bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone on-a-chip: a 3D dendritic network in a screening platform for osteocyte-targeted drugs
Authors: Lipreri Maria Veronica , Di Pompo Gemma , Boanini Elisa , Graziani Gabriela , Sassoni Enrico , Baldini Nicola , Avnet Sofia 
Published: August 2023

Abstract
Age-related musculoskeletal disorders, including osteoporosis, are frequent and associated with long lasting morbidity, in turn significantly impacting on healthcare system sustainability. There is therefore a compelling need to develop reliable preclinical models of disease and drug screening to validate novel drugs possibly on a personalized basis, without the need of in vivo assay. In the context of bone tissue, although the osteocyte (Oc) network is a well-recognized therapeutic target, current in vitro preclinical models are unable to mimic its physiologically relevant and highly complex structure. To this purpose, several features are needed, including an osteomimetic extracellular matrix, dynamic perfusion, and mechanical cues (e.g. shear stress) combined with a three-dimensional (3D) culture of Oc. Here we describe, for the first time, a high throughput microfluidic platform based on 96-miniaturized chips for large-scale preclinical evaluation to predict drug efficacy. We bioengineered a commercial microfluidic device that allows real-time visualization and equipped with multi-chips by the development and injection of a highly stiff bone-like 3D matrix, made of a blend of collagen-enriched natural hydrogels loaded with hydroxyapatite nanocrystals. The microchannel, filled with the ostemimetic matrix and Oc, is subjected to passive perfusion and shear stress. We used scanning electron microscopy for preliminary material characterization. Confocal microscopy and fluorescent microbeads were used after material injection into the microchannels to detect volume changes and the distribution of cell-sized objects within the hydrogel. The formation of a 3D dendritic network of Oc was monitored by measuring cell viability, evaluating phenotyping markers (connexin43, integrin alpha V/CD51, sclerostin), quantification of dendrites, and responsiveness to an anabolic drug. The platform is expected to accelerate the development of new drug aimed at modulating the survival and function of osteocytes.
Hydrothermal treatment of sorghum (Sorghum bicolor (L.) Moench) stalks for enhanced microfibrillated cellulose production
Authors: Roziafanto Achmad Nandang , Lazuardi Dimas Reza , Ghozali Muhammad , Sofyan Nofrijon , Chalid Mochamad 
Published: August 2023

Abstract
Microfibrillated cellulose (MFC) derived from natural fibers has gained significant interest as an environmentally friendly material for economic and ecological reasons. Sorghum (Sorghum bicolor (L.) Moench), a widely cultivated crop that generates waste during bioethanol production, holds the potential for producing MFC and can be used for enhancing polymer’s performance, particularly in terms of crystallinity. The hydrothermal treatments aimed to unbundle lignocellulose networks into MFC with reduced amorphous content and enhanced crystallinity The hydrothermal treatments, necessitating specialized apparatuses and exhibiting limited scalability, can be effectively replaced by the domestic pressure cooker, an alternative intriguing vessel for the simple, cheap, and economical hydrothermal reactor. Hydrothermal treatments using pressurized steaming methods were performed at different durations (5, 25, and 60 min), in which the fibers were positioned above the water level to enable targeted interaction with the steam. Characterization of the treated fibers namely chemical composition, morphology, crystallinity index, and thermal stability were analyzed using FTIR spectroscopy, FE-SEM, XRD, and TGA. The results demonstrate the removal of binding materials, such as amorphous hemicellulose and lignin, from the sorghum fibers, leading to fiber defibrillation and producing MFC size range from 12.2 to 19.4 μm. Hydrothermal treated fiber started to decompose at Tinitial around 275 °C–282 °C higher than fiber untreated Tinitial = 229 °C. The 5 min treatment has generated the highest crystallinity index (52%) and the highest maximum peak temperature (365.26 °C). Additionally, the treatments have increased the fibers’ crystallinity index and thermal stability, highlighting the potential use of sorghum fiber as a reinforcement candidate in natural fiber polymer composites.
Study on UV aging characteristics of low-grade asphalt in the desert climate
Authors: Song Liang , Hou Lulu , Tu Pengcheng , Fan Peng , Gao Jie 
Published: August 2023

Abstract
The Taklamakan Desert in China’s Xinjiang region faces severe heat conditions that cause rutting in asphalt pavements. In order to combat this issue, local construction management has been advocating for the utilization of low-grade asphalt with penetration levels between 20 and 50, to enhance the pavement’s resistance to rutting. However, there is limited research on the durability of low-grade asphalt under intense UV irradiation in the region. To this end, a multiscale investigation was conducted, examining three different types of asphalt (30#, 50#, and 70#), under various conditions such as virgin, UV aging, and Pressure Aging Vessel aging. Analytical techniques such as Atomic Force Microscope, Gel Permeation Chromatography, Fourier Transform Infrared Spectroscopy, Dynamic Shear Rheology, and Bending Beam Rheometer were employed. The results revealed that the surface roughness of the three types of asphalt increased by 15.50% (30#), 5.99% (50#), and 2.70% (70#) after UV aging, compared to the virgin samples. Furthermore, the adhesion properties of lower-grade asphalt were less affected by UV aging. Weight-average molecular weight of the three types of asphalt increased significantly after UV aging, with a 26.96% increase in 30#, 51.92% increase in 50#, and 43.76% increase in 70# compared to the samples prior to UV aging. The 30# asphalt with higher large molecule content exhibited slower UV aging. The 30# asphalt also exhibited the smallest increase of C=O and S=O after UV aging among the three types of asphalt. The study also found that UV aging had a lesser effect on the high- and low-temperature performance of asphalt, compared to PAV aging. Overall, the effects of UV irradiation on various properties of 30# asphalt were less pronounced than those of 50# and 70# asphalt. These findings offer valuable insights into aging resistance in the Taklamakan Desert, benefiting road contractors and the academic community.
Cancer drug response prediction with surrogate modeling-based graph neural architecture search
Authors: Oloulade Babatounde Moctard , Gao Jianliang , Chen Jiamin , Al-Sabri Raeed , Wu Zhenpeng 
Published: August 2023

Abstract

Motivation
Understanding drug–response differences in cancer treatments is one of the most challenging aspects of personalized medicine. Recently, graph neural networks (GNNs) have become state-of-the-art methods in many graph representation learning scenarios in bioinformatics. However, building an optimal handcrafted GNN model for a particular drug sensitivity dataset requires manual design and fine-tuning of the hyperparameters for the GNN model, which is time-consuming and requires expert knowledge.

Results
In this work, we propose AutoCDRP, a novel framework for automated cancer drug–response predictor using GNNs. Our approach leverages surrogate modeling to efficiently search for the most effective GNN architecture. AutoCDRP uses a surrogate model to predict the performance of GNN architectures sampled from a search space, allowing it to select the optimal architecture based on evaluation performance. Hence, AutoCDRP can efficiently identify the optimal GNN architecture by exploring the performance of all GNN architectures in the search space. Through comprehensive experiments on two benchmark datasets, we demonstrate that the GNN architecture generated by AutoCDRP surpasses state-of-the-art designs. Notably, the optimal GNN architecture identified by AutoCDRP consistently outperforms the best baseline architecture from the first epoch, providing further evidence of its effectiveness.

Availability and implementation
https://github.com/BeObm/AutoCDRP.
SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline
Authors: Luo Yanyun , Yamada Makiko , N’Tumba-Byn Thierry , Asif Hana , Gao Meng , Hu Yang , Marangoni Pauline , Liu Ying , Evans Todd , Rafii Shahin , Klein Ophir D , Voss Henning U , Hadjantonakis Anna-Katerina , Elemento Olivier , Martin Laura A , Seandel Marco 
Published: August 2023

AbstractNiche-derived growth factors support self-renewal of mouse spermatogonial stem and progenitor cells through ERK MAPK signaling and other pathways. At the same time, dysregulated growth factor-dependent signaling has been associated with loss of stem cell activity and aberrant differentiation. We hypothesized that growth factor signaling through the ERK MAPK pathway in spermatogonial stem cells is tightly regulated within a narrow range through distinct intracellular negative feedback regulators. Evaluation of candidate extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK)-responsive genes known to dampen downstream signaling revealed robust induction of specific negative feedback regulators, including Spry4, in cultured mouse spermatogonial stem cells in response to glial cell line-derived neurotrophic factor or fibroblast growth factor 2. Undifferentiated spermatogonia in vivo exhibited high levels of Spry4 mRNA. Quantitative single-cell analysis of ERK MAPK signaling in spermatogonial stem cell cultures revealed both dynamic signaling patterns in response to growth factors and disruption of such effects when Spry4 was ablated, due to dysregulation of ERK MAPK downstream of RAS. Whereas negative feedback regulator expression decreased during differentiation, loss of Spry4 shifted cell fate toward early differentiation with concomitant loss of stem cell activity. Finally, a mouse Spry4 reporter line revealed that the adult spermatogonial stem cell population in vivo is demarcated by strong Spry4 promoter activity. Collectively, our data suggest that negative feedback-dependent regulation of ERK MAPK is critical for preservation of spermatogonial stem cell fate within the mammalian testis.
Mouse primary follicles experience slow growth rates after activation and progressive increases that influence the duration of the primary follicle phase
Authors: Richard Sharon , Anderson Nicholas J , Zhou Yiran , Pankhurst Michael W 
Published: August 2023

Abstract
There are conflicting estimates of the duration of mouse primary follicle development. An accurate determination is needed for studies examining preantral follicle survival and mathematical modeling of folliculogenesis. Primary follicle granulosa cell proliferation rates are low and variable, which may explain the variation in duration estimates. In the present study, female C57Bl6/J mice were exposed to bromodeoxyuridine for 48 hours, to label the proliferating granulosa cells in a large proportion of primary follicles. The bromodeoxyuridine-containing water was then withdrawn and replaced with drug-free water and the mice were euthanized at 0, 1, 3, 6, 10, or 13 days post-bromodeoxyuridine withdrawal. Granulosa cells were bromodeoxyuridine labeled in 48% of primary follicles at day 0, but this decreased to 5% over the 13-day period, as the labeled primary follicles progressed to the secondary follicle stage. Curve-fitting estimated that the last of the bromodeoxyuridine-labeled primary follicles would progress to the secondary stage by 13.7 days. Mathematical models that assumed constant rates of primary follicle proliferation were fitted to the data, but the observed pattern of bromodeoxyuridine-labeled primary follicle disappearance could not be replicated. The level of immunoreactivity for bromodeoxyuridine and proliferating-cell nuclear antigen in primary follicles revealed follicles with no granulosa cell proliferation during the 48-h bromodeoxyuridine-exposure period had resumed proliferation 1 or 3 days later. Therefore, primary follicle granulosa cells proliferate after follicle activation, but proliferation rates gradually increase as the follicle develops. Prior estimates of primary follicle duration are inaccurate due to the assumption that follicles develop at a constant rate.
Artificial intelligence for the recognition of key anatomical structures in laparoscopic colorectal surgery
Authors: Kitaguchi Daichi , Harai Yuriko , Kosugi Norihito , Hayashi Kazuyuki , Kojima Shigehiro , Ishikawa Yuto , Yamada Atsushi , Hasegawa Hiro , Takeshita Nobuyoshi , Ito Masaaki 
Published: August 2023

Lay Summary
To prevent intraoperative organ injury, surgeons strive to identify anatomical structures as early and accurately as possible during surgery. The objective of this prospective observational study was to develop artificial intelligence (AI)-based real-time automatic organ recognition models in laparoscopic surgery and to compare its performance with that of surgeons. The time taken to recognize target anatomy between AI and both expert and novice surgeons was compared. The AI models demonstrated faster recognition of target anatomy than surgeons, especially novice surgeons. These findings suggest that AI has the potential to compensate for the skill and experience gap between surgeons.
Widespread priming of transcriptional regulatory elements by incipient accessibility or RNA polymerase II pause in early embryos of the sea urchin Strongylocentrotus purpuratus
Authors: Arenas-Mena Cesar , Akin Serhat 
Published: August 2023

Abstract
Transcriptional regulatory elements (TREs) are the primary nodes that control developmental gene regulatory networks. In embryo stages, larvae, and adult differentiated red spherule cells of the sea urchin Strongylocentrotus purpuratus, transcriptionally engaged TREs are detected by Precision Run-On Sequencing (PRO-seq), which maps genome-wide at base pair resolution the location of paused or elongating RNA polymerase II (Pol II). In parallel, TRE accessibility is estimated by the Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq). Our analysis identifies surprisingly early and widespread TRE accessibility in 4-cell cleavage embryos that is not necessarily followed by concurrent or subsequent transcription. TRE transcriptional differences identified by PRO-seq provide more contrast among embryonic stages than ATAC-seq accessibility differences, in agreement with the apparent excess of accessible but inactive TREs during embryogenesis. Global TRE accessibility reaches a maximum around the 20-hour late blastula stage, which coincides with the consolidation of major embryo regionalizations and peak histone variant H2A.Z expression. A transcriptional potency model based on labile nucleosome TRE occupancy driven by DNA sequences and the prevalence of histone variants is proposed in order to explain the basal accessibility of transcriptionally inactive TREs during embryogenesis. However, our results would not reconcile well with labile nucleosome models based on simple A/T sequence enrichment. In addition, a large number of distal TREs become transcriptionally disengaged during developmental progression, in support of an early Pol II paused model for developmental gene regulation that eventually resolves in transcriptional activation or silencing. Thus, developmental potency in early embryos may be facilitated by incipient accessibility and transcriptional pause at TREs.
An endolysin gene fromCandidatusLiberibacter asiaticus confers dual resistance to huanglongbing and citrus canker
Authors: Xu Lanzhen , Mo Kaiqing , Ran Danlu , Ma Juanjuan , Zhang Lehuan , Sun Yijia , Long Qin , Jiang Guojin , Zhao Xiaochun , Zou Xiuping 
Published: August 2023

AbstractThe most damaging citrus diseases are Huanglongbing (HLB) and citrus canker, which are caused by Candidatus Liberibacter asiaticus (CaLas) and Xanthomonas citri pv. citri (Xcc), respectively. Endolysins from bacteriophages are a possible option for disease resistance in plant breeding. Here, we report improvement of citrus resistance to HLB and citrus canker using the LasLYS1 and LasLYS2 endolysins from CaLas. LasLYS2 demonstrated bactericidal efficacy against several Rhizobiaceae bacteria and Xcc, according to inhibition zone analyses. The two genes, driven by a strong promoter from Cauliflower mosaic virus, 35S, were integrated into Carrizo citrange via Agrobacterium-mediated transformation. More than 2 years of greenhouse testing indicated that LasLYS2 provided substantial and long-lasting resistance to HLB, allowing transgenic plants to retain low CaLas titers and no obvious symptoms while also clearing CaLas from infected plants in the long term. LasLYS2 transgenic plants with improved HLB resistance also showed resistance to Xcc, indicating that LasLYS2 had dual resistance to HLB and citrus canker. A microbiome study of transgenic plants revealed that the endolysins repressed Xanthomonadaceae and Rhizobiaceae populations in roots while increasing Burkholderiaceae and Rhodanobacteraceae populations, which might boost the citrus defense response, according to transcriptome analysis. We also found that Lyz domain 2 is the key bactericidal motif of LasLYS1 and LasLYS2. Four endolysins with potential resistance to HLB and citrus canker were found based on the structures of LasLYS1 and LasLYS2. Overall, the work shed light on the mechanisms of resistance of CaLas-derived endolysins, providing insights for designing endolysins to develop broad-spectrum disease resistance in citrus.
Grapevine plantlets respond to different monochromatic lights by tuning photosynthesis and carbon allocation
Authors: Liu Menglong , Zhao Yan , Fan Peige , Kong Junhua , Wang Yongjian , Xu Xiaobo , Xu Meilong , Wang Lijun , Li Shaohua , Liang Zhenchang , Duan Wei , Dai Zhanwu 
Published: August 2023

Abstract
The quality of planting materials is the foundation for productivity, longevity, and berry quality of perennial grapevines with a long lifespan. Manipulating the nursery light spectrum may speed up the production of healthy and high-quality planting vines but the underlying mechanisms remain elusive. Herein, the effects of different monochromatic lights (green, blue, and red) on grapevine growth, leaf photosynthesis, whole-plant carbon allocation, and transcriptome reprograming were investigated with white light as control. Results showed that blue and red lights were favorable for plantlet growth in comparison with white light. Blue light repressed excessive growth, significantly increased the maximum net photosynthetic rate (Pn) of leaves by 39.58% and leaf specific weight by 38.29%. Red light increased the dry weight of the stem by 53.60%, the starch content of the leaf by 53.63%, and the sucrose content of the stem by 230%. Green light reduced all photosynthetic indexes of the grape plantlet. Photosynthetic photon flux density (PPFD)/Ci–Pn curves indicated that blue light affected photosynthetic rate depending on the light intensity and CO2 concentration. RNA-seq analysis of different organs (leaf, stem, and root) revealed a systematic transcriptome remodeling and VvCOP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1), VvHY5 (ELONGATED HYPOCOTYL5), VvHYH (HY5 HOMOLOG), VvELIP (early light-induced protein) and VvPIF3 (PHYTOCHROME INTERACTING FACTOR 3) may play important roles in this shoot-to-root signaling. Furthermore, the correlation network between differential expression genes and physiological traits indicated that VvpsbS (photosystem II subunit S), Vvpsb28 (photosystem II subunit 28), VvHYH, VvSUS4 (sucrose synthase 4), and VvALDA (fructose-bisphosphate aldolase) were pertinent candidate genes in responses to different light qualities. Our results provide a foundation for optimizing the light recipe of grape plantlets and strengthen the understanding of light signaling and carbon metabolism under different monochromatic lights.
Response of the meso- and macro-zooplankton community to long-term environmental changes in the southern North Sea
Authors: Marques R , Otto S A , Di Pane J , Boersma M , Meunier C L , Wiltshire K H , Möllmann C , Renz J 
Published: August 2023

Abstract
The North Sea (NS) is changing rapidly. Temporal variations in fishing intensity and eutrophic conditions, along with the ongoing impact of climate change, act in synergy resulting in modifications in marine communities. Although zooplankton has been extensively investigated, studies often ignore the large-sized meso- and macro-zooplankton (&gt;500 µm), including holoplankton and meroplankton taxa. Here, we examined changes in abundances and community structure of these organisms between 1975 and 2018, using univariate and multivariate analysis, at different taxonomic levels. Abrupt changes in the abundances of (sub)communities occurred during different time periods and resulted in a significant restructuration of the entire community in 2006. These changes were consistent with the regime shifts reported in the NS and were a consequence of the environmental pressures on the whole community or on specific subcommunities. In the long term, the community shifted from higher abundances of hydrozoans and holoplankton taxa to an increasing abundance of decapods. Furthermore, we reveal the environmental variables that most explain the variability in the community dynamics, highlighting the importance of temperature and top-down processes. Our study underlines the relevance of investigations at different taxonomic levels, which elucidates how distinct responses to environmental changes ultimately shape the entire community structure.