Mechanism Of Expansion Research Articles

Mechanism and optimization of sintered ultra-lightweight aggregates with sand washing slurry and red mud

Sand washing slurry, red mud, and waste sawdust are major solid wastes produced by the construction, mining, and wood processing industries, respectively. Their accumulation poses significant environmental hazards and results in substantial wastage of resources. This study utilized a novel rapid roasting method to prepare ultra-lightweight ceramsite aggregates (ULC) using sand washing slurry, red mud, and sawdust as raw materials. A new process for preparing ultra-lightweight clay aggregates (ULCA) utilizing waste sand washing sludge is proposed, achieving a utilization rate of the wash sand sludge exceeding 60%. Ultra-lightweight clay aggregates with a loose bulk density of 264.3 kg/m3 were produced. The influence of material formulation on the performance of ultra-lightweight clay aggregates was studied. The phase changes and expansion mechanism of the clay aggregates were revealed from microscopic and chemical perspectives. The synergistic effect of red mud and sawdust significantly enhanced the foaming effect of the ceramsite (i.e., porosity), reducing its loose bulk density while slowing the rate of strength reduction. Additionally, increasing the content of red mud and sawdust promoted ceramsite expansion. When the mass ratio of sand washing slurry, red mud, and sawdust was 29: 12: 1, with Fe2O3 content at 13% and sawdust content at 3%, preheating at 500°C for 5 minutes followed by roasting at 1150°C for 5 minutes produced ultra-lightweight ceramsite with a compressive strength of 1.7 MPa. This study provides a promising method for producing ULC from industrial solid wastes.

High-resolution chromosome-level genome of Scylla paramamosain provides molecular insights into adaptive evolution in crabs

BackgroundEvolutionary adaptation drives organismal adjustments to environmental pressures, exemplified in the diverse morphological and ecological adaptations seen in Decapoda crustaceans, particularly brachyuran crabs. Crabs thrive in diverse ecosystems, from coral reefs to hydrothermal vents and terrestrial habitats. Despite their ecological importance, the genetic mechanisms underpinning their developmental processes, reproductive strategies, and nutrient acquisition remain poorly understood.ResultsHere, we report a comprehensive genomic analysis of the green mud crab Scylla paramamosain using ultralong sequencing technologies, achieving a high-quality chromosome-level assembly. The refined 1.21 Gb genome, with an impressive contig N50 of 11.45 Mb, offers a valuable genomic resource. The genome exhibits 33,662 protein-coding genes, enriched in various pathways related to development and environmental adaptation. Gene family analysis shows expansion in development-related pathways and contraction in metabolic pathways, indicating niche adaptations. Notably, investigation into Hox gene regulation sheds light on their role in pleopod development, with the Abd-A gene identified as a linchpin. Post-transcriptional regulation involving novel-miR1317 negatively regulates Abd-A levels. Furthermore, the potential role of fru gene in ovarian development and the identification of novel-miR35 as a regulator of Spfru2 add complexity to gene regulatory networks. Comparative functional analysis across Decapoda species reveals neo-functionalization of the elovl6 gene in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA), suggesting its importance in environmental adaptation.ConclusionsOur findings shed light on various aspects of crab biology, including genome sequencing, assembly, and annotation, as well as gene family expansion, contraction, and regulatory mechanisms governing crucial developmental processes such as metamorphosis, reproductive strategies, and fatty acid metabolism.

Ergonomics in Bicycle Saddle Design: Application of TRIZ Innovation System Method with IPA-Kano Model Validation

This study investigates the innovative design of a bicycle saddle by incorporating sustainable ergonomics, universal design principles, and systematic innovation methods. Initially, the literature related to bicycle saddle design and its impact on the human body during riding was analyzed. The TRIZ contradiction matrix was then used to identify relevant invention principles, which served as references for the innovative design of the bicycle saddle. Biomechanics and the human–machine system analysis within human factors engineering were applied to ensure the innovative design is ergonomic and user-friendly. The design features a horizontally expandable and foldable bicycle saddle, enhancing its adaptability and sustainability. Universal design principles were applied to make the innovative design more accessible to the general public, and the prototype was simulated using Inventor drawing software. The research results include: (1) An innovative bicycle saddle design with horizontal expansion and folding functions is proposed. This design divides the saddle into three components, enabling the left and right parts to expand or retract based on user preferences. (2) A bicycle backrest design featuring vertical adjustability is introduced. It incorporates a quick-release adjustment mechanism at the junction of the backrest and saddle, allowing users to freely adjust the backrest height. (3) A quick-operation bicycle saddle design is presented, utilizing quick-release screws to facilitate the swift operation of the horizontal expansion and folding mechanisms. This validation method confirmed that the innovative design meets both sustainable ergonomic standards and user expectations. The systematic innovation approach used in this study can serve as a valuable reference for future research and design applications.

Study on microstructure characteristics and hole expansion mechanism of Ti-Nb-V microalloyed 900 MPa hot-rolled ferrite-bainite high hole expansion steel

In this study, a 900 MPa grade hot-rolled ferrite/bainite high hole expansion steel was developed using thermomechanical controlled processing (TMCP) and medium-temperature coiling with a Ti-Nb-V multi-microalloy design. The effects of cooling rates and coiling temperatures on the microstructure, mechanical properties, and hole expansion behavior were systematically investigated. The steel, coiled at 600°C and cooled at a controlled rate (10-25°C/s), demonstrated an excellent balance of strength and ductility, achieving a tensile strength of 901 MPa and elongation of 23%. The microstructure consisted of approximately 62% ferrite and 38% bainite, characterized by a uniform and fine grain distribution. The high coiling temperature increased the content of Ti-Nb-V composite precipitates, while reduced cooling times promoted the formation of smaller precipitates primarily along dislocation lines and grain boundaries. A hole expansion ratio of 77% was achieved due to the optimized grain morphology and phase ratio, with refined grains and high-angle grain boundaries impeding crack propagation. Additionally, the increased presence of secondary precipitates strengthened the soft phase ferrite and enhanced the coordinated deformation between ferrite and bainite. These combined effects significantly improved the steel's resistance to crack propagation during hole expansion, making it a promising material for applications requiring high strength and formability.

Continual compression model for online continual learning

Task-Free Continual Learning (TFCL) presents a notably demanding but realistic ongoing learning concept, aiming to address catastrophic forgetting in sequential learning systems. In this paper, we tackle catastrophic forgetting by introducing an innovative dynamic expansion framework designed to adaptively enhance the model’s capacity for novel data learning while also remembering the information learnt in the past, by using a minimal-size processing architecture. Our proposed framework incorporates three key mechanisms to mitigate model’ forgetting: (1) by employing a Maximum Mean Discrepancy (MMD)-based expansion mechanism that assesses the disparity between previously acquired knowledge and that from the new training data, serving as a signal for the model’s architecture expansion; (2) a component discarding mechanism that eliminates components characterized by redundant information, thereby optimizing the model size while fostering knowledge diversity; (3) a novel training sample selection strategy that leads to the diversity of the training data for each task. We conduct a series of TFCL experiments that demonstrate the superiority of the proposed framework over all baselines while utilizing fewer components than alternative dynamic expansion models. The results on the Split Mini ImageNet dataset, after splitting the original dataset into multiple tasks, are improved by more than 2% when compared to the closest baseline.

Metabolic pathways fueling the suppressive activity of myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSC) are considered an aberrant population of immature myeloid cells that have attracted considerable attention in recent years due to their potent immunosuppressive activity. These cells are typically absent or present in very low numbers in healthy individuals but become abundant under pathological conditions such as chronic infection, chronic inflammation and cancer. The immunosuppressive activity of MDSC helps to control excessive immune responses that might otherwise lead to tissue damage. This same immunosuppressive activity can be detrimental, particularly in cancer and chronic infection. In the cancer setting, tumors can secrete factors that promote the expansion and recruitment of MDSC, thereby creating a local environment that favors tumor progression by inhibiting the effective immune responses against cancer cells. This has made MDSC a target of interest in cancer therapy, with researchers exploring strategies to inhibit their function or reduce their numbers to improve the efficacy of cancer immunotherapies. In the context of chronic infections, MDSC can lead to persistent infections by suppressing protective immune responses thereby preventing the clearance of pathogens. Therefore, targeting MDSC may provide a novel approach to improve pathogen clearance during chronic infections. Ongoing research on MDSC aims to elucidate the exact processes behind their expansion, recruitment, activation and suppressive mechanisms. In this context, it is becoming increasingly clear that the metabolism of MDSC is closely linked to their immunosuppressive function. For example, MDSC exhibit high rates of glycolysis, which not only provides energy but also generates metabolites that facilitate their immunosuppressive activity. In addition, fatty acid metabolic pathways, such as fatty acid oxidation (FAO), have been implicated in the regulation of MDSC suppressive activity. Furthermore, amino acid metabolism, particularly arginine metabolism mediated by enzymes such as arginase-1, plays a critical role in MDSC-mediated immunosuppression. In this review, we discuss the metabolic signature of MDSC and highlight the therapeutic implications of targeting MDSC metabolism as a novel approach to modulate their immunosuppressive functions.

Genomic insights into Aspergillus tamarii TPD11: enhancing polyphyllin production and uncovering potential therapeutic applications.

The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Genome-wide analysis of Triticum aestivum bromodomain gene family and expression analysis under salt stress.

This study identified 82 wheat BRD genes, revealing both conserved evolutionary and functional characteristics across plant species and novel features specific to wheat. GTE8-12 cluster TaBRDs were found as positive response to salt stress. Bromodomain-containing proteins (BRDs) are crucial in histone acetylation "reading" and chromatin remodeling in eukaryotes. Despite some of their members showing importance in various biological processes in plants, our understanding of the BRD family in wheat (Triticum aestivum) remains limited. This study comprehensively analyzes the T. aestivum BRD (TaBRD) family. We identified 82 TaBRD genes in wheat genome encoding hydrophobic proteins with a conserved pocket structure. Phylogenetic analysis classified these genes into 16 distinct clusters, with conserved protein motifs and gene structures within clusters but diverse patterns across clusters. Gene duplication analysis revealed that whole-genome or segmental duplication events were the primary expansion mechanism for the TaBRD family, with purifying selection acting on these genes. Subcellular localization and Gene Ontology (GO) analyses indicated that TaBRD proteins are predominantly nuclear-localized and involved in transcription regulation and RNA metabolism. Promoter analysis and interaction network prediction suggested diverse regulatory mechanisms for TaBRDs. Notably, TaBRDs from the GTE8-12 cluster were enriched with cis-elements responsive to abscisic acid (ABA), methyl jasmonate (MeJA), and light, implying their involvement in physiological functions and abiotic stress responses. Expression analysis confirmed tissue-specific patterns and responsiveness to salinity stress. This comprehensive study enhances our understanding of the BRD family in higher plants and provides a foundation for developing salt-tolerant wheat varieties.

Performance evaluation of the static thrust and efficiency of an actuated biomimetic jellyfish model

Abstract This study offers an in-depth analysis of a jellyfish-inspired robotic model designed to simulate the expansion and contraction mechanisms found in natural jellyfish. By employing variable Duty Cycles to replicate the cyclic motions of the jellyfish, the thrust generation of the model is measured through static thrust assessments using a load cell, while its efficiency is evaluated using the Thrust-to-Power Ratio, TPR. The findings indicate that increasing the amplitude of the motion leads to more complex wave patterns, which in turn reduce the peak-to-peak force generated. Specifically, a 25% increase in the A/D ratio results in a significant 30% decrease in static thrust. It was observed that higher actuation frequencies do not notably influence thrust generation when the A/D ratio remains constant. Importantly, the TPR was found to be highest at an A/D ratio of 0.10, with an increase of up to 6% observed at higher Duty Cycles, suggesting that smaller actuation amplitudes are more efficient in enhancing thrust performance. These results highlight the critical role of amplitude in the efficiency of static thrust generation within a given Duty Cycle, emphasizing that lower amplitudes generally lead to higher efficiency. The study underscores the importance of optimizing both geometric and kinematic parameters for improved propulsion performance. It suggests that future research should focus on fine-tuning A/D ratios and Duty Cycles, as well as exploring alternative geometric configurations and materials to further enhance the hydrodynamic performance of jellyfish-inspired robots. The insights gained from this study provide a valuable foundation for developing more efficient and effective bio-inspired underwater vehicles.

Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.

Dynamic mutations in some human genes containing trinucleotide repeats are associated with severe neurodegenerative and neuromuscular disorders-known as Trinucleotide (or Triplet) Repeat Expansion Diseases (TREDs)-which arise when the repeat number of triplets expands beyond a critical threshold. While the mechanisms causing the DNA triplet expansion are complex and remain largely unknown, it is now recognized that the expandable repeats lead to the formation of nucleotide configurations with atypical structural characteristics that play a crucial role in TREDs. These nonstandard nucleic acid forms include single-stranded hairpins, Z-DNA, triplex structures, G-quartets and slipped-stranded duplexes. Of these, hairpin structures are the most prolific and are associated with the largest number of TREDs and have therefore been the focus of recent single-molecule FRET experiments and molecular dynamics investigations. Here, we review the structural and dynamical properties of nucleic acid hairpins that have emerged from these studies and the implications for repeat expansion mechanisms. The focus will be on CAG, GAC, CTG and GTC hairpins and their stems, their atomistic structures, their stability, and the important role played by structural interrupts.

Alien aquatic plants in Poland: Temporal and spatial distribution patterns and the effects of climate change

Distribution of alien aquatic plants in European freshwater ecosystems is still not fully recognized. Little is also known about the impact of climatic factors on the expansion of particular neophyte species in freshwater ecosystems. In this article, we present the first comprehensive assessment of the occurrence of non-native aquatic vascular plants in Poland (CE Europe), with a particular focus on: (1) inventory of the species, (2) temporal and spatial changes in their distribution, and (3) the climate impact on species occurrence and diversity. For this purpose, we collected both published and unpublished data on alien macrophytes occurrence in Poland covering past 70 years. In order to investigate the mechanism of alien aquatic plant expansion, climate data from 24 meteorological stations were analyzed. Redundancy analysis (RDA) was used to analyze the relationship between species composition and microclimate variables. In addition, Generalized Additive Model (GAM) was used to examine the response curves of neophyte species to temperature parameters.In total, we found records of 15 neophytes of alien aquatic plant taxa in Poland, including 14 species and collective taxon of Nymphaea cultivars. The most frequent was Elodea canadensis (over 25,000 records). Excluding this species, we counted more than 300 records of the occurrence of alien aquatic plants, of which three (E. nuttallii, Azolla filiculoides and Lemna turionifera) were the most abundant. Ten species occurred only in isolated sites. In addition, analyses showed a substantial increase in the number of the aquatic neophyte sites in the last 20 years that could be linked with the raised average monthly and yearly air temperatures in Poland.Our results showed a strong relationship between raised average temperatures in Poland and the spread of some species, e.g. Azolla filiculoides, while other species such as Elodea nuttallii and Lemna turionifera expanded irrespectively of this factor. The occurrence of some species (e.g. Vallisneria spiralis, Hygrophila polysperma) was exclusively associated to high thermally altered or thermally contaminated waters, and thus was limited to only a small part of the country. Our results confirm the major role of elevated temperatures (mean annual temperatures and minimum monthly temperatures) and thermally polluted freshwater ecosystems in the distribution of alien aquatic plants.

The 3D Density Structure of the South China Sea Based on Wavelet Multi-Scale Analysis of Gravity Data and Its Tectonic Implications

Due to its unique geographical location and complex geological evolution processes, the South China Sea has been a focus of extensive research. Previous studies on the density structure of the South China Sea mostly focused on 2D density structures, with relatively limited research on 3D density structures. A comprehensive study is still needed to refine the expansion mechanism and tectonic evolution of the South China Sea. In this study, we utilized wavelet multi-scale analysis of gravity data to obtain a 3D density model of the South China Sea and discussed its tectonic evolution from the pattern of density anomalies. The inversion results show that (1) the expansion of the South China Sea caused the typical thin oceanic crust and parts of the continent–ocean transition zone may fracture due to the expansion; (2) the low-density anomaly in the upper mantle of Luzon Island may indicate partial melting or the upwelling of asthenosphere materials; and (3) the expansion of the South China Sea is influenced by multiple plate forces and uneven forces affect the distribution of high-density anomalies in the upper mantle.

Study of Heat–Mass Transfer and Salt–Frost Expansion Mechanism of Sulfate Saline Soil during the Unidirectional Freezing Process

Study of Heat–Mass Transfer and Salt–Frost Expansion Mechanism of Sulfate Saline Soil during the Unidirectional Freezing Process

Utilization law of shale gas in hydraulic fracturing with the Changning–Weyuan block in China as an example

The process of extracting shale gas, particularly the study of the utilization law of shale reservoirs modified by hydraulic fracturing technology, is crucial for understanding the effective development of shale gas. This understanding can significantly influence the estimated ultimate recovery of reserves. Our study focused on Longmaxi Formation shale in the Changning–Weiyuan block. To investigate the hydraulic fracturing expansion mechanism and utilization law, we employed shale reservoir physical and mechanical characterization, indoor triaxial hydraulic fracturing experiments, and numerical simulations. The findings are as follows. The rupture pressure of hydraulic fractures increases with the peripheral pressure, and high stress is conducive to the formation of internal microfractures. Additionally, a high rate of water injection enhances fracture extensions along the direction of fluid injection. Under varying injection pressures, the length of crack extensions and number of bond damages in shale are positively correlated with the injection pressure. Conversely, under different differential ground stresses, the length of crack extensions and number of bond damages are negatively correlated with the injection pressure. The six main factors affecting the effective utilization of shale gas are as follows: the stimulated reservoir volume, number of hydraulic fracture clusters, fracture length, fracture height, number of fracture stages, and cluster spacing, accounting for 27.13%, 14.74%, 10.31%, 9.58%, 9.53%, and 9.29%, respectively, with a cumulative contribution rate of 80.58%. This study clarifies the hydraulic fracturing mechanisms of shale reservoirs and the laws governing shale gas production, providing technical support for the development of shale gas reservoirs.

Empirical Analysis on the Mechanism of Industrial Park Driving Urban Expansion: A Case Study of Xining City

Taking Xining City as an example, this article analyzes the mechanism by which industrial park construction drives the expansion of urban population size and built-up area, based on a review of the process of industrial park development and urban population growth. It also discusses future urban governance models in light of urban development trends. The research finds: (1) In the process of urban development, industrial park construction is often the initial factor in the cumulative and cyclical development of a city; (2) As the level of development improves and the mode of economic growth changes, the government should timely adjust its strategies, shifting from the expansion of industrial park construction towards structural optimization and quality improvement. The most significant difference from previous research is that this paper emphasizes the importance of government planning. This study can not only demonstrate the general process of industrial parks promoting urban expansion, but more importantly, it explains the fundamental reasons for the transition of urban expansion to adjustment from a mechanism perspective, thereby eliminating the drawbacks of simply predicting urban scale evolution through data models.

Lamellipodia-Mediated Osteoblast Haptotaxis Guided by Fibronectin Ligand Concentrations on a Multiplex Chip.

Skull morphogenesis is a complex, dynamic process involving two different germ layers and progressing to the coordinated, directional growth of individual bones. The mechanisms underlying directional growth toward the apex are not completely understood. Here, a microfluidic chip-based approach is utilized to test whether calvarial osteoblast progenitors undergo haptotaxis on a gradient of Fibronectin1 (FN1) via lamellipodia. Mimicking the embryonic cranial mesenchyme's FN1 pattern, FN1 gradients is established in the chip using computer modeling and fluorescent labeling. Primary mouse calvarial osteoblast progenitors are plated in the chip along an array of segmented gradients of adsorbed FN1. The study performs single-cell tracking and measures protrusive activity. Haptotaxis is observed at an intermediate FN1 concentration, with an average directional migration index (yFMI) of 0.07, showing a significant increase compared to the control average yFMI of -0.01. A significant increase in protrusive activity is observed during haptotaxis. Haptotaxis is an Arp2/3-dependent, lamellipodia-mediated process. Calvarial osteoblast progenitors treated with the Arp2/3 (Actin Related Protein 2/3 complex) inhibitor CK666 show significantly diminished haptotaxis, with an average yFMI of 0.01. Together, these results demonstrate haptotaxis on an FN1 gradient as a new mechanism in the apical expansion of calvarial osteoblast progenitors during development and shed light on the etiology of calvarial defects.

Three-dimensional interseismic crustal deformation in the northeastern margin of the Tibetan Plateau using GNSS and InSAR

The nature of the crustal deformation of the northeastern margin of the Tibetan Plateau is vital for elucidating the expansion mechanism of the plateau. We installed 21 continuous GNSS stations and obtained a horizontal velocity field with high spatial resolution. We also acquired a line-of-sight(LOS)velocity field with Sentinel-1 images covering the study area from 2014 to 2022. A multi-scale spherical wavelet method was employed to unify the reference frames of GNSS and InSAR data. After unifying the reference frame, the two data types achieve high consistency. Combining GNSS and InSAR velocities yielded the three-dimensional interseismic velocity field in the northeastern margin of the Tibetan Plateau. Furthermore, we analyzed the crustal deformation characteristics based on the three-dimensional deformation field. The crustal deformation exhibits a pronounced northeastward shift relative to the Ordos block, whereas the interior of the Ordos block remains remarkably stationary, behaving as a rigid unit. The Liupanshan fault is primarily characterized by uplift, devoid of any notable horizontal deformation across the fault. The left-lateral strike-slip mainly characterizes the Haiyuan fault.. The maximum east–west deformation velocity on the southern side of the fault is approximately 3.9 mm/yr, decreasing to about 1.0 mm/yr at the eastern end of the fault. The western segment of the West Qinling fault exhibits a minor east–west motion. Our result provides essential data for further study of the crustal deformation patterns.

Res-TCEANet: An expansive attention mechanism with positional correspondence based on semi-supervised temporal convolutional network for RUL estimation

The accurate prediction of Remaining Useful Life (RUL) is crucial for various applications, and the relative position of time steps between features plays a significant role in this process. However, traditional deep learning models often struggle with extracting and positional corresponding information in temporal features, especially in the presence of noise and limited labeled data. To overcome these challenges, we propose a novel semi-supervised Residual-denoising Temporal Convolutional Expansive Attention Network (Res-TCEANet). This approach introduces a unique expansive attention mechanism (EAM) that enhances the modeling of long-term dependencies by addressing the positional correspondence of features across layers. The proposed EAM distinguishes itself from existing attention mechanisms by enabling TCEANet to model long sequences with a focus on positional coherence, resulting in more robust feature extraction. The Root Mean Square Error and Score of the proposed method on C-MAPSS dataset are 10.75, 12.27, 10.82, 12.33 and 114.82, 427.05, 161.96 746.93, respectively, which have demonstrated that our method achieves the start-of-the-art performance and outperforms other models.

Evolutionary dynamics of the successful expansion of pandemic Vibrio parahaemolyticus ST3 in Latin America

The underlying evolutionary mechanisms driving global expansions of pathogen strains are poorly understood. Vibrio parahaemolyticus is one of only two marine pathogens where variants have emerged in distinct climates globally. The success of a Vibrio parahaemolyticus clone (VpST3) in Latin America- the first spread identified outside its endemic region of tropical Asia- provided an invaluable opportunity to investigate mechanisms of VpST3 expansion into a distinct marine climate. A global collection of VpST3 isolates and novel Latin American isolates were used for evolutionary population genomics, pangenome analysis and combined with oceanic climate data. We found a VpST3 population (LatAm-VpST3) introduced in Latin America well before the emergence of this clone in India, previously considered the onset of the VpST3 epidemic. LatAm-VpST3 underwent successful adaptation to local conditions over its evolutionary divergence from Asian VpST3 isolates, to become dominant in Latin America. Selection signatures were found in genes providing resilience to the distinct marine climate. Core genome mutations and accessory gene presences that promoted survival over long dispersals or increased environmental fitness were associated with environmental conditions. These results provide novel insights into the global expansion of this successful V. parahaemolyticus clone into regions with different climate scenarios.

A two-step strategy to expand primary human hepatocytes in vitro with efficient metabolic and regenerative capacities

BackgroundPrimary human hepatocytes (PHHs) are highly valuable for drug-metabolism evaluation, liver disease modeling and hepatocyte transplantation. However, their availability is significantly restricted due to limited donor sources, alongside their constrained proliferation capabilities and reduced functionality when cultured in vitro. To address this challenge, we aimed to develop a novel method to efficiently expand PHHs in vitro without a loss of function.MethodsBy mimicking the in vivo liver regeneration route, we developed a two-step strategy involving the de-differentiation/expansion and subsequent maturation of PHHs to generate abundant functional hepatocytes in vitro. Initially, we applied SiPer, a prediction algorithm, to identify candidate small molecules capable of activating liver regenerative transcription factors, thereby formulating a novel hepatic expansion medium to de-differentiate PHHs into proliferative human hepatic progenitor-like cells (ProHPLCs). These ProHPLCs were then re-differentiated into functionally mature hepatocytes using a new hepatocyte maturation condition. Additionally, we investigated the underlying mechanism of PHHs expansion under our new conditions.ResultsThe novel hepatic expansion medium containing hydrocortisone facilitated the de-differentiation of PHHs into ProHPLCs, which exhibited key hepatic progenitor characteristics and demonstrated a marked increase in proliferation capacity compared to cells cultivated in previously established expansion conditions. Remarkably, these subsequent matured hepatocytes rivaled PHHs in terms of transcriptome profiles, drug metabolizing activities and in vivo engraftment capabilities. Importantly, our findings suggest that the enhanced expansion of PHHs by hydrocortisone may be mediated through the PPARα signaling pathway and regenerative transcription factors.ConclusionsThis study presents a two-step strategy that initially induces PHHs into a proliferative state (ProHPLCs) to ensure sufficient cell quantity, followed by the maturation of ProHPLCs into fully functional hepatocytes to guarantee optimal cell quality. This approach offers a promising means of producing large numbers of seeding cells for hepatocyte-based applications.