bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastrointestinal conditions in the multiple sclerosis prodrome
Authors: Yusuf Fardowsa L. A. , Zhu Feng , Evans Charity , Fisk John D. , Zhao Yinshan , Marrie Ruth A. , Tremlett Helen 
Published: December 2023

AbstractObjectiveTo investigate gastrointestinal (GI)‐related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset.MethodsUsing linked administrative and clinical data from British Columbia (1996–2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI‐related physician visits and risk of ≥1 GI‐related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms.ResultsThe administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate/risk ratio (aRR):1.42, 95% CI: 1.10–1.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06–2.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation‐related (aRR: 1.82, 95% CI: 1.50–2.22), antiemetics/antinauseants (aRR: 1.64, 95% CI: 1.43–1.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47–1.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men = 2.32, 95% CI: 1.79–3.00; women = 1.54, 95% CI: 1.36–1.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance.InterpretationGI‐related physician visits and drug dispensations were more common in the 5 years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.
Light‐Enhanced Hypoxia‐Responsive Gene Editing for Hypoxia‐Resistant Photodynamic and Immunotherapy
Authors: Qu Suchen , Ji Yu , Fan Liansheng , Yan Tao , Zhu Gaoshuang , Song Hongxiu , Yang Kaiyong , Han Xin 
Published: December 2023

AbstractHypoxia is a key hallmark of solid tumors and can cause resistance to various treatments such as photodynamics and immunotherapy. Microenvironment‐responsive gene editing provides a powerful tool to overcome hypoxia resistance and remodel hypoxic microenvironments for enhanced tumor therapy. Here, a light‐enhanced hypoxia‐responsive multifunctional nanocarrier is developed to perform spatiotemporal specific dual gene editing for enhanced photodynamic and immunotherapy in breast cancer. As a gated molecule of nanocarrier, the degradation of azobenzene moieties under hypoxic conditions triggers controllable release of Cas9 ribonucleoprotein in hypoxic site of the tumor. Hyaluronic acid is conjugated with chloramine e6 to coat mesoporous silica nanoparticles for targeted delivery in tumors and generation of high levels of reactive oxygen species, which can result in increased hypoxia levels for effective cleavage of azobenzene bonds to improve gene editing efficiency and reduce toxic side effects with light irradiation. Moreover, dual targeting HIF‐1α and PD‐L1 in the anoxic microenvironments can overcome hypoxia resistance and remodel immune microenvironments, which reduces tumor plasticity and resistance to photodynamic and immunotherapy. In summary, a light‐enhanced hypoxia responsive nanocomposite is developed for controllable gene editing which holds great promise for synergistic hypoxia‐resistant photodynamic and immunotherapy.
Identification of PRDX5 as A Target for The Treatment of Castration‐Resistant Prostate Cancer
Authors: Wang Rong , Mi Yuanyuan , Ni Jiang , Wang Yang , Ding Lingwen , Ran Xuebin , Sun Qiaoyang , Tan Soo Yong , Koeffler H Phillip , Feng Ninghan , Chen Yong Q 
Published: December 2023

AbstractTreatment of castration‐resistant prostate cancer (CRPC) is a long‐standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking androgen receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug‐tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up‐regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration‐resistant prostate cancer.
Chemo‐Selective Single‐Cell Metabolomics Reveals the Spatiotemporal Behavior of Exogenous Pollutants During Xenopus Laevis Embryogenesis
Authors: Li Pengfei , Gao Song , Qu Wanting , Li Ying , Liu Zhen 
Published: December 2023

AbstractIn‐depth profiling of embryogenesis‐associated endogenous and exogenous metabolic changes can reveal potential bio‐effects resulting from human‐made chemicals and underlying mechanisms. Due to the lack of potent tools for monitoring spatiotemporal distribution and bio‐transformation behavior of dynamic metabolites at single‐cell resolution, however, how and to what extent environmental chemicals may influence or interfere embryogenesis largely remain unclear. Herein, a zero‐sample‐loss micro‐biopsy‐based mass spectrometric platform is presented for quantitative, chemo‐selective, high‐coverage, and minimal‐destructive profiling of development‐associated cis‐diol metabolites, which are critical for signal transduction and epigenome regulation, at both cellular level and tissue level of Xenopus laevis. Using this platform, three extraordinary findings that are otherwise hard to achieve are revealed: 1) there are characteristically different cis‐diol metabolic signatures among oocytes, anterior and posterior part of tailbud‐stage embryos; 2) halogenated cis‐diols heavily accumulate at the posterior part of tailbud‐stage embryos of Xenopus laevis; 3) dimethachlon, a kind of exogenous fungicide that is widely used as pesticide, may be bio‐transformed and accumulated in vertebrate animals in environment. Thus, this study opens a new avenue to simultaneously monitoring intercellular and intraembryonic heterogeneity of endogenous and exogenous metabolites, providing new insights into metabolic remolding during embryogenesis and putting a warning on potential environmental risk.
Two‐Dimensional Tandem Mass Spectrometry for Biopolymer Structural Analysis
Authors: Le MyPhuong T. , Holden Dylan T. , Manheim Jeremy M. , Dziekonski Eric T. , Iyer Kiran , Graham Cooks R. 
Published: December 2023

AbstractBiopolymer analysis, including proteomics and glycomics, relies heavily on the use of mass spectrometry for structural elucidation, including sequence determination. Novel methods to improve sample workup, instrument performance, and data analysis continue to be developed to address shortcomings associated with sample preparation, analysis time, data quality, and data interpretation. Here, we present a new method that couples in‐source collision‐induced dissociation (IS‐CID) with two‐dimensional tandem mass spectrometry (2D MS/MS) as a way to simplify proteomics and glycomics workflows while also providing additional insight into analyte structures over traditional MS/MS experiments. Specifically, IS‐CID is employed as a gas‐phase digestion method, i.e., to break down intact full‐length polysaccharide or peptide ions prior to mass analysis. The resulting mixtures of oligomeric ions are analyzed by 2D‐MS/MS, a technique that allows association of product ions with their precursor ions without isolation of the latter. A novel data analysis strategy is introduced to leverage the second dimension of 2D MS/MS spectra, in which stairstep patterns, representing outputs of a molecule's MSn scans, are extracted for structural interconnectivity information on the oligomer. The results demonstrate the potential applicability of 2D MS/MS strategies to the modern omics workflow and structural analysis of various classes of biopolymers.
Superfast Formation of C(sp2)−N, C(sp2)−P, and C(sp2)−S Vinylic Bonds in Water Microdroplets
Authors: Meng Yifan , Zare Richard N. , Gnanamani Elumalai 
Published: December 2023

AbstractWe report examples of C(sp2)−N, C(sp2)−S, and C(sp2)−P bond‐forming transformations in water microdroplets at room temperature and atmospheric pressure using N2 as a nebulizing gas. When an aqueous solution of vinylic acid and amine is electrosprayed (+3 kV), the corresponding C(sp2)−N product is formed in a single step, which was characterized using mass spectrometry (MS) and tandem mass spectrometry (MS2). The scope of this reaction was extended to other amines and other unsaturated acids, including acrylic (CH2=CHCOOH) and crotonic (CH3CH=CHCOOH) acids. We also found that thiols and phosphines are viable nucleophiles, and the corresponding C(sp2)−S and C(sp2)−P products are observed in positive ion mode using MS and MS2.
C−H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes
Authors: Tepaske Martijn A. , Fitterer Arnd , Verplancke Hendrik , Delony Daniel , Neben Marc C. , de Bruin Bas , Holthausen Max C. , Schneider Sven 
Published: December 2023

AbstractOxidation of an iridium(III) oxo precursor enabled the structural, spectroscopic, and quantum‐chemical characterization of the first well‐defined iridium(IV) oxo complex. Side‐by‐side examination of the proton‐coupled electron transfer thermochemistry revealed similar driving forces for the isostructural oxo complexes in two redox states due to compensating contributions from H+ and e− transfer. However, C−H activation of dihydroanthracene revealed significant hydrogen tunneling for the distinctly more basic iridium(III) oxo complex. Our findings complement the growing body of data that relate tunneling to ground state properties as predictors for the selectivity of C−H bond activation.
Manipulated Fluoro‐Ether Derived Nucleophilic Decomposition Products for Mitigating Polarization‐Induced Capacity Loss in Li‐Rich Layered Cathode
Authors: Zhang Baodan , Zhang Haitang , Luo Haiyan , Hua Haiming , Wu Xiaohong , Chen Yilong , Zhou Shiyuan , Yin Jianhua , Zhang Kang , Liao Hong‐Gang , Wang Qingsong , Zou Yeguo , Qiao Yu , Sun Shi‐Gang 
Published: December 2023

AbstractElectrolyte engineering is a fascinating choice to improve the performance of Li‐rich layered oxide cathodes (LRLO) for high‐energy lithium‐ion batteries. However, many existing electrolyte designs and adjustment principles tend to overlook the unique challenges posed by LRLO, particularly the nucleophilic attack. Here, we introduce an electrolyte modification by locally replacing carbonate solvents in traditional electrolytes with a fluoro‐ether. By benefit of the decomposition of fluoro‐ether under nucleophilic O‐related attacks, which delivers an excellent passivation layer with LiF and polymers, possessing rigidity and flexibility on the LRLO surface. More importantly, the fluoro‐ether acts as “sutures”, ensuring the integrity and stability of both interfacial and bulk structures, which contributed to suppressing severe polarization and enhancing the cycling capacity retention from 39 % to 78 % after 300 cycles for the 4.8 V‐class LRLO. This key electrolyte strategy with comprehensive analysis, provides new insights into addressing nucleophilic challenge for high‐energy anionic redox related cathode systems.
Single Idiosyncratic Ionic Generator Working in Iso‐Osmotic Solutions Via Ligand Confined Assembled in Gaps Between Nanosheets
Authors: Liu Bi‐Ying , Zhang Yu‐Hui , Qian Yongchao , Quan Di , Jia Mei‐Juan , Jin Xiao‐Yan , Zhou Min , Kong Xiang‐Yu , Jiang Lei 
Published: December 2023

AbstractNumerous reported bioinspired osmotic energy conversion systems employing cation‐/anion‐selective membranes and solutions with different salinity are actually far from the biological counterpart. The iso‐osmotic power generator with the specific ionic permselective channels (e.g., K+ or Na+ channels) which just allow specific ions to get across and iso‐osmotic solutions still remain challenges. Inspired by nature, we report a bioinspired K+‐channel by employing a K+ selective ligand, 1,1,1‐tris{[(2′‐benzylaminoformyl)phenoxy]methyl}ethane (BMP) and graphene oxide membrane. Specifically, the K+ and Na+ selectivity of the prepared system could reach up to ≈17.8, and the molecular dynamics simulation revealed that the excellent permselectivity of K+ mainly stemmed from the formed suitable channel size. Thus, we assembled the K+‐selective iso‐osmotic power generator (KSIPG) with the power density up to ≈15.1 mW/m2 between equal concentration solutions, which is higher than traditional charge‐selective osmotic power generator (CSOPG). The proposed strategy has well shown the realizable approach to construct single‐ion selective channels‐based highly efficient iso‐osmotic energy conversion systems and would surely inspire new applications in other fields, including self‐powered systems and medical materials, etc.
Accessing Pyridines via a Nitrene Internalization Process
Authors: Kotwal Namrata , Chauhan Pankaj 
Published: December 2023

AbstractPyridines are valuable pharmacophores, and their access via direct and selective transmutation of carbon atom with desired nitrogen could become crucial in drug discovery processes. However, only scarce examples can be found when it comes C‐to‐N‐transmutation reactions of aromatics that could lead to the facile synthesis of pyridines or other azaarenes. In this context, Levin and co‐workers recently disclosed a process leading to pyridines from the corresponding aryl azides via the regioselective nitrene internalization process. Notably, the transformation did not lead to any further modification of the rest of the aromatic skeleton. This innovative work enabled selectively accessing various pyridine derivatives through direct nitrogen scan operations on benzene derivatives, which were otherwise not feasible.
Identification of novel sulfathiazole‐triazolo‐chalcone hybrids as VEGFR‐2/EGFR dual inhibitors with antiangiogenic activity and apoptotic induction
Authors: Zeidan Mohamed A. , Othman Dina I. A. , Goda Fatma E. , Mostafa Amany S. 
Published: December 2023

AbstractCertain sulfathiazole‐triazolo chalcone hybrids were identified as anticancer agents with dual vascular endothelial growth factor receptor‐2 (VEGFR‐2)/epidermal growth factor receptor (EGFR) kinase inhibitory effect. All of the compounds were evaluated for their cytotoxic activity against the MCF‐7 and HepG‐2 tumor cell lines. Compounds 11g, 11h, and 11j exhibited the most potent antiproliferative activity against both cancer cell lines, with good safety toward WI‐38 normal cells. Thus, they were further assessed for VEGFR‐2 inhibitory activity. They have suppressed VEGFR‐2 enzyme at IC50 of 0.316, 0.076, and 0.189 µM, respectively in comparison to sorafenib (IC50 = 0.035 µM). EGFR enzyme inhibition was further screened for the most potent inhibitors, 11h and 11j, where they displayed enhanced potency with IC50 of 0.085 and 0.108 µM, respectively, compared to erlotinib (IC50 = 0.037 µM). Compounds 11h and 11j were additionally investigated for inhibition of comparable kinases, PDGFR‐β and B‐Raf, where results assessed adequate selectivity of both compounds toward the VEGFR‐2 and EGFR kinases. Furthermore, the wound healing assay of compound 11h manifested a percent wound closure of 65.18% in MCF‐7 cells compared to doxorubicin (58.51%) and untreated cells (97.77%), proving its antiangiogenic activity. The cell cycle assay of MCF‐7 cells treated with 11h demonstrated cell cycle arrest at the S phase. Moreover, compound 11h induced apoptosis with a 44‐fold increase compared to that induced in the control MCF‐7 cells. Molecular docking results of compounds 11h and 11j established their efficacies, and in silico studies showed convenient safety profiles with drug‐likeness properties.
Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta‐Analysis
Authors: Bechman Katie , Yang Zijing , Adas Maryam , Nagra Deepak , S. Uğuzlar Ali , Russell Mark D. , Wilson Nicky , Steer Sophia , Norton Sam , Galloway James 
Published: December 2023

ObjectiveAnterior uveitis is a common extra‐articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease‐modifying drugs in AxSpA.MethodsWe conducted a systematic review and meta‐analysis to identify phase II/III double‐blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin‐17 (anti–IL‐17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient‐exposure years (PEY) were calculated using the per‐protocol approach. Incidence rate (IR) of AU/100 person‐years were calculated by treatment group using the random effects approach. Network meta‐analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias‐2 tool.ResultsForty‐four trials were included: 17 anti‐TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL‐17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti‐TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL‐17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti‐TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL‐17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti‐TNF mAb, anti–IL‐17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti‐TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL‐17, and etanercept. All treatments were ranked superior to placebo.ConclusionAnti‐TNF mAbs, JAKi, and anti–IL‐17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.
Activatable organic probes for in situ imaging of biomolecules
Authors: Li Ke , Yang Minghui 
Published: December 2023

AbstractBiomolecules are fundamental for various chemical and biological processes of living organisms. High‐resolution in situ imaging of the dynamics and local distribution of biomolecules may facilitate better interpretation of diverse complex cell events in the biomedicine field. In different advanced imaging tools, fluorescence imaging‐based activatable organic probes can be noninvasively and effortlessly internalized into cells and can be easily modified, which is essential for the in situ imaging of targets in living organisms. We here briefly summarize the existing general design strategies of activatable organic probes for retaining the fluorescence signal inside cells. We particularly describe the bioapplication of these probes for the in situ bioimaging. This review is expected to promote the development of new molecular tools for extending the application of these in situ imaging strategies to other biomolecules.
Total Synthesis of (±)‐20‐epi‐Kopsiyunnanine K: A Domino and Stereocontrolled Approach
Authors: Huang Bo‐Jyun , Hsiao Tzu‐Ying , Fu Ke‐Chiao , Chiou Wen‐Hua 
Published: December 2023

AbstractA one‐pot route to a novel azepane‐fused tetrahydro‐β‐carboline framework from tryptyl‐4‐pentenamide derivatives has been developed, featuring the Rh‐catalyzed hydroformylation double cyclization. Subsequent alkylation in the tetracyclic system proceeded stereoselectively to form a quaternary carbon. The synthesis of (±)‐20‐epi‐kopsiyunnanine K was accomplished through the strategy.
Multicolor optogenetics for regulating flux ratio of three glycolytic pathways using EL222 and CcaSR in Escherichia coli
Authors: Akagi Hayato , Shimizu Hiroshi , Toya Yoshihiro 
Published: December 2023

AbstractOptogenetics is an attractive synthetic biology tool for controlling the metabolic flux distribution. Here, we demonstrated optogenetic flux ratio control of glycolytic pathways consisting of the Embden–Meyerhof–Parnas (EMP), pentose phosphate (PP), and Entner–Doudoroff (ED) pathways by illuminating multicolor lights using blue light‐responsive EL222 and green/red light‐responsive CcaSR in Escherichia coli. EL222 forms a dimer and binds to a particular DNA sequence under blue light; therefore, target gene expression can be reduced or induced by inserting a recognition sequence into its promoter regions. First, a flux ratio between the PP and ED pathways was controlled by blue light using EL222. After blocking the EMP pathway, the EL222‐recognition sequence was inserted between the −35 and −10 regions of gnd to repress the PP flux and was also inserted upstream of the −35 region of edd to induce ED flux. After adjusting light intensity, the PP:ED flux ratios were 60:39% and 29:70% under dark and blue light conditions, respectively. Finally, a CcaSR‐based pgi expression system was implemented to control the flux ratio between the EMP and PP + ED pathways by illuminating green/red light. The EMP:PP:ED flux ratios were 80:9:11%, 14:35:51%, and 33:5:62% under green, red, and red and blue light, respectively.
Prognostic nomogram and epidemiological analysis for lung atypical carcinoid: A SEER database and external validation study
Authors: Yi Xinglin , He Yi , Qian Gangzhen , Deng Caixia , Qin Jiayi , Zhou Xiangdong , Luo Hu 
Published: December 2023

AbstractPurposeOur study aims to delineate the epidemiological distribution of pulmonary carcinoids, including atypical carcinoid (AC) and typical carcinoid (TC), identify independent prognostic factors, develop an integrative nomogram and examine the effects of various surgical modalities on atypical carcinoid‐specific survival (ACSS).MethodsJoinpoint regression model and age‐group distribution diagram were applied to determine the epidemiological trend of the pulmonary carcinoids. Univariate and least absolute shrinkage and selection operator (LASSO)‐based Cox regression models were used to identify independent factors, and a nomogram and web‐based predictor were developed to evaluate prognosis of AC patients individually. We performed Kaplan–Meier survival analyses to compare the scope of various surgical interventions, with and without G‐computation adjustment, utilising restricted mean survival time (RMST) to assess survival disparities.ResultsA total of 1132 patients were recruited from the Surveillance, Epidemiology, and End Results database (SEER) and a separate medical centre in China. The mean age of AC patients was 63.4 years and a smoking history was identified in 79.8% of AC patients. Joinpoint analysis shows rising annual rates of new AC and carcinoid cases among lung cancers. Both the proportion of pulmonary TC and AC within the total lung cancer population exhibits an L‐shaped trend across successive age groups. The nomogram predicted 1, 3 and 5 years of AC with excellent accuracy and discrimination. Kaplan–Meier survival analyses, conducted both pre‐ and post‐adjustment, demonstrated that sublobar resection's survival outcomes were not inferior to those of lobectomy in patients with stage I‐II and stage III disease.ConclusionThis study is the first to reveal epidemiological trends in pulmonary carcinoids over the past decade and across various age cohorts. For patients with early‐stage AC, sublobar resection may be a viable surgical recommendation. The established nomogram and web‐based calculator demonstrated decent accuracy and practicality.