bluuebunny/crossref_metadata_2025 huggingface dataset:
Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging
Authors: Diez Ibai , Ortiz-Terán Laura , Ng Thomas S. C. , Albers Mark W. , Marshall Gad , Orwig William , Kim Chan-mi , Bueichekú Elisenda , Montal Victor , Olofsson Jonas , Vannini Patrizia , El Fahkri Georges , Sperling Reisa , Johnson Keith , Jacobs Heidi I. L. , Sepulcre Jorge
Published: June 2024

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.
High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1
Authors: Cui Zhanding , Liu Jinlong , Xie Chong , Wang Tao , Sun Pu , Wang Jinlong , Li Jiaoyang , Li Guoxiu , Qiu Jicheng , Zhang Ying , Li Dengliang , Sun Ying , Yin Juanbin , Li Kun , Zhao Zhixun , Yuan Hong , Bai Xingwen , Ma Xueqing , Li Pinghua , Fu Yuanfang , Bao Huifang , Li Dong , Zhang Qiang , Liu Zaixin , Cao Yimei , Zhang Jing , Lu Zengjun
Published: June 2024

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.
Current-induced domain wall motion in a van der Waals ferromagnet Fe3GeTe2
Authors: Zhang Wenjie , Ma Tianping , Hazra Binoy Krishna , Meyerheim Holger , Rigvedi Prajwal , Yin Zihan , Srivastava Abhay Kant , Wang Zhong , Gu Ke , Zhou Shiming , Wang Shouguo , Yang See-Hun , Guan Yicheng , Parkin Stuart S. P.
Published: June 2024

The manipulation of spin textures by spin currents is of fundamental and technological interest. A particularly interesting system is the 2D van der Waals ferromagnet Fe3GeTe2, in which Néel-type skyrmions have recently been observed. The origin of these chiral spin textures is of considerable interest. Recently, it was proposed that these derive from defects in the structure that lower the symmetry and allow for a bulk vector Dzyaloshinsky-Moriya interaction. Here, we demonstrate current-induced domain wall motion in Fe3GeTe2 flakes, in which the maximum domain wall velocity is an order of magnitude higher than those reported in previous studies. In heterostructures with Pt or W layers on top of the Fe3GeTe2 flakes, domain walls can be moved via a combination of spin transfer and spin-orbit torques. The competition between these torques leads to a change in the direction of domain wall motion with increasing magnitude of the injected current.
The climate benefits from cement carbonation are being overestimated
Authors: Van Roijen Elisabeth , Sethares Kati , Kendall Alissa , Miller Sabbie A.
Published: June 2024

Rapid decarbonization of the cement industry is critical to meeting climate goals. Oversimplification of direct air capture benefits from hydrated cement carbonation has skewed the ability to derive decarbonization solutions. Here, we present both global cement carbonation magnitude and its dynamic effect on cumulative radiative forcing. From 1930–2015, models suggest approximately 13.8 billion metric tons (Gt) of CO2 was re-absorbed globally. However, we show that the slow rate of carbonation leads to a climate effect that is approximately 60% smaller than these apparent benefits. Further, we show that on a per kilogram (kg) basis, demolition emissions from crushing concrete at end-of-life could roughly equal the magnitude of carbon-uptake during the demolition phase. We investigate the sensitivity of common decarbonization strategies, such as utilizing supplementary cementitious materials, on the carbonation process and highlight the importance of the timing of emissions release and uptake on influencing cumulative radiative forcing. Given the urgency of determining effective pathways for decarbonizing cement, this work provides a reference for overcoming some flawed interpretations of the benefits of carbonation.
Kagomerization of transition metal monolayers induced by two-dimensional hexagonal boron nitride
Authors: Zhou Hangyu , dos Santos Dias Manuel , Zhang Youguang , Zhao Weisheng , Lounis Samir
Published: June 2024

The kagome lattice is an exciting solid state physics platform for the emergence of nontrivial quantum states driven by electronic correlations: topological effects, unconventional superconductivity, charge and spin density waves, and unusual magnetic states such as quantum spin liquids. While kagome lattices have been realized in complex multi-atomic bulk compounds, here we demonstrate from first-principles a process that we dub kagomerization, in which we fabricate a two-dimensional kagome lattice in monolayers of transition metals utilizing an hexagonal boron nitride (h-BN) overlayer. Surprisingly, h-BN induces a large rearrangement of the transition metal atoms supported on a fcc(111) heavy-metal surface. This reconstruction is found to be rather generic for this type of heterostructures and has a profound impact on the underlying magnetic properties, ultimately stabilizing various topological magnetic solitons such as skyrmions and bimerons. Our findings call for a reconsideration of h-BN as merely a passive capping layer, showing its potential for not only reconstructing the atomic structure of the underlying material, e.g. through the kagomerization of magnetic films, but also enabling electronic and magnetic phases that are highly sought for the next generation of device technologies.
Cis-regulatory evolution of the recently expanded Ly49 gene family
Authors: Fan Changxu , Xing Xiaoyun , Murphy Samuel J. H. , Poursine-Laurent Jennifer , Schmidt Heather , Parikh Bijal A. , Yoon Jeesang , Choudhary Mayank N. K. , Saligrama Naresha , Piersma Sytse J. , Yokoyama Wayne M. , Wang Ting
Published: June 2024

Comparative genomics has revealed the rapid expansion of multiple gene families involved in immunity. Members within each gene family often evolved distinct roles in immunity. However, less is known about the evolution of their epigenome and cis-regulation. Here we systematically profile the epigenome of the recently expanded murine Ly49 gene family that mainly encode either inhibitory or activating surface receptors on natural killer cells. We identify a set of cis-regulatory elements (CREs) for activating Ly49 genes. In addition, we show that in mice, inhibitory and activating Ly49 genes are regulated by two separate sets of proximal CREs, likely resulting from lineage-specific losses of CRE activity. Furthermore, we find that some Ly49 genes are cross-regulated by the CREs of other Ly49 genes, suggesting that the Ly49 family has begun to evolve a concerted cis-regulatory mechanism. Collectively, we demonstrate the different modes of cis-regulatory evolution for a rapidly expanding gene family.
Terahertz photon to dc current conversion via magnetic excitations of multiferroics
Authors: Ogino Makiko , Okamura Yoshihiro , Fujiwara Kosuke , Morimoto Takahiro , Nagaosa Naoto , Kaneko Yoshio , Tokura Yoshinori , Takahashi Youtarou
Published: June 2024

Direct conversion from terahertz photon to charge current is a key phenomenon for terahertz photonics. Quantum geometrical description of optical processes in crystalline solids predicts existence of field-unbiased dc photocurrent arising from terahertz-light generation of magnetic excitations in multiferroics, potentially leading to fast and energy-efficient terahertz devices. Here, we demonstrate the dc charge current generation from terahertz magnetic excitations in multiferroic perovskite manganites with spin-driven ferroelectricity, while keeping an insulating state with no free carrier. It is also revealed that electromagnon, which ranges sub-terahertz to 2 THz, as well as antiferromagnetic resonance shows the giant conversion efficiency. Polar asymmetry induced by the cycloidal spin order gives rise to this terahertz-photon-induced dc photocurrent, and no external magnetic and electric bias field are required for this conversion process. The observed phenomena are beyond the conventional photovoltaics in semi-classical regime and demonstrate the essential role of quantum geometrical aspect in low-energy optical processes. Our finding establishes a paradigm of terahertz photovoltaic phenomena, paving a way for terahertz photonic devices and energy harvesting.
Global expansion of tropical cyclone precipitation footprint
Authors: Qin Lianjie , Zhu Laiyin , Liu Baoyin , Li Zixuan , Tian Yugang , Mitchell Gordon , Shen Shifei , Xu Wei , Chen Jianguo
Published: June 2024

Precipitation from tropical cyclones (TCs) can cause massive damage from inland floods and is becoming more intense under a warming climate. However, knowledge gaps still exist in changes of spatial patterns in heavy TC precipitation. Here we define a metric, DIST30, as the mean radial distance from centers of clustered heavy rainfall cells (> 30 mm/3 h) to TC center, representing the footprint of heavy TC precipitation. There is significant global increase in DIST30 at a rate of 0.34 km/year. Increases of DIST30 cover 59.87% of total TC impact areas, with growth especially strong in the Western North Pacific, Northern Atlantic, and Southern Pacific. The XGBoost machine learning model showed that monthly DIST30 variability is majorly controlled by TC maximum wind speed, location, sea surface temperature, vertical wind shear, and total water column vapor. TC poleward migration in the Northern Hemisphere contributes substantially to the DIST30 upward trend globally.
A single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)
Authors: Wang Cankun , Acosta Diana , McNutt Megan , Bian Jiang , Ma Anjun , Fu Hongjun , Ma Qin
Published: June 2024

Alzheimer’s Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce a single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD). It offers a broader spectrum of AD-related datasets, an optimized analytical pipeline, and improved usability. The database encompasses 1,053 samples (277 integrated datasets) from 67 AD-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets from 18 human and mouse brain studies. Each dataset is annotated with details such as species, gender, brain region, disease/control status, age, and AD Braak stages. ssREAD also provides an analysis suite for cell clustering, identification of differentially expressed and spatially variable genes, cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis. ssREAD is freely available at https://bmblx.bmi.osumc.edu/ssread/.
m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation
Authors: Klein Pierre , Petrić Howe Marija , Harley Jasmine , Crook Harry , Esteban Serna Sofia , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Chakrabarti Anob M. , Luisier Raphaëlle , Patani Rickie , Ramos Andres
Published: June 2024

Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.
Oxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality
Authors: Mohan Mahendra K. , Thorat Ketan , Puthiyapurayil Theja Parassini , Sunnapu Omprakash , Chandrashekharappa Sandeep , Ravula Venkatesh , Khader Rajamohammed , Sankaranarayanan Aravind , Muhammad Hadi , Vemula Praveen Kumar
Published: June 2024

Farmers from South Asian countries spray insecticides without protective gear, which leads to insecticide exposure through dermal and nasal routes. Acetylcholinesterase plays a crucial role in controlling neuromuscular function. Organophosphate and carbamate insecticides inhibit acetylcholinesterase, which leads to severe neuronal/cognitive dysfunction, breathing disorders, loss of endurance, and death. To address this issue, an Oxime-fabric is developed by covalently attaching silyl-pralidoxime to the cellulose of the fabric. The Oxime-fabric, when stitched as a bodysuit and facemask, efficiently deactivates insecticides (organophosphates and carbamates) upon contact, preventing exposure. The Oxime-fabric prevents insecticide-induced neuronal damage, neuro-muscular dysfunction, and loss of endurance. Furthermore, we observe a 100% survival rate in rats when repeatedly exposed to organophosphate-insecticide through the Oxime-fabric, while no survival is seen when organophosphate-insecticide applied directly or through normal fabric. The Oxime-fabric is washable and reusable for at least 50 cycles, providing an affordable solution to prevent insecticide-induced toxicity and lethality among farmers.
Machine learning-guided realization of full-color high-quantum-yield carbon quantum dots
Authors: Guo Huazhang , Lu Yuhao , Lei Zhendong , Bao Hong , Zhang Mingwan , Wang Zeming , Guan Cuntai , Tang Bijun , Liu Zheng , Wang Liang
Published: June 2024

Carbon quantum dots (CQDs) have versatile applications in luminescence, whereas identifying optimal synthesis conditions has been challenging due to numerous synthesis parameters and multiple desired outcomes, creating an enormous search space. In this study, we present a novel multi-objective optimization strategy utilizing a machine learning (ML) algorithm to intelligently guide the hydrothermal synthesis of CQDs. Our closed-loop approach learns from limited and sparse data, greatly reducing the research cycle and surpassing traditional trial-and-error methods. Moreover, it also reveals the intricate links between synthesis parameters and target properties and unifies the objective function to optimize multiple desired properties like full-color photoluminescence (PL) wavelength and high PL quantum yields (PLQY). With only 63 experiments, we achieve the synthesis of full-color fluorescent CQDs with high PLQY exceeding 60% across all colors. Our study represents a significant advancement in ML-guided CQDs synthesis, setting the stage for developing new materials with multiple desired properties.
Pre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development
Authors: Darbellay Fabrice , Ramisch Anna , Lopez-Delisle Lucille , Kosicki Michael , Rauseo Antonella , Jouini Zahra , Visel Axel , Andrey Guillaume
Published: June 2024

Chondrocyte differentiation controls skeleton development and stature. Here we provide a comprehensive map of chondrocyte-specific enhancers and show that they provide a mechanistic framework through which non-coding genetic variants can influence skeletal development and human stature. Working with fetal chondrocytes isolated from mice bearing a Col2a1 fluorescent regulatory sensor, we identify 780 genes and 2'704 putative enhancers specifically active in chondrocytes using a combination of RNA-seq, ATAC-seq and H3K27ac ChIP-seq. Most of these enhancers (74%) show pan-chondrogenic activity, with smaller populations being restricted to limb (18%) or trunk (8%) chondrocytes only. Notably, genetic variations overlapping these enhancers better explain height differences than those overlapping non-chondrogenic enhancers. Finally, targeted deletions of identified enhancers at the Fgfr3, Col2a1, Hhip and, Nkx3-2 loci confirm their role in regulating cognate genes. This enhancer map provides a framework for understanding how genes and non-coding variations influence bone development and diseases.
Inhibition and transport mechanisms of the ABC transporter hMRP5
Authors: Huang Ying , Xue Chenyang , Bu Ruiqian , Wu Cang , Li Jiachen , Zhang Jinqiu , Chen Jinyu , Shi Zhaoying , Chen Yonglong , Wang Yong , Liu Zhongmin
Published: June 2024

Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters.
KSHV infection of B cells primes protective T cell responses in humanized mice
Authors: Caduff Nicole , Rieble Lisa , Böni Michelle , McHugh Donal , Roshan Romin , Miley Wendell , Labo Nazzarena , Barman Sumanta , Trivett Matthew , Bosma Douwe M. T. , Rühl Julia , Goebels Norbert , Whitby Denise , Münz Christian
Published: June 2024

Kaposi sarcoma associated herpesvirus (KSHV) is associated with around 1% of all human tumors, including the B cell malignancy primary effusion lymphoma (PEL), in which co-infection with the Epstein Barr virus (EBV) can almost always be found in malignant cells. Here, we demonstrate that KSHV/EBV co-infection of mice with reconstituted human immune systems (humanized mice) leads to IgM responses against both latent and lytic KSHV antigens, and expansion of central and effector memory CD4+ and CD8+ T cells. Among these, KSHV/EBV dual-infection allows for the priming of CD8+ T cells that are specific for the lytic KSHV antigen K6 and able to kill KSHV/EBV infected B cells. This suggests that K6 may represent a vaccine antigen for the control of KSHV and its associated pathologies in high seroprevalence regions, such as Sub-Saharan Africa.
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
Authors: Johnson Scott M. , Bao Hanmei , McMahon Cailin E. , Chen Yongbin , Burr Stephanie D. , Anderson Aaron M. , Madeyski-Bengtson Katja , Lindén Daniel , Han Xianlin , Liu Jun
Published: June 2024

The I148M variant of PNPLA3 is closely associated with hepatic steatosis. Recent evidence indicates that the I148M mutant functions as an inhibitor of PNPLA2/ATGL-mediated lipolysis, leaving the role of wild-type PNPLA3 undefined. Despite showing a triglyceride hydrolase activity in vitro, PNPLA3 has yet to be established as a lipase in vivo. Here, we show that PNPLA3 preferentially hydrolyzes polyunsaturated triglycerides, mobilizing polyunsaturated fatty acids for phospholipid desaturation and enhancing hepatic secretion of triglyceride-rich lipoproteins. Under lipogenic conditions, mice with liver-specific knockout or acute knockdown of PNPLA3 exhibit aggravated liver steatosis and reduced plasma VLDL-triglyceride levels. Similarly, I148M-knockin mice show decreased hepatic triglyceride secretion during lipogenic stimulation. Our results highlight a specific context whereby the wild-type PNPLA3 facilitates the balance between hepatic triglyceride storage and secretion, and suggest the potential contribution of a loss-of-function by the I148M variant to the development of fatty liver disease in humans.
Heterogeneous peer effects of college roommates on academic performance
Authors: Cao Yi , Zhou Tao , Gao Jian
Published: June 2024

Understanding how student peers influence learning outcomes is crucial for effective education management in complex social systems. The complexities of peer selection and evolving peer relationships, however, pose challenges for identifying peer effects using static observational data. Here we use both null-model and regression approaches to examine peer effects using longitudinal data from 5,272 undergraduates, where roommate assignments are plausibly random upon enrollment and roommate relationships persist until graduation. Specifically, we construct a roommate null model by randomly shuffling students among dorm rooms and introduce an assimilation metric to quantify similarities in roommate academic performance. We find significantly larger assimilation in actual data than in the roommate null model, suggesting roommate peer effects, whereby roommates have more similar performance than expected by chance alone. Moreover, assimilation exhibits an overall increasing trend over time, suggesting that peer effects become stronger the longer roommates live together. Our regression analysis further reveals the moderating role of peer heterogeneity. In particular, when roommates perform similarly, the positive relationship between a student’s future performance and their roommates’ average prior performance is more pronounced, and their ordinal rank in the dorm room has an independent effect. Our findings contribute to understanding the role of college roommates in influencing student academic performance.
Global critical soil moisture thresholds of plant water stress
Authors: Fu Zheng , Ciais Philippe , Wigneron Jean-Pierre , Gentine Pierre , Feldman Andrew F. , Makowski David , Viovy Nicolas , Kemanian Armen R. , Goll Daniel S. , Stoy Paul C. , Prentice Iain Colin , Yakir Dan , Liu Liyang , Ma Hongliang , Li Xiaojun , Huang Yuanyuan , Yu Kailiang , Zhu Peng , Li Xing , Zhu Zaichun , Lian Jinghui , Smith William K.
Published: June 2024

During extensive periods without rain, known as dry-downs, decreasing soil moisture (SM) induces plant water stress at the point when it limits evapotranspiration, defining a critical SM threshold (θcrit). Better quantification of θcrit is needed for improving future projections of climate and water resources, food production, and ecosystem vulnerability. Here, we combine systematic satellite observations of the diurnal amplitude of land surface temperature (dLST) and SM during dry-downs, corroborated by in-situ data from flux towers, to generate the observation-based global map of θcrit. We find an average global θcrit of 0.19 m3/m3, varying from 0.12 m3/m3 in arid ecosystems to 0.26 m3/m3 in humid ecosystems. θcrit simulated by Earth System Models is overestimated in dry areas and underestimated in wet areas. The global observed pattern of θcrit reflects plant adaptation to soil available water and atmospheric demand. Using explainable machine learning, we show that aridity index, leaf area and soil texture are the most influential drivers. Moreover, we show that the annual fraction of days with water stress, when SM stays below θcrit, has increased in the past four decades. Our results have important implications for understanding the inception of water stress in models and identifying SM tipping points.
Piezoceramic membrane with built-in ultrasound for reactive oxygen species generation and synergistic vibration anti-fouling
Authors: Zhao Yang , Yang Feng , Jiang Han , Gao Guandao
Published: June 2024

Piezoceramic membranes have emerged as a prominent solution for membrane fouling control. However, the prevalent use of toxic lead and limitations of vibration-based anti-fouling mechanism impede their wider adoption in water treatment. This study introduces a Mn/BaTiO3 piezoceramic membrane, demonstrating a promising in-situ anti-fouling efficacy and mechanism insights. When applied to an Alternating Current at a resonant frequency of 20 V, 265 kHz, the membrane achieves optimal vibration, effectively mitigating various foulants such as high-concentration oil (2500 ppm, including real industrial oil wastewater), bacteria and different charged inorganic colloidal particles, showing advantages over other reported piezoceramic membranes. Importantly, our findings suggest that the built-in ultrasonic vibration of piezoceramic membranes can generate reactive oxygen species. This offers profound insights into the distinct anti-fouling processes for organic and inorganic wastewater, supplementing and unifying the traditional singular vibrational anti-fouling mechanism of piezoceramic membranes, and potentially propelling the development of piezoelectric catalytic membranes.
Type B Aortic Dissection CTA Collection with True and False Lumen Expert Annotations for the Development of AI-based Algorithms
Authors: Mayer Christian , Pepe Antonio , Hossain Sophie , Karner Barbara , Arnreiter Melanie , Kleesiek Jens , Schmid Johannes , Janisch Michael , Hannes Deutschmann , Fuchsjäger Michael , Zimpfer Daniel , Egger Jan , Mächler Heinrich
Published: June 2024

Aortic dissections (ADs) are serious conditions of the main artery of the human body, where a tear in the inner layer of the aortic wall leads to the formation of a new blood flow channel, named false lumen. ADs affecting the aorta distally to the left subclavian artery are classified as a Stanford type B aortic dissection (type B AD). This is linked to substantial morbidity and mortality, however, the course of the disease for the individual case is often unpredictable. Computed tomography angiography (CTA) is the gold standard for the diagnosis of type B AD. To advance the tools available for the analysis of CTA scans, we provide a CTA collection of 40 type B AD cases from clinical routine with corresponding expert segmentations of the true and false lumina. Segmented CTA scans might aid clinicians in decision making, especially if it is possible to fully automate the process. Therefore, the data collection is meant to be used to develop, train and test algorithms.
De novo transcriptomes of cave and surface isopod crustaceans: insights from 11 species across three suborders
Authors: Jovović Lada , Bedek Jana , Malard Florian , Bilandžija Helena
Published: June 2024

Isopods are a diverse group of crustaceans, that inhabit various environments, including terrestrial, freshwater, and marine, both on the surface and in the underground. The biological mechanisms underlying their wide range of adaptations to diverse ecological niches remain elusive. In order to unravel the molecular basis of their adaptability, we generated a comprehensive RNAseq dataset comprising 11 isopod species belonging to the three different suborders: freshwater Asellota, marine, brackish and freshwater Sphaeromatidea, and terrestrial Oniscidea, with representatives from families Asellidae, Sphaeromatidae, and Trichoniscidae, respectively. Representatives of each family were collected from both cave and surface environments, representing at least three independent cave colonization events. Three biological replicates were sequenced from each species to ensure data robustness. The 11 high-quality RNAseq datasets will serve as a valuable resource for understanding cave-specific adaptations, comparative and functional genomics, ecological annotation as well as aid in conservation efforts of these non-model organisms. Importantly, transcriptomes of eight featured species have been made publicly accessible for the first time.
A haplotype-resolved genome assembly of Malus domestica ‘Red Fuji’
Authors: Peng Haixu , Yi Yating , Li Jinrong , Qing You , Zhai Xuyang , Deng Yulin , Tian Ji , Zhang Jie , Hu Yujing , Qin Xiaoxiao , Lu Yanfen , Yao Yuncong , Wang Sen , Zheng Yi
Published: June 2024

The ‘Red Fuji’ apple (Malus domestica), is one of the most important and popular economic crops worldwide in the fruit industry. Using PacBio HiFi long reads and Hi-C reads, we assembled a high-quality haplotype-resolved genome of ‘Red Fuji’, with sizes of 668.7 and 668.8 Mb, and N50 sizes of 34.1 and 31.4 Mb. About 97.2% of sequences were anchored in 34 chromosomes. We annotated both haploid genomes, identifying a total of 95,439 protein-coding genes in the two haplotype genomes, with 98% functional annotation. The haplotype-resolved genome of ‘Red Fuji’ apple stands as a precise benchmark for an array of analyses, such as comparative genomics, transcriptomics, and allelic expression studies. This comprehensive resource is paramount in unraveling variations in allelic expression, advancing quality improvements, and refining breeding efforts.
Changes of aqueous humor cytokine profiles of patients with high intraocular pressure after PPV for retinal detachment
Authors: Zhu Chenchen , Cheng Yan , Tang Yi , Wu Hong , Liu Zaoxia
Published: June 2024

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It’s essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.
Genome wide association study and genomic risk prediction of age related macular degeneration in Israel
Authors: Grunin Michelle , Triffon Daria , Beykin Gala , Rahmani Elior , Schweiger Regev , Tiosano Liran , Khateb Samer , Hagbi-Levi Shira , Rinsky Batya , Munitz Refael , Winkler Thomas W. , Heid Iris M. , Halperin Eran , Carmi Shai , Chowers Itay
Published: June 2024

The risk of developing age-related macular degeneration (AMD) is influenced by genetic background. In 2016, the International AMD Genomics Consortium (IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score (PRS) from these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish (AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study (GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Our discovery set recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary-statistics excluding our study and developed PRSs via clumping/thresholding or LDpred2. In our discovery set, 31/34 loci reported by IAMDGC were AMD-associated (P < 0.05). Of those, all effects were directionally consistent with IAMDGC and 11 loci had a P-value under Bonferroni-corrected threshold (0.05/34 = 0.0015). At a 5 × 10−5 threshold, we discovered four suggestive associations in FAM189A1, IGDCC4, C7orf50, and CNTNAP4. Only the FAM189A1 variant was AMD-associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS + covariates had an AUC of 0.82 (95% CI 0.79–0.85) and performed better than covariates-only model (P = 5.1 × 10−9). Therefore, previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.
PDZ2-conjugated-PLGA nanoparticles are tiny heroes in the battle against SARS-CoV-2
Authors: Giacon Noah , Lo Cascio Ettore , Pennacchietti Valeria , De Maio Flavio , Santarelli Giulia , Sibilia Diego , Tiberio Federica , Sanguinetti Maurizio , Lattanzi Wanda , Toto Angelo , Arcovito Alessandro
Published: June 2024

The COVID-19 pandemic caused by SARS-CoV-2 has highlighted the urgent need for innovative antiviral strategies to fight viral infections. Although a substantial part of the overall effort has been directed at the Spike protein to create an effective global vaccination strategy, other proteins have also been examined and identified as possible therapeutic targets. Among them, although initially underestimated, there is the SARS-CoV-2 E-protein, which turned out to be a key factor in viral pathogenesis due to its role in virus budding, assembly and spreading. The C-terminus of E-protein contains a PDZ-binding motif (PBM) that plays a key role in SARS-CoV-2 virulence as it is recognized and bound by the PDZ2 domain of the human tight junction protein ZO-1. The binding between the PDZ2 domain of ZO-1 and the C-terminal portion of SARS-CoV-2 E-protein has been extensively characterized. Our results prompted us to develop a possible adjuvant therapeutic strategy aimed at slowing down or inhibiting virus-mediated pathogenesis. Such innovation consists in the design and synthesis of externally PDZ2-ZO1 functionalized PLGA-based nanoparticles to be used as intracellular decoy. Contrary to conventional strategies, this innovative approach aims to capitalize on the E protein-PDZ2 interaction to prevent virus assembly and replication. In fact, the conjugation of the PDZ2 domain to polymeric nanoparticles increases the affinity toward the E protein effectively creating a “molecular sponge” able to sequester E proteins within the intracellular environment of infected cells. Our in vitro studies on selected cellular models, show that these nanodevices significantly reduce SARS-CoV-2-mediated virulence, emphasizing the importance of exploiting viral-host interactions for therapeutic benefit.
Long-term impact of digital media on brain development in children
Authors: Nivins Samson , Sauce Bruno , Liebherr Magnus , Judd Nicholas , Klingberg Torkel
Published: June 2024

Digital media (DM) takes an increasingly large part of children’s time, yet the long-term effect on brain development remains unclear. We investigated how individual effects of DM use (i.e., using social media, playing video games, or watching television/videos) on the development of the cortex (i.e., global cortical surface area), striatum, and cerebellum in children over 4 years, accounting for both socioeconomic status and genetic predisposition. We used a prospective, multicentre, longitudinal cohort of children from the Adolescent Brain and Cognitive Development Study, aged 9.9 years when entering the study, and who were followed for 4 years. Annually, children reported their DM usage through the Youth Screen Time Survey and underwent brain magnetic resonance imaging scans every 2 years. Quadratic-mixed effect modelling was used to investigate the relationship between individual DM usage and brain development. We found that individual DM usage did not alter the development of cortex or striatum volumes. However, high social media usage was associated with a statistically significant change in the developmental trajectory of cerebellum volumes, and the accumulated effect of high-vs-low social media users on cerebellum volumes over 4 years was only β = − 0.03, which was considered insignificant. Nevertheless, the developmental trend for heavy social media users was accelerated at later time points. This calls for further studies and longer follow-ups on the impact of social media on brain development.
Breaking law of overburden rock and key mining technology for narrow coal pillar working face in isolated island
Authors: Feng Du , Zhenhua Li , Songtao Li , Xiaolei Li , Guodong Li , Xuan Fan , Hao Ren , Zhengzheng Cao
Published: June 2024

When conducting retreat mining in segmented coal pillars, the dynamic evolution of stress and overlying strata structure is more complex than conventional working faces due to the influence of adjacent working faces. Understanding and mastering the dynamic evolution patterns of overlying strata structure after retreat mining in segmented coal pillar working faces is essential for guiding the safe recovery of coal pillar resources under similar conditions. Through statistical analysis of the types of residual coal and the mining techniques, the current research status of residual coal mining system in China has been summarized. Based on the safety recovery technology system for multi-type residual coal pillar resources at Zhaogu No.2 Mine, this paper focuses on narrow coal pillar working faces in sections with fully mined-out areas on both sides. By using research methods such as on-site measurement, theoretical analysis, numerical simulation, and engineering experiments, starting from the stress state analysis and evolution law of coal seam mining, the dynamic evolution law of the overlying rock structure of sectional coal pillars has been mastered. On this basis, a stress arch mechanical model of the mining area is constructed, and the working resistance of the support is calculated and determined, ensuring the safe recovery of the working face. The research results show that before the backfilling of the sectional coal pillar working face, the working face is affected by the overlapping mining of the goaf on both sides, presenting a “bimodal” stress distribution pattern, with a stress concentration coefficient between 1.78 and 3.2. After the extraction of segmented coal pillars, stress arches consisting of high-stress zones form along both the strike and dip of the working face. The structural support provided by stress arches undergoes a dynamic evolution process of “formation-development-elevation-stabilization” as the working face advances. Following the instability and rupture of the lower basic roof hinge structure, the stress-bearing structure shifts to the higher basic roof, continuing to provide support for the surrounding rock stress in the mining space of the working face. A stress arch mechanical model for the dip and strike of the mining area is constructed , and the shape characteristics of the overlying rock stress arch in the coal pillar working face is mastered. Based on the stress distribution law and stress arch evolution characteristics of the surrounding rock of the coal pillar working face, the maximum working resistance of the support in the working face is theoretically calculated to be 9153.48kN. Compared with the measured mine pressure data, the selected support effectively ensures the safety production of the working face.
Green extraction and application of yellow natural curcumin colorant from Curcuma aromatica rhizomes for silk dyeing
Authors: Habib Noman , Batool Fatima , Adeel Shahid , Naveed Muhammad , Ali Aamir , Mia Rony , Assiri Mohammed A.
Published: June 2024

Green products such as plant tints are becoming more and more well-known worldwide due to their superior biological and ayurvedic properties. In this work, colorant from Amba Haldi (Curcuma aromatica) was isolated using microwave (MW), and bio-mordants were added to produce colorfast shades. Response surface methodology was used to develop a central composite design (CCD), which maximizes coloring variables statistically. The findings from 32 series of experiments show that excellent color depth (K/S = 12.595) was established onto MW-treated silk fabric (RS = 4 min) by employing 65 mL of radiated aqueous extract (RE = 4 min) of 5 pH cutting-edge the existence of 1.5 g/100 mL used sodium chloride at 75 °C for 45 min. It was discovered that acacia (keekar) extract (1%), pomegranate extract (2%), and pistachio extract (1.5%) were present before coloring by the use of bio-mordants. On the other hand, upon dyeing, acacia extract (1.5%), pomegranate extract (1.5%), and pistachio extract (2%) have all shown extremely strong colorfast colors. Comparatively, before dyeing, salts of Al3+ (1.5%), Fe2+ (2%), and TA (1.5%) gave good results; after dyeing, salts of Al3+ (1%) and Fe2+ (1.5%) and TA (2%) gave good results. When applied to silk fabric, MW radiation has increased the production of dyes recovered from rhizomes. Additionally, the right amount of chemical and biological mordants have been added, resulting in color fastness ratings ranging from outstanding to good. Therefore, the natural color extracted from Amba Haldi can be a sustainable option for the dyeing of silk fabric in the textile dyeing and finishing industries.
Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives
Authors: Wang Hui-Hui , Yin He-Liang , Yin Wei-Wei , Song Yong-Li , Chen Hong
Published: June 2024

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H2O}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO3)2·3H2O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H2OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal–organic frameworks, underscoring the innovative contributions of this study.
Unveiling genetic signatures associated with resilience to neonatal diarrhea in lambs through two GWAS approaches
Authors: Yaman Yalçın , Kişi Yiğit Emir , Şengül Serkan S. , Yıldırım Yasin , BAY Veysel
Published: June 2024

Neonatal diarrhea presents a significant global challenge due to its multifactorial etiology, resulting in high morbidity and mortality rates, and substantial economic losses. While molecular-level studies on genetic resilience/susceptibility to neonatal diarrhea in farm animals are scarce, prior observations indicate promising research directions. Thus, the present study utilizes two genome-wide association approaches, pKWmEB and MLM, to explore potential links between genetic variations in innate immunity and neonatal diarrhea in Karacabey Merino lambs. Analyzing 707 lambs, including 180 cases and 527 controls, revealed an overall prevalence rate of 25.5%. The pKWmEB analysis identified 13 significant SNPs exceeding the threshold of ≥ LOD 3. Moreover, MLM detected one SNP (s61781.1) in the SLC22A8 gene (p-value, 1.85eE-7), which was co-detected by both methods. A McNemar’s test was conducted as the final assessment to identify whether there are any major effective markers among the detected SNPs. Results indicate that four markers—oar3_OAR1_122352257, OAR17_77709936.1, oar3_OAR18_17278638, and s61781.1—have a substantial impact on neonatal diarrhea prevalence (odds ratio: 2.03 to 3.10; statistical power: 0.88 to 0.99). Therefore, we propose the annotated genes harboring three of the associated markers, TIAM1, YDJC, and SLC22A8, as candidate major genes for selective breeding against neonatal diarrhea.
Innovative approaches to wound healing: insights into interactive dressings and future directions
Authors: Yadav Radhika , Kumar Rohtash , Kathpalia Muskan , Ahmed Bakr , Dua Kamal , Gulati Monica , Singh Sachin , Singh Pushvinder Jit , Kumar Suneel , Shah Rohan M. , Deol Parneet Kaur , Kaur Indu Pal
Published: June 2024

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings.
An integrated electronic tag-based vertical flow assay (e-VFA) with micro-sieve and AlGaN/GaN HEMT sensors for multi-target detection in actual saliva
Authors: Gu Zhiqi , Chang Hui , Yang Guo , Xu Boxuan , Miao Bin , Li Jiadong
Published: June 2024

Herein, a brand new VFA scheme based on AlGaN/GaN HEMT sensors modified with different bio-receptors as electronic tags integrated with a micro-sieve was proposed for multi-target detection in real saliva.
Determination of 3-acetyl-11-keto-β-boswellic acid in analytical and biological samples using streamlined and robust RP-HPLC method
Authors: Priya Sakshi , Singhvi Gautam
Published: June 2024

Effective quantification of 3-acetyl-11-keto-β-boswellic acid in nanocarrier systems,in vitrodrug release samples, and skin matrices using the RP-HPLC method.
Assembly of a trapped valent CeIII/IV–TCNQ complex through metal–ligand redox cooperativity
Authors: Gupta Himanshu , Vincenzini Brett D. , Bacon Alexandra M. , Schelter Eric J.
Published: June 2024

A trapped-valent CeIII/IV–TCNQ complex is assembled through Lewis acid-promoted donor–acceptor potential shifts providing a magnetic and luminescent compound.
A diphenylphosphine oxide decorated multi-resonance TADF emitter for narrowband green electroluminescence with an EQE of 32.4%
Authors: Dong Junjie , Xu Yulin , Wang Shuni , Miao Jingsheng , Li Nengquan , Huang Zhongyan , Yang Chuluo
Published: June 2024

A multi-resonance TADF emitter with diphenylphosphine oxide decoration enables high-performance pure green OLEDs with external quantum efficiencies up to 32.4%.