bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting pleuro-alveolar junctions reverses lung fibrosis in mice
Authors: Fischer Adrian , Han Wei , Hu Shaoping , Mück-Häusl Martin , Wannemacher Juliane , Kadri Safwen , Lin Yue , Dai Ruoxuan , Christ Simon , Su Yiqun , Dasgupta Bikram , Sardogan Aydan , Deisenhofer Christoph , Dutta Subhasree , Kadri Amal , Güney Tankut Gökhan , Correa-Gallegos Donovan , Mayr Christoph H. , Hatz Rudolf , Stoleriu Mircea Gabriel , Lindner Michael , Hilgendorff Anne , Adler Heiko , Machens Hans-Günther , Schiller Herbert B. , Hauck Stefanie M. , Rinkevich Yuval
Published: January 2025

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium. The PAJ niche and the disassembly cascade is active in patient lung biopsies, persists in chronic fibrosis models, and wanes down in acute fibrosis models. Pleural-specific viral therapeutic carrying the cysteine protease inhibitor Cystatin A shuts down PAJ disassembly, reverses fibrosis and regenerates chronic fibrotic lungs. Targeting PAJ disassembly by targeting the pleura may provide a unique therapeutic avenue to treat lung fibrotic diseases.
Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface
Authors: Angelova Dafina M. , Tsolova Aleksandra , Prater Malwina , Ballasy Noura , Bacon Wendi , Hamilton Russell S. , Blackwell Danielle , Yu Ziyi , Li Xin , Liu Xin , Hemberger Myriam , Charnock-Jones D. Stephen
Published: January 2025

The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points. We show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the Syncytiotrophoblast-I lineage, initially share similar trajectories. Importantly, our functional analysis of one such lineage precursor marker, CXADR, demonstrates that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease.
Preservation of organic carbon in marine sediments sustained by sorption and transformation processes
Authors: Babakhani Peyman , Dale Andrew W. , Woulds Clare , Moore Oliver W. , Xiao Ke-Qing , Curti Lisa , Peacock Caroline L.
Published: January 2025

Controls on organic carbon preservation in marine sediments remain controversial but crucial for understanding past and future climate dynamics. Here we develop a conceptual-mathematical model to determine the key processes for the preservation of organic carbon. The model considers the major processes involved in the breakdown of organic carbon, including dissolved organic carbon hydrolysis, mixing, remineralization, mineral sorption and molecular transformation. This allows redefining of burial efficiency as preservation efficiency, which considers both particulate organic carbon and mineral-phase organic carbon. We show that preservation efficiency is almost three times higher than the conventionally defined burial efficiency and reconciles predictions with global field data. Kinetic sorption and transformation are the dominant controls on organic carbon preservation. We conclude that a synergistic effect between kinetic sorption and molecular transformation (geopolymerization) creates a mineral shuttle in which mineral-phase organic carbon is protected from remineralization in the surface sediment and released at depth. The results explain why transformed organic carbon persists over long timescales and increases with depth.
Bacteria use exogenous peptidoglycan as a danger signal to trigger biofilm formation
Authors: Vaidya Sanika , Saha Dibya , Rode Daniel K. H. , Torrens Gabriel , Hansen Mads F. , Singh Praveen K. , Jelli Eric , Nosho Kazuki , Jeckel Hannah , Göttig Stephan , Cava Felipe , Drescher Knut
Published: January 2025

For any organism, survival is enhanced by the ability to sense and respond to threats in advance. For bacteria, danger sensing among kin cells has been observed, but the presence or impacts of general danger signals are poorly understood. Here we show that different bacterial species use exogenous peptidoglycan fragments, which are released by nearby kin or non-kin cell lysis, as a general danger signal. Using microscopy and gene expression profiling of Vibrio cholerae, we find that even brief signal exposure results in a regulatory response that causes three-dimensional biofilm formation, which protects cells from a broad range of stresses, including bacteriophage predation. A diverse set of species (Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis) also respond to exogenous peptidoglycan by forming biofilms. As peptidoglycan from different Gram-negative and Gram-positive species triggered three-dimensional biofilm formation, we propose that this danger signal and danger response are conserved among bacteria.
Interfacial water confers transcription factors with dinucleotide specificity
Authors: Morgunova Ekaterina , Nagy Gabor , Yin Yimeng , Zhu Fangjie , Nayak Sonali Priyadarshini , Xiao Tianyi , Sokolov Ilya , Popov Alexander , Laughton Charles , Grubmuller Helmut , Taipale Jussi
Published: January 2025

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins. The dinucleotides were recognized either enthalpically, by an extensive water network that connects the adjacent bases to the TF, or entropically, by a hydrophobic patch that maintained interfacial water mobility. This mechanism confers differential temperature sensitivity to the optimal sites, with implications for thermal regulation of gene expression. Our results uncover the enigma of how TFs can recognize more complex local features than mononucleotides and demonstrate that water-mediated recognition is important for predicting affinities of macromolecules from their sequence.
Biological, environmental, and psychological stress and the human gut microbiome in healthy adults
Authors: Delgadillo Desiree R. , Borelli Jessica L. , Mayer Emeran A. , Labus Jennifer S. , Cross Marie P. , Pressman Sarah D.
Published: January 2025

Emerging research suggests that the gut microbiome plays a crucial role in stress. We assess stress-microbiome associations in two samples of healthy adults across three stress domains (perceived stress, stressful life events, and biological stress /Respiratory Sinus Arrhythmia; RSA). Study 1 (n = 62; mean-age = 37.3 years; 68% female) and Study 2 (n = 74; mean-age = 41.6 years; female only) measured RSA during laboratory stressors and used 16S rRNA pyrosequencing to classify gut microbial composition from fecal samples. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to predict functional pathways of metagenomes. Results showed differences in beta diversity between high and low stressful life events groups across both studies. Study 1 revealed differences in beta diversity between high and low RSA groups. In Study 1, the low perceived stress group was higher in alpha diversity than the high perceived stress group. Levels of Clostridium were negatively associated with RSA in Study 1 and levels Escherichia/Shigella were positively associated with perceived stress in Study 2. Associations between microbial functional pathways (L-lysine production and formaldehyde absorption) and RSA are discussed. Findings suggest that certain features of the gut microbiome are differentially associated with each stress domain.
Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases
Authors: Mravinacová Sára , Bergström Sofia , Olofsson Jennie , de San José Nerea Gómez , Anderl-Straub Sarah , Diehl-Schmid Janine , Fassbender Klaus , Fliessbach Klaus , Jahn Holger , Kornhuber Johannes , Landwehrmeyer G. Bernhard , Lauer Martin , Levin Johannes , Ludolph Albert C. , Prudlo Johannes , Schneider Anja , Schroeter Matthias L. , Wiltfang Jens , Steinacker Petra ,   FTLD Consortium, Otto Markus , Nilsson Peter , Månberg Anna
Published: January 2025

Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer’s disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins—neurofilament medium and myelin basic protein—showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.
Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns
Authors: Strobel Matthew R. , Zhou Yuxin , Qiu Liyan , Hofer Aldebaran M. , Chen Xuanmao
Published: January 2025

The primary cilium is a hair-like organelle that hosts molecular machinery for various developmental and homeostatic signaling pathways. Its alteration can cause rare ciliopathies such as the Bardet-Biedl and Joubert syndromes, but is also linked to Alzheimer’s disease, clinical depression, and autism spectrum disorder. These afflictions are caused by disturbances in a wide variety of genes but a common phenotype amongst them is cognitive impairment. While cilia-mediated neural function has been widely examined in early neurodevelopment, their function in the adult brain is not well understood. To help elucidate the role of cilia in neural activity, we temporally induced the ablation of IFT88, a gene encoding the intraflagellar transport 88 protein which is neccessary for ciliogenesis, in adult mice before performing memory-related behavioral assays and electroencephalogram/electromyogram (EEG/EMG) recordings. Inducible IFT88 KO mice exhibited severe learning deficits in trace fear conditioning and Morris water maze tests. They had strongly affected brainwave activity both under isoflurane induced anesthesia and during normal activity. And additionally, inducible IFT88 KO mice had altered sleep architecture and attenuated phase-amplitude coupling, a process that underlies learning and memory formation. These results highlight the growing significance of primary cilia for healthy neural function in the adult brain.
Crowd counting in domain generalization based on multi-scale attention and hierarchy level enhancement
Authors: Zhou Jiarui , Zhang Jianming , Gui Yan
Published: January 2025

In order to solve the problem of weak single domain generalization ability in existing crowd counting methods, this study proposes a new crowd counting framework called Multi-scale Attention and Hierarchy level Enhancement (MAHE). Firstly, the model can focus on both the detailed features and the macro information of structural position changes through the fusion of channel attention and spatial attention. Secondly, the addition of multi-head attention feature module facilitates the model’s capacity to effectively capture complex dependency relationships between sequence elements. In addition, the three-stage encoding and decoding processing mode enables the model to effectively represent crowd density information. Finally, the fusion of multi-scale features derived from different receptive fields is further enhanced through multi-scale hierarchy level feature fusion, thereby enabling the model to learn high-level semantic information and low-level multi-scale visual field feature information. This method enhances the model’s capacity to capture key feature information, even in highly differentiated datasets, thereby improving the model’s generalization ability on a single domain. The model has demonstrated strong generalization capabilities through extensive experiments on different datasets. This study not only improves the accuracy of crowd counting, but also introduces a new research approach for single domain generalization of crowd counting.
The appropriate nutrient conditions for methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro
Authors: Vávrová Pavlína , Janďourek Ondřej , Diepoltová Adéla , Nachtigal Petr , Konečná Klára
Published: January 2025

Polymicrobial biofilms, the reason for most chronic wound infections, play a significant role in increasing antibiotic resistance. The in vivo effectiveness of the new anti-biofilm therapy is conditioned by the profound evaluation using appropriate in vitro biofilm models. Since nutrient availability is crucial for in vitro biofilm formation, this study is focused on the impact of four selected cultivation media on the properties of methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilms. To reflect the wound environment, Tryptic soy broth, RPMI 1640 with and without glucose, and Lubbock medium were supplemented with different amounts of host effector molecules present in human plasma or sheep red blood cells. The study demonstrates that the Lubbock medium provided the most appropriate amount of nutrients regarding the biomass structure and the highest degree of tolerance to selected antimicrobials with the evident contribution of the biofilm matrix. Our results allow the rational employment of nutrition conditions within methicillin-resistant Staphylococcus aureus and Candida albicans dual-species biofilm formation in vitro for preclinical research. Additionally, one of the potential targets of a complex antibiofilm strategy, carbohydrates, was revealed since they are prevailing molecules in the matrices regardless of the cultivation media.
Trabecular meshwork ultrastructural changes in primary and secondary glaucoma
Authors: Rao Aparna , Rao Tirupathi , Banka Nagapriya , Senthil Sirisha , Jaketi Saumya
Published: January 2025

To examine ultrastructural changes in the trabecular meshwork (TM) in patients with primary and secondary glaucoma using scanning electron microscopy (SEM). This was a qualitative descriptive hospital-based study on the ultrastructure of the TM. Pure TM samples were collected after microincisional trabeculectomy from 26 patients with primary or secondary glaucoma and 10 control samples from eye bank donor corneas. SEM was used to analyze structural changes in the TM beams, corneoscleral meshwork (CSM), and juxtacanalicular (JCT) regions. Morphological features were compared between groups and correlated with histopathological findings. SEM revealed flattened and broadened TM beams in the JCT, resembling controls, often with a dumbbell configuration. Histopathological examination (HPE) and SEM showed rounded TM beams with considerable thinning, especially in primary angle-closure glaucoma (PACG), compared to primary open-angle (POAG) and pseudoexfoliation glaucoma (XFG). Maximum thinning in all primary glaucoma occurred in the CSM region, with minimal changes in the JCT region despite a reduction in cellularity in both regions. In steroid glaucoma, amorphous, glistening material was found on the TM beams in the JCT and CSM. XFG eyes displayed vesicular bodies adjacent to fibrillar material scattered diffusely over the TM beams, particularly in the CSM, differing from the platelet clumps seen in regular blood clots. TM beam thinning in primary glaucoma primarily affects the CSM region, sparing the JCT region. Amorphous deposits or vesicular bodies, seen only in steroid-induced glaucoma and XFG, suggest different mechanisms of TM damage in these glaucoma types.
Patterns of object play behaviour and its functional implications in free-flying common ravens
Authors: Bapat Awani , Kempf Anna E. , Friry Salomé , Boucherie Palmyre H. , Bugnyar Thomas
Published: January 2025

Object play has been proposed to provide individuals with information about their environment, facilitating foraging skills and tool use. In species where object play co-occurs with locomotor or social play, it may have additional functional implications, such as facilitating the evaluation of peers or forming social bonds. For instance, ravens judge others’ competitiveness via play caching and engage in social play by exchanging objects. However, most raven studies were conducted on a restricted number of individuals and under controlled captive settings. To validate these findings and to gauge the functional scope of object play under field conditions, we investigated the patterns and characteristics of object play in individually marked free-flying ravens in the Austrian Alps. Using two large data sets, we show a decrease in object play with age and a preference for playing longer with novel objects, supporting findings from captivity. We also find adults occasionally playing with objects and no difference in the duration of social or non-social object play bouts across age classes. Taken together, our findings are in line with the assumption that raven object play likely has more than one function and serves to gain information about the individual’s physical and social environment.
Narrative mobile video game-based cognitive training to enhance frontal function in patients with mild cognitive impairment
Authors: Choi Yeseul , Lim Jae-Sung , Choi Hagyun , Ryu Yong Hoe , Seong Eunkyung , Park Inseok , Kang Dong Won , Lee Jae-Hong , Kang Dong-Wha
Published: January 2025

Although cognitive training has been proposed as a possible therapeutic modality for mild cognitive impairment (MCI), most serious games focus on specific tasks. This study aimed to investigate the feasibility and efficacy of narrative video game-based cognitive intervention for MCI. A four-week (± 1-week) mobile game intervention was given to 17 MCI participants (mean age (SD) = 72.8(4.75)). At baseline and post-intervention, the participants received neuropsychological tests and a depression scale. Frontal function was assessed using the Corsi block-tapping test, Color Word Stroop Test, Controlled Oral Word Association Test, Digit Symbol Coding, and Trail Making Test-Elderly’s Version; depression was assessed using the Geriatric Depression Scale. User’s compliance and gaming experience were also evaluated. MCI patients showed significant improvements in frontal function, particularly in Digit Symbol Coding (mean ± SD, 0.47 ± 0.49, p = 0.007) and phonemic fluency (mean ± SD, 0.39 ± 0.55, p = 0.024). Each frontal subtest’s mean z-score was increased (mean ± SD, 0.44 ± 0.38, p = 0.008). Block span and depression scale remained unchanged. High adherence rates (122.35%) and favorable feedback on the gaming experience indicated that the game intervention’s usability boosted patients’ motivation and engagement. Our findings demonstrate that narrative game-based cognitive intervention was not only beneficial but also enjoyable for elderly MCI.
Brain-model neural similarity reveals abstractive summarization performance
Authors: Zhang Zhejun , Guo Shaoting , Zhou Wenqing , Luo Yingying , Zhu Yingqi , Zhang Lin , Li Lei
Published: January 2025

Deep language models (DLMs) have exhibited remarkable language understanding and generation capabilities, prompting researchers to explore the similarities between their internal mechanisms and human language cognitive processing. This study investigated the representational similarity (RS) between the abstractive summarization (ABS) models and the human brain and its correlation to the performance of ABS tasks. Specifically, representational similarity analysis (RSA) was used to measure the similarity between the representational patterns (RPs) of the BART, PEGASUS, and T5 models’ hidden layers and the human brain’s language RPs under different spatiotemporal conditions. Layer-wise ablation manipulation, including attention ablation and noise addition was employed to examine the hidden layers’ effect on model performance. The results demonstrate that as the depth of hidden layers increases, the models’ text encoding becomes increasingly similar to the human brain’s language RPs. Manipulating deeper layers leads to more substantial decline in summarization performance compared to shallower layers, highlighting the crucial role of deeper layers in integrating essential information. Notably, the study confirms the hypothesis that the hidden layers exhibiting higher similarity to human brain activity play a more critical role in model performance, with their correlations reaching statistical significance even after controlling for perplexity. These findings deepen our understanding of the cognitive mechanisms underlying language representations in DLMs and their neural correlates, potentially providing insights for optimizing and improving language models by aligning them with the human brain’s language-processing mechanisms.
Spectral optimization of supercontinuum shaping using metaheuristic algorithms, a comparative study
Authors: Hary Mathilde , Koivisto Teemu , Lukasik Sara , Dudley John M. , Genty Goëry
Published: January 2025

Supercontinuum generation in optical fiber involves complex nonlinear dynamics, making optimization challenging, and typically relying on trial-and-error or extensive numerical simulations. Machine learning and metaheuristic algorithms offer more efficient optimization approaches. We report here an experimental study of supercontinuum spectral shaping by tuning the phase of the input pulses, different optimization approaches including a genetic algorithm, particle swarm optimizer, and simulated annealing. We find that the genetic algorithm and particle swarm optimizer are more robust and perform better, with the particle swarm optimizer converging faster. Our study provides valuable insights for the systematic optimization of supercontinuum and other optical sources.
A novel deep synthesis-based insider intrusion detection (DS-IID) model for malicious insiders and AI-generated threats
Authors: Kotb Hazem M. , Gaber Tarek , AlJanah Salem , Zawbaa Hossam M. , Alkhathami Mohammed
Published: January 2025

Insider threats pose a significant challenge to IT security, particularly with the rise of generative AI technologies, which can create convincing fake user profiles and mimic legitimate behaviors. Traditional intrusion detection systems struggle to differentiate between real and AI-generated activities, creating vulnerabilities in detecting malicious insiders. To address this challenge, this paper introduces a novel Deep Synthesis Insider Intrusion Detection (DS-IID) model. The model employs deep feature synthesis to automatically generate detailed user profiles from event data and utilizes binary deep learning for accurate threat identification. The DS-IID model addresses three key issues: it (i) detects malicious insiders using supervised learning, (ii) evaluates the effectiveness of generative algorithms in replicating real user profiles, and (iii) distinguishes between real and synthetic abnormal user profiles. To handle imbalanced data, the model uses on-the-fly weighted random sampling. Tested on the CERT insider threat dataset, the DS-IID achieved 97% accuracy and an AUC of 0.99. Moreover, the model demonstrates strong performance in differentiating real from AI-generated (synthetic) threats, achieving over 99% accuracy on optimally generated data. While primarily evaluated on synthetic datasets, the high accuracy of the DS-IID model suggests its potential as a valuable tool for real-world cybersecurity applications.
Future food prices will become less sensitive to agricultural market prices and mitigation costs
Authors: Chen David Meng-Chuen , Bodirsky Benjamin , Wang Xiaoxi , Xuan Jiaqi , Dietrich Jan Philipp , Popp Alexander , Lotze-Campen Hermann
Published: January 2025

Agricultural production costs represent less than half of total food prices for higher-income countries and will likely further decrease globally. Added-value components such as transport, processing, marketing and catering show increasing importance in food value chains, especially as countries undergo a nutrition transition towards more complex and industrial food systems. Here, using a combined statistical and process-based modelling framework, we derive and project the value-added component of food prices for 136 countries and 11 different food groups, for food-at-home and food-away-from-home. We identify the declining but differentiated producer share in consumer food prices across food products, and provide scenarios of future consumer prices under a business-as-usual as well as climate mitigation scenarios. Food price increases from policies targeting agricultural producers, such as greenhouse gas taxes, are not as stark when transmitted to consumers owing to higher value added in higher-income countries, while a pronounced effect remains in lower-income countries, even in coming decades.
Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer
Authors: Ganguli Piyali , Basanta Celia C. , Acha-Sagredo Amelia , Misetic Hrvoje , Armero Maria , Mendez Akram , Zahra Aeman , Devonshire Ginny , Kelly Gavin , Freeman Adam , Green Mary , Nye Emma , Bichisecchi Anita , Bonfanti Paola ,   Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Fitzgerald Rebecca C. , Edwards Paul A. W. , Grehan Nicola , Nutzinger Barbara , Redmond Aisling M. , Loreno Christine , Abbas Sujath , Freeman Adam , Smyth Elizabeth C. , O’Donovan Maria , Miremadi Ahmad , Malhotra Shalini , Tripathi Monika , Coles Hannah , Millington Curtis , Eldridge Matthew , Secrier Maria , Devonshire Ginny , Davies Jim , Crichton Charles , Carroll Nick , Hardwick Richard H. , Safranek Peter , Hindmarsh Andrew , Sujendran Vijayendran , Hayes Stephen J. , Ang Yeng , Sharrocks Andrew , Preston Shaun R. , Bagwan Izhar , Save Vicki , Skipworth Richard J. E. , Hupp Ted R. , O’Neill J. Robert , Tucker Olga , Beggs Andrew , Taniere Philippe , Puig Sonia , Contino Gianmarco , Underwood Timothy J. , Walker Robert C. , Grace Ben L. , Lagergren Jesper , Gossage James , Davies Andrew , Chang Fuju , Mahadeva Ula , Goh Vicky , Ciccarelli Francesca D. , Sanders Grant , Berrisford Richard , Chan David , Cheong Ed , Kumar Bhaskar , Sreedharan L. , Parsons Simon L. , Soomro Irshad , Kaye Philip , Saunders John , Lovat Laurence , Haidry Rehan , Scott Michael , Sothi Sharmila , Lishman Suzy , Hanna George B. , Peters Christopher J. , Moorthy Krishna , Grabowska Anna , Turkington Richard , McManus Damian , Coleman Helen , Petty Russell D. , Bartlett Freddie , Rodriguez-Justo Manuel , Spencer Jo , Fitzgerald Rebecca C. , Ciccarelli Francesca D.
Published: January 2025

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data. Despite its cancer driver role, CDKN2A loss in BE prevents EAC initiation by counterselecting subsequent TP53 alterations. 9p21 gene co-deletions predict poor patient survival in EAC but not BE through context-dependent effects on cell cycle, oxidative phosphorylation and interferon response. Immune quantifications using bulk transcriptome, RNAscope and high-dimensional tissue imaging showed that IFNE loss reduces immune infiltration in BE, but not EAC. Mechanistically, CDKN2A loss suppresses the maintenance of squamous epithelium, contributing to a more aggressive phenotype. Our study demonstrates context-dependent roles of cancer genes during disease evolution, with consequences for cancer detection and patient management.
Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation
Authors: Estephan Hala , Tailor Arun , Parker Robert , Kreamer McKenzie , Papandreou Ioanna , Campo Leticia , Easton Alistair , Moon Eui Jung , Denko Nicholas C , Ternette Nicola , Hammond Ester M , Giaccia Amato J
Published: January 2025

Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.e., the immunopeptidome). Hypoxia decreases MHC-I expression in an oxygen-dependent manner, via activation of autophagy through the PERK arm of the unfolded protein response. Using an immunopeptidomics-based LC-MS approach, we find a significant reduction of presented antigens under hypoxia. Inhibition of autophagy under hypoxia enhances antigen presentation. In experimental tumors, reducing mitochondrial metabolism through a respiratory complex-I inhibitor increases tumor oxygenation, as well as MHC-I levels and the immunopeptidome. These data explain the molecular basis of tumor immune evasion in hypoxic conditions, and have implications for future therapeutic interventions targeting hypoxia-induced alterations in antigen presentation.
Cohesin positions the epigenetic reader Phf2 within the genome
Authors: Tang Wen , Costantino Lorenzo , Stocsits Roman , Wutz Gordana , Ladurner Rene , Hudecz Otto , Mechtler Karl , Peters Jan-Michael
Published: January 2025

Genomic DNA is assembled into chromatin by histones, and extruded into loops by cohesin. These mechanisms control important genomic functions, but whether histones and cohesin cooperate in genome regulation is poorly understood. Here we identify Phf2, a member of the Jumonji-C family of histone demethylases, as a cohesin-interacting protein. Phf2 binds to H3K4me3 nucleosomes at active transcription start sites (TSSs), but also co-localizes with cohesin. Cohesin depletion reduces Phf2 binding at sites lacking H3K4me3, and depletion of Wapl and CTCF re-positions Phf2 together with cohesin in the genome, resulting in the accumulation of both proteins in chromosomal regions called vermicelli and cohesin islands. Conversely, Phf2 depletion reduces cohesin binding at TSSs lacking CTCF and decreases the number of short cohesin loops, while increasing the length of heterochromatic B compartments. These results suggest that Phf2 is an ‘epigenetic reader’, which is translocated through the genome by cohesin-mediated DNA loop extrusion, and which recruits cohesin to active TSSs and limits the size of B compartments. These findings reveal an unexpected degree of cooperativity between epigenetic and architectural mechanisms of eukaryotic genome regulation.
Partitioning of fatty acids between membrane and storage lipids controls ER membrane expansion
Authors: Lysyganicz Pawel K , Barbosa Antonio D , Khondker Shoily , Stewart Nicolas A , Carman George M , Stansfeld Phillip J , Dymond Marcus K , Siniossoglou Symeon
Published: January 2025

Biogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane. Phospholipid diacylglycerol acyltransferases (PDATs) use endogenous phospholipids as fatty-acyl donors to generate triglyceride stored in lipid droplets. The significance of this non-canonical triglyceride biosynthesis pathway has remained elusive. We find that the activity of the yeast PDAT Lro1 is regulated by a membrane-proximal helical segment facing the luminal side of the ER bilayer. To reveal the biological roles of PDATs, we engineered an Lro1 variant with derepressed activity. We show that active Lro1 mediates retraction of ER membrane expansion driven by phospholipid synthesis. Furthermore, subcellular distribution and membrane turnover activity of Lro1 are controlled by diacylglycerol produced by the activity of Pah1, a conserved member of the lipin family. Collectively, our findings reveal a lipid-metabolic network that regulates endoplasmic reticulum biogenesis by converting phospholipids into storage lipids.
Nuclear PD-L1 triggers tumour-associated inflammation upon DNA damage
Authors: Nihira Naoe T , Wu Wenwen , Hosoi Mitsue , Togashi Yukiko , Sunada Shigeaki , Miyoshi Yasuo , Miki Yoshio , Ohta Tomohiko
Published: January 2025

Immune checkpoint inhibitors against PD-1/PD-L1 are highly effective in immunologically hot tumours such as triple-negative breast cancer, wherein constitutive DNA damage promotes inflammation, while inducing PD-L1 expression to avoid attack by cytotoxic T cells. However, whether and how PD-L1 regulates the DNA damage response and inflammation remains unclear. Here, we show that nuclear PD-L1 activates the ATR-Chk1 pathway and induces proinflammatory chemocytokines upon genotoxic stress. PD-L1 interacts with ATR and is essential for Chk1 activation and chromatin binding. cGAS-STING and NF-κB activation in the late phase of the DNA damage response is inhibited by PD-L1 deletion or by inhibitors of ATR and Chk1. Consequently, the induction of proinflammatory chemocytokines at this stage is inhibited by deletion of PD-L1, but restored by the ATR activator Garcinone C. Inhibition of nuclear localisation by PD-L1 mutations or the HDAC2 inhibitor Santacruzamate A inhibits chemocytokine induction. Conversely, the p300 inhibitor C646, which accelerates PD-L1 nuclear localisation, promotes chemocytokine induction. These findings suggest that nuclear PD-L1 strengthens the properties of hot tumours and contributes to shaping the tumour microenvironment.
High order expression dependencies finely resolve cryptic states and subtypes in single cell data
Authors: Jansma Abel , Yao Yuelin , Wolfe Jareth , Del Debbio Luigi , Beentjes Sjoerd V , Ponting Chris P , Khamseh Ava
Published: January 2025

Single cells are typically typed by clustering into discrete locations in reduced dimensional transcriptome space. Here we introduce Stator, a data-driven method that identifies cell (sub)types and states without relying on cells’ local proximity in transcriptome space. Stator labels the same single cell multiply, not just by type and subtype, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order gene expression dependencies from a sparse gene-by-cell expression matrix. Stator’s finer resolution is clear from analyses of mouse embryonic brain, and human healthy or diseased liver. Rather than only coarse-scale labels of cell type, Stator further resolves cell types into subtypes, and these subtypes into stages of maturity and/or cell cycle phases, and yet further into portions of these phases. Among cryptically homogeneous embryonic cells, for example, Stator finds 34 distinct radial glia states whose gene expression forecasts their future GABAergic or glutamatergic neuronal fate. Further, Stator’s fine resolution of liver cancer states reveals expression programmes that predict patient survival. We provide Stator as a Nextflow pipeline and Shiny App.
Development of a portable gas chromatograph–mass spectrometer embedded with a low-temperature adsorption thermal desorption module for enhanced detection of volatile organic compounds
Authors: Chen Yulin , Qiu Junwei , Xu Kai , Zhu Huijun , Zhang Shuo , Lu Xinxin , Li Xiaoxu
Published: January 2025

A low-temperature adsorption thermal desorption system was developed, and the sensitivity of low-boiling substances was improved by 11–17 times compared to ambient-temperature adsorption thermal desorption module.
Experimental approaches to evaluate solid lipid nanoparticle-based drug delivery systems
Authors: Talele Paurnima , Jadhav Anand , Sahu Saugata , Shimpi Navinchandra
Published: January 2025

Solid lipid nanoparticles (SLNs) are potential drug carriers due to the several advantages they offer.
Simultaneous determination of naphthalimide-labelled monosaccharides in P. cyrtonema Hua. polysaccharides utilizing the HPLC-UV technique
Authors: Du Jiao , Zhou Xue , Chen Leijing , Xu Liang , Wang Bin
Published: January 2025

4-Amidogen-1,8-naphthalimide (ANA) is a novel pre-column derivatization reagent that enables sensitive HPLC analysis of monosaccharide composition in P. cyrtonema Hua polysaccharides (PCPs), demonstrating its potential for quality control TCM.
Detecting CYP2C19 genes through an integrated CRISPR/Cas13a-assisted system
Authors: Mai Zhaokang , Zhou Tao , Lin Zhun
Published: January 2025

A platform integrating PCR reaction and CRISPR/Cas13a detection of three CYP2C19 genotypes on a device based on magnetic beads of three different sizes, achieving rapid, sensitive, and specific detection.
Research on a molecularly imprinted electrochemical sensor based on a graphene quantum dot-gold nanoparticle composite for the determination of 17β-estradiol
Authors: Yuan Wei , Wang Yipeng , Jiang Meng , Jin Yan , Yan Wen , Wang Qingyu , Niu Lingmei
Published: January 2025

In this study, a molecularly imprinted electrochemical sensor was constructed based on the graphene quantum dots-gold nanoparticles and it was successfully applied in the ultrasenstitive detection of 17β-estradiol.
A novel fluorescent probe for rapid and selective detection of fluoride ions in living cells
Authors: Feng Tingting , Yang Jiaxue , Wang Yi , Hu Taozhu , Yan Longjia , Le Yi , Liu Li
Published: January 2025

DTP specifically recognizes F− and allows for quantitative analysis in buffer solutions. In cellular imaging, DTP releases red fluorescence upon F− recognition, enabling the visualization of fluoride within HepG2 cells.
Anti-inflammatory and osteoconductive multi-functional nanoparticles for the regeneration of an inflamed alveolar bone defect
Authors: Jeong Hyewoo , Subramanian Keerthana , Lee Jong-Bin , Byun Hayeon , Shin Heungsoo , Yun Jeong-Ho
Published: January 2025

Anti-inflammatory, osteogenic nanoparticles (TMPs) promoted tissue regeneration in compromised tooth-extraction sockets of a canine model, offering insight for clinical applications.
Electrochemistry-enabled Ir-catalyzed C–H/N–N bond activation facilitates [3+2] annulation of phenidones with propiolates
Authors: Zhao LuLu , Yang Jianjing , Yan Kelu , Cheng Xingda , Xiao Ziyang , Wen Jiangwei
Published: January 2025

The study focuses on the development of a mild and efficient [3+2] annulation of phenidones with propiolates to access N-substituted indole alkylamides by merging electrochemistry and iridium catalysis in an undivided cell at room temperature.
Recent progress in electrochemical recycling of waste NdFeB magnets
Authors: Xu Xuan , Jia Xiaozheng , Zhao Kunyuan , Xu Peng , Jing Peng , Liu Baocang , Zhang Jun
Published: January 2025

Electrochemical recycling of waste NdFeB magnets through molten salt electrolysis and room-temperature electrolysis.
Facile synthesis of 2-sulfonylbenzothiazoles via cascade SO2−–NCS addition and S–C(sp2) coupling
Authors: Liu Wenjie , Zhang Xuehui , Wu Qian , Dong Zhi-Bing , Bi Xiaojing , Shi Enxue
Published: January 2025

Concurrent installation of benzothiazole and sulfone motifs. Readily available starting materials with diverse structures. Rapid conversions under environmentally mild conditions. High yields mainly through simple column-free purifications.
The swelling-induced fractionation strategy to mediate cellulose availability and lignin structural integrity
Authors: Tian Dong , Zhang Yu , Wang Tingjiao , Jiang Baiheng , Liu Miao , Zhao Li , Hu Jinguang , Shen Fei
Published: January 2025

This work realizes facile bagasse fractionation using choline hydroxide based alkaline deep eutectic solvents. Its swelling effect could balance the seesaw between cellulose availability and lignin structural integrity.
Dynamic restructuring of electrocatalysts in the activation of small molecules: challenges and opportunities
Authors: Wu Hsiwen , Zhang Jie
Published: January 2025

Structural transformation of electrocatalyst contributes to its catalytic activity and selectivity. Properly guided and stabilized transformation offers enhanced catalyst performance, while unregulated surface reconstruction may lead to deactivation.
Recent developments in pillar[5]arene-based nanomaterials for cancer therapy
Authors: Dai Yu , Yu Wenqiang , Cheng Yushan , Zhou Yao , Zou Jiaye , Meng Yujia , Chen Feiyu , Qian Yihan , Yao Yong
Published: January 2025

In this review, we summarize five different types of pillar[5]arene-based nanomaterials and their applications in chemotherapy, photodynamic therapy, photothermal therapy, and multimodal synergistic therapy for tumors.
Polyhydroxy starch with abundant hydroxyls and a unique structure enables uniform Zn deposition
Authors: Song Ming , Guo Zhaohe , Xu Yan , Mo Xueyao , Xu Xuena , Sun Limei , Tan Wenyi , Chao Dongliang , Zhou Wanhai
Published: January 2025

Starch, characterized by abundant hydroxyl groups and unique structural properties, reconstructs the H-bond system and promotes uniform Zn deposition. The side reactions and Zn dendrites have been inhibited.
Growth and properties of Pr-doped PMNT single crystals
Authors: Yang Chen , Guan Mingzhu , Chen Xin , Liao Fan , Sun Zhigang
Published: January 2025

Pr-doped 0.70Pb(Mg1/3Nb2/3)O3–0.30PbTiO3 (PMNT:Pr) single crystals are grown with the seed-guided Bridgman method.
B2C3N monolayers with high theoretical capacity as anode materials for lithium-ion batteries: first-principles calculations
Authors: Zou Yutong , She Yaqi , Zhao Liuxu , Liu Ailing , Sun Bo , Jiang Yuhong , Kou Chunlei , Zhang Miao , Tian Yuanye
Published: January 2025

Design of novel graphene-like B2C3N as a promising candidate for high-performance anode materials in lithium-ion batteries via first-principles calculations.
Field-dependent relaxation profiles of biomolecular systems
Authors: Kubrak Adam , Pejanovic Rajka , Kamau Kahinga , Kruk Danuta , Ferrage Fabien , Parigi Giacomo
Published: January 2025

The field dependence of the NMR relaxation rates offers the possibility to probe dynamic processes over a wide range of time scales.
Engineering the multifunctionality of Li3Y3Te2O12 garnets with Sm3+ and Tb3+ activators for solid-state lighting and luminescence thermometry
Authors: Bindhu Amrithakrishnan , Naseemabeevi Jawahar I. , Ganesanpotti Subodh
Published: January 2025

Tuning the photophysical response of Li3Y3Te2O12 garnet based on Sm3+ and Tb3+ activators for solid-state lighting and luminescence thermometry.
Vapour phase deposition of phosphonate-containing alumina thin films using dimethyl vinylphosphonate as precursor
Authors: Peñaranda Juan Santo Domingo , Dhara Arpan , Chalishazar Aditya , Minjauw Matthias M. , Dendooven Jolien , Detavernier Christophe
Published: January 2025

Atomic layer deposition of phosphonate-containing films using dimethyl vinylphosphonate (DMVP) as the phosphonate precursor.
Visible-light-induced CO-releasing properties and cytotoxicity of a Ru(ii) carbonyl complex containing 2-(pyridin-2-yl)-quinoxaline
Authors: Khaled Rabaa M. , Abo-Elfadl Mahmoud T. , Radacki Krzysztof , Abo Zeid Mona A. M. , Shehab Ola R. , Abdel-Kader Nora S. , Mostafa Gamal A. E. , Ali Essam A. , Al Neyadi Shaikha S. , Mansour Ahmed M.
Published: January 2025

The cell viability, mechanism of cell dealth, and genotoxic effect of the photoactivatable dicarbonyl Ru(ii) complex of 2-(pyridin-2-yl)quinoxaline were investigated in dark and upon exposure to 468 nm.
Cyclometalated Au(iii) complexes with alkynylphosphine oxide ligands: synthesis and photophysical properties
Authors: Luginin Maksim , Snetkov Dmitry , Sizova Anastasia , Paderina Aleksandra , Sizov Vladimir , Grachova Elena
Published: January 2025

The linker between the CC donor site and the phosphine oxide controls the photophysical properties of cyclometallic Au(iii) complexes decorated with alkynylphosphine oxides in solution and in the solid state.
Statistical assessment of an atmospheric mercury passive sampler at a regional site in South Africa
Authors: Job Xoliswa E. V. , Jaars Kerneels , van Zyl Pieter G. , MacSween Katrina , Bredenkamp Liezl , Josipovic Miroslav , Martin Lynwill G. , Vakkari Ville , Kulmala Markku , Laakso Lauri
Published: January 2025

This study evaluates the Mercury Passive Air Sampler (MerPAS®) as a cost-effective alternative to active sampling for atmospheric mercury monitoring at the Welgegund atmospheric measurement station in South Africa.
A review on environmental contamination of petroleum hydrocarbons, its effects and remediation approaches
Authors: Majeed Bzhwen Khalid , Shwan Dler M.S , Rashid Khasraw Abdullah
Published: January 2025

This review provides valuable insights into environmental contamination caused by petroleum hydrocarbons and contributes to the development of effective remediation strategies.
Development and evaluation of hydrogen peroxide mediated zinc oxide photocatalytic nanoparticles from Peepal (Ficus Religiosa) leaf extract for the treatment of actual tannery wastewater
Authors: Govindasamy Ganeshkumar , Ponnusami Arjunan Babu
Published: January 2025

Our findings offer insight into the impact of ZnO nanoparticles produced from Ficus Religiosa leaf extract on photocatalytic degradation of tannery wastewater.
Active learning assists chemical intuition identify a scalable conversion of chitin to 3-acetamido-5-acetylfuran
Authors: Pereira Juliana G. , Ravasco João M. J. M. , Bustillo Latimah , Marques Inês S. , Kao Po-Yu , Li Po-Yi , Lin Yen-Chu , Rodrigues Tiago , Bonifácio Vasco D. B. , Peixoto Andreia F. , Afonso Carlos A. M. , Gomes Rafael F. A.
Published: January 2025

This work leverages active learning to optimize 3A5AF synthesis, yielding up to 72% from NAG and 10 mg g−1 from shrimp shells. The method uses reusable commercial ionic liquids as solvent, leading to improved green metrics and ease of implementation.