected at the full flowering stage and exposed to different doses of gamma rays (0, 2.5, 5, 7.5, and 10 kGy) at the Atomic Energy Organization, Iran. The samples were kept in a refrigerator (4 °C) and in the shade (25 ± 2 °C) for 0, 120, and 240 h. This experiment was performed in a completely randomized design. Essential oil extraction was done by water distillation for 2 h. The composition of their essential oil components was identified using GC and GC/MS. Some biochemical traits, including phenol content, antioxidant capacity, and carbohydrate content, were measured. The results indicated that irradiation on the percentage of essential oil showed a statistically significant difference. In addition, the interaction effect of irradiation × storage conditions, irradiation × duration of storage, on the percentage of essential oil was significant. According to a comparison of the means, 2.5 kGy irradiation produced the highest percentage of essential oil (0.4%); in contrast, a significant decrease was detected in components with 7.5 and 10 kGy irradiation. It was observed that the percentage of some essential oil compounds decreased with the gamma-ray intensity increase. 2.5 kGy of gamma rays and shade storage conditions for 240 h led to the highest content of p-cymene and carvacrol. Nevertheless, the highest thymol content was obtained under refrigeration conditions without irradiation. The maximum phenol content and antioxidant capacity were obtained when the plants were irradiated with 2.5 and 7.5 kGy gamma rays. However, the maximum carbohydrate rate was observed in non-irradiated plants. It was concluded that low-intensity gamma rays could improve the percentage of essential oil and main components like p-cymene and carvacrol in S. mutica Fisch & C.A. Mey.