bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Dimerization of Fungal Natural Products Through Intermolecular Disulfide Bridges
Authors: Limwachiranon Jarukitt , Xu Fan , Xu Li‐Ru , Xiong Zhen‐Zhen , Han Yi , Guo Yao‐Jie , Zhang Nan , Scharf Daniel H.
Published: August 2024

The biosynthetic pathway for the production of natural products from various species often include a dimerization step which increases the structural variability and range of biological activities. These dimerization reactions are highly interesting for biocatalytic applications. Epipolythiodioxopiperazines (ETPs) are an important class of natural products whose potent bioactivities rely on disulfide bridges. ETPs often carry a transannular disulfide bridge and can be linked through C−C and C−N bonds to form dimers. In this study, we shed light on the mechanism of disulfide formation in the case of the dimeric vertihemiptellides (vhe) produced by the fungus Verticillium hemipterigenum BCC1449. These compounds feature a unique intermolecular disulfide bridge which links two monomers together. Using comparative genomics, we identified the 12‐membered vhe gene cluster. In vitro assays, kinetic analysis, and protein mutagenesis, enabled us to characterize VheT, the oxidase catalyzing an intermolecular disulfide bond formation resulting in ETP dimers. We showed that the CxxC motif of VheT plays a crucial role in catalyzing this reaction. VheT is an oxidase linking natural product monomers through intermolecular S−S bridges and could be developed into a biocatalyst for thiol specific dimerization reactions.
Intranasal Multiepitope PD‐L1‐siRNA‐Based Nanovaccine: The Next‐Gen COVID‐19 Immunotherapy
Authors: Acúrcio Rita C. , Kleiner Ron , Vaskovich‐Koubi Daniella , Carreira Bárbara , Liubomirski Yulia , Palma Carolina , Yeheskel Adva , Yeini Eilam , Viana Ana S. , Ferreira Vera , Araújo Carlos , Mor Michael , Freund Natalia T. , Bacharach Eran , Gonçalves João , Toister‐Achituv Mira , Fabregue Manon , Matthieu Solene , Guerry Capucine , Zarubica Ana , Aviel‐Ronen Sarit , Florindo Helena F. , Satchi‐Fainaro Ronit
Published: August 2024

The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are nanotechnology‐based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next‐generation multiepitope nanovaccines co‐deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD‐L1 expression. As a case study, we focused on SARS‐CoV‐2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular‐ and humoral‐specific responses against SARS‐CoV‐2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS‐CoV‐2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology‐based vaccines, it is shown that the lyophilized nanovaccine is stable for long‐term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.
Accelerated Bone Healing via Electrical Stimulation
Authors: Sun Jianfeng , Xie Wenqing , Wu Yuxiang , Li Zhou , Li Yusheng
Published: August 2024

Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.
Minimally Invasive Injectable Gel for Local Immunotherapy of Liver and Gastric Cancer
Authors: Si Xinghui , Ji Guofeng , Ma Sheng , Huang Zichao , Liu Taiyuan , Shi Zhiyuan , Zhang Yu , Li Jia , Song Wantong , Chen Xuesi
Published: August 2024

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor‐specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4‐arm polyethylene glycol hydroxylamine (4‐arm PEG‐ONH2) through oxime bonds, which can be injected through a clinic‐used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential.
Ponicidin Promotes Hepatocellular Carcinoma Mitochondrial Apoptosis by Stabilizing Keap1‐PGAM5 Complex
Authors: Zhao Bixin , Liang Zuhui , Zhang Lisheng , Jiang Lin , Xu Yuanhang , Zhang Ying , Zhang Rong , Wang Caiyan , Liu Zhongqiu
Published: August 2024

Ponicidin is a diterpenoid with demonstrated antitumor activity in clinical trials. However, the specific function and mechanism of action against hepatocellular carcinoma (HCC) remain unknown. In this study, it is found that ponicidin significantly inhibited the proliferation and migration of HCC cells. It is shown that ponicidin targets Keap1 and promotes the formation of the Keap1‐PGAM5 complex, leading to the ubiquitination of PGAM5, using biotin‐labeled ponicidin for target fishing and the HuProtTM Human Proteome Microarray V4.0. Ponicidin is found to activate the cysteine‐dependent mitochondrial pathway via PGAM5, resulting in mitochondrial damage and ROS production, thereby promoting mitochondrial apoptosis in HepG2 cells. The first in vitro cocrystal structure of the PGAM5 IE 12‐mer peptide and the Keap1 Kelch domain is obtained. Using molecular dynamics simulations to confirm the binding of ponicidin to the Keap1‐PGAM5 complex. Based on the depth‐based dynamic simulation, it is found that ponicidin can induce the tightening of the Keap1‐PGAM5 interaction pocket, thereby stabilizing the formation of the protein complex. Finally, it is observed that ponicidin effectively inhibited tumor growth and promoted tumor cell apoptosis in a BALB/c nude mouse xenograft tumor model. The results provide insight into the anti‐HCC properties of ponicidin based on a mechanism involving the Keap1‐PGAM5 complex.
Centrifugal Inertia‐Induced Directional Alignment of AgNW Network for Preparing Transparent Electromagnetic Interference Shielding Films with Joule Heating Ability
Authors: Zhao Weijun , Dong Jingwen , Li Zhaoyang , Zhou Bing , Liu Chuntai , Feng Yuezhan
Published: August 2024

Transparent electromagnetic interference (EMI) shielding is highly desired in specific visual scenes, but the challenge remains in balancing their EMI shielding effectiveness (SE) and optical transmittance. Herein, this study proposed a directionally aligned silver nanowire (AgNW) network construction strategy to address the requirement of high EMI SE and satisfactory light transmittance using a rotation spraying technique. The orientation distribution of AgNW is induced by centrifugal inertia force generated by a high‐speed rotating roller, which overcomes the issue of high contact resistance in random networks and achieves high conductivity even at low AgNW network density. Thus, the obtained transparent conductive film achieved a high light transmittance of 72.9% combined with a low sheet resistance of 4.5 Ω sq−1 and a desirable EMI SE value of 35.2 dB at X band, 38.9 dB in the K‐band, with the highest SE of 43.4 dB at 20.4 GHz. Simultaneously, the excellent conductivity endowed the film with outstanding Joule heating performance and defogging/deicing ability, ensuring the visual transparency of windows when shielding electromagnetic waves. Hence, this research presents a highly effective strategy for constructing an aligned AgNW network, offering a promising solution for enhancing the performance of optical‐electronic devices.
Ice Nucleation Mechanisms on Platinum Surfaces in PEM Fuel Cells: Effects of Surface Morphology and Wettability
Authors: Wang Jiaqi , Fan Linhao , Li Lincai , Du Qing , Jiao Kui
Published: August 2024

Understanding the ice nucleation mechanism in the catalyst layers (CLs) of proton exchange membrane (PEM) fuel cells and inhibiting icing by designing the CLs can optimize the cold start strategies, which can enhance the performance of PEM fuel cells. Herein, mitigating the structural matching and templating effects by adjusting the surface morphology and wettability can inhibit icing on the platinum (Pt) catalyst surface effectively. The Pt(211) surface can inhibit icing because the atomic spacing of (211) crystalline surface is much larger than the characteristic distance of ice crystal, thereby mitigating the structural matching effects. A water overlayer on the Pt surface induced by the strong attraction of Pt can act as a template for ice layers and plays an important role in the icing process. Buckling of water overlayer due to the larger atomic spacing of (211) crystalline surface mitigates the templating effect and inhibits icing. Moreover, the water overlayer on the hydrophobic Pt(211) surface with fewer water molecules also mitigates the templating effect, which makes ice nucleation more difficult than homogeneous nucleation. These findings reveal the ice nucleation mechanisms on the Pt catalyst surface from the molecular level and are valuable for catalyst designs to inhibit icing in CL.
Mutant Huntingtin Drives Development of an Advantageous Brain Early in Life: Evidence in Support of Antagonistic Pleiotropy
Authors: Neema Mohit , Schultz Jordan L. , Langbehn Douglas R. , Conrad Amy L. , Epping Eric A. , Magnotta Vincent A. , Nopoulos Peggy C.
Published: August 2024

Objective

Huntington's disease (HD) is a neurodegenerative disease caused by a triplet repeat expansion within the gene huntingtin (HTT). Antagonistic pleiotropy is a theory of aging that posits that some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging‐related processes. Antagonistic pleiotropy theory may explain a positive evolutionary pressure toward functionally advantageous brain development that is vulnerable to rapid degeneration. The current study investigated antagonistic pleiotropy in HD using a years‐to‐onset paradigm in a unique sample of children and young adults at risk for HD.

Methods

Cognitive, behavioral, motor, and brain structural measures from premanifest gene‐expanded (n = 79) and gene nonexpanded (n = 112) participants (6–21 years) in the Kids‐HD study were examined. All measures in the gene‐expanded group were modeled using a mixed‐effects regression approach to assess years‐to‐onset‐based changes while controlling for normal growth. Simultaneously, structure–function associations were also examined.

Results

Decades from motor onset, gene‐expanded participants showed significantly better cognitive, behavioral, and motor scores versus gene nonexpanded controls, along with larger cerebral volumes and cortical features. After this initial peak, a prolonged deterioration was observed in both functional and structural measures. Far from onset, brain measures were positively correlated with functional measures, supporting the view that functional advantages were mediated by structural differences.

Interpretation

Mutant HTT may drive the development of a larger than normal brain that subserves superior early‐life function. These findings support the antagonistic pleiotropy theory of HTT in HD, where this gene drives early advantage followed by accelerated aging processes. ANN NEUROL 2024;96:1006–1019
Highly Efficient Separation of Intermediate‐Size m‐Xylene from Xylenes via a Length‐Matched Metal–Organic Framework with Optimal Oxygen Sites Distribution
Authors: Wang Qingju , Li Yijian , Qiu Zhensong , Zhou Dengzhuo , Yang Lifeng , Suo Xian , Cui Xili , Xing Huabin
Published: August 2024

Xylene separation is crucial but challenging, especially for the preferential separation of the intermediate‐size m‐xylene from xylene mixtures. Herein, exploiting the differences in molecular length and alkyl distribution among xylenes, we present a length‐matched metal–organic framework, formulated as Al(OH)[O2C−C4H2O−CO2], featuring an effective pore size corresponding to m‐xylene molecular length combined with multiple negative O hydrogen bond donors distribution, can serve as a molecular trap for efficient preferential separation of the intermediate‐size m‐xylene. Benchmark separation performance was achieved for separating m‐xylene from a ternary mixture of m‐xylene/o‐xylene/p‐xylene, with simultaneous record‐high m‐xylene uptake (1.3 mmol g−1) and m‐xylene/p‐xylene selectivity (5.3) in the liquid‐phase competitive adsorption. Both vapor‐ and liquid‐phase fixed‐bed tests confirmed its practical separation capability with benchmark dynamic m‐xylene/p‐xylene and m‐xylene/o‐xylene selectivities, as well as excellent regenerability. The selective and strong m‐xylene binding affinity among xylene molecules was further elucidated by simulations, validating the effectiveness of such a pore environment for the separation of intermediate‐size molecules.
Coordination Desymmetrization of Copper Single‐Atom Catalyst for Efficient Nitrate Reduction
Authors: Gu Zhengxiang , Zhang Yechuan , Fu Yang , Hu Dandan , Peng Fang , Tang Yawen , Yang Huajun
Published: August 2024

Coordination engineering strategy for optimizing the catalytic performance of single‐atom catalysts (SACs) has been rapidly developed over the last decade. However, previous reports on copper SACs for nitrate reduction reactions (NO3RR) have mostly focused on symmetric coordination configurations such as Cu‐N4 and Cu‐N3. In addition, the mechanism in terms of the regulation of coordination environment and catalytic properties of SACs has not been well demonstrated. Herein, we disrupted the local symmetric structure of copper atoms by introducing unsaturated heteroatomic coordination of Cu−O and Cu−N to achieve the coordination desymmetrization of Cu‐N1O2 SACs. The Cu‐N1O2 SACs exhibit an efficient nitrate‐to‐ammonia conversion with a high FE of ~96.5 % and a yield rate of 3120 μg NH3 h−1 cm−2 at −0.60 V vs RHE. As indicated by in situ Raman spectra, the catalysts facilitate the accumulation of NO3− and the selective adsorption of *NO2, which were further confirmed by the theoretical study of surface dipole moment and orbital hybridization. Our work illustrated the correlation between the coordination desymmetrization and the catalytic performance of copper SACs for NO3RR.
Long‐Range π–π Stacking Brings High Electron Delocalization for Enhanced Photocatalytic Activity in Hydrogen‐Bonded Organic Framework
Authors: Zhang An‐An , Wang Zi‐Xiang , Fang Zhi‐Bin , Li Jin‐Lin , Liu Tian‐Fu
Published: August 2024

Unlike many studies that regulate transport and separation behaviour of photogenerated charge carriers through controlling the chemical composite, our work demonstrates this goal can be achieved through simply tuning the molecular π–π packing from short‐range to long‐range within hydrogen‐bonded organic frameworks (HOFs) without altering the building blocks or network topology. Further investigations reveal that the long‐range π–π stacking significantly promotes electron delocalization and enhances electron density, thereby effectively suppressing electron‐hole recombination and augmenting the charge transfer rate. Simultaneously, acting as a porous substrate, it boosts electron density of Pd nanoparticle loaded on its surfaces, resulting in remarkable CO2 photoreduction catalytic activity (CO generation rate: 48.1 μmol/g/h) without the need for hole scavengers. Our study provide insight into regulating the charge carrier behaviours in molecular assemblies based on hydrogen bonds, offering a new clue for efficient photocatalyst design.
Super‐Resolved Protein Imaging Using Bifunctional Light‐Up Aptamers
Authors: Grün Franziska , van den Bergh Niklas , Klevanski Maja , Verma Mrigank S. , Bühler Bastian , Nienhaus G. Ulrich , Kuner Thomas , Jäschke Andres , Sunbul Murat
Published: August 2024

Efficient labeling methods for protein visualization with minimal tag size and appropriate photophysical properties are required for single‐molecule localization microscopy (SMLM), providing insights into the organization and interactions of biomolecules in cells at the molecular level. Among the fluorescent light‐up aptamers (FLAPs) originally developed for RNA imaging, RhoBAST stands out due to its remarkable brightness, photostability, fluorogenicity, and rapid exchange kinetics, enabling super‐resolved imaging with high localization precision. Here, we expand the applicability of RhoBAST to protein imaging by fusing it to protein‐binding aptamers. The versatility of such bifunctional aptamers is demonstrated by employing a variety of protein‐binding aptamers and different FLAPs. Moreover, fusing RhoBAST with the GFP‐binding aptamer AP3 facilitates high‐ and super‐resolution imaging of GFP‐tagged proteins, which is particularly valuable in view of the widespread availability of plasmids and stable cell lines expressing proteins fused to GFP. The bifunctional aptamers compare favorably with standard antibody‐based immunofluorescence protocols, as they are 7‐fold smaller than antibody conjugates and exhibit higher bleaching‐resistance. We demonstrate the effectiveness of our approach in super‐resolution microscopy in secondary mammalian cell lines and primary neurons by RhoBAST‐PAINT, an SMLM protein imaging technique that leverages the transient binding of the fluorogenic rhodamine dye SpyRho to RhoBAST.
Upcycling of Spent LiFePO4 Cathodes to Heterostructured Electrocatalysts for Stable Direct Seawater Splitting
Authors: Li Zhen , Li Mengting , Chen Yiqun , Ye Xucun , Liu Mengjie , Lee Lawrence Yoon Suk
Published: August 2024

The pursuit of carbon‐neutral energy has intensified the interest in green hydrogen production from direct seawater electrolysis, given the scarcity of freshwater resources. While Ni‐based catalysts are known for their robust activity in alkaline water oxidation, their catalytic sites are prone to rapid degradation in the chlorine‐rich environments of seawater, leading to limited operation time. Herein, we report a Ni(OH)2 catalyst interfaced with laser‐ablated LiFePO4 (Ni(OH)2/L‐LFP), derived from spent Li‐ion batteries (LIBs), as an effective and stable electrocatalyst for direct seawater oxidation. Our comprehensive analyses reveal that the PO43− species, formed around L‐LFP, effectively repels Cl− ions during seawater oxidation, mitigating corrosion. Simultaneously, the interface between in situ generated NiOOH and Fe3(PO4)2 enhances OH− adsorption and electron transfer during the oxygen evolution reaction. This synergistic effect leads to a low overpotential of 237 mV to attain a current density of 10 mA cm−2 and remarkable durability, with only a 3.3 % activity loss after 600 h at 100 mA cm−2 in alkaline seawater. Our findings present a viable strategy for repurposing spent LIBs into high‐performance catalysts for sustainable seawater electrolysis, contributing to the advancement of green hydrogen production technologies.
Healthier information ecosystems: A definition and agenda
Authors: Introne Joshua , McKernan Brian , Corsbie‐Massay Charisse L' Pree , Rohlinger Deana , Tripodi Francesca Bolla
Published: August 2024

As digitally enabled information systems play an increasingly central role in culture and economics, their negative consequences have become apparent. This guest editorial addresses the urgent need for information scientists to take a more deliberate stance in designing and guiding the evolution of these systems. We propose a framework for conceptualizing “healthier information ecosystems” by drawing on theories from complex systems and ecological research, grounded in a value‐oriented approach. The article reviews key concepts from systems science, complex systems, and ecology, with a focus on ecosystem and adaptation research. These perspectives offer analytical approaches for decomposing information ecosystems and provide a foundation for understanding “health” in the context of evolving, open systems. Unlike natural ecosystems, information ecosystems must be evaluated according to human values; thus, we articulate a set of values as a starting point for defining health in this context. By introducing insights from beyond the field of information systems, we aim to instigate scholarly dialog, connect prior work in new ways, and reveal new opportunities for research and intervention. This connective and argumentative contribution is intended to guide future research and identify solutions to the proliferating problems in our current information ecosystems.
Protein multi‐level structure feature‐integrated deep learning method for mutational effect prediction
Authors: Pang Ai‐Ping , Luo Yongsheng , Zhou Junping , Cai Xue , Huang Lianggang , Zhang Bo , Liu Zhi‐Qiang , Zheng Yu‐Guo
Published: August 2024

Through iterative rounds of mutation and selection, proteins can be engineered to enhance their desired biological functions. Nevertheless, identifying optimal mutation sites for directed evolution remains challenging due to the vastness of the protein sequence landscape and the epistatic mutational effects across residues. To address this challenge, we introduce MLSmut, a deep learning‐based approach that leverages multi‐level structural features of proteins. MLSmut extracts salient information from protein co‐evolution, sequence semantics, and geometric features to predict the mutational effect. Extensive benchmark evaluations on 10 single‐site and two multi‐site deep mutation scanning datasets demonstrate that MLSmut surpasses existing methods in predicting mutational outcomes. To overcome the limited training data availability, we employ a two‐stage training strategy: initial coarse‐tuning on a large corpus of unlabeled protein data followed by fine‐tuning on a curated dataset of 40−100 experimental measurements. This approach enables our model to achieve satisfactory performance on downstream protein prediction tasks. Importantly, our model holds the potential to predict the mutational effects of any protein sequence. Collectively, these findings suggest that our approach can substantially reduce the reliance on laborious wet lab experiments and deepen our understanding of the intricate relationships between mutations and protein function.
Preparation and Characterization of Durian Husk‐Based Biocomposite Films Reinforced With Nanocellulose From Corn Husk and Pineapple Leaf
Authors: Siribanluehan Nattapron , Wattanachai Piyachat
Published: August 2024

This research explores the integration of corn husk nanocellulose (CHNc) and pineapple leaf nanocellulose (PLNc) as reinforcing agents in a carboxymethyl cellulose‐based film derived from durian husk (CMCDH). Through a solvent‐casting method, composite films were fabricated with varying nanocellulose contents (15, 30, and 45 wt%). Analysis using Fourier transform infrared spectroscopy and x‐ray diffraction confirmed the effectiveness of alkaline and bleaching treatments in eliminating noncellulosic components. Transmission electron microscopy image revealed the rod‐like morphology of CHNc and PLNc, with dimensions approximately 206.5 × 7.2 nm and 150.7 × 6.5 nm, respectively. The inclusion of nanocellulose decreased the transparency of CMCDH films while enhancing their tensile strength, thermal stability, and water vapor transmission rate. Notably, CMCDH/PLNc(30%) exhibited the highest tensile strength at 5.06 ± 0.83 MPa, representing a remarkable 220% increase compared to CMCDH biofilm. Thermogravimetric analysis and differential scanning calorimeter results indicated that nanocellulose incorporation delayed the film's decomposition temperature by approximately 10°C. Moreover, CMCDH/PLNc(30%) demonstrated the lowest water vapor transmission rate, marking a 20% improvement. However, the film's properties were compromised at the highest nanocellulose content (45 wt%) due to observed fiber aggregation, as revealed by scanning electron microscopy analysis.
Mechanism and rational combinations with GP‐2250, a novel oxathiazine derivative, in ovarian cancer
Authors: Kim Mark S. , Glassman Deanna , Handley Katelyn F. , Lankenau Ahumada Adrian , Jennings Nicholas B. , Bayraktar Emine , Foster Katherine , Joseph Robiya , Lee Sanghoon , Coleman Robert L. , Sood Anil K.
Published: August 2024

Background

GP‐2250, a novel analog of taurultam (TRLT), has emerged as a potent anti‐neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP‐2250 using in vitro and in vivo models.

Methods

We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse‐phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP‐2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP‐2250 alone and in combination with standard‐of‐care drugs (e.g., paclitaxel, cisplatin, topotecan, and poly ADP‐ribose polymerase [PARP] inhibitors).

Results

We investigated the cytotoxic effect of GP‐2250 in 10 ovarian cancer cell lines and found GP‐2250 combined with a PARP inhibitor had the greatest synergy. RPPA revealed that GP‐2250 inhibited hypoxia‐inducible factor‐1α, AKT, and mammalian target of rapamycin (mTOR) activation and expression. High‐resolution mass spectrometry revealed that hexokinase2 activity and protein expression were significantly reduced by GP‐2250 exposure. Furthermore, GP‐2250 reduced glycolysis and ATP synthesis in cancer cells. An in vivo pharmacodynamic experiment using the OVCAR8 mouse model demonstrated that 500 mg/kg GP‐2250 was effective in downregulating AKT and mTOR activation and expression. In the in vivo therapy experiment using an orthotopic mouse model, a combination of GP‐2250 with either PARP inhibitors or bevacizumab showed a significant reduction of tumor weights and nodules compared to those treated with a vehicle, control IgG groups, or monotherapy groups.

Conclusions

Taken together, our data indicate that GP‐2250 exerts profound effects on tumor metabolism and, in combination with PARP inhibitors or bevacizumab, showed promising anti‐tumor efficacy. These findings could have implications for the clinical development of GP‐2250.
Development and validation of FinTox: A new screening tool to assess cancer‐related financial toxicity
Authors: Badr Hoda , Han Jessie , Mims Martha
Published: August 2024

Purpose

This study aimed to develop and validate FinTox, a concise tool for screening and managing financial toxicity in oncology settings.

Methods

Development involved qualitative interviews with healthcare providers and patients, and feedback from a 7‐member expert panel resulting in a 5‐item measure that evaluates financial strain, psychological responses, and care modifications. Psychometric evaluations examined factor structure, internal consistency, test–retest reliability, and concurrent and convergent validity. Associations between FinTox scores and sociodemographic/medical factors were also analyzed using univariate and multivariable regression models.

Results

Twelve healthcare providers and 20 patients were interviewed, and 268 patients (69.8% female, 47.4% non‐Hispanic White) completed surveys including FinTox, the Comprehensive Score for Financial Toxicity (COST), health‐related quality of life (HRQOL) measures, and sociodemographic questions. FinTox demonstrated excellent internal consistency (Cronbach's alpha = 0.90) and test–retest reliability (ICC = 0.95). Significant correlations with the COST (r = −0.62, p < 0.001) and HRQOL measures corroborated content and convergent validity. Diagnostic accuracy was evidenced by a sensitivity of 72.3%, specificity of 85.2%, positive predictive value of 83.2%, and negative predictive value of 70.3%. Higher FinTox scores were also associated with receiving care at a safety‐net hospital, Black race, household income <600% of the federal poverty level, and Stage 4 cancer.

Conclusion

FinTox's robust psychometric properties and diagnostic accuracy position it as a reliable tool for detecting financial toxicity. Future research should evaluate its responsiveness to changes over time and integration into clinical workflows.
Implement practical steps to establish reputation for responsible leadership
Authors: Cain Butler
Published: August 2024

Establishing a reputation as a responsible leader within higher education takes time, effort, and consideration. Fortunately, college athletics administrators can follow a variety of practical strategies to improve their standing as reliable leaders. This article groups strategies into four categories: building a reputation for financial management, building a leadership reputation among staff, building a leadership reputation among supervisors, and supporting future leaders.
Elucidating Evolutionary Mechanisms and Variants of the Hammerhead Ribozyme Using In Vitro Selection
Authors: Brill Jake , Nurmi Connor , Li Yingfu
Published: August 2024

The Hammerhead Ribozyme (HHR) is a ubiquitous RNA enzyme that catalyzes site‐specific intramolecular cleavage. While mutations to its catalytic core have traditionally been viewed as detrimental to its activity, several discoveries of naturally occurring variants of the full‐length ribozyme challenge this notion, suggesting a deeper understanding of HHR evolution and functionality. By systematically introducing mutations at key nucleotide positions within the catalytic core, we generated single‐, double‐, and triple‐mutation libraries to explore the sequence requirements and evolution of a full‐length HHR. In vitro selection revealed many novel hammerhead variants, some of which possess mutations at nucleotides previously considered to be essential. We also demonstrate that the evolutionary trajectory of each nucleotide in the catalytic core directly correlates with their functional importance, potentially giving researchers a novel method to assess the sequence requirements of functional nucleic acids.
A retrospective of 50 years of NDCC publication: Advancing perspectives over time
Authors: Smith Everrett A. , D'Amico Mark M. , Garza Mitchell Regina , Eddy Pamela L.
Published: August 2024

When Arthur Cohen launched New Directions for Community Colleges (NDCC) in 1973, the focus was on sharing updates and practical advice for those leading and working in community colleges. At the time, scant attention was given to these institutions as most research centered on 4‐year colleges and universities. The context of community colleges matters in how finance and governance occur and in how leaders help their institutions navigate a constantly changing external environment that requires flexibility in meeting workforce needs. Fifty years have passed since the initial issue of NDCC was published, and this retrospective draws connections on three topics over time. First, this article reviews how finance and governance evolved, taking note of how the expansion of the sector and the complexity of operations altered operations. Second, a look at career and technical education (CTE) and workforce development occurs. The historical roots of vocational education in community colleges translate to new approaches to developing a skilled workforce to address employer demand. Finally, a review of leadership since the first issue was published shows how ideas of leadership have expanded and help identify new challenges leaders face.
Navigating the skill‐first economy: The evolving role of lifelong learning and career services at community colleges
Authors: Siddiqi Muddassir
Published: August 2024

The rapid pace of technological change is revolutionizing every sector of the economy, transforming how value is created and delivered to consumers through technologies like robotics, virtual reality, artificial intelligence, and the Internet of Things. This transformation underscores the need for a diverse workforce as the new skills valued and essential to employers are changing. In this context, community colleges are thrust into the national debate around the best options for educating skilled employees, given their historical role in preparing a significant portion of the national workforce and employers’ reliance on them as primary providers of middle‐skills training. A vital aspect behind this debate is elevating accountability calls from policymakers, parents, and students who question the value of a college degree and expect a return on investment in employment outcomes. Another aspect of this debate is the growing employers’ concerns about the readiness of graduates, which affects the ability of companies to implement new products, services, or business technologies. For many, there is a gap between the supply and demand of skilled workers and community colleges are not serving the needs of their students, employers, and communities. The article suggests two strategies to address the challenges associated with a skilled‐first economy and employee skills mismatch: (1) developing different approaches to credentialing by embracing lifelong learning, and (2) strengthening the collaboration between career services and employers to effectively support lifelong learning.
Dens evagination and complete invagination in the same tooth with extraoral fistula: A rare case report
Authors: Bolhari Behnam , Ghabraei Sholeh , Noori Faranak , Hashemi Nasim
Published: August 2024

Key Clinical Message

Successful management of a rare case involving both dens evaginatus and dens invaginatus in the same tooth, monitored over a 24‐month follow‐up.

Dens invaginatus (DI) is a congenital dental anomaly characterized by the presence of a tooth that resembles a “tooth within a tooth.” Conversely, dens evaginatus (DE) is a developmental anomaly distinguished by an additional tubercle or cusp on the tooth's crown. Both DI and DE can result in pulpal and periapical diseases in the affected tooth. This article presents a case of a healthy 14‐year‐old male with recurrent swelling under the chin and a wound with pus drainage on the right side of the submental area, associated with his left mandibular lateral incisor affected by both DI and DE. Clinical and radiographic examinations revealed that the tooth was necrotic and had a chronic apical abscess. Cone beam computed tomography (CBCT) confirmed Oehlers' type III DI and a talon cusp on the lingual surface of the same tooth. The patient underwent orthograde endodontic treatment. Passive ultrasonic activation of a 5.25% NaOCl solution and a mixture of Ca(OH)2 and a 2% chlorhexidine solution were utilized to effectively clean and eliminate the persistent pus discharge. After the resolution of the patient's symptoms, the apical third of the root canal and the invaginated space were filled with a plug of mineral trioxide aggregate (MTA), while the remaining root canal was filled using a sealer‐based obturation technique. A 24‐month follow‐up visit revealed complete bone regeneration in the previously affected periradicular tissues.
Unusual posterior elbow dislocation associated with radial head fracture managed nonoperatively in low‐ and middle‐income countries: A case report and literature review
Authors: Tumsifu Jean de Dieu Manegabe , Murhula Gauthier Bahizire , Munguakonkwa Paul Budema , Namugusha Alain Kabakuli , Bulabula Abasi Amisi , Maheshe Ghislain Balemba , Mgisha William , Kuhigwa Georges Toha , Cornu Olivier
Published: August 2024

Key Clinical Message

In LMICs, the nonoperative management of posterior elbow dislocation associated with radial head fracture is still a therapeutic option with favorable outcomes.

Elbow dislocation associated with radial head fracture is a rare lesion. The occurrence of such a lesion requires high energy trauma. The restoration of joint and radial head fracture that allows early mobilization is the best guarantee of a good functional outcome. We report a case of posterior elbow dislocation associated with radial head fracture managed by closed reduction and 1 week cast immobilization in neutral prono‐supination and 90°flexion followed by early mobilization was performed favorable functional outcome was obtained after 12 weeks. We review the different pattern of elbow dislocation and question the need of open reduction and internal fixation for displaced radial head fractures.
Chronic uterine inversion: Mimicking uterine cervical polyp or leiomyoma
Authors: Birge Ozer , Saibou Hamsatou , Kayar Ilkan
Published: August 2024

Key Clinical Message

The diagnosis of chronic uterine inversion occurs after birth or secondary to pathologies of the pelvic region organs. Especially, the diagnosis and treatment of isolated chronic inversion rapidly under appropriate conditions seem to reduce maternal morbidity and mortality.

Chronic uterine inversion is a rare clinical diagnosis and difficult to diagnose and treat. This is a 22‐year‐old patient with no particular history known for a month for uterine fibroid with a polyp, who gave birth through the cervix in the context of subfertility for a year. Non puerperal uterine inversion is a rare clinical condition, and it should be kept in mind that this may be uterine inversion when mass lesions causing clinical complaints are detected, especially in the vulva, vagina, and cervix uteri region. The quality of life of the patients is increased by reducing the morbidity and mortality rates by making a diagnosis with a good clinical and ultrasonographic evaluation.
Increased lung field permeability in young patients
Authors: Tanaka Ayaka , Hamakawa Masamitsu , Ishida Tadashi
Published: August 2024

Key Clinical Message

When the chest radiograph of a young patient shows lung hyperlucency, it is important to obtain a detailed clinical history of any previous episodes of childhood infection. Previous chest radiographs should be reviewed to determine whether the condition is congenital or acquired, and thus assist in a diagnosis of SJMS.
Cutaneous leishmaniasis mimicking psoriasis: A case report
Authors: Karaja Saja , Halloum Mai , Karaja Shahed , daher alhussen Abdul hadi , Qatza Ayham , Mansour Sanaa , Almasri Alae Aldin
Published: August 2024

Key Clinical Message

Scalp lesions associated with psoriasis and cutaneous leishmaniasis can be clinically indistinguishable, leading to misdiagnosis. Herein, we highlight a 70‐year‐old male initially misdiagnosed with psoriasis but subsequently confirmed to have cutaneous leishmaniasis. This emphasizes the importance of considering alternative diagnoses, especially in atypical presentations, to ensure accurate treatment.
A case of septic arthritis of the manubriosternal and chondrosternal joints
Authors: Randrianarisoa Rova Malala Fandresena , Andrianiaina Armel Mamihaja , Radinasoa Rajo Païdia , Vololontiana Hanta Marie Danielle
Published: August 2024

Key Clinical Message

Although rare, septic arthritis of the manubriosternal and chrondrosternal joints should be considered in the presence of a parasternal mass with fever and/or local signs of inflammation. MRI has an important role in the diagnosis. Blood cultures should be obtained routinely. We report an 80‐year‐old man with painful sternal swelling and fever. Chest MRI and PET scan were consistent with septic arthritis of the manubriosternal and chrondrosternal joints. Blood cultures were positive for Staphylococcus aureus. The evolution was favorable under antibiotic therapy for 6 weeks.
The role of idiosyncratic deals in shaping retirement preferences of older workers: A psychological needs perspective
Authors: Hasselgren Bune Caroline , Jonsson Robin
Published: August 2024

This study examines how idiosyncratic deals (I‐deals) affect older workers’ preferred retirement age. Drawing on basic psychological needs theory, we specifically investigate the role of need satisfaction at work in explaining this relationship. By means of confirmatory factor analysis (CFA) and structural equation modeling (SEM), our hypotheses were tested in a sample of 4234 employees aged 65 years or older in a large public‐sector organization in Sweden. The findings suggest that employees with negotiated I‐deals concerning schedule flexibility or financial incentives experienced greater need satisfaction and preferred to retire later than those without such deals. Additionally, task and work responsibility deals were shown to directly and positively predict retirement preferences. This study offers new insights into how I‐deals could delay the preferred retirement by fulfilling basic psychological needs. It may thereby inform interventions to increase need satisfaction at work and the implementation of policies for recruiting and retaining older workers.
Functionalized Metal‐Organic Framework for NADH Regeneration by Hydrogen in a Redox Flow Bioreactor
Authors: Li Feifei , Housseini Wassim EI , Zhu Qunyan , Zhang Lin , Yang Wensheng , Etienne Mathieu
Published: August 2024

The electrochemical regeneration of reduced nicotinamide adenine dinucleotide (NADH) using [Rh(Cp*)(bpy)Cl]+ holds significant promise for the industrial synthesis of chiral chemicals. However, challenges persist due to the high consumption of NADH and the limited efficiency of its cyclic regeneration, which currently hinder widespread application. To address these obstacles, based on in‐situ growth of 3D ordered metal‐organic framework (NU‐1000) on the surface of graphite felt, [Rh(Cp*)(bpy)Cl]+ were immobilized on the Zr6 nodes of NU‐1000 by solvent‐assisted ligand incorporation (SALI), and applied in a flow bioreactor. Moreover, we employ a gas diffusion electrode (GDE) to oxidize H2, providing a clean proton source for the electrochemical regeneration of NADH. Consequently, highly efficient enzymatic electrocatalytic synthesis of L‐lactate was achieved when coupled with L‐lactate dehydrogenases (LDH) as a model reaction, and the total turnover number (TTN) reached 19600 and 1750 for [Rh(Cp*)(bpy)Cl]+ and NAD+ after 48 h, corresponding to a high turnover frequency (TOF) of 2350 h−1 and 210 h−1 for [Rh(Cp*)(bpy)Cl]+ and NAD+, respectively. This work provides new insights for the construction of efficient enzymatic electrosynthesis systems in industrial production.
Platinum(II)‐Salphen Complexes as DNA Binders and Photosensitisers
Authors: Bartlett Molly , Burke Joseph , Sherin Petr , Kuimova Marina K. , Barahona Mauricio , Vilar Ramon
Published: August 2024

Current anticancer therapies suffer from issues such as off‐target side effects and the emergence of drug resistance; therefore, the discovery of alternative therapeutic approaches is vital. These can include the development of drugs with different modes of action, and the exploration of new biomolecular targets. For the former, there has been increasing interest in drugs that are activated by an external stimulus (e. g. light irradiation) to generate cytotoxic chemicals such as reactive oxygen species (ROS). For the latter, significant efforts are being directed to explore non‐canonical DNA and RNA structures (e. g. guanine‐quadruplexes), as alternative biomolecular targets. Herein we report the synthesis of a library of 21 new platinum(II)‐Salphen complexes (square planar platinum(II) complexes coordinated to tetradentate O,N,N,O‐Schiff base ligands), and the investigation, for all complexes, of their photophysical and photochemical properties, their interactions with duplex and quadruplex DNA, and their cytotoxicity against HeLa cancer cells both in the dark and upon light irradiation. Thanks to the intrinsic phosphorescence of the platinum(II) complexes, confocal microscopy was used for six of the complexes to determine their cellular permeability and localisation in two cancer cell lines (HeLa and U2OS). Altogether, these studies have allowed us to identify two lead platinum(II) complexes with high guanine‐quadruplex DNA affinity and selectivity, good cell permeability and nuclear localisation, and high cytotoxicity against HeLa cancer cells upon irradiation with no detected cytotoxicity in the dark.
Dynamic Life Cycle Assessment of Integrated Production of Steel and Methanol
Authors: Gaikwad Ankur , Schlüter Stefan
Published: August 2024

The dynamic carbon footprint profile of methanol production from steel mill gases is affected by fluctuations of steel mill gas flow rates and compositions, as well as the composition of electricity mix. The cross‐industrial network of steel mill, gas conditioning, hydrogen production, chemical synthesis, and power generation was simulated under dynamic conditions. Dynamic life cycle assessment (LCA) was carried out for computing the dynamic carbon footprint profile in 15‐min resolution for the integrated system of steel and methanol production. The dynamic LCA indicated that the CO2 emissions in a power plant, electrolytic hydrogen demand, and variations in electricity mix were the major drivers of the fluctuations in the total carbon footprint. Dynamic LCA is useful for quantifying temporal uncertainty in environmental impacts. This insight can be used to analyze uncertainty in impacts for downstream products, processes, and use cases.