bluuebunny/crossref_metadata_2025 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

Objective

To investigate gastrointestinal (GI)‐related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset.

Methods

Using 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.

Results

The 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.

Interpretation

GI‐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

Hypoxia 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

Treatment 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

In‐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

Biopolymer 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

We 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

Oxidation 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

Electrolyte 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

Numerous 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

Pyridines 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

Certain 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

Objective

Anterior 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.

Methods

We 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.

Results

Forty‐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.

Conclusion

Anti‐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

Biomolecules 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

A 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

Optogenetics 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

Purpose

Our 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).

Methods

Joinpoint 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.

Results

A 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.

Conclusion

This 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.
Synthesis and investigation of new indole‐containing vinyl sulfide derivatives: In silico and in vitro studies for potential therapeutic applications
Authors: Bonato Wille Ana Paula , Pereira da Motta Ketlyn , Pinto Brites Nathan , Luchese Cristiane , Frederico Schumacher Ricardo , Antunes Wilhelm Ethel
Published: December 2023

Indoles featuring organosulfur compounds serve as privileged structural scaffolds in various biologically active compounds. This study investigates the biological properties of five synthetic sulphenyl vinyl indoles (3 a–e) using both in silico and in vitro methods. Computational analyses employing Swiss ADME and Molinspiration software reveal the remarkable inhibitory activity of compound 3 d against proteases and kinases (scores of 0.18 and 0.06, respectively). Furthermore, it demonstrates the ability to modulate ionic and G protein‐coupled receptors (scores: −0.06 and 0.31, respectively) and serves as a ligand for nuclear receptors (score 0.15). In vitro investigations highlight the compounds′ efficacy in countering ABTS+ radical attacks and reducing lipid peroxidation levels. Particularly noteworthy is the superior efficacy of compounds 3 a, 3 b, and 3 e in DPPH (EC50 3 a: 268.5 μM) and TEAC assays (EC50 3 a: 49.9 μM; EC50 3 b: 133.4 μM, and EC50 3 e: 84.9 μM), as well as TBARS levels. Compound 3 c significantly reduces acetylcholinesterase activity, positioning itself as a noteworthy enzyme inhibitor. This study emphasizes the versatile biological potential of synthetic indole derivatives, suggesting their applicability for therapeutic purposes.
Fulvanines J−K, two rare lactam pyrrole alkaloids from Hemerocallis fulva
Authors: Lei Ya‐E. , Wang Qian , Yaermaimaiti Saimijiang , Ma Zi‐Hui , Li Miao‐Miao , Lu Yan , Chen Dao‐Feng , Wang Qi
Published: December 2023

Two rare jatropham lactam derivatives, named as fulvanines J−K (1‐2), together with six known pyrrole alkaloids, 5,5′‐oxydi(3‐methyl‐3‐pyrrolin‐2‐one) (3), (−)‐5‐hydroxy‐3‐methyl‐3‐pyrrolin‐2‐one (jatropham) (4), (±)‐5‐O‐methyljatropham (5), perlolyrine (6), butyl‐2‐formyl‐5‐(hydroxymethyl)‐1H‐pyrrole‐1‐butanoate (7), and hemerocallisamine II (8), were isolated from the flower of Hemerocallis fulva. Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti‐complementary activity in vitro, and compounds 1, 4, and 6 exhibited anti‐complement effect with CH50 values from 0.61 to 1.42 mM.
A large yolk sac malignancy in a girl, an uncommon yet challenging ovarian tumor: A case report
Authors: Poudel Aashish , Sedain Prajwal , Pokhrel Biraj , Sapkota Aakash , Chamlagain Anita , Sharma Nisha , Rajbhandary Sanyukta , Khaniya Bishal , Ojha Neebha
Published: December 2023

Key Clinical Message

Yolk sac tumors are rare and malignant germ cell tumors of the ovary occurring in children and young women. Fertility‐sparing surgical intervention with adjuvant chemotherapy has shown to improve prognosis.

We present a case of a 14‐year‐old girl who presented with the complaints of lower abdominal pain and distention. Her tumor markers were increased, and radiological investigation suggested the diagnosis of malignant left ovarian mass. Histopathology confirmed the diagnosis of Yolk sac tumor. She was subsequently managed with fertility‐sparing surgery and adjuvant chemotherapy.
Photoelectrochemical Glycerol Oxidation Coupled with Hydrogen Production
Authors: Miao Yucong , Li Zhenhua , Shao Mingfei
Published: December 2023

The catalytic oxidation of glycerol, a surplus byproduct of biodiesel, has received increasing attention due to the popular applications of its oxidation products, such as aldehydes, ketones, and carboxylates. Photoelectrochemical (PEC) methods provide a clean and sustainable pathway for glycerol oxidation and upgrading. However, selective oxidation of glycerol is a challenge due to its complex oxidation path, where the cleavage of C−O or C−C bonds at different positions can lead to a variety of products. This concept aims to describe the recent advances in PEC selective glycerol oxidation for the preparation of multiple high value‐added products, and discuss the reaction mechanism and selective production strategies in detail. Finally, the remaining challenges and future prospects for the PEC glycerol oxidation system are presented.
Oxidative Depolymerisation of Kraft Lignin: From Fabrication of Multi‐Metal‐Modified Electrodes For Vanillin Electrogeneration via Pulse Electrolysis To High‐Throughput Screening of Multi‐Metal Composites
Authors: Brix Ann Cathrin , Krysiak Olga A. , Cechanaviciutè Ieva A. , Bjelovučić Gal , Banko Lars , Ludwig Alfred , Schuhmann Wolfgang
Published: December 2023

The production of green hydrogen may be greatly aided by the use of an alternative anode reaction replacing oxygen evolution to increase energy efficiency and concomitantly generate value‐added products. Lignin, a major component of plant matter, is accumulated in large amounts in the pulp and paper industry as waste. It has excellent potential as a source of aromatic compounds and can be transformed into the much more valuable aroma chemical vanillin by electrochemical depolymerisation. We used a flow‐through model electrolyser to evaluate electrocatalyst‐modified Ni foam electrodes prepared by a scalable spray‐polymer preparation method for oxidative lignin depolymerisation. We demonstrate how pulsing, i. e. continuously cycling between a lower and a higher applied current, increases the amount of formed vanillin while improving the energy efficiency. Further, we present a scanning droplet cell‐assisted high‐throughput screening approach to discover suitable catalyst materials for lignin electrooxidation considering that a suitable electrocatalyst should exhibit high activity for lignin depolymerization and simultaneously a low activity for vanillin oxidation and oxygen evolution. Combining electrosynthesis and electrocatalysis can aid in developing new customised materials for electrochemical processes of potential industrial interest.
Objective Review on Commercially Viable Prelithiation Techniques for Lithium‐ion Batteries
Authors: Lau Victor , Kuo Chih‐ying , Lan Chung‐wen
Published: December 2023

The rapid increase in global energy storage demands has necessitated the adoption of next‐generation lithium‐ion battery anode materials. However, these anode materials′ high lithium loss and poor cycling stability hinder their commercial application. The emergence of prelithiation offers a promising strategy for improving the lithium utilization efficiency of these active materials, thereby providing a solution for the performance bottleneck of next‐generation anode materials. The current review compiled and systematically discusses recent and notable prelithiation techniques concerning its potential for commercialization. The challenges currently hindering easy commercial adoption of the various prelithiation techniques and the potential development direction of each technique are analyzed. The commercial potential of the prelithiation methods is discussed based on the following four main criteria: electrochemical performance, ambient stability, cost, and industrial scalability. Finally, insights regarding further development of each prelithiation technique are provided, considering their unique advantages and disadvantages. The current review allows the industry and researchers to compare the commercial potential of various prelithiation techniques while considering their specific circumstances.
Giant Star‐shaped meso‐substituted Fluorescent Porphyrins with Fluorenyl‐containing Arms Designed for Two‐photon Oxygen Photosensitization
Authors: Shi Limiao , Sun Zhipeng , Richy Nicolas , Blanchard‐Desce Mireille , Mongin Olivier , Paul Frédéric , Paul‐Roth Christine O.
Published: December 2023

In the continuation of previous studies on carbon‐rich meso‐tetraarylporphyrins featuring 2,7‐fluorene units at their periphery, the effect of changing the peripheral dendritic arms for linear arms on their oxygen‐photosensitizing ability, their fluorescence and their two‐photon absorption (2PA) properties is now analyzed. Thus, starburst porphyrins possessing up to twenty conjugated fluorenyl units were isolated and studied. More precisely, a series of five new free‐base porphyrins featuring fully conjugated arms incorporating an increasing number of fluorenyl groups connected via 1,2‐alkenyl spacers were synthesized, along with their Zn(II) complexes. Upon excitation in the arm‐centred π‐π* absorption band, an efficient energy transfer takes place from the peripheral fluorenyl units to the central porphyrin core, leading to intense red‐light emission and oxygen photosensitization by the latter. More interestingly, while the linear optical properties of these porphyrins were only slightly improved compared to those of their dendrimer analogues for photodynamic therapy (PDT) or fluorescence imaging, their 2PA cross‐sections were much more significantly boosted, evidencing the key role played by different structures on nonlinear optical properties. Finally, by comparison with other porphyrin‐based two‐photon photosensitizers reported in the literature, we show that these new “semi‐disconnected” starburst systems exhibit a remarkable trade‐off between intrinsic 2PA, fluorescence and oxygen photosensitization.
Metal‐Free Visible‐Light Induced Oxidative Cleavage of C(sp3)−C, and C(sp3)−N Bonds of Nitriles, Alcohols, and Amines
Authors: Borthakur Ishani , Joshi Abhisek , Kumari Saloni , Kundu Sabuj
Published: December 2023

Selective cleavage of unstrained (sp3) C−C/ C−N bonds under mild conditions is highly challenging due to the higher bond dissociation energy. A visible light mediated metal‐free oxidative dehomologation of aryl acetonitriles, primary alcohols and diols to carboxylic acids via organophotocatalyzed C(sp3)−CN, C(sp3)−C(OH) bond cleavage is reported. Notably, this methodology was further extended towards selective synthesis of aldehydes via deamination of both primary as well as secondary amines. This mild protocol features wide array of substrate variation with excellent functional group tolerance, preparative‐scale synthesis, and operational simplicity. Possible mechanisms for these transformations were demonstrated through a series of control experiments.
Synthesis of β‐Amino Acid Derivatives via Enantioselective Lewis Base Catalyzed N‐Allylation of Halogenated Amides with Morita‐Baylis‐Hillman Carbonates
Authors: Nosovska Olena , Liebing Phil , Vilotijevic Ivan
Published: December 2023

Trifluoro‐ and trichloroacetamides serving as pronucleophiles undergo enantioselective Lewis base catalyzed N‐allylation with Morita‐Baylis‐Hillman carbonates to produce enantioenriched β‐amino acid derivatives. The reactions proceed as a kinetic resolution to give the allylation products and the remaining carbonates in good yields and high enantioselectivity. The obtained products are amenable to diastereoselective derivatization to produce a library of spiro‐isoxazoline lactams.
More Electropositive is More Electronegative: Atom Size Determines C=X Group Electronegativity
Authors: Nieuwland Celine , Verdijk Ron , Fonseca Guerra Célia , Bickelhaupt F. Matthias
Published: December 2023

Opposite to what one might expect, we find that the C=X group can become effectively more, not less, electronegative when the Pauling electronegativity of atom X decreases down Groups 16, 15, and 14 of the Periodic Table. Our quantum‐chemical analyses, show that, and why, this phenomenon is a direct consequence of the increasing size of atom X down a group. These findings can be applied to tuning and improving the hydrogen‐bond donor strength of amides H2NC(=X)R by increasingly withdrawing density from the NH2 group. A striking example is that H2NC(=SiR2)R is a stronger hydrogen‐bond donor than H2NC(=CR2)R.
A robust model training strategy using hard negative mining in a weakly labeled dataset for lymphatic invasion in gastric cancer
Authors: Lee Jonghyun , Ahn Sangjeong , Kim Hyun‐Soo , An Jungsuk , Sim Jongmin
Published: December 2023

Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time‐consuming, labor‐intensive, and prone to intra‐ and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four‐step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.
The blockchain conundrum: An in‐depth examination of challenges, contributing technologies, and alternatives
Authors: Reshi Iraq Ahmad , Sholla Sahil
Published: December 2023

The accelerated development of information and communication technologies has generated a demand for data storage that is effective, transparent, immutable, and secure. Distributed ledger technology and encryption techniques such as hashing and blockchain technology revolutionised the landscape by meeting these requirements. However, blockchain must overcome obstacles such as low latency, throughput, and scalability for its full potential. Investigating blockchain's structure, types, challenges, promises, and variants is necessary to understand blockchain and its capabilities comprehensively. This paper overviews various aspects, such as emergent blockchain protocols, models, concepts, and trends. We classify blockchain variants into five essential categories, DAG, TDAG, Sharding, Consensus, and Combining methods, based on the structure each follows, and conduct a comparative analysis. In addition, we explore current research tendencies. As technology progresses, it is essential to comprehend the fundamental requirements for blockchain development.
Oxygen‐Mediated Surface Photoreactions: Exploring New Pathways for Sustainable Chemistry
Authors: Alessandri Ivano , Vassalini Irene
Published: December 2023

The Front Cover image illustrates the exploitation of photoactivated oxygen species for sustainable chemistry applications. Recent works that take advantage of oxygen‐mediated surface photoreactions for addressing key issues in the fields of sustainable chemistry, circular production of feedstocks, and environmental remediation are reviewed. Read the full text of the Concept at 10.1002/cptc.202300069.
Single‐cell immune profiling reveals markers of emergency myelopoiesis that distinguish severe from mild respiratory syncytial virus disease in infants
Authors: Zivanovic Nevena , Öner Deniz , Abraham Yann , McGinley Joseph , Drysdale Simon B. , Wildenbeest Joanne G. , Crabbe Marjolein , Vanhoof Greet , Thys Kim , Thwaites Ryan S. , Robinson Hannah , Bont Louis , Openshaw Peter J. M. , Martinón‐Torres Federico ,   RESCEU Investigators, Pollard Andrew J. , Aerssens Jeroen
Published: December 2023

Whereas most infants infected with respiratory syncytial virus (RSV) show no or only mild symptoms, an estimated 3 million children under five are hospitalized annually due to RSV disease. This study aimed to investigate biological mechanisms and associated biomarkers underlying RSV disease heterogeneity in young infants, enabling the potential to objectively categorize RSV‐infected infants according to their medical needs. Immunophenotypic and functional profiling demonstrated the emergence of immature and progenitor‐like neutrophils, proliferative monocytes (HLA‐DRLow, Ki67+), impaired antigen‐presenting function, downregulation of T cell response and low abundance of HLA‐DRLow B cells in severe RSV disease. HLA‐DRLow monocytes were found as a hallmark of RSV‐infected infants requiring hospitalization. Complementary transcriptomics identified genes associated with disease severity and pointed to the emergency myelopoiesis response. These results shed new light on mechanisms underlying the pathogenesis and development of severe RSV disease and identified potential new candidate biomarkers for patient stratification.
Quantitative disease resistance in wild Silene vulgaris to its endemic pathogen Microbotryum silenes‐inflatae
Authors: Hood Michael E. , Nelson Sydney , Cho Jae‐Hoon , Launi Michelle , Antonovics Janis , Bruns Emily L.
Published: December 2023

The evolution of disease resistances is an expected feature of plant–pathogen systems, but whether the genetics of this trait most often produces qualitative or quantitative phenotypic variation is a significant gap in our understanding of natural populations. These two forms of resistance variation are often associated with differences in number of underlying loci, the specificities of host–pathogen coevolution, as well as contrasting mechanisms of preventing or slowing the infection process. Anther‐smut disease is a commonly studied model for disease of wild species, where infection has severe fitness impacts, and prior studies have suggested resistance variation in several host species. However, because the outcome of exposing the individual host to this pathogen is binary (healthy or diseased), resistance has been previously measured at the family level, as the proportion of siblings that become diseased. This leaves uncertain whether among‐family variation reflects contrasting ratios of segregating discrete phenotypes or continuous trait variation among individuals. In the host Silene vulgaris, plants were replicated by vegetative propagation in order to quantify the infection rates of the individual genotype with the endemic anther‐smut pathogen, Microbotryum silenes‐inflatae. The variance among field‐collected families for disease resistance was significant, while there was unimodal continuous variation in resistance among genotypes. Using crosses between genotypes within ranked resistance quartiles, the offspring infection rate was predicted by the parental resistance values. While the potential remains in this system for resistance genes having major effects, as there were suggestions of such qualitative resistance in a prior study, here the quantitative disease resistance to the endemic anther‐smut pathogen is indicated for S. vulgaris. The variation in natural populations and strong heritability of the trait, combined with severe fitness consequences of anther‐smut disease, suggests that resistance in these host populations is highly capable of responding to disease‐induced selection.
Revisiting the species list of freshwater fish in Israel based on DNA barcoding
Authors: Tadmor‐Levi Roni , Feldstein‐Farkash Tamar , Milstein Dana , Golani Daniel , Leader Noam , Goren Menachem , David Lior
Published: December 2023

Israel's region forms a continental bridge; hence, the freshwater fish fauna in Israel consists of unique populations of species that originated from Africa, Asia, or Europe and are often endemic or at the edge of their distribution range. Worldwide, fish biodiversity suffers significantly from pressures and disturbances of freshwater habitats, especially in arid regions, such as in parts of Israel. Biodiversity conservation requires efficient tools for monitoring changes in populations. DNA barcoding, by complementing and enhancing species identification, provides such monitoring tools. In this study, over 200 specimens representing over 28 species were DNA barcoded and together with previously available records, a DNA barcoding database for freshwater fish of Israel was established. Of the 71 distinct barcodes generated, 37% were new, attesting to the uniqueness of fish populations in Israel. For most species, morphological and molecular species identifications agreed. However, discrepancies were found for five genera. Based on DNA barcoding, we propose Acanthobrama telavivensis as a junior synonym for Acanthobrama lissneri. In Garra spp., we propose splitting Garra nana into two species and assigning Garra rufa in the region to Garra jordanica, or possibly to two species. Israeli Pseudophoxinus kervillei is not the same species as in Syria and Lebanon. However, Pseudophoxinus syriacus might not be endangered since it is genetically very similar to Pseudophoxinus drusensis. In Israel, instead of five reported Oxynoemacheilus species, combining DNA barcoding with morphology suggests only three. Genetic and geographic separation suggested that Aphanius mento is likely a species complex. The study provides a thorough barcoding database, suggests significant species reconsiderations in the region, and highlights the Sea of Galilee and the Beit She'an valley streams as biodiversity “hotspots.” This study will therefore promote further studying of the fish species in the region and their ecology, as well as the monitoring and conservation of freshwater fish biodiversity in Israel and the region.
Species‐ and origin‐specific susceptibility to bird predation among juvenile salmonids
Authors: Säterberg Torbjörn , Jacobson Philip , Ovegård Maria , Rask Jörgen , Östergren Johan , Jepsen Niels , Florin Ann‐Britt
Published: December 2023

Juvenile salmonids often experience high mortality rates during migration and bird predation is a common source of mortality. Research suggests that hatchery‐reared salmonids are more prone to predation than wild salmonids, and that Atlantic salmon (Salmo salar) experience lower predation than Sea trout (Salmo trutta), yet telemetry studies have displayed equivocal results. Here, using a large data set on passive integrated transponder (PIT) tagged hatchery‐reared and wild juveniles of Atlantic salmon and Sea trout (25,769 individuals) we investigate predation probability by piscivorous birds (mainly Great Cormorants Phalarocorax carbo) on salmonids originating from River Dalälven in Sweden. Bird colonies and roosting sites were scanned annually (2019–2021), and the temporal dynamics of bird predation on salmonids released in 2017–2021 was assessed. Hatchery‐reared trout was clearly most susceptible to cormorant predation (0.31, 90% credibility interval [CRI] = 0.14–0.53), followed by wild trout (0.19, 90% CRI = 0.08–0.37), hatchery‐reared salmon (0.13, 90% CRI = 0.07–0.23), and wild salmon (0.08, 90% CRI = 0.04–0.14), in subsequent order. This order in predation probability was consistent across all studied tag‐ and release‐years, suggesting that the opportunistic foraging of cormorants affects the overall survival of juvenile salmonids, but that the inherent predation risk between different salmonid types differs systematically.