bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperative Photoredox and Cobalt‐Catalyzed Acceptorless Dehydrogenative Functionalization of Cyclopropylamides towards Allylic N,O‐Acyl‐acetal Derivatives
Authors: Huang Haohao , Luan Xinjun , Zuo Zhijun
Published: April 2024

We disclose herein a novel photoredox and cobalt co‐catalyzed ring‐opening/acceptorless dehydrogenative functionalization of mono‐donor cyclopropanes. This sustainable and atom‐economic approach allows the rapid assembly of a wide range of allylic N,O‐acyl‐acetal derivatives. The starting materials are readily available and the reaction features mild conditions, broad substrate scope, and excellent functional group compatibility. The optimized conditions accommodate assorted cycloalkylamides and primary, secondary, and tertiary alcohols, with applications in late‐stage functionalization of pharmaceutically relevant compounds, stimulating further utility in medicinal chemistry. Moreover, selective nucleophilic substitutions with various carbon nucleophiles were achieved in a one‐pot fashion, offering a reliable avenue to access some cyclic and acyclic derivatives.
Revealing the Influence of Electron Migration Inside Polymer Electrolyte on Li+ Transport and Interphase Reconfiguration for Li Metal Batteries
Authors: Jin Yingmin , Lin Ruifan , Li Yumeng , Zhang Xuebai , Tan Siping , Shuai Yong , Xiong Yueping
Published: April 2024

The development of highly producible and interfacial compatible in situ polymerized electrolytes for solid‐state lithium metal batteries (SSLMBs) have been plagued by insufficient transport kinetics and uncontrollable dendrite propagation. Herein, we seek to explore a rationally designed nanofiber architecture to balance all the criteria of SSLMBs, in which La0.6Sr0.4CoO3−δ (LSC) enriched with high valence‐state Co species and oxygen vacancies is developed as electronically conductive nanofillers embedded within ZnO/Zn3N2‐functionalized polyimide (Zn‐PI) nanofiber framework for the first time, to establish Li+ transport highways for poly vinylene carbonate (PVC) electrolyte and eliminate nonuniform Li deposits. Revealed by characterization and theoretical calculation under electric field, the positive‐negative electrical dipole layer in LSC derived from electron migration between Co and O atoms aids in accelerating Li+ diffusion kinetics through densified electric field around filler particle, featuring a remarkable ionic conductivity of 1.50 mS cm−1 at 25 °C and a high Li+ transference number of 0.91 without the risk of electron leakage. Integrating with the preferential sacrifice of ZnO/Zn3N2 on PI nanofiber upon immediate detection of dendritic Li, which takes part in reconfiguring hierarchical SEI chemistry dominated by LixNy/Li−Zn alloy inner layer and LiF outer layer, SSLMBs are further endowed with prolonged cycling lifespan and exceptional rate capability.
A Dielectric MXene‐Induced Self‐Built Electric Field in Polymer Electrolyte Triggering Fast Lithium‐Ion Transport and High‐Voltage Cycling Stability
Authors: Zhang Baolin , Su Yufeng , Chen Yangyang , Qi Shengguang , Li Mianrui , Zou Wenwu , Jiang Guoxing , Zhang Weifeng , Gao Yuqing , Pan Chenhui , Song Huiyu , Cui Zhiming , Zhang Chuanfang (John) , Liang Zhenxing , Du Li
Published: April 2024

Quasi‐solid polymer electrolyte (QPE) lithium (Li)‐metal battery holds significant promise in the application of high‐energy‐density batteries, yet it suffers from low ionic conductivity and poor oxidation stability. Herein, a novel self‐built electric field (SBEF) strategy is proposed to enhance Li+ transportation and accelerate the degradation dynamics of carbon‐fluorine bond cleavage in LiTFSI by optimizing the termination of MXene. Among them, the SBEF induced by dielectric Nb4C3F2 MXene effectively constructs highly conductive LiF‐enriched SEI and CEI stable interfaces, moreover, enhances the electrochemical performance of the QPE. The related Li‐ion transfer mechanism and dual‐reinforced stable interface are thoroughly investigated using ab initio molecular dynamics, COMSOL, XPS depth profiling, and ToF‐SIMS. This comprehensive approach results in a high conductivity of 1.34 mS cm−1, leading to a small polarization of approximately 25 mV for Li//Li symmetric cell after 6000 h. Furthermore, it enables a prolonged cycle life at a high voltage of up to 4.6 V. Overall, this work not only broadens the application of MXene for QPE but also inspires the great potential of the self‐built electric field in QPE‐based high‐voltage batteries.
Similarities and Differences in Benzene Reduction with Ca, Sr, Yb and Sm: Strong Evidence for Tetra‐Anionic Benzene
Authors: Thakur Sandeep Kumar , Roig Nil , Monreal‐Corona Roger , Langer Jens , Alonso Mercedes , Harder Sjoerd
Published: April 2024

Inverse sandwich complexes of Yb and Sm stabilized by a bulky β‐diketiminate (BDI) ligand have been prepared: (BDI)Ln(η6,η6‐C6H6)Ln(BDI); Ln=lanthanide. Coordinated benzene ligands can be neutral, di‐anionic or, often controversially discussed, even tetra‐anionic. The formal charge on benzene is correlated to assignment of the metal oxidation state which generally poses a problem. Herein, we take advantage of the structural similarities found when comparing CaII with YbII, and SrII with SmII complexes. In this work, we found an excellent overlap of the Ca/Yb inverse sandwich structures but a striking difference for the Sr/Sm pair. The much shorter Sm−N and Sm‐C6H6 distances are strong evidence for a SmIII‐benzene−4‐SmIII assignment. This was further supported by NMR spectroscopy, magnetic susceptibility, reactivity and comprehensive computational investigation.
Highly dispersed biochar as a sustainable filler for enhancing mechanical performance and biodegradation of polybutylene succinate
Authors: Noh Seungchan , Kim Dohyeong , Jeong Gayeon , Koo Jun Mo , Koo Jaseung
Published: April 2024

Sustainability has become increasingly important as environmental issues continue to rise. Biodegradable polymers offer a sustainable solution as they use biomass. In this study, biochar (BC) prepared by the pyrolysis of biomass was compounded with polybutylene succinate (PBS) to enhance its Young's modulus, and the residual BC was shown to amend the soil, following degradation. The incorporation of biochar into the PBS matrix is strategically achieved through a BC with treatment involving an aprotic polar solvent. This process not only reduces the size of the biochar particles but also ensures their uniform dispersion within the PBS matrix. As a result, a remarkable 2.5‐fold increase in Young's modulus is observed, reaching an impressive 571.04 MPa, compared with the baseline Young's modulus of neat PBS, which stands at 220.92 MPa. Interestingly, the degradation rate of the resulting composites was comparable to that of neat PBS despite the decrease in the number of potential hydrolysis sites owing to the increased Young's modulus of the PBS/BC composite. These sustainable composite exhibited properties different from those of conventional PBS and is expected to be used in potentially novel applications toward environmental sustainability, such as in agricultural mulch films or electronic printing.
Molecular dynamics simulations of the solubility of chitosan grafted polyacrylamide and its adsorption mechanism with kaolinite: Impact of length and distribution of branched‐chain
Authors: Zhao Wei , Zou Wenjie , Liu Fengyang , Zhang Zhijun , Li Zhengyao , Xiao Ting
Published: April 2024

Graft modification can effectively improve the flocculation performance of chitosan. In this work, molecular dynamics simulations were employed to investigate the water solubility of chitosan‐grafted polyacrylamide (CTS‐g‐PAM) and its adsorption mechanism with kaolinite, focusing on the effects of branched‐chain length and distribution. The solubility parameters obtained from the simulations align better with those calculated using the group contribution method. The radius of gyration (Rg), solvation free energy (∆GSFE), mean square displacement and diffusion coefficient were utilized to analyze changes in solubility of these CTS‐g‐PAM in aqueous solution. The adsorption interaction between CTS‐g‐PAM and kaolinite was investigated using interaction energy and diffusion coefficients. The water solubility of CTS‐g‐PAM initially increased, followed by a subsequent decrease as the length of branched‐chain increased along with a decrease in their number. Similarly, the adsorption interaction between CTS‐g‐PAM and kaolinite increased firstly followed by a decrease with increasing branched‐chain length. The magnitude of interaction energy with kaolinite (0 0 1) followed the order of CA10‐12 (−826.227 kcal/mol) >CA8‐15 (−744.583 kcal/mol) >CA6‐20 (−637.366 kcal/mol) >CA12‐10 (−598.109 kcal/mol). These trends align with the findings of flocculation tests. Our work provides a theoretical basis for designing chitosan‐based flocculants with enhanced water solubility and improved flocculation efficiency.
Postcranial anomalies of Eocene freshwater pleurodiran and cryptodiran turtles from the Spanish Duero Basin
Authors: Guerrero Andrea , Ortega Francisco , Martín de Jesús Santiago , Pérez‐García Adán
Published: April 2024

Testudines are one of the best‐represented taxonomic groups among the Paleogene taxa of the Duero Basin (Castile and Leon Autonomous Community, central Spain). Among them, Neochelys (Podocnemidide) and Allaeochelys (Carettochelyidae) are most abundant, allowing the population to be assessed for osteological anomalies. The abundance of postcranial remains of both taxa allows us to identify several individuals with potential anomalies, mostly in their shells. Some of them have already been described in previous studies, but most of them are still unpublished. The objective of this study is to analyze in detail the anomalous Neochelys and Allaeochelys remains. As a result, different categories of causal agents (such as bacteria, fungi, parasites, or trauma) have been identified as potential producers of the anomalies in these freshwater turtles. Information regarding the pathogenesis and healing stages of some of these anomalies is provided.
Comparing cranial biomechanics between Barbourofelis fricki and Smilodon fatalis: Is there a universal killing‐bite among saber‐toothed predators?
Authors: Figueirido Borja , Tucker Shane , Lautenschlager Stephan
Published: April 2024

Saber‐tooths, extinct apex predators with long and blade‐like upper canines, have appeared iteratively at least five times in the evolutionary history of vertebrates. Although saber‐tooths exhibit a relatively diverse range of morphologies, it is widely accepted that all killed their prey using the same predatory behavior. In this study, we CT‐scanned the skull of Barbourofelis fricki and compared its cranial mechanics using finite element analysis (FEA) with that of Smilodon fatalis. Our aim was to investigate potential variations in killing behavior between two dirk‐toothed sabretooths from the Miocene and Pleistocene of North America. The study revealed that B. fricki had a stoutly‐built skull capable of withstanding stress in various prey‐killing scenarios, while the skull of S. fatalis appeared less optimized for supporting stress, which highlights the highly derived saber‐tooth morphology of the former. The results may indicate that B. fricki was more of a generalist in prey‐killing compared to S. fatalis, which experiences lower stresses under stabbing loads. We hypothesize that morphological specialization in saber‐tooths does not necessarily indicate ecological specialization. Our results support the notion that morphological convergence among saber‐toothed cats may obscure differences in hunting strategies employed to dispatch their prey. Our findings challenge the assumption of the universally assumed canine‐shear biting as the prey‐killing behavior of all saber‐toothed cats. However, further research involving a wider range of dirk and scimitar‐toothed forms could provide additional insights into the diversity of cranial biomechanics within this fascinating group of extinct mammalian predators.
Nonflammable Solid‐State Polymer Electrolyte for High‐Safety and Ultra‐Stable Lithium‐Ion Batteries
Authors: Zhang Chao , Liu Jingwen , Zhang Shenghao , Wang Minghui , Lv Qingliang , Li Caixia , Wang Lei
Published: April 2024

High safety and stability in batteries are crucial factors for the large‐scale application of lithium‐ion technology. In this work, flame‐retardant aluminum diethylphosphonite (ADP) is coated by urea‐formaldehyde (UF) shell to conquer the side reactions caused by ADP during cycling process. And then the core@shell structured ADP@UF is combined with poly(ethylene oxide) (PEO), high thermal stability can be realized. When exposed to high temperatures, ADP@UF generates N⋅ and P⋅ radicals to eliminate the combustion the H⋅ and OH⋅ radical, to inhibit fire. By controlling the percentage of flame retardant added, PEO‐ADP@UF has totally achieved the effect of inflaming retarding, realizing stable electrochemical properties at the same time. The −NH2 in UF forms hydrogen bonds with PEO, and acts as a Lewis base to promote the dissociation of lithium salts to increase the lithium‐ion mobility number. Compared to PEO, battery with PEO‐ADP@UF has outstanding cycling performance (103 mAh g−1 at 1 C, 2.5–4.2 V) and long service life (800 cycles).
Multivariate data analysis on multisensor measurement for inline process monitoring of adenovirus production in HEK293 cells
Authors: Xu Xingge , Farnós Omar , Paes Barbara C. M. F. , Nesdoly Sean , Kamen Amine A.
Published: April 2024

In the era of Biopharma 4.0, process digitalization fundamentally requires accurate and timely monitoring of critical process parameters (CPPs) and quality attributes. Bioreactor systems are equipped with a variety of sensors to ensure process robustness and product quality. However, during the biphasic production of viral vectors or replication‐competent viruses for gene and cell therapies and vaccination, current monitoring techniques relying on a single working sensor can be affected by the physiological state change of the cells due to infection/transduction/transfection step required to initiate production. To address this limitation, a multisensor (MS) monitoring system, which includes dual‐wavelength fluorescence spectroscopy, dielectric signals, and a set of CPPs, such as oxygen uptake rate and pH control outputs, was employed to monitor the upstream process of adenovirus production in HEK293 cells in bioreactor. This system successfully identified characteristic responses to infection by comparing variations in these signals, and the correlation between signals and target critical variables was analyzed mechanistically and statistically. The predictive performance of several target CPPs using different multivariate data analysis (MVDA) methods on data from a single sensor/source or fused from multiple sensors were compared. An MS regression model can accurately predict viable cell density with a relative root mean squared error (rRMSE) as low as 8.3% regardless of the changes occurring over the infection phase. This is a significant improvement over the 12% rRMSE achieved with models based on a single source. The MS models also provide the best predictions for glucose, glutamine, lactate, and ammonium. These results demonstrate the potential of using MVDA on MS systems as a real‐time monitoring approach for biphasic bioproduction processes. Yet, models based solely on the multiplicity and timing of infection outperformed both single‐sensor and MS models, emphasizing the need for a deeper mechanistic understanding in virus production prediction.
Single cell analysis of Chinese hamster ovary cells during a bioprocess using a novel dynamic imaging system
Authors: Breen Laura , Flynn James , Bergin Adam , Flampouri Evangelia , Butler Michael
Published: April 2024

Reliable monitoring of mammalian cells in bioreactors is essential to biopharmaceutical production. Trypan blue exclusion is a method of determining cell density and viability that has been used for over one hundred years to monitor cells in culture and is the current standard method in biomanufacturing. This method has many disadvantages however and there is a growing demand for more detailed and in‐line measurements of cell growth in bioreactors. This article assesses a novel dynamic imaging system for single cell analysis. This data shows that comparable total cell density, viable cell density and percentage viability data shown here, generated by the imaging system, aligned well with conventional trypan blue counting methods for an industrially relevant Chinese Hamster Ovary (CHO) cell line. Furthermore, detailed statistical analysis shows that the classification system used by the PharmaFlow system can reveal trends of interest in monitoring the health of mammalian cells over a 6‐day bioreactor culture. The system is also capable of sampling at‐line, removing the necessity for taking samples off‐line and enabling real time monitoring of cells in a bioreactor culture.
Monte Carlo simulation‐guided design for size‐tuned tumor spheroid formation in 3D printed microwells
Authors: Eş Ismail , Ionescu Ana‐Maria Theodora , Görmüş Burak M. , Inci Fatih , Marques Marco P. C. , Szita Nicolas , de la Torre Lucimara Gaziola
Published: April 2024

Tumor spheroid models have garnered significant attention in recent years as they can efficiently mimic in vivo models, and in addition, they offer a more controlled and reproducible environment for evaluating the efficacy of cancer drugs. In this study, we present the design and fabrication of a micromold template to form multicellular spheroids in a high‐throughput and controlled‐sized fashion. Briefly, polydimethylsiloxane‐based micromolds at varying sizes and geometry were fabricated via soft lithography using 3D‐printed molds as negative templates. The efficiency of spheroid formation was assessed using GFP‐expressing human embryonic kidney 293 cells (HEK‐293). After 7 days of culturing, circularity and cell viability of spheroids were >0.8 and 90%, respectively. At 1500 cells/microwell of cell seeding concentration, the spheroids were 454 ± 15 μm, 459 ± 7 μm, and 451 ± 18 μm when cultured in microwells with the diameters of 0.4, 0.6, and 0.8 μm, respectively. Moreover, the distance between each microwell and surfactant treatment before cell seeding notably impacted the uniform spheroid formation. The centrifugation was the key step to collect cells on the bottom of the microwells. Our findings were further verified using a commercial microplate. Furthermore, Monte Carlo simulation confirmed the seeding conditions where the spheroids could be formed. This study showed prominent steps in investigating spheroid formation, thereby leveraging the current know‐how on the mechanism of tumor growth.
The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression
Authors: Wang Qi , Huang Yuxi , Zhu Yu , Zhang Wenlong , Wang Binfeng , Du Xuefeng , Dai Qiqiang , Zhang Fabiao , Fang Zheping
Published: April 2024

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets.

Methods

The METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it.

Results

We found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC.

Conclusion

The m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis.
How do you happen to feel? The effect of certainty–uncertainty appraisals of incidental emotions on consumer affective forecasting error
Authors: Polyportis Athanasios , Kokkinaki Flora
Published: April 2024

Consumers frequently forecast how their choices will make them feel in future consumption situations. One possible influence during such affective forecasting is their current emotional state. Although the impact of incidental emotions on consumer decision making is well established, limited research has examined the impact of incidental emotions on affective forecasting. The purpose of the present research is to contribute to the understanding of the effects of certainty–uncertainty, as a key appraisal dimension of incidental emotions, on the process and outcome of affective forecasting. The results of four experimental studies demonstrate that experiencing uncertainty associated incidental emotions, such as fear and hope, during affective forecasting, leads to smaller forecasting error compared with experiencing certainty emotions, such as anger and happiness. Furthermore, heuristic processing, as a result of the certainty versus uncertainty appraisals, plays a mediating role in the effect of certainty–uncertainty on forecasting error. The findings of the present research extend the effects of the certainty–uncertainty appraisals in the context of consumer affective forecasting and elucidate the impact of incidental emotions on decision making.
Determination of Bacterial Community Structure of Table Olive via Metagenomic Approach in Şarköy
Authors: Ucak Samet
Published: April 2024

One of the most popular pickled foods created worldwide is table olives. The aim was to identify the bacterial microbiota of table olive samples collected from Şarköy, Tekirdağ‐Türkiye using next generation sequencing and 16S metagenomic analysis. Samples were studied as non‐pre‐enriched (n : 10) and after pre‐enrichment (n : 10) to compare the effects of the enrichment process on the bacterial diversity. In non‐pre‐enriched, the most common genus found was Sphingomonas, followed by Altererythrobacter and Lysobacter. The most common phylum found was Proteobacteria, followed by Bacteroidota and Actinobacteria. In pre‐enriched, Bacillus was the most commonly detected genus, followed by Pantoea and Staphylococcus. The most frequently found phylum was Firmicutes, followed by Proteobacteria and Cyanobacteria. This study is the first study for Şarköy, which is the only table olive production place in the Tekirdağ region due to its microclimate feature. Further studies are needed in more table olive samples from different geographical areas to confirm and develop current findings.
Single dose human perinatal stem cells accelerate healing of cold‐induced rat burn wound
Authors: Jameel Fatima , Khan Irfan , Malick Tuba Shakil , Qazi Rida‐e‐Maria , Zaidi Midhat Batool , Salim Asmat , Khalil Enam A.
Published: April 2024

Temporal phases of wound healing and their corresponding healing factors are essential in wound regeneration. Mesenchymal stem cells (MSCs) accelerate wound healing via their paracrine secretions by enhancing cell migration, angiogenesis, and reducing inflammation. This study evaluated the local therapeutic effect of human umbilical cord MSCs (hUCMSCs) in the healing of cold‐induced burn wounds. An in vitro wound (scratch) was developed in rat skin fibroblasts. The culture was maintained in the conditioned medium (CM) which was prepared by inducing an artificial wound in hUCMSCs in a separate experiment. Treated fibroblasts were analyzed for the gene expression profile of healing mediators involved in wound closure. Findings revealed enhanced cell migration and increased levels of healing mediators in the treated fibroblasts relative to the untreated group. Cold‐induced burn wounds were developed in Wistar rats, followed by a single injection of hUCMSCs. Wound healing pattern was examined based on the healing phases: hemostasis/inflammation (Days 1, 3), cell proliferation (Day 7), and remodeling (Day 14). Findings exhibited enhanced wound closure in the treated wound. Gene expression, histological, and immunohistochemical analyses further confirmed enhanced wound regeneration after hUCMSC transplantation. Temporal gene expression profile revealed that the level of corresponding cytokines was substantially increased in the treated wound as compared with the control, indicating improvement in the processes of angiogenesis and remodeling, and a substantial reduction in inflammation. Histology revealed significant collagen formation along with regenerated skin layers and appendages, whereas immunohistochemistry exhibited increased neovascularization during remodeling. Leukocyte infiltration was also suppressed in the treated group. Overall findings demonstrate that a single dose of hUCMSCs enhances wound healing in vivo, and their secreted growth factors accelerate cell migration in vitro.
EH domain‐containing protein 2 (EHD2): Overview, biological function, and therapeutic potential
Authors: Zhu Guoqiang , Zhang Hu , Xia Min , Liu Yiqi , Li Mingyong
Published: April 2024

EH domain‐containing protein 2 (EHD2) is a member of the EHD protein family and is mainly located in the plasma membrane, but can also be found in the cytoplasm and endosomes. EHD2 is also a nuclear‐cytoplasmic shuttle protein. After entering the cell nuclear, EHD2 acts as a corepressor of transcription to inhibit gene transcription. EHD2 regulates a series of biological processes. As a key regulator of endocytic transport, EHD2 is involved in the formation and maintenance of endosomal tubules and vesicles, which are critical for the intracellular transport of proteins and other substances. The N‐terminal of EHD2 is attached to the cell membrane, while its C‐terminal binds to the actin‐binding protein. After binding, EHD2 connects with the actin cytoskeleton, forming the curvature of the membrane and promoting cell endocytosis. EHD2 is also associated with membrane protein trafficking and receptor signaling, as well as in glucose metabolism and lipid metabolism. In this review, we highlight the recent advances in the function of EHD2 in various cellular processes and its potential implications in human diseases such as cancer and metabolic disease. We also discussed the prospects for the future of EHD2. EHD2 has a broad prospect as a therapeutic target for a variety of diseases. Further research is needed to explore its mechanism, which could pave the way for the development of targeted treatments.
AM404 Analogs as Activators of the 20S Isoform of the Human Proteasome
Authors: Salazar‐Chaparro Andres , Kragness Kate , Feleciano Diogo , Trader Darci J.
Published: April 2024

The proteasome is a multisubunit protease system responsible for the majority of the protein turnover in eukaryotic organisms. Dysregulation of this enzymatic complex leads to protein accumulation, subsequent aggregation, and ultimately diseased states; for that reason, positive modulation of its activity has been recently investigated as a therapeutic strategy for neurodegenerative and age‐related diseases. The small molecule AM404 was recently identified as an activator of the 20S isoform of the proteasome and further exploration of the scaffold revealed the importance of the polyunsaturated fatty acid chain to elicit activity. Herein, we report the investigation of the aromatic region of the scaffold and the evaluation of the small molecules in a variety of proteasome activity and protein degradation assays. We found that derivatives A22 and A23, compared to AM404, exhibit enhanced proteasome activity in biochemical and cellular proteasome assays and more favorable cellular viability profiles. Additionally, these compounds demonstrate the ability to degrade intrinsically disordered proteins, regardless of their molecular weight, and the ability to restore the proteasome activity in the presence of toxic oligomeric α‐Syn species in a biochemical setting.
A case report of malignant struma ovarii with papillary thyroid carcinoma
Authors: Rahimi Yekta , Rabizadeh Soghra , Seifouri Sara , Seifouri Kiana , Salarvand Samane , Nakhjavani Manouchehr
Published: April 2024

Key clinical message

Struma ovarii (SO), is a rare and specialized ovarian teratoma. The treatment is controversial depending on the risk of recurrence and metastasis. Here a SO with papillary thyroid carcinoma is reported and the approach is thoroughly discussed.

Struma ovarii (SO) is a highly specialized ovarian teratoma primarily composed of thyroid tissue. Clinical features associated with SO include lower abdominal discomfort, unusual vaginal bleeding, ascites, and hyperthyroidism. While SO rarely transforms into malignancy, the optimal degree of treatment remains controversial due to the varying risks of recurrence and metastasis. In this report, we present the case of a 64‐year‐old woman experiencing abdominal pain and diagnosed with SO, accompanied by papillary thyroid carcinoma. We thoroughly discuss the evaluation and management of this rare condition.
Neuropsychiatric disorder as early clinical presentation of marantic endocarditis in patient with newly diagnosed poorly differentiated esophago‐gastric junction adenocarcinoma: A case report
Authors: Ferrentino Filomena , Campana Sara , Torri Marco , Rostagno Carlo
Published: April 2024

Key Clinical Message

Neuropsychiatric symptoms, depression, and progressive mental confusion should not be overlooked as onset symptoms of multiple cerebral ischemic lesions due to cardiac embolization. Comprehensive clinical evaluation due to progressive anemia led to the diagnosis of poorly differentiated adenocarcinoma of the esophagogastric junction as cause of embolizing nonbacterial mitral endocarditis.
Exploring subungual onycholemmal cysts: A rare case report and comprehensive literature review
Authors: Giv Toktam Safari , Movahedi Mahdiyeh , Dadkhahfar Sahar , Biglari Farsad , Rakhshan Azadeh , Mardani Ghazal , Kafiabadi Meisam Jafari
Published: April 2024

Key clinical message

Subungual Onycholemmal Cyst (SOC) is a rare nail abnormality with different clinical presentations which can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. It is necessary for dermatologists and dermatopathologist to be aware of this pathology to make the proper diagnosis and treatment. SOC is a rare nail abnormality which affects the dermis of the nail bed. SOC has different clinical presentations, including onychodystrophy, ridging, clubbing, thickening, pigmentation, or even normal appearance. It can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. In this report, we describe a 54‐year‐old man with unilateral second right finger nail onychodystrophy and onycholysis for 1 year. He did not have any history of recent trauma, pain, or bleeding. It was completely resected by surgery. Nail biopsy can contribute to the early diagnosis of SOC and improvement of treatment outcomes.
First‐trimester exposure to tofacitinib in ulcerative colitis: A case report of a healthy newborn and literature review
Authors: Arzivian Arteen , Zhang Eva , Laube Robyn , Leong Rupert
Published: April 2024

Key Clinical Message

Tofacitinib is contraindicated in pregnancy. We present a patient with ulcerative colitis on tofacitinib who had an unplanned pregnancy. Tofacitinib was ceased, switched to vedolizumab, and she gave birth to a healthy newborn at term. Case reports of reassuring outcomes provide real‐world data that assists decision‐making for future patients.
LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR‐214‐3p/UCHL1 axis
Authors: Chen Wenjing , Wang Shaoqing , Wei Dongmei , Zhai Lili , Liu Li , Pan Chunlei , Han Zhongshu , Liu Huiming , Zhong Wei , Jiang Xin
Published: April 2024

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual‐fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR‐214‐3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR‐214‐3p/UCHL1 axis.
Scutellarin alleviates microglia‐mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3β signaling pathway
Authors: Duan Zhaoda , Chen Haolun , Miao Wei , He Jing , Xu Dongyao , Qi Zhi , Yang Li , Jia Wenji , Wu Chunyun
Published: April 2024

Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV‐2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV‐2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p‐NF‐κB, TNF‐α, IL‐1β, Bax, and C‐caspase‐3. In contrast, the expression levels of p‐PI3K, p‐AKT, p‐GSK3β, and Bcl‐2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3β signaling pathway and NF‐κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3β/NF‐κB signaling pathway.
Defect Induced Structural Transition and Lipase Immobilization in Mesoporous Aluminum Metal‐Organic Frameworks
Authors: Kulandaivel Sivasankar , Yang Chun‐Chuen , Yeh Yi‐Chun , Lin Chia‐Her
Published: April 2024

The transition from disorder to order and structural transformation are distinctive metal‐organic framework (MOF) features. How to adapt or control both behaviors in MOF has rarely been studied. In this case, we demonstrate that our successful synthesis of [Al(OH)(PDA)]n (AlPDA‐53‐DEF, AlPDA‐53‐H, and AlPDA‐68) with H2PDA=4,4′‐[1,4‐phenylenebis(ethyne‐2,1‐diyl)]‐di benzoic acid has shown the intricate world of Aluminum Metal‐Organic Frameworks (Al‐MOFs). It offers profound insights into defect structures to order and transformations. AlPDA‐53‐DEF, in particular, revealed a fascinating interplay of various pore sizes within both micro and mesoporous regions, unveiling a unique lattice rearrangement phenomenon upon solvent desorption. Defects and disorders emerged as crucial impacts of transforming AlPDA‐53‐DEF, with its initially imperfect crystallinity, into the highly crystalline, hierarchically porous AlPDA‐53‐H.
Total Chemical Synthesis of Aggregation‐Prone Disulfide‐Rich Starfish Peptides
Authors: Wu Hongkang , Praveen Praveen , Handley Thomas N. G. , Chandrashekar Chaitra , Cummins Scott F. , Bathgate Ross A. D. , Hossain Mohammed Akhter
Published: April 2024

A relaxin‐like gonad‐stimulating peptide (RGP), Aso‐RGP, featuring six cysteine residues, was identified in the Crown‐of‐Thorns Starfish (COTS, Acanthaster cf. solaris) and initially produced through recombinant yeast expression. This method yielded a single‐chain peptide with an uncleaved C‐peptide (His Tag) and suboptimal purity. Our objective was to chemically synthesize Aso‐RGP in its mature form, comprising two chains (A and B) and three disulfide bridges, omitting the C‐peptide. Furthermore, we aimed to synthesize a newly identified relaxin‐like peptide, Aso‐RLP2, from COTS, which had not been previously synthesized. This paper reports the first total chemical synthesis of Aso‐RGP and Aso‐RLP2. Aso‐RGP synthesis proceeded without major issues, whereas the A‐chain of Aso‐RLP2, in its reduced and unfolded state with two free thiols, presented considerable challenges. These were initially marked by “messy” RP‐HPLC profiles, typically indicative of synthesis failure. Surprisingly, oxidizing the A‐chain significantly improved the RP‐HPLC profile, revealing the main issue was not synthesis failure but the peptide's aggregation tendency, which initially obscured analysis. This discovery highlights the critical need to account for aggregation in peptide synthesis and analysis. Ultimately, our efforts led to the successful synthesis of both peptides with purities exceeding 95 %.
Consumption of cow's milk formula in the nursery and the development of milk allergy
Authors: Elizur Arnon , Rachel‐Jossefi Shirel , Rachmiel Marianna , Eisenberg Eli , Katz Yitzhak
Published: April 2024

Background

The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE‐cow's milk allergy (IgE‐CMA) is unknown.

Methods

A cohort of 58 patients with IgE‐CMA was identified from a large scale population‐based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery.

Results

While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1–3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105–194 days (the period with highest‐risk for IgE‐CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04).

Conclusions

Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE‐CMA.
Atypical squamous cells in urine cytology are associated with a significant risk of high‐grade malignancy
Authors: Ho Linh , Elsheikh Tarik M.
Published: April 2024

Background

Atypical squamous cells (ASC) in urine cytology are rarely found, and their clinical significance is not well studied. Previous studies were limited by a small number of cases and a lack of objective grading of ASC and/or their correlation with accompanying urothelial cell abnormality (UCA).

Methods

The institutional database was searched over 10 years for urine cytology reports containing ASC or from patients who had a concurrent diagnoses of high‐grade (HG) urothelial carcinoma with squamous differentiation or squamous carcinoma. ASC were defined as keratinized squamous cells and were subcategorized as reactive, koilocytosis, low‐grade (LG) atypia, and HG atypia. Correlations with age, sex, specimen type, accompanying UCA, number of ASC, and the risk of HG malignancy (ROHM) were assessed.

Results

ASC were present in 0.15% of all urine specimens (123 of 81,018). Slides and clinical follow‐up were available on 91 patients (median age, 71 years). LG and HG squamous atypia had ROHMs of 70% and 92%, respectively. ASC not accompanied and accompanied by UCA had ROHMs of 37% and 94%, respectively. Most malignancies (34 of 67; 51%) showed rare ASC in urine. Reactive changes and koilocytosis had 0% ROHM.

Conclusions

ASC in urine cytology is a significant finding and is associated with a high ROHM. In the absence of accompanying UCA, LG squamous atypia had a lower ROHM than HG atypia. In the presence of UCA, LG and HG squamous atypia had ROHMs of over 90%. These findings suggest that ASC and their grade of atypia should be noted in the cytology report, and clinicians should be made aware of their clinical significance.
Diagnostic accuracy of International System for Reporting Serous Fluid Cytopathology: A systematic review and meta‐analysis in malignancy diagnosis
Authors: Ahuja Sana , Ahuja Rhea , Pandey Shivam , Zaheer Sufian
Published: April 2024

This study conducts the first meta‐analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords “(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)”. Articles underwent risk of bias assessment using the QUADAS‐2 tool. After excluding inadequate samples, a meta‐analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross‐sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the “atypical and higher risk categories” considered positive were 77% (95% confidence interval [CI], 68%–84%) and 95% (95% CI, 93%–97%) respectively. For the “suspicious for malignancy and higher risk categories” considered positive, sensitivity and specificity were 57% (95% CI, 49%–65%) and 100% (95% CI, 99%–100%) respectively. Sensitivity and specificity for the “malignant” category considered positive for malignancy were 70% (95% CI, 60%–77%) and 99% (95% CI, 98%–99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta‐analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy.
Analyzing color training in design education: A review from 2010 to 2022
Authors: Calvo Ivanovic Ingrid
Published: April 2024

This study was part of a doctoral research project which looked into the current issues with color education, documented by several authors in recent years. It presents a comprehensive analysis of 103 color courses taught within design programs of higher education institutions from different countries over the last 12 years, 2010–2022. The analysis aimed to define the state‐of‐the‐art of including color training within higher education design programs, identify the main didactic strategies implemented, and recognize the main critical aspects to face when proposing an innovative framework for color training. Among the formal aspects analyzed are the course level, the course duration, the student entry profile, the specific disciplinary area, the course location, the type of institution, and the language of the course. The didactic strategy elements analyzed were the learning outcomes, the contents proposed by the course, the teaching strategies implemented, and the suggested bibliography. Finally, a description of the main findings of the analysis is provided to assess how color is being taught within the design area.
A superpixel‐based color difference detection algorithm for dyed fabrics
Authors: Yuan QiLei , He ZhiYong , Wan SiJie
Published: April 2024

In order to enhance the accuracy and efficiency of color difference detection for dyed fabrics, this article introduces a novel superpixel‐based color difference detection algorithm, which exhibits three significant improvements over the previous algorithm. First, it proposes a more rational color feature extraction method to extract more detailed color features from fabric images, which uses superpixels as basic units for both color feature extraction and color difference detection. Second, the algorithm employs the CIEDE2000 color difference formula to calculate color difference values. This eliminates the need for obtaining standard fabric images as references in advance, making the process more convenient and practical. Finally, an area‐based color difference calculation method is proposed based on the human visual mechanism, ensuring that the evaluation results are more consistent with human eye observations. Experimental results demonstrate that the proposed algorithm provides more accurate and visually consistent color difference assessments compared to the previous algorithm.
Combining Desferriferrioxamine B and 1‐Hydroxy‐2‐Piperidone ((PIPO)H) to Chelate Zirconium. Solution Structure of a Model Complex of the [89Zr]Zr−DFOcyclo*−mAb Radioimmunoconjugate
Authors: Mangin Floriane , Fonquernie Osian , Jewula Pawel , Brandès Stéphane , Penouilh Marie‐José , Bonnin Quentin , Vincent Bruno , Espinosa Enrique , Aubert Emmanuel , Meyer Michel , Chambron Jean‐Claude
Published: April 2024

89Zr−immunoPET is a hot topic as 89Zr cumulates the advantages of 64Cu and 124I without their drawbacks. We report the synthesis of a model ligand of a chiral bioconjugable tetrahydroxamic chelator combining the desferriferrioxamine B siderophore and 1‐hydroxy‐2‐piperidone ((PIPO)H), a chiral cyclic hydroxamic acid derivative, and the study by NMR spectroscopy of its zirconium complex. Nuclear Overhauser effect measurements (ROESY) indicated that the complex exists in the form of two diastereomers, in 77 : 23 ratio, resulting from the combination of the central chiralities at the 3‐C of the (PIPO)H component and at the Zr4+ cation. The 44 lowest energy structures out of more than 1000 configurations/conformations returned by calculations based on density functional theory were examined. Comparison of the ROESY data and the calculated interatomic H⋅⋅⋅H distances allowed us to select the most probable configuration and conformations of the major complex.