bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study on chorus emission in an artificial magnetosphere
Authors: Saitoh Haruhiko , Nishiura Masaki , Kenmochi Naoki , Yoshida Zensho
Published: February 2024

Wave particle interaction plays an important role in geospace and space weather phenomena. Whistler mode chorus emissions, characterized by non-linear growth and frequency chirping, are common in planetary magnetospheres. They are regarded as the origin of relativistic acceleration of particles in the radiation belts and pulsating aurora. Intensive theoretical investigations and spacecraft observations have revealed several important features of chorus emissions. However, there is a need to conduct high-resolution and reproducible controlled laboratory experiments to deepen the understanding of space weather. Here, we present the spontaneous excitation of chirping whistler waves in hot-electron high-β plasma (β is the ratio of the plasma pressure to the magnetic pressure) in an “artificial magnetosphere”, a levitated dipole experiment. These experiments suggest that the generation and nonlinear growth of coherent chorus emissions are ubiquitous in dipole magnetic configuration. We anticipate that these experiments will accelerate the laboratory investigation of space weather phenomena.
Crystal-chemical origins of the ultrahigh conductivity of metallic delafossites
Authors: Zhang Yi , Tutt Fred , Evans Guy N. , Sharma Prachi , Haugstad Greg , Kaiser Ben , Ramberger Justin , Bayliff Samuel , Tao Yu , Manno Mike , Garcia-Barriocanal Javier , Chaturvedi Vipul , Fernandes Rafael M. , Birol Turan , Seyfried William E. , Leighton Chris
Published: February 2024

Despite their highly anisotropic complex-oxidic nature, certain delafossite compounds (e.g., PdCoO2, PtCoO2) are the most conductive oxides known, for reasons that remain poorly understood. Their room-temperature conductivity can exceed that of Au, while their low-temperature electronic mean-free-paths reach an astonishing 20 μm. It is widely accepted that these materials must be ultrapure to achieve this, although the methods for their growth (which produce only small crystals) are not typically capable of such. Here, we report a different approach to PdCoO2 crystal growth, using chemical vapor transport methods to achieve order-of-magnitude gains in size, the highest structural qualities yet reported, and record residual resistivity ratios ( > 440). Nevertheless, detailed mass spectrometry measurements on these materials reveal that they are not ultrapure in a general sense, typically harboring 100s-of-parts-per-million impurity levels. Through quantitative crystal-chemical analyses, we resolve this apparent dichotomy, showing that the vast majority of impurities are forced to reside in the Co-O octahedral layers, leaving the conductive Pd sheets highly pure (∼1 ppm impurity concentrations). These purities are shown to be in quantitative agreement with measured residual resistivities. We thus conclude that a sublattice purification mechanism is essential to the ultrahigh low-temperature conductivity and mean-free-path of metallic delafossites.
Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma
Authors: Tang Shaoshuai , Wang Yunzhi , Luo Rongkui , Fang Rundong , Liu Yufeng , Xiang Hang , Ran Peng , Tong Yexin , Sun Mingjun , Tan Subei , Huang Wen , Huang Jie , Lv Jiacheng , Xu Ning , Yao Zhenmei , Zhang Qiao , Xu Ziyan , Yue Xuetong , Yu Zixiang , Akesu Sujie , Ding Yuqin , Xu Chen , Lu Weiqi , Zhou Yuhong , Hou Yingyong , Ding Chen
Published: February 2024

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.
Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum
Authors: Li Eric Zhewen , Nguyen Tran Dang , Tran Thu Nguyen-Anh , Zupko Robert J. , Boni Maciej F.
Published: February 2024

Delaying and slowing antimalarial drug resistance evolution is a priority for malaria-endemic countries. Until novel therapies become available, the mainstay of antimalarial treatment will continue to be artemisinin-based combination therapy (ACT). Deployment of different ACTs can be optimized to minimize evolutionary pressure for drug resistance by deploying them as a set of co-equal multiple first-line therapies (MFT) rather than rotating therapies in and out of use. Here, we consider one potential detriment of MFT policies, namely, that the simultaneous deployment of multiple ACTs could drive the evolution of different resistance alleles concurrently and that these resistance alleles could then be brought together by recombination into double-resistant or triple-resistant parasites. Using an individual-based model, we compare MFT and cycling policies in malaria transmission settings ranging from 0.1% to 50% prevalence. We define a total risk measure for multi-drug resistance (MDR) by summing the area under the genotype-frequency curves (AUC) of double- and triple-resistant genotypes. When prevalence ≥ 1%, total MDR risk ranges from statistically similar to 80% lower under MFT policies than under cycling policies, irrespective of whether resistance is imported or emerges de novo. At 0.1% prevalence, there is little statistical difference in MDR risk between MFT and cycling.
Effect of trade on global aquatic food consumption patterns
Authors: Zhao Kangshun , Gaines Steven D. , García Molinos Jorge , Zhang Min , Xu Jun
Published: February 2024

Globalization of fishery products is playing a significant role in shaping the harvesting and use of aquatic foods, but a vigorous debate has focused on whether the trade is a driver of the inequitable distribution of aquatic foods. Here, we develop species-level mass balance and trophic level identification datasets for 174 countries and territories to analyze global aquatic food consumption patterns, trade characteristics, and impacts from 1976 to 2019. We find that per capita consumption of aquatic foods has increased significantly at the global scale, but the human aquatic food trophic level (HATL), i.e., the average trophic level of aquatic food items in the human diet, is declining (from 3.42 to 3.18) because of the considerable increase in low-trophic level aquaculture species output relative to that of capture fisheries since 1976. Moreover, our study finds that trade has contributed to increasing the availability and trophic level of aquatic foods in >60% of the world’s countries. Trade has also reduced geographic differences in the HATL among countries over recent decades. We suggest that there are important opportunities to widen the current focus on productivity gains and economic outputs to a more equitable global distribution of aquatic foods.
Reconstitution of early paclitaxel biosynthetic network
Authors: Liu Jack Chun-Ting , De La Peña Ricardo , Tocol Christian , Sattely Elizabeth S.
Published: February 2024

Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, we structurally characterize four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression in Nicotiana plants, we observe decreased levels of these proposed byproducts with a concomitant increase in the accumulation of taxadien-5α-ol, the paclitaxel precursor, by three-fold. This enables the reconstitution of a six step biosynthetic pathway, which we further show may function as a metabolic network. Our result demonstrates that six previously characterized Taxus genes can coordinatively produce key paclitaxel intermediates and serves as a crucial platform for the discovery of the remaining biosynthetic genes.
Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis
Authors: Minoia Melania , Quintana-Cordero Jany , Jetzinger Katharina , Kotan Ilgin Eser , Turnbull Kathryn Jane , Ciccarelli Michela , Masser Anna E. , Liebers Dorina , Gouarin Eloïse , Czech Marius , Hauryliuk Vasili , Bukau Bernd , Kramer Günter , Andréasson Claes
Published: February 2024

Cotranslational protein folding depends on general chaperones that engage highly diverse nascent chains at the ribosomes. Here we discover a dedicated ribosome-associated chaperone, Chp1, that rewires the cotranslational folding machinery to assist in the challenging biogenesis of abundantly expressed eukaryotic translation elongation factor 1A (eEF1A). Our results indicate that during eEF1A synthesis, Chp1 is recruited to the ribosome with the help of the nascent polypeptide-associated complex (NAC), where it safeguards eEF1A biogenesis. Aberrant eEF1A production in the absence of Chp1 triggers instant proteolysis, widespread protein aggregation, activation of Hsf1 stress transcription and compromises cellular fitness. The expression of pathogenic eEF1A2 variants linked to epileptic-dyskinetic encephalopathy is protected by Chp1. Thus, eEF1A is a difficult-to-fold protein that necessitates a biogenesis pathway starting with dedicated folding factor Chp1 at the ribosome to protect the eukaryotic cell from proteostasis collapse.
Tunable templating of photonic microparticles via liquid crystal order-guided adsorption of amphiphilic polymers in emulsions
Authors: Ma Xu , Han Yucen , Zhang Yan-Song , Geng Yong , Majumdar Apala , Lagerwall Jan P. F.
Published: February 2024

Multiple emulsions are usually stabilized by amphiphilic molecules that combine the chemical characteristics of the different phases in contact. When one phase is a liquid crystal (LC), the choice of stabilizer also determines its configuration, but conventional wisdom assumes that the orientational order of the LC has no impact on the stabilizer. Here we show that, for the case of amphiphilic polymer stabilizers, this impact can be considerable. The mode of interaction between stabilizer and LC changes if the latter is heated close to its isotropic state, initiating a feedback loop that reverberates on the LC in form of a complete structural rearrangement. We utilize this phenomenon to dynamically tune the configuration of cholesteric LC shells from one with radial helix and spherically symmetric Bragg diffraction to a focal conic domain configuration with highly complex optics. Moreover, we template photonic microparticles from the LC shells by photopolymerizing them into solids, retaining any selected LC-derived structure. Our study places LC emulsions in a new light, calling for a reevaluation of the behavior of stabilizer molecules in contact with long-range ordered phases, while also enabling highly interesting photonic elements with application opportunities across vast fields.
Global and regional ocean mass budget closure since 2003
Authors: Ludwigsen Carsten Bjerre , Andersen Ole Baltazar , Marzeion Ben , Malles Jan-Hendrik , Müller Schmied Hannes , Döll Petra , Watson Christopher , King Matt A.
Published: February 2024

In recent sea level studies, discrepancies have arisen in ocean mass observations obtained from the Gravity Recovery and Climate Experiment and its successor, GRACE Follow-On, with GRACE estimates consistently appearing lower than density-corrected ocean volume observations since 2015. These disparities have raised concerns about potential systematic biases in sea-level observations, with significant implications for our understanding of this essential climate variable. Here, we reconstruct the global and regional ocean mass change through models of ice and water mass changes on land and find that it closely aligns with both GRACE and density-corrected ocean volume observations after implementing recent adjustments to the wet troposphere correction and halosteric sea level. While natural variability in terrestrial water storage is important on interannual timescales, we find that the net increase in ocean mass over 20 years can be almost entirely attributed to ice wastage and human management of water resources.
Global freshwater fish invasion linked to the presence of closely related species
Authors: Xu Meng , Li Shao-peng , Liu Chunlong , Tedesco Pablo A. , Dick Jaimie T. A. , Fang Miao , Wei Hui , Yu Fandong , Shu Lu , Wang Xuejie , Gu Dangen , Mu Xidong
Published: February 2024

In the Anthropocene, non-native freshwater fish introductions and translocations have occurred extensively worldwide. However, their global distribution patterns and the factors influencing their establishment remain poorly understood. We analyze a comprehensive database of 14953 freshwater fish species across 3119 river basins and identify global hotspots for exotic and translocated non-native fishes. We show that both types of non-native fishes are more likely to occur when closely related to native fishes. This finding is consistent across measures of phylogenetic relatedness, biogeographical realms, and highly invaded countries, even after accounting for the influence of native diversity. This contradicts Darwin’s naturalization hypothesis, suggesting that the presence of close relatives more often signifies suitable habitats than intensified competition, predicting the establishment of non-native fish species. Our study provides a comprehensive assessment of global non-native freshwater fish patterns and their phylogenetic correlates, laying the groundwork for understanding and predicting future fish invasions in freshwater ecosystems.
Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing
Authors: Zhou Yabo , Wang Dianheng , Zhou Li , Zhou Nannan , Wang Zhenfeng , Chen Jie , Pang Ruiyang , Fu Haixia , Huang Qiusha , Dong Fang , Cheng Hui , Zhang Huafeng , Tang Ke , Ma Jingwei , Lv Jiadi , Cheng Tao , Fiskesund Roland , Zhang Xiaohui , Huang Bo
Published: February 2024

Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.
Highly permeable and shelf-stable aquaporin biomimetic membrane based on an anodic aluminum oxide substrate
Authors: Fuwad Ahmed , Ryu Hyunil , Han Eui Don , Lee Jun-Hee , Malmstadt Noah , Kim Young-Rok , Seo Young Ho , Kim Sun Min , Jeon Tae-Joon
Published: February 2024

Aquaporin (AQP) biomimetic membranes are a coming-of-age technology for water purification. Although several studies have reported aquaporin biomimetic membrane fabrication to date, these membranes show low water flux mainly due to the low porosity and inherently dense structure of the polymeric substrate materials. Herein, we report a ceramic-based aquaporin biomimetic membrane based on anodic aluminum oxide (AAO) as a substrate, which has a uniform porous structure with a high aspect ratio and pore density compared to conventional polymer substrates and exhibits a high water flux of 27.6 ± 3.6 LMH (L m−2 h−1) and superior membrane selectivity of 0.11 g L−1. Briefly, the AAO substrate was functionalized with amino-silane followed by polydopamine coating, then the AQP vesicles were immobilized on the functionalized AAO substrate surface using an electrokinetic method, and the water rejection performance of the membrane was analyzed in a forward osmosis system. Furthermore, a simple cryodesiccation method is introduced to improve the storage stability and easy transportation of aquaporin membranes, which does not require special environmental conditions to transport or store them.
3D hierarchical aquaporin-like nanoporous graphene membrane with engineered tripartite nanochannels for efficient oil/water separation
Authors: Hegab Hanaa M. , Elmekawy Ahmed , Aubry Cyril , Kallem Parashuram , Wadi Vijay S. , Banat Fawzi , Hasan Shadi W.
Published: February 2024

The aqueous system is being polluted by the untreated direct discharge of industrial oily wastewater into the ecosystem. Due to its low cost, energy economy, and sustainability, the advanced membrane filtration method is regarded as one of the best methods for treating oily wastewater. Its exceptional atomic thickness and superior amphiphilic properties of graphene oxide (GO) nanosheet make it one of the finest 2D constituents for creating membranes with high permeability. Nevertheless, the interlayer d-spacing of multi-stacked GO membranes is crucial since it is responsible for the permeability/selectivity trade-off. To efficiently separate oil-in-water emulsion using an in-situ polymerization technique, we developed an aquaporin-like 3D hierarchical multi-functionalized nanoporous graphene (NPG) membrane with tripartite nanochannels. The extraordinary, prepared membrane displayed both ultra-water-permeability of 2490 L m−2 h−1.bar along with superior selectivity. Consequently, the permeance of the aquaporin-like 3D hierarchical multi-functionalized NPG membrane achieves a higher flux than the GO membrane, while the oil rejection reaches ~97%.
Validation of portable in-clinic video-based gait analysis for prosthesis users
Authors: Cimorelli Anthony , Patel Ankit , Karakostas Tasos , Cotton R. James
Published: February 2024

Despite the common focus of gait in rehabilitation, there are few tools that allow quantitatively characterizing gait in the clinic. We recently described an algorithm, trained on a large dataset from our clinical gait analysis laboratory, which produces accurate cycle-by-cycle estimates of spatiotemporal gait parameters including step timing and walking velocity. Here, we demonstrate this system generalizes well to clinical care with a validation study on prosthetic users seen in therapy and outpatient clinics. Specifically, estimated walking velocity was similar to annotated 10-m walking velocities, and cadence and foot contact times closely mirrored our wearable sensor measurements. Additionally, we found that a 2D keypoint detector pretrained on largely able-bodied individuals struggles to localize prosthetic joints, particularly for those individuals with more proximal or bilateral amputations, but after training a prosthetic-specific joint detector video-based gait analysis also works on these individuals. Further work is required to validate the other outputs from our algorithm including sagittal plane joint angles and step length. Code for the gait transformer and the trained weights are available at https://github.com/peabody124/GaitTransformer.
Genetic variants associated with osteosarcoma risk: a systematic review and meta-analysis
Authors: Hassanain Omneya , Alaa Mahmoud , Khalifa Mohamed K. , Kamal Nehal , Albagoury Aseel , El Ghoneimy Ahmed M.
Published: February 2024

Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with osteosarcoma risk, however, the results of published studies are inconsistent. The aim of this study was to systematically review genetic association studies to identify SNPs associated with osteosarcoma risk and the effect of race on these associations. We searched the Medline, Embase, Scopus from inception to the end of 2019. Seventy-five articles were eligible for inclusion. These studies investigated the association of 190 SNPs across 79 genes with osteosarcoma, 18 SNPs were associated with the risk of osteosarcoma in the main analysis or in subgroup analysis. Subgroup analysis displayed conflicting effects between Asians and Caucasians. Our review comprehensively summarized the results of published studies investigating the association of genetic variants with osteosarcoma susceptibility, however, their potential value should be confirmed in larger cohorts in different ethnicities.
Ex-vivo validation of spatial gain sonography for the quantification of echo intensity in fascicle-aligned ultrasound images in ten anatomical muscles in Bos taurus
Authors: Rosahl Sophie C. , Rauschendorfer Philipp , Arndt Lukas , Voigtmann Thomas , Mittag Uwe , Rittweger Jörn
Published: February 2024

This study aimed to validate the concept of spatial gain sonography for quantifying texture-related echo intensity in B-mode ultrasound of skeletal muscle. Fifty-one bovine muscles were scanned postmortem using B-mode ultrasonography at varying fascicle probe angles (FPA). The relationship between mean gray values (MGV) and FPA was fitted with a sinusoidal and a linear function, the slope of which was defined as tilt echo gain (TEG). Macroscopic muscle cross sections were optically analyzed for intramuscular connective tissue (IMCT) content which was plotted against MGV at 0° FPA (MGV_00). MGV peaked at FPA 0°. Sine fits were superior to linear fits (adjusted r2-values 0.647 vs. 0.613), especially for larger FPAs. In mixed models, the pennation angle was related to TEG (P < 0.001) and MGV_00 (P = 0.035). Age was relevant for MGV_00 (P < 0.001), but not TEG (P > 0.10). The correlation between the IMCT percentage and MGV_00 was significant but weak (P = 0.026; adjusted r2 = 0.103). The relationship between fascicle probe angle and echo intensity in B-mode ultrasound can be modeled more accurately with a sinusoidal but more practically for clinical use with a linear fit. The peak mean gray value MGV_00 can be used to compare echo intensity across muscles without the bias of pennation angle.
Diabetic peripheral neuropathy among adult type 2 diabetes patients in Adama, Ethiopia: health facility-based study
Authors: Mekuria Negussie Yohannes , Tilahun Bekele Nardos
Published: February 2024

Diabetic peripheral neuropathy is the most prominent microvascular complication of diabetes mellitus and the leading cause of ulceration, amputation, and extended hospitalization. Evidence regarding the magnitude and factors associated with diabetic peripheral neuropathy is not well documented in Ethiopia, particularly in the study area. A facility-based cross-sectional study was conducted among 293 adult type 2 diabetic patients who were on treatment and follow-up from May to June 31, 2023. To select participants in the study, a systematic random sampling method was utilized. Data were collected using semi-structured questionnaires and medical record reviews. The Michigan Neuropathy Screening Instrument (MNSI) was employed to assess diabetic peripheral neuropathy. To model the association between diabetic peripheral neuropathy and independent variables, binary logistic regression model was used. An adjusted odds ratio with a 95% confidence interval was used to estimate the association and statistical significance was proclaimed at a p-value < 0.05. The magnitude of diabetic peripheral neuropathy was 14.3% (95% CI 10.4–18.0). It was 13.4% (95% CI 8.4–19.1) among males and 15.4% (95% CI 10.1–22.2) among females. Age above 60 years (AOR = 5.06, 95% CI 1.60–15.96), being rural resident (AOR = 2.41; 95% CI 1.15–5.06), duration of diabetes above 5 years (AOR = 2.48, 95% CI 1.16–5.27) and having comorbid hypertension (AOR = 2.56, 95% CI 1.24–5.28) were independently associated with diabetic peripheral neuropathy. One in seven adult type 2 diabetes patients in the study area had diabetic peripheral neuropathy. Factors such as age, place of residence, duration of diabetes, and comorbid hypertension showed positive associations with diabetic peripheral neuropathy. Thus, it is imperative to give special consideration to diabetic patients who are elderly, living in rural areas, experiencing a prolonged duration of diabetes, or dealing with comorbid hypertension.
Elevated platelet count is associated with decreased mortality from hemorrhagic stroke in hospital: a multi-center retrospective cohort study
Authors: Huang Zhenhua , Liu Chenglin , Wu Zhanxing , Xiao Xiaoyong , Chen Zhongqin , Huang Qun , Liu Dehong , Deng Zhe
Published: February 2024

This study aimed to investigate the relationship between platelet count (PC) and mortality in patients with hemorrhagic stroke (HS). The research reviewed data from 10,466 patients hospitalized in 208 hospitals in the United States from January 1, 2014, to December 31, 2015. Of these, 3262 HS patients were included in the primary analysis for those admitted to the intensive care unit (ICU). The average age of these patients was 67.05 years, with 52.79% being male. The median PC was (221.67 ± 73.78) × 109/L. Multivariate logistic regression analysis revealed that PC was a protective factor for mortality in HS patients (OR = 0.98, 95% CI 0.97–1.00, P < 0.05). Additionally, a non-linear association between PC and mortality in HS patients was found using a generalized additive model (GAM) and smooth curve fitting (penalty spline method). For the first time, a recursive algorithm identified the inflection point of platelet count as 194 × 109/L. On the left side of the inflection point, for every increase of 10 units in platelet count, the mortality rate of HS patients decreases by 10%. The study demonstrates a non-linear relationship between PC and the risk of mortality in HS patients. A platelet counts higher than the inflection point (194 × 109/L) may be a significant intervention to reduce mortality in HS patients.
Asymmetric imaging through engineered Janus particle obscurants using a Monte Carlo approach for highly asymmetric scattering media
Authors: da Mota Achiles F. , Sadafi Mohammad Mojtaba , Mosallaei Hossein
Published: February 2024

The advancement of imaging systems has significantly ameliorated various technologies, including Intelligence Surveillance Reconnaissance Systems and Guidance Systems, by enhancing target detection, recognition, identification, positioning, and tracking capabilities. These systems can be countered by deploying obscurants like smoke, dust, or fog to hinder visibility and communication. However, these counter-systems affect the visibility of both sides of the cloud. In this sense, this manuscript introduces a new concept of a smoke cloud composed of engineered Janus particles to conceal the target image on one side while providing clear vision from the other. The proposed method exploits the unique scattering properties of Janus particles, which selectively interact with photons from different directions to open up the possibility of asymmetric imaging. This approach employs a model that combines a genetic algorithm with Discrete Dipole Approximation to optimize the Janus particles' geometrical parameters for the desired scattering properties. Moreover, we propose a Monte Carlo-based approach to calculate the image formed as photons pass through the cloud, considering highly asymmetric particles, such as Janus particles. The effectiveness of the cloud in disguising a target is evaluated by calculating the Probability of Detection (PD) and the Probability of Identification (PID) based on the constructed image. The optimized Janus particles can produce a cloud where it is possible to identify a target more than 50% of the time from one side (PID > 50%) while the target is not detected more than 50% of the time from the other side (PD < 50%). The results demonstrate that the Janus particle-engineered smoke enables asymmetric imaging with simultaneous concealment from one side and clear visualization from the other. This research opens intriguing possibilities for modern obscurant design and imaging systems through highly asymmetric and inhomogeneous particles besides target detection and identification capabilities in challenging environments.
Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma
Authors: Feng Lemeng , Dai Shirui , Zhang Cheng , Zhang Wulong , Zhu Weiming , Wang Chao , He Ye , Song Weitao
Published: February 2024

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.
Iron-based compounds coordinated with phospho-polymers as biocompatible probes for dual 31P/1H magnetic resonance imaging and spectroscopy
Authors: Kracíková Lucie , Androvič Ladislav , Červený David , Jirát-Ziółkowska Natalia , Babič Michal , Švábová Monika , Jirák Daniel , Laga Richard
Published: February 2024

In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.
Evolutionary origin and distribution of amino acid mutations associated with resistance to sodium channel modulators in onion thrips, Thrips tabaci
Authors: Jouraku Akiya , Tomizawa Yui , Watanabe Kazuki , Yamada Kiyoshi , Kuwazaki Seigo , Aizawa Misato , Toda Satoshi , Sonoda Shoji
Published: February 2024

In onion thrips Thrips tabaci, reduced sensitivity of the sodium channel caused by several sodium channel mutations have been correlated with pyrethroid resistance. For this study, using mitochondrial cytochrome c oxidase subunit I gene sequences, we examined the phylogenetic relation among a total of 52 thelytokous and arrhenotokous strains with different genotypes of the sodium channel mutations. Then, we used flow cytometry to estimate their ploidy. Results showed that the strains are divisible into three groups: diploid thelytoky, triploid thelytoky, and diploid arrhenotoky. Using 23 whole genome resequencing data obtained from 20 strains out of 52, we examined their genetic relation further using principal component analysis, admixture analysis, and a fixation index. Results showed that diploid and triploid thelytokous groups are further classifiable into two based on the sodium channel mutations harbored by the respective group members (strains). The greatest genetic divergence was observed between thelytokous and arrhenotokous groups with a pair of T929I and K1774N. Nevertheless, they shared a genomic region with virtually no polymorphism around the sodium channel gene loci, suggesting a hard selective sweep. Based on these findings, we discuss the evolutionary origin and distribution of the sodium channel mutations in T. tabaci.
Enhanced visualization in endoleak detection through iterative and AI-noise optimized spectral reconstructions
Authors: Kazimierczak Wojciech , Kazimierczak Natalia , Wilamowska Justyna , Wojtowicz Olaf , Nowak Ewa , Serafin Zbigniew
Published: February 2024

To assess the image quality parameters of dual-energy computed tomography angiography (DECTA) 40-, and 60 keV virtual monoenergetic images (VMIs) combined with deep learning-based image reconstruction model (DLM) and iterative reconstructions (IR). CT scans of 28 post EVAR patients were enrolled. The 60 s delayed phase of DECTA was evaluated. Objective [noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR)] and subjective (overall image quality and endoleak conspicuity – 3 blinded readers assessment) image quality analyses were performed. The following reconstructions were evaluated: VMI 40, 60 keV VMI; IR VMI 40, 60 keV; DLM VMI 40, 60 keV. The noise level of the DLM VMI images was approximately 50% lower than that of VMI reconstruction. The highest CNR and SNR values were measured in VMI DLM images. The mean CNR in endoleak in 40 keV was accounted for as 1.83 ± 1.2; 2.07 ± 2.02; 3.6 ± 3.26 in VMI, VMI IR, and VMI DLM, respectively. The DLM algorithm significantly reduced noise and increased lesion conspicuity, resulting in higher objective and subjective image quality compared to other reconstruction techniques. The application of DLM algorithms to low-energy VMIs significantly enhances the diagnostic value of DECTA in evaluating endoleaks. DLM reconstructions surpass traditional VMIs and IR in terms of image quality.
In-vivo and in-vitro wound healing and tissue repair effect of Trametes versicolor polysaccharide extract
Authors: Teymoorian Seyedeh Kiana , Nouri Hoda , Moghimi Hamid
Published: February 2024

Regarding different medical benefits of fungi, using the medical mushroom extracts as wound-healing agents is gaining popularity. This study, evaluated the wound healing characteristics of Trametes versicolor. Anti-oxidant activity addressed by employing the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay resulting 53.7% inhibitory effect. Besides, for anti-microbial ability determination, the MIC (Minimum Inhibitory Concentration) of extract measured which Escherichia coli growth was inhibited at 1.1 mg/ml, and Staphylococcus aureus did not grow at 4.38 mg/ml of extract. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method indicated dose dependence of the extract with 63 ± 3% and 28 ± 3% viability at 1250 μg/ml and 156.25 μg/ml of extract, which higher concentration caused higher cell viability. The outcome of gene expression analysis determined that overall expression of FGF2 (Fibroblast Growth Factor 2), IL-1β (Interleukin-1β), and TGF-β1 (Transforming Growth Factor-β1) was 4 times higher at 48 h than at 24 h in treated cells, suggesting a stimulating effect on cell growth. An in-vivo animal model suggested enhanced wound healing process after treatment with 0.01 g of extract. Furthermore, the number of fibroblasts, epidermal thickness, and collagen fiber was respectively 2, 3, and threefold higher in treated mice when compared to untreated mice. The treated wounds of mice showed 100% and 60% of untreated mice of healing within 14 days. The results of this research show promise for the fungus-based wound healing treatments, which may help with tissue regeneration and the healing of cutaneous wounds.
The Drosophila ZNRF1/2 homologue, detour, interacts with HOPS complex and regulates autophagy
Authors: Nicolson Shannon , Manning Jantina A. , Lim Yoon , Jiang Xin , Kolze Erica , Dayan Sonia , Umargamwala Ruchi , Xu Tianqi , Sandow Jarrod J. , Webb Andrew I. , Kumar Sharad , Denton Donna
Published: February 2024

Autophagy, the process of elimination of cellular components by lysosomal degradation, is essential for animal development and homeostasis. Using the autophagy-dependent Drosophila larval midgut degradation model we identified an autophagy regulator, the RING domain ubiquitin ligase CG14435 (detour). Depletion of detour resulted in increased early-stage autophagic vesicles, premature tissue contraction, and overexpression of detour or mammalian homologues, ZNRF1 and ZNRF2, increased autophagic vesicle size. The ablation of ZNRF1 or ZNRF2 in mammalian cells increased basal autophagy. We identified detour interacting proteins including HOPS subunits, deep orange (dor/VPS18), Vacuolar protein sorting 16A (VPS16A), and light (lt/VPS41) and found that detour promotes their ubiquitination. The detour mutant accumulated autophagy-related proteins in young adults, displayed premature ageing, impaired motor function, and activation of innate immunity. Collectively, our findings suggest a role for detour in autophagy, likely through regulation of HOPS complex, with implications for healthy aging.
Reusability report: Unpaired deep-learning approaches for holographic image reconstruction
Authors: Zhang Yuhe , Ritschel Tobias , Villanueva-Perez Pablo
Published: February 2024

Deep-learning methods using unpaired datasets hold great potential for image reconstruction, especially in biomedical imaging where obtaining paired datasets is often difficult due to practical concerns. A recent study by Lee et al. (Nature Machine Intelligence 2023) has introduced a parameterized physical model (referred to as FMGAN) using the unpaired approach for adaptive holographic imaging, which replaces the forward generator network with a physical model parameterized on the propagation distance of the probing light. FMGAN has demonstrated its capability to reconstruct the complex phase and amplitude of objects, as well as the propagation distance, even in scenarios where the object-to-sensor distance exceeds the range of the training data. We performed additional experiments to comprehensively assess FMGAN’s capabilities and limitations. As in the original paper, we compared FMGAN to two state-of-the-art unpaired methods, CycleGAN and PhaseGAN, and evaluated their robustness and adaptability under diverse conditions. Our findings highlight FMGAN’s reproducibility and generalizability when dealing with both in-distribution and out-of-distribution data, corroborating the results reported by the original authors. We also extended FMGAN with explicit forward models describing the response of specific optical systems, which improved performance when dealing with non-perfect systems. However, we observed that FMGAN encounters difficulties when explicit forward models are unavailable. In such scenarios, PhaseGAN outperformed FMGAN.
Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation
Authors: Spinelli Elena , Damia Anna , Damarco Francesco , Gregori Beatrice , Occhipinti Federica , Busani Zara , Leali Marco , Battistin Michele , Lonati Caterina , Zhao Zhanqi , Storaci Alessandra Maria , Lopez Gianluca , Vaira Valentina , Ferrero Stefano , Rosso Lorenzo , Gatti Stefano , Mauri Tommaso
Published: February 2024

Background

Lung regions excluded from mechanical insufflation are traditionally assumed to be spared from ventilation-associated lung injury. However, preliminary data showed activation of potential mechanisms of injury within these non-ventilated regions (e.g., hypoperfusion, inflammation).

Methods

In the present study, we hypothesized that non-ventilated lung injury (NVLI) may develop within 24 h of unilateral mechanical ventilation in previously healthy pigs, and we performed extended pathophysiological measures to profile NVLI. We included two experimental groups undergoing exclusion of the left lung from the ventilation with two different tidal volumes (15 vs 7.5 ml/kg) and a control group on bilateral ventilation. Pathophysiological alteration including lung collapse, changes in lung perfusion, lung stress and inflammation were measured. Lung injury was quantified by histological score.

Results

Histological injury score of the non-ventilated lung is significantly higher than normally expanded lung from control animals. The histological score showed lower intermediate values (but still higher than controls) when the tidal volume distending the ventilated lung was reduced by 50%. Main pathophysiological alterations associated with NVLI were: extensive lung collapse; very low pulmonary perfusion; high inspiratory airways pressure; and higher concentrations of acute-phase inflammatory cytokines IL-6, IL-1β and TNF-α and of Angiopoietin-2 (a marker of endothelial activation) in the broncho-alveolar lavage. Only the last two alterations were mitigated by reducing tidal volume, potentially explaining partial protection.

Conclusions

Non-ventilated lung injury develops within 24 h of controlled mechanical ventilation due to multiple pathophysiological alterations, which are only partially prevented by low tidal volume.
Asymmetric cognitive learning mechanisms underlying the persistence of intergroup bias
Authors: Nafcha Orit , Hertz Uri
Published: February 2024

Intergroup bias, the tendency to favor ingroups and be hostile towards outgroups, underlies many societal problems and persists even when intergroup members interact and share experiences. Here we study the way cognitive learning processes contribute to the persistence of intergroup bias. Participants played a game with ingroup and outgroup bot-players that entailed collecting stars and could sacrifice a move to zap another player. We found that intergroup bias persisted as participants were more likely to zap outgroup players, regardless of their zapping behavior. Using a computational model, we found that this bias was caused by asymmetries in three learning mechanisms. Participants had a greater prior bias to zap out-group players, they learned more readily about the negative behavior of out-groups and were less likely to attribute the positive behavior of one out-group player to other out-group players. Our results uncover the way cognitive social learning mechanisms shape and confound intergroup dynamics.
RAD51 restricts DNA over-replication from re-activated origins
Authors: Muñoz Sergio , Blanco-Romero Elena , González-Acosta Daniel , Rodriguez-Acebes Sara , Megías Diego , Lopes Massimo , Méndez Juan
Published: February 2024

Eukaryotic cells rely on several mechanisms to ensure that the genome is duplicated precisely once in each cell division cycle, preventing DNA over-replication and genomic instability. Most of these mechanisms limit the activity of origin licensing proteins to prevent the reactivation of origins that have already been used. Here, we have investigated whether additional controls restrict the extension of re-replicated DNA in the event of origin re-activation. In a genetic screening in cells forced to re-activate origins, we found that re-replication is limited by RAD51 and enhanced by FBH1, a RAD51 antagonist. In the presence of chromatin-bound RAD51, forks stemming from re-fired origins are slowed down, leading to frequent events of fork reversal. Eventual re-initiation of DNA synthesis mediated by PRIMPOL creates ssDNA gaps that facilitate the partial elimination of re-duplicated DNA by MRE11 exonuclease. In the absence of RAD51, these controls are abrogated and re-replication forks progress much longer than in normal conditions. Our study uncovers a safeguard mechanism to protect genome stability in the event of origin reactivation.
Shared and distinct mechanisms of UBA1 inactivation across different diseases
Authors: Collins Jason C , Magaziner Samuel J , English Maya , Hassan Bakar , Chen Xiang , Balanda Nicholas , Anderson Meghan , Lam Athena , Fernandez-Pol Sebastian , Kwong Bernice , Greenberg Peter L , Terrier Benjamin , Likhite Mary E , Kosmider Olivier , Wang Yan , Samara Nadine L , Walters Kylie J , Beck David B , Werner Achim
Published: February 2024

Most cellular ubiquitin signaling is initiated by UBA1, which activates and transfers ubiquitin to tens of E2 enzymes. Clonally acquired UBA1 missense mutations cause an inflammatory-hematologic overlap disease called VEXAS (vacuoles, E1, X-linked, autoinflammatory, somatic) syndrome. Despite extensive clinical investigation into this lethal disease, little is known about the underlying molecular mechanisms. Here, by dissecting VEXAS-causing UBA1 mutations, we discovered that p.Met41 mutations alter cytoplasmic isoform expression, whereas other mutations reduce catalytic activity of nuclear and cytoplasmic isoforms by diverse mechanisms, including aberrant oxyester formation. Strikingly, non-p.Met41 mutations most prominently affect transthioesterification, revealing ubiquitin transfer to cytoplasmic E2 enzymes as a shared property of pathogenesis amongst different VEXAS syndrome genotypes. A similar E2 charging bottleneck exists in some lung cancer-associated UBA1 mutations, but not in spinal muscular atrophy-causing UBA1 mutations, which instead, render UBA1 thermolabile. Collectively, our results highlight the precision of conformational changes required for faithful ubiquitin transfer, define distinct and shared mechanisms of UBA1 inactivation in diverse diseases, and suggest that specific E1-E2 modules control different aspects of tissue differentiation and maintenance.
Visualized sensing of erythritol using a simple enzyme-free catechol-based hydrogel film
Authors: Zhang Xinyue , Wu Si , Feng Tao , Yan Yuanhao , Wu Shijing , Chen Yinyu , Wang Yu , Wang Qingmiao , Hu Ning , Wang Li
Published: February 2024

We report a novel non-enzymatic method based on a boronate ester that can distinguish erythritol by simple cell phone imaging.