bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative technologies to assess margin status during radical prostatectomy – a narrative review
Authors: Windisch O. , Diana M. , Tilki D. , Marra G. , Martini A. , Valerio M.
Published: July 2024

Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.
Neurochemical and genetic factors in panic disorder: a systematic review
Authors: Moraes Adriana Carvalho Natal , Wijaya Clarissa , Freire Rafael , Quagliato Laiana Azevedo , Nardi Antonio Egidio , Kyriakoulis Peter
Published: July 2024

This systematic review addresses the complex nature of Panic Disorder (PD), characterized by recurrent episodes of acute fear, with a focus on updating and consolidating knowledge regarding neurochemical, genetic, and epigenetic factors associated with PD. Utilizing the PRISMA methodology, 33 original peer-reviewed studies were identified, comprising 6 studies related to human neurochemicals, 10 related to human genetic or epigenetic alterations, and 17 animal studies. The review reveals patterns of altered expression in various biological systems, including neurotransmission, the Hypothalamic-Pituitary-Adrenal (HPA) axis, neuroplasticity, and genetic and epigenetic factors leading to neuroanatomical modifications. Noteworthy findings include lower receptor binding of GABAA and serotonin neurotransmitters in the amygdala. The involvement of orexin (ORX) neurons in the dorsomedial/perifornical region in triggering panic reactions is highlighted, with systemic ORX-1 receptor antagonists blocking panic responses. Elevated Interleukin 6 and leptin levels in PD patients suggest potential connections between stress-induced inflammatory changes and PD. Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling are implicated in panic-like responses, particularly in the dorsal periaqueductal gray (dPAG), where BDNF’s panicolytic-like effects operate through GABAA-dependent mechanisms. GABAergic neurons’ inhibitory influence on dorsomedial and posterior hypothalamus nuclei is identified, potentially reducing the excitability of neurons involved in panic-like responses. The dorsomedial hypothalamus (DMH) is highlighted as a specific hypothalamic nucleus relevant to the genesis and maintenance of panic disorder. Altered brain lactate and glutamate concentrations, along with identified genetic polymorphisms linked to PD, further contribute to the intricate neurochemical landscape associated with the disorder. The review underscores the potential impact of neurochemical, genetic, and epigenetic factors on the development and expression of PD. The comprehensive insights provided by this systematic review contribute to advancing our understanding of the multifaceted nature of Panic Disorder and pave the way for targeted therapeutic strategies.
Coupling photocatalytic CO2 reduction and CH3OH oxidation for selective dimethoxymethane production
Authors: Wang Yixuan , Liu Yang , Wang Lingling , Perumal Silambarasan , Wang Hongdan , Ko Hyun , Dong Chung-Li , Zhang Panpan , Wang Shuaijun , Nga Ta Thi Thuy , Kim Young Dok , Ji Yujing , Zhao Shufang , Kim Ji-Hee , Yee Dong-Yub , Hwang Yosep , Zhang Jinqiang , Kim Min Gyu , Lee Hyoyoung
Published: July 2024

Currently, conventional dimethoxymethane synthesis methods are environmentally unfriendly. Here, we report a photo-redox catalysis system to generate dimethoxymethane using a silver and tungsten co-modified blue titanium dioxide catalyst (Ag.W-BTO) by coupling CO2 reduction and CH3OH oxidation under mild conditions. The Ag.W-BTO structure and its electron and hole transfer are comprehensively investigated by combining advanced characterizations and theoretical studies. Strikingly, Ag.W-BTO achieve a record photocatalytic activity of 5702.49 µmol g−1 with 92.08% dimethoxymethane selectivity in 9 h of ultraviolet-visible irradiation without sacrificial agents. Systematic isotope labeling experiments, in-situ diffuse reflectance infrared Fourier-transform analysis, and theoretical calculations reveal that the Ag and W species respectively catalyze CO2 conversion to *CH2O and CH3OH oxidation to *CH3O. Subsequently, an asymmetric carbon-oxygen coupling process between these two crucial intermediates produces dimethoxymethane. This work presents a CO2 photocatalytic reduction system for multi-carbon production to meet the objectives of sustainable economic development and carbon neutrality.
Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution
Authors: Dietzen Michelle , Zhai Haoran , Lucas Olivia , Pich Oriol , Barrington Christopher , Lu Wei-Ting , Ward Sophia , Guo Yanping , Hynds Robert E. , Zaccaria Simone , Swanton Charles , McGranahan Nicholas , Kanu Nnennaya
Published: July 2024

During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find that 6%–18% of the cancer genome exhibits ART, with regions with a change from early to late replication displaying an increased mutation rate and distinct mutational signatures. Whereas regions changing from late to early replication contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART occurs relatively early during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.
Pyridine-based strategies towards nitrogen isotope exchange and multiple isotope incorporation
Authors: Feng Minghao , Norlöff Maylis , Guichard Benoit , Kealey Steven , D’Anfray Timothée , Thuéry Pierre , Taran Frédéric , Gee Antony , Feuillastre Sophie , Audisio Davide
Published: July 2024

Isotopic labeling is at the core of health and life science applications such as nuclear imaging, metabolomics and plays a central role in drug development. The rapid access to isotopically labeled organic molecules is a sine qua non condition to support these societally vital areas of research. Based on a rationally driven approach, this study presents an innovative solution to access labeled pyridines by a nitrogen isotope exchange reaction based on a Zincke activation strategy. The technology conceptualizes an opportunity in the field of isotope labeling. 15N-labeling of pyridines and other relevant heterocycles such as pyrimidines and isoquinolines showcases on a large set of derivatives, including pharmaceuticals. Finally, we explore a nitrogen-to-carbon exchange strategy in order to access 13C-labeled phenyl derivatives and deuterium labeling of mono-substituted benzene from pyridine-2H5. These results open alternative avenues for multiple isotope labeling on aromatic cores.
Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation
Authors: Kon Kazuhiro , Ode Koji L. , Mano Tomoyuki , Fujishima Hiroshi , Takahashi Riina R. , Tone Daisuke , Shimizu Chika , Shiono Shinnosuke , Yada Saori , Matsuzawa Kyoko , Yoshida Shota Y. , Yoshida Garçon Junko , Kaneko Mari , Shinohara Yuta , Yamada Rikuhiro G. , Shi Shoi , Miyamichi Kazunari , Sumiyama Kenta , Kiyonari Hiroshi , Susaki Etsuo A. , Ueda Hiroki R.
Published: July 2024

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.
Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis
Authors: Jeffers Tim L. , Purvine Samuel O. , Nicora Carrie D. , McCombs Ryan , Upadhyaya Shivani , Stroumza Adrien , Whang Ken , Gallaher Sean D. , Dohnalkova Alice , Merchant Sabeeha S. , Lipton Mary , Niyogi Krishna K. , Roth Melissa S.
Published: July 2024

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (−Fe). Cells grown in −Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.
WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis
Authors: Rodríguez Pérez Fernando , Natwick Dean , Schiff Lauren , McSwiggen David , Heckert Alec , Huey Melina , Morrison Huntly , Loo Mandy , Miranda Rafael G. , Filbin John , Ortega Jose , Van Buren Kayla , Murnock Danny , Tao Arnold , Butler Renee , Cheng Kylie , Tarvestad William , Zhang Zhengjian , Gonzalez Eric , Miller Rand M. , Kelly Marcus , Tang Yangzhong , Ho Jaclyn , Anderson Daniel , Bashore Charlene , Basham Stephen
Published: July 2024

Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood. Here, we used single-molecule tracking (SMT) in combination with a WRN inhibitor to examine WRN dynamics within the nuclei of living cancer cells. WRN inhibition traps the helicase on chromatin, requiring p97/VCP for extraction and proteasomal degradation in a MSI-H dependent manner. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation. Finally, we show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells and confirm the in vivo activity of WRN inhibition using an MSI-H mouse xenograft model. This work elucidates a regulatory mechanism for WRN that may facilitate identification of new therapeutic modalities, and highlights the use of SMT as a tool for drug discovery and mechanism-of-action studies.
Recognition of anion-water clusters by peptide-based supramolecular capsules
Authors: López-Corbalán Victoria , Fuertes Alberto , Llamas-Saiz Antonio L. , Amorín Manuel , Granja Juan R.
Published: July 2024

The biological and technological importance of anion-mediated processes has made the development of improved methods for the selective recognition of anions one of the most relevant research topics today. The hydration sphere of anions plays an important role in the functions performed by anions by forming a variety of cluster complexes. Here we describe a supramolecular capsule that recognizes hydrated anion clusters. These clusters are most likely composed of three ions that form hydrated C3 symmetry complexes that are entrapped within the supramolecular capsule of the same symmetry. The capsule is made of self-assembled α,γ-cyclic peptide containing amino acid with by five-membered rings and equipped with a tris(triazolylethyl)amine cap. To recognise the hydrated anion clusters, the hexapeptide capsule must disassemble to entrap them between its two subunits.
Eye-brain connections revealed by multimodal retinal and brain imaging genetics
Authors: Zhao Bingxin , Li Yujue , Fan Zirui , Wu Zhenyi , Shu Juan , Yang Xiaochen , Yang Yilin , Wang Xifeng , Li Bingxuan , Wang Xiyao , Copana Carlos , Yang Yue , Lin Jinjie , Li Yun , Stein Jason L. , O’Brien Joan M. , Li Tengfei , Zhu Hongtu
Published: July 2024

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer’s disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.
Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma
Authors: Hering Marvin , Madi Alaa , Sandhoff Roger , Ma Sicong , Wu Jingxia , Mieg Alessa , Richter Karsten , Mohr Kerstin , Knabe Nora , Stichling Diana , Poschet Gernot , Bestvater Felix , Frank Larissa , Utikal Jochen , Umansky Viktor , Cui Guoliang
Published: July 2024

After recognizing its ligand lipopolysaccharide, Toll-like receptor 4 (TLR4) recruits adaptor proteins to the cell membrane, thereby initiating downstream signaling and triggering inflammation. Whether this recruitment of adaptor proteins is dependent solely on protein-protein interactions is unknown. Here, we report that the sphingolipid sphinganine physically interacts with the adaptor proteins MyD88 and TIRAP and promotes MyD88 recruitment in macrophages. Myeloid cell-specific deficiency in serine palmitoyltransferase long chain base subunit 2, which encodes the key enzyme catalyzing sphingolipid biosynthesis, decreases the membrane recruitment of MyD88 and inhibits inflammatory responses in in vitro bone marrow-derived macrophage and in vivo sepsis models. In a melanoma mouse model, serine palmitoyltransferase long chain base subunit 2 deficiency decreases anti-tumor myeloid cell responses and increases tumor growth. Therefore, sphinganine biosynthesis is required for the initiation of TLR4 signal transduction and serves as a checkpoint for macrophage pattern recognition in sepsis and melanoma mouse models.
MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
Authors: Sakellaropoulos Theodore , Do Catherine , Jiang Guimei , Cova Giulia , Meyn Peter , Dimartino Dacia , Ramaswami Sitharam , Heguy Adriana , Tsirigos Aristotelis , Skok Jane A.
Published: July 2024

Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover cis regulatory elements (CREs) in a 1 Mb region around every promoter in the genome. MethNet identifies clusters of highly ranked CREs, referred to as ‘hubs’, which contribute to the regulation of multiple genes and significantly affect patient survival. Promoter-capture Hi-C confirmed that highly ranked associations involve physical interactions between CREs and their gene targets, and CRISPR interference based single-cell RNA Perturb-seq validated the functional impact of CREs. Thus, MethNet-identified CREs represent a valuable resource for unraveling complex mechanisms underlying gene expression, and for prioritizing the verification of predicted non-coding disease hotspots.
A robust cis-Mendelian randomization method with application to drug target discovery
Authors: Lin Zhaotong , Pan Wei
Published: July 2024

Mendelian randomization (MR) uses genetic variants as instrumental variables (IVs) to investigate causal relationships between traits. Unlike conventional MR, cis-MR focuses on a single genomic region using only cis-SNPs. For example, using cis-pQTLs for a protein as exposure for a disease opens a cost-effective path for drug target discovery. However, few methods effectively handle pleiotropy and linkage disequilibrium (LD) of cis-SNPs. Here, we propose cisMR-cML, a method based on constrained maximum likelihood, robust to IV assumption violations with strong theoretical support. We further clarify the severe but largely neglected consequences of the current practice of modeling marginal, instead of conditional genetic effects, and only using exposure-associated SNPs in cis-MR analysis. Numerical studies demonstrated our method’s superiority over other existing methods. In a drug-target analysis for coronary artery disease (CAD), including a proteome-wide application, we identified three potential drug targets, PCSK9, COLEC11 and FGFR1 for CAD.
Maternal inheritance of functional centrioles in two parthenogenetic nematodes
Authors: Perrier Aurélien , Guiglielmoni Nadège , Naquin Delphine , Gorrichon Kevin , Thermes Claude , Lameiras Sonia , Dammermann Alexander , Schiffer Philipp H. , Brunstein Maia , Canman Julie C. , Dumont Julien
Published: July 2024

Centrioles are the core constituent of centrosomes, microtubule-organizing centers involved in directing mitotic spindle assembly and chromosome segregation in animal cells. In sexually reproducing species, centrioles degenerate during oogenesis and female meiosis is usually acentrosomal. Centrioles are retained during male meiosis and, in most species, are reintroduced with the sperm during fertilization, restoring centriole numbers in embryos. In contrast, the presence, origin, and function of centrioles in parthenogenetic species is unknown. We found that centrioles are maternally inherited in two species of asexual parthenogenetic nematodes and identified two different strategies for maternal inheritance evolved in the two species. In Rhabditophanes diutinus, centrioles organize the poles of the meiotic spindle and are inherited by both the polar body and embryo. In Disploscapter pachys, the two pairs of centrioles remain close together and are inherited by the embryo only. Our results suggest that maternally-inherited centrioles organize the embryonic spindle poles and act as a symmetry-breaking cue to induce embryo polarization. Thus, in these parthenogenetic nematodes, centrioles are maternally-inherited and functionally replace their sperm-inherited counterparts in sexually reproducing species.
Power supply disruptions deter electric vehicle adoption in cities in China
Authors: Qiu Yueming , Deng Nana , Wang Bo , Shen Xingchi , Wang Zhaohua , Hultman Nathan , Shi Han , Liu Jie , Wang Yi David
Published: July 2024

Electrification plays a crucial role in deep decarbonization. However, electrification and power infrastructure can cause mutual challenges. We use nationwide power outage and electric vehicle adoption data in China to provide empirical evidence on how power infrastructure failures can deter electrification. We find that when the number of power outages per district increases by 1 in a given month, the number of new electric vehicles adopted per month decreases by 0.99%. A doubling of power outages in one year on average across the nation can create a depressed adoption rate for up to a decade, implying a decline of more than $ 31.3 million per year in carbon reduction benefits from electric vehicle adoptions. This paper adds to the policy discussion of the costs of increased power outages due to extreme weather and natural disasters, and the urgency for policy to address this issue to facilitate wide adoption of electrification.
In situ evidence of the magnetospheric cusp of Jupiter from Juno spacecraft measurements
Authors: Xu Y. , Arridge C. S. , Yao Z. H. , Zhang B. , Ray L. C. , Badman S. V. , Dunn W. R. , Ebert R. W. , Chen J. J. , Allegrini F. , Kurth W. S. , Qin T. S. , Connerney J. E. P. , McComas D. J. , Bolton S. J. , Wei Y.
Published: July 2024

The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter’s rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures.
Necroptosis enhances ‘don’t eat me’ signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis
Authors: Liao Cheng-Yu , Li Ge , Kang Feng-Ping , Lin Cai-Feng , Xie Cheng-Ke , Wu Yong-Ding , Hu Jian-Fei , Lin Hong-Yi , Zhu Shun-Cang , Huang Xiao-Xiao , Lai Jian-Lin , Chen Li-Qun , Huang Yi , Li Qiao-Wei , Huang Long , Wang Zu-Wei , Tian Yi-Feng , Chen Shi
Published: July 2024

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.
A synthetic antibiotic class with a deeply-optimized design for overcoming bacterial resistance
Authors: Feng Jin , Zheng Youle , Ma Wanqing , Weng Defeng , Peng Dapeng , Xu Yindi , Wang Zhifang , Wang Xu
Published: July 2024

The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.
Closed magnetic topology in the Venusian magnetotail and ion escape at Venus
Authors: Xu Shaosui , Mitchell David L. , Whittlesey Phyllis , Rahmati Ali , Livi Roberto , Larson Davin , Luhmann Janet G. , Halekas Jasper S. , Hara Takuya , McFadden James P. , Pulupa Marc , Bale Stuart D. , Curry Shannon M. , Persson Moa
Published: July 2024

Venus, lacking an intrinsic global dipole magnetic field, serves as a textbook example of an induced magnetosphere, formed by interplanetary magnetic fields (IMF) enveloping the planet. Yet, various aspects of its magnetospheric dynamics and planetary ion outflows are complex and not well understood. Here we analyze plasma and magnetic field data acquired during the fourth Venus flyby of the Parker Solar Probe (PSP) mission and show evidence for closed topology in the nightside and downstream portion of the Venus magnetosphere (i.e., the magnetotail). The formation of the closed topology involves magnetic reconnection—a process rarely observed at non-magnetized planets. In addition, our study provides an evidence linking the cold Venusian ion flow in the magnetotail directly to magnetic connectivity to the ionosphere, akin to observations at Mars. These findings not only help the understanding of the complex ion flow patterns at Venus but also suggest that magnetic topology is one piece of key information for resolving ion escape mechanisms and thus the atmospheric evolution across various planetary environments and exoplanets.
Large-area magnetic skin for multi-point and multi-scale tactile sensing with super-resolution
Authors: Hu Hao , Zhang Chengqian , Lai Xinyi , Dai Huangzhe , Pan Chengfeng , Sun Haonan , Tang Daofan , Hu Zhezai , Fu Jianzhong , Li Tiefeng , Zhao Peng
Published: July 2024

The advancements in tactile sensor technology have found wide-ranging applications in robotic fields, resulting in remarkable achievements in object manipulation and overall human-machine interactions. However, the widespread availability of high-resolution tactile skins remains limited, due to the challenges of incorporating large-sized, robust sensing units and increased wiring complexity. One approach to achieve high-resolution and robust tactile skins is to integrate a limited number of sensor units (taxels) into a flexible surface material and leverage signal processing techniques to achieve super-resolution sensing. Here, we present a magnetic skin consisting of multi-direction magnetized flexible films and a contactless Hall sensor array. The key features of the proposed sensor include the specific magnetization arrangement, K-Nearest Neighbors (KNN) clustering algorithm and convolutional neural network (CNN) model for signal processing. Using only an array of 4*4 taxels, our magnetic skin is capable of achieving super-resolution perception over an area of 48400 mm2, with an average localization error of 1.2 mm. By employing neural network algorithms to decouple the multi-dimensional signals, the skin can achieve multi-point and multi-scale perception. We also demonstrate the promising potentials of the proposed sensor in intelligent control, by simultaneously controlling two vehicles with trajectory mapping on the magnetic skin.
Single crystals of purely organic free-standing two-dimensional woven polymer networks
Authors: Xiao Ding , Jin Zhitong , Sheng Guan , Chen Liya , Xiao Xuedong , Shan Tianyu , Wang Jiao , Navik Rahul , Xu Jianping , Zhou Lin , Guo Qing-Hui , Li Guangfeng , Zhu Yihan , Stoddart J. Fraser , Huang Feihe
Published: July 2024

The aesthetic and practicality of macroscopic fabrics continue to encourage chemists to weave molecules into interlaced patterns with the aim of providing emergent physical and chemical properties when compared with their starting materials. Weaving purely organic molecular threads into flawless two-dimensional patterns remains a formidable challenge, even though its feasibility has been proposed on several occasions. Herein we describe the synthesis of a flawless, purely organic, free-standing two-dimensional woven polymer network driven by dative B−N bonds. Single crystals of this woven polymer network were obtained and its well-defined woven topology was revealed by X-ray diffraction analysis. Free-standing two-dimensional monolayer nanosheets of the woven polymer network were exfoliated from the layered crystals using Scotch Magic Tape. The surface features of the nanosheets were investigated by integrated low-dose and cryogenic electron microscopy imaging techniques. These findings demonstrate the precise construction of purely organic woven polymer networks and highlight the unique opportunities for the application of woven topologies in two-dimensional organic materials.
Annual Impervious Surface Data from 2001–2020 for West African Countries: Ghana, Togo, Benin and Nigeria
Authors: Korah Andrews , Wimberly Michael C.
Published: July 2024

Impervious surface data are increasingly important for research and planning. Despite the availability of global and local urban land cover maps, regional data are lacking in Africa. We generated annual 30 m impervious cover data from 2001–2020 for Ghana, Togo, Benin, and Nigeria using the Landsat archive. We used random forest to predict impervious cover using 11 spectral indices and applied pixel-level temporal segmentation with the LandTrendr algorithm. Processing with LandTrendr improved the accuracy of the random forest predictions, with higher predicted-observed r2 (0.81), and lower mean error (−0.03), mean absolute error (5.73%), and root mean squared error (9.93%). We classified pixels >20% impervious as developed and < = 20% impervious as undeveloped. This classification had 93% overall accuracy and similar producer’s (79%) and user’s (80%) accuracies for developed area. Our maps had higher accuracy and captured more developed areas than comparable global datasets. This is the first regionally calibrated 30 m resolution impervious dataset in West Africa, which can support research on drivers and impacts of urban expansion and planning for future growth.
Genome assembly, Full-length transcriptome, and isoform diversity of Red Snapper, Lutjanus argentimaculatus
Authors: Shekhar Mudagandur S. , Katneni Vinaya Kumar , Jangam Ashok Kumar , Krishnan Karthic , Prabhudas Sudheesh K. , Jayaraman Roja , Angel Jesudhas Raymond Jani , Kailasam Muniyandi
Published: July 2024

The mangrove red snapper, Lutjanus argentimaculatus, is a marine food fish of economic and aquaculture importance. The application of genomic selection-based breeding programs for this species is limited by the absence of a reference genome and transcriptome profiles. The current study attempted to fill this void by generating genomic and transcriptomic resources for red snapper. Using PacBio long reads, and Arima Hi-C linked reads, a scaffold-level genome assembly was generated for L. argentimaculatus. The assembly is of 1.03 Gb comprising of 400 scaffolds with N50 of 33.8 Mb and was assessed to be 97.2% complete upon benchmarking with BUSCO. Full-length transcriptome generated with PacBio Iso-Sequencing strategy using six tissues (muscle, gills, liver, kidney, stomach, and gonad) contained 56,515 isoforms belonging to 18,108 unique genes with N50 length of 3,973 bp. The resources generated will have potential applications in the functional studies, conservation, broodstock management and selective breeding programmes of L. argentimaculatus.
Antifungal, antiaflatoxigenic, and cytotoxic properties of bioactive secondary metabolites derived from Bacillus species
Authors: Abdel-Nasser Aya , Badr Ahmed N. , Fathy Hayam M. , Ghareeb Mosad A. , Barakat Olfat S. , Hathout Amal S.
Published: July 2024

Aflatoxins (AFs) are hazardous carcinogens and mutagens produced by some molds, particularly Aspergillus spp. Therefore, the purpose of this study was to isolate and identify endophytic bacteria, extract and characterize their bioactive metabolites, and evaluate their antifungal, antiaflatoxigenic, and cytotoxic efficacy against brine shrimp (Artemia salina) and hepatocellular carcinoma (HepG2). Among the 36 bacterial strains isolated, ten bacterial isolates showed high antifungal activity, and thus were identified using biochemical parameters and MALDI-TOF MS. Bioactive metabolites were extracted from two bacterial isolates, and studied for their antifungal activity. The bioactive metabolites (No. 4, and 5) extracted from Bacillus cereus DSM 31T DSM, exhibited strong antifungal capabilities, and generated volatile organic compounds (VOCs) and polyphenols. The major VOCs were butanoic acid, 2-methyl, and 9,12-Octadecadienoic acid (Z,Z) in extracts No. 4, and 5 respectively. Cinnamic acid and 3,4-dihydroxybenzoic acid were the most abundant phenolic acids in extracts No. 4, and 5 respectively. These bioactive metabolites had antifungal efficiency against A. flavus and caused morphological alterations in fungal conidiophores and conidiospores. Data also indicated that both extracts No. 4, and 5 reduced AFB1 production by 99.98%. On assessing the toxicity of bioactive metabolites on A. salina the IC50 recorded 275 and 300 µg/mL, for extracts No. 4, and 5 respectively. Meanwhile, the effect of these extracts on HepG2 revealed that the IC50 of extract No. 5 recorded 79.4 µg/mL, whereas No. 4 showed no cytotoxic activity. It could be concluded that bioactive metabolites derived from Bacillus species showed antifungal and anti-aflatoxigenic activities, indicating their potential use in food safety.
Structural and sequential regularities modulate phrase-rate neural tracking
Authors: Zhao Junyuan , Martin Andrea E. , Coopmans Cas W.
Published: July 2024

Electrophysiological brain activity has been shown to synchronize with the quasi-regular repetition of grammatical phrases in connected speech—so-called phrase-rate neural tracking. Current debate centers around whether this phenomenon is best explained in terms of the syntactic properties of phrases or in terms of syntax-external information, such as the sequential repetition of parts of speech. As these two factors were confounded in previous studies, much of the literature is compatible with both accounts. Here, we used electroencephalography (EEG) to determine if and when the brain is sensitive to both types of information. Twenty native speakers of Mandarin Chinese listened to isochronously presented streams of monosyllabic words, which contained either grammatical two-word phrases (e.g., catch fish, sell house) or non-grammatical word combinations (e.g., full lend, bread far). Within the grammatical conditions, we varied two structural factors: the position of the head of each phrase and the type of attachment. Within the non-grammatical conditions, we varied the consistency with which parts of speech were repeated. Tracking was quantified through evoked power and inter-trial phase coherence, both derived from the frequency-domain representation of EEG responses. As expected, neural tracking at the phrase rate was stronger in grammatical sequences than in non-grammatical sequences without syntactic structure. Moreover, it was modulated by both attachment type and head position, revealing the structure-sensitivity of phrase-rate tracking. We additionally found that the brain tracks the repetition of parts of speech in non-grammatical sequences. These data provide an integrative perspective on the current debate about neural tracking effects, revealing that the brain utilizes regularities computed over multiple levels of linguistic representation in guiding rhythmic computation.
The Ty1 retrotransposon harbors a DNA region that performs dual functions as both a gene silencing and chromatin insulator
Authors: Masumoto Hiroshi , Muto Hideki , Yano Koichi , Kurosaki Yohei , Niki Hironori
Published: July 2024

In various eukaryotic kingdoms, long terminal repeat (LTR) retrotransposons repress transcription by infiltrating heterochromatin generated within their elements. In contrast, the budding yeast LTR retrotransposon Ty1 does not itself undergo transcriptional repression, although it is capable of repressing the transcription of the inserted genes within it. In this study, we identified a DNA region within Ty1 that exerts its silencing effect via sequence orientation. We identified a DNA region within the Ty1 group-specific antigen (GAG) gene that causes gene silencing, termed GAG silencing (GAGsi), in which the silent chromatin in the GAGsi region is created by euchromatin-specific histone modifications. A characteristic inverted repeat (IR) sequence is present at the 5' end of this region, forming a chromatin boundary between promoter-specific chromatin upstream of the IR sequence and silent chromatin downstream of the IR sequence. In addition, Esc2 and Rad57, which are involved in DNA repair, were required for GAGsi silencing. Finally, the chromatin boundary was required for the transcription of Ty1 itself. Thus, the GAGsi sequence contributes to the creation of a chromatin environment that promotes Ty1 transcription.
3D printed rectal swabs for assessing the gut microbiome, metabolome and inflammation
Authors: Perry Robert W. , Mullish Benjamin H. , Alexander James L. , Shah Raashi , Danckert Nathan P. , Blanco Jesus Miguens , Roberts Lauren , Liu Zhigang , Chrysostomou Despoina , Radhakrishnan Shiva T. , Balarajah Sharmili , Barry Rachael , Hicks Lucy C. , Williams Horace R. T. , Marchesi Julian R.
Published: July 2024

Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development. 16S rRNA gene sequencing, qPCR and metabolite profiling (using 1H-NMR spectroscopy) were performed on swab and faecal samples from healthy participants. Faecal calprotectin and total protein analysis were performed on samples from inflammatory bowel disease (IBD) patients. There were no significant differences between both swab types and faecal samples when assessing key measures of alpha and beta diversity, and differences in the abundance of major phyla. There was a strong correlation between both swab types and faecal samples for all combined metabolites detected by NMR. In IBD patients, there was no significant difference in faecal calprotectin and total protein levels between both swab types and faecal samples. These data lead us to conclude that 3D printed swabs are equivalent to flocked swabs for the analysis of the gut microbiome, metabolome and inflammation.
Universal peptide-based potential vaccine design against canine distemper virus (CDV) using a vaccinomic approach
Authors: Rendon-Marin Santiago , Ruíz-Saenz Julián
Published: July 2024

Canine distemper virus (CDV) affects many domestic and wild animals. Variations among CDV genome linages could lead to vaccination failure. To date, there are several vaccine alternatives, such as a modified live virus and a recombinant vaccine; however, most of these alternatives are based on the ancestral strain Onderstepoort, which has not been circulating for years. Vaccine failures and the need to update vaccines have been widely discussed, and the development of new vaccine candidates is necessary to reduce circulation and mortality. Current vaccination alternatives cannot be used in wildlife animals due to the lack of safety data for most of the species, in addition to the insufficient immune response against circulating strains worldwide in domestic species. Computational tools, including peptide-based therapies, have become essential for developing new-generation vaccines for diverse models. In this work, a peptide-based vaccine candidate with a peptide library derived from CDV H and F protein consensus sequences was constructed employing computational tools. The molecular docking and dynamics of the selected peptides with canine MHC-I and MHC-II and with TLR-2 and TLR-4 were evaluated. In silico safety was assayed through determination of antigenicity, allergenicity, toxicity potential, and homologous canine peptides. Additionally, in vitro safety was also evaluated through cytotoxicity in cell lines and canine peripheral blood mononuclear cells (cPBMCs) and through a hemolysis potential assay using canine red blood cells. A multiepitope CDV polypeptide was constructed, synthetized, and evaluated in silico and in vitro by employing the most promising peptides for comparison with single CDV immunogenic peptides. Our findings suggest that predicting immunogenic CDV peptides derived from most antigenic CDV proteins could aid in the development of new vaccine candidates, such as multiple single CDV peptides and multiepitope CDV polypeptides, that are safe in vitro and optimized in silico. In vivo studies are being conducted to validate potential vaccines that may be effective in preventing CDV infection in domestic and wild animals.
Spatial tumor immune microenvironment phenotypes in ovarian cancer
Authors: Mateiou Claudia , Lokhande Lavanya , Diep Lan Hoa , Knulst Mattis , Carlsson Elias , Ek Sara , Sundfeldt Karin , Gerdtsson Anna
Published: July 2024

Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and Fibronectin. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with diffuse infiltration and a high expression of STING, while endometrioid OC had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches.
Hunting indicators for community-led wildlife management in tropical Africa
Authors: Fonteyn Davy , Fayolle Adeline , Fa Julia E. , Vanthomme Hadrien , Vigneron Philippe , Vermeulen Cédric , Malignat Rémi , Konradowski Benoît , Yia Okanabene Mexan Noel , Dibotty-di Moutsing Stéphane Axel , Pereira Dias Samuel , Deniau Christophe , Cornu Guillaume , Groschêne Marion , Cornélis Daniel
Published: July 2024

Engaging local communities is pivotal for wildlife conservation beyond protected areas, aligning with the 30 × 30 target of the Kunming-Montreal Global Biodiversity Framework. We assessed the effectiveness of 33 offtake indicators, derived from hunter declarations, in monitoring the status and extent of degradation of hunted wildlife sourced from camera trap surveys and faunal composition analysis. The rodents:ungulates ratio in offtake and the mean body mass of total offtake emerged as practical and robust indicators of faunal degradation within hunting systems, with significant potential for broader application in similar tropical forest environments. Our findings provide a blueprint for managing and conserving natural resources in tropical regions through community-based initiatives. Involving local stakeholders ensures sustainable wildlife use and fosters ownership and responsibility. This study advances conservation efforts, bridging scientific rigor with community engagement for effective biodiversity preservation.
Methods and applications of noncompetitive hapten immunoassays
Authors: Du Kai , Gao Li , Li Tinghua , Rao Wei
Published: July 2024

Noncompetitive assays for haptens typically offer higher sensitivity and a broader measurement range compared to competitive assays.
Phosphate-type zwitterionic liquid
Authors: Komori Tetsuo , Hachisu Ayumi , Ninomiya Kazuaki , Takahashi Kenji , Kuroda Kosuke
Published: July 2024

The imidazolium/phosphate zwitterionic liquid synthesised in this study satisfies all properties required for efficient cellulosic bioethanol production.