bluuebunny/crossref_metadata_2025 huggingface dataset:
DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation
Authors: Mullen Nicholas J. , Shukla Surendra K. , Thakur Ravi , Kollala Sai Sundeep , Wang Dezhen , Chaika Nina , LaBreck Drew A. , Mallareddy Jayapal Reddy , Price David H. , Natarajan Amarnath , Mehla Kamiya , Sykes David B. , Hollingsworth Michael A. , Singh Pankaj K.
Published: May 2023

Pyrimidine nucleotide biosynthesis is a druggable metabolic dependency of cancer cells, and chemotherapy agents targeting pyrimidine metabolism are the backbone of treatment for many cancers. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine biosynthesis pathway that can be targeted by clinically approved inhibitors. However, despite robust preclinical anticancer efficacy, DHODH inhibitors have shown limited single-agent efficacy in phase I clinical trials. Therefore, novel combination therapy strategies are necessary to realize the potential of these drugs. To search for therapeutic vulnerabilities induced by DHODH inhibition, we examined gene expression changes in cancer cells treated with the potent and selective DHODH inhibitor brequinar (BQ). This revealed that BQ treatment causes upregulation of antigen presentation pathway genes and cell surface MHC class I expression. Mechanistic studies showed that this effect is 1) strictly dependent on pyrimidine nucleotide depletion, 2) independent of canonical antigen presentation pathway transcriptional regulators, and 3) mediated by RNA polymerase II elongation control by positive transcription elongation factor B (P-TEFb). Furthermore, BQ showed impressive single-agent efficacy in the immunocompetent B16F10 melanoma model, and combination treatment with BQ and dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1) significantly prolonged mouse survival compared to either therapy alone. Our results have important implications for the clinical development of DHODH inhibitors and provide a rationale for combination therapy with BQ and immune checkpoint blockade.
Structure of the connexin-43 gap junction channel in a putative closed state
Authors: Qi Chao , Acosta Gutierrez Silvia , Lavriha Pia , Othman Alaa , Lopez-Pigozzi Diego , Bayraktar Erva , Schuster Dina , Picotti Paola , Zamboni Nicola , Bortolozzi Mario , Gervasio Francesco Luigi , Korkhov Volodymyr M
Published: May 2023

Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state.
Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers
Authors: Xie Yeming , Ruan Fengying , Li Yaning , Luo Meng , Zhang Chen , Chen Zhichao , Xie Zhe , Weng Zhe , Chen Weitian , Chen Wenfang , Fang Yitong , Sun Yuxin , Guo Mei , Wang Juan , Xu Shouping , Wang Hongqi , Tang Chong
Published: May 2023

As the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by simultaneously capturing the epigenetic information in single-molecular resolution. Using SCA-seq, we simultaneously disclosed spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.
Atlas of Plasmodium falciparum intraerythrocytic development using expansion microscopy
Authors: Liffner Benjamin , Cepeda Diaz Ana Karla , Blauwkamp James , Anaguano David , Frolich Sonja , Muralidharan Vasant , Wilson Danny W , Dvorin Jeffrey D , Absalon Sabrina
Published: May 2023

Apicomplexan parasites exhibit tremendous diversity in much of their fundamental cell biology, but study of these organisms using light microscopy is often hindered by their small size. Ultrastructural expansion microscopy (U-ExM) is a microscopy preparation method that physically expands the sample by ~4.5×. Here, we apply U-ExM to the human malaria parasite Plasmodium falciparum during the asexual blood stage of its lifecycle to understand how this parasite is organized in three dimensions. Using a combination of dye-conjugated reagents and immunostaining, we have cataloged 13 different P. falciparum structures or organelles across the intraerythrocytic development of this parasite and made multiple observations about fundamental parasite cell biology. We describe that the outer centriolar plaque and its associated proteins anchor the nucleus to the parasite plasma membrane during mitosis. Furthermore, the rhoptries, Golgi, basal complex, and inner membrane complex, which form around this anchoring site while nuclei are still dividing, are concurrently segregated and maintain an association to the outer centriolar plaque until the start of segmentation. We also show that the mitochondrion and apicoplast undergo sequential fission events while maintaining an association with the outer centriolar plaque during cytokinesis. Collectively, this study represents the most detailed ultrastructural analysis of P. falciparum during its intraerythrocytic development to date and sheds light on multiple poorly understood aspects of its organelle biogenesis and fundamental cell biology.
Transcriptome analysis reveals genes associated with wool fineness in merinos
Authors: Ma Shengchao , Long Li , Huang Xixia , Tian Kechuan , Tian Yuezhen , Wu Cuiling , Zhao Zhiwen
Published: May 2023

Hair/wool usually plays an important role in maintaining animal physiological activities, and the economic value of wool cannot be ignored. At present, people set higher demands on wool fineness. Hence, improving wool fineness is the concern of fine wool sheep breeding. Using RNA-Seq to screen the potential candidate genes that associate with wool fineness can provide theoretical references for fine-wool sheep breeding, and also provide us new ideas for further understand the molecular regulation mechanism of hair growth. In this study, we compared the expression pattern difference of genome-wide genes between the skin transcriptomes of Subo and Chinese Merinos. The results showed that, 16 candidate differentially expressed genes (DEGs) (Included: CACNA1S, GP5, LOC101102392, HSF5, SLITRK2, LOC101104661, CREB3L4, COL1A1, PTPRR, SFRP4, LOC443220, COL6A6, COL6A5, LAMA1, LOC114115342 and LOC101116863 genes) that may associate with wool fineness were screened, and these genes were located in signaling pathways that regulate hair follicle development, cycle or hair growth. It is worth noting that, among the 16 DEGs, COL1A1 gene has the highest expression level in Merino skins, and the fold change of LOC101116863 gene is the highest, and the structures of these two genes are both highly conserved in different species. In conclusion, we speculate that these two genes may play a key role in regulating wool fineness and respectively have similar and conserved functions in different species.
confinamiento por Covid, una oportunidad para revalorizar el juego infantil en el espacio público. El caso del barrio La Concha en Chiautempan, Tlaxcala, México
Authors: Reyes José Manuel , Lugo Laguna Porfirio Eduardo
Published: May 2023

El juego libre en la vida de los niños es una necesidad básica para su desarrollo integral. Actualmente siguen encontrando muchas dificultades como la pérdida y la negación del espacio público para poder jugar y la pandemia ha venido a incrementar esta exclusión. El caso del barrio la Concha en Chiautempan, Tlaxcala, México es una muestra de cómo se dio este proceso en un sinnúmero de barrios y colonias urbanas que han tenido que abandonar el espacio público, trayendo como consecuencia que los niños vivan el encierro en casa la mayor parte del tiempo y totalmente en tiempos pandemia. El juego libre es universal, creador de conocimiento, imaginativo, autónomo, espontáneo y social; el niño para jugar no necesita más que amigos, espacio disponible y tiempo. Por ello, la labor de los adultos debe ir encaminada a favorecer estos tres aspectos ya que, en caso contrario, puede traer severas consecuencias a los niños: físicas, emocionales y vivenciales, pero sobre todo les estaremos privando del placer de jugar.
Sociedades vinculadas a su entorno Conocimientos técnicos locales para la gestión sustentable del agua
Authors:   Universidad Tecnológica Metropolitana, Chandia-Jaure Rosa
Published: May 2023

Chile enfrenta un escenario de escasez hídrica, provocado por el cambio climático y la gestión poco eficiente de los recursos hídricos. Los asentamientos urbanos se encuentran vulnerables y deben adaptarse para garantizar la disponibilidad hídrica futura para sus habitantes y para los ecosistemas cercanos. En la búsqueda de posibles mecanismos de adaptación para enfrentar este desafío, se reflexiona sobre los aportes provenientes del conocimiento técnico heredado de antiguas sociedades sobre la gestión del agua. Se observa en estas sociedades, el reconocimiento de la cuenca hidrográfica como unidad territorial determinante de las intervenciones. El uso de materiales locales y el reconocimiento del entorno, posibilitó la construcción de un paisaje y la gestión eficiente del agua disponible, permitiendo la estabilidad de las sociedades por extensos periodos de tiempo. El conocimiento técnico ancestral, ya sea el que desarrollaron grandes civilizaciones, como también el de comunidades indígenas que aún hoy se mantienen vigentes, constituye un cuerpo integral de saberes de bajo impacto en el medio ambiente y de alta resiliencia frente a los cambios. Constituye un modelo para reorientar las estrategias para el reconocimiento del entorno y la gestión sustentable del agua, desde la gestión local de los recursos disponibles.
Walt Disney World
Authors: Santos Rennan Carvalho dos , Costa Marconi Freitas da
Published: May 2023

This research aims to analyse the influence of optimism on technology readiness and co-creation experiences in the consumption experiences of the millennial generation at Disney's theme parks as well as their relationship to customer delight. Quantitative research was carried out. The sample obtained 530 respondents, and the Structural Equation Modeling for data analysis was used. The results indicate that the consumption experiences of the Millenials are linked to factors not previously evidenced by other generations, such as the co-creation experiences and the optimism for technological readiness, which increase the degree of these experiences and can lead to consumer delight. On a practical level, it is worth highlighting the importance of theme park marketing teams understanding the behaviour of the millennial consumer, given his/her continuous growth in purchasing power compared to other generations.
Variation of Floristic Diversity along Altitudinal Gradient in Pir Panjal Forests of North Western Himalaya, India
Authors: Farooq Saima , Sofi P. A. , Pala Nazir A. , Saraf Sajad Abdullah , Gangoo S. A. , Singh Amerjeet , Masoodi T. H. , Dhekale Bhagyashree
Published: May 2023

The present study is an attempt to make a floristic inventory in Raithan Range of Pir Panjal Forest Division of, Jammu and Kashmir India. For this purpose, a preliminary study was carried with the aim to know the diversity of flora at different altitudes ranging from 1800-2800m amsl. For study purpose the area was divided into 3 different altitudes viz - 1800m, 2300m and 2800m amsl. The reported results revealed that, a total of 136 species from 58 different families and 113 genera were recorded. Out of 136 species there are 29 tree species (belonging to 16 families), 9 shrub species (6 families), 92 herb species (33 families), 4 climber species (4 families) and 2 fern species  (belonging to 2 different families). The Asteraceae and Rosaceae family were dominant in the research area, according to the data. Among different sites in the study area, site 1 (altitudinal range of 1800-2300m) showed maximum diversity of flora represented by 85 species, followed by site 2 (2300-2800m) represented by 71 species and least at site 3 (> 2800m) represented by 49 species. The study is a preliminary one and can be used for management of the species having less population for conservation and sustainable utilization.
Sobre web TV pessoais//About personal web TV
Authors: Kilpp Suzana
Published: May 2023

O artigo tece considerações críticas sobre a experiência de criar uma web TV na Internet. Apresenta o contexto, objetivos e justificativa do experimento; os problemas e questões norteadoras; as etapas do experimento; e as considerações para a pesquisa de TV resultantes da experimentação. Toma por referência a interatividade enunciada e a realizada; e a mais importante moldura televisual: a grade de programação e a programação em fluxo.
POLÍTICAS INDIGENISTAS NO BRASIL COLONIAL, IMPERIAL E REPUBLICANO: A EVOLUÇÃO DO ORDENAMENTO JURÍDICO BRASILEIRO
Authors: Melo Vinicius Holanda , Lima Martonio Mont'Alverne Barreto
Published: May 2023

O presente artigo visa investigar documentos jurídicos datados nos períodos do Brasil colonial, imperial e republicano, a fim de discutir o lugar do índio na história brasileira, abordando o ordenamento jurídico nacional diante das populações indígenas da época até os dias atuais. Desse modo, analisa-se que, desde a primeira Carta Magna de 1824, até a Constituição Federal de 1988, os nativos eram considerados desprovidos de autonomia e “não civilizados”. Por isso, deveriam ser integrados à comunhão nacional pela imposição da visão eurocentrista, das suas culturas e leis. O objetivo da pesquisa cuida de demonstrar a evolução no tratamento dos povos indígenas, conforme as análises das legislações vigentes à época, tendo como pressuposto a importância desses povos para a construção da história do Estado nacional brasileiro. O artigo será apresentado com base em estudo descritivo-analítico, utilizando-se do método dedutivo, com investigação bibliográfica em livros dos principais expoentes do tema, sítios eletrônicos e em revistas jurídicas. Conclui-se que houve uma evolução na concessão de direitos aos povos indígenas frente ao ordenamento jurídico constitucional diante da promulgação da Constituição Federal de 1988, propondo-se, na contemporaneidade, o resgate de direitos e deveres das populações autóctones e o comprometimento com a garantia destes.
Hepatitis C Virus Screening in Pregnant and Nonpregnant Women After Universal Screening Guidelines
Authors: Singh Roshni P. , Biondi Breanne , Gordon Sarah H. , Linas Benjamin P. , Epstein Rachel L.
Published: February 2025

This study examines whether hepatitis C virus screening differs among pregnant and nonpregnant women.
A Stable Broadband Antireflective Structure on MgAl2O4 Fabricated by Spatially Shaped Ultrafast Laser Pulses
Authors: Li Xun , Shan Chao , Chen Kai , Li Chen Chen , Wang Li Feng , Tan Yu , Li Ming
Published: February 2025

Subwavelength structures on MgAl2O4 hold significant technological importance in mid‐infrared (mid‐IR) optics, particularly for windows used in military mid‐IR devices that must operate under harsh conditions. Herein, a novel and efficient strategy utilizing spatially shaped femtosecond laser pulse delay for fabricating antireflective surfaces on hard, difficult‐to‐machine spinel with stable and broadband transmittance in mid‐IR waves is reported. With this method, a new micro–nanohybrid structure composed of a parabolic microhole associated with nanopores (MHNP) is achieved by optimizing Bessel femtosecond pulse delay since the subsequent pulse can irradiate at different stages of materials plasma diffusion, thermal expansion, and phase transformation. The mechanism for more stable transmittance enhancement of MHNP in broadband is explored by the finite‐difference time‐domain simulation, indicating that such localized field selective enhancement in structures is caused by the competition between interface equivalent refractive index effect and the light interference for the parabolic MHNP. As the height of the parabolic microhole and nanopore nears 1 μm and 400 nm, respectively, the resulting transmittance of MHNP with three different periods increases by 3.5–5.5% for 2.85–5.5 μm wavelength, and the maximum transmittance reaches a value of 94.4%.
Influence of a Hydrogen Addition to the Inert Gas and Subsequent Heat Treatments on the Microstructure and Mechanical Properties of Magnesium WE43 Fabricated by PBF‐LB/M
Authors: Abel Arvid , Breitbach Elmar Jonas , Holländer Hannes , Müller Michael , Griemsmann Tjorben , Klose Christian , Hermsdorf Jörg , Maier Hans Jürgen , Kaierle Stefan , Overmeyer Ludger
Published: February 2025

Additive manufacturing of magnesium alloys shows great potential for producing patient‐specific resorbable implants or lightweight parts. However, due to the reactive behavior, especially in the laser‐based powder bed fusion (PBF‐LB) fabrication process, the processing window to manufacture almost pore‐free parts is narrow compared to other materials such as titanium or steel. This article investigates optimal processing conditions for the PBF‐LB/M of WE43. To reduce the reactivity of the magnesium melt by limiting the interaction with remaining oxygen, a 3 vol% hydrogen admixture to the argon inert gas is investigated. Furthermore, long‐duration heat treatments are investigated in the range of 250–350 °C for 48 h. This study evaluates the impact of both methods on mechanical properties and microstructure. Although hydrogen seems to have no significant influence on the relative density, the microstructure, and the phase composition, it can slightly increase the tensile strength and elongation at break in the as‐built state. A heat treatment of 250 °C can increase the elongation at the break without impeding the tensile strength.
Reactive Element‐Effect Optimized Ni–Cr–W–Al Alloy for Fabricating Robust and Fluorine‐Free Superhydrophobic Coating on Al Alloy
Authors: Ai Keyu , Li Yixuan , Xu Ying , Chen Yingyu , Wang Zengyi , Zhang Yan , Han Jianhua
Published: February 2025

This study develops a readily implementable surface modification technique for Al alloys by combining electroplating alloy films with depositing stearic acid to make a durable superhydrophobic coating. Selecting Al as anode for electroplating innovatively, the introduction of Al element improves the adherence and roughness of the coating through a principle identical to the reactive element (RE) effect. Al can be preferentially combined with oxygen to reduce the partial pressure of oxygen, inhibiting outward diffusion and oxidation of the electroplated alloy components, reducing the defects formed by the outward diffusion of the metal elements and the accompanying porosity and cracks. Besides, the dense and stable nature of the oxide film formed by RE effect can better protect the Al alloy substrates from oxidation. It is shown that the crystallinity and oxidation resistance of the alloy is significantly enhanced by the RE effect. Notably, the champion water contact angle has reached 162° ± 0.7°, and a significant reduction in surface porosity is observed. This research has the potential to provide a simplified fabrication process of Ni–Cr–W alloy and pave the way for the development of durability of superhydrophobic film.
Design and Fabrication of an Enhanced Thermoresponsive PEG/Carbon Nanotube Microvalve for Efficient Flow Control in Microchannels
Authors: Samadi Mitra , Rahbar Shahrouzi Javad , Mohammadamini Fatemeh , Towfighi Farshid
Published: February 2025

Microvalves are essential in microfluidic systems, as they regulate fluid flow direction and enable critical operational functions. This study focuses on designing and fabricating a phase change polymeric microvalve utilizing polyethylene glycol (PEG) combined with multiwall carbon nanotubes (MWCNT) to improve the response time. A microchip made from polydimethylsiloxane (PDMS) features a microchannel with a cross‐sectional area of 100 × 200 µm2 where water is injected at flow rates between 10 and 100 mL min−1. In addition, effective thermal regulation is attained by implementing a nickel–chromium wire plate heater, which is meticulously controlled by a sensor to guarantee precise temperature management. The results indicate that the fabricated microvalve exhibits remarkable operational limits, withstanding a maximum tolerable pressure of 182 mmHg in the closed state. It consistently achieves an average response time of ≈170 s under various temperature conditions, underscoring its efficiency and reliability for demanding applications. Notably, the incorporation of 0.1 wt.% MWCNTs in PEG successfully reduce the response time from 180 to 130 s at an operating temperature of 60 °C, demonstrating significant potential for developing faster actuators.
Design of Double‐Sided Optical Coatings for Space Cooling Through Vertical Windows
Authors: Kwak Hyunkyu , Kim Do Hyeon , Song Young Min
Published: February 2025

Passive radiative cooling is a promising energy‐saving strategy for space cooling. Dual‐sided thermal emitters offer efficient heat removal from enclosed spaces; however, existing studies predominantly focus on rooftop applications, with limited attention to vertical surfaces, such as walls and windows. Here, a dual‐sided radiative cooling glass (DSRCG) tailored for vertical applications proposed, enhancing enclosure cooling. The DSRCG incorporates multilayer epsilon‐near‐zero materials, including Al2O3 and Si3N4, layered on a double‐sided indium‐tin‐oxide‐coated glass. The outward side of the DSRCG exhibits angular‐selective emission for efficient heat dissipation, while the inward side minimizes thermal radiation into enclosures. The visibly transparent layers enable a visible transmittance exceeding 72%. The simulation results demonstrate that the DSRCG reduces heat transfer to enclosures by 15 W m−2 compared with the conventional glass (C‐glass) at ambient temperatures above 30 °C. These findings highlight the DSRCG's potential as an energy‐saving window for reducing space‐cooling energy usage.
Lowering the Entrance Hurdle for Lab Automation: An Artificial Intelligence‐Supported, Interactive Robotic Arm for Automated, Repeated Testing Procedures
Authors: Conrad Stefan , Auth Philipp , Masselter Tom , Speck Thomas
Published: February 2025

Laboratory automation is crucial for improving efficiency and enhancing reproducibility in scientific workflows. However, industrial solutions mostly do not fit the needs of scientific institutions, such as cost efficiency, customizability, and flexibility in fast iteration cycles. This study presents a laboratory automation system that integrates affordable robotics and artificial intelligence (AI)‐driven functionalities in a modular architecture to address key challenges in research environments. The system uses a robotic arm and a large language model (LLM) as a lab assistant, enabling natural language interaction and task orchestration. In contrast to fully autonomous systems, this approach emphasizes a collaborative human‐in‐the‐loop model, ensuring adaptability and reducing reliance on artificial intelligence for task planning. Key innovations include meta‐tools for dynamic task recording and playback, low‐level information management to reduce cognitive load on the LLM, and AI‐assisted data reading for real‐time measurement extraction. The system's ability to automate complex workflows is validated in three experimental scenarios, involving sample preparation, error handling, and multi‐step measurements. The system demonstrates the ability to perform tasks with minimal user input while maintaining flexibility and adaptability to changing experimental conditions. The findings pave the way for the future of laboratory automation, where human and AI‐driven systems work seamlessly together in optimized scientific workflows.
Constructing SiAPP‐NH2@MOFs Core‐Shell Structure Toward Hierarchical Composites With Excellent Flame Retardancy, Smoke Suppression, and Electromagnetic Interference Shielding
Authors: Shi Yongqian , Han Junqiang , Yao Ansheng , Liu Miao , Wang Bibo , Zhang Cancan , Zou Hongfei
Published: February 2025

Designing multifunctional composites with high flame retardancy and excellent electromagnetic shielding performance is of significant importance. In order to address the poor flame retardant and electromagnetic shielding performances of thermoplastic polyurethane (TPU) composites, in this work, the γ‐propyl‐trimethoxysilane (KH550) functionalized silicon microencapsulated ammonium polyphosphate (SiAPP‐NH2) was synthesized using interface modulation technology. Then, SiAPP‐NH2 was combined with a copper metal–organic framework (MOF‐Cu) through microencapsulation and electrostatic self‐assembly techniques to prepare microencapsulated flame retardants (SiAPP‐NH2@MOF‐Cu). Subsequently, TPU composites were prepared through melt blending of SiAPP‐NH2@MOF‐Cu with TPU material. The results showed that the interface interaction between SiAPP‐NH2@MOF‐Cu and the TPU matrix was significantly enhanced. Compared to pure TPU, TPU/5SAN@1MC composite exhibited decreases of 78.7%, 51.3%, 59.3%, and 58.7% in peak heat release rate, total heat release, total smoke release, and total carbon dioxide release, respectively. In addition, TPU/1SAN@1MC/rGO composite achieved an average shielding effectiveness of 13.82 dB in the X‐band, enabling its broad commercial application. This study offers a promising strategy for the fabrication of TPU composites with good flame retardant and electromagnetic shielding properties.
Investigation of absorption, metabolism, and excretion of [14C]pruxelutamide (GT0918), an androgen receptor antagonist in humans
Authors: Zheng Yuan‐dong , Ma Sheng , Yuan Ya‐li , Zhang Hua , Yang Ying , Ye Feng‐zhi , Wang Mei‐yu , Chen Jie , Tong You‐zhi , Hu Tao , He Yi‐fei , Zhang Yi‐fan , Zhong Da‐fang , Miao Li‐yan , Diao Xing‐xing
Published: February 2025

Aims

The primary objective of this study was to determine the pharmacokinetics, mass balance and biotransformation of [14C]GT0918 in humans after the drug was administered to healthy Chinese male subjects.

Methods

The absorption, metabolism, and excretion (AME) of GT0918 was characterized via isotope labelling technology in six healthy Chinese male subjects after receiving a single 200 mg oral dose of [14C]GT0918 (80 μCi), and the phenotype, together with the metabolic mechanism of GT0918, was confirmed in vitro.

Results

The medium Tmax of total radioactivity was 6.00 h (4.00–8.00 h) post‐dose, and the mean Cmax was 10.5 μg eq./mL (8.7–12.3 μg eq./mL) in plasma. Drug‐related components in the plasma were eliminated slowly, with a mean t1/2 of 67.7 h (54.4–90.7 h), and the radioactivity of the plasma samples from some subjects was above the below the quantization limit (BQL) until 17 days post‐dose. After 19 days of dosing, the mean cumulative excreted radioactivity was 82.81% (79.07–86.07%) of the dose, including 29.47% (26.71–32.02%) in urine and 53.34% (52.01–55.62%) in faeces, indicating that the drug‐related components of GT0918 were mainly excreted by faeces. Metabolite profiling revealed that the parent drug was detected in plasma, as well as in faeces and not in urine. In plasma, the most abundant metabolite was GT0955, a mono‐oxidative metabolite of GT0918; in urine, the primary metabolite was GT0795, a metabolite of oxazole ring‐opening followed by N‐dealkylation; in faeces, the two main metabolites were M551 and the glucuronidation of GT0955. The majority of the metabolites were formed via an important aldehyde intermediate derived from the oxazole ring‐opening, and the intermediate was trapped by methoxyamine hydrochloride in the in‐vitro study. CYP3A4 is the main enzyme involved in the metabolism of GT0918.

Conclusions

Overall, all the dosed subjects completed the study, and GT0918 was found to be safe, with no grade II or above adverse events reported. A total dose of 82.81% was quantified in the urine (29.47%) and faeces (53.34%) of healthy adult male subjects after a single oral administration of 200 mg (80 μCi) GT0918 ([14C]GT0918). The metabolism of GT0918 is catalysed predominantly by CYP3A4, and an uncommon pathway of oxazole ring‐opening to an aldehyde intermediate has also been proposed.
Green Supply Chain Management to Spur Economic, Social, and Environmental Performance: Novel Insight From Latin American Countries
Authors: Morán Pablo David Tapia , Fan Mingyue , Sampene Agyemang Kwasi
Published: February 2025

Green supply chain management, or GSCM, has become an indispensable plan for advancing sustainable development worldwide. It can simultaneously enhance social, economic, and environmental outcomes. This study aims to investigate the impact of GSCM on key performance measures in Latin American economies and assess its implications for sustainable growth from 2000 to 2020. The analysis utilizes the method of moments quantile regression (MMQR) to estimate the long‐term nexus among the understudied series. Findings indicate that GSCM positively influences economic performance indicators like GDP, trade openness, and employment growth. Socially, GSCM is associated with enhanced human capital and is inversely related to water and air pollution deaths. Environmentally, it significantly reduces PM2.5 levels, carbon emissions, and fuel consumption. Causality analysis reveals a unidirectional influence of employment growth, human capital, and PM2.5 on GSCM and a bidirectional relationship between trade openness, carbon emissions, and pollution‐related deaths with GSCM. The study underscores the necessity for policies integrating GSCM to spur economic growth and improve public health and environmental quality across Latin American nations.
Corporate Governance and ESG Controversies: Navigating Risk‐Taking in Banks
Authors: Del Sarto Nicola
Published: February 2025

This study examines the impact of environmental, social, and governance (ESG) controversies on bank risk, focusing on the moderating role of corporate governance. Using a dynamic panel dataset of 88 European banks from 2013 to 2020, we analyze two key risk measures: the Z‐score, indicating financial stability, and risk‐weighted assets (RWAs), reflecting risk exposure. The findings reveal that banks facing ESG controversies are exposed to heightened risk, with corporate governance playing a crucial role in moderating these effects. Strong governance structures, characterized by board diversity and independence, are found to mitigate the financial risks associated with ESG controversies, whereas weak governance amplifies these risks. Our results contribute to the growing literature on ESG and bank risk by highlighting the complexities introduced by ESG controversies and the essential role of governance in managing these risks. These insights are relevant for both academics and practitioners seeking to enhance risk management frameworks in the banking sector.
Cocreating Value Through Open Circular Innovation Strategies: A Results‐Driven Work Plan and Future Research Avenues
Authors: Camilleri Mark Anthony
Published: February 2025

For the time being, there is limited research focused on open innovation approaches that promote the development and growth of stakeholder‐driven circular economy models. This article addresses this knowledge gap. Its objectives are threefold: Firstly, it describes key elements of open innovation and circular value cocreation. Secondly, it utilizes the findings from a comprehensive systematic review to identify opportunities and challenges related to the open circular innovation paradigm. Thirdly, it presents theoretical implications and an action plan, alongside future research avenues, that highlight the importance of engaging in collaborative behaviors with stakeholders. It emphasizes a cocreation culture that encourages the sharing of resources, competencies, and capabilities, while safeguarding the organizations' intellectual properties. Such practices aim to foster coupled innovation and support circular economy strategies like resource recovery, reverse logistics, and industrial symbiosis, among others. Unlike many other articles, this contribution clearly specifies that there is scope for practitioners to develop circular economy ecosystems that increase the practitioners' bottom lines, while reducing their environmental impacts.
The Dual Growth‐Value Transfer Nexus: Sustaining Corporate Performance Among Hidden Champions to Achieve Sustainable Growth
Authors: Hongbin Ying , Weiwen Chen , Cifuentes‐Faura Javier , Lijun Pang
Published: February 2025

The dual growth model is a significant characteristic of hidden champions and a key reason for their sustained competitive advantage. This work employs the dual growth model to develop a theoretical model of “dual growth model–value transfer–corporate performance.” The study results indicate that hidden champions employ a dual growth model that concurrently attains efficiency and product growth. It is found that these two factors significantly enhance the performance of the hidden champions. Moreover, the transfer of value acts as a mediating role in the expansion of products. That is the rise of efficiency and the performance of the hidden champions.
A novel deproteinization method from crude polysaccharides of Meretrix meretrix Linnaeus based on palygorskite‐chitosan composite aerogel sieving effect
Authors: Zhu Yong , Ma Jingrui , Li Xinhang , He Quanrun , Wu Bingmin , Cheng Juanjuan , Huang Song , Chen Jihang
Published: February 2025

Due to the delicious taste and remarkable bioactivities of Meretrix meretrix L., they have garnered attention in food field. However, the challenge arises when attempting to separate proteins from crude polysaccharides with similar polarity and solubility. This paper aimed to develop a novel deproteinization method from crude polysaccharides of Meretrix meretrix L. (CPM) based on palygorskite‐chitosan composite aerogel (Pal‐CS aerogel) sieving effect. We focused on the influence of aerogels' pore structure on the selective deproteinization of CPM. In comparison to palygorskite or chitosan, Pal‐CS aerogel exhibited a superior advantage in selectively deproteinization due to its unique pore structure. Furthermore, under the concentration conditions of 2% Pal and 0.8% CS, the deproteinization rate (Dr%), polysaccharide adsorption rate (Pr%) and selectivity coefficient (Kc) reached impressive values of 95.08 ± 1.47%, 3.29 ± 0.14% and 28.95 ± 0.82, respectively. The findings from pore size analysis revealed that an appropriate size ranging from 0.1 μm to 3.0 μm significantly contributed to the selectively deproteinization based on the sieving effect. The adsorption mechanism study further highlighted that hydrogen bonding predominantly dominated the interfacial interaction between aerogel and proteins. In conclusion, this work provided a new perspective for the study on deproteinization of food polysaccharides.
Fractional Order PID Controller Based‐Neural Network Algorithm for LFC in Multi‐Area Power Systems
Authors: El‐Rifaie Ali M. , Abid Slim , Ginidi Ahmed R. , Shaheen Abdullah M.
Published: February 2025

Modern power systems are increasingly challenged by frequency stability issues due to dynamic load variations and the growing complexity of interconnected networks. Traditional PID controllers, while widely utilized, struggle to address the rapid fluctuations and uncertainties inherent in contemporary multi‐area interconnected power systems (MAIPS). This paper introduces an innovative approach to Load Frequency Control (LFC) using a Fractional‐Order PID (FOPID) controller, optimized by a Neural Network Algorithm (NNA). The proposed NNA‐FOPID framework leverages the biological principles of neural networks to dynamically tune controller parameters, significantly enhancing system performance. The solution is tested under various scenarios involving step load changes across multi‐area systems. The proposed method demonstrates marked improvements over traditional PID controllers and advanced optimization techniques such as Differential Evolution (DE) and Artificial Rabbits Algorithm (ARA). The comparisons show that the FOPID controller's NNA‐based design effectively and successfully handles LFC in MAIPSs for ITAE minimizations, and statistical evaluation supports its superiority.
Heavy Metal Bioaccumulation in Solanum torvum (Sw.) (Turkey Berry) From the Bono and Ahafo Regions: Nutritional Potential and Toxicological Risks
Authors: Golly Moses K. , Amponsah Afia S. , Asei Rechiatu , Doku Emmanuel T.
Published: February 2025

Heavy metal contamination of agricultural soils and subsequent bioaccumulation in food crops poses significant public health concerns, particularly in mining regions. This study investigated heavy metal concentrations in turkey berry (Solanum torvum) fruits and associated soils from three locations in Ghana's mining belt, evaluated soil contamination indices, and assessed potential health risks from fruit consumption. Fruit and soil samples were collected from farms in Kenyasi (mining area), Sunyani, and Berekum. Samples were acid‐digested and analyzed for Fe, Zn, Cd, and Ni using flame atomic absorption spectrophotometry. Results showed elevated metal concentrations in fruits, particularly from mining‐proximate farms, with Fe (106.27 ± 2.05–218.63 ± 4.05 mg/kg), Zn (32.78 ± 2.20–68.24 ± 2.40 mg/kg), and Cd (0.58 ± 0.10–2.93 ± 0.31 mg/kg) exceeding recommended dietary intake levels. Bioconcentration factors indicated significant accumulation of Zn, Cd, and Ni in fruits, especially in mining‐impacted zones. The pollution load index suggested anthropogenic enrichment of soil metals linked to mining activities. These findings highlight the need for soil remediation in mining‐affected areas and moderation of turkey berry consumption to minimize potential health risks. This study provides crucial data for food safety monitoring and environmental management in mining‐impacted agricultural zones.
Study on the Effects of National Volume‐Based Procurement of Chemical Drugs on Chinese Patent Medicines: Lipid‐Lowering Drugs as an Example
Authors: Yang Zhao , Han Xiao , Liang Pei , Zhao Xiaoting , Zhu Qiyun , Ye Hui , Yang Chao , Jiang Bin
Published: February 2025

Background

Atherosclerotic cardiovascular disease remains the leading cause of death worldwide. This study aims to explore the impact of national volume‐based procurement (NVBP) on Chinese patent medicines and provide evidence for improving policies and promoting rational drug use.

Methods

The study was based on data from the China National Health Insurance Agency that spanned January 2019 to December 2020. Descriptive analysis was conducted using volume and expenditure as variables. Interrupted time series analysis was applied to further analyze Chinese patent medicines.

Results

The unit prices of atorvastatin and rosuvastatin decreased by 25%–96%, whereas the prices of Zhibitai and Xuezhikang fluctuated slightly. The affordability is measured as the monthly expenditure on treatment divided by the daily wage. After policy implementation, the affordability of atorvastatin and rosuvastatin improved from 0.242 to 0.014 and from 0.247 to 0.019, respectively. The defined daily doses (DDDs) for atorvastatin and rosuvastatin also increased, whereas total expenditures decreased in hospitals of all levels. Both at the national level and at all levels of hospital, the policy had no significant impact on expenditures for Zhibitai and Xuezhikang and their defined daily doses.

Conclusions

The NVBP saved costs in the short term by incorporating high‐quality, widely used lipid‐lowering drugs. Notably, the policy impacted lipid‐lowering chemical drugs, whereas Chinese patent medicines remained largely unaffected. Doctors' use of Chinese patent medicines did not decline, highlighting the clinical specificity of these medicines.
Impact of Tobacco‐21 Laws on Maternal Smoking Behavior
Authors: Bersak Tim , Lavender Makayla , Sonchak‐Ardan Lyudmyla
Published: February 2025

This study employs a logit difference‐in‐differences model to estimate the extent to which raising the tobacco purchasing age to 21 (T‐21) reduced the prevalence of smoking among mothers aged 18–20 both before and during their pregnancies. Using United States Vital Statistics data from 2012 to 2019, we estimate that counties which adopted T‐21, whether individually or as part of a state‐level policy, experienced small but statistically significant decreases in maternal smoking prior to and during their pregnancies. Our estimates also suggest that the decline in smoking during pregnancy is driven by fewer women smoking prior to pregnancy rather than increased quit rates during pregnancy. Finally, our estimation strategy also allows us to focus on the expansions in New York City and California, which are the locations with the largest number of impacted births in our sample. We estimate T‐21 decreased maternal smoking both prior to and during pregnancy in California by up to 14% from baseline. Other studies which examined T‐21 on a broader set of young adults have found larger reductions in smoking rates, suggesting that the subpopulation of young mothers who choose to smoke may be relatively less responsive to policies that raise the minimum purchase age of tobacco products.
Enhancement of gut barrier integrity by a Bacillus subtilis secreted metabolite through the GADD45A‐Wnt/β‐catenin pathway
Authors: Liu Shiqi , Cai Peiran , You Wenjing , Yang Mingshun , Tu Yuang , Zhou Yanbing , Valencak Teresa G. , Xiao Yingping , Wang Yizhen , Shan Tizhong
Published: February 2025

Inflammatory bowel disease (IBD) represents a significant challenge to global health, characterized by intestinal inflammation, impaired barrier function, and dysbiosis, with limited therapeutic options. In this study, we isolated a novel strain of Bacillus subtilis (B. subtilis) and observed promising effects in protecting against disruption of the gut barrier. Our findings indicate that the enhancement of intestinal barrier function is primarily attributed to its metabolites. We identified a novel metabolite, 2‐hydroxy‐4‐methylpentanoic acid (HMP), derived from B. subtilis, that significantly improved intestinal barrier function. We also show that growth arrest and DNA damage 45A (GADD45A) is a key regulator of mucosal barrier integrity, which is activated by HMP and subsequently activates the downstream Wnt/β‐catenin pathway. Our findings potentially contribute to the development of probiotics‐derived metabolites or targeted “postbiotics” as novel therapeutics for the treatment or prevention of IBD and other diseases associated with intestinal barrier dysfunction.
Detection of QTL associated with morphological, adaptive, and reproductive traits in common bermudagrass
Authors: Yu Shuhao , Wu Yanqi , Fang Tilin , Xiang Mingying , Fontanier Charles H. , Moss Justin Q. , Martin Dennis L.
Published: February 2025

Common bermudagrass [Cynodon dactylon (L.) Pers.] is an important turfgrass in tropical, subtropical, and warm temperate climates worldwide. However, molecular information associated with adaptive and morphological traits in this species is limited. Accordingly, the objectives of this study were to identify genomic regions associated with establishment rate, spring green‐up, drought response, leaf length and width, and stem internode length and width. We used an existing high‐density linkage map constructed with 3322 single nucleotide polymorphisms and 222 simple sequence repeat markers for “A12359” common bermudagrass. A total of 130 first‐generation selfed progeny of A12359 were evaluated in a field trial using a randomized complete block design with three replications. Thirty‐two QTL were identified as associated with the target traits. We identified 29 candidate genes from consistent and pleiotropic QTL regions. These results provide important genetic resources toward understanding the molecular information associated with the target traits as well as provide a foundation for marker‐assisted selection in bermudagrass breeding.
Investigation of plant protein products on turfgrass putting greens quality, playability, and establishment
Authors: Lindsey Alex J. , Thoms Adam W. , Hatten Chad , Perry Rachel
Published: February 2025

With an increasing concern over negative environmental impacts of synthetic fertilizer usage and production, the turfgrass industry is investigating new fertilizer sources. Plant protein products could be used as an alternative and sustainable fertilizer source in formulations; thus, research is needed to determine their effect on turfgrass systems. Replicated field studies were conducted at the University of Florida and Iowa State University to determine if plant protein products could be utilized as a turfgrass fertilizer source on established and new putting greens. Treatments included soluble corn protein (SCP) 1, SCP 2, soluble potato protein (SPP), biofertilizer, synthetic, and non‐fertilized control. Treatments were applied every 14 days throughout the growing season at 6.1 kg N ha−1 on established putting greens and 9.8 kg N ha−1 on new putting greens. On established putting greens, minimal differences were observed with plant protein products compared to the non‐fertilized, biofertilizer, and synthetic fertilizer in terms of turfgrass quality and playability. SCP 1 and SPP resulted in 6%–8% greater normalized difference vegetation index (NDVI) compared to the non‐fertilized, and SCP 1 increased NDVI by 6% relative to synthetic fertilizer. Overall, on new putting greens, all treatments resulted in 7%–13% greater percent green cover compared to the non‐fertilized. In conclusion, it appears that plant protein products have the potential to be utilized as a turfgrass fertilizer source, but the specific plant proteins and formulations may have an impact on the turfgrass response.