bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation into Recycling of Iron Oxide Scale on H13 Steel by Low‐Temperature Carbothermal Reduction Method
Authors: Wang Haojie , Jiang Xuanqi , Wang Xijie , Li Guangqiang , Chen Zhiyuan , Dai Fangqin , Wang Qiang
Published: November 2024

The current method for recovering iron oxide scale in the steel industry is not economically optimal, especially for high‐alloy scales found in alloyed steel. This study focuses on iron oxide scale containing valuable metals like chromium (Cr), molybdenum (Mo), and vanadium (V). The required carbon addition is calculated based on the iron and chromium oxides in the scale. The effects of varying carbon additions and reduction temperatures on reduction efficiency are thoroughly examined. Kinetic studies show that as temperature and carbon increase, the rate‐limiting step shifts from interfacial diffusion to interfacial reaction. Reduction experiments assess carbon utilization, metallization rate, deoxidation rate, and removal of harmful elements. Results show that high temperatures hinder sulfur (S) and phosphorus (P) removal, and excess carbon reduces carbon utilization efficiency. Optimal conditions are a carbon ratio of 0.2174 and a temperature of 1150 °C. The carbothermic reduction product requires further refinement through conventional ladle slag systems to meet the quality standards for metallic materials. Over 65% of alloying elements are recovered, though phosphorus content remains slightly higher than in finished alloy steel. The materials from this study are suitable as high‐quality intermediates for alloy steel production.
Bromine‐Substituted Cation Anchoring to Suppress Ion Migration in Alternating Cations Intercalation‐Type Perovskite for Stable X‐Ray Detection
Authors: Xu Lijun , Guan Qianwen , Ye Huang , Wu Jianbo , Li Hang , Geng Yaru , Zhang Chengshu , Zhu Zeng‐Kui , Han Zhangtong , Yin Qiuxiao , Luo Junhua
Published: November 2024

Metal halide perovskites have emerged as excellent direct X‐ray detection materials owing to their large mobility‐lifetime product, strong radiation absorption, and low‐cost preparation. However, it is still a challenge to achieve stable X‐ray detection due to the limitations associated with severe ion migration under high voltage bias. Herein, based on a bromine substitution strategy to suppress ion migration, a 2D alternating cations intercalation‐type (ACI) perovskite, (R‐MPA)(BrEA)PbBr4 (1, R‐MPA = methylphenethylamm‐onium; BrEA = 2‐bromoethylamine) is reported to achieve X‐ray detection. Specifically, introducing Br atom forms additional intermolecular interactions (i.e., Br···π) and enhances hydrogen bonding interactions, greatly improving the structure stability. Based on this enhanced interaction, 1 presents a higher activation energy of ion migration (1.05 eV) than that of (R‐MPA)EAPbBr4 resulting in a lower dark current drift of 9.17 × 10−8 nA cm−1 s−1 V−1, revealing that suppression of ion migration. Consequently, the 1‐based detector shows a high sensitivity of 2653.7 μC Gy−1 cm−2 and, most importantly, outstanding operational and environmental stability, maintaining ≈91% of its initial sensitivity at 50 V bias after 90 days in the air. This work demonstrates an efficient strategy for introducing halogen interactions via ACI to suppress ion migration for stable X‐ray detection.
DNA‐Templated Gold Nanoclusters for miRNA Diagnostics with Branched Hybridization Chain Reaction
Authors: Chai Hua , Zhu Yulin , Miao Peng
Published: November 2024

In this study, a novel nonlinear branched hybridization chain reaction (BHCR) strategy is developed for accurate biosensing and bioimaging. Four fuel strands are designed. The first two assist the growth of primary long double‐stranded chain. Meanwhile, branched tails are left, which consist the trigger of downstream HCR with the second group of fuel strands. Branched DNA nanostructures are thus formed, which significantly amplify the information of initial target miRNA. Besides, the output fluorescent signal is originated from DNA‐templated gold nanoclusters (AuNCs). Surface ligands of AuNCs always play important roles in the regulation of optical mechanisms. Herein, peptide/DNA‐stabilized AuNCs are prepared. Phosphorothioate‐modified DNA (psDNA) is used as the template for in situ synthesis. The short peptide (Tyr‐Cys‐Tyr, YCY) is introduced as the protecting ligand, which benefits significant Stokes shift via a two‐step Förster resonance energy transfer. Coupling BHCR and AuNCs, this method performs satisfactory for in vitro fluorescent biosensing and intracellular bioimaging. It exhibits potential application for the investigation of miRNA‐related bioprocesses.
Impacts of terrestrial mammalian herbivores on vegetation change in the arctic
Authors: Osterrieth Maxime , Bosker Thijs
Published: November 2024

There are increasing concerns about regional ecosystem shifts in the Arctic due to climate change. Notably, warming-induced increases in Arctic vegetation cover can have important consequences for surface energy balance, habitat changes, permafrost, and more. Mammalian herbivory is an important potential force to counteract this effect. In this systematic literature review, we examine the role of terrestrial mammalian herbivory on warming-induced increases in Arctic vegetation. We analyse the effects of terrestrial mammalian herbivory on vegetation cover, abundance, growth, survival, and ecosystem productivity. Our results show that herbivory has an overall significant negative influence on Arctic vegetation, particularly on vegetation biomass, growth, and productivity, as indicated by the Normalised Difference Vegetation Index (NDVI). Importantly, we demonstrated a significant role of herbivores in controlling carbon dioxide exchange and carbon uptake, whilst acknowledging that the relationship between herbivory and ecosystem productivity is highly complex and site-dependent. Our results confirm the important role that herbivory can play in buffering observed and predicted warming-induced Arctic vegetation increases. We also find that this is strongly affected by plant palatability, trampling occurrence, and herbivore density.

Graphical Abstract
Spinal cord stimulation induces Neurotrophin-3 to improve diabetic foot disease
Authors: Liu Yi , Li XuanPeng , Xu HaiWen , Sun Ke , Gong Hui Jun , Luo Cheng
Published: November 2024

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3’s role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS’s therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.
Proofreading student writing: a research-based stakeholder tool focused on ethical practice
Authors: Richards Fiona , Harwood Nigel
Published: November 2024

This article presents a research-based stakeholder tool informed by a study of the various types of changes proofreaders may make when proofreading a student text. Whilst the tool can be used to advise higher education students, (non-)professional proofreaders/editors, English for Academic Purposes (EAP) lecturers, writing centre tutors, and university policy makers as to appropriate forms of third-party intervention, it is primarily intended to be used as a framework that assists academics in deciding which kinds of third-party intervention are un/ethical when allowing their students to have work proofread. As such, the stakeholder tool serves a heuristic purpose in that it: 1) displays the various types of interventions proofreaders could make for an academic to consider which interventions they wish to allow, from the lightest-touch (e.g., correcting typos or spelling errors) to the heaviest-touch (e.g., substantial, wholesale rewriting of the text by the proofreader at the level of content); 2) advises academics about un/ethical forms of proofreading intervention; 3) confirms an academic has given permission for a student to seek out proofreading support whilst specifying what in the academic’s opinion is un/ethical in terms of proofreading intervention; and 4) educates and trains stakeholders in academically sound proofreading practices. This stakeholder tool is timely when considering that some current university proofreading policies are poorly worded and ambiguous, and when considering the lack of clarity about or knowledge of university proofreading guidelines by stakeholders such as staff and students.
Gompertz-Weibull {Gompertz} Type I: A Four-Parameter Generalization of the Weibull Family
Authors: Smith Scott , Diaz-Martinez Brenda
Published: November 2024

In this paper, we provide a construction method that provides greater flexibility in modeling real-world phenomenon by generalizing univariate probability distributions. The Gompertz distribution is used to provide new classes of models through T-X{Y} construction, in a manner we will define as a “proper” generalization, illustrated by application to the popular Weibull family. We provide moments and other properties of the model, including the necessary equations for maximum likelihood estimation, and we fit a set of real data to the model. A framework for classifying generalizations that includes many previously discovered methods and considerations for the research infrastructure are proposed in our methods and discussion.
Reliability and durability assessment of bridge stay cables
Authors: Teichgraeber Marco
Published: November 2024

An algorithm for the reliability and durability assessment of stay cables in bridges is presented in this study enabling their probability of failure and a safe working period to be determined under various loading scenarios. The algorithm was originally developed based on data collected from an extensive structural monitoring campaign of the biggest single-pylon concrete cable-stayed bridge in Poland and used to assess the durability of its suspension system. It was then modified to be suitable for the evaluation of stay-cables subjected to wind excitation and structural reliability of the suspension system in a real steel bridge where permanent plastic deformations occurred in the anchor zones of the stay cables. The algorithm takes into account analytical models describing the stay cables and their numerical finite element models (FEM). As such, it is a universal tool having a wide range of applications, also beyond stay cables often encountered in medium- and long-span bridges forming a critical part of the civil engineering infrastructure.
Measuring integrated accessibility for sustainable mobility: a fuzzy set approach case study
Authors: Tahmasbi Behnam , Hajian Poria , Tahmasbi Farzaneh , He Qian
Published: November 2024

Sustainable transportation is vital to climate justice and social equity. Despite the efforts to achieve sustainability, there is still a lack of adequate measurement that integrates land use and transportation systems, which can be barriers to planning implementation. With methodological improvements in fuzzy theory application, this study develops an integrated index to measure the sustainability of multimodal accessibility. We do so by defining a fuzziness degree based on the different trip purposes and modes of transportation with a case study in Isfahan, Iran. Sustainable accessibility indicators were developed for walking, biking, and public transportation to represent the performance of each transportation system, considering the integration with land-use patterns. We analyze transportation modes and the accessibility to five main urban activities, including employment opportunities, education, healthcare, shopping, and recreation services, based on the travel distances, followed by a statistical integration method with Principal Components Analysis (PCA) for each travel mode. The outcome provides insights for urban planners and transportation planners to effectively evaluate the degree of integration between transportation and land-use systems and contribute to enhancing sustainable accessibility.
Residents’ willingness to pay for sustainable solid waste management services: a case of Glenview suburb, Harare, Zimbabwe
Authors: Jerie Steven , Chireshe Amato , Shabani Tapiwa , Shabani Takunda
Published: November 2024

Solid waste generation is an inevitable outcome of anthropogenic activities, which is an issue of concern in Zimbabwe. Among other challenges, inadequate finance is a key challenge to reach sustainable waste management. This study focuses on residents’ willingness to pay for improved solid waste management services. Analytical case study research design, employing quantitative and qualitative data collection, analysis and presentation was adopted. Data was collected using questionnaires, interviews, observations while analysis was done using SPSS and content analysis. Results indicated that most respondents were house owners (53.92%) and 46.08% were tenants. Solid waste generated consists of hazardous and non-hazardous waste. Solid waste collected by the city council (57.84%), private collectors (36.27%) while remaining is collected by other individuals and scavengers. Interviews and questionnaires outcomes denote that solid waste was collected once a week (43.14%), twice a week (3.92%) and rarely collected (38.24%). Solid waste is disposed through open dumping, burning, pits and landfilling, although most of the disposal strategies pose environmental health problems. Solid waste mismanagement is attributed to lack of awareness, weak legal framework and shortage of resources, specifically finance. Questionnaire respondents (66.67%) argued that proper solid waste management is important and needs to be improved. Participants (65.69%) revealed that they were willing to pay for improved solid waste management, however, 34.31% were unwilling. Willingness to pay for improved solid waste management was determined by educational level and house ownership status. Improving residents’ willingness to pay for proper solid waste management requires an integrated approach and increasing residents' awareness.
Monthly Prediction on Summer Extreme Precipitation With a Deep Learning Approach: Experiments Over the Mid‐To‐Lower Reaches of the Yangtze River
Authors: Fan Yi , Lyu Yang , Zhu Shoupeng , Yin Zhicong , Duan Mingkeng , Zhi Xiefei , Zhou Botao
Published: November 2024

Accurate predictions of monthly extremes assume paramount importance in enabling proactive decision‐making, which however are lacked in skills even for state‐of‐the‐art dynamical models. Taking the extreme precipitation prediction over the mid‐to‐lower reaches of the Yangtze River, China, as an instance, a multi‐predictor U‐Net deep learning approach is designed to enhance the prediction over the European Center for Medium‐Range Weather Forecasts (ECMWF) model, with the single‐predictor U‐Net parallelly examined as the benchmark. Focusing on the precipitation extremes, an extreme associated component is incorporated into the model loss function for optimization. Besides, predictions composed by daily outputs with multiple lead times are imported as a comprehensive set in the training phase to augment the deep learning sample size and to emphasize enhancements in predictions at the monthly timescale as a whole. Results indicate that the multi‐predictor U‐Net effectively improves predictions of extreme summer precipitation frequency, showing distinct superiority to the raw ECMWF and the single‐predictor U‐Net. Multiple evaluation metrics indicate that the model shows a significant positive improvement ratio ranging from 65.1% to 80.0% across all grids compared to the raw ECMWF prediction, which has also been validated through applications in the two extreme summer precipitation cases in 2016 and 2020. Besides, a ranking analysis of feature importance reveals that factors such as humidity and temperature play even more crucial roles than precipitation itself in the multi‐predictor extreme precipitation prediction model at the monthly timescale. That is, in such a deep learning approach, the monthly prediction on extreme precipitation benefits significantly from the inclusion of multiple associated predictors.
Dynamically Triggered Tectonic Tremors and Earthquakes in the Caucasian Region Following the 2023 Kahramanmaraş, Türkiye, Earthquake Sequence
Authors: Yao Dongdong , Peng Zhigang , Ding Chang , Sandvol Eric , Godoladze Tea , Yetirmishli Gurban
Published: November 2024

Deep tectonic tremor has been observed along major subduction zones and several continental strike‐slip faults around the Pacific Rim and the Caribbean. However, it has not be widely identified in other tectonically active regions such as the Alpine‐Himalayan orogenic belt yet. Here we present dynamically triggered tremors and microearthquakes in the Caucasian Region following the 2023 Mw 7.8 and Mw 7.5 mainshocks in the 2023 Kahramanmaraş, Türkiye, earthquake sequence. We observe triggered deep tectonic tremors within Azerbaijan, where seismological evidences suggest pre‐existing subduction slabs. Meanwhile, we document cases of triggered earthquakes in Azerbaijan and Georgia, and Javakheti highland near the border of Georgia and Armenia. These triggered earthquakes are either associated with mud volcanism or volcanic formations. Our results highlight a variety of responses to dynamic stress perturbations, suggesting high susceptibility to dynamic stress perturbations and a broad spectrum of slip behaviors for critically stressed faults in the Caucasian region.
On the Relationship Between the Banded Hiss Distribution and Plasmapause Location: A Survey of Van Allen Probes Observations
Authors: Dong Junhu , Xiang Zheng , Ni Binbin
Published: November 2024

The plasmapause is the outer boundary of the plasmasphere and plays a crucial role in the propagation of plasma waves. We statistically investigate the relationship between the distribution of banded hiss and plasmapause locations. Wave power distributions of banded hiss are analyzed in terms of two ways: (a) the distance away from the plasmapause (ΔL) and (b) the equatorial distance away from the Earth. Statistical results show both bands of banded hiss have larger wave powers and occurrence rates near the plasmapause. The frequencies of two banded hiss waves both decrease discernably with increasing L‐shell at most magnetic local time sectors and geomagnetic activities, but remain nearly constant with increasing ΔL. The highly consistent distribution suggests both bands may be generated in the plume region. The correlation between banded hiss waves and plasmapause locations sheds new light on the generation mechanisms of banded hiss waves.
Possible Causes for the Unprecedented Low/High Tropical Cyclone Activities in the Northern Pacific/Atlantic in 2023 El Niño
Authors: Chen Kuan‐Chieh , Hong Chi‐Cherng , Chang Chi‐Chun , Chiang Jun , Chang Sheng‐Hsiang
Published: November 2024

This study reported the unprecedented tropical cyclone (TC) activity in the western North Pacific (WNP) and North Atlantic (NA) during the developing year of the 2023/2024 El Niño. The possible causes behind these unusual features were addressed. In contrast to previous El Niño events, an unusual low/high TC genesis number in the WNP/NA was identified during the typhoon season (June–November) in 2023. Meanwhile, the mean TC genesis location in the WNP exhibited a La Niña‐like northwestward shift, rarely observed in an El Niño developing year. An observational diagnosis on TC‐genesis‐related large‐scale dynamics and thermodynamics revealed that the lower/higher TC numbers in the WNP/NA were primarily attributed to an anticyclonic/cyclonic anomaly linked to trans‐basin sea surface temperature anomalies in the tropics and extratropics. Additionally, weaker intraseasonal oscillation activity compared to previous El Niños also partially contributed to fewer TCs in the WNP.
Investigating the “Too Bright” Issue Pertaining to Non‐PBL Clouds Over the South Pacific Trade‐Wind Region in CMIP6 Global Climate Models
Authors: Li J.‐L. F. , Xu Kuan‐Man , Jiang Jonathan H. , Lee Wei‐Liang , Yu Jia‐Yuh , Chern Jiun‐dar , Cesana Gregory V. , Wu Longtao , Stephens Graeme
Published: November 2024

This paper examines the “too bright” issue pertaining to non‐planetary boundary layer (PBL) clouds over the South Pacific trade‐wind region and its potential link to the falling ice radiative effects (FIREs). We run sensitivity experiments with CESM2‐CAM6 (CESM2) global climate model with FIREs on (SON) and off (NOS). The model exhibits more in‐cloud liquid water content (CLWC) and droplet above the PBL in NOS, leading to larger shortwave (SW) reflectivity at the top of the atmosphere than in SON over the trade wind regions. CMIP6 models are divided into three subsets: separately calculates the radiative effects of cloud ice and falling ice (SON2), combined (SON1) and without falling ice (NOS). SON2 models exhibit improved CLWC and SW reflectivity similar to CESM2‐SON, while NOS and SON1 models are akin to CESM2‐NOS owing to weaker surface wind stress and warmer ocean surface, caused by the lack of FIREs over the convective zones.
New Late Cretaceous Paleomagnetic Results From the Eastern Qiangtang Terrane: Implications for the Postcollisional Extrusion and Convergence of the Southeastern Tibetan Plateau
Authors: Ma Jiahui , Yang Tianshui , Han Fei , Liang Jiacheng , Jiao Xianwei , Wang Suo , Bian Weiwei , Ma Yiming , Zhang Shihong , Wu Huaichun , Li Haiyan
Published: November 2024

To refine the postcollisional extrusion and convergence history of the southeastern Tibetan Plateau, we report a quality paleomagnetic data set from Upper Cretaceous redbeds of the eastern Qiangtang Terrane (QT), where is situated at the front edge of eastern Himalayan Syntaxis. The 32 site‐mean directions provide a mean pole at 75.4°N, 176.8°E (A95 = 2.4°) and a paleolatitude of 31.8 ± 2.4°N for the Mangkang area. Comparison with reliable Late Cretaceous paleomagnetic data from the eastern QT and East Asia indicates that the eastern QT experienced a southward extrusion of 940 ± 310 km after the Late Cretaceous. Comparing Late Cretaceous paleolatitudes estimated from the eastern QT and Lhasa terrane (LT) reveals a paleolatitude difference of 2,390 ± 620 km. Such a great latitudinal convergence can be attributed to the fact that some continental terranes originally located between the eastern LT and QT were laterally extruded after the Late Cretaceous.
Research progress on aero-optical effects of hypersonic optical window with film cooling
Authors: Yi Shihe , Ding Haolin , Luo Suyiming , Sun Xiaobin , Xia Zihao
Published: November 2024

In recent years, the demand for optical imaging and detection in hypersonic aircraft has been on the rise. The high-temperature and high-pressure compressed flow field near airborne optoelectronic devices creates significant interference with light transmission, known as hypersonic aero-optical effects. This effect has emerged as a key technological challenge, limiting hypersonic optical imaging and detection capabilities. This article focuses on introducing the thermal effects and optical transmission effects of hypersonic aero-optical effects, as along with corresponding suppression techniques. In addition, this article critically reviews and succinctly summarizes the advancements made in hypersonic aero-optical effects testing technology, while also delineating avenues for future research needs in this field. In conclusion, there is an urgent call for further exploration into the study of aero-optical effects under conditions characterized by high Mach, high enthalpy, and high Reynolds number in the future.
2D4, a humanized monoclonal antibody targeting CD132, is a promising treatment for systemic lupus erythematosus
Authors: Yin Huiqi , Li Liming , Feng Xiwei , Wang Zijun , Zheng Meiling , Zhao Junpeng , Fan Xinyu , Wu Wei , Gao Lingyu , Zhan Yijing , Zhao Ming , Lu Qianjin
Published: November 2024

Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients’ lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.
ADAMTS16 drives epithelial-mesenchymal transition and metastasis through a feedback loop upon TGF-β1 activation in lung adenocarcinoma
Authors: Xiao Lingyan , Li Qian , Chen Shuaijun , Huang Yongbiao , Ma Li , Wang Yuan , Chen Junjie , Zhang Jun , Liu Andong , Yuan Xianglin , Liu Yuanhui , Liu Bo
Published: November 2024

Lung adenocarcinoma (LUAD) is the major subtype of lung cancer. The poor prognosis of LUAD patients is attributed primarily to metastasis. ADAMTS16 is a crucial member of the ADAMTS family and is involved in tumor progression. However, its role and regulatory mechanism in LUAD remain unexplored. In this study, ADAMTS16 was identified as a crucial oncogene and survival predictor in LUAD via analyses of public datasets. Clinical specimens and tissue microarrays confirmed the differential expression and prognostic value of ADAMTS16 in LUAD patients. Transcriptome data and in vitro experiments demonstrated that ADAMTS16 was positively associated with epithelial-mesenchymal transition (EMT) and the migration abilities of LUAD cells. Knockdown of ADAMTS16 attenuated lung and pleural metastasis in an animal model. Mechanistically, the results of the enzyme-linked immunosorbent assay (ELISA) and western blot (WB) suggested that ADAMTS16 activated the TGF-β signaling pathway by facilitating the conversion of LAP-TGF-β1 to active TGF-β1. Co-Immunoprecipitation (co-IP) indicated an interaction between ADAMTS16 and LAP-TGF-β1. Inhibition of ADAMTS16 impaired EMT and aggressiveness of LUAD cells, while treatment with recombinant TGF-β1 reversed this inhibition. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays indicated that SOX4 acted as a transcriptional activator of ADAMTS16 and that TGF-β1 regulated the expression of ADAMTS16 by increasing the binding of SOX4 to the promoter of ADAMTS16. Suppressing the TGF-β signaling pathway inhibited ADAMTS16 expression, EMT, and lung metastasis, whereas overexpressing SOX4 reversed this inhibition. Therefore, ADAMTS16 forms a positive feedback loop with the TGF-β1/SOX4 axis to regulate EMT and metastasis, and disruption of this feedback loop inhibits tumor progression. These findings underscore the potential of ADAMTS16 as a prognostic biomarker and therapeutic target in LUAD and offer novel insight into the mechanism of EMT and metastasis.
TSG101 depletion dysregulates mitochondria and PML NBs, triggering MAD2-overexpressing interphase cell death (MOID) through AIFM1-PML-DAXX pathway
Authors: Xi Yao , Xu Rui , Chen Shengnan , Fang Jiezhu , Duan Xiang , Zhang Yidan , Zhong Guoli , He Zhifei , Guo Yan , Li Xinyu , Tao Wenzhi , Li Yang , Li Yan , Fang Lei , Niikura Yohei
Published: November 2024

Overexpression of mitotic arrest deficiency 2 (MAD2/MAD2L1), a pivotal component of the spindle assembly checkpoint (SAC), resulted in many types of cancer. Here we show that the depletion of tumor susceptibility gene 101 (TSG101), causes synthetic dosage lethality (SDL) in MAD2-overexpressing cells, and we term this cell death MAD2-overexpressing interphase cell death (MOID). The induction of MOID depends on PML and DAXX mediating mitochondrial AIFM1-release. MAD2, TSG101, and AIF-PML-DAXX axis regulate mitochondria, PML nuclear bodies (NBs), and autophagy with close inter-dependent protein stability in survival cells. Loss of C-terminal phosphorylation(s) of TSG101 and closed (C-)MAD2-overexpression contribute to induce MOID. In survival cells, both MAD2 and TSG101 localize at PML NBs in interphase, and TSG101 Y390 phosphorylation is required for localization of TSG101 to PML NBs. PML release from PML NBs through PML deSUMOylation contributes to induce MOID. The post-transcriptional/translational cell death machinery and the non-canonical transcriptional regulation are intricately linked to MOID, and ER-MAM, may serve as a crucial intersection for MOID signaling.
Therapeutic advances in the targeting of ROR1 in hematological cancers
Authors: Tigu Adrian-Bogdan , Munteanu Raluca , Moldovan Cristian , Rares Drula , Kegyes David , Tomai Radu , Moisoiu Vlad , Ghiaur Gabriel , Tomuleasa Ciprian , Einsele Hermann , Gulei Diana , Croce Carlo M.
Published: November 2024

Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies. The development of ROR1 targeted therapies is continuously growing leading to remarkable novel therapeutical approaches using mAbs, antibody-drug conjugates, several small molecules or CAR T cells which have shown encouraging preclinical results. In the hematological field, mAbs, small molecules, BiTEs or CAR T cell therapies displayed promising outcomes with the clinical trials data encouraging the use of anti-ROR1 therapies. This paper aims to offer a comprehensive analysis of the current landscape of ROR1-targeted therapies in hematological malignancies marking the innovative approaches with promising preclinical and clinical. Offering a better understanding of structural and functional aspects of ROR1 could lead to new perspectives in targeting a wide spectrum of malignancies.
DDX3 is critical for female fertility via translational control in oogenesis
Authors: Tsai Shang-Yu , Lin Chih-Hung , Jiang Yu-Ting , Huang Guo-Jen , Pi Haiwei , Hung Hsin-Yuan , Tarn Woan-Yuh , Lai Ming-Chih
Published: November 2024

DEAD-box RNA helicase 3 (DDX3) and its homologs play a vital role in translation initiation by unwinding secondary structures of selected mRNAs. The human DDX3 gene is located on the sex chromosomes, so there are DDX3X and DDX3Y. DDX3X is ubiquitously expressed in almost all tissues and critical for embryonic development, whereas DDX3Y is only expressed in the testis and essential for male fertility. Drosophila belle (bel) is the single ortholog of DDX3, and mutations in bel cause male and female infertility. Using Drosophila bel mutants and Ddx3x conditional knockout (cKO) mice, we confirmed the pivotal role of DDX3 in female fertility and ovarian development. Drosophila bel mutants exhibited female infertility and immature egg chambers. Consistently, oocyte-specific Ddx3x knockout in mice resulted in female infertility and impaired oogenesis. We further found that immature egg chambers in Drosophila bel mutants and impaired follicular development in oocyte-specific Ddx3x cKO mice were caused by excessive apoptosis. We also identified a set of DDX3 target genes involved in oocyte meiosis and maturation and demonstrated that DDX3 is involved in their translation in human cells. Our results suggest that DDX3 is critical for female fertility via translational control in oogenesis.
Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay
Authors: Batiuk Alina , Höpfler Markus , Almeida Ana C. , Teoh En-Jie Deryn , Vadas Oscar , Vartholomaiou Evangelia , Hegde Ramanujan S. , Lin Zhewang , Gasic Ivana
Published: November 2024

Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport, and power cell division. The concentration of αβ-tubulins is tightly controlled through a posttranscriptional mechanism involving selective and regulated degradation of tubulin-encoding mRNAs. Degradation is initiated by TTC5, which recognizes tubulin-synthesizing ribosomes and recruits downstream effectors to trigger mRNA deadenylation. Here, we investigate how cells regulate TTC5 activity. Biochemical and structural proteomic approaches reveal that under normal conditions, soluble αβ-tubulins bind to and sequester TTC5, preventing it from engaging nascent tubulins at translating ribosomes. We identify the flexible C-terminal tail of TTC5 as a molecular switch, toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss of sequestration by soluble αβ-tubulins constitutively activates TTC5, leading to diminished tubulin mRNA levels and compromised microtubule-dependent chromosome segregation during cell division. Our findings provide a paradigm for how cells regulate the activity of a specificity factor to adapt posttranscriptional regulation of gene expression to cellular needs.
Synchronous motion of the Easter mantle plume and the East Pacific Rise
Authors: O’Connor John M. , Regelous Marcel , Haase Karsten M. , Hemond Christophe , Koppers Anthony A. P. , Miggins Daniel P. , Heaton Daniel E.
Published: November 2024

The Easter mantle plume has produced one of the longest hotspot tracks in the Pacific Ocean. While previous studies have focused on the eastern side extending across the Nazca Plate, we use 40Ar/39Ar isotopic and geochemical data to investigate the less explored western side around the Easter Microplate. We propose a dynamic model in which a deeper (600 km-depth), less buoyant mantle exerts a westward force on the East Pacific Rise (EPR), while a more buoyant plume region drives Easter hotspot volcanism and a localised acceleration in seafloor spreading. Our findings suggest that the Easter hotspot is the more focused surface expression of the most buoyant region of a vast, deep-seated mantle plume extending from the Pacific Large Low Shear Velocity Province (LLSVP). This challenges the traditional view of hotspots as isolated phenomena and suggests they are part of broader LLSVP-related mantle structures. Our results imply a more intricate, large-scale relationship between hotspots, mantle plumes, spreading ridges, and mantle dynamics.
A self-eliminating allelic-drive reverses insecticide resistance in Drosophila leaving no transgene in the population
Authors: Auradkar Ankush , Corder Rodrigo M. , Marshall John M. , Bier Ethan
Published: November 2024

Insecticide resistance (IR) poses a significant global challenge to public health and welfare. Here, we develop a locally-acting unitary self-eliminating allelic-drive system, inserted into the Drosophila melanogaster yellow (y) locus. The drive cassette encodes both Cas9 and a single gRNA to bias inheritance of the favored wild-type (1014 L) allele over the IR (1014 F) variant of the voltage-gated sodium ion channel (vgsc) target locus. When enduring a fitness cost, this transiently-acting drive can increase the frequency of the wild-type allele to 100%, depending on its seeding ratio, before being eliminated from the population. However, in a fitness-neutral “hover” mode, the drive maintains a constant frequency in the population, completely converting IR alleles to wild-type, even at low initial seeding ratios.
Breaking the capacity bottleneck of lithium-oxygen batteries through reconceptualizing transport and nucleation kinetics
Authors: Zhang Zhuojun , Xiao Xu , Yan Aijing , Sun Kai , Yu Jianwen , Tan Peng
Published: November 2024

The practical capacity of lithium-oxygen batteries falls short of their ultra-high theoretical value. Unfortunately, the fundamental understanding and enhanced design remain lacking, as the issue is complicated by the coupling processes between Li2O2 nucleation, growth, and multi-species transport. Herein, we redefine the relationship between the microscale Li2O2 behaviors and the macroscopic electrochemical performance, emphasizing the importance of the inherent modulating ability of Li+ ions through a synergy of visualization techniques and cross-scale quantification. We find that Li2O2 particle distributed against the oxygen gradient signifies a compatibility match for the nucleation and transport kinetics, thus enabling the output of the electrode’s maximum capacity and providing a basis for evaluating operating protocols for future applications. In this case, a 150% capacity enhancement is further achieved through the development of a universalizing methodology. This work opens the door for the rules and control of energy conversion in metal-air batteries, greatly accelerating their path to commercialization.
Deep phenotypic profiling of neuroactive drugs in larval zebrafish
Authors: Gendelev Leo , Taylor Jack , Myers-Turnbull Douglas , Chen Steven , McCarroll Matthew N. , Arkin Michelle R. , Kokel David , Keiser Michael J.
Published: November 2024

Behavioral larval zebrafish screens leverage a high-throughput small molecule discovery format to find neuroactive molecules relevant to mammalian physiology. We screen a library of 650 central nervous system active compounds in high replicate to train deep metric learning models on zebrafish behavioral profiles. The machine learning initially exploited subtle artifacts in the phenotypic screen, necessitating a complete experimental re-run with rigorous physical well-wise randomization. These large matched phenotypic screening datasets (initial and well-randomized) provide a unique opportunity to quantify and understand shortcut learning in a full-scale, real-world drug discovery dataset. The final deep metric learning model substantially outperforms correlation distance–the canonical way of computing distances between profiles–and generalizes to an orthogonal dataset of diverse drug-like compounds. We validate predictions by prospective in vitro radio-ligand binding assays against human protein targets, achieving a hit rate of 58% despite crossing species and chemical scaffold boundaries. These neuroactive compounds exhibit diverse chemical scaffolds, demonstrating that zebrafish phenotypic screens combined with metric learning achieve robust scaffold hopping capabilities.
From electrons to phase diagrams with machine learning potentials using pyiron based automated workflows
Authors: Menon Sarath , Lysogorskiy Yury , Knoll Alexander L. M. , Leimeroth Niklas , Poul Marvin , Qamar Minaam , Janssen Jan , Mrovec Matous , Rohrer Jochen , Albe Karsten , Behler Jörg , Drautz Ralf , Neugebauer Jörg
Published: November 2024

We present a comprehensive and user-friendly framework built upon the integrated development environment (IDE), enabling researchers to perform the entire Machine Learning Potential (MLP) development cycle consisting of (i) creating systematic DFT databases, (ii) fitting the Density Functional Theory (DFT) data to empirical potentials or MLPs, and (iii) validating the potentials in a largely automatic approach. The power and performance of this framework are demonstrated for three conceptually very different classes of interatomic potentials: an empirical potential (embedded atom method - EAM), neural networks (high-dimensional neural network potentials - HDNNP) and expansions in basis sets (atomic cluster expansion - ACE). As an advanced example for validation and application, we show the computation of a binary composition-temperature phase diagram for Al-Li, a technologically important lightweight alloy system with applications in the aerospace industry.
Best practice advice for asthma exacerbation prevention and management in primary care: an international expert consensus
Authors: Skolnik Neil , Yawn Barbara P. , Correia de Sousa Jaime , Vázquez María Mar Martínez , Barnard Amanda , Wright Wendy L. , Ulrich Austin , Winders Tonya , Brunton Stephen
Published: November 2024

Primary care clinicians play a key role in asthma and asthma exacerbation management worldwide because most patients with asthma are treated in primary care settings. The high burden of asthma exacerbations persists and important practice gaps remain, despite continual advances in asthma care. Lack of primary care-specific guidance, uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, and reliance on systemic corticosteroids or short-acting beta2-agonist-only therapy are challenges clinicians face today with asthma care. Evidence supports the use of inhaled corticosteroids (ICS) + fast-acting bronchodilator treatments when used as needed in response to symptoms to improve asthma control and reduce rates of exacerbations, and the symptoms that occur leading up to an asthma exacerbation provide a window of opportunity to intervene with ICS. Incorporating patient perspectives and preferences when designing asthma regimens will help patients be more engaged in their therapy and may contribute to improved adherence and outcomes. This expert consensus contains 10 Best Practice Advice Points from a panel of primary care clinicians and a patient representative, formed in collaboration with the International Primary Care Respiratory Group (IPCRG), a clinically led charitable organization that works locally and globally in primary care to improve respiratory health. The panel met virtually and developed a series of best practice statements, which were drafted and subsequently voted on to obtain consensus. Primary care clinicians globally are encouraged to review and adapt these best practice advice points on preventing and managing asthma exacerbations to their local practice patterns to enhance asthma care within their practice.
Phase 1 clinical trial of Hantaan and Puumala virus DNA vaccines delivered by needle-free injection
Authors: Hooper Jay W. , Kwilas Steven A. , Josleyn Matthew , Norris Sarah , Hutter Jack N. , Hamer Melinda , Livezey Jeffrey , Paolino Kristopher , Twomey Patrick , Koren Michael , Keiser Paul , Moon James E. , Nwaeze Ugo , Koontz Jason , Ledesma-Feliciano Carmen , Landry Nathalie , Wellington Trevor
Published: November 2024

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic zoonoses found in Asia and Europe, respectively. We conducted a randomized Phase 1 clinical trial of individual HTNV and PUUV DNA vaccines targeting the envelope glycoproteins (GnGc), as well as a combined HTNV/PUUV DNA vaccine delivered at varying doses using the PharmaJet Stratis® needle-free injection system (NCT02776761). Cohort 1 and 2 vaccines consisted of 2 mg/vaccination of HTNV or PUUV plasmid, respectively. Cohort 3 vaccine consisted of 2 mg/vaccination of 1:1 mixture of HTNV and PUUV vaccines. Vaccinations were administered on Days 0, 28, 56, and 168. The vaccines were safe and well tolerated. Neutralizing antibody responses were elicited in 7/7 (100%) subjects who received the HTNV DNA (Cohort 1) and 6/6 (100%) subjects who received the PUUV DNA (Cohort 2) vaccines alone. The combination vaccine resulted in 4/9 (44%) seroconversion against both viruses. After the first two vaccinations, the seroconversion rates for the HTNV and PUUV vaccines were >80%.
Optimum solution of power flow problem based on search and rescue algorithm
Authors: Houssein Essam H. , Ismaeel Alaa A. K. , Said Mokhtar
Published: November 2024

In order to solve the optimal power flow (OPF) problem, a unique algorithm based on a search and rescue method is applied in this study. For the OPF problem under three objective functions, the SAR offers a straightforward and reliable solution. The three objective functions are used to minimize the fuel cost, power loss and voltage deviation as a single objective function. The OPF problem for benchmark test system, including the IEEE-14 bus, IEEE-30 bus, and IEEE-57 bus, are solved by the Search and Rescue algorithm (SAR) under specific objective functions that are determined by the operational and economic performance indices of the power system. To demonstrate the efficacy and possibilities of the SAR algorithm, SAR is contrasted with alternative optimization techniques such as harmony search algorithm, gradient method, adaptive genetic algorithm, biogeography-based optimization, Artificial bee colony, gravitational search algorithm, particle swarm optimization, Jaya algorithm, enhanced genetic algorithm, modified shuffle frog leaping algorithm, practical swarm optimizer, Moth flam optimizer, whale and moth flam optimizer, grey wolf optimizer, cheap optimization algorithm and differential evolution algorithm. The value of minimum power losses based on SAR technique is equal to 0.459733441487247 MW for IEEE-14 bus. The value of minimum total fuel cost based on SAR technique is equal to 8051.12225602148 $/h for IEEE-14 bus. The value of minimum voltage deviation based on SAR technique is equal to 0.0357680148269292 for IEEE-14 bus. The value of minimum power losses based on SAR technique is equal to 2.71286428848434 MW for IEEE-30 bus. The value of minimum total fuel cost based on SAR technique is equal to 798.197578585806 $/h for IEEE-30 bus. The value of minimum voltage deviation based on SAR technique is equal to 0.0978069572088536 for IEEE-30 bus. The value of minimum total fuel cost based on SAR technique is equal to 38017.7691758245 $/h for IEEE-57 bus. The acquired results for the OPF compared to all competitor algorithms in every case of fitness function demonstrate the superiority of the SAR method.