bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals
Authors: Kreer Christoph , Lupo Cosimo , Ercanoglu Meryem S. , Gieselmann Lutz , Spisak Natanael , Grossbach Jan , Schlotz Maike , Schommers Philipp , Gruell Henning , Dold Leona , Beyer Andreas , Nourmohammad Armita , Mora Thierry , Walczak Aleksandra M. , Klein Florian
Published: November 2023

HIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction. Here, we perform unbiased sequence analyses of B cell receptor repertoires from 57 uninfected and 46 chronically HIV-1- or HCV-infected individuals and learn probabilistic models to predict the likelihood of bNAb development. We formally show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking bNAbs by their probabilities allows to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we find equal bNAb probabilities across infected and uninfected individuals. This implies that chronic infection is not a prerequisite for the generation of bNAbs, fostering the hope that HIV-1 vaccines can induce bNAb development in uninfected people.
Highly efficient octave-spanning long-wavelength infrared generation with a 74% quantum efficiency in a χ(2) waveguide
Authors: Hu Bo , Yang Xuemei , Wu Jiangen , Lu Siyi , Yang Hang , Long Zhe , He Linzhen , Luo Xing , Tian Kan , Wang Weizhe , Li Yang , Wu Han , Li Wenlong , Guo Chunyu , Yang Huan , Wang Qi Jie , Liang Houkun
Published: November 2023

The realization of compact and efficient broadband mid-infrared (MIR) lasers has enormous impacts in promoting MIR spectroscopy for various important applications. A number of well-designed waveguide platforms have been demonstrated for MIR supercontinuum and frequency comb generations based on cubic nonlinearities, but unfortunately third-order nonlinear response is inherently weak. Here, we propose and demonstrate for the first time a χ(2) micrometer waveguide platform based on birefringence phase matching for long-wavelength infrared (LWIR) laser generation with a high quantum efficiency. In a ZnGeP2-based waveguide platform, an octave-spanning spectrum covering 5–11 μm is generated through optical parametric generation (OPG). A quantum conversion efficiency of 74% as a new record in LWIR single-pass parametric processes is achieved. The threshold energy is measured as ~616 pJ, reduced by more than 1-order of magnitude as compared to those of MIR OPGs in bulk media. Our prototype micro-waveguide platform could be extended to other χ(2) birefringence crystals and trigger new frontiers of MIR integrated nonlinear photonics.
A generative adversarial network model alternative to animal studies for clinical pathology assessment
Authors: Chen Xi , Roberts Ruth , Liu Zhichao , Tong Weida
Published: November 2023

Animal studies are unavoidable in evaluating chemical and drug safety. Generative Adversarial Networks (GANs) can generate synthetic animal data by learning from the legacy animal study results, thus may serve as an alternative approach to assess untested chemicals. AnimalGAN, a GAN method to simulate 38 rat clinical pathology measures, was developed with significant robustness even for the drugs that vary significantly from these used during training, both in terms of chemical structure, drug class, and the year of FDA approval. AnimalGAN showed comparable results in hepatotoxicity assessment as using the real animal data and outperformed 12 conventional quantitative structure-activity relationship approaches. Using AnimalGAN, a virtual experiment of 100,000 rats ranked hepatotoxicity of three structurally similar drugs in a similar trend that has been observed in human population. AnimalGAN represented a significant step with artificial intelligence towards the global effort in replacement, reduction, and refinement (3Rs) of animal use.
LensAge index as a deep learning-based biological age for self-monitoring the risks of age-related diseases and mortality
Authors: Li Ruiyang , Chen Wenben , Li Mingyuan , Wang Ruixin , Zhao Lanqin , Lin Yuanfan , Chen Xinwei , Shang Yuanjun , Tu Xueer , Lin Duoru , Wu Xiaohang , Lin Zhenzhe , Xu Andi , Wang Xun , Wang Dongni , Zhang Xulin , Dongye Meimei , Huang Yunjian , Chen Chuan , Zhu Yi , Liu Chunqiao , Hu Youjin , Zhao Ling , Ouyang Hong , Li Miaoxin , Li Xuri , Lin Haotian
Published: November 2023

Age is closely related to human health and disease risks. However, chronologically defined age often disagrees with biological age, primarily due to genetic and environmental variables. Identifying effective indicators for biological age in clinical practice and self-monitoring is important but currently lacking. The human lens accumulates age-related changes that are amenable to rapid and objective assessment. Here, using lens photographs from 20 to 96-year-olds, we develop LensAge to reflect lens aging via deep learning. LensAge is closely correlated with chronological age of relatively healthy individuals (R2 > 0.80, mean absolute errors of 4.25 to 4.82 years). Among the general population, we calculate the LensAge index by contrasting LensAge and chronological age to reflect the aging rate relative to peers. The LensAge index effectively reveals the risks of age-related eye and systemic disease occurrence, as well as all-cause mortality. It outperforms chronological age in reflecting age-related disease risks (p < 0.001). More importantly, our models can conveniently work based on smartphone photographs, suggesting suitability for routine self-examination of aging status. Overall, our study demonstrates that the LensAge index may serve as an ideal quantitative indicator for clinically assessing and self-monitoring biological age in humans.
A single site ruthenium catalyst for robust soot oxidation without platinum or palladium
Authors: Li Yuanfeng , Qin Tian , Wei Yuechang , Xiong Jing , Zhang Peng , Lai Kezhen , Chi Hongjie , Liu Xi , Chen Liwei , Yu Xiaolin , Zhao Zhen , Li Lina , Liu Jian
Published: November 2023

The quest for efficient non-Pt/Pd catalysts has proved to be a formidable challenge for auto-exhaust purification. Herein, we present an approach to construct a robust catalyst by embedding single-atom Ru sites onto the surface of CeO2 through a gas bubbling-assisted membrane deposition method. The formed single-atom Ru sites, which occupy surface lattice sites of CeO2, can improve activation efficiency for NO and O2. Remarkably, the Ru1/CeO2 catalyst exhibits exceptional catalytic performance and stability during auto-exhaust carbon particle oxidation (soot), rivaling commercial Pt-based catalysts. The turnover frequency (0.218 h−1) is a nine-fold increase relative to the Ru nanoparticle catalyst. We further show that the strong interfacial charge transfer within the atomically dispersed Ru active site greatly enhances the rate-determining step of NO oxidation, resulting in a substantial reduction of the apparent activation energy during soot oxidation. The single-atom Ru catalyst represents a step toward reducing dependence on Pt/Pd-based catalysts.
Direct time-resolved observation of surface-bound carbon dioxide radical anions on metallic nanocatalysts
Authors: Jiang Zhiwen , Clavaguéra Carine , Hu Changjiang , Denisov Sergey A. , Shen Shuning , Hu Feng , Ma Jun , Mostafavi Mehran
Published: November 2023

Time-resolved identification of surface-bound intermediates on metallic nanocatalysts is imperative to develop an accurate understanding of the elementary steps of CO2 reduction. Direct observation on initial electron transfer to CO2 to form surface-bound CO2•− radicals is lacking due to the technical challenges. Here, we use picosecond pulse radiolysis to generate CO2•− via aqueous electron attachment and observe the stabilization processes toward well-defined nanoscale metallic sites. The time-resolved method combined with molecular simulations identifies surface-bound intermediates with characteristic transient absorption bands and distinct kinetics from nanosecond to the second timescale for three typical metallic nanocatalysts: Cu, Au, and Ni. The interfacial interactions are further investigated by varying the important factors, such as catalyst size and the presence of cation in the electrolyte. This work highlights fundamental ultrafast spectroscopy to clarify the critical initial step in the CO2 catalytic reduction mechanism.
Monolithic three-dimensional integration of RRAM-based hybrid memory architecture for one-shot learning
Authors: Li Yijun , Tang Jianshi , Gao Bin , Yao Jian , Fan Anjunyi , Yan Bonan , Yang Yuchao , Xi Yue , Li Yuankun , Li Jiaming , Sun Wen , Du Yiwei , Liu Zhengwu , Zhang Qingtian , Qiu Song , Li Qingwen , Qian He , Wu Huaqiang
Published: November 2023

In this work, we report the monolithic three-dimensional integration (M3D) of hybrid memory architecture based on resistive random-access memory (RRAM), named M3D-LIME. The chip featured three key functional layers: the first was Si complementary metal-oxide-semiconductor (CMOS) for control logic; the second was computing-in-memory (CIM) layer with HfAlOx-based analog RRAM array to implement neural networks for feature extractions; the third was on-chip buffer and ternary content-addressable memory (TCAM) array for template storing and matching, based on Ta2O5-based binary RRAM and carbon nanotube field-effect transistor (CNTFET). Extensive structural analysis along with array-level electrical measurements and functional demonstrations on the CIM and TCAM arrays was performed. The M3D-LIME chip was further used to implement one-shot learning, where ~96% accuracy was achieved on the Omniglot dataset while exhibiting 18.3× higher energy efficiency than graphics processing unit (GPU). This work demonstrates the tremendous potential of M3D-LIME with RRAM-based hybrid memory architecture for future data-centric applications.
Heterojunction formed via 3D-to-2D perovskite conversion for photostable wide-bandgap perovskite solar cells
Authors: Wen Jin , Zhao Yicheng , Wu Pu , Liu Yuxuan , Zheng Xuntian , Lin Renxing , Wan Sushu , Li Ke , Luo Haowen , Tian Yuxi , Li Ludong , Tan Hairen
Published: November 2023

Light-induced halide segregation constrains the photovoltaic performance and stability of wide-bandgap perovskite solar cells and tandem cells. The implementation of an intermixed two-dimensional/three-dimensional heterostructure via solution post-treatment is a typical strategy to improve the efficiency and stability of perovskite solar cells. However, owing to the composition-dependent sensitivity of surface reconstruction, the conventional solution post-treatment is suboptimal for methylammonium-free and cesium/bromide-enriched wide-bandgap PSCs. To address this, we develop a generic three-dimensional to two-dimensional perovskite conversion approach to realize a preferential growth of wider dimensionality (n ≥ 2) atop wide-bandgap perovskite layers (1.78 eV). This technique involves depositing a well-defined MAPbI3 thin layer through a vapor-assisted two-step process, followed by its conversion into a two-dimensional structure. Such a two-dimensional/three-dimensional heterostructure enables suppressed light-induced halide segregation, reduced non-radiative interfacial recombination, and facilitated charge extraction. The wide-bandgap perovskite solar cells demonstrate a champion power conversion efficiency of 19.6% and an open-circuit voltage of 1.32 V. By integrating with the thermal-stable FAPb0.5Sn0.5I3 narrow-bandgap perovskites, our all-perovskite tandem solar cells exhibit a stabilized PCE of 28.1% and retain 90% of the initial performance after 855 hours of continuous 1-sun illumination.
Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke
Authors: Wu Di , Zhou Jing , Zheng Yanrong , Zheng Yuyi , Zhang Qi , Zhou Zhuchen , Chen Xiaojie , Chen Qi , Ruan Yeping , Wang Yi , Chen Zhong
Published: November 2023

Ischemic stroke is lethal cerebrovascular disease, and reperfusion as the main strategy of blood supply restoration can cause severe ischemic brain damage. Considered as the major obstacle in medication for stroke, neuroinflammation after reperfusion undergoes dynamic progression, making precision treatment for stroke a Herculean task. In this work, we report a pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke. Intrinsic free radical scavenging and tailored mesostructure of the nanosystem can attenuate oxidative stress at the initial stage. Upon microglial overactivation at the later stage, minocycline-loaded nanosystem can timely reverse the pro-inflammatory transition in response to activated matrix metalloproteinase-2, providing on-demand regulation. Further in vivo stroke study demonstrates a higher survival rate and improved brain recovery of the sequential strategy, compared with mono-therapy and combined therapy. Complemented with satisfactory biosafety results, this adaptive nanosystem for sequential and on-demand regulation of post-stroke neuroinflammation is a promising approach to ischemic stroke therapy.
Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration
Authors: Greig Jenny A. , Martins Kelly M. , Breton Camilo , Lamontagne R. Jason , Zhu Yanqing , He Zhenning , White John , Zhu Jing-Xu , Chichester Jessica A. , Zheng Qi , Zhang Zhe , Bell Peter , Wang Lili , Wilson James M.
Published: November 2023

The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state. More than 10% of hepatocytes contained single nuclear domains of vector DNA that persisted despite the loss of transgene expression. Greater reductions in vector DNA and RNA were observed with immunogenic transgenes. Genomic integration of vector sequences, including complex concatemeric structures, were detected in 1 out of 100 cells at broadly distributed loci that were not in proximity to genes associated with hepatocellular carcinoma. Our studies suggest that AAV-mediated transgene expression in primate hepatocytes occurs in two phases: high but short-lived expression from episomal genomes, followed by much lower but stable expression, likely from integrated vectors.
CRISPR–Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames
Authors: Zheng Caishang , Wei Yanjun , Zhang Peng , Lin Kangyu , He Dandan , Teng Hongqi , Manyam Ganiraju , Zhang Zhao , Liu Wen , Lee Hye Rin Lindsay , Tang Ximing , He Wei , Islam Nelufa , Jain Antrix , Chiu Yulun , Cao Shaolong , Diao Yarui , Meyer-Gauen Sherita , Höök Magnus , Malovannaya Anna , Li Wenbo , Hu Ming , Wang Wenyi , Xu Han , Kopetz Scott , Chen Yiwen
Published: November 2023

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR–Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a primate-specific, long noncoding RNA, the expression of which is associated with poor prognosis in CRC, is low in normal tissues and is specifically elevated in CRC and several other cancer types. Mechanistically, SMIMP interacts with the ATPase-forming domains of SMC1A, the core subunit of the cohesin complex, and facilitates SMC1A binding tocis-regulatory elements to promote epigenetic repression of the tumor-suppressive cell cycle regulators encoded byCDKN1AandCDKN2B. Thus, our study reveals a cryptic microprotein as an important component of cohesin-mediated gene regulation and suggests that the ‘dark’ proteome, encoded by cryptic non-canonical ORFs, may contain potential therapeutic or diagnostic targets.
The smarty4covid dataset and knowledge base as a framework for interpretable physiological audio data analysis
Authors: Zarkogianni Konstantia , Dervakos Edmund , Filandrianos George , Ganitidis Theofanis , Gkatzou Vasiliki , Sakagianni Aikaterini , Raghavendra Raghu , Max Nikias C. L. , Stamou Giorgos , Nikita Konstantina S.
Published: November 2023

Harnessing the power of Artificial Intelligence (AI) and m-health towards detecting new bio-markers indicative of the onset and progress of respiratory abnormalities/conditions has greatly attracted the scientific and research interest especially during COVID-19 pandemic. The smarty4covid dataset contains audio signals of cough (4,676), regular breathing (4,665), deep breathing (4,695) and voice (4,291) as recorded by means of mobile devices following a crowd-sourcing approach. Other self reported information is also included (e.g. COVID-19 virus tests), thus providing a comprehensive dataset for the development of COVID-19 risk detection models. The smarty4covid dataset is released in the form of a web-ontology language (OWL) knowledge base enabling data consolidation from other relevant datasets, complex queries and reasoning. It has been utilized towards the development of models able to: (i) extract clinically informative respiratory indicators from regular breathing records, and (ii) identify cough, breath and voice segments in crowd-sourced audio recordings. A new framework utilizing the smarty4covid OWL knowledge base towards generating counterfactual explanations in opaque AI-based COVID-19 risk detection models is proposed and validated.
OIMHS: An Optical Coherence Tomography Image Dataset Based on Macular Hole Manual Segmentation
Authors: Ye Xin , He Shucheng , Zhong Xiaxing , Yu Jiafeng , Yang Shangchao , Shen Yingjiao , Chen Yiqi , Wang Yaqi , Huang Xingru , Shen Lijun
Published: November 2023

Macular holes, one of the most common macular diseases, require timely treatment. The morphological changes on optical coherence tomography (OCT) images provided an opportunity for direct observation of the disease, and accurate segmentation was needed to identify and quantify the lesions. Developments of such algorithms had been obstructed by a lack of high-quality datasets (the OCT images and the corresponding gold standard macular hole segmentation labels), especially for supervised learning-based segmentation algorithms. In such context, we established a large OCT image macular hole segmentation (OIMHS) dataset with 3859 B-scan images of 119 patients, and each image provided four segmentation labels: retina, macular hole, intraretinal cysts, and choroid. This dataset offered an excellent opportunity for investigating the accuracy and reliability of different segmentation algorithms for macular holes and a new research insight into the further development of clinical research for macular diseases, which included the retina, lesions, and choroid in quantitative analyses.
Exponential increases in high-temperature extremes in North America
Authors: Davariashtiyani Ali , Taherkhani Mohsen , Fattahpour Seyyedfaridoddin , Vitousek Sean
Published: November 2023

Global warming in the 21st century will alter the frequency of extreme climatic events, such as high-temperature anomalies and “heat waves”. Observations of extreme high temperatures during recent decades have detected upward trends in their frequency of occurrence, and recent state-of-the-art Global Climate Models (GCMs), e.g., Climate Model Intercomparison Projects (CMIPs), notably CMIP5 and CMIP6, have predicted acceleration of temperature trends and high-temperature events by 2100 under projected greenhouse-gas emission scenarios. Hence, the 21st century is expected to experience substantial shifts in the occurrence of extreme events, where present-day, extreme-but-rare high-temperature events will become common during the summer months. The increasing frequency of extreme heat may affect the health and resiliency of social, biological, and infrastructure systems in many regions worldwide, underscoring the need for accurate and reliable long-term assessments of climatic change across global and regional scales. So far, many investigations of high-temperature extremes have been carried out under end-point scenarios, e.g., by comparing GCM-projected changes in the frequency of high-temperature extremes expected in the late 21st century to the late 20th century. In this study, we use extreme value theory and decades of observations of high-temperature extremes at thousands of meteorological stations across North America to investigate continuous shifts in the frequency of extreme high-temperature events due to projected local warming trends. We find that the odds of exceedance of 50-year extreme high-temperature events increases exponentially with increases in mean local temperature. At a majority of the stations studied here, a local mean temperature increase of 0.5–1 $$^{\circ }$$

∘

C can double the odds of exceedance of 50-year extreme high-temperature events. Based on time-dependent temperature projections, the odds of exceedance of 50-year extreme high-temperature events doubles approximately every 20 years (or sooner) for $$\sim $$
∼
96% of the stations. Moreover, we find that, for $$\sim $$
∼
80% of the stations in North America, investigated here, the 50-year extreme high-temperature events will be exceeded annually before 2100.
Effect of continuous and intermittent blood flow restriction deep-squat training on thigh muscle activation and fatigue levels in male handball players
Authors: Wang Yan , Li Zhiyuan , Tongtong Che , Zhang Wenjuan , Li Xiaoxiao
Published: November 2023

We aimed to investigate acute changes before and after low-intensity continuous and intermittent blood flow restriction (BFR) deep-squat training on thigh muscle activation characteristics and fatigue level under suitable individual arterial occlusion pressure (AOP). Twelve elite male handball players were recruited. Continuous (Program 1) and intermittent (Program 2) BFR deep-squat training was performed with 30% one-repetition maximum load. Program 1 did not include decompression during the intervals, while Program 2 contained decompression during each interval. Electromyography (EMG) was performed before and after two BFR training programs in each period. EMG signals of the quadriceps femoris, posterior femoral muscles, and gluteus maximus, including the root mean square (RMS) and normalized RMS and median frequency (MF) values of each muscle group under maximum voluntary contraction (MVC), before and after training were calculated. The RMS value under MVC (RMSMVC) of the rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), and gluteus maximus (GM) decreased after continuous and intermittent BFR training programs, and those of the biceps femoris (BF) and semitendinosus (SEM) increased; The RMS standard values of the VL, BF, and SEM were significantly increased after continuous and intermittent BFR training (P < 0.05), The RMS value of GM significantly decreased after cuff inflating (P < 0.05). The MF values of RF, VM, VL, and GM decreased significantly after continuous BFR training (P < 0.05). Continuous BFR deep-squat training applied at 50% AOP was more effective than the intermittent BFR training program. Continuous application of BFR induces greater levels of acute fatigue than intermittent BFR that may translate into greater muscular training adaptations over time.
Phage therapy minimally affects the water microbiota in an Atlantic salmon (Salmo salar) rearing system while still preventing infection
Authors: Fiedler Alexander W. , Gundersen Madeleine S. , Vo Toan P. , Almaas Eivind , Vadstein Olav , Bakke Ingrid
Published: November 2023

Excessive usage of antibiotics threatens the bacterial diversity in the microbiota of animals. An alternative to antibiotics that has been suggested to not disturb the microbiota is (bacterio)phage therapy. In this study, we challenged germ-free and microbially colonized yolk sac fry of Atlantic salmon with Flavobacterium columnare and observed that the mere presence of a microbiota protected the fish against lethal infection. We then investigated the effect of phage- or oxytetracycline treatment on fish survival and rearing water bacterial community characteristics using 16S rRNA gene amplicon sequencing. Phage treatment led to an increased survival of F. columnare-challenged fish and reduced the relative amounts of the pathogen in the water microbiota. In the absence of F. columnare, phage treatment did not affect the composition or the α-diversity of the rearing water microbiota. In the presence of the phage’s host, phage treatment induced minor changes to the bacterial community composition, without affecting the α-diversity. Surprisingly, oxytetracycline treatment had no observable effect on the water microbiota and did not reduce the relative abundance of F. columnare in the water. In conclusion, we showed that phage treatment prevents mortality while not negatively affecting the rearing water microbiota, thus suggesting that phage treatment may be a suitable alternative to antibiotics. We also demonstrated a protective effect of the microbiota in Atlantic salmon yolk sac fry.
Virtual staining for pixel-wise and quantitative analysis of single cell images
Authors: Yilmaz Abdurrahim , Aydin Tuelay , Varol Rahmetullah
Published: November 2023

Immunocytochemical staining of microorganisms and cells has long been a popular method for examining their specific subcellular structures in greater detail. Recently, generative networks have emerged as an alternative to traditional immunostaining techniques. These networks infer fluorescence signatures from various imaging modalities and then virtually apply staining to the images in a digital environment. In numerous studies, virtual staining models have been trained on histopathology slides or intricate subcellular structures to enhance their accuracy and applicability. Despite the advancements in virtual staining technology, utilizing this method for quantitative analysis of microscopic images still poses a significant challenge. To address this issue, we propose a straightforward and automated approach for pixel-wise image-to-image translation. Our primary objective in this research is to leverage advanced virtual staining techniques to accurately measure the DNA fragmentation index in unstained sperm images. This not only offers a non-invasive approach to gauging sperm quality, but also paves the way for streamlined and efficient analyses without the constraints and potential biases introduced by traditional staining processes. This novel approach takes into account the limitations of conventional techniques and incorporates improvements to bolster the reliability of the virtual staining process. To further refine the results, we discuss various denoising techniques that can be employed to reduce the impact of background noise on the digital images. Additionally, we present a pixel-wise image matching algorithm designed to minimize the error caused by background noise and to prevent the introduction of bias into the analysis. By combining these approaches, we aim to develop a more effective and reliable method for quantitative analysis of virtually stained microscopic images, ultimately enhancing the study of microorganisms and cells at the subcellular level.
Unraveling the influence of trial-based motivational changes on performance monitoring stages in a flanker task
Authors: Overmeyer Rebecca , Kirschner Hans , Fischer Adrian G. , Endrass Tanja
Published: November 2023

Performance monitoring (PM) is a vital component of adaptive behavior and known to be influenced by motivation. We examined effects of potential gain (PG) and loss avoidance (LA) on neural correlates of PM at different processing stages, using a task with trial-based changes in these motivational contexts. Findings suggest more attention is allocated to the PG context, with higher amplitudes for respective correlates of stimulus and feedback processing. The PG context favored rapid responses, while the LA context emphasized accurate responses. Lower response thresholds in the PG context after correct responses derived from a drift–diffusion model also indicate a more approach-oriented response style in the PG context. This cognitive shift is mirrored in neural correlates: negative feedback in the PG context elicited a higher feedback-related negativity (FRN) and higher theta power, whereas positive feedback in the LA context elicited higher P3a and P3b amplitudes, as well as higher theta power. There was no effect of motivational context on response-locked brain activity. Given the similar frequency of negative feedback in both contexts, the elevated FRN and theta power in PG trials cannot be attributed to variations in reward prediction error. The observed variations in the FRN indicate that the effect of outcome valence is modulated by motivational salience.
Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans
Authors: Wu Zhongji , Chen Xiaowen , Wu Shangzhi , Liu Zhenwei , Li Hongwei , Mai Kailin , Peng Yinghui , Zhang Haidi , Zhang Xiaodie , Zheng Zhaocong , Fu Zian , Chen Dehui
Published: November 2023

Bronchiolitis obliterans (BO) is a chronic airway disease that was often indicated by the pathological presentation of narrowed and irreversible airways. However, the molecular mechanisms of BO pathogenesis remain unknown. Although neutrophil extracellular traps (NETs) can contribute to inflammatory disorders, their involvement in BO is unclear. This study aims to identify potential signaling pathways in BO by exploring the correlations between NETs and BO. GSE52761 and GSE137169 datasets were downloaded from gene expression omnibus (GEO) database. A series of bioinformatics analyses such as differential expression analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were performed on GSE52761 and GSE137169 datasets to identify BO potential signaling pathways. Two different types of BO mouse models were constructed to verify NETs involvements in BO. Additional experiments and bioinformatics analysis using human small airway epithelial cells (SAECs) were also performed to further elucidate differential genes enrichment with their respective signaling pathways in BO. Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes. Besides, we found that neutrophil extracellular traps (NETs) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further confirmed NETs activation in BO, where neutrophil elastase (NE) and myeloperoxidase (MPO) expression were found significantly elevated. Transcriptomic and bioinformatics analysis of NETs treated-SAECs also revealed that NETs-DEGs were primarily associated through inflammatory and epithelial-to-mesenchymal transition (EMT) -related pathways. Our study provides novel clues towards the understanding of BO pathogenesis, in which NETs contribute to BO pathogenesis through the activation of inflammatory and EMT associated pathways. The completion of our study will provide the basis for potential novel therapeutic targets in BO treatment.
Rapid and sensitive detection of Pseudomonas aeruginosa by isothermal amplification combined with Cas12a-mediated detection
Authors: Huang Siyi , Wang Xianfeng , Chen Xinchong , Liu Xiaoyu , Xu Qiuqing , Zhang Lijun , Huang Guangtao , Wu Jun
Published: November 2023

CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.
Anticorrosive performance of newly synthesized dipyridine based ionic liquids by experimental and theoretical approaches
Authors: Moustafa Amira Hossam Eldin , Abdel-Rahman Hanaa H. , Hagar Mohamed , Aouad Mohamed R. , Rezki Nadjet , Bishr Sherif A. A.
Published: November 2023

Two newly synthetic nontoxic dipyridine-based ionic liquids (PILs) with the same chain lengths and different polar groups were investigated: bispyridine-1-ium tetrafluoroborate (BPHP,TFPHP) with terminal polar groupsBrandCF3, respectively, on Carbon steel (CS) in 8M H3PO4as corrosion inhibitors. Their chemical structure was verified by performing1HNMR and13CNMR. Their corrosion inhibition was investigated by electrochemical tests, especially as mass transfer with several characterizations: Scanning electron microscope/Energy dispersive X-ray spectroscopy (SEM–EDX), UV–visible, Atomic force microscope, Atomic absorbance spectroscopy, X-ray Photoelectron Spectroscopy and Gloss value. Theoretical calculation using density functional theory by calculating several parameters, molecular electrostatic potential, Fukui Indices, and Local Dual Descriptors were performed to demonstrate the reactivity behavior and the reactive sites of two molecules with a concentration range (1.25–37.5 × 10–5M) and temperature (293–318 K). The maximum inhibition efficiency (76.19%) and uniform coverage were sufficient forBPHPat an optimum concentration of 37.5 × 10–5M with the lowest temperature of 293 K.TFPHPrecorded 71.43% at the same conditions. Two PILswere adsorbed following the El-Awady adsorption isotherm, including physicochemical adsorption. The computational findings agree with Electrochemical measurements and thus confirm CS's corrosion protection in an aggressive environment.
A novel pathway of levodopa metabolism by commensal Bifidobacteria
Authors: Cirstea M. S. , Creus-Cuadros A. , Lo C. , Yu A. C. , Serapio-Palacios A. , Neilson S. , Appel-Cresswell S. , Finlay B. B.
Published: November 2023

The gold-standard treatment for Parkinson’s disease is levodopa (L-DOPA), which is taken orally and absorbed intestinally. L-DOPA must reach the brain intact to exert its clinical effect; peripheral metabolism by host and microbial enzymes is a clinical management issue. The gut microbiota is altered in PD, with one consistent and unexplained observation being an increase in Bifidobacterium abundance among patients. Recently, certain Bifidobacterium species were shown to have the ability to metabolize L-tyrosine, an L-DOPA structural analog. Using both clinical cohort data and in vitro experimentation, we investigated the potential for commensal Bifidobacteria to metabolize this drug. In PD patients, Bifidobacterium abundance was positively correlated with L-DOPA dose and negatively with serum tyrosine concentration. In vitro experiments revealed that certain species, including B. bifidum, B. breve, and B. longum, were able to metabolize this drug via deamination followed by reduction to the compound 3,4-dihydroxyphenyl lactic acid (DHPLA) using existing tyrosine-metabolising genes. DHPLA appears to be a waste product generated during regeneration of NAD +. This metabolism occurs at low levels in rich medium, but is significantly upregulated in nutrient-limited minimal medium. Discovery of this novel metabolism of L-DOPA to DHPLA by a common commensal may help inform medication management in PD.
Effect of SGLT2 inhibition on salt-induced hypertension in female Dahl SS rats
Authors: Kravtsova Olha , Levchenko Vladislav , Klemens Christine A. , Rieg Timo , Liu Ruisheng , Staruschenko Alexander
Published: November 2023

Sodium-glucose co-transporters (SGLTs) in the kidneys play a pivotal role in glucose reabsorption. Several clinical and population-based studies revealed the beneficial effects of SGLT2 inhibition on hypertension. Recent work from our lab provided significant new insight into the role of SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension, Dahl salt-sensitive (SS) rats. Dapagliflozin (Dapa) blunted the development of salt-induced hypertension by causing glucosuria and natriuresis without changes in the Renin–Angiotensin–Aldosterone System. However, our initial study used male SS rats only, and the effect of SGLT2 inhibitors on hypertension in females has not been studied. Therefore, the goal of this study was to determine whether SGLT2 inhibition alters blood pressure and kidney function in female Dahl SS rats. The result showed that administration of Dapa for 3 weeks prevented the progression of salt-induced hypertension in female rats, similar to its effects in male SS rats. Diuresis and glucose excretion were significantly increased in Dapa-treated rats. SGLT2 inhibition also significantly attenuated kidney but not heart fibrosis. Despite significant effects on blood pressure, Dapa treatment caused minor changes to electrolyte balance and no effects on kidney and heart weights were observed. Our data suggest that SGLT2 inhibition in a non-diabetic model of salt-sensitive hypertension blunts the development of salt-induced hypertension independent of sex.
XBB.1.5 spike protein COVID-19 vaccine induces broadly neutralizing and cellular immune responses against EG.5.1 and emerging XBB variants
Authors: Patel Nita , Trost Jessica F. , Guebre-Xabier Mimi , Zhou Haixia , Norton Jim , Jiang Desheng , Cai Zhaohui , Zhu Mingzhu , Marchese Anthony M. , Greene Ann M. , Mallory Raburn M. , Kalkeri Raj , Dubovsky Filip , Smith Gale
Published: November 2023

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign.
Optimizing alpha-amylase from Bacillus amyloliquefaciens on bread waste for effective industrial wastewater treatment and textile desizing through response surface methodology
Authors: Abd-Elhalim Basma T. , Gamal Rawia F. , El-Sayed Salwa M. , Abu-Hussien Samah H.
Published: November 2023

Food waste is a major issue, with one-third of food wasted yearly. This study aimed to produce sustainably the industrial enzyme alpha-amylase using discarded bread waste. Brown (BBW) and white bread waste (WBW) were tested as growth substrates using solid-state and submerged fermentation. The biosynthesized α- amylase is applied to treat starch-heavy industrial wastewater and for textile desizing. Bacillus amyloliquefaciens showed the highest starch hydrolysis and enzyme activity on solid and liquid media. α-amylase production by B. amyloliquefaciens was optimized via a one-factor-at-a-time evaluation of production parameters. Optimal production occurred by submerged fermentation of BBW inoculated with 2% B. amyloliquefaciens at 37 °C and 200rpm for 24 h, reaching 695.2 U/mL α- amylase. The crude enzyme was immobilized on calcium alginate beads with 96.6% efficiency and kept 88.5% activity after 20 reuses, enhancing stability. A Box–Behnken design (BOX) assessed variable interactions. Response surface methodology (RSM) generated a quadratic model and analysis of variance (ANOVA analysis) fitting experimental starch hydrolysis data. Optimal conditions were pH 9, 45 °C, 70% starch, and 27.5 U/mL enzyme incubated for 15 min of contact time, with a high R2 of 0.83. ANOVA confirmed the enzyme's alkaliphilic and thermophilic nature. Using enzyme concentrations ranging from 10.9 to 695.1 U/mL, the enzyme desized textiles in 15 min at pH 9.0 and 45 °C with 96.3% efficiency. Overall, the optimized α- amylase from bread waste has industrial potential for sustainable starch processing.
A model-independent redundancy measure for human versus ChatGPT authorship discrimination using a Bayesian probabilistic approach
Authors: Bozza Silvia , Roten Claude-Alain , Jover Antoine , Cammarota Valentina , Pousaz Lionel , Taroni Franco
Published: November 2023

The academic and scientific world in general is increasingly concerned about their inability to determine and ascertain the identity of the writer of a text. More and more often the question arises as to whether a scientific article or work handed in by a student was actually produced by the alleged author of the questioned text. The role of artificial intelligence (AI) is increasingly debated due to its dangers of undeclared use. A current example is undoubtedly the undeclared use of ChatGPT to write a scientific text. The article promotes an AI model-independent redundancy measure to support discrimination between hypotheses on authorship of various multilingual texts written by humans or produced by intelligence media such as ChatGPT. The syntax of texts written by humans tends to differ from that of texts produced by AIs. This difference can be grasped and quantified even with short texts (i.e. 1800 characters). This aspect of length is extremely important, because short texts imply a greater difficulty of analysis to characterize authorship. To meet the efficiency criteria required for the evaluation of forensic evidence, a probabilistic approach is implemented. In particular, to assess the value of the redundancy measure and to offer a consistent classification criterion, a metric called Bayes factor is implemented. The proposed Bayesian probabilistic method represents an original approach in stylometry. Analyses performed over multilingual texts (English and French) covering different scientific and human areas of interest (forensic science and socio-psycho-artistic topics) reveal the feasibility of a successful authorship discrimination with limited misclassification rates. Model performance is satisfactory even with small sample sizes.
Crosstalk enables mutual activation of coupled quorum sensing pathways through “jump-start” and “push-start” mechanisms
Authors: Sanders Joseph George , Akl Hoda , Hagen Stephen J. , Xue BingKan
Published: November 2023

Many quorum sensing microbes produce more than one chemical signal and detect them using interconnected pathways that crosstalk with each other. While there are many hypotheses for the advantages of sensing multiple signals, the prevalence and functional significance of crosstalk between pathways are much less understood. We explore the effect of intracellular signal crosstalk using a simple model that captures key features of typical quorum sensing pathways: multiple pathways in a hierarchical configuration, operating with positive feedback, with crosstalk at the receptor and promoter levels. We find that crosstalk enables activation or inhibition of one output by the non-cognate signal, broadens the dynamic range of the outputs, and allows one pathway to modulate the feedback circuit of the other. Our findings show how crosstalk between quorum sensing pathways can be viewed not as a detriment to the processing of information, but as a mechanism that enhances the functional range of the full regulatory system. When positive feedback systems are coupled through crosstalk, several new modes of activation or deactivation become possible.
Dynamic mechanical properties of different types of rocks under impact loading
Authors: Wang Zixu , Huang Junhong , Chen Yanglong , Li Xinping , Liu Tingting , Meng Fei
Published: November 2023

To study the mechanical properties of different types of rocks under impact loading, static mechanical parameter tests and split-Hopkinson pressure bar (SHPB) dynamic impact experiments were conducted on five typical rock specimens. The mechanical properties and failure modes of different rock specimens under the same static and dynamic loading were investigated. The differences between numerical simulation results and laboratory test results under different constitutive models in LS-DYNA were also compared and analyzed. The results show that with the increase of SHPB impact pressure (0.5–0.8 MPa), the stress peak values of granite, marble, and limestone also increase, while gypsum and reef limestone follow no particular trend. At the same time, both HJC and RHT constitutive models can simulate the laboratory impact test results of granite, marble, and limestone, however, the gypsum and reef limestone are not modelled by the HJC constitutive model, while the RHT constitutive model can describe the deformation-damage-failure process of rock specimens with different strengths. Therefore, the RHT model can better reflect the real deformation and failure of rocks.