bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution
Authors: Liu Xuechao , Yu Jing , Li Yi , Shi Hailei , Jiao Xuelong , Liu Xiaodong , Guo Dong , Li Zequn , Tian Yulong , Dai Fan , Niu Zhaojian , Zhou Yanbing
Published: March 2024

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.
Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants
Authors: Jaumdally S. , Tomasicchio M. , Pooran A. , Esmail A. , Kotze A. , Meier S. , Wilson L. , Oelofse S. , van der Merwe C. , Roomaney A. , Davids M. , Suliman T. , Joseph R. , Perumal T. , Scott A. , Shaw M. , Preiser W. , Williamson C. , Goga A. , Mayne E. , Gray G. , Moore P. , Sigal A. , Limberis J. , Metcalfe J. , Dheda K.
Published: March 2024

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10μm and <5μm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5μm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.
Reconciling ice core CO2 and land-use change following New World-Old World contact
Authors: King Amy C. F. , Bauska Thomas K. , Brook Edward. J. , Kalk Mike , Nehrbass-Ahles Christoph , Wolff Eric. W. , Strawson Ivo , Rhodes Rachael H. , Osman Matthew B.
Published: March 2024

Ice core records of carbon dioxide (CO2) throughout the last 2000 years provide context for the unprecedented anthropogenic rise in atmospheric CO2 and insights into global carbon cycle dynamics. Yet the atmospheric history of CO2 remains uncertain in some time intervals. Here we present measurements of CO2 and methane (CH4) in the Skytrain ice core from 1450 to 1700 CE. Results suggest a sudden decrease in CO2 around 1610 CE in one widely used record may be an artefact of a small number of anomalously low values. Our analysis supports a more gradual decrease in CO2 of 0.5 ppm per decade from 1516 to 1670 CE, with an inferred land carbon sink of 2.6 PgC per decade. This corroborates modelled scenarios of large-scale reorganisation of land use in the Americas following New World-Old World contact, whereas a rapid decrease in CO2 at 1610 CE is incompatible with even the most extreme land-use change scenarios.
A programmable hybrid digital chemical information processor based on the Belousov-Zhabotinsky reaction
Authors: Sharma Abhishek , Ng Marcus Tze-Kiat , Parrilla Gutierrez Juan Manuel , Jiang Yibin , Cronin Leroy
Published: March 2024

The exponential growth of the power of modern digital computers is based upon the miniaturization of vast nanoscale arrays of electronic switches, but this will be eventually constrained by fabrication limits and power dissipation. Chemical processes have the potential to scale beyond these limits by performing computations through chemical reactions, yet the lack of well-defined programmability limits their scalability and performance. Here, we present a hybrid digitally programmable chemical array as a probabilistic computational machine that uses chemical oscillators using Belousov-Zhabotinsky reaction partitioned in interconnected cells as a computational substrate. This hybrid architecture performs efficient computation by distributing information between chemical and digital domains together with inbuilt error correction logic. The efficiency is gained by combining digital logic with probabilistic chemical logic based on nearest neighbour interactions and hysteresis effects. We demonstrated the computational capabilities of our hybrid processor by implementing one- and two-dimensional Chemical Cellular Automata demonstrating emergent dynamics of life-like entities called Chemits. Additionally, we demonstrate hybrid probabilistic logic as a viable logic for solving combinatorial optimization problems.
Sustained growth of sulfur hexafluoride emissions in China inferred from atmospheric observations
Authors: An Minde , Prinn Ronald G. , Western Luke M. , Zhao Xingchen , Yao Bo , Hu Jianxin , Ganesan Anita L. , Mühle Jens , Weiss Ray F. , Krummel Paul B. , O’Doherty Simon , Young Dickon , Rigby Matthew
Published: March 2024

Sulfur hexafluoride (SF6) is a potent greenhouse gas. Here we use long-term atmospheric observations to determine SF6 emissions from China between 2011 and 2021, which are used to evaluate the Chinese national SF6 emission inventory and to better understand the global SF6 budget. SF6 emissions in China substantially increased from 2.6 (2.3-2.7, 68% uncertainty) Gg yr−1 in 2011 to 5.1 (4.8-5.4) Gg yr−1 in 2021. The increase from China is larger than the global total emissions rise, implying that it has offset falling emissions from other countries. Emissions in the less-populated western regions of China, which have potentially not been well quantified in previous measurement-based estimates, contribute significantly to the national SF6 emissions, likely due to substantial power generation and transmission in that area. The CO2-eq emissions of SF6 in China in 2021 were 125 (117-132) million tonnes (Mt), comparable to the national total CO2 emissions of several countries such as the Netherlands or Nigeria. The increasing SF6 emissions offset some of the CO2 reductions achieved through transitioning to renewable energy in the power industry, and might hinder progress towards achieving China’s goal of carbon neutrality by 2060 if no concrete control measures are implemented.
Polymer-acid-metal quasi-ohmic contact for stable perovskite solar cells beyond a 20,000-hour extrapolated lifetime
Authors: Luo Junsheng , Liu Bowen , Yin Haomiao , Zhou Xin , Wu Mingjian , Shi Hongyang , Zhang Jiyun , Elia Jack , Zhang Kaicheng , Wu Jianchang , Xie Zhiqiang , Liu Chao , Yuan Junyu , Wan Zhongquan , Heumueller Thomas , Lüer Larry , Spiecker Erdmann , Li Ning , Jia Chunyang , Brabec Christoph J. , Zhao Yicheng
Published: March 2024

The development of a robust quasi-ohmic contact with minimal resistance, good stability and cost-effectiveness is crucial for perovskite solar cells. We introduce a generic approach featuring a Lewis-acid layer sandwiched between dopant-free semicrystalline polymer and metal electrode in perovskite solar cells, resulting in an ideal quasi-ohmic contact even at elevated temperature up to 85 °C. The solubility of Lewis acid in alcohol facilitates nondestructive solution processing on top of polymer, which boosts hole injection from polymer into metal by two orders of magnitude. By integrating the polymer-acid-metal structure into solar cells, devices exhibit remarkable resilience, retaining 96% ± 3%, 96% ± 2% and 75% ± 7% of their initial efficiencies after continuous operation in nitrogen at 35 °C for 2212 h, 55 °C for 1650 h and 85 °C for 937 h, respectively. Leveraging the Arrhenius relation, we project an impressive T80 lifetime of 26,126 h at 30 °C.
Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
Authors: Xu Chanjuan , Zhou Yiwei , Liu Yuxuan , Lin Li , Liu Peng , Wang Xiaomei , Xu Zhengyuan , Pin Jean-Philippe , Rondard Philippe , Liu Jianfeng
Published: March 2024

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria
Authors: Junk Lukas , Schmiedel Volker M. , Guha Somraj , Fischel Katharina , Greb Peter , Vill Kristin , Krisilia Violetta , van Geelen Lasse , Rumpel Klaus , Kaur Parvinder , Krishnamurthy Ramya V. , Narayanan Shridhar , Shandil Radha Krishan , Singh Mayas , Kofink Christiane , Mantoulidis Andreas , Biber Philipp , Gmaschitz Gerhard , Kazmaier Uli , Meinhart Anton , Leodolter Julia , Hoi David , Junker Sabryna , Morreale Francesca Ester , Clausen Tim , Kalscheuer Rainer , Weinstabl Harald , Boehmelt Guido
Published: March 2024

Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery. We are extending this concept by developing proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery. The anti-Mycobacterium tuberculosis (Mtb) BacPROTACs are derived from cyclomarins which, when dimerized, generate compounds that recruit and degrade ClpC1. The resulting Homo-BacPROTACs reduce levels of endogenous ClpC1 in Mycobacterium smegmatis and display minimum inhibitory concentrations in the low micro- to nanomolar range in mycobacterial strains, including multiple drug-resistant Mtb isolates. The compounds also kill Mtb residing in macrophages. Thus, Homo-BacPROTACs that degrade ClpC1 represent a different strategy for targeting Mtb and overcoming drug resistance.
Optically addressable spin defects coupled to bound states in the continuum metasurfaces
Authors: Sortino Luca , Gale Angus , Kühner Lucca , Li Chi , Biechteler Jonas , Wendisch Fedja J. , Kianinia Mehran , Ren Haoran , Toth Milos , Maier Stefan A. , Aharonovich Igor , Tittl Andreas
Published: March 2024

Van der Waals (vdW) materials, including hexagonal boron nitride (hBN), are layered crystalline solids with appealing properties for investigating light-matter interactions at the nanoscale. hBN has emerged as a versatile building block for nanophotonic structures, and the recent identification of native optically addressable spin defects has opened up exciting possibilities in quantum technologies. However, these defects exhibit relatively low quantum efficiencies and a broad emission spectrum, limiting potential applications. Optical metasurfaces present a novel approach to boost light emission efficiency, offering remarkable control over light-matter coupling at the sub-wavelength regime. Here, we propose and realise a monolithic scalable integration between intrinsic spin defects in hBN metasurfaces and high quality (Q) factor resonances, exceeding 102, leveraging quasi-bound states in the continuum (qBICs). Coupling between defect ensembles and qBIC resonances delivers a 25-fold increase in photoluminescence intensity, accompanied by spectral narrowing to below 4 nm linewidth and increased narrowband spin-readout efficiency. Our findings demonstrate a new class of metasurfaces for spin-defect-based technologies and pave the way towards vdW-based nanophotonic devices with enhanced efficiency and sensitivity for quantum applications in imaging, sensing, and light emission.
Nanopore analysis of cis-diols in fruits
Authors: Fan Pingping , Cao Zhenyuan , Zhang Shanyu , Wang Yuqin , Xiao Yunqi , Jia Wendong , Zhang Panke , Huang Shuo
Published: March 2024

Natural fruits contain a large variety of cis-diols. However, due to the lack of a high-resolution sensor that can simultaneously identify all cis-diols without a need of complex sample pretreatment, direct and rapid analysis of fruits in a hand-held device has never been previously reported. Nanopore, a versatile single molecule sensor, can be specially engineered to perform this task. A hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore modified with a sole phenylboronic acid (PBA) adapter is prepared. This engineered MspA accurately recognizes 1,2-diphenols, alditols, α-hydroxy acids and saccharides in prune, grape, lemon, different varieties of kiwifruits and commercial juice products. Assisted with a custom machine learning program, an accuracy of 99.3% is reported and the sample pretreatment is significantly simplified. Enantiomers such as DL-malic acids can also be directly identified, enabling sensing of synthetic food additives. Though demonstrated with fruits, these results suggest wide applications of nanopore in food and drug administration uses.
Effect of model methanogens on the electrochemical activity, stability, and microbial community structure of Geobacter spp. dominated biofilm anodes
Authors: Dzofou Ngoumelah Daniel , Heggeset Tonje Marita Bjerkan , Haugen Tone , Sulheim Snorre , Wentzel Alexander , Harnisch Falk , Kretzschmar Jörg
Published: March 2024

Combining anaerobic digestion (AD) and microbial electrochemical technologies (MET) in AD-MET holds great potential. Methanogens have been identified as one cause of decreased electrochemical activity and deterioration of Geobacter spp. biofilm anodes. A better understanding of the different interactions between methanogenic genera/species and Geobacter spp. biofilms is needed to shed light on the observed reduction in electrochemical activity and stability of Geobacter spp. dominated biofilms as well as observed changes in microbial communities of AD-MET. Here, we have analyzed electrochemical parameters and changes in the microbial community of Geobacter spp. biofilm anodes when exposed to three representative methanogens with different metabolic pathways, i.e., Methanosarcina barkeri, Methanobacterium formicicum, and Methanothrix soehngenii. M. barkeri negatively affected the performance and stability of Geobacter spp. biofilm anodes only in the initial batches. In contrast, M. formicicum did not affect the stability of Geobacter spp. biofilm anodes but caused a decrease in maximum current density of ~37%. M. soehngenii induced a coloration change of Geobacter spp. biofilm anodes and a decrease in the total transferred charge by ~40%. Characterization of biofilm samples after each experiment by 16S rRNA metabarcoding, whole metagenome nanopore sequencing, and shotgun sequencing showed a higher relative abundance of Geobacter spp. after exposure to M. barkeri as opposed to M. formicicum or M. soehngenii, despite the massive biofilm dispersal observed during initial exposure to M. barkeri.
Deep learning for three-dimensional segmentation of electron microscopy images of complex ceramic materials
Authors: Hirabayashi Yu , Iga Haruka , Ogawa Hiroki , Tokuta Shinnosuke , Shimada Yusuke , Yamamoto Akiyasu
Published: March 2024

The microstructure is a critical factor governing the functionality of ceramic materials. Meanwhile, microstructural analysis of electron microscopy images of polycrystalline ceramics, which are geometrically complex and composed of countless crystal grains with porosity and secondary phases, has generally been performed manually by human experts. Objective pixel-based analysis (semantic segmentation) with high accuracy is a simple but critical step for quantifying microstructures. In this study, we apply neural network-based semantic segmentation to secondary electron images of polycrystalline ceramics obtained by three-dimensional (3D) imaging. The deep-learning-based models (e.g., fully convolutional network and U-Net) by employing a dataset based on a 3D scanning electron microscopy with a focused ion beam is found to be able to recognize defect structures characteristic of polycrystalline materials in some cases due to artifacts in electron microscopy imaging. Owing to the training images with improved depth accuracy, the accuracy evaluation function, intersection over union (IoU) values, reaches 94.6% for U-Net. These IoU values are among the highest for complex ceramics, where the 3D spatial distribution of phases is difficult to locate from a 2D image. Moreover, we employ the learned model to successfully reconstruct a 3D microstructure consisting of giga-scale voxel data in a few minutes. The resolution of a single voxel is 20 nm, which is higher than that obtained using a typical X-ray computed tomography. These results suggest that deep learning with datasets that learn depth information is essential in 3D microstructural quantifying polycrystalline ceramic materials. Additionally, developing improved segmentation models and datasets will pave the way for data assimilation into operando analysis and numerical simulations of in situ microstructures obtained experimentally and for application to process informatics.
A global survey of prokaryotic genomes reveals the eco-evolutionary pressures driving horizontal gene transfer
Authors: Dmitrijeva Marija , Tackmann Janko , Matias Rodrigues João Frederico , Huerta-Cepas Jaime , Coelho Luis Pedro , von Mering Christian
Published: March 2024

Horizontal gene transfer, the exchange of genetic material through means other than reproduction, is a fundamental force in prokaryotic genome evolution. Genomic persistence of horizontally transferred genes has been shown to be influenced by both ecological and evolutionary factors. However, there is limited availability of ecological information about species other than the habitats from which they were isolated, which has prevented a deeper exploration of ecological contributions to horizontal gene transfer. Here we focus on transfers detected through comparison of individual gene trees to the species tree, assessing the distribution of gene-exchanging prokaryotes across over a million environmental sequencing samples. By analysing detected horizontal gene transfer events, we show distinct functional profiles for recent versus old events. Although most genes transferred are part of the accessory genome, genes transferred earlier in evolution tend to be more ubiquitous within present-day species. We find that co-occurring, interacting and high-abundance species tend to exchange more genes. Finally, we show that host-associated specialist species are most likely to exchange genes with other host-associated specialist species, whereas species found across different habitats have similar gene exchange rates irrespective of their preferred habitat. Our study covers an unprecedented scale of integrated horizontal gene transfer and environmental information, highlighting broad eco-evolutionary trends.
Comparison of surgical outcomes for hip fracture between older patients with and without cancer: a propensity score matching analysis
Authors: Kim Chul-Ho , Kim Kyu-pyo , Kim Ji Wan
Published: March 2024

Research on the treatment outcomes and mortality of patients with cancer and hip fractures remains limited. We aimed to assess the treatment outcomes and mortality in older patients with cancer and hip fractures. We retrospectively reviewed the data of 1264 patients aged ≥ 60 years treated for hip fractures between January 2005 and April 2022. The operation time, blood transfusion-related indicators, postoperative complications, reoperation rate, length of hospital stay, admission to the intensive care unit, mortality rate, and clinical scores were compared. We also performed survival analysis. Subsequently, 1:1 propensity-score matching was performed. In the unmatched cohort, we compared 273 patients with cancer and 991 controls. The cancer group exhibited a higher incidence of pneumonia (P = 0.025) and higher in-hospital and 1-year follow-up mortality rates (P = 0.044 and P < 0.001, respectively). In the matched cohort, the 1-year mortality rate remained higher in the cancer group (P < 0.001). The control group showed a higher survival rate in both unmatched and matched cohorts (P < 0.001 for both). The surgical outcomes for hip fractures were comparable between patients with and without cancer. We recommend surgical treatment for hip fractures in patients with cancer.
Assessment of the impact of a personalised nutrition intervention in impaired glucose regulation over 26 weeks: a randomised controlled trial
Authors: Karvela Maria , Golden Caroline T. , Bell Nikeysha , Martin-Li Stephanie , Bedzo-Nutakor Judith , Bosnic Natalie , DeBeaudrap Pierre , de Mateo-Lopez Sara , Alajrami Ahmed , Qin Yun , Eze Maria , Hon Tsz-Kin , Simón-Sánchez Javier , Sahoo Rashmita , Pearson-Stuttard Jonathan , Soon-Shiong Patrick , Toumazou Christofer , Oliver Nick
Published: March 2024

Dietary interventions can reduce progression to type 2 diabetes mellitus (T2DM) in people with non-diabetic hyperglycaemia. In this study we aimed to determine the impact of a DNA-personalised nutrition intervention in people with non-diabetic hyperglycaemia over 26 weeks. ASPIRE-DNA was a pilot study. Participants were randomised into three arms to receive either (i) Control arm: standard care (NICE guidelines) (n = 51), (ii) Intervention arm: DNA-personalised dietary advice (n = 50), or (iii) Exploratory arm: DNA-personalised dietary advice via a self-guided app and wearable device (n = 46). The primary outcome was the difference in fasting plasma glucose (FPG) between the Control and Intervention arms after 6 weeks. 180 people were recruited, of whom 148 people were randomised, mean age of 59 years (SD = 11), 69% of whom were female. There was no significant difference in the FPG change between the Control and Intervention arms at 6 weeks (− 0.13 mmol/L (95% CI [− 0.37, 0.11]), p = 0.29), however, we found that a DNA-personalised dietary intervention led to a significant reduction of FPG at 26 weeks in the Intervention arm when compared to standard care (− 0.019 (SD = 0.008), p = 0.01), as did the Exploratory arm (− 0.021 (SD = 0.008), p = 0.006). HbA1c at 26 weeks was significantly reduced in the Intervention arm when compared to standard care (− 0.038 (SD = 0.018), p = 0.04). There was some evidence suggesting prevention of progression to T2DM across the groups that received a DNA-based intervention (p = 0.06). Personalisation of dietary advice based on DNA did not result in glucose changes within the first 6 weeks but was associated with significant reduction of FPG and HbA1c at 26 weeks when compared to standard care. The DNA-based diet was effective regardless of intervention type, though results should be interpreted with caution due to the low sample size. These findings suggest that DNA-based dietary guidance is an effective intervention compared to standard care, but there is still a minimum timeframe of adherence to the intervention before changes in clinical outcomes become apparent.

Trial Registration:www.clinicaltrials.gov.ukRef: NCT03702465.
Mechanistic insights into the role of amyloid-β in innate immunity
Authors: Prosswimmer Tatum , Heng Anthony , Daggett Valerie
Published: March 2024

Colocalization of microbial pathogens and the β-amyloid peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients suggests that microbial infection may play a role in sporadic AD. Aβ exhibits antimicrobial activity against numerous pathogens, supporting a potential role for Aβ in the innate immune response. While mammalian amyloid is associated with disease, many bacteria form amyloid fibrils to fortify the biofilm that protects the cells from the surrounding environment. In the microbial AD hypothesis, Aβ aggregates in response to infection to combat the pathogen. We hypothesize that this occurs through toxic Aβ oligomers that contain α-sheet structure and form prior to fibrillization. De novo designed α-sheet peptides specifically bind to the α-sheet structure present in the oligomers of both bacterial and mammalian amyloidogenic proteins to neutralize toxicity and inhibit aggregation. Here, we measure the effect of E. coli on Aβ, including upregulation, aggregation, and toxicity. Additionally, we determined the effect of Aβ structure on E. coli amyloid fibrils, or curli comprised of the CsgA protein, and biofilm formation. We found that curli formation by E. coli increased Aβ oligomer production, and Aβ oligomers inhibited curli biogenesis and reduced biofilm cell density. Further, curli and biofilm inhibition by Aβ oligomers increased E. coli susceptibility to gentamicin. Toxic oligomers of Aβ and CsgA interact via α-sheet interactions, neutralizing their toxicity. These results suggest that exposure to toxic oligomers formed by microbial pathogens triggers Aβ oligomer upregulation and aggregation to combat infection via selective interactions between α-sheet oligomers to neutralize toxicity of both species with subsequent inhibition of fibrillization.
Modeling and analysis of hybrid-blood nanofluid flow in stenotic artery
Authors: Sarwar Lubna , Hussain Azad , Riaz Muhammad Bilal , Akbar Sobia
Published: March 2024

Current communication deals with the flow impact of blood inside cosine shape stenotic artery. The under consideration blood flow is treated as Newtonian fluid and flow is assumed to be two dimensional. The governing equation are modelled and solved by adopting similarity transformation under the stenosis assumptions. The important quantities like Prandtl number, flow parameter, blood flow rate and skin friction are attained to analyze the blood flow phenomena in stenosis. The variations of different parameters have been shown graphically. It is of interest to note that velocity increases due to change in flow parameter gamma and temperature of blood decreases by increasing nanoparticles volume fraction and Prandtl number. In the area of medicine, the most interesting nanotechnology approach is the nanoparticles applications in chemotherapy. This study provides further motivation to include more convincing consequences in the present model to represent the blood rheology.
Extraction and separation of astaxanthin with the help of pre-treatment of Haematococcus pluvialis microalgae biomass using aqueous two-phase systems based on deep eutectic solvents
Authors: Nemani Neda , Dehnavi Seyed Mohsen , Pazuki Gholamreza
Published: March 2024

The microalgae Haematococcus pluvialis are the main source of the natural antioxidant astaxanthin. However, the effective extraction of astaxanthin from these microalgae remains a significant challenge due to the rigid, non-hydrolyzable cell walls. Energy savings and high-efficiency cell disruption are essential steps in the recovery of the antioxidant astaxanthin from the cysts of H. pluvialis. In the present study, H. pluvialis microalgae were first cultured in Bold's Basal medium under certain conditions to reach the maximum biomass concentration, and then light shock was applied for astaxanthin accumulation. The cells were initially green and oval, with two flagella. As the induction time increases, the motile cells lose their flagellum and become red cysts with thick cell walls. Pre-treatment of aqueous two-phase systems based on deep eutectic solvents was used to decompose the cell wall. These systems included dipotassium hydrogen phosphate salt, water, and two types of deep eutectic solvents (choline chloride–urea and choline chloride–glucose). The results of pre-treatment of Haematococcus cells by the studied systems showed that intact, healthy cysts were significantly ruptured, disrupted, and facilitated the release of cytoplasmic components, thus facilitating the subsequent separation of astaxanthin by liquid–liquid extraction. The system containing the deep eutectic solvent of choline chloride–urea was the most effective system for cell wall degradation, which resulted in the highest ability to extract astaxanthin. More than 99% of astaxanthin was extracted from Haematococcus under mild conditions (35% deep eutectic solvent, 30% dipotassium hydrogen phosphate at 50 °C, pH = 7.5, followed by liquid–liquid extraction at 25 °C). The present study shows that the pre-treatment of two-phase systems based on deep eutectic solvent and, thus, liquid–liquid extraction is an efficient and environmentally friendly process to improve astaxanthin from the microalgae H. pluvialis.
Structural basis for the recognition of human hemoglobin by the heme-acquisition protein Shr from Streptococcus pyogenes
Authors: Senoo Akinobu , Hoshino Masato , Shiomi Toshiki , Nakakido Makoto , Nagatoishi Satoru , Kuroda Daisuke , Nakagawa Ichiro , Tame Jeremy R. H. , Caaveiro Jose M. M. , Tsumoto Kouhei
Published: March 2024

In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb. HID2 interacts with both, the protein and heme portions of Hb, explaining the specificity of HID2 for the heme-bound form of Hb, but not its heme-depleted form. Further mutational analysis shows little tolerance of HID2 to interfacial mutations, suggesting that its interaction surface with Hb could be a suitable candidate to develop efficient inhibitors abrogating the binding of Shr to Hb.
The second-order coherence analysis of number state propagation through dispersive non-Hermitian multilayered structures
Authors: Pilehvar Elnaz , Amooghorban Ehsan , Moravvej-Farshi Mohammad Kazem
Published: March 2024

To examine the second-order coherence of light propagation of quantum states in arbitrary directions through dispersive non-Hermitian optical media, we considered two sets of non-Hermitian periodic structures that consist of gain/loss unit cells. We show that each batch can satisfy the parity-time symmetry conditions at a distinct frequency. We then varied the gain/loss strength in the stable electromagnetic regime to evaluate the transmittance of N-photon number states through each structure. The results show both sets preserve their antibunching characteristics under specific incident light conditions. Furthermore, s(p)-polarized light exhibits higher (lower) second-order coherence at larger incident angles. In addition, the antibunching features of the transmitted states degrade with an increase in the number of unit cells in multilayered structures for both polarizations.
The seed dispersal syndrome hypothesis in ungulate-dominated landscapes
Authors: Fedriani Jose M. , Garrote Pedro J. , Burgos Tamara , Escribano-Ávila Gema , Morera Brayan , Virgós Emilio
Published: March 2024

The Seed Dispersal Syndrome Hypothesis (SDSH) posits that fruit traits predict the main dispersers interacting with plant species. Mammalian dispersers, relying heavily on olfactory cues, are expected to select dull-colored, scented, and larger fruits compared to birds. However, challenges like overabundant seed predators and context-dependency of frugivore-plant interactions complicate SDSH expectations. We studied the Iberian pear, Pyrus bourgaeana, an expected mammal-dispersed tree based on its fruit traits. Extensive camera-trapping data (over 35,000 records) from several tree populations and years revealed visits from seven frugivore groups, with ungulate fruit predators (59–97%) and carnivore seed dispersers (1–20%) most frequent, while birds, lagomorphs, and rodents were infrequent (0–10%). Red deer and wild boar were also the main fruit removers in all sites and years but acted as fruit and seed predators, and thus likely exert conflicting selection pressures to those exerted by seed dispersers. Although, as predicted by the SDSH, most Iberian pear fruits were consumed by large and medium-sized mammals, the traits of Iberian pear fruits likely reflect selection pressures from dispersal vectors in past times. Our results do not challenge the SDHS but do reveal the importance of considering frugivore functional roles for its adequate evaluation.
Utilizing Ni(II) complex for metal drug-gel particles in cervical cancer treatment and designing novel drugs through machine learning methods
Authors: Jiang Meiping , Wu Ruiping , Liu Dongqin , Wang Xiaoli
Published: March 2024

In the present study, a novel coordination polymer (CP) based on Ni(II), namely, [Ni(L)(D-CAM)(H2O)]n (1) (H2D-CAM = (1R,3S)-1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid and L = 3,6-bis(benzimidazol-1-yl)pyridazine), has been produced successfully through applying a mixed ligand synthesis method via reacting Ni(NO3)2·6H2O with 3,6-bis(benzimidazol-1-yl)pyridazine ligand in the presence of a carboxylic acid co-ligand. Hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) are representatives of natural polysaccharides and have good biocompatibility. Based on the chemical synthesis method, HA/CMCS hydrogel was successfully prepared. SEM showed that the lyophilized gel presented a typical macroporous structure with three-dimensional connected pores, which had unique advantages as a drug carrier. Using paclitaxel as a drug model, we further synthesized a novel paclitaxel-loaded metal gel and evaluated its therapeutic effect on cervical cancer. Finally, novel drugs from the reinforcement learning simulation are suggested to have better biological activity against ovarian cancer due to low affinity energy and stronger interaction strength towards the protein receptor.
Uncovering the microbiome landscape in sashimi delicacies
Authors: Ho Cheng‑Wei , Chen Pei‑Ying , Liao Yi-Ting , Cheng Yen-Fu , Tsou Han-Hsing , Liu Tsung‑Yun , Liang Kung-Hao
Published: March 2024

It is widely believed that a significant portion of the gut microbiota, which play crucial roles in overall health and disease, originates from the food we consume. Sashimi is a type of popular raw seafood cuisine. Its microbiome, however, remained to be thoroughly explored. The objective of this study is to explore the microbiome composition in sashimi at the time when it is served and ready to be eaten. Specifically, our tasks include investigating the diversity and characteristics of microbial profiles in sashimi with respect to the fish types. We utilized the Sanger-sequencing based DNA barcoding technology for fish species authentication and next-generation sequencing for sashimi microbiome profiling. We investigated the microbiome profiles of amberjack, cobia, salmon, tuna and tilapia sashimi, which were all identified using the MT-CO1 DNA sequences regardless of their menu offering names. Chao1 and Shannon indexes, as well as Bray–Curtis dissimilarity index were used to evaluate the alpha and beta diversities of sashimi microbiome. We successfully validated our previous observation that tilapia sashimi has a significantly higher proportions of Pseudomonas compared to other fish sashimi, using independent samples (P = 0.0010). Salmon sashimi exhibited a notably higher Chao1 index in its microbiome in contrast to other fish species (P = 0.0031), indicating a richer and more diverse microbial ecosystem. Non-Metric Multidimensional Scaling (NMDS) based on Bray–Curtis dissimilarity index revealed distinct clusters of microbiome profiles with respect to fish types. Microbiome similarity was notably observed between amberjack and tuna, as well as cobia and salmon. The relationship of microbiome similarity can be depicted as a tree which resembles partly the phylogenetic tree of host species, emphasizing the close relationship between host evolution and microbial composition. Moreover, salmon exhibited a pronounced relative abundance of the Photobacterium genus, significantly surpassing tuna (P = 0.0079), observed consistently across various restaurant sources. In conclusion, microbiome composition of Pseudomonas is significantly higher in tilapia sashimi than in other fish sashimi. Salmon sashimi has the highest diversity of microbiome among all fish sashimi that we analyzed. The level of Photobacterium is significantly higher in salmon than in tuna across all the restaurants we surveyed. These findings provide critical insights into the intricate relationship between the host evolution and the microbial composition. These discoveries deepen our understanding of sashimi microbiota, facilitating our decision in selecting raw seafood.
Explanation of the influence of geomorphometric variables on the landform classification based on selected areas in Poland
Authors: Dyba Krzysztof
Published: March 2024

In recent years, automatic image classification methods have significantly progressed, notably black box algorithms such as machine learning and deep learning. Unfortunately, such efforts only focused on improving performance, rather than attempting to explain and interpret how classification models actually operate. This article compares three state-of-the-art algorithms incorporating random forests, gradient boosting and convolutional neural networks for geomorphological mapping. It also attempts to explain how the most effective classifier makes decisions by evaluating which of the geomorphometric variables are most important for automatic mapping and how they affect the classification results using one of the explainable artificial intelligence techniques, namely accumulated local effects (ALE). This method allows us to understand the relationship between predictors and the model’s outcome. For these purposes, eight sheets of the digital geomorphological map of Poland on the scale of 1:100,000 were used as the reference material. The classification results were validated using the holdout method and cross-validation for individual sheets representing different morphogenetic zones. The terrain elevation entropy, absolute elevation, aggregated median elevation and standard deviation of elevation had the greatest impact on the classification results among the 15 geomorphometric variables considered. The ALE analysis was conducted for the XGBoost classifier, which achieved the highest accuracy of 92.8%, ahead of Random Forests at 84% and LightGBM at 73.7% and U-Net at 59.8%. We conclude that automatic classification can support geomorphological mapping only if the geomorphological characteristics in the predicted area are similar to those in the training dataset. The ALE plots allow us to analyze the relationship between geomorphometric variables and landform membership, which helps clarify their role in the classification process.
Metal leakage from orthodontic appliances chemically alters enamel surface during experimental in vitro simulated treatment
Authors: Topolska Justyna M. , Jagielska Agata , Motyl Sylwia , Kozub-Budzyń Gabriela A. , Kępa Luiza , Wagner Barbara , Wątor Katarzyna
Published: March 2024

Human enamel is composed mainly of apatite. This mineral of sorption properties is susceptible to chemical changes, which in turn affect its resistance to dissolution. This study aimed to investigate whether metal leakage from orthodontic appliances chemically alters the enamel surface during an in vitro simulated orthodontic treatment. Totally 107 human enamel samples were subjected to the simulation involving metal appliances and cyclic pH fluctuations over a period of 12 months in four complimentary experiments. The average concentrations and distribution of Fe, Cr, Ni, Ti and Cu within the enamel before and after the experiments were examined using ICP‒MS and LA‒ICP‒MS techniques. The samples exposed to the interaction with metal appliances exhibited a significant increase in average Fe, Cr and Ni (Kruskal–Wallis, p < 0.002) content in comparison to the control group. The outer layer, narrow fissures and points of contact with the metal components showed increased concentrations of Fe, Ti, Ni and Cr after simulated treatment, conversely to the enamel sealed with an adhesive system. It has been concluded that metal leakage from orthodontic appliances chemically alters enamel surface and microlesions during experimental in vitro simulated treatment.
Research on WSN reliable ranging and positioning algorithm for forest environment
Authors: Wu Peng , Yu Le , Yi Xiaomei , Xu Liang , Liu LiJuan , Yi YuTong , Jiang Tengteng , Tao Chunling
Published: March 2024

Wireless sensor network (WSN) location is a significant research area. In complex environments like forests, inaccurate signal intensity ranging is a major challenge. To address this issue, this paper presents a reliable WSN distance measurement-positioning algorithm for forest environments. The algorithm divides the positioning area into several sub-regions based on the discrete coefficient of the collected signal strength. Then, using the fitting method based on the signal intensity value of each sub-region, the algorithm derives the reference points of the logarithmic distance path loss model and path loss index. Finally, the algorithm locates target nodes using anchor nodes in different regions. Additionally, to enhance the positioning accuracy, weight values are assigned to the positioning result based on the discrete coefficient of the signal intensity in each sub-region. Experimental results demonstrate that the proposed WSN algorithm has high precision in forest environments.
Structural insights into the binding mechanism of Clr4 methyltransferase to H3K9 methylated nucleosome
Authors: Saab Christopher , Stephan Joseph , Akoury Elias
Published: March 2024

The establishment and maintenance of heterochromatin, a specific chromatin structure essential for genomic stability and regulation, rely on intricate interactions between chromatin-modifying enzymes and nucleosomal histone proteins. However, the precise trigger for these modifications remains unclear, thus highlighting the need for a deeper understanding of how methyltransferases facilitate histone methylation among others. Here, we investigate the molecular mechanisms underlying heterochromatin assembly by studying the interaction between the H3K9 methyltransferase Clr4 and H3K9-methylated nucleosomes. Using a combination of liquid-state nuclear magnetic resonance spectroscopy and cryo-electron microscopy, we elucidate the structural basis of Clr4 binding to H3K9-methylated nucleosomes. Our results reveal that Clr4 engages with nucleosomes through its chromodomain and disordered regions to promote de novo methylation. This study provides crucial insights into the molecular mechanisms governing heterochromatin formation by highlighting the significance of chromatin-modifying enzymes in genome regulation and disease pathology.
A type 4 resistant potato starch alters the cecal microbiome and gene expression in mice fed a western diet based on NHANES data
Authors: Smith Allen D. , Chen Celine , Cheung Lumei , Ward Robert E. , Jones B. Sky , Pletsch Elizabeth A. , Dawson Harry D.
Published: March 2024

Feeding the type 4 resistant starch, Versafibe 1490™ (VF), alters the microbiome, SCFA production and gene expression in the cecum and colon in mice.
Impact of Lactiplantibacillus plantarum and casein fortification on angiotensin converting enzyme inhibitory peptides in yogurt: identification and in silico analysis
Authors: Wang Jiaxu , Wang Zhimin , Zhang Mixia , Li Jiaxin , Zhao Cuisong , Ma Chunli , Ma Dexing
Published: March 2024

Lactiplantibacillus plantarum M11 in conjunction with sodium caseinate promoted the release of ACE inhibitory peptides in yogurt.
Upcycling plastic waste into fully recyclable composites through cold sintering
Authors: Lai Po-Hao , Hall Shelby L. , Lan Yi-Chen , Ai Jia-Ruey , Jaberi Arian , Sheikhi Amir , Shi Rui , Vogt Bryan D. , Gomez Enrique D.
Published: March 2024

Cold sintering enabled the upcycling of polypropylene with gypsum (CaSO4) into a fully recyclable composite, paving the way for the integration of waste into high-performance, recyclable composites.
Integrated resonance Rayleigh scattering approach utilizing Box–Behnken experimental design for the facile quantification of prucalopride in pharmaceutical tablets and human urine with sustainability assessment
Authors: Badr El-Din Khalid M. , Derayea Sayed M. , Mohammed Fatma F. , Hamad Ahmed Abdulhafez
Published: March 2024

Enhancement of the resonance Rayleigh scattering of eosin Y upon complex formation with prucalopride (PCP).
Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors
Authors: Mohd Radzuan Siti Nurshahira , Phongphane Lacksany , Abu Bakar Mohamad Hafizi , Che Omar Mohammad Tasyriq , Nor Shahril Nor Shafiqah , Supratman Unang , Harneti Desi , Wahab Habibah A. , Azmi Mohamad Nurul
Published: March 2024

New phenylisoxazole quinoxalin-2-amine hybrids 5a–i were successfully synthesised with yields of 53–85% and characterised with various spectroscopy methods.
Highly efficient removal of Sr2+ from aqueous solutions using a polyacrylic acid/crown-ether/graphene oxide hydrogel composite
Authors: Chen Sheng , Wu Lina , Wu Zhicheng , Liu Zhikun , Qiu Zhihua , Chi Lisheng
Published: March 2024

The PAA/DB18C6/GO composite was successfully synthesized by a radical cross-linking copolymerization method and was evaluated as an adsorbent for the removal of Sr2+ from simulated nuclear liquid wastes.
Block copolymer self-assembly derived mesoporous magnetic materials with three-dimensionally (3D) co-continuous gyroid nanostructure
Authors: Jousset Drouhin Amaury , Tait William R. T. , Moore William , Yu Fei , Li Yuanzhi , Werner Jörg G. , van Dover R. Bruce , Wiesner Ulrich B.
Published: March 2024

This work elucidates a route to mesoporous magnetic materials with co-continuous morphologies from block copolymer self-assembly. The co-continuous structure impacts the magnetic behavior compared to non-structured chemically-identical materials.