bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ugi four‐multicomponent reaction based synthesis, in vitro, and in silico enzymatic evaluations of new pyrazino[1,2‐a]indole‐1,4‐dione‐indole‐2‐phenylacetamides as potent inhibitors against α‐glucosidase and α‐amylase
Authors: Ahmadi Shourkaei Fatemeh , Rashidi Ranjbar Parviz , Taslimi Parham , Mahdavi Mohammad 
Published: December 2023

AbstractIn this work, synthesis and evaluation of pyrazino[1,2‐a]indole‐1,4‐dione‐indole‐2‐phenylacetamides 6 a–k as new synthetic anti‐diabetes agents were presented. These compounds were synthesized by a four‐component Ugi reaction without metal catalyst. All synthesized compounds were evaluated against α‐glucosidase and α‐amylase as two important targets in the treatment of diabetes. Approximately, all new compounds 6 a–k were more potent than positive control acarbose against these studied enzymes. The obtained potent compounds against the target enzymes were docked in the active site of the related enzyme. Docking study showed that our new potent compounds as well interacted with key residues of the target enzyme.
Enzymatic Catalysts for Hydroxamic Acid Formation: A Mini‐Review
Authors: Singh Rahul Vikram 
Published: December 2023

AbstractIn recent years, biocatalysts have emerged as crucial tool in organic synthesis, particularly for the production of drug intermediates and precursors, e.g., the synthesis of hydroxamic acids. Traditionally, hydroxamic acids were synthesized using organic chemistry methods. However, with the growing emphasis on sustainable and environment‐friendly practices, the chemical industry has increasingly turned towards green synthesis approaches. The significance of hydroxamic acids in medicinal chemistry has also contributed to the changing trends. Following the approval of certain hydroxamic acids as histone deacetylase (HDAC) inhibitors for cancer treatment by the Food and Drug Administration (US‐FDA), there has been a renewed focus on their synthesis and the development of derivatives with improved properties. As an alternative route, amidases have emerged as promising biocatalysts for hydroxamic acid synthesis through their acyltransferase activity. Recent advancements in the synthesis approaches for hydroxamic acids are reviewed. The biocatalytic routes are explored, emphasizing the use of amidases and their acyltransferase activity. The scope and potential applications of this chemoenzymatic approach in synthesizing various hydroxamic acids and their derivatives are discussed. Such advancements have the potential to revolutionize the production of these important compounds, making the synthesis process more sustainable, efficient, and economically viable.
A case of caffeine intoxication resulting in hypothermia
Authors: Ohno Takanori , Katsuki Shino , Miyamoto Kazuyuki , Kaizaki‐Mitsumoto Asuka , Kanazawa Masashi , Ito Toshitaka , Hayashi Munetaka 
Published: December 2023

Key Clinical MessageA 30‐year‐old woman arrived at our hospital with polymorphic ventricular tachycardia and hypothermia. Later, it was found that the cause was an overdose of caffeine exceeding the lethal dose. Although it is common for toxidrome caused by caffeine intoxication to produce hyperthermia, here we report a case of hypothermia.
A rare case of mycotic aortic aneurysm with Clostridium perfringens culture
Authors: Tadayon Niki , Shahsavari Saleh , Yahya Reyhane , Nourmohammadi Delaram , Jadidian Faezeh , Babaei Masoud , Mousavizade Mostafa , Vakili Kimia 
Published: December 2023

Key Clinical MessageAs only early diagnosis, prompt surgical intervention, and appropriate antibiotic therapy can decrease clostridial MAA mortality rate; keeping in mind a broad differential diagnosis in a patient with sepsis and unusual vascular symptoms is important.AbstractMycotic aortic aneurysm (MAA) is an infrequent but very consequential condition characterized by the pathological disruption of the aorta due to infection. Clostridium perfringens is a bacterium that falls under the taxonomic classification of the genus Clostridium. Although mycotic aneurysm is often not commonly linked with this infection, there are instances when it may function as a causative agent for MAA. Timely diagnosis and thorough therapeutic techniques, including surgical intervention and quick administration of appropriate antibiotics, can potentially reduce the mortality rate associated with clostridial MAA. In this study, we presented a clinical report detailing the diagnosis of a mycotic aneurysm caused by C. perfringens in the thoracic aorta in a 66‐year‐old male patient with a history of diabetes mellitus and a recent prostate biopsy. Furthermore, we discussed the surgical approach and overall management strategy to address this case.
Sample selection method using near‐infrared spectral information entropy as similarity criterion for constructing and updating peach firmness and soluble solids content prediction models
Authors: Liu Yande , He Cong , Jiang Xiaogang 
Published: December 2023

AbstractWhen using near‐infrared (NIR) techniques for analysis, model construction and maintenance updates are essential. When model construction is performed in machine learning, the sample set is usually divided into the calibration set and the validation set. The representativeness of the calibration set and the reasonable distribution of the validation set affects the accuracy of the established model. In addition, when maintaining and updating models, selecting the most informative updated sample not only improves the model prediction accuracy but also reduces sample preparation. In this paper, the spectral information entropy (SIE) is proposed to be used as a similarity criterion for dividing the sample set and use this criterion to select updated samples. The Kennard–Stone (KS) and the sample set portioning based on joint x–y distance (SPXY) methods were used for comparison to verify the superiority of the proposed method. The results showed that the model built after dividing the sample set using the SIE method has good prediction effect compared with KS and SPXY method. When predicting soluble solid content (SSC) and hardness, the prediction determination coefficient (
) was improved by more than 15%, and the root mean square error (RMSE) of prediction was reduced by 50%. In terms of model updating, selecting a small number of updated samples using the SIE method can improve the correlation coefficient (
) to more than 80%, and updated models' prediction accuracy is higher than that of KS and SPXY method. It is confirmed that the SIE method can make the NIR analysis technique more reliable.
Peroxo‐Zr/Hf‐Containing Wells‐Dawson Polyoxometalates for H2O2‐based Homogeneous, Heterogeneous, and Biphasic Oxidation Catalysis
Authors: Sundar Anusree , Maksimchuk Nataliya V. , Ivanchikova Irina D. , Zalomaeva Olga V. , Bajuk‐Bogdanović Danica , Kholdeeva Oxana A. , Ćirić‐Marjanović Gordana , Bassil Bassem S. , Kortz Ulrich 
Published: December 2023

AbstractFour peroxo‐Zr and Hf containing polyanions, [M2(O2)2(X2W17O61)2]16− (X=P, M=ZrIV (ZrP), HfIV (HfP); X=As, M=ZrIV (ZrAs), HfIV (HfAs) were synthesized and structurally characterized. The structures consist of two monolacunary Wells‐Dawson ions which are connected head‐on via two side‐on peroxo bridges. The four new polyanions are solution‐stable as shown by 31P NMR, Raman and FT‐IR spectroscopic studies. Comparative studies on alcohol oxidation with a solvent‐ and phase‐transfer catalyst‐free biphasic oxidative system with homogeneous and supported‐catalyst were performed and several noteworthy observations in reactivity and selectivity were observed, such as the highly selective ring‐opening oxidation of cyclohexanol to adipic acid. Tetra‐n‐butylammonium salts of ZrP and HfP were also synthesized to study the catalytic activity of the compounds in the homogenous H2O2‐based oxidation of olefins, α,β‐unsaturated carbonyl compounds, and thioethers in organic solvent.
Starfruit‐Shaped Zirconium Metal‐Organic Frameworks: From 3D Intermediates to 2D Nanosheet Petals with Enhanced Catalytic Activity
Authors: Tao Cheng‐an , Wang Beibei , Zhao He , Yang Xuheng , Huang Jian , Wang Jianfang 
Published: December 2023

AbstractWe present the fabrication of a novel Starfruit‐shaped metal‐organic framework (SMOF) composed of zirconium and Tetra(4‐carboxyphenyl)porphine linkers. The SMOF exhibits a unique morphology with edge‐sharing two‐dimensional (2D) nanosheet petals. Our investigation unravels a captivating transformation process, wherein three‐dimensional (3D) shuttle‐shaped MOFs form initially and subsequently evolve into 2D nanosheet‐based SMOF structures. The distinct morphology of SMOF showcases superior catalytic activity in detoxifying G‐type nerve agent and blister agent simulants, surpassing that of its 3D counterparts. This discovery of the 3D‐to‐2D transition growth pathway unlocks exciting opportunities for exploring novel strategies in advanced MOF nanostructure development, not only for catalysis but also for various other applications.
High‐Contrast Photoacoustic Imaging of Localized Cysteine in Orthotopic Breast Cancer Enabled by A Totally‐Caged Methylene Blue Probe
Authors: Xie Si , Li Xipeng , Zeng Qin , Wu Yongbo , Zhang Tao 
Published: December 2023

AbstractHigh‐contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue‐based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical “OFF‐to‐ON” absorption transition for high‐contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue‐based probe for cysteine (MB‐Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π‐conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130‐fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high‐contrast manner. Therefore, this work established an up‐to‐date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.
Cyclic Hydrocarbon Frameworks Containing Two Bismuth Atoms: Towards 9,10‐Dibismaanthracene
Authors: Rottschäfer Dennis , Reith Sascha , Schwarzmann Johannes , Tambornino Frank , Lichtenberg Crispin 
Published: December 2023

AbstractWhen bismuth atoms are incorporated into cyclic organic systems, this commonly goes along with strained or distorted molecular geometries, which can be exploited to modulate the physical and chemical properties of these compounds. In six‐membered heterocycles, bismuth atoms are often accompanied by oxygen, sulfur or nitrogen as a second hetero‐element. In this work, we present the first examples of six‐membered rings, in which two CH units are replaced by BiX moieties (X=Cl, Br, I), resulting in dihydro‐anthracene analogs. Their behavior in chemically reversible reduction reactions is explored, aiming at the generation of dibisma‐anthracene (bismanthrene). Heterometallic compounds (Bi/Fe, Bi/Mn) are introduced as potential bismanthrene surrogates, as supported by bismanthrene‐transfer to selenium. Analytical techniques used to investigate the reported compounds include NMR spectroscopy, high‐resolution mass spectrometry, single‐crystal X‐ray diffraction analyses, and DFT calculations.
Copper‐Catalyzed Sulfimidation in Aqueous Media: a Fast, Chemoselective and Biomolecule‐Compatible Reaction
Authors: Meeus Eva J. , Álvarez María , Koelman Emma , Pérez Pedro J. , Reek Joost N. H. , de Bruin Bas 
Published: December 2023

AbstractPerforming transition metal‐catalyzed reactions in cells and living systems has equipped scientists with a toolbox to study biological processes and release drugs on demand. Thus far, an impressive scope of reactions has been performed in these settings, but many are yet to be introduced. Nitrene transfer presents a rather unexplored new‐to‐nature reaction. The reaction products are frequently encountered motifs in pharmaceuticals, presenting opportunities for the controlled, intracellular synthesis of drugs. Hence, we explored the transition metal‐catalyzed sulfimidation reaction in water for future in vivo application. Two Cu(I) complexes containing trispyrazolylborate ligands (Tpx) were selected, and the catalytic system was evaluated with the aid of three fitness factors. The excellent nitrene transfer reactivity and high chemoselectivity of the catalysts, coupled with good biomolecule compatibility, successfully enabled the sulfimidation of thioethers in aqueous media. We envision that this copper‐catalyzed sulfimidation reaction could be an interesting starting point to unlock the potential of nitrene transfer catalysis in vivo.
Metal‐Free Synthesis of 2‐Aminobenzothiazoles via I2‐Catalyzed Tandem Cyclization Reaction of Amines and Carbon Disulfide
Authors: Chen Ting , Feng Wei , Yang Ruitong , Chen Shanping , Deng Guo‐Jun 
Published: December 2023

Comprehensive SummaryA convenient approach for the construction of 2‐aminobenzothiazoles via I2‐catalyzed tandem cyclization reaction of amines and carbon disulfide has been developed. The present approach starts from simple and readily available starting materials, affording a series of 2‐aminobenzothiazoles in up to 89% yields under metal‐free conditions. In this work, C—H/N—H functionalization was achieved and multiple C‐hetero bonds were successfully constructed in one pot.
Straightforward Synthesis of DFO* ‐ An Octadentate Chelator for Zirconium‐89
Authors: Guarrochena Xabier , Kronberger Julia , Tieber Manuel , Ciesielski Philipp , Mindt Thomas L. , Feiner Irene V. J. 
Published: December 2023

AbstractDFO* is an octadentate chelator able to form highly stable chelates with Zirconium‐89 (89Zr) for nuclear medicinal applications in Positron Emission Tomography (PET).[1,2] The synthesis of DFO* and its scale‐up remains challenging by reported synthetic protocols. For this reason, we set out to develop a de novo synthesis of a hydroxamate‐containing building block suitable for the coupling to the commercially available DFO (desferrioxamine B, mesylate salt) yielding, after deprotection, the desired chelator DFO* in a more efficient procedure. Highlights of the new synthesis of DFO* reported herein are less synthetic steps and the isolation of the desired product DFO* by using solid phase extraction (SPE), thus avoiding tedious HPLC purification. DFO* is obtained in excellent purity (92‐98 %) and an overall yield of approximately 29 %. In addition, the isolated trifluoroacetic acid (TFA)‐salt of DFO* displays an improved solubility in organic solvents (DMSO, DMF, methanol), which will facilitate its use for the preparation of structurally diverse derivatives suitable for bioconjugation chemistry and the development of 89Zr‐labeled radiotracers.
Naturally Occurring and Widespread Resistance to Bioactive Natural Products
Authors: Tan Bin , Zhang Qingbo , Zhang Liping , Zhu Yiguang , Zhang Changsheng 
Published: December 2023

AbstractNaturally occurring resistances diminish the effectiveness of antibiotics, and present significant challenges to human health. Human activities are usually considered as the main drivers of the dissemination of antibiotic resistance, however, the origin of the clinical antibiotic resistance can be traced to the environmental microbes, and the clinically relevant resistance determinants have already pre‐existed in nature before the antibiotics come into clinic. In this concept, we present the naturally occurring and widespread resistance determinants recently discovered during the biosynthesis study of bioactive compounds. These widely prevalent resistances in environmental microbes, including antibiotic producers and non‐producers, advance the understanding of the origin of resistance, and provide prediction for the clinically relevant resistance to aid in the rational design of more effective drug analogues to combat resistance.
Efficient sensitivity analysis for biomechanical models with correlated inputs
Authors: Hilhorst Pjotr L. J. , Quicken Sjeng , van de Vosse Frans N. , Huberts Wouter 
Published: December 2023

AbstractIn most variance‐based sensitivity analysis (SA) approaches applied to biomechanical models, statistical independence of the model input is assumed. However, often the model inputs are correlated. This might alter the interpretation of the SA results, which may severely impact the guidance provided during model development and personalization. Potential reasons for the infrequent usage of SA techniques that account for input correlation are the associated high computational costs, especially for models with many parameters, and the fact that the input correlation structure is often unknown. The aim of this study was to propose an efficient correlated global sensitivity analysis method by applying a surrogate model‐based approach. Furthermore, this article demonstrates how correlated SA should be interpreted and how the applied method can guide the modeler during model development and personalization, even when the correlation structure is not entirely known beforehand. The proposed methodology was applied to a typical example of a pulse wave propagation model and resulted in accurate SA results that could be obtained at a theoretically 27,000× lower computational cost compared to the correlated SA approach without employing a surrogate model. Furthermore, our results demonstrate that input correlations can significantly affect SA results, which emphasizes the need to thoroughly investigate the effect of input correlations during model development. We conclude that our proposed surrogate‐based SA approach allows modelers to efficiently perform correlated SA to complex biomechanical models and allows modelers to focus on input prioritization, input fixing and model reduction, or assessing the dependency structure between parameters.
Landscape of N1‐methyladenosin (m1A) modification pattern in colorectal cancer
Authors: Jiang Chunhui , Tian Yuan , Xu Chunjie , Zhang Hao , Gu Lei 
Published: December 2023

AbstractBackgroundN1‐methyladenosine (m1A) is a recently identified mRNA modification. However, it is still unclear that how m1A alteration affects the development of colorectal cancer (CRC).AimsThe landscape of m1A modification patterns regarding tumor immune microenvironment (TIME) in CRC is a lack of knowledge. Thus, this study will utilize the public database to comprehensively evaluate of multiple m1A methylation regulators in CRC.Methods and resultsWe retrospectively analyzed 398 patients with CRC and 39 healthy people for negative control, using the The Cancer Genome Atlas (TCGA) database to evaluate m1A modification patterns regarding tumor immune microenvironment (TIME) in CRC. The m1Ascore was developed via principal component analysis. And its clinical value in prognosis of CRC was further explored. Our study revealed 12 key m1A‐related DEGs including CLDN3, MUC2 and CCDC85B which are identified associated with invasion and metastasis in CRC. The most important biological processes linked to weak immune response and poor prognosis were the regulation of RNA metabolism and RNA biosynthesis. Furthermore, we found that compared to patients with low m1A scores, those with high m1A scores had higher percentage, larger tumor burdens, and worse prognosis.ConclusionSignificantly diverse m1A modification patterns can be seen in CRC. Through its impact on TIME and immunological dysfunction, the heterogeneity of m1A alteration patterns influences the prognosis of CRC. This study provided novel insights into the m1A modification in CRC which might promote the development of personalized immunotherapy strategies.
Model‐Based Dose Selection of Subcutaneous Nivolumab in Patients with Advanced Solid Tumors
Authors: Zhao Yue , Sanghavi Kinjal , Roy Amit , Murthy Bindu , Bello Akintunde , Aras Urvi , Vezina Heather 
Published: December 2023

The pharmacokinetics (PK) of intravenous (i.v.) nivolumab is well characterized. A subcutaneous (s.c.) nivolumab formulation with and without recombinant human hyaluronidase PH20 enzyme is being evaluated in CheckMate 8KX (NCT03656718). A model‐based analysis was conducted to characterize the PK of nivolumab s.c. and predict systemic exposures after i.v. and s.c. administration to guide dosing regimen selection for nivolumab s.c. A prior i.v. model was modified to incorporate an s.c. extravascular compartment and estimate the absorption rate constant and bioavailability of nivolumab s.c. Serum concentration–time data from 82 patients treated with nivolumab s.c. 720, 960, or 1,200 mg were pooled with existing i.v. data from multiple studies for model development. Prediction‐corrected visual predictive check (pcVPC) plots assessed the model's performance. Stochastic simulations were conducted to predict exposures for i.v. and s.c. administration. The data were described by a two‐compartment model with time‐varying clearance, zero‐order infusion into the central compartment after i.v. dosing, and first‐order absorption from the extravascular compartment after s.c. dosing. The pcVPC suggested that the model adequately described the observed nivolumab s.c. data. Predicted nivolumab exposures at 1,200 mg s.c. every 4 weeks (q4w) were higher than those at the approved dose of 3 mg/kg i.v. q2w and lower than those at the highest tested safe dose of 10 mg/kg i.v. q2w. Nivolumab PK is well‐characterized using the combined s.c./i.v. population PK model. The model‐based analysis facilitated a comprehensive benefit–risk assessment of nivolumab s.c. and informed selection of 1,200 mg s.c. q4w for phase III evaluation.
Direct Esterification of Alkylcarbamic Acids with Alcohols over CeO2 Catalyst
Authors: Mihara Shogen , Yabushita Mizuho , Nakagawa Yoshinao , Tomishige Keiichi 
Published: December 2023

AbstractAlkylcarbamic acids, which are easily produced via chemical absorption of CO2 into amines, have a great potential to be substrates for producing value‐added chemicals. In this research, the esterification of various alkylcarbamic acids with alcohols into alkyl N‐alkylcarbamates was demonstrated by using a heterogeneous catalyst as well as the corresponding amine additives. In the model reaction, the esterification of benzylcarbamic acid (BZA‐CA) and methanol (MeOH), the target product of methyl N‐benzylcarbamate was obtained in 64 % CO2‐based yield at 413 K in 12 h over a CeO2 catalyst, which also exhibited good reusability. In this catalytic system, the corresponding amine additive (i. e., benzylamine for BZA‐CA) had the important role in the improvement of CO2‐moiety‐based balance, allowing the precise kinetic study, in contrast to the cases without such additive. The detailed kinetic study on the target catalytic system and control systems suggested that BZA‐CA underwent the esterification by MeOH directly. The current catalytic system using the combination of CeO2 catalyst and corresponding amine additive was also demonstrated to be applicable to the synthesis of alkyl N‐alkylcarbamates from alkylcarbamic acids and alcohols with short, linear alkyl chains (≤C3).