Digital twin brain: a bridge between biological intelligence and artificial intelligence

In recent years, advances in neuroscience and artificial intelligence have paved the way for unprecedented opportunities for understanding the complexity of the brain and its emulation by computational systems. Cutting-edge advancements in neuroscience research have revealed the intricate relationship between brain structure and function, while the success of artificial neural networks highlights the importance of network architecture. Now is the time to bring them together to better unravel how intelligence emerges from the brain's multiscale repositories. In this review, we propose the Digital Twin Brain (DTB) as a transformative platform that bridges the gap between biological and artificial intelligence. It consists of three core elements: the brain structure that is fundamental to the twinning process, bottom-layer models to generate brain functions, and its wide spectrum of applications. Crucially, brain atlases provide a vital constraint, preserving the brain's network organization within the DTB. Furthermore, we highlight open questions that invite joint efforts from interdisciplinary fields and emphasize the far-reaching implications of the DTB. The DTB can offer unprecedented insights into the emergence of intelligence and neurological disorders, which holds tremendous promise for advancing our understanding of both biological and artificial intelligence, and ultimately propelling the development of artificial general intelligence and facilitating precision mental healthcare

Response of temperate forest ecosystem services to rainfall: A case study in the forest nature reserves of northern China

In the context of global climate change, temperate forests in climate-sensitive areas are inevitably affected. To deepen the understanding of the impact on precipitation changes into the relationship between key ecosystem services (ESs), this study selected net primary productivity (NPP), soil conservation (SC) and water yield (WY) of temperate forest in northern China as objects, and the Spearman correlation test and redundancy analysis were applied to analyze the response of ESs relationship to precipitation gradient. The results show that precipitation is the meteorological factor with the greatest impact (contribution 21.2%, p<0.01) on ESs and their relationships in temperate forests. The 600-700 mm precipitation gradient is the key turning point in the change of ESs relationship of WY with NPP and SC. This indicates that attention should be paid to the spatial variation of the 600-700 mm precipitation region in the future warm-wet in northern China, which should be used as a dividing line of forest management and policy development. Based on the results, future restoration projects in northern temperate forest should focus on (1) in areas with less than 600-700 mm of precipitation, attention should be paid to the selection of tree species for afforestation to maintain regional water balance; (2) in areas with more than 700 mm of precipitation, soil and water conservation projects need to be planned, especially in mountainous area. The research can not only support the management of temperate forest ecosystems in northern China, but also provide reference to other forest ecosystems to cope with climate change

Directed Self-Assembly of Heterologously Expressed Hagfish EsTKα and EsTKγ for Functional Hydrogel

Hagfish slime proteins have long been considered useful due to their potential applications in novel green, environmental, and functional bionic materials. The two main component proteins in the slime thread of hagfish, (opt)EsTKα and (opt)EsTKγ, were used as raw materials. However, the methods available to assemble these two proteins are time- and labor-intensive. The conditions affecting protein self-assembly, such as the pH of the assembly buffer, protein concentration, and the protein addition ratio, were the subject of the present research. Through a series of tests, the self-assembly results of a variety of assembly conditions were explored. Finally, a simplified protein self-assembly method was identified that allows for simple, direct assembly of the two proteins directly. This method does not require protein purification. Under the optimal assembly conditions obtained by exploration, a new gel material was synthesized from the hagfish protein through self-assembly of the (opt)EsTKα and (opt)EsTKγ. This assembly method has the benefits of being a simple, time-saving, and efficient. The self-assembled protein gel products were verified by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and contained (opt)EsTKα and (opt)EsTKγ proteins. Scanning electron microscopy (SEM) was used to investigate the self-assembled protein gel after freeze-drying, and it was observed that the self-assembled protein formed a dense, three-dimensional porous network structure, meaning that it had good water retention. Evaluation of the gel with atomic force microscopy (AFM) indicated that the surface of the protein fiber skeleton show the network-like structure and relatively smooth. Characterization by circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR) demonstrated that the two proteins were successfully assembled, and that the assembled protein had a secondary structure dominated by α-helices. The rheological properties of the self-assembled products were tested to confirm that they were indeed hydrogel property

Landscape composition and configuration relatively affect invasive pest and its associator across multiple spatial scales

Landscape structures affect pests, depending on compositional heterogeneity (the number and proportions of different habitats), configurational heterogeneity (spatial arrangement of habitats), and spatial scales. However, there is limited information on the relative effects of compositional and configurational heterogeneity on invasive pests and their associates (species that can benefit from invasive pests), and how they vary across spatial scales. In this study, we assayed the invasive pest Bactrocera dorsalis (Hendel) and its associated fly Drosophila melanogaster in 15 landscapes centered on mango orchards. We calculated landscape composition (forest percentage, mango percentage, and Shannon's diversity) and configuration (edge density) using two methods: spatial distance scales and combined scales. Spatial distance scales included buffer rings with radii of 0.5, 1.0, and 1.5 km, and combined scales referred to cutting or not cutting a smaller ring from larger ones. Our results shown that compositional heterogeneity positively affected B. dorsalis and D. melanogaster due to forest cover percentage, whereas configurational heterogeneity with high edge density negative effect on B. dorsalis. Forest cover had less of an effect on B. dorsalis than configurational heterogeneity, but the opposite effect was observed for D. melanogaster. Importantly, the direction and strength of forest cover and configurational heterogeneity to species did not vary with spatial distance scales or spatial combined scales. Thus, compositional and configurational heterogeneity exhibit differential effects on this invasive pest and its associator, and revealed that the relative effects of landscape structures are consistent across multiple scales. These results provide new insights into landscape effects on interconnected species using a diverse spatial-scale approach

High circulating CD39+ regulatory T cells predict poor survival for sepsis patients

SummaryBackgroundSepsis encompasses two phases, the ‘hyper’-reactive phase and the ‘hypo’-reactive phase. The initial inflammatory stage is quickly counterbalanced by an anti-inflammatory response, which compromises the immune system, leading to immune suppression. Regulatory T cells (Tregs) have been implicated in the pathogenesis of sepsis by inducing immunosuppression; however, the role of CD39+ Tregs in the process of sepsis is uncertain. This study investigated the dynamic levels of CD39+ Tregs and their phenotypic change in sepsis.MethodsFourteen patients with systemic inflammatory response syndrome (SIRS), 42 patients with sepsis, and 14 healthy controls were enrolled. Sequential blood samples were used to analyze the numbers of CD39+ Tregs and their phenotypic changes. Survival at 28 days was used to evaluate the capacity of CD39+ Treg levels to predict mortality in sepsis patients.ResultsSepsis patients displayed a high percentage (3.13%, 1.46%, and 0.35%, respectively) and mean fluorescence intensity (MFI) (59.65, 29.7, and 24.3, respectively) of CD39+ Tregs compared with SIRS patients and healthy subjects. High-level expression of CD39+ Tregs was correlated with the severity of sepsis, which was reflected by the sepsis-related organ failure assessment score (r=0.322 and r=0.31, respectively). In addition, the expression of CD39+ Tregs was associated with survival of sepsis patients (p<0.01). By receiver-operating characteristic (ROC) curve analysis, the percentage and MFI of CD39+ Tregs showed similar sensitivities and specificities to predict mortality (74.2% and 85.1%, and 73.9% and 84.1%, respectively). Using Kaplan–Meier curves to assess the impact of CD39+ Tregs percentage and MFI on overall survival, we found that a high CD39+ Tregs percentage (p<0.001; >4.1%) and MFI (p<0.001; >49.2) were significantly associated with mortality. Phenotypically, CD39+ Tregs from sepsis patients showed high expression of CD38 and PD-1 (p<0.01 and p<0.01 respectively).ConclusionsIncreased expression of CD39+ Tregs was associated with a poor prognosis for sepsis patients, which suggests that CD39+ Treg levels could be used as a biomarker to predict the outcome of sepsis patients

Using Integrative Analysis of DNA Methylation and Gene Expression Data in Multiple Tissue Types to Prioritize Candidate Genes for Drug Development in Obesity

Obesity has become a major public health issue which is caused by a combination of genetic and environmental factors. Genome-wide DNA methylation studies have identified that DNA methylation at Cytosine-phosphate-Guanine (CpG) sites are associated with obesity. However, subsequent functional validation of the results from these studies has been challenging given the high number of reported associations. In this study, we applied an integrative analysis approach, aiming to prioritize the drug development candidate genes from many associated CpGs. Association data was collected from previous genome-wide DNA methylation studies and combined using a sample-size-weighted strategy. Gene expression data in adipose tissues and enriched pathways of the affiliated genes were overlapped, to shortlist the associated CpGs. The CpGs with the most overlapping evidence were indicated as the most appropriate CpGs for future studies. Our results revealed that 119 CpGs were associated with obesity (p ≤ 1.03 × 10−7). Of the affiliated genes, SOCS3 was the only gene involved in all enriched pathways and was differentially expressed in both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). In conclusion, our integrative analysis is an effective approach in highlighting the DNA methylation with the highest drug development relevance. SOCS3 may serve as a target for drug development of obesity and its complications

Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients

HAART largely decreases morbidity and mortality in chronic HIV-1-infected patients, but immune nonresponders (INRs) with full viral suppression still fail to reverse the immune deficiency. This study evaluated the safety and immunological responses of human umbilical cord mesenchymal stem cell (MSC) therapy in HIV-1-infected INRs

Glutamic Acid Decarboxylase-Derived Epitopes with Specific Domains Expand CD4+CD25+ Regulatory T Cells

BACKGROUND:CD4(+)CD25(+) regulatory T cell (Treg)-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS:Splenic lymphocytes from nonobese diabetic (NOD) mice were stimulated with different glutamic acid decarboxylase (GAD)-derived epitopes for 7-10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538)-expanded CD4(+)CD25(+) T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509-528)- or p530 (GAD530-543)-expanded CD4(+)CD25(+) T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes) between the above-mentioned epitopes and MHC class II I-A(g7) were analyzed. The theoretical results showed that the epitope p524, which induced protective Tregs, possessed negative surface-electrostatic potential and bound two chains of MHC class II I-A(g7), while the epitopes p509 and p530 which had no such ability exhibited positive surface-electrostatic potential and bound one chain of I-A(g7). Furthermore, p524 bound to I-A(g7) more stably than p509 and p530. Of importance, we hypothesized and subsequently confirmed experimentally that the epitope (GAD570-585, p570), which displayed similar characteristics to p524, was a protective epitope by showing that p570-expanded CD4(+)CD25(+) T cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE:These data suggest that molecular modeling-based structural analysis of epitopes may be an instrumental tool for prediction of protective epitopes to expand functional Tregs

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data