Ginkgolic acids induce liver injury in mice through cell cycle arrest and immune stress under specific condition.

Ginkgo biloba L. is a valuable plant, which can be used for medicine, food and ornamental purposes. Despite the above benefits, the components of ginkgolic acids (GA) in ginkgo are considered to cause allergies, embryotoxicity, liver damage and some other adverse reactions. However, the mechanism of GA induced liver injury is still unclear. In this study, we developed an acute liver injury model induced by GA in mice, and investigated the mechanism of GA induced liver injury from the perspectives of oxidative stress, steatosis, apoptosis, and immune response. Intraperitoneal injection of GA (400 mg/kg) can cause liver damage. The levels of serum transaminase, oxidation and triglycerides were increased, liver fibrosis, hepatocyte apoptosis, G2/M phase arrest of the hepatic cell cycle and monocyte infiltration in the liver were detected in GA-treated mice. Flow cytometry analysis of cells separated from the spleen showed that the proportion of Th1 and Th17 cells were increased, and the proportion of Th2 cells were decreased in GA-treated mice. The rise in Th1/Th2 ratio and Th17 cell ratio usually cause inflammatory problems. At the same time, cleaved Caspase-8 and Caspase-3 were detected in hepatocytes, indicating that GA may induce apoptosis through FADD pathway. Although GA is capable of causing the above problems, the inflammation and damage in liver tissue are not severe and there are certain individual differences. Our study reveals the potential hepatotoxicity of GA in ginkgo and its mechanism of action, providing a new perspective for the intervention and prevention of ginkgo toxicity.

Toll-like receptor 9 signaling is associated with immune responses to Trypanosoma brucei infection.

Trypanosoma brucei, a causative agent of human and animal trypanosomiasis, regularly switches its major surface antigen to avoid elimination by the immune system. Toll-like receptor 9 (TLR9) is a key modulator for resistance to host-infective trypanosomes; however, the underlying molecular mechanism remains indistinct. Thus, we first approached the issue using Tlr9-mutant mice that render them non-responsive to TLR9 agonists. After infection, T cells in the spleens of Tlr9-mutant mice were analyzed by flow cytometry and a reduction in CD8+, CD4+ T, and NKT cells was observed in Tlr9-mutant mice compared to WT mice. We further found that the responses of inflammatory cytokines in the sera were reduced in Tlr9-mutant mice after T. brucei infection. The underlying molecular mechanism was that T. b. brucei DNA activated TLR9, which consequently upregulated the expression of p38 and ERK/MAPK, resulting in host resistance to trypanosome infection. In conclusion, these findings provide novel insights into the TLR9-mediated host responses to trypanosome infection.

Why are graminoid species more dominant? Trait-mediated plant-soil feedbacks shape community composition.

Species traits may determine plant interactions along with soil microbiome, further shaping plant-soil feedbacks (PSFs). However, how plant traits modulate PSFs and, consequently, the dominance of plant functional groups remains unclear. We used a combination of field surveys and a two-phase PSF experiment to investigate whether forbs and graminoids differed in PSFs and in their trait-PSF associations. When grown in forb-conditioned soils, forbs experienced stronger negative feedbacks, while graminoids experienced positive feedbacks. Graminoid-conditioned soil resulted in neutral PSFs for both functional types. Forbs with thin roots and small seeds showed more-negative PSFs than those with thick roots and large seeds. Conversely, graminoids with acquisitive root and leaf traits (i.e., thin roots and thin leaves) demonstrated greater positive PSFs than graminoids with thick roots and tough leaves. By distinguishing overall and soil biota-mediated PSFs, we found that the associations between plant traits and PSFs within both functional groups were mainly mediated by soil biota. A simulation model demonstrated that such differences in PSFs could lead to a dominance of graminoids over forbs in natural plant communities, which might explain why graminoids dominate in grasslands. Our study provides new insights into the differentiation and adaptation of plant life-history strategies under selection pressures imposed by soil biota.

Effect of Chinese quince proanthocyanidins on the inhibition of heterocyclic amines and quality of fried chicken meatballs and tofu.

Heterocyclic amines (HCAs) have potential carcinogenic and mutagenic activity and are generated in cooked protein-rich foods. Adding proanthocyanidins (PAs) to these foods before frying is an effective way to reduce HCAs. In this study, polymeric PAs (PPA) and ultrasound-assisted acid-catalyzed/catechin nucleophilic depolymerized PAs (UAPA, a type of oligomeric PA) were prepared from Chinese quince fruits (CQF). Different levels of PPA and UAPA (0.05%, 0.1%, and 0.15%) were added to chicken meatballs and tofu; then these foods were fried, and the content of HCAs in them after frying was investigated. The results showed that PPA and, particularly, UAPA significantly inhibited the formation of HCAs in fried meatballs and tofu, and this inhibition was dose-dependent. The inhibition of HCAs by both PPA and UAPA was stronger in the chicken meatballs than in fried tofu. The level of total HCAs was significantly reduced by 57.84% (from 11.93 to 5.03 ng/g) after treatment of meatballs with 0.15% UAPA, with inhibition rates of 78.94%, 50.37%, and 17.81% for norharman, harman, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), respectively. Of note, there was a negative correlation between water, lipid, protein, creatine, and glucose content and HCA content in the crust, interior, and whole (crust-plus-interior) measurements of all fried samples. Interestingly, PPA and UAPA were found more effective in inhibiting HCAs in the exterior crust than in the interior of the fried chicken meatballs. These results provide evidence that further studies on the reduction of the formation of harmful HCAs in fried foods by adding CQF PAs could be valuable to the fried food industry. PRACTICAL APPLICATION: Chinese quince proanthocyanidins treatments significantly inhibited the generation of heterocyclic amines (HCAs) in chicken meatballs and tofu when deep-fried. These results suggest that Chinese quince proanthocyanidins can be used as natural food additive for reducing HCAs in fried foods, laying the foundation for using Chinese quince fruit proanthocyanidins for HCA inhibition in the food industry.

Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori.

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.

Nicotinamide Supplementation Mitigates Oxidative Injury of Bovine Intestinal Epithelial Cells through Autophagy Modulation.

The small intestine is important to the digestion and absorption of rumen undegradable nutrients, as well as the barrier functionality and immunological responses in ruminants. Oxidative stress induces a spectrum of pathophysiological symptoms and nutritional deficits, causing various gastrointestinal ailments. Previous studies have shown that nicotinamide (NAM) has antioxidant properties, but the potential mechanism has not been elucidated. The aim of this study was to explore the effects of NAM on hydrogen peroxide (H2O2)-induced oxidative injury in bovine intestinal epithelial cells (BIECs) and its potential mechanism. The results showed that NAM increased the cell viability and total antioxidant capacity (T-AOC) and decreased the release of lactate dehydrogenase (LDH) in BIECs challenged by H2O2. The NAM exhibited increased expression of catalase, superoxide dismutase 2, and tight junction proteins. The expression of autophagy-related proteins was increased in BIECs challenged by H2O2, and NAM significantly decreased the expression of autophagy-related proteins. When an autophagy-specific inhibitor was used, the oxidative injury in BIECs was not alleviated by NAM, and the T-AOC and the release of LDH were not affected. Collectively, these results indicated that NAM could alleviate oxidative injury in BIECs by enhancing antioxidant capacity and increasing the expression of tight junction proteins, and autophagy played a crucial role in the alleviation.

COF-SiO2@Fe3O4 Composite for Magnetic Solid-Phase Extraction of Pyrethroid Pesticides in Vegetables.

Pyrethroid pesticides (PYRs) have found widespread application in agriculture for the protection of fruit and vegetable crops. Nonetheless, excessive usage or improper application may allow the residues to exceed the safe limits and pose a threat to consumer safety. Thus, there is an urgent need to develop efficient technologies for the elimination or trace detection of PYRs from vegetables. Here, a simple and efficient magnetic solid-phase extraction (MSPE) strategy was developed for the simultaneous purification and enrichment of five PYRs in vegetables, employing the magnetic covalent organic framework nanomaterial COF-SiO2@Fe3O4 as an adsorbent. COF-SiO2@Fe3O4 was prepared by a straightforward solvothermal method, using Fe3O4 as a magnetic core and benzidine and 3,3,5,5-tetraaldehyde biphenyl as the two building units. COF-SiO2@Fe3O4 could effectively capture the targeted PYRs by virtue of its abundant π-electron system and hydroxyl groups. The impact of various experimental parameters on the extraction efficiency was investigated to optimize the MSPE conditions, including the adsorbent amount, extraction time, elution solvent type and elution time. Subsequently, method validation was conducted under the optimal conditions in conjunction with gas chromatography-mass spectrometry (GC-MS). Within the range of 5.00-100 µg·kg-1 (1.00-100 µg·kg-1 for bifenthrin and 2.5-100 µg·kg-1 for fenpropathrin), the five PYRs exhibited a strong linear relationship, with determination coefficients ranging from 0.9990 to 0.9997. The limits of detection (LODs) were 0.3-1.5 µg·kg-1, and the limits of quantification (LOQs) were 0.9-4.5 µg·kg-1. The recoveries were 80.2-116.7% with relative standard deviations (RSDs) below 7.0%. Finally, COF-SiO2@Fe3O4, NH2-SiO2@Fe3O4 and Fe3O4 were compared as MSPE adsorbents for PYRs. The results indicated that COF-SiO2@Fe3O4 was an efficient and rapid selective adsorbent for PYRs. This method holds promise for the determination of PYRs in real samples.

Negative Emotions Will Be Welcomed: The Effect of Upward Comparison on Counterhedonic Consumption.

Upward comparisons are prevalent in life and have a significant influence on consumer psychology and subsequent behavior. Previous research examined the effects of upward comparisons on consumption behavior, mainly focusing on behavior that evokes positive emotions (e.g., donation behavior, sustainable consumption) or behavior that evokes negative emotions (e.g., impulsive consumption, compulsive consumption) and less on behavior that evokes both negative emotions and positive emotions (i.e., counterhedonic consumption). This research examined the effect of upward comparisons on counterhedonic consumption. Five studies (N = 1111) demonstrated that upward comparison (vs. non-upward comparison) leads to counterhedonic consumption, and this effect is mediated by relative deprivation (Studies 2 and 3). In addition, this research showed that the comparison targets moderate the effects of upward comparisons on counterhedonic consumption. Specifically, when the comparison target is a friend, an upward comparison (vs. non-upward comparison) leads to counterhedonic consumption. When the comparison target is a stranger, an upward comparison (vs. non-upward comparison) has no significant influence on counterhedonic consumption (Study 5). Our findings extend the research on upward comparisons, relative deprivation, and counterhedonic consumption.

Bottom-up Growth of Convex Sphere with Adjustable Cu(0)/Cu(I) Interfaces for Effective C2 Production from CO2 Electroreduction.

One challenge confronting the Cu2O catalysts in the electrocatalysis of carbon dioxide reduction reaction (CO2RR) is the reduction of active Cu(I) species, resulting in low selectivity and quick deactivation. In this study, we for the first time introduce a bottom-up growth of convex sphere with adjustable Cu(0)/Cu(I) interfaces (Cux@Cu2O convex spheres). Interestingly, the interfaces are dynamically modulated by varying hydrothermal time, thus regulating the conversion of C1 and C2 products. In particular, the 4 h hydrothermal treatment applied to Cu0.25@Cu2O convex sphere with the favorable Cu(0)/Cu(I) interface results in the highest selectivity for C2 products (90.5%). In situ Fourier-transform infrared spectroscopy measurements and density functional theory calculations reveal that the Cu(0)/Cu(I) interface lowers the energy barrier for the production of ethylene and ethanol while increasing the coverage of localized *CO adsorbate for increased dimerization. This work establishes a novel approach for transforming the state of valence-sensitive electrocatalysts into high-value energy-related engineering products.

Design and optimization of an octuple-electrode array for micro-particle chain rotation via electrorotation integrated with machine vision technology.

Microparticle rotation is an important process in biomedical engineering, such as biosensors, cell injection or cell morphology. Single particle rotation has been widely investigated, while rotation of particle chains has gained rare attention. In this paper, we utilize a noncontact manipulation method to rotate microparticle chains via electrorotation by designing an octuple-electrode array (OEA). Finite element simulations were conducted for analyzing the desired electrode field and optimizing the structure of microelectrode pairs. The direction of the electric field in the workspace is investigated with different voltage signal inputs through specially designed circuits. In the experiment, microparticles are driven to form several chains in the proposed electrode fields. With the rotation of the electric field, particle chains could be rotated synchronously. Automated rotation and detection of polystyrene microspheres and yeast cell chains are achieved using machine vision technology. Results show that the proposed method could be utilized to rotate ordered microparticles with an appropriate input signal.

De novo urinary incontinence and lower urinary tract symptoms after colpocleisis: A single-center prospective study.

Background: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now. Purpose: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms. Methods: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients' satisfaction. Results: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory -6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P < 0.001). The patients' quality of life indicated by Urinary Distress Inventory-6 and Urinary Impact Questionnaire-7 scores were significantly improved postoperatively (26.27 vs. 13.39, and 19.13 vs. 6.05, P < 0.05). Conclusion: The incidence of de novo urinary incontinence after colpocleisis was very low. Patients' quality of life, and low urinary tract symptoms were significantly improved after colpocleisis.

Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.

The heterogeneity of CARM1 controls first cell fate bias during early mouse development. However, how this heterogeneity is established is unknown. Here, we show that Carm1 mRNA is of a variety of specific exon-skipping splicing (ESS) isoforms in mouse two-cell to four-cell embryos that contribute to CARM1 heterogeneity. Disruption of paraspeckles promotes the ESS of Carm1 precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1 pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGET recruits paraspeckles to the Carm1 gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1 pre-mRNAs and promotes its ESS in the absence of LincGET. Finally, we find that the ESS seen in mouse two-cell to four-cell embryos decreases CARM1 protein levels and leads to trophectoderm fate bias. Our findings demonstrate that alternative splicing of CARM1 has an important role in first cell fate determination.

Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex.

Silver compounds have favorable properties as promising anticancer drug candidates, such as low side effects, anti-inflammatory properties, and high potential to overcome drug resistance. However, the exact mechanism by which Ag(i) confers anticancer activity remains unclear, which hinders further development of anticancer applications of silver compounds. Here, we combine thermal proteome profiling, cysteine profiling, and ubiquitome profiling to study the molecular mechanisms of silver(i) complexes supported by non-toxic thiourea (TU) ligands. Through the formation of AgTU complexes, TU ligands deliver Ag+ ions to cancer cells and tumour xenografts to elicit inhibitory potency. Our chemical proteomics studies show that AgTU acts on the ubiquitin-proteasome system (UPS) and disrupts protein homeostasis, which has been identified as a main anticancer mechanism. Specifically, Ag+ ions are released from AgTU in the cellular environment, directly target the 19S proteasome regulatory complex, and may oxidize its cysteine residues, thereby inhibiting proteasomal activity and accumulating ubiquitinated proteins. After AgTU treatment, proteasome subunits are massively ubiquitinated and aberrantly aggregated, leading to impaired protein homeostasis and paraptotic death of cancer cells. This work reveals the unique anticancer mechanism of Ag(i) targeting the 19S proteasome regulatory complex and opens up new avenues for optimizing silver-based anticancer efficacy.

Feasibility and prognostic value of tissue motion annular displacement in patients with heart transplantation.

BACKGROUND: Tissue motion of mitral annular displacement (TMAD) assessment has proved to be an effective method for several cardiovascular diseases including hypertrophic cardiomyopathy, heart failure, non-ST-elevation myocardial infarction, etc. However, there are no studies exploring the feasibility of TMAD in heart transplantation (HT) recipients, and the predictive value of this parameter for adverse outcomes in these patients remains unknown. Consequently, this study aimed to evaluate the feasibility of TMAD in the evaluation of left ventricular (LV) systolic function in clinically well adult HT patients, and further investigate the prognostic value of TMAD. METHODS: Echocardiography was performed in 155 adult HT patients and 49 healthy subjects. All the subjects were examined by conventional transthoracic two-dimensional echocardiography and two-dimensional speckle tracking echocardiography (2D-STE) with evaluation of the LV end-diastolic diameter, LV end-diastolic volume index, LV end-systolic volume index, interventricular septal thickness, left atrial diameter, mitral annular plane systolic excursion (MAPSE), LV ejection fraction (LVEF), TMAD and LV global longitudinal strain (LVGLS). The end point was defined as all-causes mortality or posttransplant related hospitalization during follow up. Cox proportional hazards regression was performed to evaluate the prognostic value of the parameters for predicting poor outcomes in HT patients. RESULTS: A significant positive correlation was found between the measurements of TMAD and LVGLS (r = .714, p < .001). TMAD obtained by 2D-STE had good reproducibility. The LVGLS and TMAD were significantly lower in HT group than in control group (both p < .001). In HT patients, compared with event free group, adverse outcome group displayed reduced TMAD and LVGLS, and elevated age (p < .001, < .001, = .017, respectively). Patients with higher TMAD (> 9.1 mm) had comparatively better survival when stratified by cutoff value (log-rank p < .001). LVGLS and TMAD were independently associated with adverse outcomes in multivariable analysis (both p < .001). CONCLUSION: Assessment of TMAD is effective for evaluating LV longitudinal systolic function and predicting adverse outcomes in clinically well adult HT patients.

High Performance Nacre Fibers by Engineering Interfacial Entanglement.

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

Influence of Strong Shear Field on Structure and Performance of HDPE/PA6 In Situ Microfibril Composites.

As one of the most widely applied general-purpose plastics, high-density polyethylene (HDPE) exhibits good comprehensive performance. However, mechanical strength limits its wider application. In this work, we introduced the engineering plastic PA6 as a dispersed phase to modify the HDPE matrix and applied multiple shears generated by vibration to the polymer melt during the packing stage of injection molding. SEM, 2D-WXRD and 2D-SAXS were used to characterize the morphology and structure of the samples. The results show that under the effect of a strong shear field, the dispersed phase in the composites can form in situ microfibers and numerous high-strength shish-kebab and hybrid shish-kebab structures are formed. Additionally, the distribution of fibers and high-strength oriented structures in the composites expands to the core region with the increase in vibration times. As a result, the tensile strength, tensile modulus and surface hardness of VIM-6 can reach a high level of 66.5 MPa, 981.4 MPa and 72, respectively. Therefore, a high-performance HDPE product is successfully prepared in this study, which is of great importance for expanding the application range of HDPE products.

Prioritization of organic contaminants in China's groundwater based on national-scale monitoring data and their persistence, bioaccumulation, and toxicity.

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.

Accurate Finite Element Simulations of Dynamic Behaviour: Constitutive Models and Analysis with Deep Learning.

Owing to the challenge of capturing the dynamic behaviour of metal experimentally, high-precision numerical simulations have become essential for analysing dynamic characteristics. In this study, calculation accuracy was improved by analysing the impact of constitutive models using the finite element (FE) model, and the deep learning (DL) model was employed for result analysis. The results showed that FE simulations with these models effectively capture the elastic-plastic response, and the ZA model exhibits the highest accuracy, with a 26.0% accuracy improvement compared with other models at 502 m/s for Hugoniot elastic limit (HEL) stress. The different constitutive models offer diverse descriptions of stress during the elastic-plastic response because of temperature effects. Concurrently, the parameters related to the yield strength at quasi-static influence the propagation speed of elastic waves. Calculation show that the yield strength at quasi-static of 6061 Al adheres to y = ax + b for HEL stress. The R-squared (R2) and mean absolute error (MAE) values of the DL model for HEL stress predictions are 0.998 and 0.0062, respectively. This research provides a reference for selecting constitutive models for simulation under the same conditions.

Network pharmacology combined with affinity ultrafiltration to elucidate the potential compounds of Shaoyao Gancao Fuzi Decoction for the treatment of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao Gancao Fuzi Decoction (SGFD), has been employed for thousands of years in the treatment of rheumatoid arthritis (RA) with remarkable clinical efficacy. However, the material basis underlying the effectiveness of SGFD still remains unclear. AIM OF THE REVIEW: This study aims to elucidate the material basis of SGFD through the application of network pharmacology and biological affinity ultrafiltration. RESULTS: UPLC-Q-TOF-MS/MS was employed to characterize the components in SGFD, the identified 145 chemical components were mainly categorized into alkaloids, flavonoids, triterpenoids, and monoterpenoids according to the structures. Network pharmacology method was utilized to identify potential targets and signaling pathways of SGFD in the RA treatment, and the anti-inflammatory and anti-RA effects of SGFD were validated through in vivo and in vitro experiments. Moreover, as the significant node in the pharmacology network, TNF-α, a classical therapeutic target in RA, was subsequent employed to screen the interacting compounds in SGFD via affinity ultrafiltration screening method, 6 active molecules (i.e.,glycyrrhizic acid, paeoniflorin, formononetin, isoliquiritigenin, benzoyl mesaconitine, and glycyrrhetinic acid) were exhibited significant interactions. Finally, the significant anti-inflammatory and anti-TNF-α effects of these compounds were validated at the cellular level. CONCLUSIONS: In conclusion, this study comprehensively elucidates the pharmacodynamic material basis of SGFD, offering a practical reference model for the systematic investigation of traditional Chinese medicine formulas.

Toxoplasma sortilin interacts with secretory proteins and it is critical for parasite proliferation.

BACKGROUND: The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored. METHODS: A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined. RESULTS: The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii. CONCLUSION: The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies.