bluuebunny/crossref_metadata_2025 huggingface dataset:
Manipulating Electron Redistribution in Ni2P for Enhanced Alkaline Seawater Electrolysis
Authors: Liu Xiaobin , Yu Qingping , Qu Xinyue , Wang Xinping , Chi Jingqi , Wang Lei
Published: September 2023

Developing bifunctional electrocatalyst for seawater splitting remains a persistent challenge. Herein, an approach is proposed through density functional theory (DFT) preanalysis to manipulate electron redistribution in Ni2P addressed by cation doping and vacancy engineering. The needle‐like Fe‐doped Ni2P with P vacancy (Fe‐Ni2Pv) is successfully synthesized on nickel foam, exhibiting a superior bifunctional hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) catalytic activity for seawater electrolysis in alkaline condition. As a result, bifunctional Fe‐Ni2Pv achieves the industrially required current densities of 1.0 and 3.0 A cm−2 at low voltages of 1.68 and 1.73 V, respectively, for seawater splitting at 60 °C in 6.0 m KOH circumstances. The theoretical calculation and the experimental results collectively reveal the reasons for the enhancement of catalyst activity. Specifically, Fe doping and P vacancies can accelerate the reconstruction of OER active species and optimize the hydrogen adsorption free energy (ΔGH*) for HER. In addition, the active sites of Fe‐Ni2Pv are identified, where P vacancies greatly improve the electrical conductivity and Ni sites are the dominant OER active centers, meanwhile Fe atoms as active centers for the HER. The study provides a deep insight into the exploration for the enhancement of activity of nickel‐based phosphide catalysts and the identification of their real active centers.
Enantioselective Regulation of Short‐Chain Dehydrogenases via Key Sites in its Loop and Adjacent Regions for the Enantiodivergent Reduction of Difficult‐To‐Reduce Ketones
Authors: Qin Lei , Su Xin , Wang Jun , Wu Lunjie , Zou Man , Gu Jie , Xu Yan , Nie Yao
Published: September 2023

Short‐chain dehydrogenases (SDRs) are powerful catalysts for the asymmetric reduction of prochiral ketones in pharmaceutical products. Herein, through gene mining and evolutionary analysis, we obtained two major types of SDRs (SDR‐1 and SDR‐2) for the enantioselective complementary reduction of N‐Boc‐piperidone, which gives the corresponding product (R)‐ or (S)‐N‐Boc‐piperidol, an intermediate of the interleukin inhibitor and lymphoma treatment drug (imbruvica), respectively. By integrating multiple sequence alignment, site‐directed mutagenesis and computational modeling, we proposed a “loop regulation” mechanism for the enantioselective control of SDRs, through which residues in the loop region could potentially fine‐tune their enantioselectivity. Further, site‐directed mutagenesis assays showed that two key residues (L201 and F205 for SDR‐1, F92 and H93 for SDR‐2) in the loop and its adjacent region played critical roles in fine‐tuning the enantioselectivity of SDRs. Understanding this mechanism of SDR stereo preference in catalyzing asymmetric reduction, we further switched the enantioselectivity of the homologous enzymes. The obtained enzymes catalyzed the enantiodivergent synthesis of chiral heterocyclic alcohols with different ring sizes and substituents (25–99% conversion and 25–99% ee (R/S)), including piperidols, 4‐hydroxy azepanes, 3‐hydroxy azepanes and pyrrolidinols. These findings could potentially guide future attempts at protein engineering of stereoselective SDRs.
Triple Cross‐linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K/Akt/NF‐κB and MAPK Signaling Pathways
Authors: Wang Shuangqing , Liu Yanhong , Sun Qianwen , Zeng Bowen , Liu Chao , Gong Liming , Wu Hao , Chen Liqing , Jin Mingji , Guo Jianpeng , Gao Zhonggao , Huang Wei
Published: September 2023

Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application.
Direct Ink Writing 3D Printing for High‐Performance Electrochemical Energy Storage Devices: A Minireview
Authors: Zeng Li , Ling Shangwen , Du Dayue , He Hanna , Li Xiaolong , Zhang Chuhong
Published: September 2023

Despite tremendous efforts that have been dedicated to high‐performance electrochemical energy storage devices (EESDs), traditional electrode fabrication processes still face the daunting challenge of limited energy/power density or compromised mechanical compliance. 3D thick electrodes can maximize the utilization of z‐axis space to enhance the energy density of EESDs but still suffer from limitations in terms of poor mechanical stability and sluggish electron/ion transport. Direct ink writing (DIW), an eminent branch of 3D printing technology, has gained popularity in the manufacture of 3D electrodes with intricately designed architectures and rationally regulated porosity, promoting a triple boost in areal mass loading, ion diffusion kinetics, and mechanical flexibility. This focus review highlights the fundamentals of printable inks and typical configurations of 3D‐printed devices. In particular, preparation strategies for high‐performance and multifunctional 3D‐printed EESDs are systemically discussed and classified according to performance evaluation metrics such as high areal energy density, high power density, high volumetric energy density, and mechanical flexibility. Challenges and prospects for the fabrication of high‐performance 3D‐printed EESDs are outlined, aiming to provide valuable insights into this thriving field.
Paper‐Based Hydroelectric Generators for Water Evaporation‐Induced Electricity Generation
Authors: Zhang Jingjing , Cui Peng , Wang Jingjing , Meng Huan , Ge Ying , Feng Can , Liu Huimin , Meng Yao , Zhou Zunkang , Xuan Ningning , Zhang Bao , Cheng Gang , Du Zuliang
Published: September 2023

The research presented in this paper introduces a novel environmental energy‐harvesting technology that harnesses electricity from the evaporation of water using porous structural materials. Specifically, a strategy employing paper‐based hydroelectric generators (p‐HEGs) is proposed to capture the energy produced during water evaporation and convert it into usable electricity. The p‐HEGs offer several advantages, including simplicity in fabrication, low cost, and reusability. To evaluate their effectiveness, the water evaporation‐induced electrical output performance of four different p‐HEGs are compared. Among the variants tested, the p‐HEG combining wood pulp and polyester fiber exhibits the best output performance. At room temperature, this particular p‐HEG generates a short‐circuit current and open‐circuit voltage of ≈0.4 µA and 0.3 V, respectively, thereby demonstrating excellent electrical stability. Furthermore, the electrical current and voltage generated by the p‐HEG through water evaporation are able to power an LED light, both individually and in series and parallel connections. This study delves into the potential of electricity harvesting from water evaporation and establishes it as a viable method for renewable energy applications.
Analysis of 60 patients with relapsed or refractory T‐cell acute lymphoblastic leukemia and T‐cell lymphoblastic lymphoma treated with CD7‐targeted chimeric antigen receptor‐T cell therapy
Authors: Zhang Xian , Yang Junfang , Li Jingjing , Qiu Liyuan , Zhang Jianping , Lu Yue , Zhao Yan‐li , Jin David , Li Jianqiang , Lu Peihua
Published: September 2023

While the use of chimeric antigen receptor‐T (CAR‐T) therapy for T‐cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long‐term remission for patients with refractory/relapsed (R/R) T‐cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T‐ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T‐ALL 35, T‐LBL 25) received a single dose of naturally selected anti‐CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105/kg), a medium dose (1 to 1.5 × 106/kg), and a high dose (2 × 106/kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2‐year overall survival and progression‐free survival (PFS) were 63.5% (95% CI 47.7–79.4) and 53.7% (95% CI, 38.9–68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1‐year PFS 67.2% (95% CI 51.9–82.4) versus 15.0% (95% CI 0–40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR‐T therapy is effective in treating R/R T‐ALL/LBL patients with promising PFS while maintaining a manageable safety profile.
Men's household water fetching in India: Gender inequity is associated with greater responsibility and related risks
Authors: Brewis Alexandra , Choudhary Neetu , Wutich Amber
Published: September 2023

Introduction

Household water fetching elevates physical and emotional harms, and these are generally assumed to accrue to women due to gendered labor assignments. But even in cases like India where fetching remains a highly feminized task, there are households where the primary responsibility is assumed by men.

Methods

We test the proposition that men's responsibility for water fetching is predicted by greater gender equity, reflected in measures of wives' empowerment. We used an extremely large, nationally representative Demographic and Health Survey dataset from India (2019–2020), narrowed to only households in which spouses co‐reside with off‐plot water sources (N = 10 616), and applying a multinomial regression approach.

Results

In >20% of households, men are the primary fetchers. They are more likely to have primary responsibility when water is more distant, privately purchased, or transported by vehicle. Contrary to predictions, men assume greater responsibility for household water fetching as their wives' empowerment measuresdecreaseand when they want to control their movement.

Conclusion

Married men in India sometimes assume responsibility for water fetching, but this is not explained by greater household gender equity. The findings also suggest that when men are responsible for fetching they have heightened risk of some forms of physical trauma but less relative psychological harm. Detailing why men fetch water matters for identifying and mitigating the physical and emotion harms of bearing responsibility for water labor, with implications for how gender should be conceptualized in water interventions intending to improve health and well‐being.
Synthesis and characterization of biodegradable and photocrosslinkable multi‐block poly(ether‐ester): Molecular‐weight and component of the polyethylene glycol segment dependence
Authors: Cai Chaoyi , Chen Zhifan , Ye Shufen , Zhang Rong , Pan Xiaodi , Yang Rong , Li Jinchun
Published: September 2023

This work synthesized a series of biodegradable thermoplastic elastomer PBSFG via an esterification polycondensation reaction. The influence of the soft segment PEG molecular weight and component on the thermal behavior, mechanical property, and degradation performance of PBSFG were investigated. The results showed that the PEG component plays a major part in the properties of PBSFG. Upon reaching a PEG component concentration of 40% within PBSFG, the yielding phenomenon becomes imperceptible on the stress–strain curves, signifying the onset of a plastic‐to‐elastomer transition. In the case of PBSFG40‐6k, a remarkable tensile strength of 23.5 MPa and an elongation at break measuring 576% were achieved, thereby displaying tensile properties on par with those of PBAT. Thanks to the unsaturated structure, the mechanical properties of PBSFG can be enhanced by UV irradiation. Finally, Candida cylindracea lipase catalytic degradation experiments showed that PBSFG is a biodegradable polyester, which is beneficial in reducing environmental plastic pollution.
Low‐cost and high‐performance poly(butylene adipate‐co‐terephthalate)/thermoplastic starch blends prepared by an eccentric rotor extruder: Morphology, rheological behavior, thermal and mechanical properties
Authors: Xu Mohong , Li Fengqing , Yan Xiangyu , Li Jiqian , Jia Ligeng , Liu Zhigang , He Hezhi , Li Yi , Zhu Zhiwen
Published: September 2023

Due to similar processing and mechanical properties, poly(butylene adipate‐co‐terephthalate) (PBAT) is expected to be a fully‐biodegradable alternative to low‐density polyethylene (LDPE) packaging films, thereby alleviating environmental pollution caused by waste packaging films. However, the higher price of PBAT limits its large‐scale practical application in the packaging field. Blending with thermoplastic starch (TPS) to prepare PBAT/TPS blends can reduce the cost. In this work, the PBAT/TPS blends with different compositions were prepared using a novel eccentric rotor extruder dominated by an extensional flow field. With increasing the TPS content, a transition from the sea‐island phase structure to the bicontinuous phase structure occurred near the composition ratio of 50/50. Moreover, the dynamic mechanical analysis results showed that the compatibility between PBAT and TPS first improved and then deteriorated as the TPS content increased. As a result, the elongation at break first decreased slightly from ~1585% for the PBAT/TPS(90/10) blend to ~1263% for the PBAT/TPS(70/30) blend and dropped sharply to ~130% for the PBAT/TPS(40/60) blend. The knowledge obtained from this study will help us further understand the effect of the TPS phase on the micro‐morphology and macro‐properties of the PBAT/TPS blends, which is important for the future preparation of high‐performance PBAT/TPS blends.
Anisotropic properties of additively manufactured concrete elements
Authors: Lindner Marco , Gliniorz Ralf , Funke Henrik , Gelbrich Sandra
Published: September 2023

Robotic concrete extrusion is a novel additive manufacturing process (three‐dimensional concrete printing) and is part of a continuously digitally controlled value chain. According to the state of the art, concrete is considered to be an isotropic material due to the manufacturing process. However, for the additive manufacturing process, the isotropic approach has to be reconsidered due to the layered structure. It can be assumed that due to the layered structure, the material properties vary depending on the deposition direction and the geometry of the layers. The aim of the work was to record the material‐technical characteristics of extruded elements manufactured according to standards in comparison with concrete recipes. Process‐related influences on the mechanical parameters of additively manufactured concrete elements were examined and evaluated in more detail. Based on the findings obtained, the dimensioning, design and measurement of components can be carried out and thus guidelines for components can be derived. With these derived guidelines, the material utilization and economic efficiency can be improved.
Are people with autism prosopagnosic?
Authors: Kamensek Todd , Susilo Tirta , Iarocci Grace , Oruc Ipek
Published: September 2023

Difficulties in various face processing tasks have been well documented in autism spectrum disorder (ASD). Several meta‐analyses and numerous case–control studies have indicated that this population experiences a moderate degree of impairment, with a small percentage of studies failing to detect any impairment. One possible account of this mixed pattern of findings is heterogeneity in face processing abilities stemming from the presence of a subpopulation of prosopagnosic individuals with ASD alongside those with normal face processing skills. Samples randomly drawn from such a population, especially relatively smaller ones, would vary in the proportion of participants with prosopagnosia, resulting in a wide range of group‐level deficits from mild (or none) to severe across studies. We test this prosopagnosic subpopulation hypothesis by examining three groups of participants: adults with ASD, adults with developmental prosopagnosia (DP), and a comparison group. Our results show that the prosopagnosic subpopulation hypothesis does not account for the face impairments in the broader autism spectrum. ASD observers show a continuous and graded, rather than categorical, heterogeneity that span a range of face processing skills including many with mild to moderate deficits, inconsistent with a prosopagnosic subtype account. We suggest that pathogenic origins of face deficits for at least some with ASD differ from those of DP.
CITIES: Clinical trials with intercurrent events simulator
Authors: Wahab Ahmad Hakeem Abdul , Qu Yongming , Michiels Hege , Luo Junxiang , Zhuang Run , McDaniel Dominique , Xi Dong , Polverejan Elena , Gilbert Steven , Ruberg Stephen , Sabbaghi Arman
Published: September 2023

Although clinical trials are often designed with randomization and well‐controlled protocols, complications will inevitably arise in the presence of intercurrent events (ICEs) such as treatment discontinuation. These can lead to missing outcome data and possibly confounding causal inference when the missingness is a function of a latent stratification of patients defined by intermediate outcomes. The pharmaceutical industry has been focused on developing new methods that can yield pertinent causal inferences in trials with ICEs. However, it is difficult to compare the properties of different methods developed in this endeavor as real‐life clinical trial data cannot be easily shared to provide benchmark data sets. Furthermore, different methods consider distinct assumptions for the underlying data‐generating mechanisms, and simulation studies often are customized to specific situations or methods. We develop a novel, general simulation model and corresponding Shiny application in R for clinical trials with ICEs, aptly named the Clinical Trials with Intercurrent Events Simulator (CITIES). It is formulated under the Rubin Causal Model where the considered treatment effects account for ICEs in clinical trials with repeated measures. CITIES facilitates the effective generation of data that resemble real‐life clinical trials with respect to their reported summary statistics, without requiring the use of the original trial data. We illustrate the utility of CITIES via two case studies involving real‐life clinical trials that demonstrate how CITIES provides a comprehensive tool for practitioners in the pharmaceutical industry to compare methods for the analysis of clinical trials with ICEs on identical, benchmark settings that resemble real‐life trials.
A joint Bayesian framework for missing data and measurement error using integrated nested Laplace approximations
Authors: Skarstein Emma , Martino Sara , Muff Stefanie
Published: September 2023

Measurement error (ME) and missing values in covariates are often unavoidable in disciplines that deal with data, and both problems have separately received considerable attention during the past decades. However, while most researchers are familiar with methods for treating missing data, accounting for ME in covariates of regression models is less common. In addition, ME and missing data are typically treated as two separate problems, despite practical and theoretical similarities. Here, we exploit the fact that missing data in a continuous covariate is an extreme case of classical ME, allowing us to use existing methodology that accounts for ME via a Bayesian framework that employs integrated nested Laplace approximations (INLA) and thus to simultaneously account for both ME and missing data in the same covariate. As a useful by‐product, we present an approach to handle missing data in INLA since this corresponds to the special case when no ME is present. In addition, we show how to account for Berkson ME in the same framework. In its broadest generality, the proposed joint Bayesian framework can thus account for Berkson ME, classical ME, and missing data, or any combination of these in the same or different continuous covariates of the family of regression models that are feasible with INLA. The approach is exemplified using both simulated and real data. We provide extensive and fully reproducible Supporting Information with thoroughly documented examples using R‐INLA and inlabru.
Sensitive spectrofluorimetric determination of the prokinetic drug prucalopride succinate based on supramolecular aggregation approach with evaluation of method greenness: application to content uniformity test
Authors: Derayea Sayed M. , Mohammed Fatma F. , Badr El‐Din Khalid M.
Published: September 2023

The prokinetic drug, prucalopride (PCP) succinate, was determined using a new spectrofluorimetric approach with a highly sensitive, rapid, and simple procedure. The method exploited the enhancement of the inherent native fluorescence of PCP by micellar aggregation with sodium lauryl sulfate (SLS) as an anionic surfactant. Different factors that could affect the fluorescence intensity were carefully studied in order to achieve the maximal fluorescence signal. Measurement of the enhanced fluorescence was done at 354 nm after the excitation at 276 nm. The fluorescence intensity–concentration plot was rectilinear in the concentration range of 50–600 ng/ml with detection and quantitation limits of 13.9 and 42.1 ng/ml, respectively. The method underwent validation according to the International Council for Harmonisation criteria in order to assess its analytical performance, and promising results were achieved that proved the validity and reliability of the method. Furthermore, the method was employed effectively for the analysis of the cited drug in commercial pharmaceutical tablets.
Identification of an Alepterolic Acid Derivative as a Potent Anti‐Breast‐Cancer Agent via Inhibition of the Akt/p70S6K Signaling Pathway
Authors: Wang Nina , Zhang Lei , Yu Junjie , Chang Kaili , Fan Minghui , Liu Zi , Ma Liang , Cao Jianguo , Huang Guozheng
Published: September 2023

Alepterolic acid is a diterpene occurring in the fern Aleuritopteris argentea with potential biological activity that warrants further structural modification. In the present work, sixteen alepterolic acid derivatives were synthesized and evaluated for their anticancer activities. Among them, N‐[m‐(trifluoromethoxy)phenyl] alepterolamide displayed comparable activity (IC50=4.20±0.21 μM) in MCF‐7 cells. Moreover, mechanistic investigations indicated this compound was significantly capable of diminishing cell proliferation and viability of MCF‐7 cells. After treatment with N‐[m‐(trifluoromethoxy)phenyl] alepterolamide, a significant increase in cleaved caspase‐9, cleaved caspase‐3, cleaved poly (ADP‐ribose) polymerase (PARP) and Bax/Bcl2 ratio were observed in MCF‐7 cells, leading to caspase‐dependent apoptotic pathways. Further studies showed this compound promoted cellular apoptosis and inhibited migration in MCF‐7 cells via modulation of the Akt/p70S6K signaling pathway. All these results revealed the potential of N‐[m‐(trifluoromethoxy)phenyl] alepterolamide as an appealing therapeutic drug candidate for breast cancer.
Noninvasive diagnosis of Ascaris lumbricoides in the common bile duct: A pediatric case report of acute pancreatitis
Authors: Samir Komal , Subash Tushar , Subash Arun , Bilal Hammad , Shah Hussain Haider , Dave Tirth
Published: September 2023

Key Clinical Message

This case report highlights the importance of considering parasitic infections, particularly Ascaris lumbricoides, as a possible cause of acute pancreatitis in children, especially in endemic regions. Noninvasive imaging techniques, such as ultrasonography, can play a crucial role in the early detection and diagnosis of this unusual presentation. Timely administration of anthelmintic therapy led to the resolution of symptoms and prevented the need for invasive procedures. Healthcare providers should be vigilant about the diverse clinical manifestations of ascariasis, and regular deworming programs and health education are essential in minimizing the burden of this neglected tropical disease among children.

Ascariasis is a common public health problem globally but it is more prevalent in school‐age children and it often goes undiagnosed, leading to severe complications. The purpose of this report is to spread awareness of its unusual presentation and how to judiciously use noninvasive approaches for its diagnosis. We present a case of a 10‐year‐old girl that was presented in pediatric emergency with gradually worsening epigastric pain. Initial lab work‐up showed elevated pancreatic enzymes which lead to the diagnosis of acute pancreatitis. The patient was managed in the line of acute pancreatitis and with further evaluation by imaging techniques such as ultrasound and CT‐scan abdomen, Ascaris lumbricoides (A. lumbricoides) was visualized. She was then treated with prophylactic antibiotics and antiparasitic medications, which resolved her symptoms and the child responded to the treatment. In children, parasites should be considered as a cause of acute pancreatitis by clinicians, especially in low‐income countries, and before performing invasive procedures, noninvasive approaches should be considered as an initial option. This can save the patient from multiple invasive procedure and its severe complications.
Charge Transfer in Be−Ru Compounds
Authors: Agnarelli Laura , Prots Yurii , Krnel Mitja , Svanidze Eteri , König Markus , Schmidt Marcus , Burkhardt Ulrich , Leithe‐Jasper Andreas , Grin Yuri
Published: September 2023

During the investigation of the binary system Be−Ru two new phases – Be7Ru4and Be12Ru7– with similar compositions (63.6 at. % Be and 63.2 at. % Be, respectively), are discovered. They both represent new structural prototypes. The phases are located between Be2Ru (Fe2P‐type structure) and Be3Ru2(U3Si2‐type structure) in the phase diagram. This explains why their crystal structures, solved and refined from single crystal X‐ray diffraction data, are described as 2D intergrowth of Fe2P and U3Si2motives. The calculated electronic density of stats (DOS) reveals pronounced minima in the vicinity of the Fermi level for both compounds. Position‐space analysis of chemical bonding exhibits the formation of three‐ and four‐atomic polar bonds, involving both, Ru and Be, atoms, and a strong charge transfer from Be to the more electronegative Ru.
Intramolecular Electron Transfer in Multi‐Redox Systems Based on Cyclic [3]Spirobifluorenylene Compound**
Authors: Imai Tomoya , Sakamaki Daisuke , Aoyagi Shinobu , Amaya Toru
Published: September 2023

Cyclic [3]spirobifluorenylene with bulky alkyl groups at the ends (1) was designed and synthesized to investigate the electron transfer phenomena in a π‐conjugated system including orthogonal π‐conjugated chains. The three bifluorenyl units in 1 are conjugated to each other via spiro‐conjugation, resulting in the splitting of the HOMO levels to a small extent. Therefore, the SOMO‐HOMO gap of the radical cation species is small, which is considered to allow the facile intramolecular electron transfer. The electronic properties of 1 and its partial structures were characterized by absorption and fluorescence measurements and electrochemical analysis. From the electrochemical oxidation, the interchain Coulombic repulsion was observed. In the TD‐DFT calculations for the radical cation species of 1, the geometry‐featured interchain electronic transitions were visualized by NTO calculations. The radical cation species of 1 generated by chemical oxidation with SbCl5 exhibited a broadened and lower‐energy NIR absorption band exceeding 2000 nm. Considering the results of the TD‐DFT calculations, the NIR band of the radical cation of 1 was attributed to the intramolecular electron transfer processes among the bifluorenyl units in the macrocycle. ESR experiments also indicated the delocalization of a spin of 1⋅+ in the whole molecule via hole hopping in the ESR time scale at room temperature. This work demonstrates the usefulness of spiro‐conjugation as a bridging unit in molecular wires to facilitate smooth electron transfer.
Association of living alone with clinical outcomes in patients with heart failure: A systematic review and meta‐analysis
Authors: Chen Haibo , Liu Fuwei , Luo Jun , Tu Yating , Huang Shan , Zhu Wengen
Published: September 2023

Living alone is an objective sign of social isolation. It is uncertain whether living alone worsens clinical outcomes in heart failure (HF) patients. We aimed to assess how living alone affected clinical outcomes in individuals with HF. We searched the electronic databases of PubMed, Embase, and Cochrane from 1990 to April 2022 for studies comparing living alone with HF. A random‐effects model with inverse variance was used to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Seven studies were deemed to meet the standards. In patients with HF, compared with living with others, living alone was associated with an elevated risk of any hospitalization at the 30‐day (HR: 1.78, 95% CI: 1.09–2.89), 90‐day (HR: 1.24, 95% CI: 1.02–1.51), or ≥1‐year (HR: 1.14, 95% CI: 1.04–1.26) follow‐up periods. HF patients living alone also had a greater risk of any hospitalization or death at the 30‐day (HR: 1.56, 95% CI: 1.15–2.11), 90‐day (HR: 1.26, 95% CI: 1.05–1.50), and ≥1‐year (HR: 1.18, 95% CI: 1.09–1.28) follow‐up periods. However, patients living alone had no increased risk of all‐cause death at the 30‐day (HR: 1.0, 95% CI: 0.19–5.36), 90‐day (HR: 0.46, 95% CI: 0.03–7.42), or ≥ 1‐year (HR: 1.10, 95% CI: 0.73–1.67) follow‐up periods. In comparison to living with others, living alone was associated with an increased risk of any hospitalization but not all‐cause death in HF patients.
Fluorescent‐guided surgery and the use of indocyanine green sentinel lymph node mapping in the pediatric and young adult oncology population
Authors: Johnston Michael E. , Farooqui Zishaan A. , Nagarajan Rajaram , Pressey Joseph G. , Turpin Brian , Dasgupta Roshni
Published: September 2023

Background

Technetium‐99 (99mTc) lymphoscintigraphy with blue dye injection is an accepted method for sentinel lymph node (SLN) mapping, but blue dye has known adverse effects, and injection of 99mTc may increase time under anesthesia for pediatric patients. Indocyanine green (ICG) may serve as an adjunct to assist with visibility and identification of SLNs. We hypothesized that sensitivity of ICG was similar to blue dye in SLN biopsies.

Methods

Thirty patients (36 procedures with 96 total specimens) underwent preoperative intradermal injection of 99mTc, followed by intradermal injection of isosulfan blue and ICG. Test characteristics of blue dye, ICG, and 99mTc included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

ICG had a sensitivity of 87% and PPV of 83% for detection of 99mTc‐hot lymph nodes; blue dye had a sensitivity of 44% and PPV of 97%. For detection of pathologically confirmed lymph nodes, ICG had a sensitivity of 84% and a positive predictive value (PPV) of 91%. 99mTc had a sensitivity of 82% and a PPV of 94%. ICG had no significant difference in odds of being positive in pathology‐confirmed lymph nodes compared to 99mTc (odds ratio [OR], 0.818; 95% confidence interval [CI], 0.3–2.172; p = .823) and had higher odds than isosulfan blue (OR, 0.025, 95% CI, 0.001–0.148; p < .001).

Conclusion

This study established the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. ICG was safe, more efficacious than blue dye, and may obviate the need for lymphoscintigraphy in selected patients resulting in reduced time under anesthesia.
Glu‐derived Zwitterionic Micelles Conquering the Intestinal Mucosal Barrier toward Oral Delivery
Authors: Liu Kedong , Chen Yun , Yang Dutao , Cai Yanfei , Yang Zhaoqi , Jin Jian
Published: September 2023

Amino acid transporters with different categories are highly expressed in intestinal epithelial cells for maintaining the essential metabolism of body. The zwitterionic property of amino acid with α‐amino and α‐carboxyl also has tremendous potential to conquer the mucus barrier. Therefore, Glu‐derived amphiphilic block polymers [i. e., poly(lactic acid)‐b‐poly(glutamine)25 (PPQ) and poly(lactic acid)‐b‐poly(glutamate)25 (PPD)] were rational designed and Glu‐derived zwitterionic micelles (PPQ‐M and PPD‐M) were further prepared toward oral delivery. In comparison with PEGylated micelles (PEG‐M), PPD‐M and PPQ‐M possessed superior mucus permeability. In addition, enhanced cellular internalization capacity was also detected in both zwitterionic micelles, which was mainly mediated by multiple amino acid transporters. The cellular uptake efficiency of PPQ‐M was obviously higher than that of PPD‐M due to the glutamine constitutional unit of PPQ‐M with higher affinity to amino acid transporters. Furthermore, the retrograde pathway played an important role in the intracellular transport (including transcytosis) of both zwitterionic micelles. Excellent villi absorption of zwitterionic micelles was observed in situ, which gave a convincing evidence for oral delivery application prospect. The results of this research demonstrated that Glu‐derived zwitterionic micelles with distinguished capacity of conquering intestinal mucosal barrier, have promising potential toward oral delivery.
Targeted demethylation of the CDO1 promoter based on CRISPR system inhibits the malignant potential of breast cancer cells
Authors: Yang Jiaojiao , Sun Liyue , Liu Xiao‐Yun , Huang Chan , Peng Junling , Zeng Xinxin , Zheng Hailin , Cen Wenjian , Xu Yu‐Xia , Zhu Weijie , Wu Xiao‐Yan , Ling Dongyi , Zhang Lu‐Lu , Wei Mingbiao , Liu Ye , Wang Deshen , Wang Feng‐Hua , Li Yu‐Hong , Li Qin , Du Ziming
Published: September 2023

Background

Cysteine dioxygenase 1 (CDO1) is frequently methylated, and its expression is decreased in many human cancers including breast cancer (BC). However, the functional and mechanistic aspects of CDO1 inactivation in BC are poorly understood, and the diagnostic significance of serum CDO1 methylation remains unclear.

Methods

We performed bioinformatics analysis of publicly available databases and employed MassARRAY EpiTYPER methylation sequencing technology to identify differentially methylated sites in the CDO1 promoter of BC tissues compared to normal adjacent tissues (NATs). Subsequently, we developed a MethyLight assay using specific primers and probes for these CpG sites to detect the percentage of methylated reference (PMR) of the CDO1 promoter. Furthermore, both LentiCRISPR/dCas9‐Tet1CD‐based CDO1‐targeted demethylation system and CDO1 overexpression strategy were utilized to detect the function and underlying mechanism of CDO1 in BC. Finally, the early diagnostic value of CDO1 as a methylation biomarker in BC serum was evaluated.

Results

CDO1 promoter was hypermethylated in BC tissues, which was related to poor prognosis (p < .05). The CRISPR/dCas9‐based targeted demethylation system significantly reduced the PMR of CDO1 promotor and increased CDO1 expression in BC cells. Consequently, this leads to suppression of cell proliferation, migration and invasion. Additionally, we found that CDO1 exerted a tumour suppressor effect by inhibiting the cell cycle, promoting cell apoptosis and ferroptosis. Furthermore, we employed the MethyLight to detect CDO1 PMR in BC serum, and we discovered that serum CDO1 methylation was an effective non‐invasive biomarker for early diagnosis of BC.

Conclusions

CDO1 is hypermethylated and acts as a tumour suppressor gene in BC. Epigenetic editing of abnormal CDO1 methylation could have a crucial role in the clinical treatment and prognosis of BC. Additionally, serum CDO1 methylation holds promise as a valuable biomarker for the early diagnosis and management of BC.
Minimal residual disease assessment in B‐cell precursor acute lymphoblastic leukemia by semi‐automated identification of normal hematopoietic cells: A EuroFlow study
Authors: Verbeek Martijn W. C. , Rodríguez Beatriz Soriano , Sedek Lukasz , Laqua Anna , Buracchi Chiara , Buysse Malicorne , Reiterová Michaela , Oliveira Elen , Morf Daniela , Oude Alink Sjoerd R. , Barrena Susana , Kohlscheen Saskia , Nierkens Stefan , Hofmans Mattias , Fernandez Paula , de Costa Elaine Sobral , Mejstrikova Ester , Szczepanski Tomasz , Slota Lukasz , Brüggemann Monika , Gaipa Giuseppe , Grigore Georgiana , van Dongen Jacques J. M. , Orfao Alberto , van der Velden Vincent H. J.
Published: September 2023

Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). However, data‐analysis remains mainly expert‐dependent. In this study, we designed and validated an Automated Gating & Identification (AGI) tool for MRD analysis in BCP‐ALL patients using the two tubes of the EuroFlow 8‐color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow‐up samples from 174 BCP‐ALL patients, stained with the EuroFlow BCP‐ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra‐expert concordance (100%) and good inter‐expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP‐ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.
Immunoreactivity of TTF‐1, GATA‐3, CEA, and p16/Ki67 cocktail in Cellprep®‐processed control samples: Comparison of long‐term storage in vials and slides
Authors: Ryu Ayumi , Honma Keiichiro , Umeno Yoshimi , Uefuji Fusayo , Muramatsu Takako , Nishimura Sanako , Tanada Satoshi , Yamamoto Takashi , Nagata Shigenori , Yamasaki Tomoyuki , Ohue Masayuki
Published: September 2023

Introduction

Cellprep® (CP) is a novel liquid‐based cytology (LBC) system. This study aimed to assess the immunoreactivity of control samples stored long‐term under two storage conditions using CP.

Methods

The immunoreactivity in control samples was evaluated under two sample storage conditions: CP vial storage at room temperature (RT: 20–25°C) and CP slide storage in a refrigerator (2–6°C). Clinical samples as controls (total: positive/negative) were immunostained using thyroid transcription factor‐1 (TTF‐1) (20: 14/6), GATA binding protein 3 (GATA‐3) (13: 10/3), carcinoembryonic antigen (CEA) (23: 15/8), and the p16/Ki67 cocktail (20: 12/8) markers. The first immunocytochemistry (ICC) was performed within 1 month using CP vials stored at RT. Samples stored in CP vials and on CP slides were used for the second (within 3–6 months) and third (within 6–11 months) ICCs. Compared with the first ICC, the concordance of immunoreactivity for the second and third ICCs was evaluated using the weighted kappa coefficient.

Results

For TTF‐1, CEA, and the p16/Ki67 cocktail markers, ICC controls had stable immunoreactivity for a minimum of 6 months when samples were stored in CP vials (kappa coefficients >0.8), whereas for GATA‐3, they were for 3 months. On CP slides, only for the p16/Ki67 cocktail, ICC controls had stable immunoreactivity for at least 3 months (kappa coefficient >0.8).

Conclusion

Clinical samples as ICC controls revealed consistently more stable immunoreactivity in CP vials than on CP slides for TTF‐1, GATA‐3, CEA, and the p16/Ki67 cocktail markers.
PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic (PREEMPT‐HF) study design and enrolment
Authors: Boehmer John , Sauer Andrew J. , Gardner Roy , Stolen Craig M. , Kwan Brian , Wariar Ramesh , Ruble Stephen
Published: September 2023

Aims

The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions.

Methods and results

The PREEMPT‐HF study is a global, multicentre, prospective, observational, single‐arm, post‐market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in‐clinic visit at 12 months was required for collection of all‐cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction < 25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%).

Conclusions

The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes.
From simple to complex: Protein‐based biomarker discovery in tuberculosis
Authors: Mousavian Zaynab , Källenius Gunilla , Sundling Christopher
Published: September 2023

Tuberculosis (TB) is a deadly infectious disease that affects millions of people globally. TB proteomics signature discovery has been a rapidly growing area of research that aims to identify protein biomarkers for the early detection, diagnosis, and treatment monitoring of TB. In this review, we have highlighted recent advances in this field and how it is moving from the study of single proteins to high‐throughput profiling and from only using proteomics to include additional types of data in multi‐omics studies. We have further covered the different sample types and experimental technologies used in TB proteomics signature discovery, focusing on studies of HIV‐negative adults. The published signatures were defined as either coming from hypothesis‐based protein targeting or from unbiased discovery approaches. The methodological approaches influenced the type of proteins identified and were associated with the circulating protein abundance. However, both approaches largely identified proteins involved in similar biological pathways, including acute‐phase responses and T‐helper type 1 and type 17 responses. By analysing the frequency of proteins in the different signatures, we could also highlight potential robust biomarker candidates. Finally, we discuss the potential value of integration of multi‐omics data and the importance of control cohorts and signature validation.
A Cobalt Complex from Terpyridine‐Based Peptoid as an Efficient Catalyst for Visible Light Driven Water Oxidation
Authors: Pahar Suraj , Majee Karunamay , Maayan Galia
Published: September 2023

We report on the first peptoid‐based catalyst for visible light driven water oxidation, the complex TPT2Co. Peptoids are N‐substituted glycine oligomers, and TPT is a peptoid trimer incorporating terpyridine ligand, an ethanolic group as a proton acceptor and a non‐catalytic benzyl group. We explored the ability of TPT2Co to perform as a catalyst for water oxidation in phosphate buffer at pH 9.5, in the presence of the photosensitizer [Ru(bpy)3]2+ and the sacrificial electron acceptor Na2S2O8. We demonstrated that TPT2Co can catalyze water oxidation by a blue LED with an intensity of only 1.5 mW/cm2 towards oxygen production at pH 9.5 with a maximal TON of 28.1 in 45 min. The stability of TPT2Co during the light‐driven water oxidation as well as its ability to stabilize the photosensitizer were confirmed by a combination of UV‐Vis, IR and ESI‐MS analysis.
Synthetic Approaches to Ribosyl Adenosine 5′,5′′‐Diphosphate Fragment of Poly(ADP‐ribose)
Authors: Hagino Rui , Mozaki Keita , Komura Naoko , Imamura Akihiro , Ishida Hideharu , Ando Hiromune , Tanaka Hide‐Nori
Published: September 2023

Ribosyl adenosine 5′,5′′‐diphosphate is a poly(ADP‐ribose) fragment covalently bonded to a protein during post‐translational modification. Poly(ADP‐ribose) is involved in several biological processes such as DNA repair and cancerization. Herein, we report the development of two synthetic approaches to the poly(ADP‐ribose) fragment via a common precursor. The major difficulty in the synthesis of the fragment is the α‐(1′′→2′)‐glycosidic bond formation between the ribose and adenosine because of the lack of neighboring group participation and low reactivity of the 2′‐hydroxyl group. The first approach employed an indirect method that involved stepwise assembly of the ribosyl adenosine framework by O‐ribofuranosylation of a commercially available ribose acceptor and subsequent N‐glycosylation of N6‐benzoyl adenine (14 linear longest sequence (LLS) steps, 11 pots, 6.8 % overall yield). In the second approach, the direct O‐ribofuranosylation of a known 6‐chloropurine riboside acceptor was adopted (12 LLS steps, 10 pots, 4.8 % overall yield). Thus, two practical synthetic approaches to the target fragment were successfully established in terms of the number of LLS steps, pots, and overall yield. Furthermore, the precursor was converted into a conjugation‐ready building block, primed for application in ADP‐ribose oligomer synthesis.