Next-Generation Simulation Illuminates Scientific Problems of Organised Complexity

As artificial intelligence becomes increasingly prevalent in scientific research, data-driven methodologies appear to overshadow traditional approaches in resolving scientific problems. In this Perspective, we revisit a classic classification of scientific problems and acknowledge that a series of unresolved problems remain. Throughout the history of researching scientific problems, scientists have continuously formed new paradigms facilitated by advances in data, algorithms, and computational power. To better tackle unresolved problems, especially those of organised complexity, a novel paradigm is necessitated. While recognising that the strengths of new paradigms have expanded the scope of resolvable scientific problems, we aware that the continued advancement of data, algorithms, and computational power alone is hardly to bring a new paradigm. We posit that the integration of paradigms, which capitalises on the strengths of each, represents a promising approach. Specifically, we focus on next-generation simulation (NGS), which can serve as a platform to integrate methods from different paradigms. We propose a methodology, sophisticated behavioural simulation (SBS), to realise it. SBS represents a higher level of paradigms integration based on foundational models to simulate complex systems, such as social systems involving sophisticated human strategies and behaviours. NGS extends beyond the capabilities of traditional mathematical modelling simulations and agent-based modelling simulations, and therefore, positions itself as a potential solution to problems of organised complexity in complex systems

Research on surface roughness of circular arc cut by ASJ

Izrađen je potpuni faktorijalni plan eksperimenata za istraživanje učinaka tlaka mlaza, reznog posmaka i polumjera kružnog luka na površinsku hrapavost kružnog luka rezanog mlazom abrazivne otopine - abrasive suspension jet (ASJ). Ortogonalnim planom eksperimenata analizirala se veličina djelovanja parametara na hrapavost rezne površine na različitim dubinama. Smanjivanje brzine prijelaza je najučinkovitija metoda za smanjenje površinske hrapavosti. Uz to, usporedbom topografije rezne površine s onom pomoću AWJ, ustanovilo se da je površina sastavljena od četiri zone: inicijalna zona, glatka zona, prijelazna zona i gruba zona. Konačno, primijenjena je metoda multipne linearne regresije za postavljanje modela hrapavosti površine na različitim dubinama, što se eksperimentima potvrdilo kao pouzdano. Zaključci mogu poslužiti kao teorijski vodič za poboljšanje učinkovitosti rezanja pomoću ASJ.Full factorial design of experiments was developed in order to investigate the effects of jet pressure, cutting feed, and circular arc radius upon the one response variable surface roughness of circular arc cut by abrasive suspension jet (ASJ). And orthogonal design of experiments was used for analysing the magnitude of effects of parameters on roughness of the cutting surface at different depths. Slowing down the traverse speed is the most effective method to reduce the surface roughness. In addition, comparing the topography of the cutting surface with that by AWJ, it is found that the surface also consists of four zones: initial zone, smooth zone, transition zone and rough zone. Finally, the multiple linear regression was employed to establish the model of cutting surface roughness at different depths, which was proved to be reliable by experiments. The conclusions can provide theoretical guidance for improving the cutting efficiency of ASJ

BHDPC Is a Novel Neuroprotectant That Provides Anti-neuroinflammatory and Neuroprotective Effects by Inactivating NF-κB and Activating PKA/CREB.

Microglia-mediated neuroinflammatory responses are inevitable and important pathological processes in several kinds of disorder of the central nervous system (CNS). Therefore, alleviating activated microglia-induced inflammatory process might be a valuable therapeutic approach to neuroinflammation-related diseases. In the present study, we investigated BHDPC, a novel neuroprotectant discovered in our previous study that had anti-inflammatory effects under neuroinflammatory conditions. First, we found that BHDPC could inhibit neuroinflammatory responses and promote microglial M2 phenotype polarization in both lipopolysaccharide (LPS)-activated BV-2 microglia l cells. Furthermore, BHDPC provided protective actions against neuroinflammation-induced neurotoxicity in HT22 mouse hippocampal cells co-cultured with activated BV-2 microglia. Further experiments demonstrated that BHDPC could suppress LPS-induced activation of transcription factor nuclear factor kappa B (NF-κB) via interfering with the degradation of the inhibitor of kappa B (IκB) and phosphorylation of IκB, the IκB kinase (IKK). Moreover, we also found that BHDPC could induce phosphorylation of cAMP-dependent protein kinase A (PKA) and cAMP-response element-binding protein (CREB) in BV-2 microglial cells. Also, using the PKA-specific inhibitor, we found that BHDPC-induced CREB phosphorylation was dependent on PKA, which also contributed to BHDPC-mediated anti-inflammation and neuroprotection

Modulation of virulence and metabolic profiles in Klebsiella pneumoniae under indole-mediated stress response

Indole, a crucial bacterial signaling molecule, plays a fundamental role in regulating various physiological processes within bacteria, including growth, acid tolerance, biofilm development, motility, and other cellular functions. Its regulatory influence extends beyond indole-producing bacteria, significantly impacting the physiological activities in non-indole-producing species. In this study, we demonstrate that indole enhances the pathogenicity and viability of Klebsiella pneumoniae using the Galleria mellonella infection model and serum killing assay. Concurrently, indole has varying effects on biofilm formation in K. pneumoniae, with some strains showing enhanced biofilm formation ability. To elucidate the underlying molecular mechanisms, transcriptome analysis revealed that indole exposure in K. pneumoniae led to the upregulation of genes associated with pili formation and iron acquisition systems, while simultaneously inducing oxidative stress responses. Additionally, our analysis uncovered extensive metabolic remodeling. Specifically, we observed significant upregulation of genes involved in simple carbohydrate utilization pathways, including those responsible for galactose, mannose, and maltose metabolism, as well as enhanced expression of genes associated with pyrimidine biosynthesis. These findings collectively indicate that indole enhances the intestinal colonization and pathogenicity of K. pneumoniae primarily by modulation of fimbriae expression and metabolic pathway regulation

Inhibitory effects of betulinic acid on LPS-induced neuroinflammation involve M2 microglial polarization via CaMKKβ-dependent AMPK activation

In response to the microenvironment, microglia may polarize into either an M1 pro-inflammatory phenotype, exacerbating neurotoxicity, or an M2 anti-inflammatory phenotype, conferring neuroprotection. Betulinic acid (BA) is a naturally pentacyclic triterpenoid with considerable anti-inflammatory properties. Here, we aim to investigate the potential effects of BA on microglial phenotype polarization and to reveal the underlying mechanisms of action. First, we confirmed that BA promoted M2 polarization and inhibited M1 polarization in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Then, we demonstrated that the effect of BA on microglial polarization was dependent on AMP-activated protein kinase (AMPK) activation, as evidenced by the fact that both AMPK inhibitor compound C and AMPK siRNA abolished the M2 polarization promoted by BA. Moreover, we found that calmodulin-dependent protein kinase kinase β (CaMKKβ), but not liver kinase B1, was the upstream kinase required for BA-mediated AMPK activation and microglial M2 polarization, via the use of both the CaMKKb inhibitor STO-609 and CaMKKβ siRNA. Finally, BA enhanced AMPK phosphorylation and promoted M2 microglial polarization in the cerebral cortex of LPSinjected mice brains, which was attenuated by pre-administration of the AMPK inhibitor. This study demonstrated that BA promoted M2 polarization of microglia, thus conferring anti-neuroinflammatory effects via CaMKKβ-dependent AMPK activation

Analyses of a chromosome-scale genome assembly reveal the origin and evolution of cultivated chrysanthemum

DATA AVAILABILITY : The raw sequencing data generated in this study have been deposited in the NCBI under accession PRJNA796762 and PRJNA895586 The chloroplast andmitochondrial genome were also available at GenBank under the accession number OP104251 and OP104742 respectively. The assembled genome sequences and annotations are available at Figshare [https://doi.org/10.6084/m9.figshare.21655364.v2]. The Arabidopsis ABCE and chrysanthemum CYC2 genes were used as query sequences for gene family identification, which are available at Figshare [https://doi.org/10.6084/m9.figshare.21610305]. Source data are provided with this paper.Chrysanthemum (Chrysanthemum morifolium Ramat.) is a globally important ornamental plant with great economic, cultural, and symbolic value. However, research on chrysanthemum is challenging due to its complex genetic background. Here, we report a near-complete assembly and annotation for C. morifolium comprising 27 pseudochromosomes (8.15 Gb; scaffold N50 of 303.69Mb). Comparative and evolutionary analyses reveal a whole-genome triplication (WGT) event shared by Chrysanthemum species approximately 6 million years ago (Mya) and the possible lineage-specific polyploidization of C. morifolium approximately 3 Mya. Multilevel evidence suggests that C. morifolium is likely a segmental allopolyploid. Furthermore, a combination of genomics and transcriptomics approaches demonstrate the C. morifolium genome can be used to identify genes underlying key ornamental traits. Phylogenetic analysis of CmCCD4a traces the flower colour breeding history of cultivated chrysanthemum. Genomic resources generated from this study could help to accelerate chrysanthemum genetic improvement.The National Natural Science Foundation of China, the Natural Science Fund of Jiangsu Province, China Agriculture Research System, the National Key Research and Development Program of China, the “JBGS” Project of Seed Industry Revitalisation in Jiangsu Province, the European Union’s Horizon 2020 research and innovation program from European Research Council, the Methusalem funding from Ghent University, and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institution.https://www.nature.com/ncomms/am2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-15:Life on lan