bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new mechanism of cancer initiation that involves the transformation of hepatocytes into preneoplastic single hepatocytes and minifoci positive for glutathione S‐transferase P‐form (GST‐P) in rat livers: 3D analysis using a vibratome
Authors: Satoh Kimihiko 
Published: September 2024

AbstractBackgroundCancer initiation has long been “unknowable” in biology and medicine. In 1987, however, Moore and our research group observed single hepatocytes and minifoci that were strongly positive for glutathione S‐transferase P‐form (GST‐P) in the rat liver as early as 2 to 3 days after initiation by diethylnitrosamine prior to the induction of GST‐P+ foci and nodules. The induction of GST‐P+ single hepatocytes, precursors of GST‐P+ foci and nodules, was considered genetic. But, the details of the induction mechanism have remained unclear despite various examinations over a long period.MethodsMale Sprague‐Dawley rats (aged 6 weeks) were fed a basal diet containing either benzyl isothiocyanate (BITC, 0.5% by wt) or 2‐acetylaminofluorene (AAF, 0.04%) ad libitum for appropriate time intervals. All animals were anesthetized and euthanized. The livers obtained were excised, cut into 3‐ to 4‐mm‐thick slices and fixed in cold acetone at 4 °C. The liver specimens were then sliced into 25‐µm‐thick sections in PBS using an automated microtome (Vibratome 1500 Sectioning System, Vibratome Products, NY, USA). Immunocytochemical staining was performed in free solution, and the results were examined via digital light microscopy (Coolscope, Nikon, Tokyo).Results3D analysis using a vibratome showed that GST‐P is rapidly excreted into the bile of the liver of animals in response to strong carcinogenic stress caused by promoters or initiators. “Rapid biliary excretion of GST‐P” was widely and commonly observed in all hepatocytes, GST‐P+ single hepatocytes, minifoci, foci and nodules under appropriate conditions. Surprisingly, on the basis of these key findings, a new mechanism of cancer initiation involving the transformation of hepatocytes into GST‐P+ single hepatocytes and minifoci in animal livers was identified. In addition, the initiation process was determined to be nongenetic because mutation is an invisible rare event.ConclusionsThis short review describes several details about breakthrough findings on cancer initiation in rat livers, the application of 3D analysis to other cancers and the importance in the genetic analysis in malignant diseases.
Polysaccharides from Tremella Fuciformis Enhance Glucose and Lipid Metabolism in HepG2 Cells Through Activating the AMPK Signaling Pathway
Authors: Song Haizhao , Lu Jing , Deng Rou 
Published: September 2024

AbstractPolysaccharides have gained substantial attention for their diverse biological activities. The present study was conucted to elucidate the effects and molecular mechanisms of Tremella fuciformis‐derived polysaccharides (PTP‐3a) on glucose and lipid metabolism in palmitic acid (PA) ‐ treated HepG2 cells. Multiple parameters were assessed following PTP‐3a treatment, including lipid accumulation, glycogen content, glucose consumption, and enzyme activities, including pyruvate kinase (PK) and hexokinase (HK). Additionally, the expression levels of genes associated with glucose and lipid metabolism was evaluated using western blot analysis. PTP‐3a effectively inhibited lipid accumulation, promoted the glucose consumption, increased the amount of cellular glycogen, and enhanced PK and HK activities in PA‐treated cells. Furthermore, PTP‐3a induced a significant increase in the p‐AMPK/AMPK ratio and the expression level of PPARa, while decreasing the expression levels of SREBP, FAS, ACC, and SOCS3. In conclusion, these findings suggested that PTP‐3a exerted beneficial effects on glucose and lipid metabolism by activating the AMPK signaling pathway, resulting in the inhibition of lipogenesis, promotion of fatty acid oxidation, and enhancement of cellular glycogen synthesis and glycolysis. These findings hold clinical relevance and provide a foundation for potential treatments for non‐alcoholic fatty liver disease (NAFLD) and and related metabolic disorders.
Biosensor‐Guided Engineering of a Baeyer‐Villiger Monooxygenase for Aliphatic Ester Production
Authors: Sakoleva Thaleia , Vesenmaier Florian , Koch Lena , Schunke Jarne E. , Novak Kay D. , Grobe Sascha , Dörr Mark , Bornscheuer Uwe T. , Bayer Thomas 
Published: September 2024

AbstractEsters are valuable aroma compounds and can be produced enzymatically by Baeyer‐Villiger monooxygenases (BVMOs) from (aliphatic) ketone precursors. However, a genetically encoded biosensor system for the assessment of BVMO activity and the detection of reaction products is missing. In this work, we assembled a synthetic enzyme cascade – featuring an esterase, an alcohol dehydrogenase, and LuxAB – in the heterologous host Escherichia coli. Target esters are produced by a BVMO, subsequently cleaved, and the corresponding alcohol oxidized through the artificial pathway. Ultimately, aldehyde products are detected in vivo by LuxAB, a luciferase from Photorhabdus luminescens that emits bioluminescence upon the oxidation of aldehydes to the corresponding carboxylates. This biosensor system greatly accelerated the screening and selection of active BVMO variants from a focused library, omitting commonly used low‐throughput chromatographic analysis. Engineered enzymes accepted linear aliphatic ketones such as 2‐undecanone and 2‐dodecanone and exhibited improved ester formation.
Mechanisms in the Synthesis of S‐Alcohols with 1,4‐NADH Biomimetic Co‐factor N‐Benzyl‐1,4‐dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study
Authors: Farina Matteo , Capone Matteo , Bodo Enrico , Fish Richard H. , Aschi Massiliano , Marrone Alessandro , Daidone Isabella 
Published: September 2024

AbstractThe enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S‐alcohols, when the natural co‐factor, 1,4‐dihyronicotinamide adenine dinucleotide, 1,4‐NADH, was replaced with biomimetic co‐factor, N‐benzyl‐1,4‐dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co‐factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η1‐keto‐S‐η2‐5,6‐1,4‐dihydronicotinamide‐Zn(II) complex, was previously investigated with a model of the HLADH−Zn(II) catalytic site (J. Organometal. Chem. 2021, 943, 121810). Presently, we studied canonical and alternative mechanisms compared to models of the entire enzyme structure. We disproved the η2‐Zn(II) complex, and discovered a canonical hydride transfer from biomimetic 1,4‐NADH, 1, to the Zn(II) bound prochiral ketone substrate, followed by a new proton relay, consisting of a water chain connecting His51 to Ser48 that accomplished the S‐alkoxy anion's protonation to yield the final S‐alcohol product. The HLADH catalysis, with biomimetic co‐factor, 1, that replaced the ribose group, the 5′‐diphosphate groups, and the adenine nucleotide with a N‐benzyl group, has provided a new paradigm for the design of other structures of 1,4‐NADH biomimetic co‐factors, including their economic value in biocatalysis reactions.
Acute kidney injury requiring dialysis after endovascular intervention for acute deep venous thrombosis: A case report and literature review
Authors: Al‐Mannai Najlaa Essa A. H. , Sibira Dalal , Alsuwaidi Hissa , Elmagdoub Ayman , Habas Elmukhtar , Alfitori Gamal 
Published: September 2024

Key Clinical MessagePercutaneous precutaneous mechanical thrombectomy has been used for clot dissolution and removal in selected cases of iliofemoral deep vein thrombosis. Intravascular Hemolysis and hemoglobinuria caused by pharmachomechanical chather directed thrombolysis (PCDT) devices like the Angiojet is associated with an increased risk of acute kidney injury (AKI). Acute tubular necrosis that is severe enough to require hemodialysis can occur. Clinicians should be aware of this potential risk to ensure early recognition and timely referral to the nephrologist, and a clear explanation of the risk of AKI should be given to the patients undergoing this procedure.AbstractLower extremity deep vein thrombosis (DVT) is a frequently encountered medical condition, and one that can lead to death or major disability if not promptly treated. Anticoagulation alone may not always be enough for complete treatment. It has been reported that early thrombus removal can rapidly relieve symptoms and prevent disease progression in some selected cases. Percutaneous pharmacomechanical thrombectomy has been used for clot dissolution and removal in such cases. AngioJet is an increasingly used method of percutaneous mechanical thrombectomy for DVT that can cause intravascular hemolysis and potentially acute kidney injury (AKI). We report here a case of a 39 years old lady who developed severe AKI (illustrated by creatinine level of 664 μmol/L (7.5 mg/dL), bicarb of 13 mmol/L and being anuric), requiring hemodialysis secondary to intravascular hemolysis and hemoglobinuria that occurred immediately after the use of AngioJet pharmacomechanical catheter‐directed technique to treat an extensive iliofemoral DVT.
Simple/Commercially Available Lewis Acid in Anionic Ring‐Opening Polymerization: Powerful Compounds with Multiple Applications in Macromolecular Engineering
Authors: Illy Nicolas , Fu Hongqing , Mongkhoun Emma 
Published: September 2024

AbstractSimple and commercially available Lewis acids (LAs) are commonly used catalysts in anionic ring‐opening polymerization (AROP) reactions. In particular, for the AROP of epoxides, the addition of a Lewis acid allows the transition from a so‐called end‐chain mechanism to a monomer‐activated mechanism. The presence of the LA simultaneously leads to a decrease in the reactivity of active centers through the formation of a three‐species ate complex and to the activation of the monomer by LA coordination to the oxygen atom of the oxirane ring. These two effects result in both an increase in propagation kinetics and a decrease in transfer reactions, which has enabled the synthesis of high molecular weight polyethers. However, the impact of Lewis acids goes far beyond these classic effects. They have indeed enabled the polymerization of new functional monomers as well as the synthesis of heterotelechelic macromolecules. Also widely used as catalysts in copolymerization reactions (statistical, sequential, and alternating) Lewis acids can strongly influence the composition and sequence of monomer units in macromolecules. Finally, Lewis acids can also significantly influence the architecture of the obtained macromolecules. This review aims to list the various contributions of Lewis acids to macromolecular engineering and illustrate them with well‐chosen examples.
Cost‐Effective Solutions for Lithium‐Ion Battery Manufacturing: Comparative Analysis of Olefine and Rubber‐Based Alternative Binders for High‐Energy Ni‐Rich NCM Cathodes
Authors: Montes Susan , Beutl Alexander , Paolella Andrea , Jahn Marcus , Tron Artur 
Published: September 2024

AbstractPromoting safer and more cost‐effective lithium‐ion battery manufacturing practices, while also advancing recycling initiatives, is intrinsically tied to reducing reliance on fluorinated polymers like polyvinylidene difluoride (PVDF) as binders and minimizing the use of hazardous and expensive solvents such as N‐methyl pyrrolidone (NMP). In pursuit of this objective, olefin‐ and rubber‐based polymers have been investigated as promising alternatives for binder materials in high‐energy Ni‐rich LiNixCoyMnzO2 (NCM, x≥0.8) cathodes for lithium‐ion batteries (LIBs). Alternative binders such as polyisobutylene (PIB), poly(styrene‐butadiene‐styrene) (SBS), nitrile butadiene rubber (NBR), and its hydrogenated version (HNBR) offer versatile solutions. These polymers can be dissolved in industrial solvents, such as toluene, and have been further processed into homogeneous cathode slurries, thus facilitating the manufacturing of high‐energy Ni‐rich NCM cathodes for lithium‐ion batteries. The evaluation of NCM811 cathodes obtained from PIB, SBS, NBR, and HNBR has involved a thorough assessment of their physical and chemical properties, electrochemical performance, and production expenses, compared with NCM811 cathodes based on PVDF. Notably, cathodes employing PIB and HNBR have exhibited outstanding qualities, showcasing high specific capacity and remarkable electrochemical stability akin to PVDF‐based counterparts. Furthermore, the alternative binders′ superior adhesion, elasticity, and thermal stability have facilitated obtaining uniform and mechanically stable cathode films. Furthermore, using toluene, with its low vapor pressure, has significantly reduced energy costs associated with drying processes, thereby enhancing the overall cost‐effectiveness of the NCM811 cathodes.
Near‐Infrared Spectroscopy and Aquaphotomics in Cancer Research: A Pilot Study
Authors: Surkova Anastasiia , Boichenko Ekaterina , Bibikova Olga , Artyushenko Viacheslav , Muncan Jelena , Tsenkova Roumiana 
Published: September 2024

ABSTRACTCurrently, the majority of methods to monitor cancer treatment through the analysis of body fluids are based on a highly selective detection of single molecules or cells. In this study, we are considering the analysis of the aqueous medium of liquid samples, that is, water, itself, using aquaphotomics and near‐infrared spectroscopy (NIR) for spectral data acquisition and processing, within cancer research. Water, as a molecular system, is a rich source of information about the current state of a patient, which can be extracted from near‐infrared spectra of liquid samples via simple algorithms based on multivariate data analysis. The reported results, obtained ex vivo of body fluids, demonstrate the potential of aquaphotomics in cancer research.
Lasamide Containing Sulfonylpiperazines as Effective Agents for the Management of Glaucoma Associated Symptoms
Authors: Kilbile Jaydeo T. , Sapkal Suryakant B. , Renzi Gioele , D'Agostino Ilaria , Boudjelal Mohamed , Tamboli Yasinalli , Cutarella Luigi , Mori Mattia , Sgambellone Silvia , Villano Serafina , Marri Silvia , Lucarini Laura , Carradori Simone , Carta Fabrizio , Supuran Claudiu T. 
Published: September 2024

AbstractA series of 2,4‐dichloro‐5‐{[4‐(phenylsulfonyl)piperazin‐1‐yl]carbonyl}benzenesulfonamides were designed and synthesized through amidation of Lasamide 1 with substituted piperazines. The newly obtained compounds demonstrated remarkable inhibition potency and selectivity for the human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) II isoform. Selected compounds 7 and 9 were investigated in an in vivo model of glaucoma and showed relevant performances, with the latter being able to last the effect up to 4 hours. The results herein reported are in sustainment of Lasamide derivatives as a new class of compounds potentially exploitable for the management of uncontrolled intra ocular pressure (IOP).
Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites
Authors: Erb‐Zohar Katharina , Bonsmann Susanne , Pausch Jörg , Sumner Melanie , Birkmann Alexander , Zimmermann Holger , Halabi Atef , Kropeit Dirk 
Published: September 2024

AbstractTwo trials were performed to evaluate the effect of renal and hepatic impairment on the pharmacokinetics of pritelivir and its metabolites. The renal impairment trial included subjects with mild, moderate, and severe impairment, while the hepatic impairment trial included subjects with moderate impairment. Both trials recruited a matched control group of healthy subjects. Following a single oral dose of 100 mg of pritelivir, mild and moderate renal impairment and moderate hepatic impairment did not have a clinically relevant effect on the pharmacokinetics of pritelivir. In subjects with severe renal impairment, pritelivir exposure (area under the plasma concentration‐time curve from time 0 to infinity (AUC0‐inf) was 57% higher compared with controls. Pritelivir plasma protein binding was similar in subjects and controls with renal impairment, while the free fraction was higher in subjects with moderate hepatic impairment, increasing unbound pritelivir exposure by 23%. For the metabolites pyridinyl phenyl acetic acid (PPA), amino thiazole sulfonamide (ATS), and PPA‐acyl glucuronide, generally higher exposure was observed with increasing degree of renal impairment (ie, moderate to severe), but not with mild impairment. A modest effect of moderate hepatic impairment was observed for PPA and ATS. Pritelivir was safe and well tolerated in healthy subjects and subjects with renal or hepatic impairment.
Piercing the Shadows: Exploring the Influence of Signal Preprocessing on Interpreting Ultrasensitive Bioelectronic Sensor Data
Authors: Caputo Mariapia , Sarcina Lucia , Scandurra Cecilia , Catacchio Michele , Piscitelli Matteo , Franco Cinzia Di , Bollella Paolo , Scamarcio Gaetano , Torsi Luisa , Macchia Eleonora 
Published: September 2024

AbstractThe development of ultrasensitive electronic sensors for in vitro diagnostics is essential for the reliable monitoring of asymptomatic individuals before illness proliferation or progression. These platforms are increasingly valued for their potential to enable timely diagnosis and swift prognosis of infectious or progressive diseases. Typically, the responses from these analytical tools are recorded as digital signals, with electronic data offering simpler processing compared to spectral and optical data. However, preprocessing electronic data from potentiometric biosensor arrays is still in its infancy compared to more established optical technologies. This study utilized the Single‐Molecule with a Large Transistor (SiMoT) array, which has achieved a Technology Readiness Level of 5, to explore the impact of data preprocessing on electronic biosensor outcomes. A dataset consisting of plasma and cyst fluid samples from 37 patients with pancreatic precursor cyst lesions was analyzed. The findings revealed that standard signal preprocessing can produce misleading conclusions due to artifacts introduced by mathematical transformations. The study offers strategies to mitigate these effects, ensuring that data interpretation remains accurate and reflective of the underlying biochemical information in the samples.
Effect of Synthesis Temperature on Performance of Phenazine‐Based Cathode for Sodium Dual‐Ion Batteries
Authors: Wang Xuan , Li Jianlin , Liu Yifan , Li Dong , Ma Mingbo , Xie Yuehong , You Wenzhi , Zheng Aqun , Xiong Lilong 
Published: September 2024

AbstractOrganic materials have attracted much attention in the field of electrochemical energy storage due to their ecological sustainability, abundant resources and structural designability. However, low electrical conductivity and severe agglomeration of organic materials lead to poor discharge capacity and reaction kinetics in batteries. Herein, the morphology of the phenazine‐based organic polymer poly(5,10‐diphenylphenazine) (PDPPZ) was modified by varying the synthesis temperature. PDPPZ‐165 °C with an exceptional porous structure provides abundant reaction channels for rapid charge transfer and diffusion that improves the reaction kinetics in sodium dual‐ion batteries. Therefore, PDPPZ‐165 °C cathode possesses excellent rapid charge‐discharge capability delivering a specific capacity of 119.2 mAh g−1 at 40 C. Furthermore, a high specific capacity of 124.7 mAh g−1 can be provided even at a high loading of 16 mg cm−2 at 0.5 C with a capacity retention of 86.4 % after 500 cycles. This work could afford new insights for optimizing the performance of organic cathode materials in sodium dual‐ion batteries.
Micro‐bacterial assessment of disposable gowns with a focus on green endoscopy in gastrointestinal endoscopy procedures: A Japanese pilot study for healthcare waste reduction
Authors: Naito Sakiko , Nakamura Itaru , Muramatsu Takahiro , Kagawa Yasuyuki , Fukuzawa Masakatsu , Itoi Takao 
Published: September 2024

AbstractObjectiveThis study aimed to implement green endoscopy through the microbiological assessment of gowning techniques during endoscopy to reduce carbon emissions and separate medical waste.MethodsTwenty‐five patients who performed esophagogastroduodenoscopy from March to May 2024 were included in this study. Four sections of the isolation gowns (anterior, posterior, right, and left) were cut into 2 cm2 after endoscopy, and the rate of microbial contamination was examined using the stamp method.ResultsThe endoscopic examination time was 8 min (6−12), and endoscopy was performed by 10 expert endoscopists, six endoscopists, and nine residents. The overall isolation gown contamination rate was 56%, with 25%, 20.8%, 20.8%, and 33.3% in the front, back, as well as right and left arms, respectively. The rates of isolation gown contamination rates in the expert endoscopists, endoscopists, and residents groups were 30%, 50%, and 77.8%, respectively, with a higher rate in the residents group. Regardless of the physician's performance, bacterial detection was consistently higher in the left arm (42.9% vs. 40% vs. 25%; p = 0.093). The detected bacteria comprised 58% Gram‐positive and 42% Gram‐negative organisms, including those from tap water used for endoscopy bacteria and obtained from the participant's skin or mouth. No pathogenic organisms were detected.ConclusionsThe bacteria detected in disposable gowns after gastrointestinal endoscopy were non‐pathogenic. Thus, our findings suggest that changing all personal protective equipment of respective endoscopes might not be essential. We advocate for green endoscopy to achieve sustainable development goals and reduce medical waste.
New Transcriptomic Biomarkers for Detection of the Recombinant Human Erythropoietin (rHuEPO) MirCERA in Horses
Authors: Loup Benoit , André François , Leuenberger Nicolas , Marchand Alexandre , Barnabé Agnès , Delcourt Vivian , Garcia Patrice , Popot Marie‐Agnès , Bailly‐Chouriberry Ludovic 
Published: September 2024

ABSTRACTDetection and monitoring of biomarkers related to doping is particularly suitable for the development of analytical strategies dedicated to indirect detection of banned substances. Previous studies in horses have already allowed the investigation of transcriptomic biomarkers in equine blood associated with reGH and rHuEPO administrations. Our most recent developments continue to focus on the discovery and monitoring of transcriptomic biomarkers for the control of ESAs, and a collaborative study with WADA‐accredited doping control laboratories has recently been initiated to conduct a pilot study. In humans, three mRNAs (ALAS2, CA1, and SLC4A1) were previously observed to be differentially expressed after blood doping and were associated with immature red blood cells, the so‐called circulating reticulocytes. In horses, circulating reticulocytes are rarely observed even after rHuEPO administration. With the improved primers that detect the equine orthologues of the human mRNAs from the ALAS2, CA1, and SLC4A1 genes, we can now report the first evidence of the detection of the three biomarkers in equine blood. In addition, an upregulation of the mRNA levels of the three genes was observed after analysis of blood samples collected from MirCERA‐treated animals, with kinetics similar to those previously documented in humans. Our data suggest that ALAS2 and CA1 are promising indirect biomarkers for the detection of recombinant EPO abuse in horses, as observed in humans.