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Abstract. As a complementary and alternative medicine (CAM), traditional Chinese medicine (TCM) represents an established medical system with a rich history and abundant clinical experience. TCM is an empirical medicine, the process of which is analogous to ChatGPT’s learning and development model. In TCM, inquiry is a relatively objective way of traditional syndrome differentiation. Although various artificial intelligence systems related to TCM consultation exist, their interactive abilities remain limited. The study standardized the primary complaint and instructed ChatGPT to simulate a TCM practitioner, conducting three comprehensive inquiry tests. The results yielded unexpected conclusions, revealing that ChatGPT could simulate a TCM practitioner’s inquiry with patients, confirming its potential in the field of TCM inquiry. However, current applications still pose certain limitations and risks. Hence, to integrate ChatGPT-like language models with traditional TCM AI to establish an associative mode that can facilitate TCM diagnosis and treatment with more convenience and standardization is crucial, yet at the same time, it should be treated very carefully.

Quorum sensing inhibitors (QSIs), as a kind of ideal antibiotic substitutes, have been recommended to be used in combination with traditional antibiotics in medical and aquaculture fields. Due to the co-existence of QSIs and antibiotics in environmental media, it is necessary to evaluate their joint risk. However, there is little information about the acute toxicity of mixtures for QSIs and antibiotics. In this study, 10 QSIs and 3 sulfonamides (SAs, as the representatives for traditional antibiotics) were selected as the test chemicals, and their acute toxic effects were determined using the bioluminescence of Aliivibrio fischeri (A. fischeri) as the endpoint. The results indicated that SAs and QSIs all induced S-shaped dose-responses in A. fischeri bioluminescence. Furthermore, SAs possessed greater acute toxicity than QSIs, and luciferase (Luc) might be the target protein of test chemicals. Based on the median effective concentration (EC50) for each test chemical, QSI-SA mixtures were designed according to equitoxic (EC50(QSI):EC50(SA) = 1:1) and non-equitoxic ratios (EC50(QSI):EC50(SA) = 1:10, 1:5, 1:0.2, and 1:0.1). It could be observed that with the increase of QSI proportion, the acute toxicity of QSI-SA mixtures enhanced while the corresponding TU values decreased. Furthermore, QSIs contributed more to the acute toxicity of test binary mixtures. The joint toxic actions of QSIs and SAs were synergism for 23 mixtures, antagonism for 12 mixtures, and addition for 1 mixture. Quantitative structure–activity relationship (QSAR) models for the acute toxicity QSIs, SAs, and their binary mixtures were then constructed based on the lowest CDOCKER interaction energy (Ebind-Luc) between Luc and each chemical and the component proportion in the mixture. These models exhibited good robustness and predictive ability in evaluating the toxicity data and joint toxic actions of QSIs and SAs. This study provides reference data and applicable QSAR models for the environmental risk assessment of QSIs, and gives a new perspective for exploring the joint effects of QSI-antibiotic mixtures.

This paper investigates a metamaterial cylindrical shell with local resonators for broadband longitudinal wave attenuation. A three-component phononic crystal metamaterial cylindrical shell that opens local resonant bandgaps at low frequencies is formed by periodically inserting a lead column coated with soft rubber into an ordinary cylindrical shell. First, the governing equations of elastic wave propagation in cylindrical shell structures are derived through coordinate transformation. Subsequently, numerical models of the metamaterial cylindrical shell are established, and the dispersion relation and vibration transmission characteristics of this structure are calculated using the Finite Element Method (FEM). Finally, in order to further broaden the bandgaps and the strong suppression range of the structure, a multiple-graded-resonator metamaterial cylindrical shell with three different local resonators is also proposed. These local resonators have different start frequencies and locations of their longitudinal wave bandgaps, so they can be combined to produce a wider overall bandgap. Numerical results show that this kind of multiple-graded-resonator metamaterial cylindrical shell has a good vibration suppression effect on longitudinal waves in the range of approximately 180–710 Hz and the vibration suppression effect can reach −40 dB at best. In addition, experimental results on vibration transmission characteristics show good agreement with the numerical results. This work provides a new idea and method for the development of acoustic metamaterials to obtain broadband and low-frequency bandgaps for cylindrical shell structures.

Adipose-derived stem cells (ADSCs) are able to modulate the immune response and are used for treating ulcerative colitis (UC). However, it is possible that ADSCs from patients with inflammatory or autoimmune disorders may show defective immunosuppression. We investigated the use of ADSCs from UC patients for autologous cell treatment, specifically, ADSCs from healthy donors (H-ADSCs) and UC patients (P-ADSCs) in terms of various functions, including differentiation, proliferation, secretion, and immunosuppression. The efficacy of P-ADSCs for treating UC was examined in mouse models of acute or chronic colitis. Both H-ADSCs and P-ADSCs were similar in cell morphology, size, adipogenic differentiation capabilities, and cell surface markers. We found that P-ADSCs had lower proliferative capacity, cloning ability, and osteogenic and chondrogenic differentiation potential than H-ADSCs. P-ADSCs exhibited a diminished capacity to inhibit peripheral blood mononuclear cell proliferation, suppress CD25 and CD69 marker expression, decrease the production of inflammation-associated cytokines interferon-γ and tumor necrosis factor-α, and reduce their cytotoxic effect on A549 cells. When primed with inflammatory cytokines, P-ADSCs secreted lower levels of prostaglandin E2, indoleamine 2, 3-dioxygenase, and tumor necrosis factor-α–induced protein 6, which mediated their reduced immunopotency. Moreover, P-ADSCs exhibited weaker therapeutic effects than H-ADSCs, determined by disease activity, histology, myeloperoxidase activity, and body weight. These findings indicate that the immunosuppressive properties of ASCs are affected by donor metabolic characteristics. This study shows, for the first time, the presence of defective ADSC immunosuppression in UC, indicating that autologous transplantation of ADSCs may be inappropriate for patients with UC.

Krüppel-like factor 5 (KLF5) can both promote and suppress cell migration, but the underlying mechanisms have not been elucidated. In this study, we show that the function of KLF5 in epithelial-mesenchymal transition (EMT) and migration of liver cancer cells depends on the status of the cellular tumor antigen p53 (p53). Furthermore, zinc finger E-box-binding homeobox 2 (ZEB2) is the main regulator of KLF5 in EMT in liver cancer cells in the context of p53 loss. Most importantly, the regulation of ZEB2 by p53 and KLF5 is indirect and that miR-192 mediates this regulation. Finally, we find that in invasive liver cancer, KLF5 is absent in the context of p53 loss or mutation.

The actin cytoskeleton of hepatic stellate cells (HSCs) is reorganized when they are cultured in 3D collagen matrices. Here, we investigated the molecular mechanism of actin cytoskeleton reorganization in HSCs cultured in 3D floating collagen matrices (FCM) compared to those on 2D polystyrene surfaces (PS). First, we found that the generation of dendritic cellular processes was controlled by Rac1. Next, we examined the differential gene expression of HSCs cultured on 2D PS and in 3D FCM by RNA-Seq and focused on the changes of actin cytoskeleton reorganization-related molecular components and guanine nucleotide exchange factors (GEFs). The results showed that the expression of genes associated with actin cytoskeleton reorganization-related cellular components, filopodia and lamellipodia, were significantly decreased, but podosome-related genes was significantly increased in 3D FCM. Furthermore, we found that a Rac1-specific GEF, ARHGEF4, played roles in morphological changes, migration and podosome-related gene expression in HSCs cultured in 3D FCM. Abbreviations: 2D PS: 2-dimensional polystyrene surface; 3D FCM: 3-dimensional floating collagen matrices; ARHGEF4: Rho guanine nucleotide exchange factor 4; ARHGEF6: Rho guanine nucleotide exchange factor 6; GEF: guanine nucleotide exchange factor; HSC: hepatic stellate cell

EGF has been shown to stimulate the growth of animals. In this study, the content of EGF in chicken embryos (gallus EGF, gEGF) aged from 1 to 20 days of incubation were determined by ELISA kit, and the 5-day-old chicken embryos with the highest content of 5593 pg/g were selected to make gEGF crude extracts. A total of 1500 1-day-old Xianju chickens were randomly divided into five groups with six replicates of 50 chickens each. The control group was fed a basal diet, and other treatment diets were supplemented with 4, 8, 16 and 32 ng/kg gEGF crude extract, respectively. The experiment lasted for 30 days. Chicks were harvested at the end of the experiment, and liver, spleen, thymus, bursa and serum samples were collected. Results showed that average daily gain (ADG) and average daily feed intake (ADFI) of 16 ng/kg group were higher than those in the control group (p < 0.05). The serum uric acid (UA) of the 16 ng/kg group was reduced (p < 0.01), and the serum alkaline phosphatase (AKP) of the 16 ng/kg group increased (p < 0.01). The gEGF extract also increased chick’s antioxidant capacity, decreased malondialdehyde (MDA) and increased catalase (CAT) in the liver and serum of 16 ng/kg groups in compared to the control group (p < 0.01). Furthermore, immunity was improved by the addition of gEGF to broiler diets. The serum immunoglobin A (IgA) content of 8 and 16 ng/kg groups and the serum immunoglobin M (IgM) content of 4 and 8 ng/kg groups were increased (p < 0.05) compared to the control group. The bursa index of each experimental group was higher than the control group (p < 0.01). These findings demonstrate that the crude extract of gEGF prepared in this experiment could improve the growth performance, antioxidant capacity and immunity of broilers.

Objectives. To investigate CD4+CD25+FoxP3+ T regulatory cells (Tregs) in the peripheral blood of patients with atopic dermatitis (AD) and its correlation with disease severity. Methods. Blood samples from 79 AD patients before and after four-week conventional treatment were collected. Cell counts of CD4+CD25+FoxP3+Tregs, CD4+CD25+FoxP3-T effector cells (Teffs), and CD4+IL-10+Tregs were analyzed by flow cytometry. Serum levels of IL-4, IL-10, IL-12, IL-13, IFN-γ, and TGF-β were measured by ELISA. Results. The pretreatment cell count of CD4+CD25+FoxP3+Tregs positively correlated with disease severity in all patients (P

Ninhydrin-based fluorometric quantification of phenylalanine is one of the most widely used methods for hyperphenylalaninemia (HPA) screening in neonates due to its high sensitivity, high accuracy, and low cost. Here we report an increase of false positive cases in neonatal HPA screening with this method, caused by contamination of blood specimen collection devices during the printing process. Through multiple steps of verification, the contaminants were identified from ink circles printed on the collection devices to indicate the positions and sizes of blood drops. Blood specimens from HPA-negative persons collected on these contaminated collection devices showed positive results in the fluorometric tests, but negative results in tandem mass spectroscopy (MS/MS) experiments. Contaminants on the collection devices could be extracted by 80% ethanol and showed an absorption peak around 245 nm, suggesting that these contaminants may contain benzene derivatives with similar structure to phenylalanine. High-performance liquid chromatography (HPLC) analysis of the ethanol extracts from contaminated collection devices identified two prominent peaks specifically from the devices. Methyl-2-benzoylbenzoate (MBB, CAS#606-28-0) was found as one of the major chemicals from contaminated collection devices. This report aims to remind colleagues in the field of this potential contamination and call for tighter regulation and quality control of specimen collection devices.

Liver fibrosis, a major cause of morbidity and mortality worldwide, leads to liver damage, seriously threatening human health. In our previous study, we demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) was upregulated in fibrotic liver tissue and involved in the migration and lamellipodia formation of hepatic stellate cells (HSCs). In this study, we evaluated PHP14 as a therapeutic target for liver fibrosis and investigated the mechanism by which it mediates liver fibrosis. AAV-shPhpt1 administration significantly attenuates CCl4-induced liver fibrosis in mice. In particular, fibrosis-associated inflammatory infiltration was significantly suppressed after PHP14 knockdown. Mechanistically, PHP14 regulated macrophage recruitment, infiltration, and migration by affecting podosome formation of macrophages. Inhibition of PHP14 decreased the expression of the fibrogenic signature at the early stage of liver fibrogenesis and the activation of HSCs in vivo. Thus, PHP14 can be considered a potential therapeutic target for liver fibrosis. [ABSTRACT FROM AUTHOR]

In this paper, we present a stable and decentralized control strategy for multiagent systems (swarms) to capture a moving target in a specific formation. The coordination framework uses artificial potentials to take care of both tracking and formation tasks. First, a basic controller is designed based on a kinematic model. After that, sliding mode control technique is used to force the agents with general vehicle dynamics to obey the required motion. Finally, specific potential functions are discussed and corresponding simulation results are given. [ABSTRACT FROM AUTHOR]