bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractFarmers 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

AbstractCarbon 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

AbstractChondrocyte 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

AbstractHuman 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

AbstractKaposi 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

AbstractThe 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

AbstractUnderstanding 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

AbstractDuring 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

AbstractPiezoceramic 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

AbstractAortic 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

AbstractIsopods 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

AbstractThe ‘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

AbstractHigh 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

AbstractThe 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

AbstractThe 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.