bluuebunny/crossref_metadata_2025 huggingface dataset:
Siglec-6 as a therapeutic target for cell migration and adhesion in chronic lymphocytic leukemia
Authors: Nunes Jessica , Tafesse Rakeb , Mao Charlene , Purcell Matthew , Mo Xiaokui , Zhang Liwen , Long Meixiao , Cyr Matthew G. , Rader Christoph , Muthusamy Natarajan
Published: June 2024

Siglec-6 is a lectin receptor with restricted expression in the placenta, mast cells and memory B-cells. Although Siglec-6 is expressed in patients with chronic lymphocytic leukemia (CLL), its pathophysiological role has not been elucidated. We describe here a role for Siglec-6 in migration and adhesion of CLL B cells to CLL- bone marrow stromal cells (BMSCs) in vitro and compromised migration to bone marrow and spleen in vivo. Mass spectrometry analysis revealed interaction of Siglec-6 with DOCK8, a guanine nucleotide exchange factor. Stimulation of MEC1-002 CLL cells with a Siglec-6 ligand, sTn, results in Cdc42 activation, WASP protein recruitment and F-actin polymerization, which are all associated with cell migration. Therapeutically, a Siglec-6/CD3-bispecific T-cell-recruiting antibody (T-biAb) improves overall survival in an immunocompetent mouse model and eliminates CLL cells in a patient derived xenograft model. Our findings thus reveal a migratory role for Siglec-6 in CLL, which can be therapeutically targeted using a Siglec-6 specific T-biAb.
Reconstructing higher-order interactions in coupled dynamical systems
Authors: Malizia Federico , Corso Alessandra , Gambuzza Lucia Valentina , Russo Giovanni , Latora Vito , Frasca Mattia
Published: June 2024

Higher-order interactions play a key role for the operation and function of a complex system. However, how to identify them is still an open problem. Here, we propose a method to fully reconstruct the structural connectivity of a system of coupled dynamical units, identifying both pairwise and higher-order interactions from the system time evolution. Our method works for any dynamics, and allows the reconstruction of both hypergraphs and simplicial complexes, either undirected or directed, unweighted or weighted. With two concrete applications, we show how the method can help understanding the complexity of bacterial systems, or the microscopic mechanisms of interaction underlying coupled chaotic oscillators.
Characterization and regulation of cell cycle-independent noncanonical gene targeting
Authors: Saito Shinta , Adachi Noritaka
Published: June 2024

Homology-dependent targeted DNA integration, generally referred to as gene targeting, provides a powerful tool for precise genome modification; however, its fundamental mechanisms remain poorly understood in human cells. Here we reveal a noncanonical gene targeting mechanism that does not rely on the homologous recombination (HR) protein Rad51. This mechanism is suppressed by Rad52 inhibition, suggesting the involvement of single-strand annealing (SSA). The SSA-mediated gene targeting becomes prominent when DSB repair by HR or end-joining pathways is defective and does not require isogenic DNA, permitting 5% sequence divergence. Intriguingly, loss of Msh2, loss of BLM, and induction of a target-site DNA break all significantly and synergistically enhance SSA-mediated targeted integration. Most notably, SSA-mediated integration is cell cycle-independent, occurring in the G1 phase as well. Our findings provide unequivocal evidence for Rad51-independent targeted integration and unveil multiple mechanisms to regulate SSA-mediated targeted as well as random integration.
A single-cell atlas of pig gastrulation as a resource for comparative embryology
Authors: Simpson Luke , Strange Andrew , Klisch Doris , Kraunsoe Sophie , Azami Takuya , Goszczynski Daniel , Le Minh Triet , Planells Benjamin , Holmes Nadine , Sang Fei , Henson Sonal , Loose Matthew , Nichols Jennifer , Alberio Ramiro
Published: June 2024

Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development. We highlight heterochronicity in extraembryonic cell-types, despite the broad conservation of cell-type-specific transcriptional programs. We apply these findings in combination with functional investigations, to outline conserved spatial, molecular, and temporal events during definitive endoderm specification. We find early FOXA2 + /TBXT- embryonic disc cells directly form definitive endoderm, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none of these progenitors undergo epithelial-to-mesenchymal transition. Endoderm/Node fate hinges on balanced WNT and hypoblast-derived NODAL, which is extinguished upon endodermal differentiation. These findings emphasise the interplay between temporal and topological signalling in fate determination during gastrulation.
Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression
Authors: Zhukovsky Peter , Tio Earvin S. , Coughlan Gillian , Bennett David A. , Wang Yanling , Hohman Timothy J. , Pizzagalli Diego A. , Mulsant Benoit H. , Voineskos Aristotle N. , Felsky Daniel
Published: June 2024

Approximately 40% of dementia cases could be prevented or delayed by modifiable risk factors related to lifestyle and environment. These risk factors, such as depression and vascular disease, do not affect all individuals in the same way, likely due to inter-individual differences in genetics. However, the precise nature of how genetic risk profiles interact with modifiable risk factors to affect brain health is poorly understood. Here we combine multiple data resources, including genotyping and postmortem gene expression, to map the genetic landscape of brain structure and identify 367 loci associated with cortical thickness and 13 loci associated with white matter hyperintensities (P < 5×10−8), with several loci also showing a significant association with cognitive function. We show that among 220 unique genetic loci associated with cortical thickness in our genome-wide association studies (GWAS), 95 also showed evidence of interaction with depression or cardiovascular conditions. Polygenic risk scores based on our GWAS of inferior frontal thickness also interacted with hypertension in predicting executive function in the Canadian Longitudinal Study on Aging. These findings advance our understanding of the genetic underpinning of brain structure and show that genetic risk for brain and cognitive health is in part moderated by treatable mid-life factors.
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
Authors: Dans Madeline G. , Boulet Coralie , Watson Gabrielle M. , Nguyen William , Dziekan Jerzy M. , Evelyn Cindy , Reaksudsan Kitsanapong , Mehra Somya , Razook Zahra , Geoghegan Niall D. , Mlodzianoski Michael J. , Goodman Christopher Dean , Ling Dawson B. , Jonsdottir Thorey K. , Tong Joshua , Famodimu Mufuliat Toyin , Kristan Mojca , Pollard Harry , Stewart Lindsay B. , Brandner-Garrod Luke , Sutherland Colin J. , Delves Michael J. , McFadden Geoffrey I. , Barry Alyssa E. , Crabb Brendan S. , de Koning-Ward Tania F. , Rogers Kelly L. , Cowman Alan F. , Tham Wai-Hong , Sleebs Brad E. , Gilson Paul R.
Published: June 2024

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
Chemogenomics for NR1 nuclear hormone receptors
Authors: Isigkeit Laura , Schallmayer Espen , Busch Romy , Brunello Lorene , Menge Amelie , Elson Lewis , Müller Susanne , Knapp Stefan , Stolz Alexandra , Marschner Julian A. , Merk Daniel
Published: June 2024

Nuclear receptors (NRs) regulate transcription in response to ligand binding and NR modulation allows pharmacological control of gene expression. Although some NRs are relevant as drug targets, the NR1 family, which comprises 19 NRs binding to hormones, vitamins, and lipid metabolites, has only been partially explored from a translational perspective. To enable systematic target identification and validation for this protein family in phenotypic settings, we present an NR1 chemogenomic (CG) compound set optimized for complementary activity/selectivity profiles and chemical diversity. Based on broad profiling of candidates for specificity, toxicity, and off-target liabilities, sixty-nine comprehensively annotated NR1 agonists, antagonists and inverse agonists covering all members of the NR1 family and meeting potency and selectivity standards are included in the final NR1 CG set. Proof-of-concept application of this set reveals effects of NR1 members in autophagy, neuroinflammation and cancer cell death, and confirms the suitability of the set for target identification and validation.
Ecological drivers of ultraviolet colour evolution in snakes
Authors: Crowell Hayley L. , Curlis John David , Weller Hannah I. , Davis Rabosky Alison R.
Published: June 2024

Ultraviolet (UV) colour patterns invisible to humans are widespread in nature. However, research bias favouring species with conspicuous colours under sexual selection can limit our assessment of other ecological drivers of UV colour, like interactions between predators and prey. Here we demonstrate widespread UV colouration across Western Hemisphere snakes and find stronger support for a predator defence function than for reproduction. We find that UV colouration has evolved repeatedly in species with ecologies most sensitive to bird predation, with no sexual dichromatism at any life stage. By modelling visual systems of potential predators, we find that snake conspicuousness correlates with UV colouration and predator cone number, providing a plausible mechanism for selection. Our results suggest that UV reflectance should not be assumed absent in “cryptically coloured” animals, as signalling beyond human visual capacities may be a key outcome of species interactions in many taxa for which UV colour is likely underreported.
Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection
Authors: Tisoncik-Go Jennifer , Stokes Caleb , Whitmore Leanne S. , Newhouse Daniel J. , Voss Kathleen , Gustin Andrew , Sung Cheng-Jung , Smith Elise , Stencel-Baerenwald Jennifer , Parker Edward , Snyder Jessica M. , Shaw Dennis W. , Rajagopal Lakshmi , Kapur Raj P. , Adams Waldorf Kristina M. , Gale Michael
Published: June 2024

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.
Intracranial EEG signals disentangle multi-areal neural dynamics of vicarious pain perception
Authors: Tan Huixin , Zeng Xiaoyu , Ni Jun , Liang Kun , Xu Cuiping , Zhang Yanyang , Wang Jiaxin , Li Zizhou , Yang Jiaxin , Han Chunlei , Gao Yuan , Yu Xinguang , Han Shihui , Meng Fangang , Ma Yina
Published: June 2024

Empathy enables understanding and sharing of others’ feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others’ pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.
Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors
Authors: Sun Linmao , Liu Yufeng , Guo Xinyu , Cui Tianming , Wu Chenghui , Tao Jie , Cheng Cheng , Chu Qi , Ji Changyong , Li Xianying , Guo Hongrui , Liang Shuhang , Zhou Huanran , Zhou Shuo , Ma Kun , Zhang Ning , Wang Jiabei , Liu Yao , Liu Lianxin
Published: June 2024

Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.
Protective roles of thrombomodulin in cisplatin-induced nephrotoxicity through the inhibition of oxidative and endoplasmic reticulum stress
Authors: Yamamoto Hiroki , Ishida Yuko , Zhang Siying , Osako Miyu , Nosaka Mizuho , Kuninaka Yumi , Ishigami Akiko , Iwahashi Yuya , Aragane Miki , Matsumoto Lennon , Kimura Akihiko , Kondo Toshikazu
Published: June 2024

Cisplatin is an effective chemotherapeutic agent widely used for the treatment of various solid tumors. However, cisplatin has an important limitation in its use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Thrombomodulin (TM) is well known not only for its role as a cofactor in the clinically important natural anticoagulation pathway but also for its anti-inflammatory properties. Here, we investigated the effects of TM in cisplatin-induced AKI. In mice intraperitoneally injected with 15 mg/kg cisplatin, TM (10 mg/kg) or PBS was administered intravenously at 24 h after cisplatin injection. TM significantly attenuated cisplatin-induced nephrotoxicity with the suppressed elevation of blood urea nitrogen and serum creatinine, and reduced histological damages. Actually, TM treatment significantly alleviated oxidative stress-induced apoptosis by reducing reactive oxygen species (ROS) levels in cisplatin-treated renal proximal tubular epithelial cells (RPTECs) in vitro. Furthermore, TM clarified cisplatin-induced apoptosis by reducing caspase-3 levels. In addition, TM attenuated the endoplasmic reticulum (ER) stress signaling pathway in both renal tissues and RPTECs to protect the kidneys from cisplatin-induced AKI. These findings suggest that TM is a potential protectant against cisplatin-induced nephrotoxicity through suppressing ROS generation and ER stress in response to cisplatin.
Stability evaluation of open-pit mine slope based on Bayesian optimization 1D-CNN
Authors: Lyu Jinguo , Hu Taihong , Liu Guangwei , Cao Bo , Wang Wenqi , Li Shixu
Published: June 2024

As mechanized open-pit coal mining intensifies, assessing and predicting slope stability has become increasingly important. To address the limitations of traditional mechanical calculations, numerical simulations, and physical experiments, this paper identifies the key factors impacting slope stability in open-pit mines and develops a multi-parameter sample data set. The study employs hyperparameters optimized using a Bayesian algorithm, introduces additional convolutional layers, and combines the Adam optimizer with dropout techniques to enhance the feature extraction and performance of one-dimensional convolutional neural networks (1D-CNN). This leads to a Bayesian-optimized one-dimensional convolutional neural network (B-1D MCNN) model for predicting slope stability.The study evaluates the classification performance and accuracy of various models for slope stability, including BP neural networks, genetic algorithm-optimized convolutional neural networks, 1D-CNN, and B-1D MCNN, using accuracy, precision, and F1-score as metrics. The analysis also examines the influence of factor indicators and training set length on the model's output to assess its generalization capabilities.The research findings suggest that: (1) the B-1D MCNN model for evaluating slope stability demonstrates the capability to accurately depict the nonlinear correlation between influencing factors and slope stability. (2) Compared with other models, the B-1D MCNN model has shown enhancements of 10.96% to 27.85%, 10.26% to 28.55%, and 8.98% to 25.05% in terms of Accuracy, F1-Score, and Precision, respectively. (3) As the length of the training dataset increases, the performance of the model improves accordingly. (4) The B-1D MCNN model shows a generalization power of 87.5%.
Numerical simulation research on thermal insulation performance of composite heat-insulation zone structure in hydrothermal high-temperature mine
Authors: Li Yanhe , Wan Zhijun , Yu Zhenzi , Shi Peng , Zhang Bo , Zhang Yuan
Published: June 2024

In hydrothermal high-temperature abnormal mines, the composite heat-insulation zone structure, formed through a combination of guniting and grouting, serves to mitigate heat dissipation from the surrounding rock into the airflow. To comprehensively understand the thermal insulation performance of the composite heat-insulation zone structure, this study employs numerical simulation to analyze the following aspects: the variation in the temperature field within the surrounding rock of the roadway without insulation, the influence of structural parameters of the composite heat-insulation zone on temperature distribution in the surrounding rock of the roadway, and the thermal insulation effectiveness of the composite heat-insulation zone with varying structures. The findings indicate that the temperature distribution within the surrounding rock of the roadway lacking a heat-insulation zone is relatively uniform. However, as ventilation time extends, the heat regulation zone within the surrounding rock gradually extends deeper, ultimately forming an elliptical cooling area. The composite heat-insulation zone structure effectively mitigates heat transfer from deeper surrounding rock to the roadway wall, consequently altering the scope of the roadway's heat regulation zone. Enhancing the thermal insulation performance of the composite heat-insulation zone structure can be achieved by increasing the thickness of the thermal insulation layer, adjusting grouting rate and depth, and reducing the thermal conductivity of insulation materials. The thermal insulation effectiveness of the thermal insulation layer surpasses that of the grouting layer, with its performance primarily influenced by the thermal conductivity of the materials used. Simulation results demonstrate that the composite heat-insulation zone structure reduces the maximum heat flux on the roadway wall from 47.4 to 37.7 W/m2, resulting in a 20% reduction in heat transfer from deeper surrounding rock. These findings offer valuable insights for implementing thermal insulation techniques in hydrothermal high-temperature anomaly mines.
Unveiling green corrosion inhibitor of Aloe vera extracts for API 5L steel in seawater environment
Authors: Royani Ahmad , Hanafi Muhammad , Mubarak Nabisab Mujawar , Priyotomo Gadang , Aigbodion Victor Sunday , Musabikha Siti , Manaf Azwar
Published: June 2024

This study evaluated Aloe vera extract as a green inhibitor to prevent corrosion in seawater environments. A. vera extract was produced by maceration with methanol﻿–water at room temperature. Electrochemical techniques were used to evaluate the corrosion inhibitor effectiveness of the A. vera extract. The morphology of the corrosion products was analyzed by FE-SEM equipped with EDS and AFM. FT-IR and LCMS characterized the functional and structural groups in this extract. The electrochemical measurements show that A. vera extract could effectively reduce the corrosion of API 5L steel in seawater environments. Inhibition efficiency (IE) increases with increasing concentration. Optimal corrosion inhibition efficiency of around 83.75% (PDP) and 88.60% (EIS) was obtained by adding 300 mg L−1 of extract at 310 K. Furthermore, the higher the concentration of A. vera extract, the greater the activation energy (Ea), with the highest activation energy being 48.24 kJ mol−1 for the concentration of 300 mg L−1. Conversely, increasing the temperature and exposure duration reduces the corrosion inhibition efficiency (IE) values; the best exposure period was 30 min with 88.34% IE by a concentration of 300 mg L−1 at 300 K. This corrosion inhibition is achieved by the adsorption process of A. vera bioactive on metal surfaces with a mixed inhibitor through a physisorption-chemisorption mechanism. This finding was confirmed by the smoother surface morphology of the steel treated with A. vera extract than without. This unveiling investigation found that A. vera extract has the potential to be an environmentally friendly corrosion inhibitor in the seawater environment.
Rapid photocatalytic dye degradation, enhanced antibacterial and antifungal activities of silver stacked zinc oxide garnished on carbon nanotubes
Authors: Wagh Snehal S. , Chougale Akanksha S. , Survase Avinash A. , Patil Rajendra S. , Naik Nithesh , Naushad Mu. , Pathan Habib M.
Published: June 2024

A composite of Zinc oxide loaded with 5-weight % silver decorated on carbon nanotubes (Ag-loaded ZnO: CNT) was synthesized using a simple refluxed chemical method. The influence of deviation in the weight % of carbon nanotube loading on photocatalytic dye degradation (methylene blue and rose bengal) and antibiotic (antimicrobial and antifungal) performance was investigated in this study. The light capture ability of Ag-loaded ZnO:CNT in the visible region was higher in photocatalytic activity than that of Ag-loaded ZnO and ZnO:CNT. The bandgap of the Ag-loaded ZnO: CNT was tuned owing to the surface plasmon resonance effect. The photocatalytic degradation investigations were optimized by varying the wt% in CNTs, pH of dye solution, concentration of the dye solution, and amount of catalytic dose. Around 100% photocatalytic efficiency in 2 min against MB dye was observed for Ag doped ZnO with 10 wt% CNT composite at pH 9, at a rate constant 1.48 min−1. Bipolaris sorokiniana fungus was first time tested against a composite material, which demonstrated optimum fungal inhibition efficiency of 48%. They were also tested against the bacterial strains Staphylococcus aureus, Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium, which showed promising antibacterial activity compared to commercially available drugs. The composite of Ag doped ZnO with 5 wt% CNT has shown competitive zone inhibition efficacy of 21.66 ± 0.57, 15.66 ± 0.57, 13.66 ± 0.57 against bacterial strains Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium which were tested for the first time against Ag-loaded ZnO:CNT.
Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion
Authors: He Ping , Jiang Chen , Ni Jianqiang , Zhang Xiaoxuan , Wu Zhifeng , Chen Gengjing , Huang Jin , Dai Zheng , Ji Wei , Li Lei , Chen Kefei , Shi Yachen
Published: June 2024

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.
The chloroplast genome sequences of Ipomoea alba and I. obscura (Convolvulaceae): genome comparison and phylogenetic analysis
Authors: Sudmoon Runglawan , Kaewdaungdee Sanit , Ho Hao Xuan , Lee Shiou Yih , Tanee Tawatchai , Chaveerach Arunrat
Published: June 2024

Ipomoea species have diverse uses as ornamentals, food, and medicine. However, their genomic information is limited; I. alba and I. obscura were sequenced and assembled. Their chloroplast genomes were 161,353 bp and 159,691 bp, respectively. Both genomes exhibited a quadripartite structure, consisting of a pair of inverted repeat (IR) regions, which are separated by the large single-copy (LSC) and small single-copy (SSC) regions. The overall GC content was 37.5% for both genomes. A total of 104 and 93 simple sequence repeats, 50 large repeats, and 30 and 22 short tandem repeats were identified in the two chloroplast genomes, respectively. G and T were more preferred than C and A at the third base position based on the Parity Rule 2 plot analysis, and the neutrality plot revealed correlation coefficients of 0.126 and 0.105, indicating the influence of natural selection in shaping the codon usage bias in most protein-coding genes (CDS). Genome comparative analyses using 31 selected Ipomoea taxa from Thailand showed that their chloroplast genomes are rather conserved, but the presence of expansion or contraction of the IR region was identified in some of these Ipomoea taxa. A total of five highly divergent regions were identified, including the CDS genes accD, ndhA, and ndhF, as well as the intergenic spacer regions psbI-atpA and rpl32-ccsA. Phylogenetic analysis based on both the complete chloroplast genome sequence and CDS datasets of 31 Ipomoea taxa showed that I. alba is resolved as a group member for series (ser.) Quamoclit, which contains seven other taxa, including I. hederacea, I. imperati, I. indica, I. nil, I. purpurea, I. quamoclit, and I. × sloteri, while I. obscura is grouped with I. tiliifolia, both of which are under ser. Obscura, and is closely related to I. biflora of ser. Pes-tigridis. Divergence time estimation using the complete chloroplast genome sequence dataset indicated that the mean age of the divergence for Ipomoeeae, Argyreiinae, and Astripomoeinae, was approximately 29.99 Mya, 19.81 Mya, and 13.40 Mya, respectively. The node indicating the divergence of I. alba from the other members of Ipomoea was around 10.06 Mya, and the split between I. obscura and I. tiliifolia is thought to have happened around 17.13 Mya. The split between the I. obscura accessions from Thailand and Taiwan is thought to have taken place around 0.86 Mya.
Kidney volume-to-birth weight ratio as an estimate of nephron endowment in extremely low birth weight preterm infants
Authors: Villani Gabriele , Zaza Pierluigi , Lamparelli Raffaella , Maffei Gianfranco
Published: June 2024

In humans, nephrogenesis is completed by 32–36 weeks gestation, with a highly variable total number of nephrons, ranging from 200,000 to over 2 million. Premature birth disrupts the development and maturation of the kidneys, leading to a reduction in the final number of nephrons. Due to significant genetic variability in the number of nephrons among individuals, it is crucial to identify premature infants with fewer nephrons at birth as early as possible. These infants are more susceptible to developing renal failure with advancing age compared to those with a higher nephron endowment. Bedside ultrasound, an effective and non-invasive tool, is practical for identifying newborns with a lower nephron count. However, renal volume alone cannot reliably indicate the number of nephrons due to substantial variability at birth, influenced by gestational age when nephron maturation is incomplete. This variability in kidney volumes persists as newborns grow. In this observational study we hypothesize that the relationship between renal volume and birth weight may serve as an indicator of nephron endowment in premature infants with birth weight less than 1000 g. This finding could represent the basis for defining appropriate surveillance protocols and developing targeted therapeutic approaches.
The high expression of ADRM1 in hepatocellular carcinoma is closely related to tumor immune infiltration and is regulated by miR-891a-5p
Authors: Shao Ziqi , Wang Yuan , He Yuejun , Zhang Chen , Zhao Yandong , Zhang Mimi , Li Qiang , Wang Jian
Published: June 2024

Liver cancer is one of the most common malignant tumors worldwide. Although some progress has been made in the diagnosis and treatment of Hepatocellular carcinoma (HCC), the diagnosis and treatment of HCC is still facing great challenges because of the high mortality rate and poor prognosis of HCC. The purpose of this study was to explore the relationship between adhesion-regulating molecule1 (ADRM1), and liver cancer, and the relationship between prognoses. ADRM1 is highly expressed in tumors and is closely associated with the prognosis of patients with liver cancer. In our previous study, we found that ADRM1 was highly expressed in HCC and was closely related to tumor immune and immune checkpoint levels in HCC. We validated the immune expression of ADRM1 in liver cancer cells using flow cytometry. In hepatocellular carcinoma tissues, miR-891a-5p regulates ADRM1. Upregulation of miR-891a-5p upregulates ADRM1, and downregulation of miR-891a-5p downregulates ADRM1. It is suggested that ADRM1 plays a key role in the occurrence and development of hepatocellular carcinoma. This study is expected to provide new ideas for the research and development of anti-HCC drugs targeting miR-891a-5p/ADRM1. However, further trials are needed to confirm these results and explore the actual results in patients with HCC.
Exploring the effects of naringin on oxidative stress-impaired osteogenic differentiation via the Wnt/β-catenin and PI3K/Akt pathways
Authors: Wang Hui , Liang Jun , Wang Yiran , Zheng Junyuan , Liu Ying , Zhao Yiyang , Ma Yixuan , Chen Pei , Yang Xufang
Published: June 2024

This study aimed to explore naringin’s potential to promote the osteogenic differentiation of MC3T3-E1 under oxidative stress. It delved into Nar’s connection with the Wnt/β-catenin and PI3K/Akt signaling pathways. Initially, 2911 OP-related genes were analyzed, revealing close ties with the PI3K/Akt and Wnt pathways alongside oxidative stress. Nar’s potential targets—ESR1, HSP90AA1, and ESR2—were identified through various databases and molecular docking studies confirmed Nar’s affinity with ESR1 and HSP90AA1. Experiments established optimal concentrations for Nar and H2O2. H2O2 at 0.3 mmol/L damaged MC3T3-E1 cells, alleviated by 0.1 µmol/L Nar. Successful establishment of oxidative stress models was confirmed by DCFH-DA probe and NO detection. Nar exhibited the ability to enhance osteogenic differentiation, counteracting oxidative damage. It notably increased osteoblast-related protein expression in MC3T3-E1 cells under oxidative stress. The study found Nar’s positive influence on GSK-3β phosphorylation, β-catenin accumulation, and pathway-related protein expression, all critical in promoting osteogenic differentiation. The research concluded that Nar effectively promotes osteogenic differentiation in MC3T3-E1 cells under oxidative stress. It achieved this by activating the Wnt/β-catenin and PI3K/Akt pathways, facilitating GSK-3β phosphorylation, and enhancing β-catenin accumulation, pivotal in osteogenesis.
Head movement dynamics in dystonia: a multi-centre retrospective study using visual perceptive deep learning
Authors: Peach Robert , Friedrich Maximilian , Fronemann Lara , Muthuraman Muthuraman , Schreglmann Sebastian R. , Zeller Daniel , Schrader Christoph , Krauss Joachim K. , Schnitzler Alfons , Wittstock Matthias , Helmers Ann-Kristin , Paschen Steffen , Kühn Andrea , Skogseid Inger Marie , Eisner Wilhelm , Mueller Joerg , Matthies Cordula , Reich Martin , Volkmann Jens , Ip Chi Wang
Published: June 2024

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.
From wearable sensor data to digital biomarker development: ten lessons learned and a framework proposal
Authors: Daniore Paola , Nittas Vasileios , Haag Christina , Bernard Jürgen , Gonzenbach Roman , von Wyl Viktor
Published: June 2024

Wearable sensor technologies are becoming increasingly relevant in health research, particularly in the context of chronic disease management. They generate real-time health data that can be translated into digital biomarkers, which can provide insights into our health and well-being. Scientific methods to collect, interpret, analyze, and translate health data from wearables to digital biomarkers vary, and systematic approaches to guide these processes are currently lacking. This paper is based on an observational, longitudinal cohort study, BarKA-MS, which collected wearable sensor data on the physical rehabilitation of people living with multiple sclerosis (MS). Based on our experience with BarKA-MS, we provide and discuss ten lessons we learned in relation to digital biomarker development across key study phases. We then summarize these lessons into a guiding framework (DACIA) that aims to informs the use of wearable sensor data for digital biomarker development and chronic disease management for future research and teaching.
Androgen-responsive FOXP4 is a target for endometrial carcinoma
Authors: Kayahashi Kayo , Hasan Mahadi , Khatun Anowara , Kohno Susumu , Terakawa Jumpei , Horike Shin-ichi , Toyoda Natsumi , Matsuoka Ayumi , Iizuka Takashi , Obata Takeshi , Ono Masanori , Mizumoto Yasunari , Takahashi Chiaki , Fujiwara Hiroshi , Daikoku Takiko
Published: June 2024

Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Ptenff/PRcre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Ptenff/PRcre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.
Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors
Authors: Zhou Jintong , Xia Mingyu , Huang Zhenghui , Qiao Hang , Yang Guang , Qian Yunan , Li Peifeng , Zhang Zhaolun , Gao Xinai , Jiang Lubin , Wang Jing , Li Wei , Fang Pengfei
Published: June 2024

Aminoacyl-tRNA synthetases (aaRSs) play a central role in the translation of genetic code, serving as attractive drug targets. Within this family, the lysyl-tRNA synthetase (LysRS) constitutes a promising antimalarial target. ASP3026, an anaplastic lymphoma kinase (ALK) inhibitor was recently identified as a novel Plasmodium falciparum LysRS (PfLysRS) inhibitor. Here, based on cocrystal structures and biochemical experiments, we developed a series of ASP3026 analogues to improve the selectivity and potency of LysRS inhibition. The leading compound 36 showed a dissociation constant of 15.9 nM with PfLysRS. The inhibitory efficacy on PfLysRS and parasites has been enhanced. Covalent attachment of l-lysine to compound 36 resulted in compound 36K3, which exhibited further increased inhibitory activity against PfLysRS but significantly decreased activity against ALK. However, its inhibitory activity against parasites did not improve, suggesting potential future optimization directions. This study presents a new example of derivatization of kinase inhibitors repurposed to inhibit aaRS.
Implementation of binarized neural networks immune to device variation and voltage drop employing resistive random access memory bridges and capacitive neurons
Authors: Ezzadeen Mona , Majumdar Atreya , Valorge Olivier , Castellani Niccolo , Gherman Valentin , Regis Guillaume , Giraud Bastien , Noel Jean-Philippe , Meli Valentina , Bocquet Marc , Andrieu Francois , Querlioz Damien , Portal Jean-Michel
Published: June 2024

Resistive Random Access Memories (ReRAM) arrays provides a promising basement to deploy neural network accelerators based on near or in memory computing. However most popular accelerators rely on Ohm’s and Kirchhoff’s laws to achieve multiply and accumulate, and thus are prone to ReRAM variability and voltage drop in the memory array, and thus need sophisticated readout circuits. Here we propose a robust binary neural network, based on fully differential capacitive neurons and ReRAM synapses, used in a resistive bridge fashion. We fabricated a network layer with up to 23 inputs that we extrapolated to large numbers of inputs through simulation. Defining proper programming and reading conditions, we demonstrate the high resilience of this solution with a minimal accuracy drop, compared to a software baseline, on image classification tasks. Moreover, our solution can achieve a peak energy efficiency, comparable with the state of the art, when projected to a 22 nanometer technology.
A novel approach to anxiety level prediction using small sets of judgment and survey variables
Authors: Bari Sumra , Kim Byoung-Woo , Vike Nicole L. , Lalvani Shamal , Stefanopoulos Leandros , Maglaveras Nicos , Block Martin , Strawn Jeffrey , Katsaggelos Aggelos K. , Breiter Hans C.
Published: June 2024

Anxiety, a condition characterized by intense fear and persistent worry, affects millions each year and, when severe, is distressing and functionally impairing. Numerous machine learning frameworks have been developed and tested to predict features of anxiety and anxiety traits. This study extended these approaches by using a small set of interpretable judgment variables (n = 15) and contextual variables (demographics, perceived loneliness, COVID-19 history) to (1) understand the relationships between these variables and (2) develop a framework to predict anxiety levels [derived from the State Trait Anxiety Inventory (STAI)]. This set of 15 judgment variables, including loss aversion and risk aversion, models biases in reward/aversion judgments extracted from an unsupervised, short (2–3 min) picture rating task (using the International Affective Picture System) that can be completed on a smartphone. The study cohort consisted of 3476 de-identified adult participants from across the United States who were recruited using an email survey database. Using a balanced Random Forest approach with these judgment and contextual variables, STAI-derived anxiety levels were predicted with up to 81% accuracy and 0.71 AUC ROC. Normalized Gini scores showed that the most important predictors (age, loneliness, household income, employment status) contributed a total of 29–31% of the cumulative relative importance and up to 61% was contributed by judgment variables. Mediation/moderation statistics revealed that the interactions between judgment and contextual variables appears to be important for accurately predicting anxiety levels. Median shifts in judgment variables described a behavioral profile for individuals with higher anxiety levels that was characterized by less resilience, more avoidance, and more indifference behavior. This study supports the hypothesis that distinct constellations of 15 interpretable judgment variables, along with contextual variables, could yield an efficient and highly scalable system for mental health assessment. These results contribute to our understanding of underlying psychological processes that are necessary to characterize what causes variance in anxiety conditions and its behaviors, which can impact treatment development and efficacy.
A nitrogen-doped carbon fiber coating embedded in the separator for stable zinc batteries
Authors: Luo Dingzhong , Wu Jiae , Deng Wentao , Zou Guoqiang , Hou Hongshuai , Ji Xiaobo
Published: June 2024

We developed a separator coating incorporating nitrogen-doped carbon fibers (NCF700) positioned within the separator to establish a uniform and dense pathway for zinc ion transport and facilitate the even deposition of zinc ions.
A porous aromatic cage-based electrochemical sensor for enantioselective recognition of DOPA
Authors: Kou Junning , Zhu Ziyu , Jiang Jianzhu , Chen Li , Zhang Kunhao , Shan Guogang , Wang Xinlong , Su Zhongmin , Sun Chunyi
Published: June 2024

We prepared a C60 encapsulated porous organic cage as an electrochemical chiral sensor to exhibit efficient recognition ability for DOPA enantiomers.
Facile synthesis of CeO2-decorated W@Co-MOF heterostructures as a highly active and durable electrocatalyst for overall water splitting
Authors: Su Chang , Wang Dan , Wang Wenchang , Mitsuzaki Naotoshi , Chen Zhidong
Published: June 2024

A high-performance self-supporting and heterostructure constructed electrocatalyst is reported for HER and OER using an electrochemical deposition method for W@Co-MOF combined with CeO2 by in situ growth on nickel foam (CeO2/W@Co-MOF/NF).
Comparison of selectivity and sensitivity of various ferric selective electrodes prepared using N-((bis(dimethyl amino)methylene)carbamothioyl)benzamide
Authors: Ghaemi Mehrdad , Hajiaghababaei Leila , Najafpour Jamshid , Shahvelayati Ashraf Sadat , Tehrani Ramin M. A.
Published: June 2024

A variety of new ferric-selective potentiometric sensors were fabricated using a new ionophore and their selectivity and sensitivity were investigated experimentally and theoretically.
Water vapor effect on the physico-geometrical reaction pathway and kinetics of the multistep thermal dehydration of calcium chloride dihydrate
Authors: Kato Kazuki , Hotta Mito , Koga Nobuyoshi
Published: June 2024

Reaction pathway and kinetics of the multistep thermal dehydration behavior of inorganic hydrates are regulated by atmospheric and self-generated water vapor in a geometrically constrained reaction scheme.
Modelling molecular composition of SOA from toluene photo-oxidation at urban and street scales
Authors: Sartelet Karine , Wang Zhizhao , Lannuque Victor , Iyer Siddharth , Couvidat Florian , Sarica Thibaud
Published: June 2024

Near-explicit chemical mechanisms representing toluene SOA formation are reduced using the GENOA algorithm and used in 3D simulations of air quality over Greater Paris and in the streets of a district near Paris.