S3: Social-network Simulation System with Large Language Model-Empowered Agents

Social network simulation plays a crucial role in addressing various challenges within social science. It offers extensive applications such as state prediction, phenomena explanation, and policy-making support, among others. In this work, we harness the formidable human-like capabilities exhibited by large language models (LLMs) in sensing, reasoning, and behaving, and utilize these qualities to construct the S$^3$ system (short for $\textbf{S}$ocial network $\textbf{S}$imulation $\textbf{S}$ystem). Adhering to the widely employed agent-based simulation paradigm, we employ prompt engineering and prompt tuning techniques to ensure that the agent's behavior closely emulates that of a genuine human within the social network. Specifically, we simulate three pivotal aspects: emotion, attitude, and interaction behaviors. By endowing the agent in the system with the ability to perceive the informational environment and emulate human actions, we observe the emergence of population-level phenomena, including the propagation of information, attitudes, and emotions. We conduct an evaluation encompassing two levels of simulation, employing real-world social network data. Encouragingly, the results demonstrate promising accuracy. This work represents an initial step in the realm of social network simulation empowered by LLM-based agents. We anticipate that our endeavors will serve as a source of inspiration for the development of simulation systems within, but not limited to, social science

Radionuclide Labeling and Evaluation of Candidate Radioligands for PET Imaging of Histone Deacetylase in the Brain

Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza®), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study epigenetic regulation and HDAC engagement for drug development for diseases including cancer and psychiatric disorders. 6-([18F]Fluoroacetamido)-1-hexanoicanilide ([18F]FAHA) was recently developed as a HDAC substrate and shows moderate blood–brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate- and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [18F]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration.Chemistry and Chemical Biolog

Effects of treatment with Astragalus Membranaceus on function of rat leydig cells

Background Astragalus membranaceus (AM) is a Chinese traditional herb which has been reported to have broad positive effects on many diseases, including hepatitis, heart disease, diabetes and skin disease. AM can promote cell proliferation, increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and inhibit apoptosis by regulating the transcription of proto-oncogenes controlling cell death. While AM is included in some commercially available “testosterone boosting supplements”, studies directly testing ability of AM to modulate testosterone production are lacking. In the present study, we examined the effects of AM on Leydig cell function in vitro. Methods Rat Leydig cells were purified and treated with AM at different concentrations (0 μg/mL, 10 μg/mL, 20 μg/mL, 50 μg/mL, 100 μg/mL and 150 μg/mL) and cell counting-8 (CCK-8) assay, Enzyme-linked immunosorbent assay, quantitative real time PCR and analysis of activities of SOD and GPx were done respectively. Results Treatment with 100 μg/mL (P \u3c 0.05) and 150 μg/mL AM (P \u3c 0.01) significantly increased Leydig cell numbers. Treatment with AM (20 μg/mL, 50 μg/mL and 100 μg/mL) significantly increased testosterone production (P \u3c 0.01). In addition, increased Leydig cell SOD and GPx activities were observed in response to 20 μg/mL and 50 μg/mL AM treatment (P \u3c 0.01). Furthermore, expression of Bax mRNA was significantly decreased (P \u3c 0.01), and the ratio of Bcl-2/Bax mRNA was significantly increased in response to 20 μg/mL AM in the culture medium (P \u3c 0.05). Conclusions Results supported a beneficial effect of AM on multiple aspects of rat Leydig cell function in vitro including testosterone production

Children neuropsychological and behavioral scale-revision 2016 in the early detection of autism spectrum disorder

BackgroundThe Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) is a widely used developmental assessment tool for children aged 0–6 years in China. The communication warning behavior subscale of CNBS-R2016 is used to assess the symptoms of autism spectrum disorder (ASD), and its value of >30 points indicates ASD based on CNBS-R2016. However, we observed that children with relatively lower values were also diagnosed with ASD later on in clinical practice. Thus, this study aimed to identify the suitable cutoff value for ASD screening recommended by the communication warning behavior of CNBS-R2016.Materials and methodsA total of 90 typically developing (TD) children and 316 children with developmental disorders such as ASD, developmental language disorder (DLD), and global developmental delay (GDD; 130 in the ASD group, 100 in the DLD group, and 86 in the GDD group) were enrolled in this study. All subjects were evaluated based on the CNBS-R2016. The newly recommended cutoff value of communication warning behavior for screening ASD was analyzed with receiver operating curves.ResultsChildren in the ASD group presented with lower developmental levels than TD, DLD, and GDD groups in overall developmental quotient assessed by CNBS-R2016. We compared the consistency between the scores of communication warning behavior subscale and Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Diagnostic Observation Schedule, second edition (ADOS-2), and clinical diagnosis for the classification of ASD at a value of 30 based on the previously and newly recommended cutoff value of 12 by the CNBS-R2016. The Kappa values between the communication warning behavior and ABC, CARS, ADOS-2, and clinical diagnosis were 0.494, 0.476, 0.137, and 0.529, respectively, with an agreement rate of 76.90%, 76.26%, 52.03%, and 82.27%, respectively, when the cutoff point was 30. The corresponding Kappa values were 0.891, 0.816, 0.613, and 0.844, respectively, and the corresponding agreement rate was 94.62%, 90.82%, 90.54%, and 93.10%, respectively, when the cutoff point was 12.ConclusionThe communication warning behavior subscale of CNBS-R2016 is important for screening ASD. When the communication warning behavior score is 12 points or greater, considerable attention and further comprehensive diagnostic evaluation for ASD are required to achieve the early detection and diagnosis of ASD in children

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions—a case report

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient’s gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient’s symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms

Modulation of nucleobindin-1 and nucleobindin-2 by caspases

Nucleobindin-1 and nucleobindin-2 are multifunctional proteins that interact with Ca2+, nucleic acids, and various regulatory proteins in different signaling pathways. So far, our understanding of the regulation of the biological functions of nucleobindins remains limited. In our proteome-wide selection for downstream caspase substrates, both nucleobindin-1 and nucleobindin-2 are found to be the downstream substrates of caspases. We report here the detailed analyses of the cleavage of nucleobindins by caspases. Significantly, the caspase cleavage sites are located exactly at one of the Ca2+-binding EF-hand motifs. Our results suggest that the functions of nucleobindins could be modulated by caspase-mediated cleavage in apoptosis