bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric tube perforation penetrating the pericardium after esophagectomy that needed surgical repair
Authors: Akutsu Tomohiro , Endo Akira , Okuzawa Hiraaki , Suzuki Keisuke , Yonekawa Chisato , Hoshi Hiromasa , Otomo Yasuhiro
Published: June 2023

Background

As the prognosis of esophageal cancer surgery has improved, reports on postoperative complications of gastric tubes have increased. Among them, gastric tube ulcer perforation is infrequent but often severe and difficult to treat.

Case Presentation

A 73‐year‐old man had undergone thoracoscopic subtotal esophagectomy and laparoscopic‐assisted gastric tube reconstruction via the retrosternal route for thoracic esophageal cancer 8 years previously. He was transferred to our hospital with a diagnosis of gastric tube ulcer perforation, penetrating the pericardium. Emergency surgery was performed to remove the gastric tube, followed by immediate reconstruction by right colon interposition. The patient was discharged on postoperative day 142.

Conclusion

We report a rare complication of gastric tube ulcer perforation, penetrating the pericardium, after esophagectomy for esophageal cancer. It was successfully treated with appropriate surgical management.
Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy
Authors: Liu Wanling , Zhang Yihong , Wei Gen , Zhang Minxuan , Li Tong , Liu Quanyi , Zhou Zijun , Du Yan , Wei Hui
Published: June 2023

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase‐ and glutathione peroxidase‐like activities, named MSe1, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low‐density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E‐deficient (ApoE−/−) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.
Electrocatalytic Urea Synthesis with 63.5 % Faradaic Efficiency and 100 % N‐Selectivity via One‐step C−N coupling
Authors: Zhang Xiaoran , Zhu Xiaorong , Bo Shuowen , Chen Chen , Cheng Kai , Zheng Jianyun , Li Shuang , Tu Xiaojin , Chen Wei , Xie Chao , Wei Xiaoxiao , Wang Dongdong , Liu Yingying , Chen Pinsong , Jiang San Ping , Li Yafei , Liu Qinghua , Li Conggang , Wang Shuangyin
Published: June 2023

Electrocatalytic urea synthesis via coupling N2 and CO2 provides an effective route to mitigate energy crisis and close carbon footprint. However, the difficulty on breaking N≡N is the main reason that caused low efficiencies for both electrocatalytic NH3 and urea synthesis, which is the bottleneck restricting their industrial applications. Herein, a new mechanism to overcome the inert of the nitrogen molecule was proposed by elongating N≡N instead of breaking N≡N to realize one‐step C−N coupling in the process for urea production. We constructed a Zn−Mn diatomic catalyst with axial chloride coordination, Zn−Mn sites display high tolerance to CO poisoning and the Faradaic efficiency can even be increased to 63.5 %, which is the highest value that has ever been reported. More importantly, negligible N≡N bond breakage effectively avoids the generation of ammonia as intermediates, therefore, the N‐selectivity in the co‐electrocatalytic system reaches100 % for urea synthesis. The previous cognition that electrocatalysts for urea synthesis must possess ammonia synthesis activity has been broken. Isotope‐labelled measurements and Operando synchrotron‐radiation Fourier transform infrared spectroscopy validate that activation of N−N triple bond and nitrogen fixation activity arise from the one‐step C−N coupling process of CO species with adsorbed N2 molecules.
A Click Chemistry‐Based Artificial Metallo‐Nuclease
Authors: Gibney Alex , de Paiva Raphael E. F. , Singh Vandana , Fox Robert , Thompson Damien , Hennessy Joseph , Slator Creina , McKenzie Christine J. , Johansson Pegah , McKee Vickie , Westerlund Fredrik , Kellett Andrew
Published: June 2023

Artificial metallo‐nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3‐triazole linker produced by the Cu‐catalysed azide‐alkyne cycloaddition (CuAAC) reaction can be directed to build Cu‐binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl‐thiophene to develop TC‐Thio, a bioactive C3‐symmetric ligand in which three thiophene‐triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X‐ray crystallography and forms multinuclear CuII and CuI complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, CuII‐TC‐Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide‐ and peroxide‐dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.
Chiral Phosphoric Acid Catalyzed Asymmetric Hydrolysis of Biaryl Oxazepines for the Synthesis of Axially Chiral Biaryl Amino Phenol Derivatives
Authors: Wei Liwen , Li Jiaomeng , Zhao Yi , Zhou Qinglong , Wei Zhikang , Chen Yuhang , Zhang Xinglong , Yang Xing
Published: June 2023

The development of catalytic asymmetric reaction with water as the reactant is challenging due to the reactivity‐ and stereoselectivity‐control issues resulted from the low nucleophilicity and the small size of water. We disclose herein a chiral phosphoric acid (CPA) catalyzed atroposelective ring‐opening reaction of biaryl oxazepines with water. A series of biaryl oxazepines undergo the CPA catalyzed asymmetric hydrolysis in a highly enantioselective manner. The key for the success of this reaction is the use of a new SPINOL‐derived CPA catalyst and the high reactivity of biaryl oxazepine substrates towards water under acidic conditions. Density functional theory calculations suggest that the reaction proceeds via a dynamic kinetic resolution pathway and the CPA catalyzed addition of water to the imine group is both enantio‐ and rate‐determining.
Surface Adsorbed Hydroxyl: A Double‐Edged Sword in Electrochemical CO2 Reduction over Oxide‐Derived Copper
Authors: Wei Daixing , Wang Yiqing , Dong Chung‐Li , Thi Thuy Nga Ta , Shi Yuchuan , Wang Jialin , Zhao Xiaoli , Dong Fan , Shen Shaohua
Published: June 2023

Oxide‐derived Cu (OD−Cu) featured with surface located sub‐20 nm nanoparticles (NPs) created via surface structure reconstruction was developed for electrochemical CO2 reduction (ECO2RR). With surface adsorbed hydroxyls (OHad) identified during ECO2RR, it is realized that OHad, sterically confined and adsorbed at OD−Cu by surface located sub‐20 nm NPs, should be determinative to the multi‐carbon (C2) product selectivity. In situ spectral investigations and theoretical calculations reveal that OHad favors the adsorption of low‐frequency *CO with weak C≡O bonds and strengthens the *CO binding at OD−Cu surface, promoting *CO dimerization and then selective C2 production. However, excessive OHad would inhibit selective C2 production by occupying active sites and facilitating competitive H2 evolution. In a flow cell, stable C2 production with high selectivity of ∼60 % at −200 mA cm−2 could be achieved over OD−Cu, with adsorption of OHad well steered in the fast flowing electrolyte.
Rhodium‐Catalyzed Regio‐ and Diastereoselective [3+2] Cycloaddition of gem‐Difluorinated Cyclopropanes with Internal Olefins
Authors: Zeng Yaxin , Xia Ying
Published: June 2023

Direct synthesis of gem‐difluorinated carbocyclic molecules represents a longstanding challenge in organic chemistry. Herein, a Rh‐catalyzed [3+2] cycloaddition reaction between readily available gem‐difluorinated cyclopropanes (gem‐DFCPs) and internal olefins has been developed, enabling the efficient synthesis of gem‐difluorinated cyclopentanes with good functional group compatibility, excellent regioselectivity and good diastereoselectivity. The resulting gem‐difluorinated products can undergo downstream transformations to access various mono‐fluorinated cyclopentenes and cyclopentanes. This reaction demonstrates the use of gem‐DFCPs as a type of “CF2” C3 synthon for cycloaddition under transition metal catalysis, which provides potential strategy for synthesizing other gem‐difluorinated carbocyclic molecules.
Oxa‐TriQuinoline: A New Entry to Aza‐Oxa‐Crown Architectures**
Authors: Kobayashi Toi , Kumagai Naoya
Published: June 2023

A new 15‐membered‐macrocyclic molecular entity, oxa‐TriQuinoline (o‐TQ), was designed and synthesized. In o‐TQ, three oxygen atoms were joined onto three quinoline units at the 2‐ and 8‐positions in a head‐to‐tail fashion by three‐fold SNAr reactions, giving rise to the characteristic N3O3 aza‐oxa‐crown architecture. o‐TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π–π and CH–π interactions. In the presence of the CuI cation, the non‐emissive o‐TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o‐TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem‐difluorinated terminus.
Diazulenorubicene as a Non‐benzenoid Isomer of peri‐Tetracene with Two Sets of 5/7/5 Membered Rings Showing Good Semiconducting Properties
Authors: Qin Liyuan , Huang Yan‐Ying , Wu Botao , Pan Jinliang , Yang Junfang , Zhang Jing , Han Guangchao , Yang Suyu , Chen Liangliang , Yin Zheng , Shu Yilin , Jiang Lang , Yi Yuanping , Peng Qian , Zhou Xiong , Li Cheng , Zhang Guanxin , Zhang Xi‐Sha , Wu Kai , Zhang Deqing
Published: June 2023

Non‐benzenoid polycyclic aromatic hydrocarbons (PAHs) have received a lot of attention because of their unique optical, electronic, and magnetic properties, but their synthesis remains challenging. Herein, we report a non‐benzenoid isomer of peri‐tetracene, diazulenorubicene (DAR), with two sets of 5/7/5 membered rings synthesized by a (3+2) annulation reaction. Compared with the precursor containing only 5/7 membered rings, the newly formed five membered rings switch the aromaticity of the original heptagon/pentagon from antiaromatic/aromatic to non‐aromatic/antiaromatic respectively, modify the intermolecular packing modes, and lower the LUMO levels. Notably, compound 2 b (DAR‐TMS) shows p‐type semiconducting properties with a hole mobility up to 1.27 cm2 V−1 s−1. Moreover, further extension to larger non‐benzenoid PAHs with 19 rings was achieved through on‐surface chemistry from the DAR derivative with one alkynyl group.
Borane‐Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio‐ and Diastereoselective Construction of trans‐2,3‐Disubstituted‐1,2,3,4‐Tetrahydroquinoxalines
Authors: Luo Zhenli , Li Zhewei , Zhao Haoqiang , Yang Ji , Xu Lijin , Lei Ming , Fan Qinghua , Walsh Patrick J.
Published: June 2023

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4‐tetrahydroquinoxalines. However, enantio‐ and diastereoselective access to trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair‐based catalyst generated via in situ hydroboration of 2‐vinylnaphthalene with HB(C6F5)2 allows for the one‐pot tandem cyclization/hydrosilylation of 1,2‐diaminobenzenes and 1,2‐diketones with commercially available PhSiH3 to exclusively afford trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane‐based catalyst derived from HB(C6F5)2 and a binaphthyl‐based chiral diene to give rise to enantioenriched trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with almost complete diastereo‐ and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20‐gram scale production are demonstrated. The enantio‐ and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.
Synthetic Peptide Antibodies as TNF‐α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF‐α in THP‐1 Derived Macrophages
Authors: Herrera León Claudia , Kalacas Noel Angelo , Mier Alejandra , Sakhaii Peyman , Merlier Franck , Prost Elise , Maffucci Irene , Montagna Valentina , Mora‐Radó Helena , Dhal Pradeep K. , Tse Sum Bui Bernadette , Haupt Karsten
Published: June 2023

Tumor Necrosis Factor‐α (TNF‐α) is a cytokine that is normally produced by immune cells when fighting an infection. But, when too much TNF‐α is produced as in autoimmune diseases, this leads to unwanted and persistent inflammation. Anti‐TNF‐α monoclonal antibodies have revolutionized the therapy of these disorders by blocking TNF‐α and preventing its binding to TNF‐α receptors, thus suppressing the inflammation. Herein, we propose an alternative in the form of molecularly imprinted polymer nanogels (MIP‐NGs). MIP‐NGs are synthetic antibodies obtained by nanomoulding the 3‐dimensional shape and chemical functionalities of a desired target in a synthetic polymer. Using an in‐house developed in silico rational approach, epitope peptides of TNF‐α were generated and ‘synthetic peptide antibodies’ were prepared. The resultant MIP‐NGs bind the template peptide and recombinant TNF‐α with high affinity and selectivity, and can block the binding of TNF‐α to its receptor. Consequently they were applied to neutralize pro‐inflammatory TNF‐α in the supernatant of human THP‐1 macrophages, leading to a downregulation of the secretion of pro‐inflammatory cytokines. Our results suggest that MIP‐NGs, which are thermally and biochemically more stable and easier to manufacture than antibodies, and cost‐effective, are very promising as next generation TNF‐α inhibitors for the treatment of inflammatory diseases.
Circumpentacene with Open‐Shell Singlet Diradical Character
Authors: Jiang Qing , Wei Haipeng , Hou Xudong , Chi Chunyan
Published: June 2023

Circumacenes (CAs) are a distinctive type of benzenoid polycyclic aromatic hydrocarbons where an acene unit is completely enclosed by a layer of outer fused benzene rings. Despite their unique structures, the synthesis of CAs is challenging, and until recently, the largest CA molecule synthesized was circumanthracene. In this study, we report the successful synthesis of an extended circumpentacene derivative 1, which represents the largest CA molecule synthesized to date. Its structure was confirmed by X‐ray crystallographic analysis and its electronic properties were systematically investigated by both experiments and theoretical calculations. It shows a unique open‐shell diradical character due to the existence of extended zigzag edges, with a moderate diradical character index (y0=39.7 %) and a small singlet‐triplet energy gap (ΔES‐T=−4.47 kcal/mol). It exhibits a dominant local aromatic character with π‐electrons delocalized in the individual aromatic sextet rings. It has a small HOMO–LUMO energy gap and displays amphoteric redox behavior. The electronic structures of its dication and dianion can be considered as doubly charged structures in which two coronene units are fused with a central aromatic benzene ring. This study provides a new route toward stable multizigzag‐edged graphene‐like molecules with open‐shell di/polyradical character.
Bis(1‐Methyl‐ortho‐Carboranyl)Borane
Authors: Akram Manjur O. , Tidwell John R. , Dutton Jason L. , Martin Caleb D.
Published: June 2023

The Lewis superacid, bis(1‐methyl‐ortho‐carboranyl)borane, is rapidly accessed in two steps. It is a very effective hydroboration reagent capable of B−H addition to alkenes, alkynes, and cyclopropanes. To date, this is the first identified Lewis superacidic secondary borane and most reactive neutral hydroboration reagent.
Electron Donor Coordinated Metal‐Organic Framework to Enhance Photoelectrochemical Performance
Authors: Kong Weisu , Zhu Da , Zhang Yong , Luo Rengan , Ma Jing , Lei Jianping , Ju Huangxian
Published: June 2023

To enhance photoelectrochemical (PEC) performance, additional electron donor/acceptor is generally required to inhibit the electron‐hole recombination. However, the enhancement is limited due to the long‐distance diffusion. Herein a self‐supplying electron strategy is designed for PEC enhancement by coordinating an electron donor 1.4‐diazabicyclo[2.2.2]octane (Dabco) in metal–organic framework (MOF). The intrareticular photoelectron transfer mechanism in mixed‐ligand MOF (m‐MOF) is experimentally revealed and verified by density functional theory calculations. The presence of Dabco efficiently inhibits the electron‐hole recombination due to the self‐supplying electrons and longer electron lifetime in the framework, and thus leads to 23.2‐fold enhancement of photocurrent. As proof of concept, a simple PEC method is constructed with the designed m‐MOF to demonstrate its application in sensitive bioanalysis. This work provides a new avenue for improving the PEC performance of nanomaterials.
Comparative digital reconstruction of Pica pica and Struthio camelus and their cranial suture ontogenies
Authors: Plateau Olivia , Green Todd L. , Gignac Paul M. , Foth Christian
Published: June 2023

To date, several studies describe post‐hatching ontogenetic variation in birds; however, none of these studies document and compare ontogenetic variation of the entire skull in multiple avian species. Therefore, we studied ontogenetic skull variation of two bird species with very different ecologies, Pica pica, and Struthio camelus, using μCT based 3D reconstructions. For each specimen, we performed bone‐by‐bone segmentation in order to visualize and describe the morphological variation of each bone during ontogeny and estimated the average sutural closure of the skulls to identify different ontogenetic stages. Although bone fusion of P. pica occurs more rapidly than that of S. camelus the general sequence of bone fusion follows a similar trend from posterior to anterior, but a more detailed analysis reveals some interspecific variation in the fusion patterns. Although growth persists over a longer period in S. camelus than in P. pica and adults of the former species are significantly larger, the skull of the most mature S. camelus is still less fused than that of P. pica. Different growth and fusion patterns of the two species indicate that the interspecific ontogenetic variation could be related to heterochronic developments. Nevertheless, this hypothesis needs to be tested in a broader phylogenetic framework in order to detect the evolutionary direction of the potential heterochronic transformations.
Craniogenetic studies in Sus scrofa: With emphasis on the ‘orbitosphenoid’ problem
Authors: Maier Wolfgang , Lächele Ulla , Ruf Irina
Published: June 2023

The orbitosphenoid is a skeletal element of the endocranium of extant mammals. However, it has also been described in many of their fossil ancestors. Craniogenetic studies show that it is composed of two types of bone: first, the cartilaginous ala orbitalis and parts of the trabecular plate are transformed by endochondral ossification; second, so‐called ‘appositional bone’ (‘Zuwachsknochen’) arises directly from the perichondrium of the two optic pilae and spreads in all directions and overlays the remaining cartilage and the endochondral ossifications. For some time, both bone types can be distinguished microscopically, but later in craniogenesis they fuse completely to become the presphenoid sensu lato of the osteocranium. We interpret the ‘appositional bone’ as neomorphic mode to reinforce the endocranial bone structures, which are the ossification of the delicate cartilaginous template of the chondrocranium. We studied the ossifications of the presphenoidal skull region in a series of ontogenetic stages of the pig Sus scrofa. We applied conventional histology as well as stained and unstained μCT scans. We can show the above‐mentioned modes of ossification, and we can demonstrate the contribution of ‘appositional bone’ well into neonatal and infantile stages. The ossifications of the presphenoid (including the orbitosphenoid) are very slender in therapsids and early mammaliaforms as previously described by other authors. In mammaliaforms, they tend to become thicker and closely connected with the frontal bone, which may be due to the contribution of neomorphic appositional bone. We assume that thereby the presphenoid sensu lato becomes an enforcement of the orbital pillars.
Performance of a new family of modular, bed‐supported, chromatography devices
Authors: Platteau Gerald , Stroehlein Guido , Alstine James Van , Nagaya Masayoshi
Published: June 2023

Prepacked chromatography columns and cassette filtration units offer many advantages in bioprocessing. These include reduced labor costs and processing times, ease of storage, and enhanced process flexibility. Rectangular formats are particularly attractive as they can be easily stacked and multiplexed together for continuous processing. Cylindrical chromatography beds have dominated bioprocessing even though their bed support and pressure‐flow performance vary with bed dimensions. This work presents the performance of novel, rhombohedral chromatography devices with internally supported beds. They are compatible with existing chromatography workstations and can be packed with any standard commercial resin. The devices offer pressure‐flow characteristics independent of container‐volume, simple multiplexing, and separation performance comparable to cylindrical columns. Their bi‐planar, internal bed support allows mechanically less‐rigid resins to be used at up to four times higher maximal linear velocities, and productivities approaching 200 g/L/h for affinity resins, compared to the 20 g/L/h typical of many column‐based devices. Three 5 L devices should allow processing of up to 3 kg of monoclonal antibody per hour.
Protection of biomanufacturing processes from virus contamination through upstream virus filtration of cell culture media
Authors: Wieser Andreas , Modrof Jens , Kreil Thomas R.
Published: June 2023

Cell‐based manufacturing processes have occasionally been exposed to adventitious viruses, leading to manufacturing interruptions and unstable supply situations. The rapid progress of advanced therapy medicinal products needs innovative approaches to avoid any unwelcome reminder of the universal presence of viruses. Here, we investigated upstream virus filtration as a clearance step for any product too complex for downstream interventions. Culture media virus filtration was investigated with respect to virus clearance capacities under extreme conditions such as high process feed loading (up to ~19,000 L/m²), long duration (up to 34 days), and multiple process interruptions (up to 21 h). The small nonenveloped Minute virus of mice was used as relevant target virus, and as worse‐case challenge for the investigated virus filters with a stipulated pore‐size of about 20 nm. Certain filters—especially of the newer second generation—were capable of effective virus clearance despite the harsh regimen they were subjected to. The biochemical parameters for un‐spiked control runs showed the filters to have no measurable impact on the composition of the culture media. Based on these findings, this technology seems to be quite feasible for large volume premanufacturing process culture media preparations.
Preparation of amentoflavone‐loaded DSPE‐PEG2000 micelles with improved bioavailability and in vitro antitumor efficacy
Authors: Feng Yuan , Wang Jin , Zhang Shuaishuai , Li Yanan , Wang Boxin , Zhang Jiayuan , Qiu Yingzhe , Zhang Yi , Zhang Yuanyuan
Published: June 2023

To overcome the poor aqueous solubility and enhance the anticancer effects of amentoflavone (AF), a nontoxic and biodegradable amphiphilic copolymer, poly(ethyleneglycol)‐distearoylphosphatidylethanolamine (DSPE‐PEG2000), was introduced to prepare AF micelles using the thin‐film hydration method. Amentoflavone was successfully encapsulated into the core, achieving an encapsulation efficiency of 98.80 ± 0.24% and a drug loading efficiency of 2.96 ± 0.12%. The resulting micelles exhibited a spherical shape with a particle size of approximately 25.99 nm. The solubility of AF was significant improved by 412‐fold, and cumulative drug release studies showed that AF release was much faster from the micelles compared with the free drug. The release of AF was sustained over time and followed a degradation‐based kinetic model, similar to polymeric systems. After oral administration, the AF‐loaded micelles demonstrated an enhanced oral bioavailability, which was 3.79 times higher than that of free AF. In vitro evaluations of the micelles’ antitumor effects revealed a significantly greater efficacy compared with free AF. These findings highlight the tremendous potential of DSPE‐PEG2000 micelles as a drug delivery carrier for improving the solubility and therapeutic efficacy of AF.
The competition between private label and national brand through the signal of Euro‐leaf
Authors: Schena Rosamartina , Morrone Domenico , Russo Angeloantonio
Published: June 2023

The current study aims to determine the effect on consumer behaviour when an ecological signal, such as an eco‐label, is provided on various food packaging. In particular, this work aims to understand the strategic role of the eco‐label as a brand equity by introducing a new theoretical model of eco‐brand equity from a consumer perspective. Through a sample of 1.075 Italian consumers, their behaviour and preferences are modelled for 10 types of food using the presence of the brand and the private label with and without the eco‐label as control conditions. In particular, the eco‐label reflects some specific attributes of a brand, for example, loyalty, quality, reputation and association, demonstrating its brand equity. The findings support the hypothesis that the eco‐label has a brand value capable of reducing information asymmetries, increasing confidence and credibility in the agri‐food market. From a theoretical perspective, this research identifies the eco‐label as extrinsic signals able to affect consumers' behaviour. Moreover, the findings of this study present practical implications supporting the process towards more sustainable systems in the food sector.
Seeing the data for the trees: Assessing the data maturity and readiness of a UK forestry company
Authors: Martí‐Rosselló Teresa , Duncan Andrew J. , Bowditch Euan
Published: June 2023

A large UK forestry company has been used as the case study to assess the organisational aspects that hinder forestry organisations from reaching data maturity and becoming data driven. This study focuses on the organisational aspects of dealing with data, as they are often disregarded in favour of dealing only with the technical aspects. The barriers to reaching data maturity have been assessed by means of an online survey distributed across the company. Additionally, the study explores how willing the company is to make changes towards becoming more data driven, assess the data capabilities of the company, identify which benefits of harnessing data are viewed more positively and to estimate the data maturity level of the organisation. The results showed that the company case study was in the early‐mid stages of data maturity with significant opportunity for improvement. The main barriers identified were cultural, along with some other organisational barriers related to data roles and data strategy. Improving the data maturity of the organisation case study consisted of increasing data‐skills, prioritising data‐driven decision making at management level and finally elaborating an organisation‐wide data strategy.
Sustainable business models and conflict indices for sustainable decision‐making: An application to decommissioning versus reusing offshore gas platforms
Authors: Zagonari Fabio
Published: June 2023

This paper combines theoretical sustainable business models and conflict indices in making practical sustainable (i.e., participatory decisions involving economic, social, and environmental features within weak or strong sustainability paradigms) and rational (i.e., informed and consistent decisions within substantive or instrumental rationality) decisions with respect to what, who, where, when, and how to act. The case study, focused on an offshore gas platform, identified when (i.e., the end as opposed to the beginning of extraction activities) and where (i.e., the economic, social, and environmental contexts of the Adriatic Sea in Abruzzo region, Italy). A face‐to‐face questionnaire, submitted to stakeholders, produced the relative weights required by the tested sustainable business models (Lüdeke‐Freund et al., 2018), and it reached a conclusion about how (i.e., in favor of the majority as opposed to average decisions). An application of a linear conflict index (Fasth et al., 2018) highlighted a lack of stakeholders' representativeness and knowledge and solved these issues with a 50% increase of stakeholders involved and an additional discussion with originally invited stakeholders on specific topics, respectively. In summary, the methodology suggested in this paper produced a (strong) sustainable and (substantive) rational decision about what and who based on relative weights expressed by representative and informed stakeholders being engaged at the smallest cost and with the largest support. Thus, the contribution of this paper is twofold: Theoretically, choices among alternative sustainable businesses depend on the adopted sustainability paradigm, and practically, choices among alternative sustainable businesses should be identified according to the adopted sustainability paradigm.
Differential risk of 23 site‐specific incident cancers and cancer‐related mortality among patients with metabolic dysfunction‐associated fatty liver disease: a population‐based cohort study with 9.7 million Korean subjects
Authors: Chung Goh Eun , Yu Su Jong , Yoo Jeong‐Ju , Cho Yuri , Lee Kyu‐na , Shin Dong Wook , Kim Yoon Jun , Yoon Jung‐Hwan , Han Kyungdo , Cho Eun Ju
Published: June 2023

Introduction

Although an association between metabolic dysfunction‐associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all‐ and site‐specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease.

Methods

Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single‐etiology MAFLD (S‐MAFLD) or MAFLD of pure metabolic origin; (2) mixed‐etiology MAFLD (M‐MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non‐MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events.

Results

Among the 9,718,182 participants, the prevalence of S‐MAFLD and M‐MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow‐up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer‐related deaths occurred among the entire cohort. Compared with the non‐MAFLD group, the risk of all‐cancer incidence and mortality was slightly higher among patients in the S‐MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02−1.04; mortality, aHR = 1.06; 95% CI: 1.04−1.08) and highest among patients with M‐MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29−1.32; mortality, aHR = 1.45; 95% CI: 1.42−1.48, respectively). The M‐MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all‐cancer incidence (aHR = 1.38, 95% CI = 1.36–1.39), followed by the M‐MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06–1.11). Similar trends were observed for cancer‐related mortality.

Conclusions

MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer‐related outcomes.
Parthenolide inhibits proliferation and invasion, promotes apoptosis, and reverts the cell–cell adhesion loss through downregulation of NF‐κB pathway TNF‐α‐activated in colorectal cancer cells
Authors: Gehren Adriana S. , de Souza Waldemir F. , Sousa‐Squiavinato Annie C. M. , Ramos Diego A. A. , Pires Bruno R. B. , Abdelhay Eliana S. F. W. , Morgado‐Diaz Jose A.
Published: June 2023

The activation of the nuclear factor‐κB (NF‐κB) pathway has been associated with the development and progression of colorectal cancer (CRC). Parthenolide (PTL), a well‐known inhibitor of the NF‐κB pathway, has emerged as an alternative treatment. However, whether PTL activity is tumor cell‐specific and dependent on the mutational background has not been defined. This study investigated the antitumor role of PTL after tumor necrosis factor‐α (TNF‐α) stimulation in various CRC cell lines with different mutational statuses of TP53. We observed that CRC cells displayed different patterns of basal p‐IκBα levels; PTL reduced cell viability according to p‐IκBα levels and p‐IκBα levels varied among the cell lines according to the time of TNF‐α stimulation. High concentrations of PTL reduced more effectively p‐IκBα levels than low doses of PTL. However, PTL increased total IκBα levels in Caco‐2 and HT‐29 cells. In addition, PTL treatment downregulated p‐p65 levels in HT‐29 and HCT‐116 cells stimulated by TNF‐α in a dose‐dependent manner. Moreover, PTL induced cell death via apoptosis and reduced the proliferation rate of TNF‐α‐treated HT‐29 cells. Finally, PTL downregulated the messenger RNA levels of interleukin‐1β, a downstream cytokine of NF‐κB, reverted the E‐cadherin‐mediated disorganization of cell–cell contacts, and decreased the invasion of HT‐29 cells. Together, these results suggest a differential antitumoral activity of PTL on CRC cells with different mutational statuses of TP53, modulating cell death, survival, and proliferation underlying the NF‐κB pathway TNF‐α‐induced. Therefore, PTL has emerged as a potential treatment for CRC in an inflammatory NF‐κB‐dependent manner.
Periprocedural myocardial infarction in patients undergoing complex versus noncomplex percutaneous coronary intervention
Authors: Piccolo Raffaele , Leone Attilio , Simonetti Fiorenzo , Avvedimento Marisa , Angellotti Domenico , Manzi Lina , Verde Nicola , Spaccarotella Carmen Anna Maria , Di Serafino Luigi , Cirillo Plinio , Gargiulo Giuseppe , Fortunato Giuliana , Franzone Anna , Esposito Giovanni
Published: June 2023

Background

Limited data are available on the risk of periprocedural myocardial infarction (MI) in patients undergoing complex versus noncomplex percutaneous coronary intervention (PCI).

Methods

We assessed the risk of periprocedural MI according to the fourth Universal definition of myocardial infarction (UDMI) and several other criteria among patients undergoing elective PCI in a prospective, single‐center registry. Complex PCI included at least one of the following: 3 coronary vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, treatment of chronic total occlusion, and use of rotational atherectomy.

Results

Between 2017 and 2021, we included 1010 patients with chronic coronary syndrome, of whom 226 underwent complex PCI (22.4%). The rate of periprocedural MI according to the fourth UDMI was significantly higher in complex compared to noncomplex PCI patients (26.5% vs. 14.5%, p < 0.001). Additionally, periprocedural MI was higher in the complex PCI group using SCAI (4% vs. 1.1%, p = 0.009), ARC‐2 (13.7% vs. 8.0%, p = 0.013), ISCHEMIA (5.8% vs. 1.7%, p = 0.002), and EXCEL criteria (4.9% vs. 2.0%, p = 0.032). SYNTAX periprocedural MI occurred at low rates in both groups (0.9% vs. 0.6%, p = 0.657). Complex PCI was an independent predictor of the fourth UDMI periprocedural MI (odds ratio [OR] 1.54, 95% confidence interval [CI]: 1.04–2.27, p = 0.031).

Conclusions

In patients with chronic coronary syndrome undergoing elective PCI, complex PCI is associated with a significantly higher risk of periprocedural MI using multiple definitions. These findings highlight the importance of considering upfront this risk in the planning of complex PCI procedures.
Syringomatous adenoma of the nipple: A case series and systematic review
Authors: Park Sean K. , Samat Sajjaad H. , Whitelock Courtney M. , Fortes Thais
Published: June 2023

Key Clinical Message

SAN should be considered in the setting of nipple discharge or morphology changes with typical histological findings. There are limited published cases of SAN, and workup of this pathology is still not clear to date.

Syringomatous adenoma of the nipple (SAN) is known to be a rare benign breast neoplasm. With a few cases documented in the literature, preoperatively diagnosing this tumor is a challenge, which often leads to invasive procedure such as mass excision with nipple removal. This study was aimed at presenting a case report of SAN and to conduct a review of published cases. Literature search was conducted through PubMed databases. Articles published from year 1983 to March of 2022 were included. Only histologically confirmed cases of SAN were included. The review was performed according to the PRISMA guidelines. Twenty‐eight cases, including the newly reported case, were included in the review after going through inclusion criteria. The mean age at diagnosis was 44 ± 16 years. 7% were male. The most common presentation was palpable mass. Preoperative biopsy was done for 9 cases, out of which 7 did not indicate typical histopathological characteristic of SAN. Most common treatment was wide local excision with nipple removal. Immunohistochemical staining of the resected tumor was performed in 16 cases postoperatively. 32.1% (9/28) utilized p63 in constellation with histologic findings. Five cases that utilized staining also used Estrogen Receptor (ER) marker, while three used progesterone receptor (PR) marker. SAN should be considered in the setting of nipple discharge or morphology changes with typical histological findings. There are limited published cases of SAN, and workup of this pathology is still not clear to date. The case presented here and our comprehensive literature review suggest that pathohistological findings of SAN can be heterogeneous. Clinicians would also benefit from recognizing these variances. Further research and reported cases are needed to confidently diagnose SAN, which may open doors for less aggressive surgical treatment or surveillance option for asymptomatic patients.
SN2 versus E2 Competition of Cyclic Ethers
Authors: Hansen Thomas , Vermeeren Pascal , Zijderveld Kim W. J. , Bickelhaupt F. Matthias , Hamlin Trevor A.
Published: June 2023

We have quantum chemically studied the influence of ring strain on the competition between the two mechanistically different SN2 and E2 pathways using a series of archetypal ethers as substrate in combination with a diverse set of Lewis bases (F−, Cl−, Br−, HO−, H3CO−, HS−, H3CS−), using relativistic density functional theory at ZORA‐OLYP/QZ4P. The ring strain in the substrate is systematically increased on going from a model acyclic ether to a 6‐ to 5‐ to 4‐ to 3‐membered ether ring. We have found that the activation energy of the SN2 pathway sharply decreases when the ring strain of the system is increased, thus on going from large to small cyclic ethers, the SN2 reactivity increases. In contrast, the activation energy of the E2 pathway generally rises along this same series, that is, from large to small cyclic ethers. The opposing reactivity trends induce a mechanistic switch in the preferred reaction pathway for strong Lewis bases from E2, for large cyclic substrates, to SN2, for small cyclic substrates. Weak Lewis bases are unable to overcome the higher intrinsic distortivity of the E2 pathway and, therefore, always favor the less distortive SN2 reaction.
The Oxidation of Oxygen and Sulfur‐Containing Heterocycles by Cytochrome P450 Enzymes
Authors: Podgorski Matthew N. , Keto Angus B. , Coleman Tom , Bruning John B. , De Voss James J. , Krenske Elizabeth H. , Bell Stephen G.
Published: June 2023

The cytochrome P450 (CYP) superfamily of monooxygenase enzymes play important roles in the metabolism of molecules which contain heterocyclic, aromatic functional groups. Here we study how oxygen‐ and sulfur‐containing heterocyclic groups interact with and are oxidized using the bacterial enzyme CYP199A4. This enzyme oxidized both 4‐(thiophen‐2‐yl)benzoic acid and 4‐(thiophen‐3‐yl)benzoic acid almost exclusively via sulfoxidation. The thiophene oxides produced were activated towards Diels‐Alder dimerization after sulfoxidation, forming dimeric metabolites. Despite X‐ray crystal structures demonstrating that the aromatic carbon atoms of the thiophene ring were located closer to the heme than the sulfur, sulfoxidation was still favoured with 4‐(thiophen‐3‐yl)benzoic acid. These results highlight a preference of this cytochrome P450 enzyme for sulfoxidation over aromatic hydroxylation. Calculations predict a strong preference for homodimerization of the enantiomers of the thiophene oxides and the formation of a single major product, in broad agreement with the experimental data. 4‐(Furan‐2‐yl)benzoic acid was oxidized to 4‐(4′‐hydroxybutanoyl)benzoic acid using a whole‐cell system. This reaction proceeded via a γ‐keto‐α,β‐unsaturated aldehyde species which could be trapped in vitro using semicarbazide to generate a pyridazine species. The combination of the enzyme structures, the biochemical data and theoretical calculations provides detailed insight into the formation of the metabolites formed from these heterocyclic compounds.
Cyaphide‐Azide 1,3‐Dipolar Cycloaddition Reactions: Scope and Applicability
Authors: Yang Eric S. , Mapp Alex , Taylor Andrew , Beer Paul D. , Goicoechea Jose M.
Published: June 2023

Several examples of the cyaphide‐azide 1,3‐dipolar cycloaddition reaction to afford metallo‐triazaphospholes are reported. The gold(I) triazaphospholes Au(IDipp)(CPN3R) (IDipp=1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene; R=tBu, Ad, Dipp), magnesium(II) triazaphospholes, {Mg(DippNacNac)(CPN3R)}2 (DippNacNac=CH{C(CH3)N(Dipp)}2, Dipp=2,6‐diisopropylphenyl; R=tBu, Bn), and germanium(II) triazaphosphole Ge(DippNacNac)‐(CPN3tBu) can be prepared straightforwardly, under mild conditions and in good yields, in a manner reminiscent of the classic alkyne‐azide click reaction (albeit without a catalyst). This reactivity can be extended to compounds with two azide functional groups such as 1,3‐diazidobenzene. It is shown that the resulting metallo‐triazaphospholes can be used as precursors to carbon‐functionalized species, including protio‐ and iodo‐triazaphospholes.
The Interaction Between Interface Morphology of Particles with Anisotropic Effect of Interface Kinetics in an Alloy Melt
Authors: Zheng Guanjie , Chen Mingwen , Yang Chunmei , Liu Nan
Published: June 2023

The conventional theory of crystal growth presents an irreversible outward increase of the crystal size through solute deposition on the nuclei; however, the asymptotic solution of the dynamics model of the particle reveals that the crystal growth undergoes a locally reversible inward growth process in the early stage of crystal growth. Immediately after nucleation, some parts of the interface first grow inward through solute rejection along certain crystal orientations from the interface of nucleation, while the other parts of the interface grow outward through solute deposition along other crystal orientations. Until the inward growth attains a certain distance, the interface grows outward along each crystal orientation. This growth behavior is attributed to the interaction between interface morphology of particles with the anisotropic effect of interface kinetics. Through a systematic variation of the anisotropy parameters, the particle exhibits a continuous transition from one growth morphology to other growth morphologies. During the morphological transition process, as initial concentration increases, the growth of the particle is inhibited in the preferred growth directions, whereas it is facilitated in other growth directions. As a result, the interface morphologies of the particle with different petal‐shaped morphologies in the early stage of crystal growth are formed.
Advances of Modified Lignin as Substitute to Develop Lignin‐Based Phenol‐Formaldehyde Resin Adhesives
Authors: Peng Zhenwen , Jiang Xiao , Si Chuanling , Joao Cárdenas‐Oscanoa Aldo , Huang Caoxing
Published: June 2023

Traditionally, phenols used to prepare phenol‐formaldehyde (PF) resin adhesives are obtained from phenolic compounds and various chemicals, which are extracted from petroleum‐based raw materials. Lignin, a sustainable phenolic macromolecule in the cell wall of biomass with an aromatic ring and a phenolic hydroxyl group similar to those of phenol, can be an ideal substitute for phenol in PF resin adhesives. However, only a few lignin‐based adhesives are produced on a large scale in industry, mainly because of the low activity of lignin. Preparing lignin‐based PF resin adhesives with exceptional achievements by modifying lignin instead of phenol is an efficient method to improve the economic benefits and protect the environment. In this review, the latest progress in the preparation of PF resin adhesives via lignin modification, including chemical, physical, and biological modifications, is discussed. In addition, the advantages and disadvantages of different lignin modification methods for adhesives are compared and discussed, and future research directions for the synthesis of lignin‐based PF resin adhesives are proposed.