bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey
Authors: Mehdi S. M. A. , Costa A. P. , Svob C. , Pan L. , Dartora W. J. , Talati A. , Gameroff M. J. , Wickramaratne P. J. , Weissman M. M. , McIntire L. B. J.
Published: March 2024

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011–2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.
Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer
Authors: Zhang Shuman , Yun Duo , Yang Hao , Eckstein Markus , Elbait Gihan Daw , Zhou Yaxing , Lu Yanxi , Yang Hai , Zhang Jinping , Dörflein Isabella , Britzen-Laurent Nathalie , Pfeffer Susanne , Stemmler Marc P. , Dahl Andreas , Mukhopadhyay Debabrata , Chang David , He Hang , Zeng Siyuan , Lan Bin , Frey Benjamin , Hampel Chuanpit , Lentsch Eva , Gollavilli Paradesi Naidu , Büttner Christian , Ekici Arif B. , Biankin Andrew , Schneider-Stock Regine , Ceppi Paolo , Grützmann Robert , Pilarsky Christian
Published: March 2024

Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.
Novel meriolin derivatives activate the mitochondrial apoptosis pathway in the presence of antiapoptotic Bcl-2
Authors: Schmitt Laura , Lechtenberg Ilka , Drießen Daniel , Flores-Romero Hector , Skowron Margaretha A. , Sekeres Marlena , Hoppe Julia , Krings Karina S. , Llewellyn Tanya R. , Peter Christoph , Stork Björn , Qin Nan , Bhatia Sanil , Nettersheim Daniel , Fritz Gerhard , García-Sáez Ana J. , Müller Thomas J. J. , Wesselborg Sebastian
Published: March 2024

Meriolin derivatives represent a new class of kinase inhibitors with a pronounced cytotoxic potential. Here, we investigated a newly synthesized meriolin derivative (termed meriolin 16) that displayed a strong apoptotic potential in Jurkat leukemia and Ramos lymphoma cells. Meriolin 16 induced apoptosis in rapid kinetics (within 2–3 h) and more potently (IC50: 50 nM) than the previously described derivatives meriolin 31 and 36 [1]. Exposure of Ramos cells to meriolin 16, 31, or 36 for 5 min was sufficient to trigger severe and irreversible cytotoxicity. Apoptosis induction by all three meriolin derivatives was independent of death receptor signaling but required caspase-9 and Apaf-1 as central mediators of the mitochondrial death pathway. Meriolin-induced mitochondrial toxicity was demonstrated by disruption of the mitochondrial membrane potential (ΔΨm), mitochondrial release of proapoptotic Smac, processing of the dynamin-like GTPase OPA1, and subsequent fragmentation of mitochondria. Remarkably, all meriolin derivatives were able to activate the mitochondrial death pathway in Jurkat cells, even in the presence of the antiapoptotic Bcl-2 protein. In addition, meriolins were capable of inducing cell death in imatinib-resistant K562 and KCL22 chronic myeloid leukemia cells as well as in cisplatin-resistant J82 urothelial carcinoma and 2102EP germ cell tumor cells. Given the frequent inactivation of the mitochondrial apoptosis pathway by tumor cells, such as through overexpression of antiapoptotic Bcl-2, meriolin derivatives emerge as promising therapeutic agents for overcoming treatment resistance.
New estimates indicate that males are not larger than females in most mammal species
Authors: Tombak Kaia J. , Hex Severine B. S. W. , Rubenstein Daniel I.
Published: March 2024

Sexual size dimorphism has motivated a large body of research on mammalian mating strategies and sexual selection. Despite some contrary evidence, the narrative that larger males are the norm in mammals—upheld since Darwin’sDescent of Man—still dominates today, supported by meta-analyses that use coarse measures of dimorphism and taxonomically-biased sampling. With newly-available datasets and primary sources reporting sex-segregated means and variances in adult body mass, we estimate statistically-determined rates of sexual size dimorphism in mammals, sampling taxa by their species richness at the family level. Our analyses of wild, non-provisioned populations representing >400 species indicate that although males tend to be larger than females when dimorphism occurs, males are not larger in most mammal species, suggesting a need to revisit other assumptions in sexual selection research.
Deep-sea hiatus record reveals orbital pacing by 2.4 Myr eccentricity grand cycles
Authors: Dutkiewicz Adriana , Boulila Slah , Dietmar Müller R.
Published: March 2024

Astronomical forcing of Earth’s climate is embedded in the rhythms of stratigraphic records, most famously as short-period (104–105 year) Milankovitch cycles. Astronomical grand cycles with periods of millions of years also modulate climate variability but have been detected in relatively few proxy records. Here, we apply spectral analysis to a dataset of Cenozoic deep-sea hiatuses to reveal a ~2.4 Myr eccentricity signal, disrupted by episodes of major tectonic forcing. We propose that maxima in the hiatus cycles correspond to orbitally-forced intensification of deep-water circulation and erosive bottom current activity, linked to eccentricity maxima and peaks in insolation and seasonality. A prominent episode of cyclicity disturbance coincides with the Paleocene-Eocene Thermal Maximum (PETM) at ~56 Myr ago, and correlates with a chaotic orbital transition in the Solar System evident in several astronomical solutions. This hints at a potential intriguing coupling between the PETM and Solar System chaos.
Liquid metals for boosting stability of zeolite catalysts in the conversion of methanol to hydrocarbons
Authors: Zhou Yong , Santos Sara , Shamzhy Mariya , Marinova Maya , Blanchenet Anne-Marie , Kolyagin Yury G. , Simon Pardis , Trentesaux Martine , Sharna Sharmin , Ersen Ovidiu , Zholobenko Vladimir L. , Saeys Mark , Khodakov Andrei Y. , Ordomsky Vitaly V.
Published: March 2024

Methanol-to-hydrocarbons (MTH) process has been considered one of the most practical approaches for producing value-added products from methanol. However, the commonly used zeolite catalysts suffer from rapid deactivation due to coke deposition and require regular regeneration treatments. We demonstrate that low-melting-point metals, such as Ga, can effectively promote more stable methanol conversion in the MTH process by slowing coke deposition and facilitating the desorption of carbonaceous species from the zeolite. The ZSM-5 zeolite physically mixed with liquid gallium exhibited an enhanced lifetime in the MTH reaction, which increased by a factor of up to ~14 as compared to the parent ZSM-5. These results suggest an alternative route to the design and preparation of deactivation-resistant zeolite catalysts.
Strategies for robust renovation of residential buildings in Switzerland
Authors: Galimshina Alina , Moustapha Maliki , Hollberg Alexander , Lasvaux Sébastien , Sudret Bruno , Habert Guillaume
Published: March 2024

Building renovation is urgently required to reduce the environmental impact associated with the building stock. Typically, building renovation is performed by envelope insulation and/or changing the fossil-based heating system. The goal of this paper is to provide strategies for robust renovation considering uncertainties on the future evolution of climate, energy grid, and user behaviors, amongst others by applying life cycle assessment and life cycle cost analysis. The study includes identifying optimal renovation options for the envelope and heating systems for building representatives from all construction periods that are currently in need of renovation in Switzerland. The findings emphasize the paramount importance of heating system replacements across all construction periods. Notably, when incorporating bio-based insulation materials, a balance emerges between environmental impact reduction and low energy operation costs. This facilitates robust, equitable, and low-carbon transformations in Switzerland and similar Northern European contexts while avoiding a carbon spike due to the embodied carbon of the renovation.
Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology
Authors: Stanley Kate E. , Jatsenko Tatjana , Tuveri Stefania , Sudhakaran Dhanya , Lannoo Lore , Van Calsteren Kristel , de Borre Marie , Van Parijs Ilse , Van Coillie Leen , Van Den Bogaert Kris , De Almeida Toledo Rodrigo , Lenaerts Liesbeth , Tejpar Sabine , Punie Kevin , Rengifo Laura Y. , Vandenberghe Peter , Thienpont Bernard , Vermeesch Joris Robert
Published: March 2024

Circulating cell-free DNA (cfDNA) fragments have characteristics that are specific to the cell types that release them. Current methods for cfDNA deconvolution typically use disease tailored marker selection in a limited number of bulk tissues or cell lines. Here, we utilize single cell transcriptome data as a comprehensive cellular reference set for disease-agnostic cfDNA cell-of-origin analysis. We correlate cfDNA-inferred nucleosome spacing with gene expression to rank the relative contribution of over 490 cell types to plasma cfDNA. In 744 healthy individuals and patients, we uncover cell type signatures in support of emerging disease paradigms in oncology and prenatal care. We train predictive models that can differentiate patients with colorectal cancer (84.7%), early-stage breast cancer (90.1%), multiple myeloma (AUC 95.0%), and preeclampsia (88.3%) from matched controls. Importantly, our approach performs well in ultra-low coverage cfDNA datasets and can be readily transferred to diverse clinical settings for the expansion of liquid biopsy.
Completing the loop of the Late Jurassic–Early Cretaceous true polar wander event
Authors: Hou Yifei , Zhao Pan , Qin Huafeng , Mitchell Ross N. , Li Qiuli , Hao Wenxing , Zhang Min , Ward Peter D. , Yuan Jie , Deng Chenglong , Zhu Rixiang
Published: March 2024

The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155–147 Myr ago (~1.5° Myr−1), immediately followed by an ~ 10° northward displacement between 147–141 Myr ago (~1.6° Myr−1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic–Cretaceous extinction and endemism.
Inhibition of urease-mediated ammonia production by 2-octynohydroxamic acid in hepatic encephalopathy
Authors: Evstafeva Diana , Ilievski Filip , Bao Yinyin , Luo Zhi , Abramovic Boris , Kang Sunghyun , Steuer Christian , Montanari Elita , Casalini Tommaso , Simicic Dunja , Sessa Dario , Mitrea Stefanita-Octavian , Pierzchala Katarzyna , Cudalbu Cristina , Armbruster Chelsie E. , Leroux Jean-Christophe
Published: March 2024

Hepatic encephalopathy is a neuropsychiatric complication of liver disease which is partly associated with elevated ammonemia. Urea hydrolysis by urease-producing bacteria in the colon is often mentioned as one of the main routes of ammonia production in the body, yet research on treatments targeting bacterial ureases in hepatic encephalopathy is limited. Herein we report a hydroxamate-based urease inhibitor, 2-octynohydroxamic acid, exhibiting improved in vitro potency compared to hydroxamic acids that were previously investigated for hepatic encephalopathy. 2-octynohydroxamic acid shows low cytotoxic and mutagenic potential within a micromolar concentration range as well as reduces ammonemia in rodent models of liver disease. Furthermore, 2-octynohydroxamic acid treatment decreases cerebellar glutamine, a product of ammonia metabolism, in male bile duct ligated rats. A prototype colonic formulation enables reduced systemic exposure to 2-octynohydroxamic acid in male dogs. Overall, this work suggests that urease inhibitors delivered to the colon by means of colonic formulations represent a prospective approach for the treatment of hepatic encephalopathy.
Neuropathogenesis-on-chips for neurodegenerative diseases
Authors: Amartumur Sarnai , Nguyen Huong , Huynh Thuy , Kim Testaverde S. , Woo Ran-Sook , Oh Eungseok , Kim Kyeong Kyu , Lee Luke P. , Heo Chaejeong
Published: March 2024

Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.
ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway
Authors: Yang Sile F. , Nelson Christopher B. , Wells Jadon K. , Fernando Madushan , Lu Robert , Allen Joshua A. M. , Malloy Lisa , Lamm Noa , Murphy Vincent J. , Mackay Joel P. , Deans Andrew J. , Cesare Anthony J. , Sobinoff Alexander P. , Pickett Hilda A.
Published: March 2024

The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.
Molecular sieving of iso-butene from C4 olefins with simultaneous high 1,3-butadiene and n-butene uptakes
Authors: Liu Junhui , Xiong Hanting , Shuai Hua , Liu Xing , Peng Yong , Wang Lingmin , Wang Pengxiang , Zhao Zhiwei , Deng Zhenning , Zhou Zhenyu , Chen Jingwen , Chen Shixia , Zeng Zheling , Deng Shuguang , Wang Jun
Published: March 2024

Iso-butene (iso-C4H8) is an important raw material in chemical industry, whereas its efficient separation remains challenging due to similar molecular properties of C4 olefins. The ideal adsorbent should possess simultaneous high uptakes for 1,3-butadiene (C4H6) and n-butene (n-C4H8) counterparts, endowing high efficiency for iso-C4H8 separation in adsorption columns. Herein, a sulfate-pillared adsorbent, SOFOUR-DPDS-Ni (DPDS = 4,4′-dipyridyldisulfide), is reported for the efficient iso-C4H8 separation from binary and ternary C4 olefin mixtures. The rigidity in pore sizes and shapes of SOFOUR-DPDS-Ni exerts the molecular sieving of iso-C4H8, while exhibiting high C4H6 and n-C4H8 uptakes. The benchmark Henry’s selectivity for C4H6/iso-C4H8 (2321.8) and n-C4H8/iso-C4H8 (233.5) outperforms most reported adsorbents. Computational simulations reveal the strong interactions for C4H6 and n-C4H8. Furthermore, dynamic breakthrough experiments demonstrate the direct production of high-purity iso-C4H8 (>99.9%) from C4H6/iso-C4H8 (50/50, v/v), n-C4H8/iso-C4H8 (50/50, v/v), and C4H6/n-C4H8/iso-C4H8 (50/15/35, v/v/v) gas-mixtures.
Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia
Authors: Koshiyama Daisuke , Nishimura Ryoichi , Usui Kaori , Fujioka Mao , Tada Mariko , Kirihara Kenji , Araki Tsuyoshi , Kawakami Shintaro , Okada Naohiro , Koike Shinsuke , Yamasue Hidenori , Abe Osamu , Kasai Kiyoto
Published: March 2024

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.
A biogeographical appraisal of the threatened South East Africa Montane Archipelago ecoregion
Authors: Bayliss Julian , Bittencourt-Silva Gabriela B. , Branch William R. , Bruessow Carl , Collins Steve , Congdon T. Colin E. , Conradie Werner , Curran Michael , Daniels Savel R. , Darbyshire Iain , Farooq Harith , Fishpool Lincoln , Grantham Geoffrey , Magombo Zacharia , Matimele Hermenegildo , Monadjem Ara , Monteiro Jose , Osborne Jo , Saunders Justin , Smith Paul , Spottiswoode Claire N. , Taylor Peter J. , Timberlake Jonathan , Tolley Krystal A. , Tovela Érica , Platts Philip J.
Published: March 2024

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the ‘South East Africa Montane Archipelago’ (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains’ great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)—one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.
Integrative methods reveal multiple drivers of diversification in rice paddy snakes
Authors: Bernstein Justin M. , Voris Harold K. , Stuart Bryan L. , Karns Daryl R. , McGuire Jimmy A. , Iskandar Djoko T. , Riyanto Awal , Calderón-Acevedo Camilo A. , Brown Rafe M. , Gehara Marcelo , Soto-Centeno J. Angel , Ruane Sara
Published: March 2024

Divergence dating analyses in systematics provide a framework to develop and test biogeographic hypotheses regarding speciation. However, as molecular datasets grow from multilocus to genomic, sample sizes decrease due to computational burdens, and the testing of fine-scale biogeographic hypotheses becomes difficult. In this study, we use coalescent demographic models to investigate the diversification of poorly known rice paddy snakes from Southeast Asia (Homalopsidae:Hypsiscopus), which have conflicting dates of origin based on previous studies. We use coalescent modeling to test the hypothesis thatHypsiscopusdiversified 2.5 mya during the Khorat Plateau uplift in Thailand. Additionally, we use ecological niche analyses to identify potential differences in the niche space of the two most widely distributed species in the past and present. Our results suggestHypsiscopusdiversified ~ 2.4 mya, supporting that the Khorat Plateau may have initiated the diversification of rice paddy snakes. We also find significant niche differentiation and shifts between species ofHypsiscopus, indicating that environmental differences may have sustained differentiation of this genus after the Khorat Plateau uplift. Our study expands on the diversification history of snakes in Southeast Asia, and highlights how results from smaller multilocus datasets can be useful in developing and testing biogeographic hypotheses alongside genomic datasets.
Production and characterization of rhamnolipids by Pseudomonas aeruginosa isolated in the Amazon region, and potential antiviral, antitumor, and antimicrobial activity
Authors: Cerqueira dos Santos Sidnei , Araújo Torquato Chayenna , de Alexandria Santos Darlisson , Orsato Alexandre , Leite Karoline , Serpeloni Juliana Mara , Losi-Guembarovski Roberta , Romão Pereira Erica , Dyna André Luiz , Lopes Barboza Mario Gabriel , Fernandes Arakawa Matheus Hideki , Pires Bitencourt José Augusto , da Cruz Silva Sebastião , da Silva Sá Giulian César , Dias Rodrigues Pamela , Quintella Cristina Maria , Faccin-Galhardi Lígia Carla
Published: March 2024

Biosurfactants encompass structurally and chemically diverse molecules with surface active properties, and a broad industrial deployment, including pharmaceuticals. The interest is growing mainly for the low toxicity, biodegradability, and production from renewable sources. In this work, the optimized biosurfactant production by Pseudomonas aeruginosa BM02, isolated from the soil of a mining area in the Brazilian Amazon region was assessed, in addition to its antiviral, antitumor, and antimicrobial activities. The optimal conditions for biosurfactant production were determined using a factorial design, which showed the best yield (2.28 mg/mL) at 25 °C, pH 5, and 1% glycerol. The biosurfactant obtained was characterized as a mixture of rhamnolipids with virucidal properties against Herpes Simplex Virus, Coronavirus, and Respiratory Syncytial Virus, in addition to antimicrobial properties against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecium), at 50 µg/mL. The antitumor activity of BS (12.5 µg/mL) was also demonstrated, with potential selectivity in reducing the proliferation of breast tumor cells, after 1 min of exposure. These results demonstrate the importance of studying the interconnection between cultivation conditions and properties of industrially important compounds, such as rhamnolipid-type biosurfactant from P. aeruginosa BM02, a promising and sustainable alternative in the development of new antiviral, antitumor, and antimicrobial prototypes.
The use of NADH anisotropy to investigate mitochondrial cristae alignment
Authors: Smith Holly. E. , Mackenzie Alasdair M. , Seddon Chloe , Mould Rhys , Kalampouka Ifi , Malakar Partha , Needham Sarah R. , Beis Konstantinos , Bell Jimmy D. , Nunn Alistair , Botchway Stanley W.
Published: March 2024

Life may be expressed as the flow of electrons, protons, and other ions, resulting in large potential difference. It is also highly photo-sensitive, as a large proportion of the redox capable molecules it relies on are chromophoric. It is thus suggestive that a key organelle in eukaryotes, the mitochondrion, constantly adapt their morphology as part of the homeostatic process. Studying unstained in vivo nano-scale structure in live cells is technically very challenging. One option is to study a central electron carrier in metabolism, reduced nicotinamide adenine dinucleotide (NADH), which is fluorescent and mostly located within mitochondria. Using one and two-photon absorption (340–360 nm and 730 nm, respectively), fluorescence lifetime imaging and anisotropy spectroscopy of NADH in solution and in live cells, we show that mitochondria do indeed appear to be aligned and exhibit high anisotropy (asymmetric directionality). Aqueous solution of NADH showed an anisotropy of ~ 0.20 compared to fluorescein or coumarin of < 0.1 and 0.04 in water respectively and as expected for small organic molecules. The anisotropy of NADH also increased further to 0.30 in the presence of proteins and 0.42 in glycerol (restricted environment) following two-photon excitation, suggesting more ordered structures. Two-photon NADH fluorescence imaging of Michigan Cancer Foundation-7 (MCF7) also showed strong anisotropy of 0.25 to 0.45. NADH has a quantum yield of fluorescence of 2% compared to more than 40% for photoionisation (electron generation), when exposed to light at 360 nm and below. The consequence of such highly ordered and directional NADH patterns with respect to electron ejection upon ultra-violet (UV) excitation could be very informative—especially in relation to ascertaining the extent of quantum effects in biology, including electron and photonic cascade, communication and modulation of effects such as spin and tunnelling.
Impairments in the early consolidation of spatial memories via group II mGluR agonism in the mammillary bodies
Authors: Milczarek Michal M. , Perry James C. , Amin Eman , Haniffa Salma , Hathaway Thomas , Vann Seralynne D.
Published: March 2024

mGluR2 receptors are widely expressed in limbic brain regions associated with memory, including the hippocampal formation, retrosplenial and frontal cortices, as well as subcortical regions including the mammillary bodies. mGluR2/3 agonists have been proposed as potential therapeutics for neurological and psychiatric disorders, however, there is still little known about the role of these receptors in cognitive processes, including memory consolidation. To address this, we assessed the effect of the mGluR2/3 agonist, eglumetad, on spatial memory consolidation in both mice and rats. Using the novel place preference paradigm, we found that post-sample injections of eglumetad impaired subsequent spatial discrimination when tested 6 h later. Using the immediate early gene c-fos as a marker of neural activity, we showed that eglumetad injections reduced activity in a network of limbic brain regions including the hippocampus and mammillary bodies. To determine whether the systemic effects could be replicated with more targeted manipulations, we performed post-sample infusions of the mGluR2/3 agonist 2R,4R-APDC into the mammillary bodies. This impaired novelty discrimination on a place preference task and an object-in-place task, again highlighting the role of mGluR2/3 transmission in memory consolidation and demonstrating the crucial involvement of the mammillary bodies in post-encoding processing of spatial information.
Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases
Authors: Kahraman Seda , Karakaya Serdar , Kaplan Muhammed Ali , Goksu Sema Sezgin , Ozturk Akin , Isleyen Zehra Sucuoglu , Hamdard Jamshid , Yildirim Sedat , Dogan Tolga , Isik Selver , Celebi Abdussamet , Gulbagci Burcu Belen , Paksoy Nail , Dogan Mutlu , Turk Haci Mehmet , Bilici Ahmet , Tatli Ali Murat , Akbas Sinem , Turan Nedim , Hacibekiroglu Ilhan , Dogu Gamze Gokoz , Aydiner Adnan , Sumbul Ahmet Taner , Akyurek Serap , Yalciner Merih , Demirkazik Ahmet , Gursoy Pinar , Aykan Musa Baris , Sahin Elif , Karadag İbrahim , Kostek Osman , Er Muhammed Muhiddin , Artaç Mehmet , Duzkopru Yakup , Aydin Dincer , Isik Deniz , Karakas Yusuf , Kilickap Saadettin , Erol Cihan , Demir Bilgin , Civelek Burak , Ergun Yakup , Akinci Muhammed Bulent , Dogan Izzet , Karadurmus Nuri , Yumuk Perran Fulden , Sendur Mehmet Ali Nahit
Published: March 2024

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood–brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10–14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8–22.2). The median overall survival (OS) was 29 months (95% CI, 25.2–33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.
Electrochemical determination of ascorbic acid using palladium supported on N-doped graphene quantum dot modified electrode
Authors: Mohammadnezhad K. , Ahour F. , Keshipour S.
Published: March 2024

To precise screening concentration of ascorbic acid (AA), a novel electrochemical sensor was prepared using palladium nanoparticles decorated on nitrogen-doped graphene quantum dot modified glassy carbon electrode (PdNPs@N-GQD/GCE). For this purpose, nitrogen doped GQD nanoparticles (N-GQD) were synthesized from a citric acid condensation reaction in the presence of ethylenediamine and subsequently modified by palladium nanoparticles (PdNPs). The electrochemical behavior of AA was investigated, in which the oxidation peak appeared at 0 V related to the AA oxidation. Considering the synergistic effect of Pd nanoparticles as an active electrocatalyst, and N-GQD as an electron transfer accelerator and electrocatalytic activity improving agent, PdNPs@N-GQD hybrid materials showed excellent activity in the direct oxidation of AA. In the optimal conditions, the voltammetric response was linear in the range from 30 to 700 nM and the detection limit was calculated to be 23 nM. The validity and the efficiency of the proposed sensor were successfully tested and confirmed by measuring AA in real samples of chewing tablets, and fruit juice.
Two bits dual-band switchable terahertz absorber enabled by composite graphene and vanadium dioxide metamaterials
Authors: Barzegar-Parizi Saeedeh , Ebrahimi Amir , Ghorbani Kamran
Published: March 2024

This article presents the design of a 2-bit dual-band switchable terahertz absorber using a stacked combination of graphene and vanadium dioxide (VO2) metamaterials. For the first time, the proposed absorber design offers four switchable states by controlling the conductivity of graphene and VO2 metamaterial layers. The lower absorption band is produced by the graphene metamaterial, whereas the upper band is implemented by the VO2 metamaterial pattern. The structure shows two absorption bands (State 11) at 0.745–0.775 THz and 2.3–5.63 THz, when the Fermi graphene level of graphene is 0.2 eV and the VO2 is in the metallic phase. The lower absorption band is turned off, while keeping the upper band (State 01), when the graphene Fermi level is 0 eV and the VO2 layer is in the metallic phase. The upper absorption band is turned off, while preserving the lower absorption band (State 10) by switching the VO2 into the insulator phase and keeping the graphene Fermi level at 0.2 eV. Finally, both of the absorption bands are turned off by setting the graphene Fermi level to 0 eV and switching the VO2 into the insulating phase. Equivalent circuit modelling analysis and full-wave electromagnetic simulations are used to explain the operation principle of the proposed absorber. Very good agreement is obtained between the theoretical analysis and the simulations confirming the presented design principle for the 2-bit switchable absorber.
Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients
Authors: Thanapirom Kessarin , Treeprasertsuk Sombat , Choudhury Ashok , Verma Nipun , Dhiman Radha Krishan , Al Mahtab Mamun , Devarbhavi Harshad , Shukla Akash , Hamid Saeed Sadiq , Jafri Wasim , Tan Soek Siam , Lee Guan H. , Ghazinyan Hasmik , Sood Ajit , Kim Dong Joon , Eapen C. E. , Tao Han , Yuemin Nan , Dokmeci A. Kadir , Sahu Manoj , Arora Anil , Kumar Ashish , Kumar Ramesh , Prasad V. G. Mohan , Shresta Ananta , Sollano Jose , Payawal Diana Alcantara , Lau George , Sarin Shiv Kumar
Published: March 2024

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.
Machine learning study using 2020 SDHS data to determine poverty determinants in Somalia
Authors: Hassan Abdirizak A. , Muse Abdisalam Hassan , Chesneau Christophe
Published: March 2024

Extensive research has been conducted on poverty in developing countries using conventional regression analysis, which has limited prediction capability. This study aims to address this gap by applying advanced machine learning (ML) methods to predict poverty in Somalia. Utilizing data from the first-ever 2020 Somalia Demographic and Health Survey (SDHS), a cross-sectional study design is considered. ML methods, including random forest (RF), decision tree (DT), support vector machine (SVM), and logistic regression, are tested and applied using R software version 4.1.2, while conventional methods are analyzed using STATA version 17. Evaluation metrics, such as confusion matrix, accuracy, precision, sensitivity, specificity, recall, F1 score, and area under the receiver operating characteristic (AUROC), are employed to assess the performance of predictive models. The prevalence of poverty in Somalia is notable, with approximately seven out of ten Somalis living in poverty, making it one of the highest rates in the region. Among nomadic pastoralists, agro-pastoralists, and internally displaced persons (IDPs), the poverty average stands at 69%, while urban areas have a lower poverty rate of 60%. The accuracy of prediction ranged between 67.21% and 98.36% for the advanced ML methods, with the RF model demonstrating the best performance. The results reveal geographical region, household size, respondent age group, husband employment status, age of household head, and place of residence as the top six predictors of poverty in Somalia. The findings highlight the potential of ML methods to predict poverty and uncover hidden information that traditional statistical methods cannot detect, with the RF model identified as the best classifier for predicting poverty in Somalia.
Spatiotemporal heterogeneity in meteorological and hydrological drought patterns and propagations influenced by climatic variability, LULC change, and human regulations
Authors: Li Yunyun , Huang Yi , Li Yanchun , Zhang Hongxue , Fan Jingjing , Deng Qian , Wang Xuemei
Published: March 2024

This study aims to quantify meteorological–hydrological drought propagations and examine the potential impacts by climatic variability, LULC change (LULC), and human regulations. An integrated observation-modeling framework quantifies drought propagation intervals and assesses mechanisms influencing hydrological droughts. Meteorological droughts are characterized using the Standardized Precipitation Evapotranspiration Index (SPEI), and hydrological droughts are assessed through the Standardized Streamflow Index (SSI) across diverse climatic zones. Cross-correlation analysis between SPEI and SSI time series identifies the lag time associated with the highest correlation as the drought propagation interval. Mechanisms are investigated via a coupled empirical-process modeling framework incorporating the Soil and Water Assessment Tool (SWAT). Discrepancies between simulated and observed SSI time series help quantify the extent of human regulation impacts on hydrological drought characteristics and propagation. The Yellow River Basin (YRB), divided into six subzones based on climate characteristics, is selected as the case study. Key findings include: (1) Meteorological droughts were extremely severe across most YRB during the 1990s, while the 2000s showed some mitigation primarily due to precipitation increases. (2) Hydrological droughts and propagation times from meteorology to hydrology demonstrated substantial spatiotemporal variability. In general, summer propagation times were shorter than other seasons. (3) Propagation times were shorter in arid regions with cropland or built-up land cover versus grassland and woodland, while the reverse held for humid regions. (4) Human regulations prolonged propagation times, likely due to reservoir regulations designed to overcome water deficits. While the YRB is the focus of this paper, the methodologies and findings are applicable to other regions worldwide to enhance drought forecasting and water resource management. In various hydrological and climatic contexts worldwide.
Tapping into the human spinal locomotor centres with transspinal stimulation
Authors: Skiadopoulos Andreas , Knikou Maria
Published: March 2024

Human locomotion is controlled by spinal neuronal networks of similar properties, function, and organization to those described in animals. Transspinal stimulation affects the spinal locomotor networks and is used to improve standing and walking ability in paralyzed people. However, the function of locomotor centers during transspinal stimulation at different frequencies and intensities is not known. Here, we document the 3D joint kinematics and spatiotemporal gait characteristics during transspinal stimulation at 15, 30, and 50 Hz at sub-threshold and supra-threshold stimulation intensities. We document the temporal structure of gait patterns, dynamic stability of joint movements over stride-to-stride fluctuations, and limb coordination during walking at a self-selected speed in healthy subjects. We found that transspinal stimulation (1) affects the kinematics of the hip, knee, and ankle joints, (2) promotes a more stable coordination at the left ankle, (3) affects interlimb coordination of the thighs, and (4) intralimb coordination between thigh and foot, (5) promotes greater dynamic stability of the hips, (6) increases the persistence of fluctuations in step length variability, and lastly (7) affects mechanical walking stability. These results support that transspinal stimulation is an important neuromodulatory strategy that directly affects gait symmetry and dynamic stability. The conservation of main effects at different frequencies and intensities calls for systematic investigation of stimulation protocols for clinical applications.
Transcranial direct current stimulation suggests a causal role of the medial prefrontal cortex in learning social hierarchy
Authors: Qu Chen , Huang Yulong , Philippe Rémi , Cai Shenggang , Derrington Edmund , Moisan Frédéric , Shi Mengke , Dreher Jean-Claude
Published: March 2024

Social hierarchies can be inferred through observational learning of social relationships between individuals. Yet, little is known about the causal role of specific brain regions in learning hierarchies. Here, using transcranial direct current stimulation, we show a causal role of the medial prefrontal cortex (mPFC) in learning social versus non-social hierarchies. In a Training phase, participants acquired knowledge about social and non-social hierarchies by trial and error. During a Test phase, they were presented with two items from hierarchies that were never encountered together, requiring them to make transitive inferences. Anodal stimulation over mPFC impaired social compared with non-social hierarchy learning, and this modulation was influenced by the relative social rank of the members (higher or lower status). Anodal stimulation also impaired transitive inference making, but only during early blocks before learning was established. Together, these findings demonstrate a causal role of the mPFC in learning social ranks by observation.
Mineral oil emulsion species and concentration prediction using multi-output neural network based on fluorescence spectra in the solar-blind UV band
Authors: Gong Bowen , Mao Shilei , Li Xinkai , Chen Bo
Published: March 2024

The accurate monitoring of oil spills is crucial for effective oil spill recovery, volume determination, and cleanup.
3D printing nacre powder/sodium alginate scaffold loaded with PRF promotes bone tissue repair and regeneration
Authors: Liu Bin , Hu Cewen , Huang Xinyue , Qin Kaiqi , Wang Lei , Wang Zhilong , Liang Jiachen , Xie Fuqiang , Fan Zengjie
Published: March 2024

A 3D printed bionic trabecular bone scaffold based on nacre powder and sodium alginate is used for skull regeneration, and platelet-rich fibrin accelerates bone repair.
Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy
Authors: Zhang Hui-Feng , Yu Huan , Pan Shuang-Xue , Zhang Chuang , Ma Ying-Hui , Zhang Yan-Fei , Zuo Li-Li , Hao Cheng-Yi , Lin Xiao-Ying , Geng Hao , Wu Di , Mu Shang-Qiang , Yu Wei-Lun , Shi Nian-Qiu
Published: March 2024

We co-modified R9 and iNGR on the liposome surface to obtain Lip-mbPDS. The penetration of Lip-mbPDS into multiple biointerfaces has enabled it to demonstrate good anti-tumor ability for CD13-positive HT1080 cells both in vivo and ex vivo.
Optimization of lipid assisted polymeric nanoparticles for siRNA delivery and cancer immunotherapy
Authors: Lin Song , Jing Houjin , Du Xiaojiao , Yang Xianzhu , Wang Jun
Published: March 2024

A siRNA delivery system was developed using clinically approved mPEG-b-PLGA, cationic lipid and ionizable lipid for siRNA delivery and cancer immunotherapy.
Multi-task scattering-model classification and parameter regression of nanostructures from small-angle scattering data
Authors: Yildirim Batuhan , Doutch James , Cole Jacqueline M.
Published: March 2024

Machine learning (ML) can be employed at the data-analysis stage of small-angle scattering (SAS) experiments.